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Sample records for golgi retrograde trafficking

  1. 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.

  2. 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...

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

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    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.

  4. 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

  5. Eeyarestatin 1 interferes with both retrograde and anterograde intracellular trafficking pathways.

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    Mina-Olga Aletrari

    Full Text Available The small molecule Eeyarestatin I (ESI inhibits the endoplasmic reticulum (ER-cytosol dislocation and subsequent degradation of ERAD (ER associated protein degradation substrates. Toxins such as ricin and Shiga/Shiga-like toxins (SLTx are endocytosed and trafficked to the ER. Their catalytic subunits are thought to utilise ERAD-like mechanisms to dislocate from the ER into the cytosol, where a proportion uncouples from the ERAD process, recovers a catalytic conformation and destroys their cellular targets. We therefore investigated ESI as a potential inhibitor of toxin dislocation.Using cytotoxicity measurements, we found no role for ES(I as an inhibitor of toxin dislocation from the ER, but instead found that for SLTx, ESI treatment of cells was protective by reducing the rate of toxin delivery to the ER. Microscopy of the trafficking of labelled SLTx and its B chain (lacking the toxic A chain showed a delay in its accumulation at a peri-nuclear location, confirmed to be the Golgi by examination of SLTx B chain metabolically labelled in the trans-Golgi cisternae. The drug also reduced the rate of endosomal trafficking of diphtheria toxin, which enters the cytosol from acidified endosomes, and delayed the Golgi-specific glycan modifications and eventual plasma membrane appearance of tsO45 VSV-G protein, a classical marker for anterograde trafficking.ESI acts on one or more components that function during vesicular transport, whilst at least one retrograde trafficking pathway, that of ricin, remains unperturbed.

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

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    Soonthornsit, Jeerawat [Laboratory for Cell and Developmental Biology, Department of Molecular Biosciences, Faculty of Life Sciences, Kyoto Sangyo University, Motoyama, Kamigamo, Kita, Kyoto 603-8555 (Japan); Yamaguchi, Yoko; Tamura, Daisuke [Division of Life Sciences, Graduate School of Natural Science and Technology, Kanazawa University, Kakuma, Kanazawa 920-1192 (Japan); Ishida, Ryuichi; Nakakoji, Yoko; Osako, Shiho [Laboratory for Cell and Developmental Biology, Department of Molecular Biosciences, Faculty of Life Sciences, Kyoto Sangyo University, Motoyama, Kamigamo, Kita, Kyoto 603-8555 (Japan); Yamamoto, Akitsugu [Department of Animal Bioscience, Nagahama Institute of Bio-Science and Technology, 266 Tamura, Nagahama, Shiga, 526‐0829 (Japan); Nakamura, Nobuhiro, E-mail: osaru3@cc.kyoto-su.ac.jp [Laboratory for Cell and Developmental Biology, Department of Molecular Biosciences, Faculty of Life Sciences, Kyoto Sangyo University, Motoyama, Kamigamo, Kita, Kyoto 603-8555 (Japan); Division of Life Sciences, Graduate School of Natural Science and Technology, Kanazawa University, Kakuma, Kanazawa 920-1192 (Japan)

    2014-11-01

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

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

    Science.gov (United States)

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

    2014-11-01

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

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

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    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

  9. 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

  10. VPS35 regulates developing mouse hippocampal neuronal morphogenesis by promoting retrograde trafficking of BACE1

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    Chun-Lei Wang

    2012-10-01

    VPS35, a major component of the retromer, plays an important role in the selective endosome-to-Golgi retrieval of membrane proteins. Dysfunction of retromer is a risk factor for neurodegenerative disorders, but its function in developing mouse brain remains poorly understood. Here we provide evidence for VPS35 promoting dendritic growth and maturation, and axonal protein transport in developing mouse hippocampal neurons. Embryonic hippocampal CA1 neurons suppressing Vps35 expression by in utero electroporation of its micro RNAs displayed shortened apical dendrites, reduced dendritic spines, and swollen commissural axons in the neonatal stage, those deficits reflecting a defective protein transport/trafficking in developing mouse neurons. Further mechanistic studies showed that Vps35 depletion in neurons resulted in an impaired retrograde trafficking of BACE1 (β1-secretase and altered BACE1 distribution. Suppression of BACE1 expression in CA1 neurons partially rescued both dendritic and axonal deficits induced by Vps35-deficiency. These results thus demonstrate that BACE1 acts as a critical cargo of retromer in vitro and in vivo, and suggest that VPS35 plays an essential role in regulating apical dendritic maturation and in preventing axonal spheroid formation in developing hippocampal neurons.

  11. Cholesterol depletion of enterocytes. Effect on the Golgi complex and apical membrane trafficking

    DEFF Research Database (Denmark)

    Hansen, Gert Helge; Niels-Christiansen, L L; Thorsen, Evy

    2000-01-01

    Intestinal brush border enzymes, including aminopeptidase N and sucrase-isomaltase, are associated with "rafts" (membrane microdomains rich in cholesterol and sphingoglycolipids). To assess the functional role of rafts in the present work, we studied the effect of cholesterol depletion on apical......, the rates of the Golgi-associated complex glycosylation and association with rafts of newly synthesized aminopeptidase N were reduced, and less of the enzyme had reached the brush border membrane after 2 h of labeling. In contrast, the basolateral Na(+)/K(+)-ATPase was neither missorted nor raft......-associated. Our results implicate the Golgi complex/trans-Golgi network in raft formation and suggest a close relationship between this event and apical membrane trafficking....

  12. 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...

  13. 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

  14. 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.

  15. IntraGolgi distribution of the Conserved Oligomeric Golgi (COG) complex

    International Nuclear Information System (INIS)

    Vasile, Eliza; Oka, Toshihiko; Ericsson, Maria; Nakamura, Nobuhiro; Krieger, Monty

    2006-01-01

    The Conserved Oligomeric Golgi (COG) complex is an eight-subunit (Cog1-8) peripheral Golgi protein involved in membrane trafficking and glycoconjugate synthesis. COG appears to participate in retrograde vesicular transport and is required to maintain normal Golgi structure and function. COG mutations interfere with normal transport, distribution, and/or stability of Golgi proteins associated with glycoconjugate synthesis and trafficking, and lead to failure of spermatogenesis in Drosophila melanogaster, misdirected migration of gonadal distal tip cells in Caenorhabditis elegans, and type II congenital disorders of glycosylation in humans. The mechanism by which COG influences Golgi structure and function is unclear. Immunogold electron microscopy was used to visualize the intraGolgi distribution of a functional, hemagglutinin epitope-labeled COG subunit, Cog1-HA, that complements the Cog1-deficiency in Cog1-null Chinese hamster ovary cells. COG was found to be localized primarily on or in close proximity to the tips and rims of the Golgi's cisternae and their associated vesicles and on vesicles and vesiculo-tubular structures seen on both the cis and trans-Golgi Network faces of the cisternal stacks, in some cases on COPI containing vesicles. These findings support the proposal that COG is directly involved in controlling vesicular retrograde transport of Golgi resident proteins throughout the Golgi apparatus

  16. Balanced trafficking between the ER and the Golgi apparatus increases protein secretion in yeast

    DEFF Research Database (Denmark)

    Bao, Jichen; Huang, Mingtao; Petranovic, Dina

    2018-01-01

    of ADP-ribosylation factor GTP activating proteins, Gcs1p and Glo3p, which are involved in the process of COPI-coated vesicle formation. Engineering the retrograde trafficking increased the secretion of alpha-amylase but did not induce production of reactive oxygen species. An expanded ER membrane......The yeast Saccharomyces cerevisiae is widely used as a cell factory to produce recombinant proteins. However, S. cerevisiae naturally secretes only a few proteins, such as invertase and the mating alpha factor, and its secretory capacity is limited. It has been reported that engineering protein...... recombinant proteins, endoglucanase I from Trichoderma reesei and glucan-1,4-alpha-glucosidase from Rhizopus oryzae, indicating overexpression of GLO3 in a SEC16 moderate overexpression strain might be a general strategy for improving production of secreted proteins by yeast....

  17. 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

  18. Structurally optimized analogs of the retrograde trafficking inhibitor Retro-2cycl limit Leishmania infections.

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    Craig, Evan; Huyghues-Despointes, Charles-Eugene; Yu, Chun; Handy, Emma L; Sello, Jason K; Kima, Peter E

    2017-05-01

    In infected mammalian cells, Leishmania parasites reside within specialized compartments called parasitophorous vacuoles (LPVs). We have previously shown that Retro-2, a member of a novel class of small retrograde pathway inhibitors caused reduced LPV sizes and lower parasite numbers during experimental L. mexicana sp. infections. The purpose of this study was to determine if structural analogs of Retro-2cycl reported to have superior potency in the inhibition of retrograde pathway-dependent phenomena (i.e., polyomavirus cellular infection by polyomavrius and Shiga toxin trafficking in cells) are also more effective than the parent compound at controlling Leishmania infections. In addition to their effects on LPV development, we show that two optimized analogs of Retro-2cycl, DHQZ 36 and DHQZ 36.1 limit Leishmania amazonensis infection in macrophages at EC50 of 13.63+/-2.58μM and10.57+/-2.66μM, respectively, which is significantly lower than 40.15μM the EC50 of Retro-2cycl. In addition, these analogs caused a reversal in Leishmania induced suppression of IL-6 release by infected cells after LPS activation. Moreover, we show that in contrast to Retro-2cycl that is Leishmania static, the analogs can kill Leishmania parasites in axenic cultures, which is a desirable attribute for any drug to treat Leishmania infections. Together, these studies validate and extend the published structure-activity relationship analyses of Retro-2cycl.

  19. Insights into the internalization and retrograde trafficking of Dengue 2 virus in BHK-21 cells.

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    Nidhi Shrivastava

    Full Text Available BACKGROUND: Dengue virus (DENV enters cells via endocytosis, traffics to perinuclear (PN region, the site of morphogenesis and exits by exocytosis. This study aims to understand the role of dynamin II, endosomes, microtubules (MT and dynein in the early events of DENV replication. FINDINGS: Using double immunoflourescence labelling of DENV-2 infected BHK-21 cells it was observed that the surface envelope (E protein of the virion associated with dynamin II from 0-30 min post infection (p.i.. The sphincter like array of dynamin II supported its pinchase-like activity. The association with endosomes was observed from 0 min at cell periphery to 30 min in the perinuclear (PN region, suggesting that internalization continued for 30 min. Association of E protein with alpha-tubulin was observed from 8 h indicating that it was the newly translated protein that trafficked on the MT. Dynein was found to associate with the E protein from 4 h in the cytoplasm to 48 h in the PN region and dissociate at 72 h. Association of E protein with dynein was confirmed by immunoprecipitation. Overexpression of dynamitin, which disrupts the dynein complex, resulted in loss of trafficking of viral E and core proteins. The findings corroborated with the growth kinetics assessed by quantitation of viral RNA in infected BHK-21 cells. The detection of E protein at 4 h-8 h correlated with detectable increase in viral RNA from 8 h. The detection of high concentrations of E protein in the PN region at 24-48 h coincided with release of virus into the supernatant starting from 36 h p.i. The dissociation of dynein from E protein by 72 h was coincident with maximum release of virus, hinting at a possible negative feedback for viral protein translation. CONCLUSION: The study shows for the first time the association of dynamin II with DENV-2 during entry and dynein dependent retrograde trafficking of DENV proteins on microtubules.

  20. 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.

  1. Retrograde trafficking of tracer protein by the internal ovarian epithelium in gravid goodeid teleosts.

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    Schindler, J F

    1990-02-01

    Gravid goodeid females harbor embryos in a preformed ovarian cavity for prolonged periods of gestation. Various nutrients for embryonic growth are provided by the internal ovarian epithelium (IOE). Its cells flatten during late stages of gestation and form an attenuated layer of cytoplasm covering a dense network of protruding capillaries, with the nuclear domains mostly recessing between the vascular meshes. The IOE in both Xenotoca eiseni and Girardinichthys viviparus exhibit morphological features associated with vesicular transport of macromolecules. The amounts of rough endoplasmic reticulum in the IOE cells seem insufficient to effectively synthesise proteinaceous secretions. Apparently, it rather serves as a transit route for serum-derived products. Cationized ferritin (CF) was injected into the ovarian cavity of gravid females. The electrostatic ligand spotwise attached to the luminal surface of the IOE and gained access by adsorptive micropinocytosis. Many tracer molecules were sequestered into lysosome-like vacuoles that became increasingly swollen after prolonged incubation intervals. In addition, CF traversed the IOE within small vesicles. At the basal pole of the cells the contents of transcytotic vesicles were evacuated, and localization of small CF-clusters was regularly in the basement lamina, in the underlying connective tissue, in vacuoles within migrant cells, in vesicular compartments of the capillary endothelia, in capillary lumina, and in intravascular leucocytes. Tracer molecules were never observed to enter stacked Golgi cisternae. Since the cationic marker probably follows retrograde pathways of the protein secretion, the experimental data support the morphologically derived conclusions that postulate a major role for the IOE in transepithelial transport.

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

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    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.

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

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    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

  4. The golgin GMAP-210 is required for efficient membrane trafficking in the early secretory pathway.

    Science.gov (United States)

    Roboti, Peristera; Sato, Keisuke; Lowe, Martin

    2015-04-15

    Golgins are coiled-coil proteins that participate in membrane-tethering events at the Golgi complex. Golgin-mediated tethering is thought to be important for vesicular trafficking and Golgi organization. However, the degree to which individual golgins contribute to these processes is poorly defined, and it has been proposed that golgins act in a largely redundant manner. Previous studies on the golgin GMAP-210 (also known as TRIP11), which is mutated in the rare skeletal disorder achondrogenesis type 1A, have yielded conflicting results regarding its involvement in trafficking. Here, we re-investigated the trafficking role of GMAP-210, and found that it is indeed required for efficient trafficking in the secretory pathway. GMAP-210 acts at both the endoplasmic reticulum (ER)-to-Golgi intermediate compartment (ERGIC) and Golgi complex during anterograde trafficking, and is also required for retrograde trafficking to the ER. Using co-depletion experiments, we also found that GMAP-210 acts in a partially redundant manner with the golgin GM130 to ensure efficient anterograde cargo delivery to the cis-Golgi. In summary, our results indicate a role for GMAP-210 in several trafficking steps at the ER-Golgi interface, some of which are partially redundant with another golgin, namely GM130 (also known as GOLGA2). © 2015. Published by The Company of Biologists Ltd.

  5. Human Ubc9 is involved in intracellular HIV-1 Env stability after trafficking out of the trans-Golgi network in a Gag dependent manner.

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    Christopher R Bohl

    Full Text Available The cellular E2 Sumo conjugase, Ubc9 interacts with HIV-1 Gag, and is important for the assembly of infectious HIV-1 virions. In the previous study we demonstrated that in the absence of Ubc9, a defect in virion assembly was associated with decreased levels of mature intracellular Envelope (Env that affected Env incorporation into virions and virion infectivity. We have further characterized the effect of Ubc9 knockdown on HIV Env processing and assembly. We found that gp160 stability in the endoplasmic reticulum (ER and its trafficking to the trans-Golgi network (TGN were unaffected, indicating that the decreased intracellular mature Env levels in Ubc9-depleted cells were due to a selective degradation of mature Env gp120 after cleavage from gp160 and trafficked out of the TGN. Decreased levels of Gag and mature Env were found to be associated with the plasma membrane and lipid rafts, which suggest that these viral proteins were not trafficked correctly to the assembly site. Intracellular gp120 were partially rescued when treated with a combination of lysosome inhibitors. Taken together our results suggest that in the absence of Ubc9, gp120 is preferentially degraded in the lysosomes likely before trafficking to assembly sites leading to the production of defective virions. This study provides further insight in the processing and packaging of the HIV-1 gp120 into mature HIV-1 virions.

  6. 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.

  7. The epithelial cell cytoskeleton and intracellular trafficking. I. Shiga toxin B-subunit system: retrograde transport, intracellular vectorization, and more.

    Science.gov (United States)

    Johannes, Ludger

    2002-07-01

    Many intracellular transport routes are still little explored. This is particularly true for retrograde transport between the plasma membrane and the endoplasmic reticulum. Shiga toxin B subunit has become a powerful tool to study this pathway, and recent advances on the molecular mechanisms of transport in the retrograde route and on its physiological function(s) are summarized. Furthermore, it is discussed how the study of retrograde transport of Shiga toxin B subunit allows one to design new methods for the intracellular delivery of therapeutic compounds.

  8. 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

  9. Proteomic dissection of the Arabidopsis Golgi and trans-Golgi network

    DEFF Research Database (Denmark)

    Parsons, Harriet Tempé; Drakakaki, Georgia; Heazlewood, Joshua L.

    2013-01-01

    The plant Golgi apparatus and trans-Golgi network are major endomembrane trafficking hubs within the plant cell and are involved in a diverse and vital series of functions to maintain plant growth and development. Recently, a series of disparate technical approaches have been used to isolate...

  10. Rsp5 ubiquitin ligase is required for protein trafficking in Saccharomyces cerevisiae COPI mutants.

    Directory of Open Access Journals (Sweden)

    Katarzyna Jarmoszewicz

    Full Text Available Retrograde trafficking from the Golgi to the endoplasmic reticulum (ER depends on the formation of vesicles coated with the multiprotein complex COPI. In Saccharomyces cerevisiae ubiquitinated derivatives of several COPI subunits have been identified. The importance of this modification of COPI proteins is unknown. With the exception of the Sec27 protein (β'COP neither the ubiquitin ligase responsible for ubiquitination of COPI subunits nor the importance of this modification are known. Here we find that the ubiquitin ligase mutation, rsp5-1, has a negative effect that is additive with ret1-1 and sec28Δ mutations, in genes encoding α- and ε-COP, respectively. The double ret1-1 rsp5-1 mutant is also more severely defective in the Golgi-to-ER trafficking compared to the single ret1-1, secreting more of the ER chaperone Kar2p, localizing Rer1p mostly to the vacuole, and increasing sensitivity to neomycin. Overexpression of ubiquitin in ret1-1 rsp5-1 mutant suppresses vacuolar accumulation of Rer1p. We found that the effect of rsp5 mutation on the Golgi-to-ER trafficking is similar to that of sla1Δ mutation in a gene encoding actin cytoskeleton proteins, an Rsp5p substrate. Additionally, Rsp5 and Sla1 proteins were found by co-immunoprecipitation in a complex containing COPI subunits. Together, our results show that Rsp5 ligase plays a role in regulating retrograde Golgi-to-ER trafficking.

  11. 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)

  12. A TOCA/CDC-42/PAR/WAVE functional module required for retrograde endocytic recycling

    Science.gov (United States)

    Bai, Zhiyong; Grant, Barth D.

    2015-01-01

    Endosome-to-Golgi transport is required for the function of many key membrane proteins and lipids, including signaling receptors, small-molecule transporters, and adhesion proteins. The retromer complex is well-known for its role in cargo sorting and vesicle budding from early endosomes, in most cases leading to cargo fusion with the trans-Golgi network (TGN). Transport from recycling endosomes to the TGN has also been reported, but much less is understood about the molecules that mediate this transport step. Here we provide evidence that the F-BAR domain proteins TOCA-1 and TOCA-2 (Transducer of Cdc42 dependent actin assembly), the small GTPase CDC-42 (Cell division control protein 42), associated polarity proteins PAR-6 (Partitioning defective 6) and PKC-3/atypical protein kinase C, and the WAVE actin nucleation complex mediate the transport of MIG-14/Wls and TGN-38/TGN38 cargo proteins from the recycling endosome to the TGN in Caenorhabditis elegans. Our results indicate that CDC-42, the TOCA proteins, and the WAVE component WVE-1 are enriched on RME-1–positive recycling endosomes in the intestine, unlike retromer components that act on early endosomes. Furthermore, we find that retrograde cargo TGN-38 is trapped in early endosomes after depletion of SNX-3 (a retromer component) but is mainly trapped in recycling endosomes after depletion of CDC-42, indicating that the CDC-42–associated complex functions after retromer in a distinct organelle. Thus, we identify a group of interacting proteins that mediate retrograde recycling, and link these proteins to a poorly understood trafficking step, recycling endosome-to-Golgi transport. We also provide evidence for the physiological importance of this pathway in WNT signaling. PMID:25775511

  13. Subcellular Trafficking of the Papillomavirus Genome during Initial Infection: The Remarkable Abilities of Minor Capsid Protein L2

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    Samuel K. Campos

    2017-12-01

    Full Text Available Since 2012, our understanding of human papillomavirus (HPV subcellular trafficking has undergone a drastic paradigm shift. Work from multiple laboratories has revealed that HPV has evolved a unique means to deliver its viral genome (vDNA to the cell nucleus, relying on myriad host cell proteins and processes. The major breakthrough finding from these recent endeavors has been the realization of L2-dependent utilization of cellular sorting factors for the retrograde transport of vDNA away from degradative endo/lysosomal compartments to the Golgi, prior to mitosis-dependent nuclear accumulation of L2/vDNA. An overview of current models of HPV entry, subcellular trafficking, and the role of L2 during initial infection is provided below, highlighting unresolved questions and gaps in knowledge.

  14. Golgi structure formation, function, and post-translational modifications in mammalian cells.

    Science.gov (United States)

    Huang, Shijiao; Wang, Yanzhuang

    2017-01-01

    The Golgi apparatus is a central membrane organelle for trafficking and post-translational modifications of proteins and lipids in cells. In mammalian cells, it is organized in the form of stacks of tightly aligned flattened cisternae, and dozens of stacks are often linked laterally into a ribbon-like structure located in the perinuclear region of the cell. Proper Golgi functionality requires an intact architecture, yet Golgi structure is dynamically regulated during the cell cycle and under disease conditions. In this review, we summarize our current understanding of the relationship between Golgi structure formation, function, and regulation, with focus on how post-translational modifications including phosphorylation and ubiquitination regulate Golgi structure and on how Golgi unstacking affects its functions, in particular, protein trafficking, glycosylation, and sorting in mammalian cells.

  15. Arf6-Dependent Intracellular Trafficking of Pasteurella multocida Toxin and pH-Dependent Translocation from Late Endosomes

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    Tracy P. M. Chong

    2011-03-01

    Full Text Available The potent mitogenic toxin from Pasteurella multocida (PMT is the major virulence factor associated with a number of epizootic and zoonotic diseases caused by infection with this respiratory pathogen. PMT is a glutamine-specific protein deamidase that acts on its intracellular G-protein targets to increase intracellular calcium, cytoskeletal, and mitogenic signaling. PMT enters cells through receptor-mediated endocytosis and then translocates into the cytosol through a pH-dependent process that is inhibited by NH4Cl or bafilomycin A1. However, the detailed mechanisms that govern cellular entry, trafficking, and translocation of PMT remain unclear. Co-localization studies described herein revealed that while PMT shares an initial entry pathway with transferrin (Tfn and cholera toxin (CT, the trafficking pathways of Tfn, CT, and PMT subsequently diverge, as Tfn is trafficked to recycling endosomes, CT is trafficked retrograde to the ER, and PMT is trafficked to late endosomes. Our studies implicate the small regulatory GTPase Arf6 in the endocytic trafficking of PMT. Translocation of PMT from the endocytic vesicle occurs through a pH-dependent process that is also dependent on both microtubule and actin dynamics, as evidenced by inhibition of PMT activity in our SRE-based reporter assay, with nocodazole and cytochalasin D, respectively, suggesting that membrane translocation and cytotoxicity of PMT is dependent on its transfer to late endosomal compartments. In contrast, disruption of Golgi-ER trafficking with brefeldin A increased PMT activity, suggesting that inhibiting PMT trafficking to non-productive compartments that do not lead to translocation, while promoting formation of an acidic tubulovesicle system more conducive to translocation, enhances PMT translocation and activity.

  16. BPIFB6 Regulates Secretory Pathway Trafficking and Enterovirus Replication.

    Science.gov (United States)

    Morosky, Stefanie; Lennemann, Nicholas J; Coyne, Carolyn B

    2016-05-15

    Bactericidal/permeability-increasing protein (BPI) fold-containing family B, member 3 (BPIFB3) is an endoplasmic reticulum (ER)-localized host factor that negatively regulates coxsackievirus B (CVB) replication through its control of the autophagic pathway. Here, we show that another member of the BPIFB family, BPIFB6, functions as a positive regulator of CVB, and other enterovirus, replication by controlling secretory pathway trafficking and Golgi complex morphology. We show that similar to BPIFB3, BPIFB6 localizes exclusively to the ER, where it associates with other members of the BPIFB family. However, in contrast to our findings that RNA interference (RNAi)-mediated silencing of BPIFB3 greatly enhances CVB replication, we show that silencing of BPIFB6 expression dramatically suppresses enterovirus replication in a pan-viral manner. Mechanistically, we show that loss of BPIFB6 expression induces pronounced alterations in retrograde and anterograde trafficking, which correlate with dramatic fragmentation of the Golgi complex. Taken together, these data implicate BPIFB6 as a key regulator of secretory pathway trafficking and viral replication and suggest that members of the BPIFB family participate in diverse host cell functions to regulate virus infections. Enterovirus infections are associated with a number of severe pathologies, such as aseptic meningitis, dilated cardiomyopathy, type I diabetes, paralysis, and even death. These viruses, which include coxsackievirus B (CVB), poliovirus (PV), and enterovirus 71 (EV71), co-opt the host cell secretory pathway, which controls the transport of proteins from the endoplasmic reticulum to the Golgi complex, to facilitate their replication. Here we report on the identification of a novel regulator of the secretory pathway, bactericidal/permeability-increasing protein (BPI) fold-containing family B, member 6 (BPIFB6), whose expression is required for enterovirus replication. We show that loss of BPIFB6 expression

  17. BPIFB6 Regulates Secretory Pathway Trafficking and Enterovirus Replication

    Science.gov (United States)

    Morosky, Stefanie; Lennemann, Nicholas J.

    2016-01-01

    ABSTRACT Bactericidal/permeability-increasing protein (BPI) fold-containing family B, member 3 (BPIFB3) is an endoplasmic reticulum (ER)-localized host factor that negatively regulates coxsackievirus B (CVB) replication through its control of the autophagic pathway. Here, we show that another member of the BPIFB family, BPIFB6, functions as a positive regulator of CVB, and other enterovirus, replication by controlling secretory pathway trafficking and Golgi complex morphology. We show that similar to BPIFB3, BPIFB6 localizes exclusively to the ER, where it associates with other members of the BPIFB family. However, in contrast to our findings that RNA interference (RNAi)-mediated silencing of BPIFB3 greatly enhances CVB replication, we show that silencing of BPIFB6 expression dramatically suppresses enterovirus replication in a pan-viral manner. Mechanistically, we show that loss of BPIFB6 expression induces pronounced alterations in retrograde and anterograde trafficking, which correlate with dramatic fragmentation of the Golgi complex. Taken together, these data implicate BPIFB6 as a key regulator of secretory pathway trafficking and viral replication and suggest that members of the BPIFB family participate in diverse host cell functions to regulate virus infections. IMPORTANCE Enterovirus infections are associated with a number of severe pathologies, such as aseptic meningitis, dilated cardiomyopathy, type I diabetes, paralysis, and even death. These viruses, which include coxsackievirus B (CVB), poliovirus (PV), and enterovirus 71 (EV71), co-opt the host cell secretory pathway, which controls the transport of proteins from the endoplasmic reticulum to the Golgi complex, to facilitate their replication. Here we report on the identification of a novel regulator of the secretory pathway, bactericidal/permeability-increasing protein (BPI) fold-containing family B, member 6 (BPIFB6), whose expression is required for enterovirus replication. We show that loss of

  18. Rab9-dependent retrograde transport and endosomal sorting of the endopeptidase furin

    Science.gov (United States)

    Chia, Pei Zhi Cheryl; Gasnereau, Isabelle; Lieu, Zi Zhao; Gleeson, Paul A.

    2011-01-01

    The endopeptidase furin and the trans-Golgi network protein TGN38 are membrane proteins that recycle between the TGN and plasma membrane. TGN38 is transported by a retromer-dependent pathway from early endosomes to the TGN, whereas the intracellular transport of furin is poorly defined. Here we have identified the itinerary and transport requirements of furin. Using internalisation assays, we show that furin transits the early and late endosomes en route to the TGN. The GTPase Rab9 and the TGN golgin GCC185, components of the late endosome-to-TGN pathway, were required for efficient TGN retrieval of furin. By contrast, TGN38 trafficking was independent of Rab9 and GCC185. To identify the sorting signals for the early endosome-to-TGN pathway, the trafficking of furin–TGN38 chimeras was investigated. The diversion of furin from the Rab9-dependent late-endosome-to-TGN pathway to the retromer-dependent early-endosome-to-TGN pathway required both the transmembrane domain and cytoplasmic tail of TGN38. We present evidence to suggest that the length of the transmembrane domain is a contributing factor in endosomal sorting. Overall, these data show that furin uses the Rab9-dependent pathway from late endosomes and that retrograde transport directly from early endosomes is dependent on both the transmembrane domain and the cytoplasmic tail. PMID:21693586

  19. 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

  20. 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...

  1. Sphingomyelin synthases regulate protein trafficking and secretion.

    Directory of Open Access Journals (Sweden)

    Marimuthu Subathra

    Full Text Available Sphingomyelin synthases (SMS1 and 2 represent a class of enzymes that transfer a phosphocholine moiety from phosphatidylcholine onto ceramide thus producing sphingomyelin and diacylglycerol (DAG. SMS1 localizes at the Golgi while SMS2 localizes both at the Golgi and the plasma membrane. Previous studies from our laboratory showed that modulation of SMS1 and, to a lesser extent, of SMS2 affected the formation of DAG at the Golgi apparatus. As a consequence, down-regulation of SMS1 and SMS2 reduced the localization of the DAG-binding protein, protein kinase D (PKD, to the Golgi. Since PKD recruitment to the Golgi has been implicated in cellular secretion through the trans golgi network (TGN, the effect of down-regulation of SMSs on TGN-to-plasma membrane trafficking was studied. Down regulation of either SMS1 or SMS2 significantly retarded trafficking of the reporter protein vesicular stomatitis virus G protein tagged with GFP (VSVG-GFP from the TGN to the cell surface. Inhibition of SMSs also induced tubular protrusions from the trans Golgi network reminiscent of inhibited TGN membrane fission. Since a recent study demonstrated the requirement of PKD activity for insulin secretion in beta cells, we tested the function of SMS in this model. Inhibition of SMS significantly reduced insulin secretion in rat INS-1 cells. Taken together these results provide the first direct evidence that both enzymes (SMS1 and 2 are capable of regulating TGN-mediated protein trafficking and secretion, functions that are compatible with PKD being a down-stream target for SMSs in the Golgi.

  2. The conserved dileucine- and tyrosine-based motifs in MLV and MPMV envelope glycoproteins are both important to regulate a common Env intracellular trafficking

    Directory of Open Access Journals (Sweden)

    Lopez-Vergès Sandra

    2006-09-01

    Full Text Available Abstract Background Retrovirus particles emerge from the assembly of two structural protein components, Gag that is translated as a soluble protein in the cytoplasm of the host cells, and Env, a type I transmembrane protein. Because both components are translated in different intracellular compartments, elucidating the mechanisms of retrovirus assembly thus requires the study of their intracellular trafficking. Results We used a CD25 (Tac chimera-based approach to study the trafficking of Moloney murine leukemia virus and Mason-Pfizer monkey virus Env proteins. We found that the cytoplasmic tails (CTs of both Env conserved two major signals that control a complex intracellular trafficking. A dileucine-based motif controls the sorting of the chimeras from the trans-Golgi network (TGN toward endosomal compartments. Env proteins then follow a retrograde transport to the TGN due to the action of a tyrosine-based motif. Mutation of either motif induces the mis-localization of the chimeric proteins and both motifs are found to mediate interactions of the viral CTs with clathrin adaptors. Conclusion This data reveals the unexpected complexity of the intracellular trafficking of retrovirus Env proteins that cycle between the TGN and endosomes. Given that Gag proteins hijack endosomal host proteins, our work suggests that the endosomal pathway may be used by retroviruses to ensure proper encountering of viral structural Gag and Env proteins in cells, an essential step of virus assembly.

  3. 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

  4. 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...

  5. 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

  6. From mucolipidosis type IV to Ebola: TRPML and two-pore channels at the crossroads of endo-lysosomal trafficking and disease.

    Science.gov (United States)

    Grimm, Christian; Butz, Elisabeth; Chen, Cheng-Chang; Wahl-Schott, Christian; Biel, Martin

    2017-11-01

    What do lysosomal storage disorders such as mucolipidosis type IV have in common with Ebola, cancer cell migration, or LDL-cholesterol trafficking? LDL-cholesterol, certain bacterial toxins and viruses, growth factors, receptors, integrins, macromolecules destined for degradation or secretion are all sorted and transported via the endolysosomal system (ES). There are several pathways known in the ES, e.g. the degradation, the recycling, or the retrograde trafficking pathway. The ES comprises early and late endosomes, lysosomes and recycling endosomes as well as autophagosomes and lysosome related organelles. Contact sites between the ES and the endoplasmic reticulum or the Golgi apparatus may also be considered part of it. Dysfunction of this complex intracellular machinery can cause or contribute to the development of a number of diseases ranging from neurodegenerative, infectious, or metabolic diseases to retinal and pigmentation disorders as well as cancer and autophagy-related diseases. Endolysosomal ion channels such as mucolipins (TRPMLs) and two-pore channels (TPCs) play an important role in intracellular cation/calcium signaling and homeostasis and appear to critically contribute to the proper function of the endolysosomal trafficking network. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Anterograde trafficking of KCa3.1 in polarized epithelia is Rab1- and Rab8-dependent and recycling endosome-independent.

    Directory of Open Access Journals (Sweden)

    Claudia A Bertuccio

    Full Text Available The intermediate conductance, Ca2+-activated K+ channel (KCa3.1 targets to the basolateral (BL membrane in polarized epithelia where it plays a key role in transepithelial ion transport. However, there are no studies defining the anterograde and retrograde trafficking of KCa3.1 in polarized epithelia. Herein, we utilize Biotin Ligase Acceptor Peptide (BLAP-tagged KCa3.1 to address these trafficking steps in polarized epithelia, using MDCK, Caco-2 and FRT cells. We demonstrate that KCa3.1 is exclusively targeted to the BL membrane in these cells when grown on filter supports. Following endocytosis, KCa3.1 degradation is prevented by inhibition of lysosomal/proteosomal pathways. Further, the ubiquitylation of KCa3.1 is increased following endocytosis from the BL membrane and PR-619, a deubiquitylase inhibitor, prevents degradation, indicating KCa3.1 is targeted for degradation by ubiquitylation. We demonstrate that KCa3.1 is targeted to the BL membrane in polarized LLC-PK1 cells which lack the μ1B subunit of the AP-1 complex, indicating BL targeting of KCa3.1 is independent of μ1B. As Rabs 1, 2, 6 and 8 play roles in ER/Golgi exit and trafficking of proteins to the BL membrane, we evaluated the role of these Rabs in the trafficking of KCa3.1. In the presence of dominant negative Rab1 or Rab8, KCa3.1 cell surface expression was significantly reduced, whereas Rabs 2 and 6 had no effect. We also co-immunoprecipitated KCa3.1 with both Rab1 and Rab8. These results suggest these Rabs are necessary for the anterograde trafficking of KCa3.1. Finally, we determined whether KCa3.1 traffics directly to the BL membrane or through recycling endosomes in MDCK cells. For these studies, we used either recycling endosome ablation or dominant negative RME-1 constructs and determined that KCa3.1 is trafficked directly to the BL membrane rather than via recycling endosomes. These results are the first to describe the anterograde and retrograde trafficking of KCa3

  8. Human Trafficking

    Science.gov (United States)

    Wilson, David McKay

    2011-01-01

    The shadowy, criminal nature of human trafficking makes evaluating its nature and scope difficult. The U.S. State Department and anti-trafficking groups estimate that worldwide some 27 million people are caught in a form of forced servitude today. Public awareness of modern-day slavery is gaining momentum thanks to new abolitionist efforts. Among…

  9. Retrograde peri-implantitis

    Directory of Open Access Journals (Sweden)

    Mohamed Jumshad

    2010-01-01

    Full Text Available Retrograde peri-implantitis constitutes an important cause for implant failure. Retrograde peri-implantitis may sometimes prove difficult to identify and hence institution of early treatment may not be possible. This paper presents a report of four cases of (the implant placed developing to retrograde peri-implantitis. Three of these implants were successfully restored to their fully functional state while one was lost due to extensive damage. The paper highlights the importance of recognizing the etiopathogenic mechanisms, preoperative assessment, and a strong postoperative maintenance protocol to avoid retrograde peri-implant inflammation.

  10. Characterization of ATP7A missense mutants suggests a correlation between intracellular trafficking and severity of Menkes disease

    DEFF Research Database (Denmark)

    Skjørringe, Tina; Pedersen, Per Amstrup; Thorborg, Sidsel Salling

    2017-01-01

    Menkes disease (MD) is caused by mutations in ATP7A, encoding a copper-transporting P-type ATPase which exhibits copper-dependent trafficking. ATP7A is found in the Trans-Golgi Network (TGN) at low copper concentrations, and in the post-Golgi compartments and the plasma membrane at higher...

  11. Rebooting Trafficking

    Directory of Open Access Journals (Sweden)

    Nicholas de Villiers

    2016-09-01

    Full Text Available While popular psychology and appeals to emotion have unfortunately dominated discussions of ‘sex trafficking’, this article suggests that feminist psychoanalytic film theory and theories of affect are still useful for making sense of the appeal of sensational exposés like Lifetime Television’s Human Trafficking (2005. The dynamic of identification with (and impersonation of a human trafficking ‘victim’ by the rescuing Immigration and Customs Enforcement agent (Mira Sorvino is particularly worthy of scrutiny. Film theory about the ‘rebooting’ of film franchises (iconic brands like Batman also helps explain the preponderance of similar programming—Sex Slaves (2005, Selling the Girl Next Door (2011, Trafficked (2016—and the way contemporary discourses of human trafficking have effectively rebranded the myth of ‘white slavery’.

  12. The trans-Golgi Network and the Golgi Stacks Behave Independently During Regeneration After Brefeldin A Treatment in Tobacco BY-2 Cells.

    Science.gov (United States)

    Ito, Yoko; Toyooka, Kiminori; Fujimoto, Masaru; Ueda, Takashi; Uemura, Tomohiro; Nakano, Akihiko

    2017-04-01

    The trans-Golgi network (TGN) plays an essential role in intracellular membrane trafficking. In plant cells, recent live-cell imaging studies have revealed the dynamic behavior of the TGN independent from the Golgi apparatus. In order to better understand the relationships between the two organelles, we examined their dynamic responses to the reagent brefeldin A (BFA) and their recovery after BFA removal. Golgi markers responded to BFA similarly over a range of concentrations, whereas the behavior of the TGN was BFA concentration dependent. The TGN formed aggregates at high concentrations of BFA; however, TGN proteins relocalized to numerous small vesicular structures dispersed throughout the cytoplasm at lower BFA concentrations. During recovery from weak BFA treatment, the TGN started to regenerate earlier than the completion of the Golgi. The regeneration of the two organelles proceeded independently of each other for a while, and eventually was completed by their association. Our data suggest that there is some degree of autonomy for the regeneration of the TGN and the Golgi in tobacco BY-2 cells. © The Author 2017. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  13. Rab7b at the intersection of intracellular trafficking and cell migration.

    Science.gov (United States)

    Distefano, Marita Borg; Kjos, Ingrid; Bakke, Oddmund; Progida, Cinzia

    2015-01-01

    Rab proteins are small GTPases essential for controlling and coordinating intracellular traffic. The small GTPase Rab7b regulates the retrograde transport from late endosomes toward the Trans-Golgi Network (TGN), and is important for the proper trafficking of several receptors such as Toll-like receptors (TLRs) and sorting receptors. We recently identified the actin motor protein myosin II as a new interaction partner for Rab7b, and found that Rab7b transport is dependent on myosin II. Interestingly, we also discovered that Rab7b influences the phosphorylation state of myosin II by controlling the activation status of the small GTPase RhoA. Consequently, Rab7b is important for the remodeling of actin filaments in processes such as stress fiber formation, cell adhesion, polarization and cell migration. Our finding that Rab7b can control actomyosin reorganization reveals yet another important role for Rab proteins, in addition to their already established role as master regulators of intracellular transport. Here we discuss our findings and speculate how they can explain the importance of Rab7b in dendritic cells (DCs).

  14. Retrograde pulmonary arteriography

    International Nuclear Information System (INIS)

    Calcaterra, G.; Lam, J.; Losekoot, T.G.

    1984-01-01

    The authors performed retrograde pulmonary arteriography by means of a pulmonary venous wedge injection in 10 patients with no demonstrable intrapericardial pulmonary arteries by 'conventional' angiographic techniques. In all cases but one, the procedure demonstrated the feasibility of a further operation. No complications were observed. Retrograde pulmonary arteriography is an important additional method for determining the existence of surgically accessible pulmonary arteries when other techniques have failed. (Auth.)

  15. 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....

  16. 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.

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

    Science.gov (United States)

    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.

  18. 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.

  19. 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.

  20. The golgin GMAP-210 is required for efficient membrane trafficking in the early secretory pathway

    OpenAIRE

    Roboti, Peristera; Sato, Keisuke; Lowe, Martin

    2015-01-01

    Golgins are coiled-coil proteins that participate in membrane-tethering events at the Golgi complex. Golgin-mediated tethering is thought to be important for vesicular trafficking and Golgi organization. However, the degree to which individual golgins contribute to these processes is poorly defined, and it has been proposed that golgins act in a largely redundant manner. Previous studies on the golgin GMAP-210 (also known as TRIP11), which is mutated in the rare skeletal disorder achondrogene...

  1. The Proteome of the Isolated Chlamydia trachomatis Containing Vacuole Reveals a Complex Trafficking Platform Enriched for Retromer Components.

    Directory of Open Access Journals (Sweden)

    Lukas Aeberhard

    2015-06-01

    Full Text Available Chlamydia trachomatis is an important human pathogen that replicates inside the infected host cell in a unique vacuole, the inclusion. The formation of this intracellular bacterial niche is essential for productive Chlamydia infections. Despite its importance for Chlamydia biology, a holistic view on the protein composition of the inclusion, including its membrane, is currently missing. Here we describe the host cell-derived proteome of isolated C. trachomatis inclusions by quantitative proteomics. Computational analysis indicated that the inclusion is a complex intracellular trafficking platform that interacts with host cells' antero- and retrograde trafficking pathways. Furthermore, the inclusion is highly enriched for sorting nexins of the SNX-BAR retromer, a complex essential for retrograde trafficking. Functional studies showed that in particular, SNX5 controls the C. trachomatis infection and that retrograde trafficking is essential for infectious progeny formation. In summary, these findings suggest that C. trachomatis hijacks retrograde pathways for effective infection.

  2. 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.

  3. 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.

  4. Membrane Trafficking Modulation during Entamoeba Encystation.

    Science.gov (United States)

    Herman, Emily; Siegesmund, Maria A; Bottery, Michael J; van Aerle, Ronny; Shather, Maulood Mohammed; Caler, Elisabet; Dacks, Joel B; van der Giezen, Mark

    2017-10-09

    Entamoeba histolytica is an intestinal parasite that infects 50-100 million people and causes up to 55,000 deaths annually. The transmissive form of E. histolytica is the cyst, with a single infected individual passing up to 45 million cysts per day, making cyst production an attractive target for infection control. Lectins and chitin are secreted to form the cyst wall, although little is known about the underlying membrane trafficking processes supporting encystation. As E. histolytica does not readily form cysts in vitro, we assessed membrane trafficking gene expression during encystation in the closely related model Entamoeba invadens. Genes involved in secretion are up-regulated during cyst formation, as are some trans-Golgi network-to-endosome trafficking genes. Furthermore, endocytic and general trafficking genes are up-regulated in the mature cyst, potentially preserved as mRNA in preparation for excystation. Two divergent dynamin-related proteins found in Entamoeba are predominantly expressed during cyst formation. Phylogenetic analyses indicate that they are paralogous to, but quite distinct from, classical dynamins found in human, suggesting that they may be potential drug targets to block encystation. The membrane-trafficking machinery is clearly regulated during encystation, providing an additional facet to understanding this crucial parasitic process.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  7. BACE1 protein endocytosis and trafficking are differentially regulated by ubiquitination at lysine 501 and the Di-leucine motif in the carboxyl terminus.

    Science.gov (United States)

    Kang, Eugene L; Biscaro, Barbara; Piazza, Fabrizio; Tesco, Giuseppina

    2012-12-14

    β-Site amyloid precursor protein-cleaving enzyme (BACE1) is a membrane-tethered member of the aspartyl proteases that has been identified as β-secretase. BACE1 is targeted through the secretory pathway to the plasma membrane and then is internalized to endosomes. Sorting of membrane proteins to the endosomes and lysosomes is regulated by the interaction of signals present in their carboxyl-terminal fragment with specific trafficking molecules. The BACE1 carboxyl-terminal fragment contains a di-leucine sorting signal ((495)DDISLL(500)) and a ubiquitination site at Lys-501. Here, we report that lack of ubiquitination at Lys-501 (BACE1K501R) does not affect the rate of endocytosis but produces BACE1 stabilization and accumulation of BACE1 in early and late endosomes/lysosomes as well as at the cell membrane. In contrast, the disruption of the di-leucine motif (BACE1LLAA) greatly impairs BACE1 endocytosis and produces a delayed retrograde transport of BACE1 to the trans-Golgi network (TGN) and a delayed delivery of BACE1 to the lysosomes, thus decreasing its degradation. Moreover, the combination of the lack of ubiquitination at Lys-501 and the disruption of the di-leucine motif (BACE1LLAA/KR) produces additive effects on BACE1 stabilization and defective internalization. Finally, BACE1LLAA/KR accumulates in the TGN, while its levels are decreased in EEA1-positive compartments indicating that both ubiquitination at Lys-501 and the di-leucine motif are necessary for the trafficking of BACE1 from the TGN to early endosomes. Our studies have elucidated a differential role for the di-leucine motif and ubiquitination at Lys-501 in BACE1 endocytosis, trafficking, and degradation and suggest the involvement of multiple adaptor molecules.

  8. BACE1 Protein Endocytosis and Trafficking Are Differentially Regulated by Ubiquitination at Lysine 501 and the Di-leucine Motif in the Carboxyl Terminus*

    Science.gov (United States)

    Kang, Eugene L.; Biscaro, Barbara; Piazza, Fabrizio; Tesco, Giuseppina

    2012-01-01

    β-Site amyloid precursor protein-cleaving enzyme (BACE1) is a membrane-tethered member of the aspartyl proteases that has been identified as β-secretase. BACE1 is targeted through the secretory pathway to the plasma membrane and then is internalized to endosomes. Sorting of membrane proteins to the endosomes and lysosomes is regulated by the interaction of signals present in their carboxyl-terminal fragment with specific trafficking molecules. The BACE1 carboxyl-terminal fragment contains a di-leucine sorting signal (495DDISLL500) and a ubiquitination site at Lys-501. Here, we report that lack of ubiquitination at Lys-501 (BACE1K501R) does not affect the rate of endocytosis but produces BACE1 stabilization and accumulation of BACE1 in early and late endosomes/lysosomes as well as at the cell membrane. In contrast, the disruption of the di-leucine motif (BACE1LLAA) greatly impairs BACE1 endocytosis and produces a delayed retrograde transport of BACE1 to the trans-Golgi network (TGN) and a delayed delivery of BACE1 to the lysosomes, thus decreasing its degradation. Moreover, the combination of the lack of ubiquitination at Lys-501 and the disruption of the di-leucine motif (BACE1LLAA/KR) produces additive effects on BACE1 stabilization and defective internalization. Finally, BACE1LLAA/KR accumulates in the TGN, while its levels are decreased in EEA1-positive compartments indicating that both ubiquitination at Lys-501 and the di-leucine motif are necessary for the trafficking of BACE1 from the TGN to early endosomes. Our studies have elucidated a differential role for the di-leucine motif and ubiquitination at Lys-501 in BACE1 endocytosis, trafficking, and degradation and suggest the involvement of multiple adaptor molecules. PMID:23109336

  9. Economics of human trafficking.

    Science.gov (United States)

    Wheaton, Elizabeth M; Schauer, Edward J; Galli, Thomas V

    2010-01-01

    Because freedom of choice and economic gain are at the heart of productivity, human trafficking impedes national and international economic growth. Within the next 10 years, crime experts expect human trafficking to surpass drug and arms trafficking in its incidence, cost to human well-being, and profitability to criminals (Schauer and Wheaton, 2006: 164-165). The loss of agency from human trafficking as well as from modern slavery is the result of human vulnerability (Bales, 2000: 15). As people become vulnerable to exploitation and businesses continually seek the lowest-cost labour sources, trafficking human beings generates profit and a market for human trafficking is created. This paper presents an economic model of human trafficking that encompasses all known economic factors that affect human trafficking both across and within national borders. We envision human trafficking as a monopolistically competitive industry in which traffickers act as intermediaries between vulnerable individuals and employers by supplying differentiated products to employers. In the human trafficking market, the consumers are employers of trafficked labour and the products are human beings. Using a rational-choice framework of human trafficking we explain the social situations that shape relocation and working decisions of vulnerable populations leading to human trafficking, the impetus for being a trafficker, and the decisions by employers of trafficked individuals. The goal of this paper is to provide a common ground upon which policymakers and researchers can collaborate to decrease the incidence of trafficking in humans.

  10. Protein trafficking and maturation regulate intramembrane proteolysis.

    Science.gov (United States)

    Morohashi, Yuichi; Tomita, Taisuke

    2013-12-01

    Intramembrane-cleaving proteases (I-CLiPs) are membrane embedded proteolytic enzymes. All substrates identified so far are also membrane proteins, involving a number of critical cellular signaling as well as human diseases. After synthesis and assembly at the endoplasmic reticulum, membrane proteins are exported to the Golgi apparatus and transported to their sites of action. A number of studies have revealed the importance of the intracellular membrane trafficking in i-CLiP-mediated intramembrane proteolysis, not only for limiting the unnecessary encounter between i-CLiPs and their substrate but also for their cleavage site preference. In this review, we will discuss recent advances in our understanding of how each i-CLiP proteolysis is regulated by intracellular vesicle trafficking. This article is part of a Special Issue entitled: Intramembrane Proteases. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. 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.

  12. 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.

  13. 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

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

    Directory of Open Access Journals (Sweden)

    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

  15. Endoscopic retrograde cholanglopancreatography

    International Nuclear Information System (INIS)

    Horii, S.C.; Garra, B.S.; Zeman, R.K.; Krasner, B.H.; Lo, S.C.B.; Davros, W.J.; Silverman, P.M.; Cattau, E.L.; Fleischer, D.E.; Benjamin, S.B.S.B.

    1989-01-01

    As part of the clinical evaluation of image management and communications system (IMACS), the authors undertook a prospective study to compare conventional film versus digitized film viewed on a workstation. Twenty-five each of normal and abnormal endoscopic retrograde cholangiopancreatographic (ERCP) studies were digitized with a 1,684 x 2,048-pixel matrix and evaluated in a single-blind fashion on the workstation. The resulting interpretations were then compared with those resulting from interpretation of film (spot film and 100-mm photospot) images. They report that no significant differences were found in ability to see anatomic detail or pathology. A second study involved performing 10 ERCP studies in a lithotripsy suite equipped with biplane digital fluoroscopy. The digital video displays were comparable in quality to that of film. Progress is being made in using the IMACS for archiving and retrieval of all current ERCP images

  16. Squalestatin alters the intracellular trafficking of a neurotoxic prion peptide

    Directory of Open Access Journals (Sweden)

    Williams Alun

    2007-11-01

    Full Text Available Abstract Background Neurotoxic peptides derived from the protease-resistant core of the prion protein are used to model the pathogenesis of prion diseases. The current study characterised the ingestion, internalization and intracellular trafficking of a neurotoxic peptide containing amino acids 105–132 of the murine prion protein (MoPrP105-132 in neuroblastoma cells and primary cortical neurons. Results Fluorescence microscopy and cell fractionation techniques showed that MoPrP105-132 co-localised with lipid raft markers (cholera toxin and caveolin-1 and trafficked intracellularly within lipid rafts. This trafficking followed a non-classical endosomal pathway delivering peptide to the Golgi and ER, avoiding classical endosomal trafficking via early endosomes to lysosomes. Fluorescence resonance energy transfer analysis demonstrated close interactions of MoPrP105-132 with cytoplasmic phospholipase A2 (cPLA2 and cyclo-oxygenase-1 (COX-1, enzymes implicated in the neurotoxicity of prions. Treatment with squalestatin reduced neuronal cholesterol levels and caused the redistribution of MoPrP105-132 out of lipid rafts. In squalestatin-treated cells, MoPrP105-132 was rerouted away from the Golgi/ER into degradative lysosomes. Squalestatin treatment also reduced the association between MoPrP105-132 and cPLA2/COX-1. Conclusion As the observed shift in peptide trafficking was accompanied by increased cell survival these studies suggest that the neurotoxicity of this PrP peptide is dependent on trafficking to specific organelles where it activates specific signal transduction pathways.

  17. 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.

  18. 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.

  19. Novel Class of Potential Therapeutics that Target Ricin Retrograde Translocation

    Directory of Open Access Journals (Sweden)

    Veronika Redmann

    2013-12-01

    Full Text Available Ricin toxin, an A-B toxin from Ricinus communis, induces cell death through the inhibition of protein synthesis. The toxin binds to the cell surface via its B chain (RTB followed by its retrograde trafficking through intracellular compartments to the ER where the A chain (RTA is transported across the membrane and into the cytosol. Ricin A chain is transported across the ER membrane utilizing cellular proteins involved in the disposal of aberrant ER proteins by a process referred to as retrograde translocation. Given the current lack of therapeutics against ricin intoxication, we developed a high-content screen using an enzymatically attenuated RTA chimera engineered with a carboxy-terminal enhanced green fluorescent protein (RTAE177Qegfp to identify compounds that target RTA retrograde translocation. Stabilizing RTAE177Qegfp through the inclusion of proteasome inhibitor produced fluorescent peri-nuclear granules. Quantitative analysis of the fluorescent granules provided the basis to discover compounds from a small chemical library (2080 compounds with known bioactive properties. Strikingly, the screen found compounds that stabilized RTA molecules within the cell and several compounds limited the ability of wild type RTA to suppress protein synthesis. Collectively, a robust high-content screen was developed to discover novel compounds that stabilize intracellular ricin and limit ricin intoxication.

  20. 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.

  1. 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.

  2. Smuggled or trafficked?

    Directory of Open Access Journals (Sweden)

    Jacqueline Bhabha

    2006-05-01

    Full Text Available The UN Convention Against Transnational Organized Crime (TNC and its two Protocols on Trafficking and Smuggling, adopted in 2000, seek to distinguish between trafficking and smuggling. In reality these distinctions are often blurred. A more nuanced approach is needed to ensure protection for all those at risk.

  3. An imaging flow cytometry method to assess ricin trafficking in A549 human lung epithelial cells.

    Science.gov (United States)

    Jenner, Dominic; Chong, Damien; Walker, Nicola; Green, A Christopher

    2018-02-01

    The endocytosis and trafficking of ricin in mammalian cells is an important area of research for those producing ricin anti-toxins and other ricin therapeutics. Ricin trafficking is usually observed by fluorescence microscopy techniques. This gives good resolution and leads to a detailed understanding of the internal movement of ricin within cells. However, microscopy techniques are often hampered by complex analysis and quantification techniques, and the inability to look at ricin trafficking in large populations of cells. In these studies we have directly labelled ricin and assessed if its trafficking can be observed using Imaging Flow Cytometry (IFC) both to the cytoplasmic region of cells and specifically to the Golgi apparatus. Using IDEAS® data analysis software the specific fluorescence location of the ricin within the cells was analysed. Then, using cytoplasmic masking techniques to quantify the number of cells with endocytosed cytoplasmic ricin or cells with Golgi-associated ricin, kinetic endocytosis curves were generated. Here we present, to the authors' knowledge, the first example of using imaging flow cytometry for evaluating the subcellular transport of protein cargo, using the trafficking of ricin toxin in lung cells as a model. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  4. 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).

  5. Exo- and endocytotic trafficking of SCAMP2.

    Science.gov (United States)

    Toyooka, Kiminori; Matsuoka, Ken

    2009-12-01

    Exo- and endocytotic membrane trafficking is an essential process for transport of secretory proteins, extracellular glycans, transporters and lipids in plant cells. Using secretory carrier membrane protein 2 (SCAMP2) as a marker for secretory vesicles and tobacco BY-2 cells as a model system, we recently demonstrated that SCAMP2 positive structures containing secretory materials are transported from the Golgi apparatus to the plasma membrane (PM) and/or cell plate. This structure is consisted with clustered vesicles and was thus named the secretory vesicle cluster (SVC). Here, we have utilized the reversible photoswitching fluorescent protein Dronpa1 to trace the movement of SCAMP2 on the PM and cell plate. Activated SCAMP2-Dronpa fluorescence on the PM and cell plate moved into the BY-2 cells within several minutes, but did not spread around PM. This is consistent with recycling of SCAMP2 among endomembrane compartments such as the TGN, PM and cell plate. The relationship between SVC-mediated trafficking and exo- and endocytosis of plant cells is discussed taking into account this new data and knowledge provided by recent reports.

  6. Endoscopic retrograde cholangiopancreatography and endoscopic ...

    African Journals Online (AJOL)

    An approach to suspected gallstone pancreatitis'based on endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincterotomy (ES) was adopted in 1976 and was followed in 29 patients. ERCp became the routine method of early biliary tract assessment when gallstone pancreatitis was suspected on ...

  7. Colonic perforation following endoscopic retrograde ...

    African Journals Online (AJOL)

    We highlight a potentially lethal complication of acute severe pancreatitis that may not be suspected in severely ill patients. A 41-year-old woman developed acute severe pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP) for suspected choledocholithiasis. When her condition deteriorated ...

  8. GADD34 Function in Protein Trafficking Promotes Adaptation to Hyperosmotic Stress in Human Corneal Cells

    Directory of Open Access Journals (Sweden)

    Dawid Krokowski

    2017-12-01

    Full Text Available Summary: GADD34, a stress-induced regulatory subunit of the phosphatase PP1, is known to function in hyperosmotic stress through its well-known role in the integrated stress response (ISR pathway. Adaptation to hyperosmotic stress is important for the health of corneal epithelial cells exposed to changes in extracellular osmolarity, with maladaptation leading to dry eye syndrome. This adaptation includes induction of SNAT2, an endoplasmic reticulum (ER-Golgi-processed protein, which helps to reverse the stress-induced loss of cell volume and promote homeostasis through amino acid uptake. Here, we show that GADD34 promotes the processing of proteins synthesized on the ER during hyperosmotic stress independent of its action in the ISR. We show that GADD34/PP1 phosphatase activity reverses hyperosmotic-stress-induced Golgi fragmentation and is important for cis- to trans-Golgi trafficking of SNAT2, thereby promoting SNAT2 plasma membrane localization and function. These results suggest that GADD34 is a protective molecule for ocular diseases such as dry eye syndrome. : Here, Krokowski et al. show that GADD34/PP1 protects the microtubule network, prevents Golgi fragmentation, and preserves protein trafficking independent of its action in the integrated stress response (ISR. In osmoadaptation, GADD34 facilitates trans-Golgi-mediated processing of the endoplasmic reticulum (ER-synthesized amino acid transporter SNAT2, which in turn increases amino acid uptake. Keywords: SNAT2, GADD34, hyperosmotic stress, amino acid transport, Golgi fragmentation, ISR

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Host cell interactions of outer membrane vesicle-associated virulence factors of enterohemorrhagic Escherichia coli O157: Intracellular delivery, trafficking and mechanisms of cell injury

    Science.gov (United States)

    Greune, Lilo; Jarosch, Kevin-André; Steil, Daniel; Zhang, Wenlan; He, Xiaohua; Lloubes, Roland; Fruth, Angelika; Kim, Kwang Sik; Schmidt, M. Alexander; Dobrindt, Ulrich; Mellmann, Alexander; Karch, Helge

    2017-01-01

    Outer membrane vesicles (OMVs) are important tools in bacterial virulence but their role in the pathogenesis of infections caused by enterohemorrhagic Escherichia coli (EHEC) O157, the leading cause of life-threatening hemolytic uremic syndrome, is poorly understood. Using proteomics, electron and confocal laser scanning microscopy, immunoblotting, and bioassays, we investigated OMVs secreted by EHEC O157 clinical isolates for virulence factors cargoes, interactions with pathogenetically relevant human cells, and mechanisms of cell injury. We demonstrate that O157 OMVs carry a cocktail of key virulence factors of EHEC O157 including Shiga toxin 2a (Stx2a), cytolethal distending toxin V (CdtV), EHEC hemolysin, and flagellin. The toxins are internalized by cells via dynamin-dependent endocytosis of OMVs and differentially separate from vesicles during intracellular trafficking. Stx2a and CdtV-B, the DNase-like CdtV subunit, separate from OMVs in early endosomes. Stx2a is trafficked, in association with its receptor globotriaosylceramide within detergent-resistant membranes, to the Golgi complex and the endoplasmic reticulum from where the catalytic Stx2a A1 fragment is translocated to the cytosol. CdtV-B is, after its retrograde transport to the endoplasmic reticulum, translocated to the nucleus to reach DNA. CdtV-A and CdtV-C subunits remain OMV-associated and are sorted with OMVs to lysosomes. EHEC hemolysin separates from OMVs in lysosomes and targets mitochondria. The OMV-delivered CdtV-B causes cellular DNA damage, which activates DNA damage responses leading to G2 cell cycle arrest. The arrested cells ultimately die of apoptosis induced by Stx2a and CdtV via caspase-9 activation. By demonstrating that naturally secreted EHEC O157 OMVs carry and deliver into cells a cocktail of biologically active virulence factors, thereby causing cell death, and by performing first comprehensive analysis of intracellular trafficking of OMVs and OMV-delivered virulence factors

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

    Science.gov (United States)

    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

  12. Sex for Sale: Globalization and Human Trafficking

    OpenAIRE

    Aiello, Annmarie

    2009-01-01

    The practice of trafficking has many different facets; drug trafficking, arms trafficking and human trafficking complete the top three illegal trafficking practices today. Human trafficking may be the third highest illegal trafficking practice, however there is inadequate mainstream information on the affects of the trade and horrifying issues that incorporate trafficking in human beings. This paper will discuss how the globalized world has been enabling trafficking in human beings with a con...

  13. UK victims of trafficking

    Directory of Open Access Journals (Sweden)

    Bob Burgoyne

    2006-05-01

    Full Text Available Analysis of court cases shows how hard it is forvictims of trafficking to win the right to remain in the UK. Case law is inconsistent and more research and data collection are urgently needed.

  14. Trafficking in Persons Report

    Science.gov (United States)

    2009-06-01

    people Burmese Lu kon ku de Trade in people French La traite des personnes The trade of people Japanese Jinshin bai bai The buying and selling of...commercial sex among young men. In 2008, the government partially funded an NGO to conduct an anti-trafficking awareness campaign in cinemas and in...A significant number of Japanese women and girls have also been reported as sex trafficking victims. During the last year, a number of Paraguayan

  15. α-Synuclein-induced lysosomal dysfunction occurs through disruptions in protein trafficking in human midbrain synucleinopathy models.

    Science.gov (United States)

    Mazzulli, Joseph R; Zunke, Friederike; Isacson, Ole; Studer, Lorenz; Krainc, Dimitri

    2016-02-16

    Parkinson's disease (PD) is an age-related neurodegenerative disorder characterized by the accumulation of protein aggregates comprised of α-synuclein (α-syn). A major barrier in treatment discovery for PD is the lack of identifiable therapeutic pathways capable of reducing aggregates in human neuronal model systems. Mutations in key components of protein trafficking and cellular degradation machinery represent important risk factors for PD; however, their precise role in disease progression and interaction with α-syn remains unclear. Here, we find that α-syn accumulation reduced lysosomal degradation capacity in human midbrain dopamine models of synucleinopathies through disrupting hydrolase trafficking. Accumulation of α-syn at the cell body resulted in aberrant association with cis-Golgi-tethering factor GM130 and disrupted the endoplasmic reticulum-Golgi localization of rab1a, a key mediator of vesicular transport. Overexpression of rab1a restored Golgi structure, improved hydrolase trafficking and activity, and reduced pathological α-syn in patient neurons. Our work suggests that enhancement of lysosomal hydrolase trafficking may prove beneficial in synucleinopathies and indicates that human midbrain disease models may be useful for identifying critical therapeutic pathways in PD and related disorders.

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

    Directory of Open Access Journals (Sweden)

    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

  17. 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.

  18. Combating illicit trafficking

    International Nuclear Information System (INIS)

    Biro, L.L.; Grama, E.V.

    2002-01-01

    Full text: National Commission for Nuclear Activities Control (CNCAN) is the national authority, which is contact point for illicit trafficking and coordinates all measures and activities to combat and prevent illicit trafficking with nuclear material and radioactive sources. Legal framework regarding illicit trafficking has been improved due to new Physical Protection Regulations, Regulations on using the DBT, Regulations on requirements for qualification of guards and physical protection personnel, Design Basis Threat for each nuclear facility to avoid the unauthorized removal or theft of nuclear material or radioactive sources. New amendments of the Law for the safe deployment of nuclear activities, Law no. 111/1996, republished, in respect of illicit trafficking with nuclear material and radioactive sources are in the process to be approved by the Parliament. CNCAN is member of the Romanian Non-proliferation Group that is an interdepartmental mechanism of cooperation entered into force in August 1999. During the sessions of this group there are discussions focused on the preventing and combating illicit trafficking with nuclear material and radioactive sources. CNCAN is member of the Interministerial Council that controls import and export with strategic products including nuclear material, non nuclear material and equipment pertinent for proliferation of nuclear weapons. An Emergency Mobile Unit has been created in 2001 that contains instruments (gamma dose rate instruments portable and personal, contaminometers, mini MCA with CdZnTe detector, a CANBERRA Inspector with Nal, CdZnTe and HPGe detectors and 2 FiedSPEC, a mobile laboratory, 2 cars and individual equipment). CNCAN is cooperating with the Police through a National Plan to verify the authorization holders in order to prevent and combat illicit trafficking, and to find the orphan sources. CNCAN is the beneficiary of the PECO Project initiated by the European Commission in cooperation with the IAEA and

  19. 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.

  20. 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.

  1. 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.

  2. Retrograde curves of solidus and solubility

    International Nuclear Information System (INIS)

    Vasil'ev, M.V.

    1979-01-01

    The investigation was concerned with the constitutional diagrams of the eutectic type with ''retrograde solidus'' and ''retrograde solubility curve'' which must be considered as diagrams with degenerate monotectic transformation. The solidus and the solubility curves form a retrograde curve with a common retrograde point representing the solubility maximum. The two branches of the Aetrograde curve can be described with the aid of two similar equations. Presented are corresponding equations for the Cd-Zn system and shown is the possibility of predicting the run of the solubility curve

  3. Trafficking of Kv2.1 Channels to the Axon Initial Segment by a Novel Nonconventional Secretory Pathway

    DEFF Research Database (Denmark)

    Jensen, Camilla Stampe; Watanabe, Shoji; Stas, Jeroen Ingrid

    2017-01-01

    the localization of Kv2.1 in these two different membrane compartments in cultured rat hippocampal neurons of mixed sex. Our data uncover a unique ability of Kv2.1 channels to use two molecularly distinct trafficking pathways to accomplish this. Somatodendritic Kv2.1 channels are targeted by the conventional...... secretory pathway, whereas axonal Kv2.1 channels are targeted by a nonconventional trafficking pathway independent of the Golgi apparatus. We further identified a new AIS trafficking motif in the C-terminus of Kv2.1, and show that putative phosphorylation sites in this region are critical for the restricted.......SIGNIFICANCE STATEMENT Our study uncovered a novel mechanism that targets the Kv2.1 voltage-gated potassium channel to two distinct trafficking pathways and two distinct subcellular destinations: the somatodendritic plasma membrane and that of the axon initial segment. We also identified a distinct motif, including...

  4. The first retrograde Trojan asteroid

    Science.gov (United States)

    Wiegert, Paul; Connors, Martin; Veillet, Christian

    2018-04-01

    There are about six thousand asteroids which share Jupiter's orbit around the Sun. Called the 'Trojan asteroids', they co-exist easily with this giant planet because they travel in the same direction as it ('direct' or 'prograde' motion), and remain roughly 60 degrees ahead of or behind it in its orbit. Newly discovered asteroid 2015 BZ509 is on a retrograde orbit, but is nonetheless in a state dynamically analogous to that of the prograde Trojans. The discovery circumstances and the nature of the motion of this curious asteroid -the first of its kind- will be outlined.

  5. Sonourethrography compared to retrograde urethrography

    International Nuclear Information System (INIS)

    Kim, Jong Chul; Chang, Nam Sik; Park, Cheong Hee; Rhee, Byung Chul; Kong, Jae Chul; Park, Jong Yoon

    1989-01-01

    A total of 15 patients with suspected urethral stricture or fistula underwent conventional retrograde urethrography and following sonourethrography with saline infusion or voiding against Eschmann penile clamp, in Gyeongsang and Chungnam National University Hospital from July, 1989 to June, 1989. The sonographic findings were as diagnostic as the roentgen findings in 12 patients. When the length of the strictures assessed by each imaging modality was compared to measurement at open urothroplasty of 2 patients, sonourethrography was consistently more accurate. Urethroscopy was done in all cases. Sonourethrography using distension technique of the urethra enabled classification of the degree of spongiofibrosis, thus provided the guidance of direct vision internal urethrotomy in 9 patients. In 2 patients, the sonourethrogram identified periurethral tumor and urethral polyp which were not definitely analysed on the retrograde urethrogram. In the patient of posttraumatic postoperative urethrorectal fistula, residual fistuous tract was seen on both examinations. In 1 patient of stricture with severe periurethral scar, urethral stricture recurred after graft. No patient reported significant discomfort during the sonourethrogram. The sonourethrogram provided valuable, dynamic. 3 dimensional information about the luminal and extraluminal anatomy and pathology of the anterior urethra. The new method of sonourethrogram allows for the appropriate decision to be made easier for optimal treatment of urethal stricture, etc, and can be used as a follow up study

  6. Specific Sorting and Post-Golgi trafficking of Dendritic Potassium Channels in Living Neurons

    DEFF Research Database (Denmark)

    Jensen, Camilla Stampe; Watanabe, Shoji; Rasmussen, Hanne Borger

    2014-01-01

    Proper membrane localization of ion channels is essential for the function of neuronal cells. Particularly, the computational ability of dendrites depends on the localization of different ion channels in specific sub-compartments. However, the molecular mechanisms which control ion channel...

  7. Retrograde amnesia in patients with Alzheimer's disease

    NARCIS (Netherlands)

    Meeter, M.; Eijsackers, E; Mulder, J

    2006-01-01

    Patients with mild to moderate Alzheimer's disease and normal controls were tested on two retrograde memory tests, one based on public events, and the other querying autobiographical memory. On both tests, patients showed strong decrements as compared to normal controls, pointing to retrograde

  8. Membrane Trafficking and Vesicle Fusion

    Indian Academy of Sciences (India)

    IAS Admin

    protein and the data can be cor- related with cellular .... these mutant cells under the electron microscope and found a large number of ... trans-Golgi network and early ..... Arrows represent the flow of membrane traffic: black arrows – antero-.

  9. 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

  10. Sequential phosphorylation of GRASP65 during mitotic Golgi disassembly

    Directory of Open Access Journals (Sweden)

    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.

  11. Advances in endoscopic retrograde cholangiopancreatography

    Directory of Open Access Journals (Sweden)

    WANG Xiangping

    2018-03-01

    Full Text Available Endoscopic retrograde cholangiopancreatography (ERCP is a well-established advanced endoscopic technique for the diagnosis and treatment of pancreatobiliary diseases. New advances have been made in the treatment concept and techniques of ERCP in recent years. This article elaborates on the recent advances in ERCP, including the application of pancreatic duct stent, non-steroidal anti-inflammatory drugs, and aggressive hydration to prevent postoperative pancreatitis, covered metal stent for the treatment of benign bile duct stenosis, intraluminal radiofrequency ablation for malignant bile duct stenosis, extracorporeal shockwave lithotripsy and covered metal stent for the treatment of chronic pancreatitis, peroral choledochoscopy for qualitative diagnosis of bile duct stenosis and huge refractory stones, definition of difficult intubation, timing of pre-cut technique, and ERCP after gastrointestinal reconstruction.

  12. Retrograde transurethral balloon dilation of the prostate

    International Nuclear Information System (INIS)

    Castaneda, F.; Reddy, P.; Wasserman, N.F.; Lund, G.; Hulbert, J.; Hunter, D.; Castaneda-Zuniga, W.R.; Amplatz, K.

    1986-01-01

    A series of patients with documented benign prostatic hypertrophy evaluated by urodynamic studies, voiding cystourethrography, retrograde urethrography, and MR imaging underwent dilation performed using a retrograde transurethral approach with 25-mm balloon dilators inflated at a pressure of 3-4 atm for 10 minutes. Immediately after the procedure, retrograde and voiding cystourethrography as well as MR imaging were performed. A Foley catheter was left in place for 24 hours. Complete relief of symptoms has occurred in all of the patients during the follow-up period. No significant complications other than transient hematuria resulted from the procedure. Results of the comparison studies and of MR imaging are discussed

  13. Imp2, the PSTPIP homolog in fission yeast, affects sensitivity to the immunosuppressant FK506 and membrane trafficking in fission yeast

    International Nuclear Information System (INIS)

    Kita, Ayako; Higa, Mari; Doi, Akira; Satoh, Ryosuke; Sugiura, Reiko

    2015-01-01

    Cytokinesis is a highly ordered process that divides one cell into two cells, which is functionally linked to the dynamic remodeling of the plasma membrane coordinately with various events such as membrane trafficking. Calcineurin is a highly conserved serine/threonine protein phosphatase, which regulates multiple biological functions, such as membrane trafficking and cytokinesis. Here, we isolated imp2-c3, a mutant allele of the imp2 + gene, encoding a homolog of the mouse PSTPIP1 (proline-serine-threonine phosphatase interacting protein 1), using a genetic screen for mutations that are synthetically lethal with calcineurin deletion in fission yeast. The imp2-c3 mutants showed a defect in cytokinesis with multi-septated phenotypes, which was further enhanced upon treatment with the calcineurin inhibitor FK506. Notably, electron micrographs revealed that the imp2-c3 mutant cells accumulated aberrant multi-lamella Golgi structures and putative post-Golgi secretory vesicles, and exhibited fragmented vacuoles in addition to thickened septa. Consistently, imp2-c3 mutants showed a reduced secretion of acid phosphatase and defects in vacuole fusion. The imp2-c3 mutant cells exhibited a weakened cell wall, similar to the membrane trafficking mutants identified in the same genetic screen such as ypt3-i5. These findings implicate the PSTPIP1 homolog Imp2 in Golgi/vacuole function, thereby affecting various cellular processes, including cytokinesis and cell integrity. - Highlights: • We isolated imp2-c3, in a synthetic lethal screen with calcineurin in fission yeast. • The imp2 + gene encodes a component of the actin contractile ring similar to Cdc15. • The imp2-c3 mutants showed defects in cytokinesis, which were exacerbated by FK506. • The imp2-c3 mutants were defective in membrane trafficking and cell wall integrity. • Our study revealed a novel role for Imp2 in the Golgi/vacuolar membrane trafficking

  14. Imp2, the PSTPIP homolog in fission yeast, affects sensitivity to the immunosuppressant FK506 and membrane trafficking in fission yeast

    Energy Technology Data Exchange (ETDEWEB)

    Kita, Ayako; Higa, Mari [Laboratory of Molecular Pharmacogenomics, School of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka 577-8502 (Japan); Doi, Akira [Laboratory of Molecular Pharmacogenomics, School of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka 577-8502 (Japan); Japan Society for the Promotion of Science, 1-8 Chiyoda-ku, Tokyo 102-8472 (Japan); Satoh, Ryosuke [Laboratory of Molecular Pharmacogenomics, School of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka 577-8502 (Japan); Sugiura, Reiko, E-mail: sugiurar@phar.kindai.ac.jp [Laboratory of Molecular Pharmacogenomics, School of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka 577-8502 (Japan)

    2015-02-13

    Cytokinesis is a highly ordered process that divides one cell into two cells, which is functionally linked to the dynamic remodeling of the plasma membrane coordinately with various events such as membrane trafficking. Calcineurin is a highly conserved serine/threonine protein phosphatase, which regulates multiple biological functions, such as membrane trafficking and cytokinesis. Here, we isolated imp2-c3, a mutant allele of the imp2{sup +} gene, encoding a homolog of the mouse PSTPIP1 (proline-serine-threonine phosphatase interacting protein 1), using a genetic screen for mutations that are synthetically lethal with calcineurin deletion in fission yeast. The imp2-c3 mutants showed a defect in cytokinesis with multi-septated phenotypes, which was further enhanced upon treatment with the calcineurin inhibitor FK506. Notably, electron micrographs revealed that the imp2-c3 mutant cells accumulated aberrant multi-lamella Golgi structures and putative post-Golgi secretory vesicles, and exhibited fragmented vacuoles in addition to thickened septa. Consistently, imp2-c3 mutants showed a reduced secretion of acid phosphatase and defects in vacuole fusion. The imp2-c3 mutant cells exhibited a weakened cell wall, similar to the membrane trafficking mutants identified in the same genetic screen such as ypt3-i5. These findings implicate the PSTPIP1 homolog Imp2 in Golgi/vacuole function, thereby affecting various cellular processes, including cytokinesis and cell integrity. - Highlights: • We isolated imp2-c3, in a synthetic lethal screen with calcineurin in fission yeast. • The imp2{sup +} gene encodes a component of the actin contractile ring similar to Cdc15. • The imp2-c3 mutants showed defects in cytokinesis, which were exacerbated by FK506. • The imp2-c3 mutants were defective in membrane trafficking and cell wall integrity. • Our study revealed a novel role for Imp2 in the Golgi/vacuolar membrane trafficking.

  15. 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...

  16. Women trafficking: causes, concerns, care!

    Science.gov (United States)

    Khowaja, Shaneela Sadaruddin; Tharani, Ambreen Jawed; Agha, Ajmal; Karamaliani, Rozina Sherali

    2012-08-01

    Pakistan is both a country of origin and destination as far as women trafficking is concerned. Poverty, gender discrimination, lack of education, and ignorance about legal rights are some of the underlying causes. Available data suggest several areas of concern, like, for instance: direct health effects, maladaptive coping leading to the use of illicit drugs, and inaccessibility to healthcare facilities. Therefore, numerous interventions would be required at three levels: the prevention of trafficking, the protection of victims and the prosecution of the traffickers.

  17. Health implications of human trafficking.

    Science.gov (United States)

    Richards, Tiffany A

    2014-01-01

    Freedom is arguably the most cherished right in the United States. But each year, approximately 14,500 to 17,500 women, men and children are trafficked into the United States for the purposes of forced labor or sexual exploitation. Human trafficking has significant effects on both physical and mental health. This article describes the features of human trafficking, its physical and mental health effects and the vital role nurses can play in providing care to this vulnerable population. © 2014 AWHONN.

  18. Human Trafficking and National Morality

    Directory of Open Access Journals (Sweden)

    William R. DI PIETRO

    2015-12-01

    Full Text Available The paper proposes that national morality is an important variable for explaining national anti-trafficking policy. It uses cross country regression analysis to see whether or not empirically national morality is a determinant of anti-trafficking policy. The findings of the paper are consistent with the notion that improved levels of national morality lead to better national anti-trafficking policy. National morality is found to be statistically relevant for national anti-trafficking policy when controlling for the extent of democracy, the share of the private sector in the economy, and the degree of globalization.

  19. Retrograde prostatic urethroplasty with balloon catheter

    International Nuclear Information System (INIS)

    Castaneda, F.; Reddy, P.; Hulbert, J.; Letourneau, J.G.; Hunter, D.W.; Castaneda-Zuniga, W.R.; Amplatz, K.

    1987-01-01

    The authors performed retrograde prostatic urethroplasty in 18 patients using a 25-mm urethroplasty balloon catheter. The procedure was performed on an outpatient basis under local anesthesia. Voiding cystourethrography, retrograde urethrography, rectal US, and MRE imaging were performed before and immediately after the procedure and at 2 weeks and 3, 6, 12, and 18 months. Long-term results at 18 months and possible clinical implications are discussed

  20. Combating Human Trafficking with Deep Multimodal Models

    OpenAIRE

    Tong, Edmund; Zadeh, Amir; Jones, Cara; Morency, Louis-Philippe

    2017-01-01

    Human trafficking is a global epidemic affecting millions of people across the planet. Sex trafficking, the dominant form of human trafficking, has seen a significant rise mostly due to the abundance of escort websites, where human traffickers can openly advertise among at-will escort advertisements. In this paper, we take a major step in the automatic detection of advertisements suspected to pertain to human trafficking. We present a novel dataset called Trafficking-10k, with more than 10,00...

  1. Illicit Nuclear Trafficking Scams

    International Nuclear Information System (INIS)

    Moore, G.M.

    2010-01-01

    Nuclear Trafficking Scams are situations where the scam artist(s) offer something (material or information) that is not what he/she/they represent it to be. Example of a scam is when attempt is made to sell fake nuclear material. The offered material may not be nuclear material or may be of a lower grade. The offered material may not actually exist . Radioactive material may be offered as nuclear material. A small sample of actual nuclear material may be offered, but the bulk material may be something else.

  2. WD60/FAP163 is a dynein intermediate chain required for retrograde intraflagellar transport in cilia

    Science.gov (United States)

    Patel-King, Ramila S.; Gilberti, Renée M.; Hom, Erik F. Y.; King, Stephen M.

    2013-01-01

    Retrograde intraflagellar transport (IFT) is required for assembly of cilia. We identify a Chlamydomonas flagellar protein (flagellar-associated protein 163 [FAP163]) as being closely related to the D1bIC(FAP133) intermediate chain (IC) of the dynein that powers this movement. Biochemical analysis revealed that FAP163 is present in the flagellar matrix and is actively trafficked by IFT. Furthermore, FAP163 copurified with D1bIC(FAP133) and the LC8 dynein light chain, indicating that it is an integral component of the retrograde IFT dynein. To assess the functional role of FAP163, we generated an RNA interference knockdown of the orthologous protein (WD60) in planaria. The Smed-wd60(RNAi) animals had a severe ciliary assembly defect that dramatically compromised whole-organism motility. Most cilia were present as short stubs that had accumulated large quantities of IFT particle–like material between the doublet microtubules and the membrane. The few remaining approximately full-length cilia had a chaotic beat with a frequency reduced from 24 to ∼10 Hz. Thus WD60/FAP163 is a dynein IC that is absolutely required for retrograde IFT and ciliary assembly. PMID:23864713

  3. 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

  4. 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

  5. Arabidopsis SNAREs SYP61 and SYP121 coordinate the trafficking of plasma membrane aquaporin PIP2;7 to modulate the cell membrane water permeability.

    Science.gov (United States)

    Hachez, Charles; Laloux, Timothée; Reinhardt, Hagen; Cavez, Damien; Degand, Hervé; Grefen, Christopher; De Rycke, Riet; Inzé, Dirk; Blatt, Michael R; Russinova, Eugenia; Chaumont, François

    2014-07-01

    Plant plasma membrane intrinsic proteins (PIPs) are aquaporins that facilitate the passive movement of water and small neutral solutes through biological membranes. Here, we report that post-Golgi trafficking of PIP2;7 in Arabidopsis thaliana involves specific interactions with two syntaxin proteins, namely, the Qc-SNARE SYP61 and the Qa-SNARE SYP121, that the proper delivery of PIP2;7 to the plasma membrane depends on the activity of the two SNAREs, and that the SNAREs colocalize and physically interact. These findings are indicative of an important role for SYP61 and SYP121, possibly forming a SNARE complex. Our data support a model in which direct interactions between specific SNARE proteins and PIP aquaporins modulate their post-Golgi trafficking and thus contribute to the fine-tuning of the water permeability of the plasma membrane. © 2014 American Society of Plant Biologists. All rights reserved.

  6. HUMAN TRAFFICKING DRUG TRAFFICKING, AND THE DEATH PENALTY

    Directory of Open Access Journals (Sweden)

    Felicity Gerry

    2016-12-01

    Full Text Available Both Australia and Indonesia have made commitments to combatting human trafficking.  Through the experience of Mary Jane Veloso it can be seen that it is most often the vulnerable ‘mule’ that is apprehended by law enforcement and not the powerful leaders of crime syndicates. It is unacceptable that those vulnerable individuals may face execution for acts committed under threat of force, coercion, fraud, deception or abuse of power. For this reason it is vital that a system of victim identification is developed, including better training for law enforcement, legal representatives and members of the judiciary. This paper builds on submissions by authors for Australian Parliamentary Inquiry into Human Trafficking, and focusses on issues arising in the complex cross section of human trafficking, drug trafficking, and the death penalty with particular attention on identifying victims and effective reporting mechanisms in both Australia and Indonesia. It concludes that, in the context of human trafficking both countries could make three main improvements to law and policy, among others, 1 enactment of laws that create clear mandatory protection for human trafficking victims; 2 enactment of criminal laws that provides complete defence for victim of human trafficking; 3 enactment of corporate reporting mechanisms. Systemic protection and support is not sufficiently available without clear legislative protection as this paper suggests together with standardised referral mechanisms and effective financial reporting mechanisms. The implementation can be achieved through collaborative responses and inter-agency coordination with data collection and properly trained specialists.

  7. A retrograde object near Jupiter's orbit

    Science.gov (United States)

    Connors, M.; Wiegert, P.

    2018-02-01

    Asteroid 2007 VW266 is among the rare objects with a heliocentric retrograde orbit, and its semimajor axis is within a Hill sphere radius of that of Jupiter. This raised the interesting possibility that it could be in co-orbital retrograde resonance with Jupiter, a second "counter-orbital" object in addition to recently discovered 2015 BZ509. We find instead that the object is in 13/14 retrograde mean motion resonance (also referred to as 13/-14). The object is shown to have entered its present orbit about 1700 years ago, and it will leave it in about 8000 years, both through close approach to Jupiter. Entry and exit states both avoid 1:1 retrograde resonance, but the retrograde nature is preserved. The temporary stable state is due to an elliptic orbit with high inclination keeping nodal passages far from the associated planet. We discuss the motion of this unusual object based on modeling and theory, and its observational prospects.

  8. Induced oligomerization targets Golgi proteins for degradation in lysosomes.

    Science.gov (United States)

    Tewari, Ritika; Bachert, Collin; Linstedt, Adam D

    2015-12-01

    Manganese protects cells against forms of Shiga toxin by down-regulating the cycling Golgi protein GPP130. Down-regulation occurs when Mn binding causes GPP130 to oligomerize and traffic to lysosomes. To determine how GPP130 is redirected to lysosomes, we tested the role of GGA1 and clathrin, which mediate sorting in the canonical Golgi-to-lysosome pathway. GPP130 oligomerization was induced using either Mn or a self-interacting version of the FKBP domain. Inhibition of GGA1 or clathrin specifically blocked GPP130 redistribution, suggesting recognition of the aggregated GPP130 by the GGA1/clathrin-sorting complex. Unexpectedly, however, GPP130's cytoplasmic domain was not required, and redistribution also occurred after removal of GPP130 sequences needed for its normal cycling. Therefore, to test whether aggregate recognition might be a general phenomenon rather than one involving a specific GPP130 determinant, we induced homo-oligomerization of two unrelated Golgi-targeted constructs using the FKBP strategy. These were targeted to the cis- and trans-Golgi, respectively, using domains from mannosidase-1 and galactosyltransferase. Significantly, upon oligomerization, each redistributed to peripheral punctae and was degraded. This occurred in the absence of detectable UPR activation. These findings suggest the unexpected presence of quality control in the Golgi that recognizes aggregated Golgi proteins and targets them for degradation in lysosomes. © 2015 Tewari 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).

  9. Expression and Trafficking of the γ Subunit of Na,K-ATPase in Hypertonically Challenged IMCD3 Cells

    International Nuclear Information System (INIS)

    Pihakaski-Maunsbach, Kaarina; Nonaka, Shoichi; Maunsbach, Arvid B.

    2008-01-01

    The γ subunit (FXYD2) of Na,K-ATPase is an important regulator of the sodium pump. In this investigation we have analysed the trafficking of γ to the plasma membrane in cultures of inner medullary collecting duct cells (IMCD3) following acute hypertonic challenge and brefeldin A (BFA) treatment. Following hypertonic challenging for 24 hr immunofluorescence labeling revealed initial co-localization of the γ subunit and 58K Golgi protein in the cytoplasm, but no co-localization of α1 and Golgi protein. Exposure of the challenged cells to BFA prevented the subsequent incorporation of γ into the basolateral plasma membrane. The γ subunit instead remained in cytoplasmic vesicles while cell proliferation and cell viability decreased simultaneously. Following removal of BFA from the hypertonic medium the IMCD3 cells recovered with distinct expression of γ in the basolateral membrane. The α1 subunit was only marginally influenced by BFA. The results demonstrate that the γ subunit trafficks to the plasma membrane via the Golgi apparatus, despite the absence of a signal sequence. The results also suggest that the γ and α subunits do not traffic together to the plasma membrane, and that the γ and α subunit have different turnover rates during these experimental conditions

  10. 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

  11. Mena–GRASP65 interaction couples actin polymerization to Golgi ribbon linking

    Science.gov (United States)

    Tang, Danming; Zhang, Xiaoyan; Huang, Shijiao; Yuan, Hebao; Li, Jie; Wang, Yanzhuang

    2016-01-01

    In mammalian cells, the Golgi reassembly stacking protein 65 (GRASP65) has been implicated in both Golgi stacking and ribbon linking by forming trans-oligomers through the N-terminal GRASP domain. Because the GRASP domain is globular and relatively small, but the gaps between stacks are large and heterogeneous, it remains puzzling how GRASP65 physically links Golgi stacks into a ribbon. To explore the possibility that other proteins may help GRASP65 in ribbon linking, we used biochemical methods and identified the actin elongation factor Mena as a novel GRASP65-binding protein. Mena is recruited onto the Golgi membranes through interaction with GRASP65. Depleting Mena or disrupting actin polymerization resulted in Golgi fragmentation. In cells, Mena and actin were required for Golgi ribbon formation after nocodazole washout; in vitro, Mena and microfilaments enhanced GRASP65 oligomerization and Golgi membrane fusion. Thus Mena interacts with GRASP65 to promote local actin polymerization, which facilitates Golgi ribbon linking. PMID:26538023

  12. Human liver cell trafficking mutants: characterization and whole exome sequencing.

    Directory of Open Access Journals (Sweden)

    Fei Yuan

    Full Text Available The HuH7 liver cell mutant Trf1 is defective in membrane trafficking and is complemented by the casein kinase 2α subunit CK2α''. Here we identify characteristic morphologies, trafficking and mutational changes in six additional HuH7 mutants Trf2-Trf7. Trf1 cells were previously shown to be severely defective in gap junction functions. Using a Lucifer yellow transfer assay, remarkable attenuation of gap junction communication was revealed in each of the mutants Trf2-Trf7. Electron microscopy and light microscopy of thiamine pyrophosphatase showed that several mutants exhibited fragmented Golgi apparatus cisternae compared to parental HuH7 cells. Intracellular trafficking was investigated using assays of transferrin endocytosis and recycling and VSV G secretion. Surface binding of transferrin was reduced in all six Trf2-Trf7 mutants, which generally correlated with the degree of reduced expression of the transferrin receptor at the cell surface. The mutants displayed the same transferrin influx rates as HuH7, and for efflux rate, only Trf6 differed, having a slower transferrin efflux rate than HuH7. The kinetics of VSV G transport along the exocytic pathway were altered in Trf2 and Trf5 mutants. Genetic changes unique to particular Trf mutants were identified by exome sequencing, and one was investigated in depth. The novel mutation Ile34Phe in the GTPase RAB22A was identified in Trf4. RNA interference knockdown of RAB22A or overexpression of RAB22AI34F in HuH7 cells caused phenotypic changes characteristic of the Trf4 mutant. In addition, the Ile34Phe mutation reduced both guanine nucleotide binding and hydrolysis activities of RAB22A. Thus, the RAB22A Ile34Phe mutation appears to contribute to the Trf4 mutant phenotype.

  13. Structural Disorder Provides Increased Adaptability for Vesicle Trafficking Pathways

    Science.gov (United States)

    Tompa, Peter

    2013-01-01

    Vesicle trafficking systems play essential roles in the communication between the organelles of eukaryotic cells and also between cells and their environment. Endocytosis and the late secretory route are mediated by clathrin-coated vesicles, while the COat Protein I and II (COPI and COPII) routes stand for the bidirectional traffic between the ER and the Golgi apparatus. Despite similar fundamental organizations, the molecular machinery, functions, and evolutionary characteristics of the three systems are very different. In this work, we compiled the basic functional protein groups of the three main routes for human and yeast and analyzed them from the structural disorder perspective. We found similar overall disorder content in yeast and human proteins, confirming the well-conserved nature of these systems. Most functional groups contain highly disordered proteins, supporting the general importance of structural disorder in these routes, although some of them seem to heavily rely on disorder, while others do not. Interestingly, the clathrin system is significantly more disordered (∼23%) than the other two, COPI (∼9%) and COPII (∼8%). We show that this structural phenomenon enhances the inherent plasticity and increased evolutionary adaptability of the clathrin system, which distinguishes it from the other two routes. Since multi-functionality (moonlighting) is indicative of both plasticity and adaptability, we studied its prevalence in vesicle trafficking proteins and correlated it with structural disorder. Clathrin adaptors have the highest capability for moonlighting while also comprising the most highly disordered members. The ability to acquire tissue specific functions was also used to approach adaptability: clathrin route genes have the most tissue specific exons encoding for protein segments enriched in structural disorder and interaction sites. Overall, our results confirm the general importance of structural disorder in vesicle trafficking and

  14. The FTLD risk factor TMEM106B and MAP6 control dendritic trafficking of lysosomes

    Science.gov (United States)

    Schwenk, Benjamin M; Lang, Christina M; Hogl, Sebastian; Tahirovic, Sabina; Orozco, Denise; Rentzsch, Kristin; Lichtenthaler, Stefan F; Hoogenraad, Casper C; Capell, Anja; Haass, Christian; Edbauer, Dieter

    2014-01-01

    TMEM106B is a major risk factor for frontotemporal lobar degeneration with TDP-43 pathology. TMEM106B localizes to lysosomes, but its function remains unclear. We show that TMEM106B knockdown in primary neurons affects lysosomal trafficking and blunts dendritic arborization. We identify microtubule-associated protein 6 (MAP6) as novel interacting protein for TMEM106B. MAP6 over-expression inhibits dendritic branching similar to TMEM106B knockdown. MAP6 knockdown fully rescues the dendritic phenotype of TMEM106B knockdown, supporting a functional interaction between TMEM106B and MAP6. Live imaging reveals that TMEM106B knockdown and MAP6 overexpression strongly increase retrograde transport of lysosomes in dendrites. Downregulation of MAP6 in TMEM106B knockdown neurons restores the balance of anterograde and retrograde lysosomal transport and thereby prevents loss of dendrites. To strengthen the link, we enhanced anterograde lysosomal transport by expressing dominant-negative Rab7-interacting lysosomal protein (RILP), which also rescues the dendrite loss in TMEM106B knockdown neurons. Thus, TMEM106B/MAP6 interaction is crucial for controlling dendritic trafficking of lysosomes, presumably by acting as a molecular brake for retrograde transport. Lysosomal misrouting may promote neurodegeneration in patients with TMEM106B risk variants. PMID:24357581

  15. Popliteal versus tibial retrograde access for subintimal arterial flossing with antegrade-retrograde intervention (SAFARI) technique.

    Science.gov (United States)

    Hua, W R; Yi, M Q; Min, T L; Feng, S N; Xuan, L Z; Xing, J

    2013-08-01

    This study aimed to ascertain differences in benefit and effectiveness of popliteal versus tibial retrograde access in subintimal arterial flossing with the antegrade-retrograde intervention (SAFARI) technique. This was a retrospective study of SAFARI-assisted stenting for long chronic total occlusion (CTO) of TASC C and D superficial femoral lesions. 38 cases had superficial femoral artery lesions (23 TASC C and 15 TASC D). All 38 cases underwent SAFARI-assisted stenting. The ipsilateral popliteal artery was retrogradely punctured in 17 patients. A distal posterior tibial (PT) or dorsalis pedis (DP) artery was retrogradely punctured in 21 patients, and 16 of them were punctured after open surgical exposure. SAFARI technical success was achieved in all cases. There was no significant difference in 1-year primary patency (75% vs. 78.9%, p = .86), secondary patency (81.2% vs. 84.2%, p = .91) and access complications (p = 1.00) between popliteal and tibial retrograde access. There was statistical difference in operation time between popliteal (140.1 ± 28.4 min) and tibial retrograde access with PT/DP punctures after surgical vessel exposure (120.4 ± 23.0 min, p = .04). The SAFARI technique is a safe and feasible option for patients with infrainguinal CTO (TASC II C and D). The PT or DP as the retrograde access after surgical vessel exposure is a good choice when using the SAFARI technique. Copyright © 2013 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

  16. Brown dwarfs in retrogradely precessing cataclysmic variables?

    Directory of Open Access Journals (Sweden)

    Martin E.L.

    2011-07-01

    Full Text Available We compare Smoothed Particle Hydrodynamic simulations of retrogradely precessing accretion disks that have a white dwarf primary and a main sequence secondary with observational data and with theory on retrograde precession via tidal torques like those by the Moon and the Sun on the Earth [1, 2]. Assuming the primary does not accrete much of the mass lost from the secondary, we identify the theoretical low mass star/brown dwarf boundary. We find no observational candidates in our study that could qualify as brown dwarfs.

  17. Role of LRRK2 in the regulation of dopamine receptor trafficking.

    Directory of Open Access Journals (Sweden)

    Mauro Rassu

    Full Text Available Mutations in LRRK2 play a critical role in both familial and sporadic Parkinson's disease (PD. Up to date, the role of LRRK2 in PD onset and progression remains largely unknown. However, experimental evidence highlights a critical role of LRRK2 in the control of vesicle trafficking that in turn may regulate different aspects of neuronal physiology. We have analyzed the role of LRRK2 in regulating dopamine receptor D1 (DRD1 and D2 (DRD2 trafficking. DRD1 and DRD2 are the most abundant dopamine receptors in the brain. They differ in structural, pharmacological and biochemical properties, as well as in localization and internalization mechanisms. Our results indicate that disease-associated mutant G2019S LRRK2 impairs DRD1 internalization, leading to an alteration in signal transduction. Moreover, the mutant forms of LRRK2 affect receptor turnover by decreasing the rate of DRD2 trafficking from the Golgi complex to the cell membrane. Collectively, our findings are consistent with the conclusion that LRRK2 influences the motility of neuronal vesicles and the neuronal receptor trafficking. These findings have important implications for the complex role that LRRK2 plays in neuronal physiology and the possible pathological mechanisms that may lead to neuronal death in PD.

  18. Nuclear functions and subcellular trafficking mechanisms of the epidermal growth factor receptor family

    Science.gov (United States)

    2012-01-01

    Accumulating evidence suggests that various diseases, including many types of cancer, result from alteration of subcellular protein localization and compartmentalization. Therefore, it is worthwhile to expand our knowledge in subcellular trafficking of proteins, such as epidermal growth factor receptor (EGFR) and ErbB-2 of the receptor tyrosine kinases, which are highly expressed and activated in human malignancies and frequently correlated with poor prognosis. The well-characterized trafficking of cell surface EGFR is routed, via endocytosis and endosomal sorting, to either the lysosomes for degradation or back to the plasma membrane for recycling. A novel nuclear mode of EGFR signaling pathway has been gradually deciphered in which EGFR is shuttled from the cell surface to the nucleus after endocytosis, and there, it acts as a transcriptional regulator, transmits signals, and is involved in multiple biological functions, including cell proliferation, tumor progression, DNA repair and replication, and chemo- and radio-resistance. Internalized EGFR can also be transported from the cell surface to several intracellular compartments, such as the Golgi apparatus, the endoplasmic reticulum, and the mitochondria, in addition to the nucleus. In this review, we will summarize the functions of nuclear EGFR family and the potential pathways by which EGFR is trafficked from the cell surface to a variety of cellular organelles. A better understanding of the molecular mechanism of EGFR trafficking will shed light on both the receptor biology and potential therapeutic targets of anti-EGFR therapies for clinical application. PMID:22520625

  19. Synaptojanin 1 is required for endolysosomal trafficking of synaptic proteins in cone photoreceptor inner segments.

    Directory of Open Access Journals (Sweden)

    Ashley A George

    Full Text Available Highly polarized cells such as photoreceptors require precise and efficient strategies for establishing and maintaining the proper subcellular distribution of proteins. The signals and molecular machinery that regulate trafficking and sorting of synaptic proteins within cone inner segments is mostly unknown. In this study, we show that the polyphosphoinositide phosphatase Synaptojanin 1 (SynJ1 is critical for this process. We used transgenic markers for trafficking pathways, electron microscopy, and immunocytochemistry to characterize trafficking defects in cones of the zebrafish mutant, nrc(a14 , which is deficient in phosphoinositide phosphatase, SynJ1. The outer segments and connecting cilia of nrc(a14 cone photoreceptors are normal, but RibeyeB and VAMP2/synaptobrevin, which normally localize to the synapse, accumulate in the nrc(a14 inner segment. The structure of the Endoplasmic Reticulum in nrc(a14 mutant cones is normal. Golgi develop normally, but later become disordered. Large vesicular structures accumulate within nrc(a14 cone photoreceptor inner segments, particularly after prolonged incubation in darkness. Cone inner segments of nrc (a14 mutants also have enlarged acidic vesicles, abnormal late endosomes, and a disruption in autophagy. This last pathway also appears exacerbated by darkness. Taken altogether, these findings show that SynJ1 is required in cones for normal endolysosomal trafficking of synaptic proteins.

  20. Retrograde amnesia after electroconvulsive therapy: a temporary effect?

    NARCIS (Netherlands)

    Meeter, M.; Murre, J.M.J.; Janssen, S.M.J.; Birkenhager, T.; van den Broek, W.W.

    2011-01-01

    Objective: Although electroconvulsive therapy (ECT) is generally considered effective against depression, it remains controversial because of its association with retrograde memory loss. Here, we assessed memory after ECT in circumstances most likely to yield strong retrograde amnesia. Method: A

  1. Functional Outcomes of the Knee after Retrograde and Antegrade ...

    African Journals Online (AJOL)

    of femur shaft fractures although retrograde technique is gaining acceptance. Although ... Antegrade group, while the rate of knee stiffness was higher in the retrograde .... reaching direct and indirect social economic effect within the society.

  2. Benzyl alcohol induces a reversible fragmentation of the Golgi apparatus and inhibits membrane trafficking between endosomes and the trans-Golgi network

    DEFF Research Database (Denmark)

    Simm, Roger; Kvalvaag, Audun Sverre; van Deurs, Bo

    2017-01-01

    Benzyl alcohol (BnOH) is widely used as a component of foods, cosmetics, household products and medical products. It is generally considered to be safe for human use, however, it has been connected to a number of adverse effects, including hypersensitivity reactions and neonatal deaths. Bn...

  3. PIST regulates the intracellular trafficking and plasma membrane expression of Cadherin 23

    Directory of Open Access Journals (Sweden)

    Oshima Kazuo

    2010-10-01

    Full Text Available Abstract Background The atypical cadherin protein cadherin 23 (CDH23 is crucial for proper function of retinal photoreceptors and inner ear hair cells. As we obtain more and more information about the specific roles of cadherin 23 in photoreceptors and hair cells, the regulatory mechanisms responsible for the transport of this protein to the plasma membrane are largely unknown. Results PIST, a Golgi-associated, PDZ domain-containing protein, interacted with cadherin 23 via the PDZ domain of PIST and the C-terminal PDZ domain-binding interface (PBI of cadherin 23. By binding to cadherin 23, PIST retained cadherin 23 in the trans-Golgi network of cultured cells. The retention was released when either of the two known cadherin 23-binding proteins MAGI-1 and harmonin was co-expressed. Similar to MAGI-1 and harmonin, PIST was detected in mouse inner ear sensory hair cells. Conclusions PIST binds cadherin 23 via its PDZ domain and retains cadherin 23 in trans-Golgi network. MAGI-1 and harmonin can compete with PIST for binding cadherin 23 and release cadherin 23 from PIST's retention. Our finding suggests that PIST, MAGI-1 and harmonin collaborate in intracellular trafficking of cadherin 23 and regulate the plasma membrane expression of cadherin 23.

  4. Illicit Trafficking of Natural Radionuclides

    International Nuclear Information System (INIS)

    Friedrich, Steinhaeusler; Lyudmila, Zaitseva

    2008-01-01

    Natural radionuclides have been subject to trafficking worldwide, involving natural uranium ore (U 238), processed uranium (yellow cake), low enriched uranium ( 20% U 235), radium (Ra 226), polonium (Po 210), and natural thorium ore (Th 232). An important prerequisite to successful illicit trafficking activities is access to a suitable logistical infrastructure enabling an undercover shipment of radioactive materials and, in case of trafficking natural uranium or thorium ore, capable of transporting large volumes of material. Covert en route diversion of an authorised uranium transport, together with covert diversion of uranium concentrate from an operating or closed uranium mines or mills, are subject of case studies. Such cases, involving Israel, Iran, Pakistan and Libya, have been analyzed in terms of international actors involved and methods deployed. Using international incident data contained in the Database on Nuclear Smuggling, Theft and Orphan Radiation Sources (DSTO) and international experience gained from the fight against drug trafficking, a generic Trafficking Pathway Model (TPM) is developed for trafficking of natural radionuclides. The TPM covers the complete trafficking cycle, ranging from material diversion, covert material transport, material concealment, and all associated operational procedures. The model subdivides the trafficking cycle into five phases: (1) Material diversion by insider(s) or initiation by outsider(s); (2) Covert transport; (3) Material brokerage; (4) Material sale; (5) Material delivery. An Action Plan is recommended, addressing the strengthening of the national infrastructure for material protection and accounting, development of higher standards of good governance, and needs for improving the control system deployed by customs, border guards and security forces

  5. Illicit Trafficking of Natural Radionuclides

    Science.gov (United States)

    Friedrich, Steinhäusler; Lyudmila, Zaitseva

    2008-08-01

    Natural radionuclides have been subject to trafficking worldwide, involving natural uranium ore (U 238), processed uranium (yellow cake), low enriched uranium (20% U 235), radium (Ra 226), polonium (Po 210), and natural thorium ore (Th 232). An important prerequisite to successful illicit trafficking activities is access to a suitable logistical infrastructure enabling an undercover shipment of radioactive materials and, in case of trafficking natural uranium or thorium ore, capable of transporting large volumes of material. Covert en route diversion of an authorised uranium transport, together with covert diversion of uranium concentrate from an operating or closed uranium mines or mills, are subject of case studies. Such cases, involving Israel, Iran, Pakistan and Libya, have been analyzed in terms of international actors involved and methods deployed. Using international incident data contained in the Database on Nuclear Smuggling, Theft and Orphan Radiation Sources (DSTO) and international experience gained from the fight against drug trafficking, a generic Trafficking Pathway Model (TPM) is developed for trafficking of natural radionuclides. The TPM covers the complete trafficking cycle, ranging from material diversion, covert material transport, material concealment, and all associated operational procedures. The model subdivides the trafficking cycle into five phases: (1) Material diversion by insider(s) or initiation by outsider(s); (2) Covert transport; (3) Material brokerage; (4) Material sale; (5) Material delivery. An Action Plan is recommended, addressing the strengthening of the national infrastructure for material protection and accounting, development of higher standards of good governance, and needs for improving the control system deployed by customs, border guards and security forces.

  6. INTERNATIONAL COOPERATION AGAINST HUMAN TRAFFICKING

    OpenAIRE

    Ionita COCHINTU; Laura TUTUNARU; Narcisa Mihaela STOICU; Daniela Cristina VALEA

    2011-01-01

    Trafficking in human beings, a phenomenon with global dimensions constitutes a serious violation of human rights, dignity and freedom, a social phenomenon with negative consequences for the entire society. Countries have been concerned over the time to find the most effective policy measures to combat and prevent human trafficking, and in this regard the United Nations, the European Union and the Council of Europe have developed a series of international documents which established an interna...

  7. Voltage-Dependent Intrinsic Bursting in Olfactory Bulb Golgi Cells

    Science.gov (United States)

    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…

  8. 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

  9. Botulinum neurotoxins A and E undergo retrograde axonal transport in primary motor neurons.

    Directory of Open Access Journals (Sweden)

    Laura Restani

    2012-12-01

    Full Text Available The striking differences between the clinical symptoms of tetanus and botulism have been ascribed to the different fate of the parental neurotoxins once internalised in motor neurons. Tetanus toxin (TeNT is known to undergo transcytosis into inhibitory interneurons and block the release of inhibitory neurotransmitters in the spinal cord, causing a spastic paralysis. In contrast, botulinum neurotoxins (BoNTs block acetylcholine release at the neuromuscular junction, therefore inducing a flaccid paralysis. Whilst overt experimental evidence supports the sorting of TeNT to the axonal retrograde transport pathway, recent findings challenge the established view that BoNT trafficking is restricted to the neuromuscular junction by highlighting central effects caused by these neurotoxins. These results suggest a more complex scenario whereby BoNTs also engage long-range trafficking mechanisms. However, the intracellular pathways underlying this process remain unclear. We sought to fill this gap by using primary motor neurons either in mass culture or differentiated in microfluidic devices to directly monitor the endocytosis and axonal transport of full length BoNT/A and BoNT/E and their recombinant binding fragments. We show that BoNT/A and BoNT/E are internalised by spinal cord motor neurons and undergo fast axonal retrograde transport. BoNT/A and BoNT/E are internalised in non-acidic axonal carriers that partially overlap with those containing TeNT, following a process that is largely independent of stimulated synaptic vesicle endo-exocytosis. Following intramuscular injection in vivo, BoNT/A and TeNT displayed central effects with a similar time course. Central actions paralleled the peripheral spastic paralysis for TeNT, but lagged behind the onset of flaccid paralysis for BoNT/A. These results suggest that the fast axonal retrograde transport compartment is composed of multifunctional trafficking organelles orchestrating the simultaneous transfer

  10. Studies of retrograde memory: A long-term view

    OpenAIRE

    Warrington, Elizabeth K.

    1996-01-01

    Studies of retrograde amnesia are reviewed. First, the issues of temporal gradients of retrograde amnesia are discussed. Second, the question of the anatomical substrates of this syndrome are considered. Finally, some evidence for fractionation of different classes of memoranda within the retrograde time period are presented.

  11. Topographic Anterograde and Retrograde Memory for Spatial ...

    African Journals Online (AJOL)

    The present study was on the effects of haloperidol injection on anterograde and retrograde topographic memories for spatial behaviours in Long Evan rats. Twelve Long Evan albino rats weighing 0.5 – 0.8 kg (6 males, 6 females) were used for the study. Complex Maze Box of 14 unit T Alley from the Royal Institute of ...

  12. Liver parenchumography following endoscopic retrograde cholangiopancreatography (ERCP)

    International Nuclear Information System (INIS)

    Revert, A.; Arana, E.; Pertejo, V.; Berenguer, M.; Masip, M.J.

    1998-01-01

    Focal liver opacification during endoscopic retrograde cholangiography (ERCP) is an uncommon complication caused by excessive pressure during contrast injection. In this situation, ERCP must be interrupted and the position of the cannula checked. We recommend that these images be excluded from the diagnosis of tumor or cystic cavities. 4 refs

  13. Kinematics of turnaround and retrograde axonal transport

    International Nuclear Information System (INIS)

    Snyder, R.E.

    1986-01-01

    Rapid axonal transport of a pulse of 35 S-methionine-labelled material was studied in vitro in the sensory neurons of amphibian sciatic nerve using a position-sensitive detector. For 10 nerves studied at 23.0 +/- 0.2 degrees C it was found that a pulse moved in the anterograde direction characterized by front edge, peak, and trailing edge transport rates of (mm/d) 180.8 +/- 2.2 (+/- SEM), 176.6 +/- 2.3, and 153.7 +/- 3.0, respectively. Following its arrival at a distal ligature, a smaller pulse was observed to move in the retrograde direction characterized by front edge and peak transport rates of 158.0 +/- 7.3 and 110.3 +/- 3.5, respectively, indicating that retrograde transport proceeds at a rate of 0.88 +/- 0.04 that of anterograde. The retrograde pulse was observed to disperse at a rate greater than the anterograde. Reversal of radiolabel at the distal ligature began 1.49 +/- 0.15 h following arrival of the first radiolabel. Considerable variation was seen between preparations in the way radiolabel accumulated in the end (ligature) regions of the nerve. Although a retrograde pulse was seen in all preparations, in 7 of 10 preparations there was no evidence of this pulse accumulating within less than 2-3 mm of a proximal ligature; however, accumulation was observed within less than 5 mm in all preparations

  14. Synchronous Retrograde and Micturating Cysto Urethrography A ...

    African Journals Online (AJOL)

    Background: Retrograde Urethrography (RUG) combined with Micturating cystourethrography (MCUG) is imaging method of choice for studying the urethra and its 1-9 abnormalities . Though there are many modern imaging modalities that are also useful but these are not available in most developing countries. Even the ...

  15. To discuss illicit nuclear trafficking

    Energy Technology Data Exchange (ETDEWEB)

    Balatsky, Galya I [Los Alamos National Laboratory; Severe, William R [Los Alamos National Laboratory; Wallace, Richard K [Los Alamos National Laboratory

    2010-01-01

    The Illicit nuclear trafficking panel was conducted at the 4th Annual INMM workshop on Reducing the Risk from Radioactive and Nuclear Materials on February 2-3, 2010 in Washington DC. While the workshop occurred prior to the Nuclear Security Summit, April 12-13 2010 in Washington DC, some of the summit issues were raised during the workshop. The Communique of the Washington Nuclear Security Summit stated that 'Nuclear terrorism is one of the most challenging threats to international security, and strong nuclear security measures are the most effective means to prevent terrorists, criminals, or other unauthorized actors from acquiring nuclear materials.' The Illicit Trafficking panel is one means to strengthen nuclear security and cooperation at bilateral, regional and multilateral levels. Such a panel promotes nuclear security culture through technology development, human resources development, education and training. It is a tool which stresses the importance of international cooperation and coordination of assistance to improve efforts to prevent and respond to incidents of illicit nuclear trafficking. Illicit trafficking panel included representatives from US government, an international organization (IAEA), private industry and a non-governmental organization to discuss illicit nuclear trafficking issues. The focus of discussions was on best practices and challenges for addressing illicit nuclear trafficking. Terrorism connection. Workshop discussions pointed out the identification of terrorist connections with several trafficking incidents. Several trafficking cases involved real buyers (as opposed to undercover law enforcement agents) and there have been reports identifying individuals associated with terrorist organizations as prospective plutonium buyers. Some specific groups have been identified that consistently search for materials to buy on the black market, but no criminal groups were identified that specialize in nuclear materials or isotope

  16. Retrograde Renal Cooling to Minimize Ischemia

    Directory of Open Access Journals (Sweden)

    Janet L. Colli

    2013-01-01

    Full Text Available Objective: During partial nephrectomy, renal hypothermia has been shown to decrease ischemia induced renal damage which occurs from renal hilar clamping. In this study we investigate the infusion rate required to safely cool the entire renal unit in a porcine model using retrograde irrigation of iced saline via dual-lumen ureteral catheter. Materials and Methods: Renal cortical, renal medullary, bowel and rectal temperatures during retrograde cooling in a laparoscopic porcine model were monitored in six renal units. Iced normal saline was infused at 300 cc/hour, 600 cc/hour, 1000 cc/hour and gravity (800 cc/hour for 600 seconds with and without hilar clamping. Results: Retrograde cooling with hilar clamping provided rapid medullary renal cooling and significant hypothermia of the medulla and cortex at infusion rates ≥ 600 cc/hour. With hilar clamping, cortical temperatures decreased at -0.9° C/min. reaching a threshold temperature of 26.9° C, and medullary temperatures decreased at -0.90 C/min. reaching a temperature of 26.1° C over 600 seconds on average for combined data at infusion rates ≥ 600 cc/hour. The lowest renal temperatures were achieved with gravity infusion. Without renal hilum clamping, retrograde cooling was minimal at all infusion rates. Conclusions: Significant renal cooling by gravity infusion of iced cold saline via a duel lumen catheter with a clamped renal hilum was achieved in a porcine model. Continuous retrograde irrigation with iced saline via a two way ureteral catheter may be an effective method to induce renal hypothermia in patients undergoing robotic assisted and/or laparoscopic partial nephrectomy.

  17. cis-Golgi proteins accumulate near the ER exit sites and act as the scaffold for Golgi regeneration after brefeldin A treatment in tobacco BY-2 cells.

    Science.gov (United States)

    Ito, Yoko; Uemura, Tomohiro; Shoda, Keiko; Fujimoto, Masaru; Ueda, Takashi; Nakano, Akihiko

    2012-08-01

    The Golgi apparatus forms stacks of cisternae in many eukaryotic cells. However, little is known about how such a stacked structure is formed and maintained. To address this question, plant cells provide a system suitable for live-imaging approaches because individual Golgi stacks are well separated in the cytoplasm. We established tobacco BY-2 cell lines expressing multiple Golgi markers tagged by different fluorescent proteins and observed their responses to brefeldin A (BFA) treatment and BFA removal. BFA treatment disrupted cis, medial, and trans cisternae but caused distinct relocalization patterns depending on the proteins examined. Medial- and trans-Golgi proteins, as well as one cis-Golgi protein, were absorbed into the endoplasmic reticulum (ER), but two other cis-Golgi proteins formed small punctate structures. After BFA removal, these puncta coalesced first, and then the Golgi stacks regenerated from them in the cis-to-trans order. We suggest that these structures have a property similar to the ER-Golgi intermediate compartment and function as the scaffold of Golgi regeneration.

  18. PIN-G – A novel reporter for imaging and defining the effects of trafficking signals in membrane proteins

    Directory of Open Access Journals (Sweden)

    Hu Weiwen

    2006-03-01

    Full Text Available Abstract Background The identification of protein trafficking signals, and their interacting mechanisms, is a fundamental objective of modern biology. Unfortunately, the analysis of trafficking signals is complicated by their topography, hierarchical nature and regulation. Powerful strategies to test candidate motifs include their ability to direct simpler reporter proteins, to which they are fused, to the appropriate cellular compartment. However, present reporters are limited by their endogenous expression, paucity of cloning sites, and difficult detection in live cells. Results Consequently, we have engineered a mammalian expression vector encoding a novel trafficking reporter – pIN-G – consisting of a simple, type I integral protein bearing permissive intra/extracellular cloning sites, green fluorescent protein (GFP, cMyc and HA epitope tags. Fluorescence imaging, flow cytometry and biochemical assays of transfected HEK293 cells, confirm the size, topology and surface expression of PIN-G. Moreover, a pIN-G fusion construct, containing a Trans-Golgi Network (TGN targeting determinant, internalises rapidly from the cell surface and localises to the TGN. Additionally, another PIN-G fusion protein and its mutants reveal trafficking determinants in the cytoplasmic carboxy terminus of Kv1.4 voltage-gated potassium channels. Conclusion Together, these data indicate that pIN-G is a versatile, powerful, new reporter for analysing signals controlling membrane protein trafficking, surface expression and dynamics.

  19. Doppler-guided retrograde catheterization system

    Science.gov (United States)

    Frazin, Leon J.; Vonesh, Michael J.; Chandran, Krishnan B.; Khasho, Fouad; Lanza, George M.; Talano, James V.; McPherson, David D.

    1991-05-01

    The purpose of this study was to investigate a Doppler guided catheterization system as an adjunctive or alternative methodology to overcome the disadvantages of left heart catheterization and angiography. These disadvantages include the biological effects of radiation and the toxic and volume effects of iodine contrast. Doppler retrograde guidance uses a 20 MHz circular pulsed Doppler crystal incorporated into the tip of a triple lumen multipurpose catheter and is advanced retrogradely using the directional flow information provided by the Doppler waveform. The velocity detection limits are either 1 m/second or 4 m/second depending upon the instrumentation. In a physiologic flow model of the human aortic arch, multiple data points revealed a positive wave form when flow was traveling toward the catheter tip indicating proper alignment for retrograde advancement. There was a negative wave form when flow was traveling away from the catheter tip if the catheter was in a branch or bent upon itself indicating improper catheter tip position for retrograde advancement. In a series of six dogs, the catheter was able to be accurately advanced from the femoral artery to the left ventricular chamber under Doppler signal guidance without the use of x-ray. The potential applications of a Doppler guided retrograde catheterization system include decreasing time requirements and allowing safer catheter guidance in patients with atherosclerotic vascular disease and suspected aortic dissection. The Doppler system may allow left ventricular pressure monitoring in the intensive care unit without the need for x-ray and it may allow left sided contrast echocardiography. With pulse velocity detection limits of 4 m/second, this system may allow catheter direction and passage into the aortic root and left ventricle in patients with aortic stenosis. A modification of the Doppler catheter may include transponder technology which would allow precise catheter tip localization once the

  20. 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.

  1. A Dual Role for the Nonreceptor Tyrosine Kinase Pyk2 during the Intracellular Trafficking of Human Papillomavirus 16.

    Science.gov (United States)

    Gottschalk, Elinor Y; Meneses, Patricio I

    2015-09-01

    The infectious process of human papillomaviruses (HPVs) has been studied considerably, and many cellular components required for viral entry and trafficking continue to be revealed. In this study, we investigated the role of the nonreceptor tyrosine kinase Pyk2 during HPV16 pseudovirion infection of human keratinocytes. We found that Pyk2 is necessary for infection and appears to be involved in the intracellular trafficking of the virus. Small interfering RNA-mediated reduction of Pyk2 resulted in a significant decrease in infection but did not prevent viral entry at the plasma membrane. Pyk2 depletion resulted in altered endolysosomal trafficking of HPV16 and accelerated unfolding of the viral capsid. Furthermore, we observed retention of the HPV16 pseudogenome in the trans-Golgi network (TGN) in Pyk2-depleted cells, suggesting that the kinase could be required for the viral DNA to exit the TGN. While Pyk2 has previously been shown to function during the entry of enveloped viruses at the plasma membrane, the kinase has not yet been implicated in the intracellular trafficking of a nonenveloped virus such as HPV. Additionally, these data enrich the current literature on Pyk2's function in human keratinocytes. In this study, we investigated the role of the nonreceptor tyrosine kinase Pyk2 during human papillomavirus (HPV) infection of human skin cells. Infections with high-risk types of HPV such as HPV16 are the leading cause of cervical cancer and a major cause of genital and oropharyngeal cancer. As a nonenveloped virus, HPV enters cells by interacting with cellular receptors and established cellular trafficking routes to ensure that the viral DNA reaches the nucleus for productive infection. This study identified Pyk2 as a cellular component required for the intracellular trafficking of HPV16 during infection. Understanding the infectious pathways of HPVs is critical for developing additional preventive therapies. Furthermore, this study advances our knowledge of

  2. Understanding human trafficking in the United States.

    Science.gov (United States)

    Logan, T K; Walker, Robert; Hunt, Gretchen

    2009-01-01

    The topic of modern-day slavery or human trafficking has received increased media and national attention. However, to date there has been limited research on the nature and scope of human trafficking in the United States. This article describes and synthesizes nine reports that assess the U.S. service organizations' legal representative knowledge of, and experience with, human trafficking cases, as well as information from actual cases and media reports. This article has five main goals: (a) to define what human trafficking is, and is not; (b) to describe factors identified as contributing to vulnerability to being trafficked and keeping a person entrapped in the situation; (c) to examine how the crime of human trafficking differs from other kinds of crimes in the United States; (d) to explore how human trafficking victims are identified; and, (e) to provide recommendations to better address human trafficking in the United States.

  3. Vagal withdrawal during endoscopic retrograde cholangiopancreatography

    DEFF Research Database (Denmark)

    Christensen, M; Rasmussen, Verner; Schulze, S

    2000-01-01

    BACKGROUND: Patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) are at risk of developing cardiorespiratory complications, but the mechanism is still unknown. Treatment with metoprolol 2 h before the endoscopy has been shown to decrease the incidence of myocardial ischaemia......: The existence of a defence-like reaction ('vagal withdrawal') during ERCP has been shown. Metoprolol given 2 h before the procedure did not affect the occurrence of this phenomenon. The interaction of other periendoscopic factors is still unclear and should be studied further....

  4. An unusual experience with endoscopic retrograde cholangiopancreatography

    Directory of Open Access Journals (Sweden)

    Mallikarjun Patil

    2013-01-01

    Full Text Available The endoscopic retrograde cholangiopancreatography (ERCP is known for its varied diagnostic and therapeutic utility for a variety of disorders. However it has greater likelihood of procedure related complications among the endoscopic procedures of gastrointestinal tract. The extraluminal hemorrhagic complications following ERCP are potentially life threatening though relatively rare. We present a 50 year patient with choledocholithiasis and cholelithiasis developing rare complication of subcapsular hepatic hematoma, following ERCP due to guide wire injury.

  5. Complications of bladder distension during retrograde urethrography.

    Science.gov (United States)

    Barsanti, J A; Crowell, W; Losonsky, J; Talkington, F D

    1981-05-01

    A severe, ulcerative cystitis that resulted in macroscopic hematuria occurred in 8 of 20 healthy dogs undergoing a series of diagnostic tests. Four of the remaining 12 dogs had mild bladder lesions consisting of submucosal edema and hemorrhage. Nine of the 20 dogs developed urinary tract infection after the procedures. These complications seemed associated with the radiographic technique of retrograde urethrography performed when the urinary bladder was distended. To test this hypothesis, retrograde urethrography was performed on 5 additional dogs. With the bladder undistended, no complications occurred. However, distention of these same dogs' bladders for 1 minute or less with sterile lactated Ringer's solution administered through a Foley catheter in the penile urethra resulted in a macroscopic hematuria in all 5 dogs which persisted for 24 hours. A microscopic hematuria continued for 5 days. One dog developed a bacterial urinary tract infection. A severe fibrinopurulent cystitis was present at necropsy of 2 dogs 2 days after distention. The morphologic changes in the bladder gradually diminished over 7 days, but mild submucosal edema and hemorrhage were still present when 2 dogs were necropsied, 7 days after distention. These studies indicated that retrograde urethrography in dogs may be complicated by hemorrhagic cystitis and urinary tract infection if performed with urinary bladder distention.

  6. Does Legalized Prostitution Increase Human Trafficking?

    OpenAIRE

    Seo-Young Cho; Axel Dreher; Eric Neumayer

    2011-01-01

    This paper investigates the impact of legalized prostitution on human trafficking inflows. According to economic theory, there are two opposing effects of unknown magnitude. The scale effect of legalized prostitution leads to an expansion of the prostitution market, increasing human trafficking, while the substitution effect reduces demand for trafficked women as legal prostitutes are favored over trafficked ones. Our empirical analysis for a cross-section of up to 150 countries shows that th...

  7. Barriers to combating human trafficking in Colombia

    OpenAIRE

    Wilcox, Daniel Joseph

    2015-01-01

    Approved for public release; distribution is unlimited Despite international and domestic policies and programs intended to combat human trafficking, Colombia remains one of the countries with the highest instances of human trafficking in the Western Hemisphere. Factors contributing to human trafficking in Colombia, such as internal violence and displacement, drug trafficking, a weak central government, and widespread corruption, have overpowered what energies the government marshaled agai...

  8. 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.

  9. 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.

  10. Security Implications of Human-Trafficking Networks

    Science.gov (United States)

    2007-06-15

    to those security concerns. Background How is Human Trafficking Carried Out? While trafficking victims are often found in sweatshops , domestic...labor. This type of trafficking is often found in agricultural labor, the production of goods (typically called sweatshops ) and construction labor

  11. Multisite tyrosine phosphorylation of the N-terminus of Mint1/X11α by Src kinase regulates the trafficking of amyloid precursor protein.

    Science.gov (United States)

    Dunning, Christopher J R; Black, Hannah L; Andrews, Katie L; Davenport, Elizabeth C; Conboy, Michael; Chawla, Sangeeta; Dowle, Adam A; Ashford, David; Thomas, Jerry R; Evans, Gareth J O

    2016-05-01

    Mint/X11 is one of the four neuronal trafficking adaptors that interact with amyloid precursor protein (APP) and are linked with its cleavage to generate β-amyloid peptide, a key player in the pathology of Alzheimer's disease. How APP switches between adaptors at different stages of the secretory pathway is poorly understood. Here, we show that tyrosine phosphorylation of Mint1 regulates the destination of APP. A canonical SH2-binding motif ((202) YEEI) was identified in the N-terminus of Mint1 that is phosphorylated on tyrosine by C-Src and recruits the active kinase for sequential phosphorylation of further tyrosines (Y191 and Y187). A single Y202F mutation in the Mint1 N-terminus inhibits C-Src binding and tyrosine phosphorylation. Previous studies observed that co-expression of wild-type Mint1 and APP causes accumulation of APP in the trans-Golgi. Unphosphorylatable Mint1 (Y202F) or pharmacological inhibition of Src reduced the accumulation of APP in the trans-Golgi of heterologous cells. A similar result was observed in cultured rat hippocampal neurons where Mint1(Y202F) permitted the trafficking of APP to more distal neurites than the wild-type protein. These data underline the importance of the tyrosine phosphorylation of Mint1 as a critical switch for determining the destination of APP. The regulation of amyloid precursor protein (APP) trafficking is poorly understood. We have discovered that the APP adapter, Mint1, is phosphorylated by C-Src kinase. Mint1 causes APP accumulation in the trans-Golgi network, whereas inhibition of Src or mutation of Mint1-Y202 permits APP recycling. The phosphorylation status of Mint1 could impact on the pathological trafficking of APP in Alzheimer's disease. © 2016 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.

  12. P120-Catenin Regulates Early Trafficking Stages of the N-Cadherin Precursor Complex.

    Directory of Open Access Journals (Sweden)

    Diana P Wehrendt

    Full Text Available It is well established that binding of p120 catenin to the cytoplasmic domain of surface cadherin prevents cadherin endocytosis and degradation, contributing to cell-cell adhesion. In the present work we show that p120 catenin bound to the N-cadherin precursor, contributes to its anterograde movement from the endoplasmic reticulum (ER to the Golgi complex. In HeLa cells, depletion of p120 expression, or blocking its binding to N-cadherin, increased the accumulation of the precursor in the ER, while it decreased the localization of mature N-cadherin at intercellular junctions. Reconstitution experiments in p120-deficient SW48 cells with all three major isoforms of p120 (1, 3 and 4 had similar capacity to promote the processing of the N-cadherin precursor to the mature form, and its localization at cell-cell junctions. P120 catenin and protein tyrosine phosphatase PTP1B facilitated the recruitment of the N-ethylmaleimide sensitive factor (NSF, an ATPase involved in vesicular trafficking, to the N-cadherin precursor complex. Dominant negative NSF E329Q impaired N-cadherin trafficking, maturation and localization at cell-cell junctions. Our results uncover a new role for p120 catenin bound to the N-cadherin precursor ensuring its trafficking through the biosynthetic pathway towards the cell surface.

  13. Human Sirtuin 2 Localization, Transient Interactions, and Impact on the Proteome Point to Its Role in Intracellular Trafficking.

    Science.gov (United States)

    Budayeva, Hanna G; Cristea, Ileana M

    2016-10-01

    Human sirtuin 2 (SIRT2) is an NAD + -dependent deacetylase that primarily functions in the cytoplasm, where it can regulate α-tubulin acetylation levels. SIRT2 is linked to cancer progression, neurodegeneration, and infection with bacteria or viruses. However, the current knowledge about its interactions and the means through which it exerts its functions has remained limited. Here, we aimed to gain a better understanding of its cellular functions by characterizing SIRT2 subcellular localization, the identity and relative stability of its protein interactions, and its impact on the proteome of primary human fibroblasts. To assess the relative stability of SIRT2 interactions, we used immunoaffinity purification in conjunction with both label-free and metabolic labeling quantitative mass spectrometry. In addition to the expected associations with cytoskeleton proteins, including its known substrate TUBA1A, our results reveal that SIRT2 specifically interacts with proteins functioning in membrane trafficking, secretory processes, and transcriptional regulation. By quantifying their relative stability, we found most interactions to be transient, indicating a dynamic SIRT2 environment. We discover that SIRT2 localizes to the ER-Golgi intermediate compartment (ERGIC), and that this recruitment requires an intact ER-Golgi trafficking pathway. Further expanding these findings, we used microscopy and interaction assays to establish the interaction and coregulation of SIRT2 with liprin-β1 scaffolding protein (PPFiBP1), a protein with roles in focal adhesions disassembly. As SIRT2 functions may be accomplished via interactions, enzymatic activity, and transcriptional regulation, we next assessed the impact of SIRT2 levels on the cellular proteome. SIRT2 knockdown led to changes in the levels of proteins functioning in membrane trafficking, including some of its interaction partners. Altogether, our study expands the knowledge of SIRT2 cytoplasmic functions to define a

  14. Routledge handbook of human trafficking

    NARCIS (Netherlands)

    Rijken, Conny; Piotrowicz, Ryszard; Uhl, Baerbe Heide

    2017-01-01

    Trafficking in human beings (THB) has been described as modern slavery. It is a serious criminal activity that has significant ramifications for the human rights of the victims. It poses major challenges to the state, society and individual victims. THB is not a static given but a constantly

  15. Anti-Human Trafficking Interventions

    Science.gov (United States)

    Davy, Deanna

    2016-01-01

    Since the early 2000s, a significant number of programs and policies have been developed and implemented to prevent and combat human trafficking. At the international, regional and national levels, government, and international, and nongovernment organizations have established plans of action, conducted training, developed policy tools, and…

  16. Membrane Trafficking and Vesicle Fusion

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 19; Issue 5. Membrane Trafficking and Vesicle Fusion: Post-Palade Era Researchers Win the Nobel Prize. Riddhi Atul Jani Subba Rao Gangi Setty. General Article Volume 19 Issue 5 May 2014 pp 421-445 ...

  17. Retrograde amnesia for semantic information in Alzheimer's disease

    OpenAIRE

    Meeter, M.; Kollen, A.; Scheltens, P.

    2005-01-01

    Patients with mild to moderate Alzheimer's disease and normal controls were tested on a retrograde amnesia test with semantic content (Neologism and Vocabulary Test, or NVT), consisting of neologisms to be defined. Patients showed a decrement as compared to normal controls, pointing to retrograde amnesia within semantic memory. No evidence for a gradient within this amnesia was found, although one was present on an autobiographic test of retrograde amnesia that had a wider time scale. Several...

  18. Journeys through the Golgi--taking stock in a new era.

    Science.gov (United States)

    Emr, Scott; Glick, Benjamin S; Linstedt, Adam D; Lippincott-Schwartz, Jennifer; Luini, Alberto; Malhotra, Vivek; Marsh, Brad J; Nakano, Akihiko; Pfeffer, Suzanne R; Rabouille, Catherine; Rothman, James E; Warren, Graham; Wieland, Felix T

    2009-11-16

    The Golgi apparatus is essential for protein sorting and transport. Many researchers have long been fascinated with the form and function of this organelle. Yet, despite decades of scrutiny, the mechanisms by which proteins are transported across the Golgi remain controversial. At a recent meeting, many prominent Golgi researchers assembled to critically evaluate the core issues in the field. This report presents the outcome of their discussions and highlights the key open questions that will help guide the field into a new era.

  19. Human trafficking and the healthcare professional.

    Science.gov (United States)

    Barrows, Jeffrey; Finger, Reginald

    2008-05-01

    Despite the legislation passed in the 19th century outlawing human slavery, it is more widespread today than at the conclusion of the civil war. Modern human slavery, termed human trafficking, comes in several forms. The most common type of human trafficking is sex trafficking, the sale of women and children into prostitution. Labor trafficking is the sale of men, women, and children into hard labor for which they receive little or no compensation. Other forms of trafficking include child soldiering, war brides, and organ removal. Healthcare professionals play a critical role in both finding victims of human trafficking while they are still in captivity, as well as caring for their mental and physical needs upon release. Those working in the healthcare profession need to be educated regarding how a trafficking victim may present, as well as their unique healthcare needs.

  20. Anterograde and Retrograde Amnesia following Bitemporal Infarction

    Directory of Open Access Journals (Sweden)

    A. Schnider

    1994-01-01

    Full Text Available A patient suffered very severe anterograde and retrograde amnesia following infarction of both medial temporal lobes (hippocampus and adjacent cortex and the left inferior temporo-occipital area. The temporal stem and the amygdala were intact; these structures do not appear to be critical for new learning in humans. Extension of the left-sided infarct into the inferior temporo-occipital lobe, an area critically involved in visual processing, appears to be responsible for our patient's loss of remote memories.

  1. Huntingtin-associated protein-1 (HAP1) regulates endocytosis and interacts with multiple trafficking-related proteins.

    Science.gov (United States)

    Mackenzie, Kimberly D; Lim, Yoon; Duffield, Michael D; Chataway, Timothy; Zhou, Xin-Fu; Keating, Damien J

    2017-07-01

    Huntingtin-associated protein 1 (HAP1) was initially identified as a binding partner of huntingtin, mutations in which underlie Huntington's disease. Subcellular localization and protein interaction data indicate that HAP1 may be important in vesicle trafficking, cell signalling and receptor internalization. In this study, a proteomics approach was used for the identification of novel HAP1-interacting partners to attempt to shed light on the physiological function of HAP1. Using affinity chromatography with HAP1-GST protein fragments bound to Sepharose columns, this study identified a number of trafficking-related proteins that bind to HAP1. Interestingly, many of the proteins that were identified by mass spectrometry have trafficking-related functions and include the clathrin light chain B and Sec23A, an ER to Golgi trafficking vesicle coat component. Using co-immunoprecipitation and GST-binding assays the association between HAP1 and clathrin light chain B has been validated in vitro. This study also finds that HAP1 co-localizes with clathrin light chain B. In line with a physiological function of the HAP1-clathrin interaction this study detected a dramatic reduction in vesicle retrieval and endocytosis in adrenal chromaffin cells. Furthermore, through examination of transferrin endocytosis in HAP1 -/- cortical neurons, this study has determined that HAP1 regulates neuronal endocytosis. In this study, the interaction between HAP1 and Sec23A was also validated through endogenous co-immunoprecipitation in rat brain homogenate. Through the identification of novel HAP1 binding partners, many of which have putative trafficking roles, this study provides us with new insights into the mechanisms underlying the important physiological function of HAP1 as an intracellular trafficking protein through its protein-protein interactions. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Biopolitical management, economic calculation and "trafficked women".

    Science.gov (United States)

    Berman, Jacqueline

    2010-01-01

    Narratives surrounding human trafficking, especially trafficking in women for sex work, employ gendered and racialized tropes that have among their effects, a shrouding of women's economic decision-making and state collusion in benefiting from their labour. This paper explores the operation of these narratives in order to understand the ways in which they mask the economics of trafficking by sensationalizing the sexual and criminal aspects of it, which in turn allows the state to pursue political projects under the guise of a benevolent concern for trafficked women and/or protection of its own citizens. This paper will explore one national example: Article 18 of Italian Law 40 (1998). I argue that its passage has led to an increase in cooperation with criminal prosecution of traffickers largely because it approaches trafficked women as capable of making decisions about how and what they themselves want to do. This paper will also consider a more global approach to trafficking embedded in the concept of "migration management", an International Organization for Migration (IOM) framework that is now shaping EU, US and other national immigration laws and policies that impact trafficking. It will also examine the inherent limitations of both the national and global approach as an occasion to unpack how Article 18 and Migration Management function as forms of biopolitical management that participate in the production of "trafficking victims" into a massified population to be managed, rather than engender a more engaged discussion of what constitutes trafficking and how to redress it.

  3. Retrograde prostatic urethroplasty with a balloon catheter

    International Nuclear Information System (INIS)

    Castaneda, F.; Reddy, P.; Hulbert, J.; Letourneau, J.G.; Hunter, D.W.; Castaneda-Zuniga, W.R.; Amplatz, K.

    1987-01-01

    Twenty-five patients with prostatism and documented BPH who were candidates for transurethral resection of the prostate were dilated for 10 minutes with 25-mm urethroplasty balloons using a retrograde transurethral approach. The procedure was performed under local anesthesia using 2% viscous lidocaine on an outpatient basis. A mild discomfort was experienced by all patients with a moderate urgency sensation. Mild transient hematuria was present in all, which cleared in 4 to 6 hours. Dysuria usually lasted for 72 hours. Significant improvement has been seen in the relief of symptoms in patients without middle-lobe hypertrophy as documented by uroflow studies, voiding cystourethrograms, and retrograde urethrograms. In patients with middle-lobe hypertrophy, moderate improvement in uroflow studies was observed, which correlated well with symptomatic improvement. Rectal US and MR studies have shown no evidence of intraprostatic or periprostatic abnormalities. No complications have been encountered so far. The longest current follow-up is 20 months, with a mean of 10 months

  4. IAEA Illicit Trafficking Database (ITDB)

    International Nuclear Information System (INIS)

    2010-01-01

    The IAEA Illicit Trafficking Database (ITDB) was established in 1995 as a unique network of points of contact connecting 100 states and several international organizations. Information collected from official sources supplemented by open-source reports. The 1994 - GC 38, resolution intensifies the activities through which the Agency is currently supporting Member States in this field. Member states were notified of completed database in 1995 and invited to participate. The purpose of the I TDB is to facilitate exchange of authoritative information among States on incidents of illicit trafficking and other related unauthorized activities involving nuclear and other radioactive materials; to collect, maintain and analyse information on such incidents with a view to identifying common threats, trends, and patterns; use this information for internal planning and prioritisation and provide this information to member states and to provide a reliable source of basic information on such incidents to the media, when appropriate

  5. A Healthy Live Birth Following ICSI with Retrograde Ejaculated Sperm

    African Journals Online (AJOL)

    AJRH Managing Editor

    Retrograde ejaculation, sometimes called dry orgasm, refers to the medical condition when semen enters the urinary bladder. (retrograde) instead of emerging through the penis after orgasm (antegrade). In some instances, a very minute quantity of antegrade semen appears in the ejaculate and may or may not be devoid of ...

  6. Using Kinesthetic Activities to Teach Ptolemaic and Copernican Retrograde Motion

    Science.gov (United States)

    Richards, Ted

    2012-01-01

    This paper describes a method for teaching planetary retrograde motion, and the Ptolemaic and Copernican accounts of retrograde motion, by means of a series kinesthetic learning activities (KLAs). In the KLAs described, the students literally walk through the motions of the planets in both systems. A retrospective statistical analysis shows that…

  7. Retrograde amnesia for semantic information in Alzheimer's disease

    NARCIS (Netherlands)

    Meeter, M.; Kollen, A.; Scheltens, P.

    2005-01-01

    Patients with mild to moderate Alzheimer's disease and normal controls were tested on a retrograde amnesia test with semantic content (Neologism and Vocabulary Test, or NVT), consisting of neologisms to be defined. Patients showed a decrement as compared to normal controls, pointing to retrograde

  8. Retrograde amnesia for semantic information in Alzheimer’s disease

    NARCIS (Netherlands)

    Meeter, M.; Knollen, A.; Scheltens, P.

    2005-01-01

    Patients with mild to moderate Alzheimer's disease and normal controls were tested on a retrograde amnesia test with semantic content (Neologism and Vocabulary Test, or NVT), consisting of neologisms to be defined. Patients showed a decrement as compared to normal controls, pointing to retrograde

  9. Disrupting circadian rhythms in rats induces retrograde amnesia

    NARCIS (Netherlands)

    Fekete, Mátyás; Ree, J.M. van; Niesink, Raymond J.M.; Wied, D. de

    1985-01-01

    Disrupting circadian organization in rats by phase-shifting the illumination cycle or by exposure to a reversed day/night cycle or to continuous light, resulted in retrograde amnesia for passive avoidance behavior. This retrograde amnesia induced by phase-shifting lasted at least 2 days, and

  10. Adenosine receptor desensitization and trafficking.

    Science.gov (United States)

    Mundell, Stuart; Kelly, Eamonn

    2011-05-01

    As with the majority of G-protein-coupled receptors, all four of the adenosine receptor subtypes are known to undergo agonist-induced regulation in the form of desensitization and trafficking. These processes can limit the ability of adenosine receptors to couple to intracellular signalling pathways and thus reduce the ability of adenosine receptor agonists as well as endogenous adenosine to produce cellular responses. In addition, since adenosine receptors couple to multiple signalling pathways, these pathways may desensitize differentially, while the desensitization of one pathway could even trigger signalling via another. Thus, the overall picture of adenosine receptor regulation can be complex. For all adenosine receptor subtypes, there is evidence to implicate arrestins in agonist-induced desensitization and trafficking, but there is also evidence for other possible forms of regulation, including second messenger-dependent kinase regulation, heterologous effects involving G proteins, and the involvement of non-clathrin trafficking pathways such as caveolae. In this review, the evidence implicating these mechanisms is summarized for each adenosine receptor subtype, and we also discuss those issues of adenosine receptor regulation that remain to be resolved as well as likely directions for future research in this field. Copyright © 2010 Elsevier B.V. All rights reserved.

  11. Loss of Optineurin In Vivo Results in Elevated Cell Death and Alters Axonal Trafficking Dynamics

    Science.gov (United States)

    Paulus, Jeremiah D.; Link, Brian A.

    2014-01-01

    Mutations in Optineurin have been associated with ALS, glaucoma, and Paget’s disease of bone in humans, but little is known about how these mutations contribute to disease. Most of the cellular consequences of Optineurin loss have come from in vitro studies, and it remains unclear whether these same defects would be seen in vivo. To answer this question, we assessed the cellular consequences of Optineurin loss in zebrafish embryos to determine if they showed the same defects as have been described in the in vitro studies. We found that loss of Optineurin resulted in increased cell death, as well as subtle cell morphology, cell migration and vesicle trafficking defects. However, unlike experiments on cells in culture, we found no indication that the Golgi apparatus was disrupted or that NF-κB target genes were upregulated. Therefore, we conclude that in vivo loss of Optineurin shows some, but not all, of the defects seen in in vitro work. PMID:25329564

  12. Modeling electric bicycle's lane-changing and retrograde behaviors

    Science.gov (United States)

    Tang, Tie-Qiao; Luo, Xiao-Feng; Zhang, Jian; Chen, Liang

    2018-01-01

    Recently, electric bicycle (EB) has been one important traffic tool due to its own merits. However, EB's motion behaviors (especially at a signalized/non-signalized intersection) are more complex than those of vehicle since it always has lane-changing and retrograde behaviors. In this paper, we propose a model to explore EB's lane-changing and retrograde behaviors on a road with a signalized intersection. The numerical results indicate that the proposed model can qualitatively describe each EB's lane-changing and retrograde behaviors near a signalized intersection, and that lane-changing and retrograde behaviors have prominent impacts on the signalized intersection (i.e., prominent jams and congestions occur). The above results show that EB should be controlled as a vehicle, i.e., lane-changing and retrograde behaviors at a signalized intersection should strictly be prohibited to improve the operational efficiency and traffic safety at the signalized intersection.

  13. 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.

  14. Golgi enrichment and proteomic analysis of developing Pinus radiata xylem by free-flow electrophoresis.

    Directory of Open Access Journals (Sweden)

    Harriet T Parsons

    Full Text Available Our understanding of the contribution of Golgi proteins to cell wall and wood formation in any woody plant species is limited. Currently, little Golgi proteomics data exists for wood-forming tissues. In this study, we attempted to address this issue by generating and analyzing Golgi-enriched membrane preparations from developing xylem of compression wood from the conifer Pinus radiata. Developing xylem samples from 3-year-old pine trees were harvested for this purpose at a time of active growth and subjected to a combination of density centrifugation followed by free flow electrophoresis, a surface charge separation technique used in the enrichment of Golgi membranes. This combination of techniques was successful in achieving an approximately 200-fold increase in the activity of the Golgi marker galactan synthase and represents a significant improvement for proteomic analyses of the Golgi from conifers. A total of thirty known Golgi proteins were identified by mass spectrometry including glycosyltransferases from gene families involved in glucomannan and glucuronoxylan biosynthesis. The free flow electrophoresis fractions of enriched Golgi were highly abundant in structural proteins (actin and tubulin indicating a role for the cytoskeleton during compression wood formation. The mass spectrometry proteomics data associated with this study have been deposited to the ProteomeXchange with identifier PXD000557.

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

    NARCIS (Netherlands)

    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.

    2016-01-01

    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

  16. 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

  17. 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.

  18. Mena-GRASP65 interaction couples actin polymerization to Golgi ribbon linking.

    Science.gov (United States)

    Tang, Danming; Zhang, Xiaoyan; Huang, Shijiao; Yuan, Hebao; Li, Jie; Wang, Yanzhuang

    2016-01-01

    In mammalian cells, the Golgi reassembly stacking protein 65 (GRASP65) has been implicated in both Golgi stacking and ribbon linking by forming trans-oligomers through the N-terminal GRASP domain. Because the GRASP domain is globular and relatively small, but the gaps between stacks are large and heterogeneous, it remains puzzling how GRASP65 physically links Golgi stacks into a ribbon. To explore the possibility that other proteins may help GRASP65 in ribbon linking, we used biochemical methods and identified the actin elongation factor Mena as a novel GRASP65-binding protein. Mena is recruited onto the Golgi membranes through interaction with GRASP65. Depleting Mena or disrupting actin polymerization resulted in Golgi fragmentation. In cells, Mena and actin were required for Golgi ribbon formation after nocodazole washout; in vitro, Mena and microfilaments enhanced GRASP65 oligomerization and Golgi membrane fusion. Thus Mena interacts with GRASP65 to promote local actin polymerization, which facilitates Golgi ribbon linking. © 2016 Tang 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).

  19. 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.

  20. A role for Sar1 and ARF1 GTPases during Golgi biogenesis in the protozoan parasite Trypanosoma brucei

    Science.gov (United States)

    Yavuz, Sevil; Warren, Graham

    2017-01-01

    A single Golgi stack is duplicated and partitioned into two daughter cells during the cell cycle of the protozoan parasite Trypanosoma brucei. The source of components required to generate the new Golgi and the mechanism by which it forms are poorly understood. Using photoactivatable GFP, we show that the existing Golgi supplies components directly to the newly forming Golgi in both intact and semipermeabilized cells. The movement of a putative glycosyltransferase, GntB, requires the Sar1 and ARF1 GTPases in intact cells. In addition, we show that transfer of GntB from the existing Golgi to the new Golgi can be recapitulated in semipermeabilized cells and is sensitive to the GTP analogue GTPγS. We suggest that the existing Golgi is a key source of components required to form the new Golgi and that this process is regulated by small GTPases. PMID:28495798

  1. The political aspects of human trafficking

    Directory of Open Access Journals (Sweden)

    N. M. Lukach

    2014-01-01

    The negative international results of human trafficking are researched by the author. Namely, problems of governance organization that are created by powerful criminal groups of human traffickers and smugglers, mass stay of a significant number of non­citizens in the country; formation of the negative international image of the origin, destination or transit country as the state which is unable to counter effectively illegal migration and human trafficking.

  2. Gun Trafficking and the Southwest Border

    Science.gov (United States)

    2009-07-29

    felons, drug traffickers, and juvenile gang members from acquiring firearms from gun traffickers. These criminals often acquire firearms from persons...renounced their U.S. citizenship; (8) persons restrained under a court-order from harassing, stalking , or threatening an intimate partner or child of... gang members from acquiring firearms from gun traffickers. These criminals often acquire firearms from a person who otherwise is not prohibited to

  3. Organized crime-trafficking with human being

    OpenAIRE

    Jelenová, Jana

    2011-01-01

    Organized crime - Trafficking in human beings This thesis deals with the criminal offence of trafficking in human beings under Sec. 168 of the Czech Criminal Code. A trafficking in human being is not a frequent criminal offence but with its consequences belongs to the most dangerous crimes. After the Velvet revolution the relevance of this crime has raised subsequently and therefore the regulation of this crime requires particular attention. It is important to find new ways and improve curren...

  4. Human Trafficking in the Emergency Department

    OpenAIRE

    Patel, Ronak B; Ahn, Roy; Burke, Thomas F

    2010-01-01

    Human trafficking continues to persist, affecting up to 200 million people worldwide. As clinicians in emergency departments commonly encounter victims of intimate partner violence, some of these encounters will be with trafficking victims. These encounters provide a rare opportunity for healthcare providers to intervene and help. This case report of a human trafficking patient from a teaching hospital illustrates the complexity in identifying these victims. Clinicians can better identify pot...

  5. Human organ trafficking in the cyber space

    Directory of Open Access Journals (Sweden)

    Vuletić Dejan

    2009-01-01

    Full Text Available The accelerated growth of the information-communication technology use brought about cyber crime as a new form of crime connected with the misuse of computer network. Human trafficking and human organ trafficking are changing in line with the state-of-art technological achievements i.e. becoming more and more characteristic of cyber space. Passing appropriate regulations at both national and international levels presents an important step in solving the problem of human organ trafficking through Internet.

  6. 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.

  7. Trafficking through COPII stabilises cell polarity and drives secretion during Drosophila epidermal differentiation.

    Directory of Open Access Journals (Sweden)

    Michaela Norum

    2010-05-01

    Full Text Available The differentiation of an extracellular matrix (ECM at the apical side of epithelial cells implies massive polarised secretion and membrane trafficking. An epithelial cell is hence engaged in coordinating secretion and cell polarity for a correct and efficient ECM formation.We are studying the molecular mechanisms that Drosophila tracheal and epidermal cells deploy to form their specific apical ECM during differentiation. In this work we demonstrate that the two genetically identified factors haunted and ghost are essential for polarity maintenance, membrane topology as well as for secretion of the tracheal luminal matrix and the cuticle. We show that they code for the Drosophila COPII vesicle-coating components Sec23 and Sec24, respectively, that organise vesicle transport from the ER to the Golgi apparatus.Taken together, epithelial differentiation during Drosophila embryogenesis is a concerted action of ECM formation, plasma membrane remodelling and maintenance of cell polarity that all three rely mainly, if not absolutely, on the canonical secretory pathway from the ER over the Golgi apparatus to the plasma membrane. Our results indicate that COPII vesicles constitute a central hub for these processes.

  8. From the endoplasmic reticulum to the plasma membrane: mechanisms of CFTR folding and trafficking.

    Science.gov (United States)

    Farinha, Carlos M; Canato, Sara

    2017-01-01

    CFTR biogenesis starts with its co-translational insertion into the membrane of endoplasmic reticulum and folding of the cytosolic domains, towards the acquisition of a fully folded compact native structure. Efficiency of this process is assessed by the ER quality control system that allows the exit of folded proteins but targets unfolded/misfolded CFTR to degradation. If allowed to leave the ER, CFTR is modified at the Golgi and reaches the post-Golgi compartments to be delivered to the plasma membrane where it functions as a cAMP- and phosphorylation-regulated chloride/bicarbonate channel. CFTR residence at the membrane is a balance of membrane delivery, endocytosis, and recycling. Several adaptors, motor, and scaffold proteins contribute to the regulation of CFTR stability and are involved in continuously assessing its structure through peripheral quality control systems. Regulation of CFTR biogenesis and traffic (and its dysregulation by mutations, such as the most common F508del) determine its overall activity and thus contribute to the fine modulation of chloride secretion and hydration of epithelial surfaces. This review covers old and recent knowledge on CFTR folding and trafficking from its synthesis to the regulation of its stability at the plasma membrane and highlights how several of these steps can be modulated to promote the rescue of mutant CFTR.

  9. The calcium-binding protein ALG-2 regulates protein secretion and trafficking via interactions with MISSL and MAP1B proteins.

    Science.gov (United States)

    Takahara, Terunao; Inoue, Kuniko; Arai, Yumika; Kuwata, Keiko; Shibata, Hideki; Maki, Masatoshi

    2017-10-13

    Mobilization of intracellular calcium is essential for a wide range of cellular processes, including signal transduction, apoptosis, and vesicular trafficking. Several lines of evidence have suggested that apoptosis-linked gene 2 (ALG-2, also known as PDCD6 ), a calcium-binding protein, acts as a calcium sensor linking calcium levels with efficient vesicular trafficking, especially at the endoplasmic reticulum (ER)-to-Golgi transport step. However, how ALG-2 regulates these processes remains largely unclear. Here, we report that M APK1- i nteracting and s pindle- s tabilizing (MISS)- l ike (MISSL), a previously uncharacterized protein, interacts with ALG-2 in a calcium-dependent manner. Live-cell imaging revealed that upon a rise in intracellular calcium levels, GFP-tagged MISSL (GFP-MISSL) dynamically relocalizes in a punctate pattern and colocalizes with ALG-2. MISSL knockdown caused disorganization of the components of the ER exit site, the ER-Golgi intermediate compartment, and Golgi. Importantly, knockdown of either MISSL or ALG-2 attenuated the secretion of se creted a lkaline p hosphatase (SEAP), a model secreted cargo protein, with similar reductions in secretion by single- and double-protein knockdowns, suggesting that MISSL and ALG-2 act in the same pathway to regulate the secretion process. Furthermore, ALG-2 or MISSL knockdown delayed ER-to-Golgi transport of procollagen type I. We also found that ALG-2 and MISSL interact with microtubule-associated protein 1B (MAP1B) and that MAP1B knockdown reverts the reduced secretion of SEAP caused by MISSL or ALG-2 depletion. These results suggest that a change in the intracellular calcium level plays a role in regulation of the secretory pathway via interaction of ALG-2 with MISSL and MAP1B. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

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

    Science.gov (United States)

    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.

  11. 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.

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

    Science.gov (United States)

    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.

  13. Diagnosis and treatment with endoscopic retrograde cholangiopancreatography

    International Nuclear Information System (INIS)

    Soendenaa, K.; Horn, A.; Viste, A.

    1994-01-01

    Endoscopic retrograde cholangiopancreatography (ERCP) was carried out for the first time in 1968. Five years later endoscopic sphincterotomy was performed. Since then both modalities have become established as necessary adjuncts in the diagnosis and treatment of patients with pathology in the bile duct or pancreas. The main indication is common bile duct stone, and as a consequence of this treatment fewer patients are now treated surgically. Patients with malignant bile duct obstruction can be given reasonable palliation of both jaundice and pruritus and therefore improved quality of life. Some reports indicate that endoscopic drainage may be useful for pancreatic stenosis. Complications are few, but vigilance and prompt treatment is necessary to keep morbidity at a minimum. Follow-up after several years shows that sphincterotomy is successful also in the long term. The authors discuss the present diagnostic and therapeutic situation. 31 refs., 2 tabs

  14. Human trafficking and exploitation: A global health concern.

    Science.gov (United States)

    Zimmerman, Cathy; Kiss, Ligia

    2017-11-01

    In this collection review, Cathy Zimmerman and colleague introduce the PLOS Medicine Collection on Human Trafficking, Exploitation and Health, laying out the magnitude of the global trafficking problem and offering a public health policy framework to guide responses to trafficking.

  15. Our experiences on retrograde intrarenal surgery

    Directory of Open Access Journals (Sweden)

    Namık Kemal Hatipoğlu

    2014-03-01

    Full Text Available Objective: To evaluate outcomes of the cases who had undergone retrograde intrarenal surgery (RIRS in our clinics. Methods: Outcomes of 100 cases who had undergone RIRS because of renal stones between February 2012, and May 2013 were retrospectively evaluated. Results: Study population consisted of 35 female and 65 male patients with a mean age of 36.81(1-76 years. RIRS was performed with the indication of rest double J (D-J stent (n=1, and renal stone (n=99. Mean stone size was 15.26 (5-27 mm. Preoperatively, 61 cases (61% had preexisting D-J stents, while 39 (39% cases were stentless. Access sheaths were used in 86 (86% cases, while in 14 (14% cases the procedure was applied without using an access sheath. Mean operative, and fluoroscopy times were 52.72 (10-120 minus, and 57.32 (10-180 seconds, respectively. Postoperatively D-J stents were implanted in 88 (88% cases, and 12 (12% cases were stent-free. Mean hospital time was 1.3 (1-7 days. After one month postoperatively, stone-free rate was achieved in 87 (87% patients. Clinically insignificant residual stone fragments (CIRF 6 (6%, and residual stones 7 (7% were also detected. The latter group consisted of cases with horseshoe kidney (n=1, pelvic kidney (n=1, and kyphoscoliosis (n=1. Also in two case procedure was terminated prematurely, because of blurring of the vision secondary to bleeding. Apart from these patients, any preoperative complication did not develop. During follow-up period, urinary tract infection developed in 3 patients with resultant renal parenchymal damage in one patient. In one patient, D-J stent migrated into ureter. Conclusion: Retrograde intrarenal surgery is an effective and safe technique in the management of renal stones.

  16. 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.

  17. Key challenges in the combat of human trafficking : Evaluating the EU trafficking strategy and EU trafficking directive

    NARCIS (Netherlands)

    Bosma, Alice; Rijken, Conny

    2016-01-01

    The problem of trafficking in human beings (THB) is still omnipresent in Europe, despite the numerous preventive and retributive actions taken. This article evaluates the two most important EU-instruments to combat trafficking: the EU Directive and the EU Strategy. Based on secondary analysis of

  18. PRODUCTION OF NEAR-EARTH ASTEROIDS ON RETROGRADE ORBITS

    International Nuclear Information System (INIS)

    Greenstreet, S.; Gladman, B.; Ngo, H.; Granvik, M.; Larson, S.

    2012-01-01

    While computing an improved near-Earth object (NEO) steady-state orbital distribution model, we discovered in the numerical integrations the unexpected production of retrograde orbits for asteroids that had originally exited from the accepted main-belt source regions. Our model indicates that ∼0.1% (a factor of two uncertainty) of the steady-state NEO population (perihelion q < 1.3 AU) is on retrograde orbits. These rare outcomes typically happen when asteroid orbits flip to a retrograde configuration while in the 3:1 mean-motion resonance with Jupiter and then live for ∼0.001 to 100 Myr. The model predicts, given the estimated near-Earth asteroid (NEA) population, that a few retrograde 0.1-1 km NEAs should exist. Currently, there are two known MPC NEOs with asteroidal designations on retrograde orbits which we therefore claim could be escaped asteroids instead of devolatilized comets. This retrograde NEA population may also answer a long-standing question in the meteoritical literature regarding the origin of high-strength, high-velocity meteoroids on retrograde orbits.

  19. Phosphatidylinositol-4,5-bisphosphate is required for KCNQ1/KCNE1 channel function but not anterograde trafficking.

    Directory of Open Access Journals (Sweden)

    Alice A Royal

    Full Text Available The slow delayed-rectifier potassium current (IKs is crucial for human cardiac action potential repolarization. The formation of IKs requires co-assembly of the KCNQ1 α-subunit and KCNE1 β-subunit, and mutations in either of these subunits can lead to hereditary long QT syndrome types 1 and 5, respectively. It is widely recognised that the KCNQ1/KCNE1 (Q1/E1 channel requires phosphatidylinositol-4,5-bisphosphate (PIP2 binding for function. We previously identified a cluster of basic residues in the proximal C-terminus of KCNQ1 that form a PIP2/phosphoinositide binding site. Upon charge neutralisation of these residues we found that the channel became more retained in the endoplasmic reticulum, which raised the possibility that channel-phosphoinositide interactions could play a role in channel trafficking. To explore this further we used a chemically induced dimerization (CID system to selectively deplete PIP2 and/or phosphatidylinositol-4-phosphate (PI(4P at the plasma membrane (PM or Golgi, and we subsequently monitored the effects on both channel trafficking and function. The depletion of PIP2 and/or PI(4P at either the PM or Golgi did not alter channel cell-surface expression levels. However, channel function was extremely sensitive to the depletion of PIP2 at the PM, which is in contrast to the response of other cardiac potassium channels tested (Kir2.1 and Kv11.1. Surprisingly, when using the CID system IKs was dramatically reduced even before dimerization was induced, highlighting limitations regarding the utility of this system when studying processes highly sensitive to PIP2 depletion. In conclusion, we identify that the Q1/E1 channel does not require PIP2 or PI(4P for anterograde trafficking, but is heavily reliant on PIP2 for channel function once at the PM.

  20. Dynamics of the retrograde 1/1 mean motion resonance

    Science.gov (United States)

    Huang, Yukun; Li, Miao; Li, Junfeng; Gong, Shengping

    2018-04-01

    Mean motion resonances are very common in the solar system. Asteroids in mean motion resonances with giant planets have been studied for centuries. But it was not until recently that asteroids in retrograde mean motion resonances with Jupiter and Saturn were discovered. The newly discovered asteroid, 2015 BZ509 is confirmed to be the first asteroid in retrograde 1:1 mean motion resonance (or retrograde co-orbital resonance) with Jupiter, which gives rise to our interests in its unique resonant dynamics. In this study, we thoroughly investigate the phase-space structure of the retrograde 1:1 resonance within the framework of the circular restricted three-body problem. We begin by constructing a simple integrable approximation for the planar retrograde resonance with the Hamiltonian approach and show that the variables definition of the retrograde resonance is very different to the prograde one. When it comes to the disturbing function, we abandon the classical series expansion approach, whereas numerically carry out the averaging process on the disturbing function in closed form. The phase portrait of the retrograde 1:1 resonance is depicted with the level curves of the averaged Hamiltonian. We find that the topological structure of phase space for the retrograde 1:1 resonance is very different to other resonances, due to the consistent existence of the collision separatrix. And the surprising bifurcation of equilibrium point around 180° (i.e., the apocentric libration center) has never been found in any other mean motion resonances before. We thoroughly analyze the novel apocentric librations and find that close encounter with the planet does not always lead to the disruption of a stable apocentric libration. Afterwards, we examine the Kozai dynamics inside the mean motion resonance with the similar Hamiltonian approach and explain why the exact resonant point does not exist in the 3D retrograde 1:1 resonance model.

  1. The formation of retrograde planetary orbits by close stellar encounters

    Directory of Open Access Journals (Sweden)

    Ford E. B.

    2011-02-01

    Full Text Available We consider the growing number of observations of the RossiterMcLaughlin effect in transiting planets, which seem to suggest that ~30% of transiting planets are in highly inclined or retrograde orbits. We consider the dense cluster environment in which stars are born and investigate whether perturbations from passing stars can drive planetary systems into retrograde configurations. We find that fly-bys can result in significantly more inclination excitation than might naively be expected from impulse approximations, leading to several percent of stellar systems possessing planets in retrograde orbits.

  2. Using Kinesthetic Activities to Teach Ptolemaic and Copernican Retrograde Motion

    Science.gov (United States)

    Richards, Ted

    2012-06-01

    This paper describes a method for teaching planetary retrograde motion, and the Ptolemaic and Copernican accounts of retrograde motion, by means of a series kinesthetic learning activities (KLAs). In the KLAs described, the students literally walk through the motions of the planets in both systems. A retrospective statistical analysis shows that students who participated in these activities performed better on examination questions pertaining to retrograde motion than students who did not. Potential explanations for this result, including the breaking of classroom routine, the effect of body movement on conceptual memory, and egocentric spatial proprioception, are considered.

  3. The Palermo Protocol: Trafficking Takes it All

    Directory of Open Access Journals (Sweden)

    Jónína Einarsdóttir

    2014-12-01

    Full Text Available The Palermo Protocol is the outcome of bargain and lobbying with global institutions, NGOs and government representatives embattling to enforce their interests. The outcome is the concept of trafficking that embraces the struggles against prostitution, slavery and child labour. This broad concept has allowed various local cultural practices and survival strategies of those who live under difficult conditions to become classified as trafficking. While such definition may facilitate fundraising there are adverse consequences to be considered. Firstly, hazardous conditions of children that obviously are not trafficking tend to become ignored. Second, the victims of “real” trafficking become invisible by the excessive number of children allegedly trafficked. Third, the broad definition of trafficking has contributed to criminalization of whole communities and consequent conflicts between NGOs engaged in anti-trafficking activities and the communities involved. Such a situation is not in the best interest of the children involved. Rather than spending huge amount of resources on the conventional anti-trafficking measures there is a need to address the root causes of whatsoever unacceptable condition a child is suffering from.

  4. 78 FR 40619 - Combating Wildlife Trafficking

    Science.gov (United States)

    2013-07-05

    ... derivative parts and products (together known as ``wildlife trafficking'') represent an international crisis... trafficking in accordance with the following objectives: (a) in appropriate cases, the United States shall... Quality; (xii) the Office of Science and Technology Policy; (xiii) the Office of Management and Budget...

  5. Human Trafficking. Ministering to The 'Invisible' Victim.

    Science.gov (United States)

    Scanlon, Colleen; Krausa, Laura

    2016-07-01

    Human trafficking is modern-day slavery - an insidious, criminal industry that gener- ates billions of dollars in labor trafficking alone. It knows no boundary of continent, country, race or class; it is a shattering, impartial predator that robs individuals of their basic human dignity.

  6. TRACE-ing human trafficking : Project Findings

    NARCIS (Netherlands)

    Rijken, Conny; Pijnenburg, Annick

    2016-01-01

    Human trafficking is one of the largest criminal enterprises in the world. It is a multi-billion-dollar crime of global scale. This is because human trafficking as a criminal enterprise continues to evolve as a high profit-low risk business for perpetrators and challenges policy makers, law

  7. A Proteomics Approach to Membrane Trafficking

    NARCIS (Netherlands)

    Groen, A.J.; Vries, de S.C.; Lilley, K.S.

    2008-01-01

    Membrane trafficking, including that of integral membrane proteins as well as peripherally associated proteins, appears to be a vital process common to all eukaryotes. An important element of membrane trafficking is to determine the protein composition of the various endomembrane compartments. A

  8. Regulation of ER-Golgi Transport Dynamics by GTPases in Budding Yeast

    Directory of Open Access Journals (Sweden)

    Yasuyuki Suda

    2018-01-01

    Full Text Available A large number of proteins are synthesized de novo in the endoplasmic reticulum (ER. They are transported through the Golgi apparatus and then delivered to their proper destinations. The ER and the Golgi play a central role in protein processing and sorting and show dynamic features in their forms. Ras super family small GTPases mediate the protein transport through and between these organelles. The ER-localized GTPase, Sar1, facilitates the formation of COPII transport carriers at the ER exit sites (ERES on the ER for the transport of cargo proteins from the ER to the Golgi. The Golgi-localized GTPase, Arf1, controls intra-Golgi, and Golgi-to-ER transport of cargo proteins by the formation of COPI carriers. Rab GTPases localized at the Golgi, which are responsible for fusion of membranes, are thought to establish the identities of compartments. Recent evidence suggests that these small GTPases regulate not only discrete sites for generation/fusion of transport carriers, but also membrane dynamics of the organelles where they locate to ensure the integrity of transport. Here we summarize the current understandings about the membrane traffic between these organelles and highlight the cutting-edge advances from super-resolution live imaging of budding yeast, Saccharomyces cerevisiae.

  9. 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.

  10. 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.

  11. Was Trafficking in Persons Really Criminalised?

    Directory of Open Access Journals (Sweden)

    Kristiina Kangaspunta

    2015-04-01

    Full Text Available This paper examines the successes and setbacks in the criminal justice response to trafficking in persons. While today, the majority of countries have passed specific legislation criminalising human trafficking in response to the United Nations Protocol to Prevent, Suppress and Punish Trafficking in Persons, Especially Women and Children, there are still very few convictions of trafficking. Using currently available knowledge, this paper discusses four possible reasons for low conviction rates. Further, the paper suggests that due to the heavy dependency on victim testimonies when prosecuting trafficking in persons crimes, members of criminal organisations that are easily identifiable by victims may face criminal charges more frequently than other members of the criminal group, particularly those in positions of greater responsibility who profit the most from the criminal activities. In this context, the exceptionally high number of women among convicted offenders is explored.

  12. Medical tourism and organ trafficking

    Directory of Open Access Journals (Sweden)

    Athena Smith

    2012-01-01

    Full Text Available The growth of medical tourism in developing nations has not only helped the local economies but also has assisted patients from the developed world to seek treatment at a lower cost. However, the expansion of the sector has been stigmatized by the growth of organ trafficking that facilitates organ transplantation to those who can afford it. Although developing countries have been taking measures to prohibit the sale of organs, the large gap between demand and supply has fuelled a black market that involves the "brokers", the medical personnel and the poor whose abuse and exploitation is fuelled by the expansion of the sector and the illegitimate opportunities it creates on the side. The problem is exacerbated by the low supply in developed countries, where living potential donors appear to be misinformed about the process and hesitate to register as donors. The need for a nationwide campaign of awareness is urgently needed as the expansion of medical tourism has the potential of encouraging a further rise in organ trafficking.

  13. Antegrade or Retrograde Accessory Pathway Conduction: Who Dies First?

    Directory of Open Access Journals (Sweden)

    Claudio Hadid, MD

    2012-05-01

    Full Text Available A 36 year-old man with Wolff Parkinson White syndrome due to a left-sided accessory pathway (AP was referred for catheter ablation. Whether abolition of antegrade and retrograde AP conduction during ablation therapy occurs simultaneously, is unclear. At the ablation procedure, radiofrequency delivery resulted in loss of preexcitation followed by a short run of orthodromic tachycardia with eccentric atrial activation, demonstrating persistence of retrograde conduction over the AP after abolition of its antegrade conduction. During continued radiofrequency delivery at the same position, the fifth non-preexcitated beat failed to conduct retrogradely and the tachycardia ended. In this case, antegrade AP conduction was abolished earlier than retrograde conduction.

  14. Prostatic urethra malformation associated with retrograde ejaculation: a case report.

    Science.gov (United States)

    Zhao, Kai; Zhang, Jianzhong; Xu, Aiming; Zhang, Cheng; Wang, Zengjun

    2016-12-21

    Retrograde ejaculation can have anatomical, neurogenic, or pharmacological causes. Among these factors, malformation of the prostatic urethra is an uncommon cause. We describe a 29-year-old Han Chinese man with absence of his verumontanum combined with ejaculatory duct cysts, and no other cause for ejaculatory dysfunction. His verumontanum was replaced by a deep groove adjacent to his bladder neck, which could significantly influence bladder neck contraction. In addition, the large cysts in the ejaculatory duct could obstruct the anterior outlet of his prostatic urethra and prevent seminal fluid flow in an anterograde direction. There are few reports of retrograde ejaculation associated with congenital malformations of the posterior urethra. Malformations associated with bladder neck laxity and increased tone of the prostatic urethral outlet can contribute to retrograde ejaculation. Malformation of the prostatic urethra is an uncommon cause of retrograde ejaculation, and can be difficult to treat.

  15. Huge biloma after endoscopic retrograde cholangiopancreatography and endoscopic biliary sphincterotomy

    Directory of Open Access Journals (Sweden)

    Harith M. Alkhateeb

    2015-01-01

    Conclusions: (1 Following endoscopic retrograde cholangiopancreatography, a patient’s complaints should not be ignored. (2 A massive biloma can occur due to such procedures. (3 Conservative treatment with minimal invasive technique can prove to be effective.

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

    Science.gov (United States)

    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.

  17. Retrograde Melting and Internal Liquid Gettering in Silicon

    Energy Technology Data Exchange (ETDEWEB)

    Hudelson, Steve; Newman, Bonna K.; Bernardis, Sarah; Fenning, David P.; Bertoni, Mariana I.; Marcus, Matthew A.; Fakra, Sirine C.; Lai, Barry; Buonassisi, Tonio

    2011-07-01

    Retrograde melting (melting upon cooling) is observed in silicon doped with 3d transition metals, via synchrotron-based temperature-dependent X-ray microprobe measurements. Liquid metal-silicon droplets formed via retrograde melting act as efficient sinks for metal impurities dissolved within the silicon matrix. Cooling results in decomposition of the homogeneous liquid phase into solid multiple-metal alloy precipitates. These phenomena represent a novel pathway for engineering impurities in semiconductor-based systems.

  18. Retrograde vs. Antegrade Puncture for Infra-Inguinal Angioplasty

    International Nuclear Information System (INIS)

    Nice, C.; Timmons, G.; Bartholemew, P.; Uberoi, R.

    2003-01-01

    This study was done to compare antegrade punctures with a retrograde puncture technique for infrainguinal angioplasty. A group of 100 consecutive patients (71 men, 29 women) were randomized for antegrade puncture or retrograde puncture of the common femoral artery. Following retrograde puncture the guidewire was 'turned' and placed into the superficial femoral artery. The time for gaining access, screening time, radiation dose, patient height, weight and complications were recorded. All patients were reviewed the day after the procedure and within 3 months. Data from 46 patients (34 males and 12 females) in the retrograde group and 44 (28 males and 16 females) in the antegrade group were available for analysis. Mean procedure time,screening time, radiation dose, height and weight were 8.3 minutes(range 3-22), 2.1 minutes (0.3-6.5), 7950 mGy cm -2 (820-71250), 169 cm (149-204) and 79 kg (32-108) for retrograde puncture and 8 min (2-60), 0.7 min (0.0-3.2), 1069 mGycm -2 (0-15400), 169 cm (152-186) and 75 kg (39-125) for antegrade punctures, respectively. An average of 1.2 (1-2) punctures was required for retrograde and 1.75 (1-8) for antegrade. Seven small hematomas occurred with antegrade and three for retrograde puncture.Retrograde puncture is technically easier with a tendency to fewer complications but results in a higher radiation dose. This technique should be used in difficult patients at high risk of haematoma formation

  19. Mismatch analysis of humeral nailing. Antegrade versus retrograde insertion

    International Nuclear Information System (INIS)

    Mahaisavariya, B.; Jiamwatthanachai, P.; Aroonjarattham, P.; Aroonjarattham, K.; Wongcumchang, M.; Sitthiseripratip, K.

    2011-01-01

    Closed humeral nailing is now considered an alternative treatment for humeral-shaft fracture. The nail can be inserted with either the antegrade or retrograde method. We investigated and compared the problem of geometric mismatch of the humeral nail to the humerus between the two methods of insertion. The study was performed using virtual simulation based on computed tomography (CT) data of 76 Thai cadaveric humeri and the commonly used Russell-Taylor humeral nail 8 mm in diameter and 220 mm long. Mismatch of the nail to the intact humerus was analyzed and compared between the antegrade and retrograde nailing approaches. The results showed: the diameter of the medullary canal averaged 7.9-13.8 mm; the minimal reaming diameter to accommodate virtual nail insertion averaged 8.8-14.8 mm for the antegrade and 8.8-29.3 mm for the retrograde approach; the minimal reaming thickness of the inner cortex averaged 0.1-1.5 mm for the antegrade and 0.1-9.9 mm for the retrograde approach; the percentages of cortical bone removed prior to nail insertion were 3.8-107.1% and 3.8-1,287.6% for the antegrade and retrograde approaches, respectively; the eccentricity of the nail-medullary canal center were 0.4-3.4 and 0.4-10.6 mm for the antegrade and retrograde approaches, respectively. Less mismatching occurred with antegrade nailing than with the retrograde approach. Retrograde nailing requires excessive reaming at the distal part of the humerus to accommodate nail insertion. This may create bone weakness and the risk of supracondylar fracture. (author)

  20. RABA Members Act in Distinct Steps of Subcellular Trafficking of the FLAGELLIN SENSING2 Receptor[W

    Science.gov (United States)

    Choi, Seung-won; Tamaki, Takayuki; Ebine, Kazuo; Uemura, Tomohiro; Ueda, Takashi; Nakano, Akihiko

    2013-01-01

    Cell surface proteins play critical roles in the perception of environmental stimuli at the plasma membrane (PM) and ensuing signal transduction. Intracellular localization of such proteins must be strictly regulated, which requires elaborate integration of exocytic and endocytic trafficking pathways. Subcellular localization of Arabidopsis thaliana FLAGELLIN SENSING2 (FLS2), a receptor that recognizes bacterial flagellin, also depends on membrane trafficking. However, our understanding about the mechanisms involved is still limited. In this study, we visualized ligand-induced endocytosis of FLS2 using green fluorescent protein (GFP)-tagged FLS2 expressed in Nicotiana benthamiana. Upon treatment with the flg22 peptide, internalized FLS2-GFP from the PM was transported to a compartment with properties intermediate between the trans-Golgi network (TGN) and the multivesicular endosome. This compartment gradually discarded the TGN characteristics as it continued along the trafficking pathway. We further found that FLS2 endocytosis involves distinct RABA/RAB11 subgroups at different steps. Moreover, we demonstrated that transport of de novo–synthesized FLS2 to the PM also involves a distinct RABA/RAB11 subgroup. Our results demonstrate the complex regulatory system for properly localizing FLS2 and functional differentiation in RABA members in endo- and exocytosis. PMID:23532067

  1. Tracking Traffickers. The IAEA Incident and Trafficking Database

    International Nuclear Information System (INIS)

    Webb, Greg

    2013-01-01

    Radioactive material is missing from a hospital. Contaminated metal is found in a scrap yard. Smugglers try to peddle nuclear- weapon-usable material. These different scenarios illustrate the risks that these materials can pose to human safety and security. To assess those risks and to develop strategies to reduce them, States must understand the implications and the scope of such incidents that are occurring around the world. To better understand and respond to these events, the IAEA maintains an Incident and Trafficking Database (ITDB) which collects information from 122 participating States and some select international organizations. They are asked to share data on a voluntary basis about incidents in which nuclear and other radioactive material has fallen ''out of regulatory control.'' This could mean reporting cases of material that has gone missing, or discoveries of material where none was expected. The cases range from the innocent misplacement of industrial radioactive sources to criminal smuggling efforts which could aid terrorist acts. This information is shared among ITDB participants, and IAEA analysts try to identify trends and characteristics that could help prevent the misuse of these potentially dangerous materials. ''The ITDB has become an internationally recognized tool for States to study the extent and nature of these incidents,'' said John Hilliard, head of the Information Management and Coordination Section that administers the database. ''We've learned a lot by studying them, and we hope the information helps us prevent accidents or crimes in the future.'' The IAEA established the database in 1995 after States became alarmed by a growing number of trafficking incidents in the early 1990s. The service was originally operated by the Department of Safeguards, but later moved to the Department of Nuclear Safety and Security, where the Office of Nuclear Security now administers all the data collection and analysis

  2. Distant retrograde orbits and the asteroid hazard

    Science.gov (United States)

    Perozzi, Ettore; Ceccaroni, Marta; Valsecchi, Giovanni B.; Rossi, Alessandro

    2017-08-01

    Distant Retrograde Orbits (DROs) gained a novel wave of fame in space mission design because of their numerous advantages within the framework of the US plans for bringing a large asteroid sample in the vicinity of the Earth as the next target for human exploration. DROs are stable solutions of the three-body problem that can be used whenever an object, whether of natural or artificial nature, is required to remain in the neighborhood of a celestial body without being gravitationally captured by it. As such, they represent an alternative option to Halo orbits around the collinear Lagrangian points L1 and L2. Also known under other names ( e.g., quasi-satellite orbits, cis-lunar orbits, family- f orbits) these orbital configurations found interesting applications in several mission profiles, like that of a spacecraft orbiting around the small irregularly shaped satellite of Mars Phobos or the large Jovian moon Europa. In this paper a basic explanation of the DRO dynamics is presented in order to clarify some geometrical properties that characterize them. Their accessibility is then discussed from the point of view of mission analysis under different assumptions. Finally, their relevance within the framework of the present asteroid hazard protection programs is shown, stressing the significant increase in warning time they would provide in the prediction of impactors coming from the direction of the Sun.

  3. Increased sinusoidal volume and solute extraction during retrograde liver perfusion

    International Nuclear Information System (INIS)

    Bass, N.M.; Manning, J.A.; Weisiger, R.A.

    1989-01-01

    Retrograde isolated liver perfusion has been used to probe acinar functional heterogeneity, but the hemodynamic effects of backward flow have not been characterized. In this study, extraction of a long-chain fatty acid derivative, 12-N-methyl-7-nitrobenzo-2-oxa-1,3-diazol-amino stearate (12-NBDS), was greater during retrograde than during anterograde perfusion of isolated rat liver. To determine whether hemodynamic differences between anterograde and retrograde perfused livers could account for this finding, the hepatic extracellular space was measured for both directions of flow by means of [ 14 C]sucrose washout during perfusion as well as by direct measurement of [ 14 C]sucrose entrapped during perfusion. A three- to fourfold enlargement of the total hepatic extracellular space was found during retrograde perfusion by both approaches. Examination of perfusion-fixed livers by light microscopy and morphometry revealed that marked distension of the sinusoids occurred during retrograde perfusion and that this accounts for the observed increase in the [ 14 C]sucrose space. These findings support the hypothesis that maximum resistance to perfusate flow in the isolated perfused rat liver is located at the presinusoidal level. In addition, increased transit time of perfusate through the liver and greater sinusoidal surface area resulting from sinusoidal distension may account for the higher extraction of 12-NBDS and possibly other compounds by retrograde perfused liver

  4. The inherent catastrophic traps in retrograde CTO PCI.

    Science.gov (United States)

    Wu, Eugene B; Tsuchikane, Etsuo

    2018-05-01

    When we learn to drive, our driving instructor tells us how to check the side mirror and turn your head to check the blind spot before changing lanes. He tells us how to stop at stop signs, how to drive in slippery conditions, the safe stopping distances, and these all make our driving safe. Similarly, when we learn PCI, our mentors teach us to seat the guiding catheter co-axially, to wire the vessel safely, to deliver balloon and stents over the wire, to watch the pressure of the guiding, in order that we perform PCI safely and evade complications. In retrograde CTO PCI, there is no such published teaching. Also many individual mentors have not had the wide experience to see all the possible complications of retrograde CTO PCI and, therefore, may not be able to warn their apprentice. As the number of retrograde procedures increase worldwide, there is a corresponding increase in catastrophic complications, many of which, we as experts, can see are easily avoidable. To breach this gap in knowledge, this article describes 12 commonly met inherent traps in retrograde CTO PCI. They are inherent because by arranging our equipment in the manner to perform retrograde CTO PCI, these complications are either induced directly or happen easily. We hope this work will enhance safety of retrograde CTO PCI and avoid many catastrophic complications for our readers and operators. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  5. Dysfunction of bovine endogenous retrovirus K2 envelope glycoprotein is related to unsuccessful intracellular trafficking.

    Science.gov (United States)

    Nakaya, Yuki; Miyazawa, Takayuki

    2014-06-01

    Endogenous retroviruses (ERVs) are the remnants of retroviral infection of ancestral germ cells. Mutations introduced into ERVs halt the production of infectious agents, but their effects on the function of retroviral proteins are not fully understood. Retroviral envelope glycoproteins (Envs) are utilized in membrane fusion during viral entry, and we recently identified intact coding sequences for bovine endogenous retrovirus K1 (BERV-K1) and BERV-K2 Envs. Amino acid sequences of BERV-K1 Env (also called Fematrin-1) and BERV-K2 Env are similar, and both viruses are classified in the genus Betaretrovirus. While Fematrin-1 plays an important role in cell-to-cell fusion in bovine placenta, the BERV-K2 envelope gene is marginally expressed in vivo, and its recombinant Env protein is defective in membrane fusion due to inefficient cleavage of surface (SU) and transmembrane subunits. Here, we conducted chimeric analyses of Fematrin-1 and BERV-K2 Envs and revealed that defective maturation of BERV-K2 Env contributed to failed intracellular trafficking. Fluorescence microscopy and flow cytometric analysis suggested that in contrast to Fematrin-1 Env, BERV-K2 Env could not be transported from the endoplasmic reticulum to the trans-Golgi network, where cellular proteases required for processing retroviral Envs are localized. We also identified that one of the responsive regions of this phenomenon resided within a 65-amino-acid region of BERV-K2 SU. This is the first report to identify that retroviral Env SU is involved in the regulation of intracellular trafficking, and it may help to elucidate the maturation process of Fematrin-1 and other related Envs. Retroviruses utilize envelope glycoproteins (Envs) to enter host target cells. Mature retroviral Env is a heterodimer, which consists of surface (SU) and transmembrane (TM) subunits that are generated by the cleavage of an Env precursor protein in the trans-Golgi network. SU and TM mediate the recognition of the entry

  6. Human trafficking and the dental professional.

    Science.gov (United States)

    O'Callaghan, Michael G

    2012-05-01

    "Human trafficking" is a term for a modern form of slavery. It is a criminal human rights violation and a significant health issue. Dental professionals can assist in recognizing victims of trafficking. The author conducted a PubMed search of the English-language literature through May 2011, which yielded no articles meeting the search criteria "dentistry" and "human trafficking prostitution." Given these results, the author reviewed articles published in medical journals, reports from both governmental and nongovernmental agencies and lay literature. The author examines the present state of human trafficking and provides information--including specific questions to ask--to help dentists identify victims. In addition, the author suggests means of notifying authorities and assisting trafficking victims. He also examines the health care needs of these patients. Human trafficking is a global problem, with thousands of victims in the United States, including many women and children. Dentists have a responsibility to act for the benefit of others, which includes detecting signs of abuse and neglect. Dental professionals are on the front lines with respect to encountering and identifying potential victims who seek dental treatment. Dentists can combat human trafficking by becoming informed and by maintaining vigilance in their practices.

  7. Update: What Nurses Need to Know about Human Trafficking.

    Science.gov (United States)

    Washburn, Joy

    Nurses are key people who interact with victims of human trafficking in healthcare and other settings. This article provides a current overview of human trafficking, explains legal definitions, elements for protocols in healthcare settings when trafficking is suspected, nursing roles and responses, interview tools, resources, public health recommendations, and nursing education approaches to address human trafficking.

  8. 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...

  9. 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...

  10. Decreasing Human Trafficking through Sex Work Decriminalization.

    Science.gov (United States)

    Albright, Erin; D'Adamo, Kate

    2017-01-01

    In order to decrease human trafficking, health care workers should support the full decriminalization of prostitution. Similar to trafficking in other forms of labor, preventing trafficking in the sex trade requires addressing the different forms of marginalization that create vulnerable communities. By removing punitive laws that prevent reporting of exploitation and abuse, decriminalization allows sex workers to work more safely, thereby reducing marginalization and vulnerability. Decriminalization can also help destigmatize sex work and help resist political, social, and cultural marginalization of sex workers. © 2017 American Medical Association. All Rights Reserved.

  11. How to Use a Trafficked Woman. The Alliance between Political and Criminal Trafficking Organisations

    Directory of Open Access Journals (Sweden)

    John Davies

    2011-03-01

    Full Text Available The principal argument of this paper is that migrant women with secure mobility rights and supportive social networks can avoid or mitigate many trafficking harms. However the paper contends that some actors have conspired to prevent such circumstances so as to pursue diverse political agendas at the expense of migrant women. The paper’s analysis restructures the trafficking contest from organised criminals versus law enforcement agencies to principally a contest between migrant women and those political agents who benefit from the moral panic associated with trafficking. It is then argued that it is these more sophisticated political actors rather than organised criminals and the clients of sex workers are the most important stakeholders in sustaining or exploiting trafficking harm. Therefore, it is concluded that resolving many trafficking harms in the EEA could be achieved by subverting political traffickers through improving migration policy rather than fighting organised crime.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  13. Nuclear trafficking latest statistics released

    International Nuclear Information System (INIS)

    2005-01-01

    Full text: Countries reported 121 incidents to the IAEA in 2004 of illicit trafficking and other unauthorized activities involving nuclear and other radioactive materials, newly released statistics from the Agency's Illicit Trafficking Database (ITDB) show. The ITDB report also shows that one incident was reported since 2003 that involved fissile material - highly enriched uranium (HEU) or plutonium - that is needed to make a nuclear weapon. It occurred in June 2003 when an individual was arrested in possession of 170 grams of HEU, attempting to illegally transport it across the border. During the two-year period 2003-2004, the number of incidents reported by States substantially increased compared with previous years. 'Improved reporting may in part account for it,' the report said. 'The majority of the incidents reported in 2003-2004 showed no evidence of criminal activity.' The Past Twelve Years: 1993 - 2004 Nuclear Weapons Grade Material. Since the database started in 1993, there have been eighteen confirmed incidents involving trafficking in HEU and plutonium. A few of these incidents involved seizures of kilogram quantities of weapons-usable nuclear material but most involved very small quantities. In some of the cases the seized material was allegedly a sample of larger quantities available for illegal sale or at risk of theft. More than two dozens incidents involved trace amounts of plutonium sources. Table can be viewed: Incidents involving HEU and Pu confirmed to the ITDB (1993-2004). Nuclear Materials. In the past twelve years, 220 incidents involved nuclear materials. The majority of confirmed cases with nuclear materials involved low-grade nuclear materials, mostly in the form of reactor fuel pellets, and natural uranium, depleted uranium and thorium. While the quantities of these materials have been rather small to be significant for nuclear proliferation or use in a terrorist nuclear explosive device, these cases are indicative of gaps in the control

  14. Female sex trafficking: conceptual issues, current debates, and future directions.

    Science.gov (United States)

    Meshkovska, Biljana; Siegel, Melissa; Stutterheim, Sarah E; Bos, Arjan E R

    2015-01-01

    Female sex trafficking is a pressing concern. In this article, we provide a comprehensive overview of relevant issues regarding the concept of female sex trafficking and research in the field of human trafficking, drawing on a variety of disciplines, including economics, gender and sexuality studies, psychology, sociology, law, and social work. We discuss the debates surrounding the definition of human trafficking, compare and contrast it with human smuggling, and outline connections between female sex trafficking and the issue of sex work and prostitution. We further discuss the history and current estimations of female sex trafficking. We then outline the main actors in female sex trafficking, including trafficked persons, traffickers, clients, and service providers, and we overview the trafficking process from recruitment to identification, recovery, and (re)integration. Finally, we conclude with recommendations for future research that tie together the concepts of vulnerability, exploitation, and long-term recovery and (re)integration.

  15. Perdagangan Orang (Trafficking) sebagai Pelanggaran Hak Asasi Manusia

    OpenAIRE

    Munthe, Riswan

    2015-01-01

    Human trafficking is garbage of civilization which is hard to be fought. This sentence provide an invasion for all that human trafficking is a common enemy. Human trafficking is often done by agent who has national even international network, has power, strong physically and arrogance. Due to the victim of human trafficking is the group in the lower class of economy and education. Generally the victim of human trafficking is everyone without exception. Since Indonesian independence, it is con...

  16. Trafficking in Persons: The U.S. and International Response

    Science.gov (United States)

    2006-07-07

    lucrative business of international trafficking; ! the high demand, worldwide, for trafficked women and children as sex workers, cheap sweatshop labor , and...raid brothels, women are often detained and punished, subjected to human rights abuses in jail, and swiftly deported. Few steps have been taken to...of trafficking. Many countries have no specific laws aimed at trafficking in humans . Traffickers and Their Victims Chinese, Asian, Mexican, Central

  17. The concept of exploitation in international human trafficking law

    OpenAIRE

    von der Pütten, Tuija Kaarina

    2017-01-01

    Human trafficking is commonly known as a criminal practice that takes place in the framework of sex trade: women and children are trafficked within a state, or from one state to another, for the purpose of sexual exploitation. Similarly, the early 20th century international conventions aimed to tackle ‘white slave traffic’, trafficking of women and children for sexual exploitation. However, it is misleading to see trafficking only within this context. People are trafficked so that they can be...

  18. 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.

  19. 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

  20. 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.

  1. Neurobeachin regulates neurotransmitter receptor trafficking to synapses

    NARCIS (Netherlands)

    Nair, R.; Lauks, J.; Jung, S; Cooke, N.E.; de Wit, H.; Brose, N.; Kilimann, M.W.; Verhage, M.; Rhee, J.

    2013-01-01

    The surface density of neurotransmitter receptors at synapses is a key determinant of synaptic efficacy. Synaptic receptor accumulation is regulated by the transport, postsynaptic anchoring, and turnover of receptors, involving multiple trafficking, sorting, motor, and scaffold proteins. We found

  2. Human trafficking law and social structures.

    Science.gov (United States)

    Wooditch, Alese

    2012-08-01

    Human trafficking has only recently emerged at the forefront of policy reform, even in developed nations. Yet, heightened awareness of the issue has not translated into effective policy as the majority of nations have ineffective antitrafficking practices; many countries have failed to criminalize human trafficking, whereas others do not actively enforce statutes in place. By applying Black's theory of law, this study offers a preliminary understanding into the variation of global prosecutorial efforts in human trafficking and adequacy of antitrafficking law. To isolate this relationship, the effects of trafficking markets are controlled. As with prior research, the study finds limited support for the theory. The article concludes with a discussion on the implications of the quantity of antitrafficking law and morphology association for policy development.

  3. Subcellular localization analysis of the closely related Fps/Fes and Fer protein-tyrosine kinases suggests a distinct role for Fps/Fes in vesicular trafficking.

    Science.gov (United States)

    Zirngibl, R; Schulze, D; Mirski, S E; Cole, S P; Greer, P A

    2001-05-15

    The subcellular localizations of the Fps/Fes and closely related Fer cytoplasmic tyrosine kinases were studied using green fluorescent protein (GFP) fusions and confocal fluorescence microscopy. In contrast to previous reports, neither kinase localized to the nucleus. Fer was diffusely cytoplasmic throughout the cell cycle. Fps/Fes also displayed a diffuse cytoplasmic localization, but in addition it showed distinct accumulations in cytoplasmic vesicles as well as in a perinuclear region consistent with the Golgi. This localization was very similar to that of TGN38, a known marker of the trans Golgi. The localization of Fps/Fes and TGN38 were both perturbed by brefeldin A, a fungal metabolite that disrupts the Golgi apparatus. Fps/Fes was also found to colocalize to various extents with several Rab proteins, which are members of the monomeric G-protein superfamily involved in vesicular transport between specific subcellular compartments. Using Rabs that are involved in endocytosis (Rab5B and Rab7) or exocytosis (Rab1A and Rab3A), we showed that Fps/Fes is localized in both pathways. These results suggest that Fps/Fes may play a general role in the regulation of vesicular trafficking. Copyright 2001 Academic Press.

  4. Liberal coercion? Prostitution, human trafficking and policy

    OpenAIRE

    Cho, Seo-young

    2013-01-01

    Liberal prostitution policy aims at improving labour conditions for prostitutes and protecting victims of forced prostitution. Its policy orientation predicts that the policy choice of liberalizing prostitution is positively associated with better protection policy for trafficking victims and enhanced anti-trafficking measures. In this paper, I investigate empirically whether the legalization of prostitution improves protection policy for victims, as it is presumed. The results of my analysis...

  5. Barriers to Combating Human Trafficking in Colombia

    Science.gov (United States)

    2015-03-01

    citizens and potential delinquents must perceive that the detention and punishment of offenders is likely,” but that “penal institutions in Latin...America are unable to apprehend dangerous delinquents efficiently, which means that the deterrence does not work well in that region.”84 Likewise, “lack...monitor statistics on trafficking cases, including victim information “to help determine areas where Colombians are vulnerable to being trafficked

  6. RNA trafficking in parasitic plant systems

    Science.gov (United States)

    LeBlanc, Megan; Kim, Gunjune; Westwood, James H.

    2012-01-01

    RNA trafficking in plants contributes to local and long-distance coordination of plant development and response to the environment. However, investigations of mobile RNA identity and function are hindered by the inherent difficulty of tracing a given molecule of RNA from its cell of origin to its destination. Several methods have been used to address this problem, but all are limited to some extent by constraints associated with accurately sampling phloem sap or detecting trafficked RNA. Certain parasitic plant species form symplastic connections to their hosts and thereby provide an additional system for studying RNA trafficking. The haustorial connections of Cuscuta and Phelipanche species are similar to graft junctions in that they are able to transmit mRNAs, viral RNAs, siRNAs, and proteins from the host plants to the parasite. In contrast to other graft systems, these parasites form connections with host species that span a wide phylogenetic range, such that a high degree of nucleotide sequence divergence may exist between host and parasites and allow confident identification of most host RNAs in the parasite system. The ability to identify host RNAs in parasites, and vice versa, will facilitate genomics approaches to understanding RNA trafficking. This review discusses the nature of host–parasite connections and the potential significance of host RNAs for the parasite. Additional research on host–parasite interactions is needed to interpret results of RNA trafficking studies, but parasitic plants may provide a fascinating new perspective on RNA trafficking. PMID:22936942

  7. RNA trafficking in parasitic plant systems

    Directory of Open Access Journals (Sweden)

    Megan L LeBlanc

    2012-08-01

    Full Text Available RNA trafficking in plants contributes to local and long-distance coordination of plant development and response to the environment. However, investigations of mobile RNA identity and function are hindered by the inherent difficulty of tracing a given molecule of RNA from its cell of origin to its destination. Several methods have been used to address this problem, but all are limited to some extent by constraints associated with accurately sampling phloem sap or detecting trafficked RNA. Certain parasitic plant species form symplastic connections to their hosts and thereby provide an additional system for studying RNA trafficking. The haustorial connections of Cuscuta and Phelipanche species are similar to graft junctions in that they are able to transmit mRNAs, viral RNAs, siRNAs and proteins from the host plants to the parasite. In contrast to other graft systems, these parasites form connections with host species that span a wide phylogenetic range, such that a high degree of nucleotide sequence divergence may exist between host and parasites and allow confident identification of most host RNAs in the parasite system. The ability to identify host RNAs in parasites, and vice versa, will facilitate genomics approaches to understanding RNA trafficking. This review discusses the nature of host parasite connections and the potential significance of host RNAs for the parasite. Additional research on host-parasite interactions is needed to interpret results of RNA trafficking studies, but parasitic plants may provide a fascinating new perspective on RNA trafficking.

  8. Criteria for retrograde rotation of accreting black holes

    Science.gov (United States)

    Mikhailov, A. G.; Piotrovich, M. Yu; Gnedin, Yu N.; Natsvlishvili, T. M.; Buliga, S. D.

    2018-06-01

    Rotating supermassive black holes produce jets and their origin is connected to the magnetic field that is generated by accreting matter flow. There is a point of view that electromagnetic fields around rotating black holes are brought to the hole by accretion. In this situation the prograde accreting discs produce weaker large-scale black hole threading magnetic fields, implying weaker jets than in retrograde regimes. The basic goal of this paper is to find the best candidates for retrograde accreting systems in observed active galactic nuclei. We show that active galactic nuclei with low Eddington ratio are really the best candidates for retrograde systems. This conclusion is obtained for kinetically dominated Fanaroff-Riley class II radio galaxies, flat-spectrum radio-loud narrow-line Seyfert I galaxies and a number of nearby galaxies. Our conclusion is that the best candidates for retrograde systems are the noticeable population of active galactic nuclei in the Universe. This result corresponds to the conclusion that in the merging process the interaction of merging black holes with a retrograde circumbinary disc is considerably more effective for shrinking the binary system.

  9. Mercury Retrograde Effect in Capital Markets: Truth or Illusion?

    Directory of Open Access Journals (Sweden)

    Murgea Aurora

    2016-06-01

    Full Text Available From the most ancient times, the astrological beliefs have played an important role in human history, thinking, world-views, language and other elements of social culture. The practice of relating the movement of celestial bodies to events in financial markets is relatively newer but despite the inconsistency between financial astrology and standard economic or financial theory, it seems to be largely spread among capital market traders. This paper evaluates one of the astrological effects on the capital market, more precisely the Mercury retrograde effect on US capital market. Despite the fact that it is just an optical illusion the astrological tradition says that Mercury retrograde periods are characterized by confusion and miscommunications. The trades could be less effective, the individuals more prone to make mistakes so there is a long-held belief that it is better to avoid set plans during Mercury retrograde, signing contracts, starting new ventures or open new stock market positions. The main findings of this study are lower return’s volatilities in the Mercury retrograde periods, inconsistent with the astrologic theories assumptions but consistent with the idea that trader’s beliefs in Mercury retrograde effect could change the market volatility exactly in the opposite sense than the predicted one.

  10. ATG5 overexpression is neuroprotective and attenuates cytoskeletal and vesicle-trafficking alterations in axotomized motoneurons.

    Science.gov (United States)

    Leiva-Rodríguez, Tatiana; Romeo-Guitart, David; Marmolejo-Martínez-Artesero, Sara; Herrando-Grabulosa, Mireia; Bosch, Assumpció; Forés, Joaquim; Casas, Caty

    2018-05-24

    Injured neurons should engage endogenous mechanisms of self-protection to limit neurodegeneration. Enhancing efficacy of these mechanisms or correcting dysfunctional pathways may be a successful strategy for inducing neuroprotection. Spinal motoneurons retrogradely degenerate after proximal axotomy due to mechanical detachment (avulsion) of the nerve roots, and this limits recovery of nervous system function in patients after this type of trauma. In a previously reported proteomic analysis, we demonstrated that autophagy is a key endogenous mechanism that may allow motoneuron survival and regeneration after distal axotomy and suture of the nerve. Herein, we show that autophagy flux is dysfunctional or blocked in degenerated motoneurons after root avulsion. We also found that there were abnormalities in anterograde/retrograde motor proteins, key secretory pathway factors, and lysosome function. Further, LAMP1 protein was missorted and underglycosylated as well as the proton pump v-ATPase. In vitro modeling revealed how sequential disruptions in these systems likely lead to neurodegeneration. In vivo, we observed that cytoskeletal alterations, induced by a single injection of nocodazole, were sufficient to promote neurodegeneration of avulsed motoneurons. Besides, only pre-treatment with rapamycin, but not post-treatment, neuroprotected after nerve root avulsion. In agreement, overexpressing ATG5 in injured motoneurons led to neuroprotection and attenuation of cytoskeletal and trafficking-related abnormalities. These discoveries serve as proof of concept for autophagy-target therapy to halting the progression of neurodegenerative processes.

  11. 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...

  12. 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).

  13. 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

  14. Fluoroscopically guided pyeloureteral interventions using a retrograde perurethral approach

    International Nuclear Information System (INIS)

    Amendola, M.A.; Banner, M.P.; Pollack, H.M.; Gordon, R.L.; Van Arsdalen, K.N.

    1987-01-01

    Employing standard interventional equipment, fluoroscopy, and partially or completely inserted ureteral catheters for access, the authors performed 168 perurethral interventional procedures since 1985. Procedures have included insertion of double (n = 42) or single pigtail stents (n = 47), advancement of retrograde ureteral catheters with or without displacement of a ureteral stone to the renal pelvis (n = 42), urothelial biopsy (n = 30), balloon dilation of ureteral structures (n = 3), ureteral stone extraction (n = 1), and conversion of retrograde to antegrade catheters for balloon dilation of ureteropelvic junction strictures (n = 3). This retrograde approach often obviates the need for antegrade interventional procedures (including percutaneous nephrostomy and ureteral stenting), ureteroscopy, or surgery. Indications, techniques, pitfalls, and complications are illustrated

  15. The hidden crime: human trafficking.

    Science.gov (United States)

    Clause, Kristen J; Lawler, Kate Byrnes

    2013-01-01

    As the primary contact in the health care system, nurses can play a role in combating this crime and assisting the victims. Assessment for abuse, neglect, trauma, recurrent sexually transmitted infections (STIs) and fear of a controlling partner is critical. Following up on "red flags" and understanding methods of safe questioning can make the difference between slavery and recovery for victims. Nurses must also know the professional referrals in their areas once a potential victim has been identified. This may be a very dangerous undertaking and must be handled by experienced personnel. Referrals to forensic nurses or physicians, domestic violence professionals or law enforcement may be indicated. Initially, a nurse may want to consult with the agency social worker for guidance. Human trafficking is a human rights crime. Unfortunately, it is more prevalent in all types of communities than most people suspect. Nurses can be heroes to the victims through understanding of this crime and vigilance in the assessment and care of all people they encounter in their practices.

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

    Science.gov (United States)

    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.

  17. 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).

  18. Dynamic trafficking of wheat γ-gliadin and of its structural domains in tobacco cells, studied with fluorescent protein fusions

    Science.gov (United States)

    Francin-Allami, Mathilde; Saumonneau, Amélie; Lavenant, Laurence; Bouder, Axelle; Sparkes, Imogen; Hawes, Chris; Popineau, Yves

    2011-01-01

    Prolamins, the main storage proteins of wheat seeds, are synthesized and retained in the endoplasmic reticulum (ER) of the endosperm cells, where they accumulate in protein bodies (PBs) and are then exported to the storage vacuole. The mechanisms leading to these events are unresolved. To investigate this unconventional trafficking pathway, wheat γ-gliadin and its isolated repeated N-terminal and cysteine-rich C-terminal domains were fused to fluorescent proteins and expressed in tobacco leaf epidermal cells. The results indicated that γ-gliadin and both isolated domains were able to be retained and accumulated as protein body-like structures (PBLS) in the ER, suggesting that tandem repeats are not the only sequence involved in γ-gliadin ER retention and PBLS formation. The high actin-dependent mobility of γ-gliadin PBLS is also reported, and it is demonstrated that most of them do not co-localize with Golgi body or pre-vacuolar compartment markers. Both γ-gliadin domains are found in the same PBLS when co-expressed, which is most probably due to their ability to interact with each other, as indicated by the yeast two-hybrid and FRET-FLIM experiments. Moreover, when stably expressed in BY-2 cells, green fluorescent protein (GFP) fusions to γ-gliadin and its isolated domains were retained in the ER for several days before being exported to the vacuole in a Golgi-dependent manner, and degraded, leading to the release of the GFP ‘core’. Taken together, the results show that tobacco cells are a convenient model to study the atypical wheat prolamin trafficking with fluorescent protein fusions. PMID:21617248

  19. Dynein is the motor for retrograde axonal transport of organelles

    International Nuclear Information System (INIS)

    Schnapp, B.J.; Reese, T.S.

    1989-01-01

    Vesicular organelles in axons of nerve cells are transported along microtubules either toward their plus ends (fast anterograde transport) or toward their minus ends (retrograde transport). Two microtubule-based motors were previously identified by examining plastic beads induced to move along microtubules by cytosol fractions from the squid giant axon: (i) an anterograde motor, kinesin, and (ii) a retrograde motor, which is characterized here. The retrograde motor, a cytosolic protein previously termed HMW1, was purified from optic lobes and extruded axoplasm by nucleotide-dependent microtubule affinity and release; microtubule gliding was used as the assay of motor activity. The following properties of the retrograde motor suggest that it is cytoplasmic dynein: (i) sedimentation at 20-22 S with a heavy chain of Mr greater than 200,000 that coelectrophoreses with the alpha and beta subunits of axonemal dynein, (ii) cleavage by UV irradiation in the presence of ATP and vanadate, and (iii) a molecular structure resembling two-headed dynein from axonemes. Furthermore, bead movement toward the minus end of microtubules was blocked when axoplasmic supernatants were treated with UV/vanadate. Treatment of axoplasmic supernatant with UV/vanadate also blocks the retrograde movement of purified organelles in vitro without changing the number of anterograde moving organelles, indicating that dynein interacts specifically with a subgroup of organelles programmed to move toward the cell body. However, purified optic lobe dynein, like purified kinesin, does not by itself promote the movement of purified organelles along microtubules, suggesting that additional axoplasmic factors are necessary for retrograde as well as anterograde transport

  20. 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.

  1. A new retrograde transillumination technique for videolaryngoscopic tracheal intubation

    DEFF Research Database (Denmark)

    Biro, P; Fried, E; Schlaepfer, M

    2018-01-01

    This single-centre, prospective trial was designed to assess the efficacy of a new retrograde transillumination device called the 'Infrared Red Intubation System' (IRRIS) to aid videolaryngoscopic tracheal intubation. We included 40 adult patients, who were undergoing elective urological surgery......-10])), credibility (10 (8-10 [5-10])) and ease of use (10 (9-10 [8-10])). Tracheal intubation with the system lasted 26 (16-32 [6-89]) s. No alternative technique of securing the airway was necessary. The lowest SpO2 during intubation was 98 (97-99 [91-100])%. We conclude that this method of retrograde...

  2. 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.

  3. 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

  4. 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.

  5. Transneuronal retrograde dual viral labelling of central autonomic circuitry : possibilities and pitfalls

    NARCIS (Netherlands)

    Ter Horst, GJ

    2000-01-01

    Viral retrograde transneuronal labelling has become an important neuroanatomical tract-tracing tool for characterization of Limbic neuronal networks. Recently, dual viral retrograde transneuronal labelling has been introduced; a method employing differential transgene expression of two genetically

  6. Sub-cellular trafficking of phytochemicals explored using auto-fluorescent compounds in maize cells

    Directory of Open Access Journals (Sweden)

    Grotewold Erich

    2003-12-01

    Full Text Available Abstract Background Little is known regarding the trafficking mechanisms of small molecules within plant cells. It remains to be established whether phytochemicals are transported by pathways similar to those used by proteins, or whether the expansion of metabolic pathways in plants was associated with the evolution of novel trafficking pathways. In this paper, we exploited the induction of green and yellow auto-fluorescent compounds in maize cultured cells by the P1 transcription factor to investigate their targeting to the cell wall and vacuole, respectively. Results We investigated the accumulation and sub-cellular localization of the green and yellow auto-fluorescent compounds in maize BMS cells expressing the P1 transcription factor from an estradiol inducible promoter. We established that the yellow fluorescent compounds accumulate inside the vacuole in YFBs that resemble AVIs. The green fluorescent compounds accumulate initially in the cytoplasm in large spherical GFBs. Cells accumulating GFBs also contain electron-dense structures that accumulate initially in the ER and which later appear to fuse with the plasma membrane. Structures resembling the GFBs were also observed in the periplasmic space of plasmolized cells. Ultimately, the green fluorescence accumulates in the cell wall, in a process that is insensitive to the Golgi-disturbing agents BFA and monensin. Conclusions Our results suggest the presence of at least two distinct trafficking pathways, one to the cell wall and the other to the vacuole, for different auto-fluorescent compounds induced by the same transcription factor in maize BMS cells. These compartments represent two of the major sites of accumulation of phenolic compounds characteristic of maize cells. The secretion of the green auto-fluorescent compounds occurs by a pathway that does not involve the TGN, suggesting that it is different from the secretion of most proteins, polysaccharides or epicuticular waxes. The

  7. Characterising the online weapons trafficking on cryptomarkets.

    Science.gov (United States)

    Rhumorbarbe, Damien; Werner, Denis; Gilliéron, Quentin; Staehli, Ludovic; Broséus, Julian; Rossy, Quentin

    2018-02-01

    Weapons related webpages from nine cryptomarkets were manually duplicated in February 2016. Information about the listings (i.e. sales proposals) and vendors' profiles were extracted to draw an overview of the actual online trafficking of weapons. Relationships between vendors were also inferred through the analysis of online digital traces and content similarities. Weapons trafficking is mainly concentrated on two major cryptomarkets. Besides, it accounts for a very small proportion of the illicit trafficking on cryptomarkets compared to the illicit drugs trafficking. Among all weapon related listings (n=386), firearms only account for approximately 25% of sales proposal since the proportion of non-lethal and melee weapons is important (around 46%). Based on the recorded pseudonyms, a total of 96 vendor profiles were highlighted. Some pseudonyms were encountered on several cryptomarkets, suggesting that some vendors may manage accounts on different markets. This hypothesis was strengthened by comparing pseudonyms to online traces such as PGP keys, images and profiles descriptions. Such a method allowed to estimate more accurately the number of vendors offering weapons across cryptomarkets. Finally, according to the gathered data, the extent of the weapons trafficking on the cryptomarkets appear to be limited compared to other illicit goods. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Debate: Strategically Working in Parallel to Traffickers

    Directory of Open Access Journals (Sweden)

    Vincent Tournecuillert

    2014-09-01

    Full Text Available Let’s be realistic, counter-trafficking teams will never be as effective as the proactive and flexible networks of outlaws that violate the rights of millions of people each year. The ‘bad guys’ operate without the same financial limitations such as bureaucratic red tape and donor criteria, and take advantage of patchy and often uncoordinated border surveillance that is chronically untrained in detecting trafficking in persons.  Non-governmental organisations (NGOs involved in the fight against human trafficking—and in direct contact with presumed victims (their status is not assessed until at a stage later than this initial contact—are in a diametrically opposite situation. They must carefully abide by the national and international legal frameworks that their criminal antagonists ignore. Donors and national authorities operate within the constraints of geographic target areas and funding cycles. Since counter-trafficking actors neither create the markets nor devise the routes for trafficking, their strategic cross-border (or long distance partnerships are always a few steps behind the traffickers, if not many steps behind, and rarely efficient.

  9. Medical education and human trafficking: using simulation.

    Science.gov (United States)

    Stoklosa, Hanni; Lyman, Michelle; Bohnert, Carrie; Mittel, Olivia

    2017-01-01

    Healthcare providers have the potential to play a crucial role in human trafficking prevention, identification, and intervention. However, trafficked patients are often unidentified due to lack of education and preparation available to healthcare professionals at all levels of training and practice. To increase victim identification in healthcare settings, providers need to be educated about the issue of trafficking and its clinical presentations in an interactive format that maximizes learning and ultimately patient-centered outcomes. In 2014, University of Louisville School of Medicine created a simulation-based medical education (SBME) curriculum to prepare students to recognize victims and intervene on their behalf. The authors share the factors that influenced the session's development and incorporation into an already full third year medical curriculum and outline the development process. The process included a needs assessment for the education intervention, development of objectives and corresponding assessment, implementation of the curriculum, and finally the next steps of the module as it develops further. Additional alternatives are provided for other medical educators seeking to implement similar modules at their home institution. It is our hope that the description of this process will help others to create similar interactive educational programs and ultimately help trafficking survivors receive the care they need. HCP: Healthcare professional; M-SIGHT: Medical student instruction in global human trafficking; SBME: Simulation-based medical education; SP: Standardized patient; TIC: Trauma-informed care.

  10. Medical education and human trafficking: using simulation

    Science.gov (United States)

    Stoklosa, Hanni; Lyman, Michelle; Bohnert, Carrie; Mittel, Olivia

    2017-01-01

    ABSTRACT Healthcare providers have the potential to play a crucial role in human trafficking prevention, identification, and intervention. However, trafficked patients are often unidentified due to lack of education and preparation available to healthcare professionals at all levels of training and practice. To increase victim identification in healthcare settings, providers need to be educated about the issue of trafficking and its clinical presentations in an interactive format that maximizes learning and ultimately patient-centered outcomes. In 2014, University of Louisville School of Medicine created a simulation-based medical education (SBME) curriculum to prepare students to recognize victims and intervene on their behalf. The authors share the factors that influenced the session’s development and incorporation into an already full third year medical curriculum and outline the development process. The process included a needs assessment for the education intervention, development of objectives and corresponding assessment, implementation of the curriculum, and finally the next steps of the module as it develops further. Additional alternatives are provided for other medical educators seeking to implement similar modules at their home institution. It is our hope that the description of this process will help others to create similar interactive educational programs and ultimately help trafficking survivors receive the care they need. Abbreviations: HCP: Healthcare professional; M-SIGHT: Medical student instruction in global human trafficking; SBME: Simulation-based medical education; SP: Standardized patient; TIC: Trauma-informed care PMID:29228882

  11. The loss of episodic memories in retrograde amnesia: single-case and group studies.

    OpenAIRE

    Kopelman, M D; Kapur, N

    2001-01-01

    Retrograde amnesia in neurological disorders is a perplexing and fascinating research topic. The severity of retrograde amnesia is not well correlated with that of anterograde amnesia, and there can be disproportionate impairments of either. Within retrograde amnesia, there are various dissociations which have been claimed-for example, between the more autobiographical (episodic) and more semantic components of memory. However, the associations of different types of retrograde amnesia are als...

  12. 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....

  13. 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.

  14. Retrograde pylorogastric intussusception – Case report and review

    Directory of Open Access Journals (Sweden)

    Efrat Avinadav

    2016-07-01

    Full Text Available A case of gastric outlet obstruction in an infant due to retrograde intussusception of the pylorus into the stomach is presented. This anomaly is extremely rare, with almost no reports in the literature. The patient underwent formal Heineke-Mikulicz pyloroplasty with an uneventful recovery and resumed full enteral feeding.

  15. Retrograde ejaculation and sexual dysfunction in men with diabetes mellitus

    DEFF Research Database (Denmark)

    Fedder, J; Kaspersen, Maja Døvling; Brandslund, I

    2013-01-01

    Retrograde ejaculation (RE) and erectile dysfunction may be caused by diabetes mellitus (DM), but the prevalence of RE among DM patients is unknown. A prospective, blinded case-control study comparing men with DM with matched controls according to RE and erectile dysfunction was performed. Twenty...

  16. Case Report: A Healthy Live Birth Following ICSI with Retrograde ...

    African Journals Online (AJOL)

    Intracytoplasmic sperm injection (ICSI) has been employed to achieve fertilization in some cases of male subfertility e.g. severe oligoasthenoteratozoospermia. Assisted reproductive techniques to aid conception in cases of retrograde ejaculation have been described extensively elsewhere but there is paucity of knowledge ...

  17. Retrograde amnesia after electroconvulsive therapy: a temporary effect?

    Science.gov (United States)

    Meeter, Martijn; Murre, Jaap M J; Janssen, Steve M J; Birkenhager, Tom; van den Broek, W W

    2011-07-01

    Although electroconvulsive therapy (ECT) is generally considered effective against depression, it remains controversial because of its association with retrograde memory loss. Here, we assessed memory after ECT in circumstances most likely to yield strong retrograde amnesia. A cohort of patients undergoing ECT for major depression was tested before and after ECT, and again at 3-months follow-up. Included were 21 patients scheduled to undergo bilateral ECT for severe major depression and 135 controls matched for gender, age, education, and media consumption. Two memory tests were used: a verbal learning test to assess anterograde memory function, and a remote memory test that assessed memory for news during the course of one year. Before ECT the patients' scores were lower than those of controls. They were lower again after treatment, suggesting retrograde amnesia. At follow-up, however, memory for events before treatment had returned to the pre-ECT level. Memory for events in the months after treatment was as good as that of controls. The sample size in this study was not large. Moreover, memory impairment did not correlate with level of depression, which may be due to restriction of range. Our results are consistent with the possibility that ECT as currently practiced does not cause significant lasting retrograde amnesia, but that amnesia is mostly temporary and related to the period of impairment immediately following ECT. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. Retrograde jejunal intussusception after total gastrectomy: A case ...

    African Journals Online (AJOL)

    Retrograde jejunal intussusception is a rare disease. A 60‑year‑old female patient was hospitalized due to vomiting for 2 days, with a history of radical gastrectomy plus esophagus jejunum Rouxs‑en‑Y. On examination, there was a palpable wax‑like mass on the left‑hand side underneath the umbilicus. Computerized ...

  19. Retrograde jejunal intussusception after total gastrectomy: A case ...

    African Journals Online (AJOL)

    2015-11-02

    Nov 2, 2015 ... Retrograde jejunal intussusception is a rare disease. A 60-year-old female patient was hospitalized due to vomiting for 2 days, with a history of radical gastrectomy plus esophagus jejunum Rouxs-en-Y. On examination, there was a palpable wax-like mass on the left-hand side underneath the umbilicus.

  20. Rutinemaessig endoskopisk retrograd kolangiopankreatikografi kan ikke anbefales ved galdestenspankreatitis

    DEFF Research Database (Denmark)

    Ainsworth, Alan Patrick; Svendsen, Lars Bo

    2009-01-01

    Danish guidelines recommend that patients with presumed severe gallstone-induced acute pancreatitis (GAP) should receive endoscopic retrograde cholangiopancreatography (ERCP) within 72 hours. The results of a newly performed meta-analysis show that acute ERCP in patients with GAP does not reduce...

  1. TRANSIT TIMING VARIATIONS FOR INCLINED AND RETROGRADE EXOPLANETARY SYSTEMS

    International Nuclear Information System (INIS)

    Payne, Matthew J.; Ford, Eric B.; Veras, Dimitri

    2010-01-01

    We perform numerical calculations of the expected transit timing variations (TTVs) induced on a hot-Jupiter by an Earth-mass perturber. Motivated by the recent discoveries of retrograde transiting planets, we concentrate on an investigation of the effect of varying relative planetary inclinations, up to and including completely retrograde systems. We find that planets in low-order (e.g., 2:1) mean-motion resonances (MMRs) retain approximately constant TTV amplitudes for 0 deg. 170 deg. Systems in higher order MMRs (e.g., 5:1) increase in TTV amplitude as inclinations increase toward 45 deg., becoming approximately constant for 45 deg. 135 deg. Planets away from resonance slowly decrease in TTV amplitude as inclinations increase from 0 deg. to 180 deg., whereas planets adjacent to resonances can exhibit a huge range of variability in TTV amplitude as a function of both eccentricity and inclination. For highly retrograde systems (135 deg. < i ≤ 180 deg.), TTV signals will be undetectable across almost the entirety of parameter space, with the exceptions occurring when the perturber has high eccentricity or is very close to an MMR. This high inclination decrease in TTV amplitude (on and away from resonance) is important for the analysis of the known retrograde and multi-planet transiting systems, as inclination effects need to be considered if TTVs are to be used to exclude the presence of any putative planetary companions: absence of evidence is not evidence of absence.

  2. Endoskopisk ultralydvejledt rendezvouskolangiografi ved mislykket endoskopisk retrograd kolangiopankreatikografi

    DEFF Research Database (Denmark)

    Boman, Pia Snedker; Perdawid, Sharafaden Karim; Lykkegaard, John

    2012-01-01

    In this case report we describe an alternative method of cholangiography. Endoscopic retrograde cholangiopancreatography (ERCP) was not successful in a patient with choledocolithiasis. A combined endoscopic ultrasound (EUS) and ERCP procedure was performed and a stent was inserted in the common...

  3. Endoscopic retrograde cholangiopancreatography causes reduced myocardial blood flow

    DEFF Research Database (Denmark)

    Christensen, M; Hendel, H W; Rasmussen, V

    2002-01-01

    BACKGROUND AND STUDY AIMS: Previous studies have shown that up to 50% of healthy patients may develop ST-segment changes during upper gastrointestinal endoscopy. The aim of the study was to evaluate myocardial blood flow in patients during endoscopic retrograde cholangiopancreatography (ERCP...

  4. A study of retrograde degeneration of median nerve forearm ...

    African Journals Online (AJOL)

    Introduction: Carpal tunnel syndrome (CTS) is a disorder of the hand which results from compression of the median nerve within its fibro-osseous tunnel at the wrist. The slowing in the forearm motor conduction velocity suggests the presence of retrograde degeneration. Existing studies conflict regarding a correlation ...

  5. A rare cause of coffee-ground vomiting: Retrograde jejunogastric ...

    African Journals Online (AJOL)

    Retrograde jejunogastric intussusception is a well-recognised, rare, but potentially fatal long-term complication of gastrojejunostomy or Billroth II reconstruction. Only about 200 cases have been reported in the literature to date. Diagnosis of this condition is difficult in most cases. To avoid mortality, earlydiagnosis and prompt ...

  6. Developing a Repeatable Methodology to Calculate Retrograde Planning Factors

    Science.gov (United States)

    2015-01-01

    supply chain inefficiencies, changes in demand xiv rates, operational tempo, task force organization, drawdown, and redeployment, for which the...and its causes, most notably the effect of supply chain inefficiencies on serviceable retrograde. It should be noted that, because of data limitations... supplies and equipment, and housekeeping supplies and equipment Class IIIP Packaged petroleum products; includes fuel in collapsible containers less

  7. Treatment of lower extremity arterial occlusive through retrograde access

    International Nuclear Information System (INIS)

    Liu Xueqiang; Guo Pingfan; Zhang Jinchi; Cai Fanggang

    2012-01-01

    Objective: To explore the clinical significance of retrograde access for the interventional treatment of lower extremity arterial occlusive diseases when the occluded segment of lower extremity artery could not be reached through antegrade access. Methods: Twenty-seven cases (male 17, female 10; age range 32-89 years) were retrospectively investigated, including 18 with lower limb arteriosclerosis obliterans, 7 with diabetic foot and 2 with thromboangiitis obliterans. According to the Fontaine staging, 6 cases were classified as Fontaine Ⅱ, 11 were classified as Fontaine Ⅲ and 10 were classified as Fontaine Ⅳ. All cases underwent endovascular operation through antegrade access first with an attempt to cross the occlusive segment, but in vain. So retrograde access was tried via puncture of pedis dorsalis or posterior tibial artery or exposure of lateral branches of posterior tibial artery, peroneal artery or dorsal artery by open surgery,which followed by Percutaneous transluminal angiography and (or) stenting. Results: The operation through retrograde access was successful in all cases with obvious improvement of ischemic symptoms. Hematoma at the puncture site occurred in 3 patients, and paresthesia of toes occurred in 1 after dorsalis pedis arteriotomy. No severe perioperative complication occurred. The average ankle brachial index increased from 0.37 ± 0.11 preoperatively to 0.85 ± 0.12 postoperatively. Conclusions: Retrograde access could be used as an alternative strategy in lower extremity arterial occlusive diseases when the occluded segment could not reach through antegrade access. (authors)

  8. Patterns and Processes of Recruitment and Trafficking into sex Work ...

    African Journals Online (AJOL)

    Patterns and Processes of Recruitment and Trafficking into sex Work in Nigeria. ... The recruitment patterns and trafficking processes were characterized with incidences of deception, extortion, violence and ... AJOL African Journals Online.

  9. Understanding the link between trafficking in persons and HIV and ...

    African Journals Online (AJOL)

    Keywords: HIV, trafficking in persons, labour, Tanzania ..... Myths about HIV transmission and AIDS cure in some parts of the world are likely to fuel trafficking in persons. Surfacing beliefs among men that 'having sex with virgin girls could.

  10. Role of Occupational Therapy in Combating Human Trafficking.

    Science.gov (United States)

    Gorman, Kathleen W; Hatkevich, Beth Ann

    Human trafficking is a modern-day form of slavery that includes sex trafficking, labor trafficking, and trafficking of children. It is estimated that 35.8 million people are enslaved around the world. Because of the traumatic experiences that victims of human trafficking encounter, the needs of victims are extensive and require the services of several providers, including health care providers, for victims to transform into survivors and thrivers. Currently, the role of occupational therapy is minimal and unexplored. The profession of occupational therapy has the capacity of having a profound role in both providing client-centered care services to victims and survivors of human trafficking and partaking in preventive advocacy efforts to combat human trafficking. Further advocacy efforts are required to promote the profession of occupational therapy in combating human trafficking. Copyright © 2016 by the American Occupational Therapy Association, Inc.

  11. Trafficking in Persons: The U.S. and International Response

    National Research Council Canada - National Science Library

    Miko, Francis T

    2006-01-01

    .... The overwhelming majority of those trafficked are women and children. According to the most recent Department of State estimates, between 600,000 and 800,000 people are trafficked across borders each year...

  12. Bacterial pathogen manipulation of host membrane trafficking.

    Science.gov (United States)

    Asrat, Seblewongel; de Jesús, Dennise A; Hempstead, Andrew D; Ramabhadran, Vinay; Isberg, Ralph R

    2014-01-01

    Pathogens use a vast number of strategies to alter host membrane dynamics. Targeting the host membrane machinery is important for the survival and pathogenesis of several extracellular, vacuolar, and cytosolic bacteria. Membrane manipulation promotes bacterial replication while suppressing host responses, allowing the bacterium to thrive in a hostile environment. This review provides a comprehensive summary of various strategies used by both extracellular and intracellular bacteria to hijack host membrane trafficking machinery. We start with mechanisms used by bacteria to alter the plasma membrane, delve into the hijacking of various vesicle trafficking pathways, and conclude by summarizing bacterial adaptation to host immune responses. Understanding bacterial manipulation of host membrane trafficking provides insights into bacterial pathogenesis and uncovers the molecular mechanisms behind various processes within a eukaryotic cell.

  13. Endocytosis and Endosomal Trafficking in Plants.

    Science.gov (United States)

    Paez Valencia, Julio; Goodman, Kaija; Otegui, Marisa S

    2016-04-29

    Endocytosis and endosomal trafficking are essential processes in cells that control the dynamics and turnover of plasma membrane proteins, such as receptors, transporters, and cell wall biosynthetic enzymes. Plasma membrane proteins (cargo) are internalized by endocytosis through clathrin-dependent or clathrin-independent mechanism and delivered to early endosomes. From the endosomes, cargo proteins are recycled back to the plasma membrane via different pathways, which rely on small GTPases and the retromer complex. Proteins that are targeted for degradation through ubiquitination are sorted into endosomal vesicles by the ESCRT (endosomal sorting complex required for transport) machinery for degradation in the vacuole. Endocytic and endosomal trafficking regulates many cellular, developmental, and physiological processes, including cellular polarization, hormone transport, metal ion homeostasis, cytokinesis, pathogen responses, and development. In this review, we discuss the mechanisms that mediate the recognition and sorting of endocytic and endosomal cargos, the vesiculation processes that mediate their trafficking, and their connection to cellular and physiological responses in plants.

  14. Public Perceptions of Human Trafficking in Moldova

    Directory of Open Access Journals (Sweden)

    Jill Robinson

    2011-11-01

    Full Text Available Human trafficking is a widely studied phenomenon. Comparing public perceptions of trafficking to institutional (i.e. the academy, governmental and non-governmental organizations perceptions gives a richer understanding of the problem. The data for this study were collected in and around Chisinau, Moldova in the summer of 2004. Public discourse provides a more intimate "portraiture" of the issue, but the public also demonstrated a complex level of understanding of this social problem in this study. Its view is juxtaposed against an institutional view of human trafficking as explored through a literature review. Combining institutional and public perceptions and knowledge of a social problem is helpful in not only establishing a more thorough understanding of the social problem and guiding policy decisions, but in exploring the experiences victims may face at the community level.

  15. A novel Golgi retention signal RPWS for tumor suppressor UBIAD1.

    Directory of Open Access Journals (Sweden)

    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.

  16. 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.

  17. Role of adaptor proteins and clathrin in the trafficking of human kidney anion exchanger 1 (kAE1) to the cell surface.

    Science.gov (United States)

    Junking, Mutita; Sawasdee, Nunghathai; Duangtum, Natapol; Cheunsuchon, Boonyarit; Limjindaporn, Thawornchai; Yenchitsomanus, Pa-thai

    2014-07-01

    Kidney anion exchanger 1 (kAE1) plays an important role in acid-base homeostasis by mediating chloride/bicarbornate (Cl-/HCO3-) exchange at the basolateral membrane of α-intercalated cells in the distal nephron. Impaired intracellular trafficking of kAE1 caused by mutations of SLC4A1 encoding kAE1 results in kidney disease - distal renal tubular acidosis (dRTA). However, it is not known how the intracellular sorting and trafficking of kAE1 from trans-Golgi network (TGN) to the basolateral membrane occurs. Here, we studied the role of basolateral-related sorting proteins, including the mu1 subunit of adaptor protein (AP) complexes, clathrin and protein kinase D, on kAE1 trafficking in polarized and non-polarized kidney cells. By using RNA interference, co-immunoprecipitation, yellow fluorescent protein-based protein fragment complementation assays and immunofluorescence staining, we demonstrated that AP-1 mu1A, AP-3 mu1, AP-4 mu1 and clathrin (but not AP-1 mu1B, PKD1 or PKD2) play crucial roles in intracellular sorting and trafficking of kAE1. We also demonstrated colocalization of kAE1 and basolateral-related sorting proteins in human kidney tissues by double immunofluorescence staining. These findings indicate that AP-1 mu1A, AP-3 mu1, AP-4 mu1 and clathrin are required for kAE1 sorting and trafficking from TGN to the basolateral membrane of acid-secreting α-intercalated cells. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Child Labor Trafficking in the United States: A Hidden Crime

    OpenAIRE

    Kaufka Walts, Katherine

    2017-01-01

    Emerging research brings more attention to labor trafficking in the United States. However, very few efforts have been made to better understand or respond to labor trafficking of minors. Cases of children forced to work as domestic servants, in factories, restaurants, peddling candy or other goods, or on farms may not automatically elicit suspicion from an outside observer as compared to a child providing sexual services for money. In contrast to sex trafficking, labor trafficking is often t...

  19. Conceptual basis of preventing and combating human trafficking in Ukraine

    OpenAIRE

    N. M. Lukach

    2015-01-01

    The activities of international organizations against human trafficking is considered in the article. Today human trafficking gained the grand scale of its spreading and affected all countries and regions, including Ukraine. Nowadays there are a lot of kinds and forms of human exploitation. Human trafficking has put the challenge to the international community and calls for its immediate resolution. Combating human trafficking are at all levels from global to regional and national. The int...

  20. Human trafficking: fighting the illicit economy with the legitimate economy

    OpenAIRE

    Shelley, Louise; Bain, Christina

    2015-01-01

    Since the beginning of research on human trafficking, there has been attention paid to the challenges surrounding the illicit economy. In creating new strategies and initiatives on combatting human trafficking, there needs to be more discussion surrounding the legitimate economy and how the business sector can make an impact in the fight against trafficking. Currently, there is a growing movement of businesses that are looking to address human trafficking through training, education, and lead...

  1. The Victim Handling Model of Human Trafficking Through Economic Independence

    OpenAIRE

    Nuraeny, Henny; Utami, Tanti Kirana

    2016-01-01

    Human Trafficking is a modern trading of human slavery. Human Trafficking is also one of the worst forms of violation of human dignity that results in trauma to the victims. To that end, there should be a comprehensive treatment for victims. The problems that can be studied is whether a model that can be applied in the treatment of victims of trafficking in Cianjur and disseminating technical how models Handling of Victims of Human Trafficking in Cianjur. This study used normative juridical a...

  2. The hotel industry's role in combatting sex trafficking

    OpenAIRE

    Winters, Brandon R.

    2017-01-01

    Approved for public release; distribution is unlimited Human trafficking is a global concern that victimizes countless individuals worldwide. The hotel industry, which traffickers often exploit, is in a unique position to assist in the prevention of sex trafficking; therefore, it plays a vital role in the overall fight against human trafficking. This thesis applies policy analysis and exploratory research to understand how and to what degree the U.S.-based hotel industry can affect efforts...

  3. Human trafficking in Germany: strengthening victim's human rights

    OpenAIRE

    Follmar-Otto, Petra; Rabe, Heike

    2009-01-01

    The first study - "A human rights approach against human trafficking - International obligations and the status of implementation in Germany" - analyses how the prohibition of human trafficking and the resulting state obligations are anchored in human rights. The more recent specialised international agreements on human trafficking and law-making in the European Union are then presented. The emphasis is on the Council of Europe Convention, which professes to treat human trafficking in a human...

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

    Science.gov (United States)

    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.

  5. Human Diseases Associated with Form and Function of the Golgi Complex

    Directory of Open Access Journals (Sweden)

    Jeremy C. Simpson

    2013-09-01

    Full Text Available The Golgi complex lies at the heart of the secretory pathway and is responsible for modifying proteins and lipids, as well as sorting newly synthesized molecules to their correct destination. As a consequence of these important roles, any changes in its proteome can negatively affect its function and in turn lead to disease. Recently, a number of proteins have been identified, which when either depleted or mutated, result in diseases that affect various organ systems. Here we describe how these proteins have been linked to the Golgi complex, and specifically how they affect either the morphology, membrane traffic or glycosylation ability of this organelle.

  6. 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.

  7. Investigating Internalization and Intracellular Trafficking of GPCRs

    DEFF Research Database (Denmark)

    Foster, Simon R; Bräuner-Osborne, Hans

    2017-01-01

    for signal transduction. One of the major mechanisms for GPCR regulation involves their endocytic trafficking, which serves to internalize the receptors from the plasma membrane and thereby attenuate G protein-dependent signaling. However, there is accumulating evidence to suggest that GPCRs can signal...... independently of G proteins, as well as from intracellular compartments including endosomes. It is in this context that receptor internalization and intracellular trafficking have attracted renewed interest within the GPCR field. In this chapter, we will review the current understanding and methodologies...

  8. 78 FR 70571 - Advisory Council on Wildlife Trafficking; Rescheduled Meeting

    Science.gov (United States)

    2013-11-26

    ... Advisory Council on Wildlife Trafficking (Council) will hold a meeting to discuss committee structure and organization, the National Strategy to Combat Wildlife Trafficking, and other council business as appropriate... Council organization and process, 2. The National Strategy to Combat Wildlife Trafficking, and 3. Other...

  9. Child organ trafficking: global reality and inadequate international response.

    Science.gov (United States)

    Bagheri, Alireza

    2016-06-01

    In organ transplantation, the demand for human organs has grown far faster than the supply of organs. This has opened the door for illegal organ trade and trafficking including from children. Organized crime groups and individual organ brokers exploit the situation and, as a result, black markets are becoming more numerous and organized organ trafficking is expanding worldwide. While underprivileged and vulnerable men and women in developing countries are a major source of trafficked organs, and may themselves be trafficked for the purpose of illegal organ removal and trade, children are at especial risk of exploitation. With the confirmed cases of children being trafficked for their organs, child organ trafficking, which once called a "modern urban legend", is a sad reality in today's world. By presenting a global picture of child organ trafficking, this paper emphasizes that child organ trafficking is no longer a myth but a reality which has to be addressed. It argues that the international efforts against organ trafficking and trafficking in human beings for organ removal have failed to address child organ trafficking adequately. This chapter suggests that more orchestrated international collaboration as well as development of preventive measure and legally binding documents are needed to fight child organ trafficking and to support its victims.

  10. Human trafficking and exploitation: A global health concern.

    Directory of Open Access Journals (Sweden)

    Cathy Zimmerman

    2017-11-01

    Full Text Available In this collection review, Cathy Zimmerman and colleague introduce the PLOS Medicine Collection on Human Trafficking, Exploitation and Health, laying out the magnitude of the global trafficking problem and offering a public health policy framework to guide responses to trafficking.

  11. Human Trafficking: A Review for Mental Health Professionals

    Science.gov (United States)

    Yakushko, Oksana

    2009-01-01

    This article provides a review of current research on human trafficking for mental health practitioners and scholars. In addition to an overview of definitions, causes and processes of trafficking, the article highlights mental health consequences of trafficking along with suggestions for treatment of survivors. Directions for counseling services,…

  12. Trafficking of Children in Albania: Patterns of Recruitment and Reintegration

    Science.gov (United States)

    Gjermeni, Eglantina; Van Hook, Mary P.; Gjipali, Saemira; Xhillari, Lindita; Lungu, Fatjon; Hazizi, Anila

    2008-01-01

    Problem: Many children in Albania and other countries of Eastern Europe are being trafficked as part of the global business of human trafficking. Objectives: The study sought to identify the patterns of child trafficking involving Albanian children, and especially children's views of the role of family issues and the nature of the trafficking…

  13. a Study of Akachi Adimora-Ezeigbo's Trafficked

    African Journals Online (AJOL)

    Trafficking is frowned at in Nigeria, yet people are perpetually trafficked. In this research work, the researcher examines the novel in line with sociological approach so that the ills of human trafficking as it is a case in the contemporary society would be seen. The researcher believes that when the ills are exposed, there ...

  14. 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

  15. 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.

  16. 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...

  17. Debate - Achievements of the Trafficking Protocol: Perspectives from the former UN Special Rapporteur on Trafficking in Persons

    OpenAIRE

    Joy N Ezeilo

    2015-01-01

    The United Nations (UN) Protocol to Prevent, Suppress and Punish Trafficking in Persons, Especially Women and Children, Supplementing the UN Convention against Transnational Organized Crime, 2000 (Trafficking Protocol), is a watershed in galvanising the global movement against human trafficking. Thanks to the Protocol, international and regional bodies, along with civil society groups, have become involved in researching the issue and supporting anti-trafficking efforts; and states have begun...

  18. South Africa - safe haven for human traffickers? Employing the arsenal of existing law to combat human trafficking

    OpenAIRE

    Kruger, H B; Oosthuizen, H

    2012-01-01

    aving ratified the Protocol to Prevent, Suppress and Punish Trafficking in Persons, Especially Women and Children, South Africa is obliged to adopt legislative measures that criminalise human trafficking and comply with other standards laid down in this international instrument. However, by mid-2011, South Africa had not enacted the required comprehensive counter-trafficking legislation. The question that now arises is if the absence of such anti-trafficking legislation poses an insurmountabl...

  19. AP1S3 Mutations Are Associated with Pustular Psoriasis and Impaired Toll-like Receptor 3 Trafficking

    Science.gov (United States)

    Setta-Kaffetzi, Niovi; Simpson, Michael A.; Navarini, Alexander A.; Patel, Varsha M.; Lu, Hui-Chun; Allen, Michael H.; Duckworth, Michael; Bachelez, Hervé; Burden, A. David; Choon, Siew-Eng; Griffiths, Christopher E.M.; Kirby, Brian; Kolios, Antonios; Seyger, Marieke M.B.; Prins, Christa; Smahi, Asma; Trembath, Richard C.; Fraternali, Franca; Smith, Catherine H.; Barker, Jonathan N.; Capon, Francesca

    2014-01-01

    Adaptor protein complex 1 (AP-1) is an evolutionary conserved heterotetramer that promotes vesicular trafficking between the trans-Golgi network and the endosomes. The knockout of most murine AP-1 complex subunits is embryonically lethal, so the identification of human disease-associated alleles has the unique potential to deliver insights into gene function. Here, we report two founder mutations (c.11T>G [p.Phe4Cys] and c.97C>T [p.Arg33Trp]) in AP1S3, the gene encoding AP-1 complex subunit σ1C, in 15 unrelated individuals with a severe autoinflammatory skin disorder known as pustular psoriasis. Because the variants are predicted to destabilize the 3D structure of the AP-1 complex, we generated AP1S3-knockdown cell lines to investigate the consequences of AP-1 deficiency in skin keratinocytes. We found that AP1S3 silencing disrupted the endosomal translocation of the innate pattern-recognition receptor TLR-3 (Toll-like receptor 3) and resulted in a marked inhibition of downstream signaling. These findings identify pustular psoriasis as an autoinflammatory phenotype caused by defects in vesicular trafficking and demonstrate a requirement of AP-1 for Toll-like receptor homeostasis. PMID:24791904

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Trafficking as a Human Rights Violation: Is South Africa's Curriculum Stuck in a Traffick Jam?

    Science.gov (United States)

    du Preez, Petro; Simmonds, Shan

    2013-01-01

    Human trafficking is a form of modern day slavery and is often collectively referred to as a human rights violation. However, human trafficking is more complex than this suggests as this article attempts to demonstrate. It begins by describing the landscape of international trends in human trafficking, with particular attention to child…

  2. Sinai Trafficking: Origin and Definition of a New Form of Human Trafficking

    Directory of Open Access Journals (Sweden)

    Mirjam van Reisen

    2015-02-01

    Full Text Available The phenomenon that is coined “Sinai Trafficking” started in 2009 in the Sinai desert. It involves the abduction, extortion, sale, torture, sexual violation and killing of men, women and children. Migrants, of whom the vast majority are from Eritrean descent, are abducted and brought to the Sinai desert, where they are sold and resold, extorted for very high ransoms collected by mobile phone, while being brutally and “functionally” tortured to support the extortion. Many of them die in Sinai. Over the last five years broadcasting stations, human rights organisations and academics have reported on the practices in the Sinai and some of these reports have resulted in some confusion on the modus operandi. Based on empirical research by the authors and the analysis of data gathered in more than 200 recorded interviews with Sinai hostages and survivors on the practices, this article provides a definition of Sinai Trafficking. It argues that the term Sinai Trafficking can be used to differentiate a particular new set of criminal practices that have first been reported in the Sinai Peninsula. The article further examines how the new phenomenon of Sinai Trafficking can be framed into the legal human trafficking definition. The interconnectedness of Sinai Trafficking with slavery, torture, ransom collection, extortion, sexual violence and other severe crimes is presented to substantiate the use of the trafficking framework. The plight of Sinai survivors in Israel and Egypt is explained to illustrate the cyclical process of the trafficking practices especially endured by Eritreans, introduced as the Human Trafficking Cycle. The article concludes by setting out areas for further research.

  3. Human Trafficking, Globalisation and Transnational Feminist Responses

    NARCIS (Netherlands)

    T-D. Truong (Thanh-Dam)

    2014-01-01

    textabstractThis paper presents a historical overview of feminist frameworks for analysis and advocacy on human trafficking. It traces the major differences and similarities in the forms of knowledge produced since the Anti-White Slavery campaigns nearly two centuries ago. It highlights how

  4. Counter Trafficking System Development "Analysis Training Program"

    Energy Technology Data Exchange (ETDEWEB)

    Peterson, Dennis C. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2010-12-01

    This document will detail the training curriculum for the Counter-Trafficking System Development (CTSD) Analysis Modules and Lesson Plans are derived from the United States Military, Department of Energy doctrine and Lawrence Livermore National Laboratory (LLNL), Global Security (GS) S Program.

  5. Ovarian Cystadenoma in a Trafficked Patient.

    Science.gov (United States)

    Titchen, Kanani E; Katz, Douglas; Martinez, Kidian; White, Krishna

    2016-05-01

    The topic of child sex trafficking is receiving increased attention both in the lay press and in research articles. Recently, a number of physician organizations have issued policy statements calling for the education and involvement of physicians in combating this form of "modern-day slavery." Primary care and emergency medicine physicians have led these efforts, but a number of these victims may present to surgeons. Surgeons are in a unique position to identify trafficked patients; during the process of undraping, intubation, and surgical preparation, signs of trafficking such as tattoos, scars, dental injuries, and bruising may be evident. In addition, these patients may have specific needs in terms of anesthesia and postoperative care due to substance abuse. Here, we report the case of an 18-year-old girl with a history of sexual exploitation who presents for cystadenoma excision. To our knowledge, this is the first report of a sex-trafficked pediatric patient presenting for surgery. Copyright © 2016 by the American Academy of Pediatrics.

  6. Global recycling - waste trafficking in disguise?

    DEFF Research Database (Denmark)

    Kamuk, Bettina; Hansen, Jens Aage

    2007-01-01

    Recycling is used as cover for illegal exporting of hazardous wastes (waste trafficking). This happens in spite of international conventions and codes of good conduct. Additional rules and recommendations are suggested to initiatiate local and national action and compliance with international...

  7. Advocacy of Trafficking Campaigns: A Controversy Story

    Science.gov (United States)

    Saiz-Echezarreta, Vanesa; Alvarado, María-Cruz; Gómez-Lorenzini, Paulina

    2018-01-01

    The construction, visualization and stabilization of public problems require the mobilization of civil society groups concerned about these issues to actively engage in the demand for actions and policies. This paper explores the institutional campaigns against human trafficking and sexual exploitation in Spain between 2008 and 2017 and their role…

  8. Global Human Trafficking and Child Victimization.

    Science.gov (United States)

    Greenbaum, Jordan; Bodrick, Nia

    2017-12-01

    Trafficking of children for labor and sexual exploitation violates basic human rights and constitutes a major global public health problem. Pediatricians and other health care professionals may encounter victims who present with infections, injuries, posttraumatic stress disorder, suicidality, or a variety of other physical or behavioral health conditions. Preventing child trafficking, recognizing victimization, and intervening appropriately require a public health approach that incorporates rigorous research on the risk factors, health impact, and effective treatment options for child exploitation as well as implementation and evaluation of primary prevention programs. Health care professionals need training to recognize possible signs of exploitation and to intervene appropriately. They need to adopt a multidisciplinary, outward-focused approach to service provision, working with nonmedical professionals in the community to assist victims. Pediatricians also need to advocate for legislation and policies that promote child rights and victim services as well as those that address the social determinants of health, which influence the vulnerability to human trafficking. This policy statement outlines major issues regarding public policy, medical education, research, and collaboration in the area of child labor and sex trafficking and provides recommendations for future work. Copyright © 2017 by the American Academy of Pediatrics.

  9. Human Trafficking as Lever for Feminist Voices?

    DEFF Research Database (Denmark)

    Spanger, Marlene

    2011-01-01

    that lies behind policies on prostitution by identifying ruptures and discursive struggles which lead to transformations of the policy field. In particular, this article investigates how the problematisation of human trafficking has created space for a feminist discourse breakthrough within the policy field...

  10. Trafficking in persons : A victim's perspective

    NARCIS (Netherlands)

    Rijken, Conny; Rijken, Conny; Piotrowicz, Ryszard; Uhl, Baerbel Heide

    2017-01-01

    Historically, protection and assistance to victims of human trafficking in many countries is anchored in migration law and dependent on whether or not a residence permit is granted to the victim. Apart from some limited exceptions, cooperation with law enforcement authorities in criminal

  11. Conceptual basis of preventing and combating human trafficking in Ukraine

    Directory of Open Access Journals (Sweden)

    N. M. Lukach

    2015-05-01

    The basic mechanisms and instruments of international community against human trafficking are explored by the author and also the ways of solving problems is proposed. In the article based on the international experience of combating human trafficking and the latest national legislation conceptual basics of preventing and counteracting human trafficking in Ukraine are examined. Including: improvement of laws against human trafficking and improvement of law enforcement; changing the the status of persons and support for persons from risk groups; increasing the level of public awareness, especially persons from risk groups; the qualified help to victims of trafficking.

  12. 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

  13. 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.

  14. 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.

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

    Science.gov (United States)

    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.

  16. 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.

  17. 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...

  18. 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

  19. Ileal Varices Treated with Balloon-Occluded Retrograde Transvenous Obliteration.

    Science.gov (United States)

    Sato, Takahiro; Yamazaki, Katsu; Toyota, Jouji; Karino, Yoshiyasu; Ohmura, Takumi; Akaike, Jun

    2009-04-01

    A 55-year-old man with hepatitis B virus antigen-positive liver cirrhosis was admitted to our hospital with anal bleeding. Colonoscopy revealed blood retention in the entire colon, but no bleeding lesion was found. Computed tomography images showed that vessels in the ileum were connected to the right testicular vein, and we suspected ileal varices to be the most probable cause of bleeding. We immediately performed double balloon enteroscopy, but failed to find any site of bleeding owing to the difficulty of fiberscope insertion with sever adhesion. Using a balloon catheter during retrograde transvenous venography, we found ileal varices communicating with the right testicular vein (efferent vein) with the superior mesenteric vein branch as the afferent vein of these varices. We performed balloon occluded retrograde transvenous obliteration by way of the efferent vein of the varices and have detected no further bleeding in this patient one year after treatment.

  20. Retrograde Jejuno-Jejunal Intussusception after Total Gastrectomy

    Directory of Open Access Journals (Sweden)

    Akira Yoneda

    2008-08-01

    Full Text Available An eighty-year-old female was transferred to the hospital after experiencing abdominal pain and nausea. She had had a history of total gastrectomy for gastric cancer 14 years previously. Abdominal X-ray revealed a localized expansion of the small bowel. Computed tomography revealed a mass with a lamellar structure in a concentric circle. With a tentative diagnosis of small bowel obstruction due to intussusception, she underwent emergency operation. Laparotomy revealed a retrograde jejuno-jejunal intussusception. Bowel resection was performed due to the severe ischemic damage. All reported intussusception cases after total gastrectomy displayed retrograde characteristics and could occur both during the early and late period after surgery. It is important to consider the possibility of intussusception for patients presenting with acute abdomen who have previously undergone gastric resection.

  1. Vps35-deficiency impairs SLC4A11 trafficking and promotes corneal dystrophy.

    Directory of Open Access Journals (Sweden)

    Wei Liu

    Full Text Available Vps35 (vacuolar protein sorting 35 is a major component of retromer that selectively promotes endosome-to-Golgi retrieval of transmembrane proteins. Dysfunction of retromer is a risk factor for the pathogenesis of Parkinson's disease (PD and Alzheimer's disease (AD. However, Vps35/retromer's function in the eye or the contribution of Vps35-deficiency to eye degenerative disorders remains to be explored. Here we provide evidence for a critical role of Vps35 in mouse corneal dystrophy. Vps35 is expressed in mouse and human cornea. Mouse cornea from Vps35 heterozygotes (Vps35+/- show features of dystrophy, such as loss of both endothelial and epithelial cell densities, disorganizations of endothelial, stroma, and epithelial cells, excrescences in the Descemet membrane, and corneal edema. Additionally, corneal epithelial cell proliferation was reduced in Vps35-deficient mice. Intriguingly, cell surface targeting of SLC4A11, a membrane transport protein (OH- /H+ /NH3 /H2O of corneal endothelium, whose mutations have been identified in patients with corneal dystrophy, was impaired in Vps35-deficient cells and cornea. Taken together, these results suggest that SLC4A11 appears to be a Vps35/retromer cargo, and Vps35-regulation of SLC4A11 trafficking may underlie Vps35/retromer regulation of corneal dystrophy.

  2. Plasminogen Activator Inhibitor-1 Controls Vascular Integrity by Regulating VE-Cadherin Trafficking.

    Directory of Open Access Journals (Sweden)

    Anna E Daniel

    Full Text Available Plasminogen activator inhibitor-1 (PAI-1, a serine protease inhibitor, is expressed and secreted by endothelial cells. Patients with PAI-1 deficiency show a mild to moderate bleeding diathesis, which has been exclusively ascribed to the function of PAI-1 in down-regulating fibrinolysis. We tested the hypothesis that PAI-1 function plays a direct role in controlling vascular integrity and permeability by keeping endothelial cell-cell junctions intact.We utilized PAI-039, a specific small molecule inhibitor of PAI-1, to investigate the role of PAI-1 in protecting endothelial integrity. In vivo inhibition of PAI-1 resulted in vascular leakage from intersegmental vessels and in the hindbrain of zebrafish embryos. In addition PAI-1 inhibition in human umbilical vein endothelial cell (HUVEC monolayers leads to a marked decrease of transendothelial resistance and disrupted endothelial junctions. The total level of the endothelial junction regulator VE-cadherin was reduced, whereas surface VE-cadherin expression was unaltered. Moreover, PAI-1 inhibition reduced the shedding of VE-cadherin. Finally, we detected an accumulation of VE-cadherin at the Golgi apparatus.Our findings indicate that PAI-1 function is important for the maintenance of endothelial monolayer and vascular integrity by controlling VE-cadherin trafficking to and from the plasma membrane. Our data further suggest that therapies using PAI-1 antagonists like PAI-039 ought to be used with caution to avoid disruption of the vessel wall.

  3. Structural features of the KPI domain control APP dimerization, trafficking, and processing.

    Science.gov (United States)

    Ben Khalifa, Naouel; Tyteca, Donatienne; Marinangeli, Claudia; Depuydt, Mathieu; Collet, Jean-François; Courtoy, Pierre J; Renauld, Jean-Christophe; Constantinescu, Stefan; Octave, Jean-Noël; Kienlen-Campard, Pascal

    2012-02-01

    The two major isoforms of human APP, APP695 and APP751, differ by the presence of a Kunitz-type protease inhibitor (KPI) domain in the extracellular region. APP processing and function is thought to be regulated by homodimerization. We used bimolecular fluorescence complementation (BiFC) to study dimerization of different APP isoforms and mutants. APP751 was found to form significantly more homodimers than APP695. Mutation of dimerization motifs in the TM domain did not affect fluorescence complementation, but native folding of KPI is critical for APP751 homodimerization. APP751 and APP695 dimers were mostly localized at steady state in the Golgi region, suggesting that most of the APP751 and 695 dimers are in the secretory pathway. Mutation of the KPI led to the retention of the APP homodimers in the endoplasmic reticulum. We finally showed that APP751 is more efficiently processed through the nonamyloidogenic pathway than APP695. These findings provide new insight on the particular role of KPI domain in APP dimerization. The correlation observed between dimerization, subcellular localization, and processing suggests that dimerization acts as an efficient regulator of APP trafficking in the secretory compartments that has major consequences on its processing.

  4. Biomechanical Strength of Retrograde Fixation in Proximal Third Scaphoid Fractures.

    Science.gov (United States)

    Daly, Charles A; Boden, Allison L; Hutton, William C; Gottschalk, Michael B

    2018-04-01

    Current techniques for fixation of proximal pole scaphoid fractures utilize antegrade fixation via a dorsal approach endangering the delicate vascular supply of the dorsal scaphoid. Volar and dorsal approaches demonstrate equivalent clinical outcomes in scaphoid wrist fractures, but no study has evaluated the biomechanical strength for fractures of the proximal pole. This study compares biomechanical strength of antegrade and retrograde fixation for fractures of the proximal pole of the scaphoid. A simulated proximal pole scaphoid fracture was produced in 22 matched cadaveric scaphoids, which were then assigned randomly to either antegrade or retrograde fixation with a cannulated headless compression screw. Cyclic loading and load to failure testing were performed and screw length, number of cycles, and maximum load sustained were recorded. There were no significant differences in average screw length (25.5 mm vs 25.6 mm, P = .934), average number of cyclic loading cycles (3738 vs 3847, P = .552), average load to failure (348 N vs 371 N, P = .357), and number of catastrophic failures observed between the antegrade and retrograde fixation groups (3 in each). Practical equivalence between the 2 groups was calculated and the 2 groups were demonstrated to be practically equivalent (upper threshold P = .010). For this model of proximal pole scaphoid wrist fractures, antegrade and retrograde screw configuration have been proven to be equivalent in terms of biomechanical strength. With further clinical study, we hope surgeons will be able to make their decision for fixation technique based on approaches to bone grafting, concern for tenuous blood supply, and surgeon preference without fear of poor biomechanical properties.

  5. A cadaveric study of surgical landmarks for retrograde parotidectomy

    Directory of Open Access Journals (Sweden)

    Wenjie Zhong

    2016-08-01

    Conclusion: The findings indicate that all three landmarks are useful for surgeons to locate the facial nerve branches during retrograde parotidectomy. Since all three landmarks were consistent indicators for the corresponding facial nerve branches, the surgeon has more than one option should one landmark be obscured by tumors. The optimal landmark is the distance from A to MM because it is shortest and most reliable, followed by RMV to MM, and Z to B.

  6. Rutinemaessig endoskopisk retrograd kolangiopankreatikografi kan ikke anbefales ved galdestenspankreatitis

    DEFF Research Database (Denmark)

    Ainsworth, Alan Patrick; Svendsen, Lars Bo

    2009-01-01

    Danish guidelines recommend that patients with presumed severe gallstone-induced acute pancreatitis (GAP) should receive endoscopic retrograde cholangiopancreatography (ERCP) within 72 hours. The results of a newly performed meta-analysis show that acute ERCP in patients with GAP does not reduce...... the risk of complications, and ERCP is therefore not to be used routinely in GAP patients. The possible benefits of replacing ERCP with either endoscopic ultrasonography or magnetic resonance cholangiopancreatograhy have yet to be demonstrated. Udgivelsesdato: 2009-Aug-31...

  7. South Africa – Safe Haven for Human Traffickers? Employing the Arsenal of Existing Law to Combat Human Trafficking

    Directory of Open Access Journals (Sweden)

    H Oosthuizen

    2012-03-01

    Full Text Available aving ratified the Protocol to Prevent, Suppress and Punish Trafficking in Persons, Especially Women and Children, South Africa is obliged to adopt legislative measures that criminalise human trafficking and comply with other standards laid down in this international instrument. However, by mid-2011, South Africa had not enacted the required comprehensive counter-trafficking legislation. The question that now arises is if the absence of such anti-trafficking legislation poses an insurmountable obstacle to the prosecution of traffickers for trafficking-related activities. In asking this question the article examines the utilisation of existing crimes in order to prosecute and punish criminal activities committed during the human trafficking process. Firstly, a selection of existing common law and statutory crimes that may often be applicable to trafficking related activities is mapped out. Secondly, transitional trafficking provisions in the Children's Act 38 of 2005 and the Criminal Law (Sexual Offences and Related Matters Amendment Act 32 of 2007 are discussed. Finally, since the Prevention and Combating of Trafficking in Persons Bill B7 of 2010 will in all probability be enacted in the near future, the use of other criminal law provisions in human trafficking prosecutions, even after the passing of this bill into law, is reflected upon.

  8. Neurovascular Structures at Risk With Curved Retrograde TTC Fusion Nails.

    Science.gov (United States)

    de Cesar Netto, Cesar; Johannesmeyer, David; Cone, Brent; Araoye, Ibukunoluwa; Hudson, Parke William; Sahranavard, Bahman; Johnson, Michael; Shah, Ashish

    2017-10-01

    The purpose of this study was to assess the risk of iatrogenic injury to plantar neurovascular structures of the foot during insertion of a curved retrograde tibiotalocalcaneal (TTC) fusion nail. Ten below-knee thawed fresh-frozen cadaveric specimens underwent curved retrograde nailing of the ankle. The shortest distance between the nail and the main plantar neurovascular branches and injured structures were recorded during dissection. We also evaluated the relative position of these structures along 2 lines (AB, connecting the calcaneus to the first metatarsal, and BC, connecting the first and fifth metatarsal). The lateral plantar artery was found to be in direct contact with the nail 70% of the time, with a macroscopic laceration 30% of the time. The Baxter nerve was injured 20% of the time, as was the lateral plantar nerve. The medial plantar artery and nerve were never injured. The most proximal structure to cross line AB was the Baxter nerve followed by the lateral plantar artery, the nail, the lateral plantar nerve, and the medial plantar nerve. Our cadaveric anatomic study found that the most common structures at risk for iatrogenic injury by lateral curved retrograde TTC fusion nails were the lateral plantar artery and nerve, and the Baxter nerve. Determination of a true neurovascular safe zone is challenging and therefore warrants careful operative dissection to minimize neurovascular injuries.

  9. A retrograde co-orbital asteroid of Jupiter.

    Science.gov (United States)

    Wiegert, Paul; Connors, Martin; Veillet, Christian

    2017-03-29

    Recent theoretical work in celestial mechanics has revealed that an asteroid may orbit stably in the same region as a planet, despite revolving around the Sun in the sense opposite to that of the planet itself. Asteroid 2015 BZ 509 was discovered in 2015, but with too much uncertainty in its measured orbit to establish whether it was such a retrograde co-orbital body. Here we report observations and analysis that demonstrates that asteroid 2015 BZ 509 is indeed a retrograde co-orbital asteroid of the planet Jupiter. We find that 2015 BZ 509 has long-term stability, having been in its current, resonant state for around a million years. This is long enough to preclude precise calculation of the time or mechanism of its injection to its present state, but it may be a Halley-family comet that entered the resonance through an interaction with Saturn. Retrograde co-orbital asteroids of Jupiter and other planets may be more common than previously expected.

  10. The Retrograde and Retroperitoneal Totally Laparoscopic Hysterectomy for Endometrial Cancer

    Directory of Open Access Journals (Sweden)

    Eugenio Volpi

    2012-01-01

    Full Text Available Introduction. We retrospectively report our experience with the utilization of an original procedure for total laparoscopic hysterectomy based on completely retrograde and retroperitoneal technique for surgical staging and treatment of the endometrial cancer. The surgical, financial, and oncological advantages are here discussed. Methods. The technique used here has been based on a combination of a retroperitoneal approach with a retrograde and lateral dissection of the bladder and retrograde culdotomy with variable resection of parametrium. No disposable instruments and no uterine manipulator were utilized. Results. Intraoperative and postoperative complications were observed in 10% of the cases overall. Operative time length and mean haemoglobin drop value results were 129 min and 125 mL, respectively. Most patients were dismissed on days 3–5 from the hospital. Seventy-eight percent of the patients were alive with no evidence of disease at mean followup of 49 months. Conclusions. Our original laparoscopic technique is based on a retroperitoneal approach in order to rapidly control main uterine vessels coagulation, constantly check the ureter, and eventually decide type and site of lymph nodes removal. This procedure has important cost saving implications and the avoidance of uterine manipulator is of matter in case such as these of uterine malignancy.

  11. 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

  12. 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.

  13. Psychogenic amnesia: syndromes, outcome, and patterns of retrograde amnesia.

    Science.gov (United States)

    Harrison, Neil A; Johnston, Kate; Corno, Federica; Casey, Sarah J; Friedner, Kimberley; Humphreys, Kate; Jaldow, Eli J; Pitkanen, Mervi; Kopelman, Michael D

    2017-09-01

    There are very few case series of patients with acute psychogenic memory loss (also known as dissociative/functional amnesia), and still fewer studies of outcome, or comparisons with neurological memory-disordered patients. Consequently, the literature on psychogenic amnesia is somewhat fragmented and offers little prognostic value for individual patients. In the present study, we reviewed the case records and neuropsychological findings in 53 psychogenic amnesia cases (ratio of 3:1, males:females), in comparison with 21 consecutively recruited neurological memory-disordered patients and 14 healthy control subjects. In particular, we examined the pattern of retrograde amnesia on an assessment of autobiographical memory (the Autobiographical Memory Interview). We found that our patients with psychogenic memory loss fell into four distinct groups, which we categorized as: (i) fugue state; (ii) fugue-to-focal retrograde amnesia; (iii) psychogenic focal retrograde amnesia following a minor neurological episode; and (iv) patients with gaps in their memories. While neurological cases were characterized by relevant neurological symptoms, a history of a past head injury was actually more common in our psychogenic cases (P = 0.012), perhaps reflecting a 'learning episode' predisposing to later psychological amnesia. As anticipated, loss of the sense of personal identity was confined to the psychogenic group. However, clinical depression, family/relationship problems, financial/employment problems, and failure to recognize the family were also statistically more common in that group. The pattern of autobiographical memory loss differed between the psychogenic groups: fugue cases showed a severe and uniform loss of memories for both facts and events across all time periods, whereas the two focal retrograde amnesia groups showed a 'reversed' temporal gradient with relative sparing of recent memories. After 3-6 months, the fugue patients had improved to normal scores for facts

  14. 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...

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

    Science.gov (United States)

    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

  16. Getting out of the game: desistance from drug trafficking.

    Science.gov (United States)

    Campbell, Howard; Hansen, Tobin

    2012-11-01

    This ethnographic study was conducted along the U.S.-Mexico border, the centre of the western hemispheric illicit drugs trade. It examines factors that encouraged or discouraged drug traffickers to "get out of the game" (a common slang reference to leaving the drug business). In-depth, life history interviews were conducted of thirty ex-traffickers in the El Paso/Ciudad Juárez area. Participants discussed their experiences exiting drug trafficking and their retrospective, often conflicted, feelings about the trade. Although leaving drug trafficking is a complex and multi-faceted process, the principle factors for study participants were (1) punishment (by authorities or other traffickers), (2) self-image and identity, (3) social ties, (4) life course changes and (5) drug use/abuse. Traffickers often want to quit, but their divided self-identities make it difficult to relinquish the power and exhilaration they derive from the illicit drugs business. Harm reduction policies are needed that address the embeddedness of trafficker identities in dense webs of family, community, street gangs and transnational cartels, and the larger society, as well as the seductive appeal of Hollywood and pro-cartel narco-media. Traffickers need pathways that allow them to exit the illicit drugs business without surrendering their identity. Prison sentences are not enough to encourage traffickers to stop-also needed are culturally sensitive policies that help traffickers get out of the game and stay out. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Human Trafficking: How Nurses Can Make a Difference.

    Science.gov (United States)

    Scannell, Meredith; MacDonald, Andrea E; Berger, Amanda; Boyer, Nichole

    Human trafficking is a human rights violation and a global health problem. Victims of human trafficking have medical and mental health sequelae requiring specific healthcare interventions. Healthcare professionals may be the initial contact that these victims make outside the world of trafficking. Healthcare professionals are key agents in the identification of human trafficking, which is essential in eliminating this public health problem. Unfortunately, healthcare professionals are not always able to detect signs of human trafficking. Failure to detect results in missed opportunities to assist victims. This is a case report of a victim of human trafficking who presented to an emergency department with medical and mental health issues. Despite numerous encounters with different healthcare professionals, signs and symptoms of human trafficking were not identified. Skilled assessment made by a forensic nurse alerted the healthcare team to clear features of human trafficking associated with this person. Through this case report we illustrate the key role the nurse played in identifying signs of human trafficking. Improvement of human trafficking educational programs is highlighted as a key adjunct to improving detection and facilitating the proper treatment of victims.

  18. 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).

  19. 'Trafficking' or 'personal use': do people who regularly inject drugs understand Australian drug trafficking laws?

    Science.gov (United States)

    Hughes, Caitlin E; Ritter, Alison; Cowdery, Nicholas; Sindicich, Natasha

    2014-11-01

    Legal thresholds for drug trafficking, over which possession of an illicit drug is deemed 'trafficking' as opposed to 'personal use', are employed in all Australian states and territories excepting Queensland. In this paper, we explore the extent to which people who regularly inject drugs understand such laws. Participants from the seven affected states/territories in the 2012 Illicit Drug Reporting System (n = 823) were asked about their legal knowledge of trafficking thresholds: whether, if arrested, quantity possessed would affect legal action taken; and the quantities of heroin, methamphetamine, cocaine and cannabis that would constitute an offence of supply. Data were compared against the actual laws to identify the accuracy of knowledge by drug type and state, and sociodemographics, use and purchasing patterns related to knowledge. Most Illicit Drug Reporting System participants (77%) correctly said that quantity possessed would affect charge received. However, only 55.8% nominated any specific quantity that would constitute an offence of supply, and of those 22.6% nominated a wrong quantity, namely a quantity that was larger than the actual quantity for supply (this varied by state and drug). People who regularly inject drugs have significant gaps in knowledge about Australian legal thresholds for drug trafficking, particularly regarding the actual threshold quantities. This suggests that there may be a need to improve education for this population. Necessity for accurate knowledge would also be lessened by better design of Australian drug trafficking laws. © 2014 Australasian Professional Society on Alcohol and other Drugs.

  20. Drosophila VAMP7 regulates Wingless intracellular trafficking.

    Science.gov (United States)

    Gao, Han; He, Fang; Lin, Xinhua; Wu, Yihui

    2017-01-01

    Drosophila Wingless (Wg) is a morphogen that determines cell fate during development. Previous studies have shown that endocytic pathways regulate Wg trafficking and signaling. Here, we showed that loss of vamp7, a gene required for vesicle fusion, dramatically increased Wg levels and decreased Wg signaling. Interestingly, we found that levels of Dally-like (Dlp), a glypican that can interact with Wg to suppress Wg signaling at the dorsoventral boundary of the Drosophila wing, were also increased in vamp7 mutant cells. Moreover, Wg puncta in Rab4-dependent recycling endosomes were Dlp positive. We hypothesize that VAMP7 is required for Wg intracellular trafficking and the accumulation of Wg in Rab4-dependent recycling endosomes might affect Wg signaling.

  1. Incunabular Immunological Events in Prion Trafficking

    Science.gov (United States)

    Michel, Brady; Meyerett-Reid, Crystal; Johnson, Theodore; Ferguson, Adam; Wyckoff, Christy; Pulford, Bruce; Bender, Heather; Avery, Anne; Telling, Glenn; Dow, Steven; Zabel, Mark D.

    2012-01-01

    While prions probably interact with the innate immune system immediately following infection, little is known about this initial confrontation. Here we investigated incunabular events in lymphotropic and intranodal prion trafficking by following highly enriched, fluorescent prions from infection sites to draining lymph nodes. We detected biphasic lymphotropic transport of prions from the initial entry site upon peripheral prion inoculation. Prions arrived in draining lymph nodes cell autonomously within two hours of intraperitoneal administration. Monocytes and dendritic cells (DCs) required Complement for optimal prion delivery to lymph nodes hours later in a second wave of prion trafficking. B cells constituted the majority of prion-bearing cells in the mediastinal lymph node by six hours, indicating intranodal prion reception from resident DCs or subcapsulary sinus macrophages or directly from follicular conduits. These data reveal novel, cell autonomous prion lymphotropism, and a prominent role for B cells in intranodal prion movement. PMID:22679554

  2. ACTUAL ISSUES OF COMBATING ILLEGAL DRUG TRAFFICKING

    Directory of Open Access Journals (Sweden)

    Mikhail Sharov

    2016-02-01

    Full Text Available The article is devoted to research of current situation in the field of drug trafficking and its impact on the rule of law, economy, public health and safety of the state as a whole. Proposes specific ways to counter — increase the efficiency of the entire system of state bodies. To solve the problems, determined the content of such a legal category as the subject of prosecutorial and Supervisory relationships of the species under investigation.

  3. A Comprehensive Approach to Combating Illicit Trafficking

    Science.gov (United States)

    2010-06-01

    based in terms of production and sale. For example, ac- cording to the 2007 UN World Drug Re- port, drugs such as marijuana , which can be produced...and/or trafficking of heroin, cocaine, and synthetic drugs and precursors� • Crimes against Persons Unit (SC3)—Its main roles and responsibilities are...support, and coordinate law enforcement investigations; and identify links between different investigations in the area of synthetic drugs and precursors

  4. Morphine Induces Splenocyte Trafficking into the CNS

    OpenAIRE

    Olin, Michael R; Oh, Seunguk; Roy, Sabita; Peterson, Phillip K; Molitor, Thomas

    2011-01-01

    Opioids significantly alter functional responses of lymphocytes following activation. Morphine, an opioid derivative, alters the Th1 to Th2 response and modulates functional responses such as cytolytic activity and proliferation. Although there has been extensive research involving morphine’s effects on lymphocytes, little is known about the effects morphine has on lymphocyte trafficking. The objective of the study was to use in vivo bioluminescent imaging to determine morphine’s effect on th...

  5. Effects of inulin with different degree of polymerization on gelatinization and retrogradation of wheat starch.

    Science.gov (United States)

    Luo, Denglin; Li, Yun; Xu, Baocheng; Ren, Guangyue; Li, Peiyan; Li, Xuan; Han, Sihai; Liu, Jianxue

    2017-08-15

    The effects of three types of inulin, including FS (DP≤10), FI (DP of 2-60) and FXL (DP≥23), on the gelatinization and retrogradation characteristics of wheat starch were investigated. As the concentration of inulin added into starch increased, the gelatinization temperature increased whereas the breakdown value decreased, and the value of setback first decreased and then increased slightly. The three types of inulin with lower concentrations (inulin showed a significant suppression of starch retrogradation in the addition range of 5-7.5%. They can all inhibit amylose retrogradation, but accelerate amylopectin retrogradation. Inulin with lower DP has stronger effects on the starch retrogradation. Generally, the three types of inulin can all retard the retrogradation performance of wheat starch to some extent in the long-term storage. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Etiological Aspects of Human Trafficking in Kosovo

    Directory of Open Access Journals (Sweden)

    Emine Abdyli

    2017-08-01

    Full Text Available Human trafficking is considered one of the most serious criminal offences, which is presented as a contemporary form of slavery and which implies the most brutal violation of basic human rights, which are guaranteed by international and law and national law. The phenomenon of human trafficking is present in many countries in transition (such as Kosovo, namely in those countries which were affected by internal political, economic, social, educational, etc. changes, and in such situations the perpetrators of this offense are in a very favorable position to victimize society. Therefore, this paper will focus on external criminogenic factors that influence the growth of this negative phenomenon, including the difficult economic situation, poverty and unemployment, poor housing, migration of people, domestic violence, the impact of mass media in society, lack of border control and insufficient effectiveness of institutions to deal with law enforcement. The paper is based on literature review, statistical data and interviews by treating the subject theoretically, legislatively and practically. To successfully fight against human trafficking, relevant authorities should more closely approach the etiological treatment of this negative phenomenon.

  7. Child human trafficking victims: challenges for the child welfare system.

    Science.gov (United States)

    Fong, Rowena; Berger Cardoso, Jodi

    2010-08-01

    Since the passing of the Victims of Trafficking and Violence Protection Act in 2000 and its reauthorization by President George Bush in 2008, federal, state and community efforts in identifying and providing services for victims of human trafficking have significantly improved. However, most of the research and resources for trafficking victims have been directed towards adults rather than children. Researchers agree that there is a growing number of sexually exploited and trafficked children in the United States yet few programs emphasize the unique experiences and special needs of this population. This article examines commercial sexual exploitation of children; differentiates the needs and problems between child prostitution and victims of human trafficking; reviews and critiques current treatment practices; and summarizes challenges and successes in working with child victims of human trafficking, offering practice and policy recommendations. Published by Elsevier Ltd.

  8. Health Care and Human Trafficking: We are Seeing the Unseen.

    Science.gov (United States)

    Chisolm-Straker, Makini; Baldwin, Susie; Gaïgbé-Togbé, Bertille; Ndukwe, Nneka; Johnson, Pauline N; Richardson, Lynne D

    2016-01-01

    This study aimed to build the evidence base around human trafficking (HT) and health in the U.S. by employing a quantitative approach to exploring the notion that health care providers encounter this population. Furthermore, this study sought to describe the health care settings most frequented by victims of human trafficking. This was an anonymous, retrospective study of survivors of U.S.-based human trafficking. One hundred and seventy-three participants who endured U.S.-based human trafficking were surveyed. The majority (68%, n=117) of participants were seen by a health care provider while being trafficked. Respondents most frequently reported visiting emergency/urgent care practitioners (56%), followed by primary care providers, dentists, and obstetricians/gynecologists (OB/GYNs). While health care providers are serving this patient population, they do not consistently identify them as victims of human trafficking.

  9. Human Trafficking, Mental Illness, and Addiction: Avoiding Diagnostic Overshadowing.

    Science.gov (United States)

    Stoklosa, Hanni; MacGibbon, Marti; Stoklosa, Joseph

    2017-01-01

    This article reviews an emergency department-based clinical vignette of a trafficked patient with co-occurring pregnancy-related, mental health, and substance use disorder issues. The authors, including a survivor of human trafficking, draw on their backgrounds in addiction care, human trafficking, emergency medicine, and psychiatry to review the literature on relevant general health and mental health consequences of trafficking and propose an approach to the clinical complexities this case presents. In their discussion, the authors explicate the deleterious role of implicit bias and diagnostic overshadowing in trafficked patients with co-occurring addiction and mental illness. Finally, the authors propose a trauma-informed, multidisciplinary response to potentially trafficked patients. © 2017 American Medical Association. All Rights Reserved.

  10. 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

  11. Barcoding of GPCR trafficking and signaling through the various trafficking roadmaps by compartmentalized signaling networks.

    Science.gov (United States)

    Bahouth, Suleiman W; Nooh, Mohammed M

    2017-08-01

    Proper signaling by G protein coupled receptors (GPCR) is dependent on the specific repertoire of transducing, enzymatic and regulatory kinases and phosphatases that shape its signaling output. Activation and signaling of the GPCR through its cognate G protein is impacted by G protein-coupled receptor kinase (GRK)-imprinted "barcodes" that recruit β-arrestins to regulate subsequent desensitization, biased signaling and endocytosis of the GPCR. The outcome of agonist-internalized GPCR in endosomes is also regulated by sequence motifs or "barcodes" within the GPCR that mediate its recycling to the plasma membrane or retention and eventual degradation as well as its subsequent signaling in endosomes. Given the vast number of diverse sequences in GPCR, several trafficking mechanisms for endosomal GPCR have been described. The majority of recycling GPCR, are sorted out of endosomes in a "sequence-dependent pathway" anchored around a type-1 PDZ-binding module found in their C-tails. For a subset of these GPCR, a second "barcode" imprinted onto specific GPCR serine/threonine residues by compartmentalized kinase networks was required for their efficient recycling through the "sequence-dependent pathway". Mutating the serine/threonine residues involved, produced dramatic effects on GPCR trafficking, indicating that they played a major role in setting the trafficking itinerary of these GPCR. While endosomal SNX27, retromer/WASH complexes and actin were required for efficient sorting and budding of all these GPCR, additional proteins were required for GPCR sorting via the second "barcode". Here we will review recent developments in GPCR trafficking in general and the human β 1 -adrenergic receptor in particular across the various trafficking roadmaps. In addition, we will discuss the role of GPCR trafficking in regulating endosomal GPCR signaling, which promote biochemical and physiological effects that are distinct from those generated by the GPCR signal transduction

  12. Retrograde contrast radiography of the distal portions of the intestinal tract in foals

    International Nuclear Information System (INIS)

    Fischer, A.T.; Yarbrough, T.Y.

    1995-01-01

    A technique for retrograde contrast radiography of the distal portions of the intestinal tract of foals was developed and then performed in 25 foals (1 to 30 days old) with colic. Retrograde contrast radiography was shown to be sensitive (100%) and specific (100%) for evaluating obstruction of the small colon or transverse colon. It was slightly less sensitive (86%) and specific (83%) for evaluation of the entire large colon, particularly in older foals. Retrograde contrast radiography provided increased diagnostic capability, compared with that for noncontrast radiography. Retrograde contrast radiography can provide valuable information when evaluating foals with colic and should be part of the diagnostic evaluation

  13. Modern Day Slavery: What Drives Human Trafficking in Europe?

    OpenAIRE

    Hernandez, Diego; Rudolph, Alexandra

    2011-01-01

    At a time of increased attention on the international agenda for human trafficking, this paper examines the determinants of human trafficking inflows to 13 European countries based on official records. By employing a fixed effects zero-inflated, negative binomial gravity-type model, we address data characteristics appropriately. The econometric analysis suggests that human trafficking occurs in well established routes for migrants and refugees. Victims are more likely to be transported to, an...

  14. ANTROPOLOGIS TENTANG TRAFFICKING TKW DI MALAYSIA: ANTARA ADA DAN TIADA

    Directory of Open Access Journals (Sweden)

    Tri Marhaeni Pudji Astuti

    2011-12-01

    Full Text Available Trafficking has existed since the period of kingdoms in Java, going on to the colonialism period, andto the present time. Its meaning is broadening beyond human trading into the matters related to violence,blackmailing, and forcing. Trafficking happens not only within one specific area, but has crossed theborder of countries, indicating the existence of an international net. The mushrooming of trafficking isdue to weak law and political commitment of the concerning countries. Moreover, the bilateral talk tobanish trafficking has not been maximally conducted. The actors of trafficking vary from man-powerbrokers, agents, taxi drivers, and even officers (of transmigration and police offices. Trafficking happens invarious places ranging from luxurious spots or starred-hotels to plantations and areas which accommodatea lot of migrants. The victims are usually in so unfavorable bargaining positions that they are muchdependent on those traffickers. This dependency is the impact of imbalanced gender relation. Based onsome existing cases, it is indicated that the women’s lack of power, strength, information, and educationare often misused by the traffickers to take them as their preys. That is why empowering migrant womenis very crucial. One of the ways is empowering them through their realization that this need comes fromtheir own selves, not from any force outside. Besides, there should be strong commitment from the stateto seriously implement the law against any traffickers. Cooperation between the concerning countriesare also needed, for instance by issuing common regulations to banish trafficking.Keywords: Trafficking, migrant women, receiving country, sending country, trafficker

  15. USSOCOM’s Role in Addressing Human Trafficking

    Science.gov (United States)

    2010-12-02

    world. However, despite those alarming numbers, 62 countries have yet to convict a trafficker under laws in compliance with the Palermo Protocol.7...Against Transnational Organized Crime( Palermo Protocol), Palermo , Italy, 2000. 8 US Department of State, 2010 Trafficking In Persons Report...activities with the proceeds from narcotics trafficking. Terrorist groups such as the FARC in Colombia , Al Qaida in Afghanistan, and groups around

  16. Human Trafficking in Southeast Asia: Causes and Policy Implications

    Science.gov (United States)

    2009-06-01

    Trafficking (Thailand, 2007), 1. 21 Sheila Jeffreys, “Globalizing Sexual Exploitation, Sex Tourism and the Traffic in Women,” Leisure Studies, vol...trafficking. Economically, Cambodia has lagged far behind its successful neighboring countries of Thailand, Indonesia, Singapore and Malaysia , leaving...trafficked to Thailand and Malaysia , it is likely that the government had numerous opportunities to take action under the new legislation but simply failed

  17. Antropologis Tentang Trafficking Tkw Di Malaysia: Antara Ada Dan Tiada

    OpenAIRE

    Astuti, Tri Marhaeni Pudji

    2008-01-01

    Trafficking has existed since the period of kingdoms in Java, going on to the colonialism period, andto the present time. Its meaning is broadening beyond human trading into the matters related to violence,blackmailing, and forcing. Trafficking happens not only within one specific area, but has crossed theborder of countries, indicating the existence of an International net. The mushrooming of trafficking isdue to weak law and political commitment of the concerning countries. Moreover, the bi...

  18. ANTROPOLOGIS TENTANG TRAFFICKING TKW DI MALAYSIA: ANTARA ADA DAN TIADA

    OpenAIRE

    Tri Marhaeni Pudji Astuti

    2011-01-01

    Trafficking has existed since the period of kingdoms in Java, going on to the colonialism period, andto the present time. Its meaning is broadening beyond human trading into the matters related to violence,blackmailing, and forcing. Trafficking happens not only within one specific area, but has crossed theborder of countries, indicating the existence of an international net. The mushrooming of trafficking isdue to weak law and political commitment of the concerning countries. Moreover, the bi...

  19. 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 ...

  20. 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.

  1. 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.

  2. 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...

  3. The IAEA's Illicit Trafficking Database Programme

    International Nuclear Information System (INIS)

    Anzelon, G.; Hammond, W.; Nicholas, M.

    2001-01-01

    Full text: As part of its overall programme on nuclear material security, the IAEA has since 1995 maintained a database of incidents of trafficking in nuclear materials and other radioactive sources. The Illicit Trafficking Database Programme (ITDP) is intended to assist Member States by alerting them to current incidents, by facilitating exchange of reliable, detailed information about incidents, and by identifying any common threads or trends that might assist States in combating illicit trafficking. The ITDP also seeks to better inform the public by providing basic information to the media concerning illicit trafficking events. Approximately 70 States have joined this programme for collecting and sharing information on trafficking incidents. Reporting States have the opportunity to designate what information may be shared with other States and what may be shared with the public. In cases where the IAEA's first information about a possible incident comes from news media or other open sources rather than from a State notification, the information first is evaluated, and then, if warranted, the relevant State or States are contacted to request confirmation or clarification of an alleged incident. During 2000, as a result of experience gained working with information on illicit nuclear trafficking, the IAEA developed of a flexible and comprehensive new database system. The new system has an open architecture that accommodates structured information from States, in-house information, open-source articles, and other information sources, such as pictures, maps and web links. The graphical user interface allows data entry, maintenance and standard and ad-hoc reporting. The system also is linked to a Web-based query engine, which enables searching of both structured and open-source information. For the period 1 January 1993 through 31 March 2001, the database recorded more than 550 incidents, of which about two-thirds have been confirmed by States. (Some of these

  4. Fluoroscopic guidance of retrograde exchange of ureteral stents in women.

    Science.gov (United States)

    Chang, Ruey-Sheng; Liang, Huei-Lung; Huang, Jer-Shyung; Wang, Po-Chin; Chen, Matt Chiung-Yu; Lai, Ping-Hong; Pan, Huay-Ben

    2008-06-01

    The purpose of this study was to review our experience with fluoroscopically guided retrograde exchange of ureteral stents in women. During a 48-month period, 28 women (age range, 38-76 years) were referred to our department for retrograde exchange of a ureteral stent. The causes of urinary obstruction were tumor compression in 26 patients and benign fibrotic stricture in two patients. A large-diameter snare catheter (25-mm single loop or 18- to 35-mm triple loop) or a foreign body retrieval forceps (opening width, 11.3 mm) was used to grasp the bladder end of the stent under fluoroscopic guidance. The technique entailed replacement of a patent or occluded ureteral stent with a 0.035- or 0.018-inch guidewire with or without the aid of advancement of an angiographic sheath. A total of 54 ureteral stents were exchanged with a snare catheter in 42 cases or a forceps in 12 cases. One stent misplaced too far up the ureter was replaced successfully through antegrade percutaneous nephrostomy. Ten occluded stents, including one single-J stent, were managed with a 0.018-inch guidewire in three cases, advancement of an angiographic sheath over the occluded stent into the ureter in five cases, and recannulation of the ureteral orifice with a guidewire in two cases. No complications of massive hemorrhage, ureter perforation, or infection were encountered. With proper selection of a snare or forceps catheter, retrograde exchange of ureteral stents in women can be easily performed under fluoroscopic guidance with high technical success and a low complication rate.

  5. Human Trafficking and Commercialization of Surrogacy in India

    Directory of Open Access Journals (Sweden)

    Pyali Chatterjee

    2014-10-01

    Full Text Available The Supreme Court of India, In Baby Manji Yamada versus Union of India & Anr. [2008] INSC 1656, popularly known as Manji Case, declared that Commercial Surrogacy is legal in India. As we know that, India is a developing country and here, most of the peoples are very poor and illiterate. Recently, human trafficking was increase with an uncontrollable rate in the entire world. In addition, making Commercialization of Surrogacy legal had already give birth to a new form of trafficking. Where, illiterate women from poor section is trafficked to run the reproductive industry of the Surrogacy. As we know that the traffickers, they used to trafficked girls/women for prostitution but now after the legalization of Commercial Surrogacy, they will trafficked girl/women for the reproductive industry as a raw material. The Immoral Trafficking Prevention Act (ITPA, 1956 and Sections 366(A and 372 of the Indian Penal Code, 1860 are the existing laws of India, which deals with human trafficking. However, none of these provisions contains any solution, to deal with this new serious issue of trafficking of women/girls for the purpose of Commercial Surrogacy in reproductive industries. These existing laws as well as the pending draft bill of Assisted Reproductive Technologies (ART Regulation Bill, 2010 needs an amendment to check this crime against women once again to protect the rights and health of the women.

  6. Accountability and the Use of Raids to Fight Trafficking

    Directory of Open Access Journals (Sweden)

    Melissa Ditmore

    2012-06-01

    Full Text Available Accountability in anti-trafficking efforts is a crucial but often overlooked aspect of deciding whether such efforts are truly rooted in a human rights framework. In a rush to help, and inspired by sensationalised views of what human trafficking is, many campaigns actually harm the very people they are supposed to assist. Law enforcement raids are one such effort, as they do not take into account the very different power dynamics between the actor engaging in the raid, and the person who is subject to the raid. Data from the United States suggests that raids conducted by local law enforcement agencies are an ineffective means of locating and identifying trafficked persons. Research also reveals that raids are all too frequently accompanied by violations of the human rights of trafficked persons and sex workers alike, and can therefore be counterproductive to the underlying goals of anti-trafficking initiatives. Findings suggest that a rights-based and “survivor-centred” approach to trafficking in persons requires the development and promotion of alternative methods of identifying and protecting the rights of trafficked persons which prioritise the needs, agency, and self-determination of trafficking survivors. They also indicate that preventative approaches, which address the circumstances that facilitate trafficking in persons, should be pursued over law enforcement based responses.

  7. Child Labor Trafficking in the United States: A Hidden Crime

    Directory of Open Access Journals (Sweden)

    Katherine Kaufka Walts

    2017-06-01

    Full Text Available Emerging research brings more attention to labor trafficking in the United States. However, very few efforts have been made to better understand or respond to labor trafficking of minors. Cases of children forced to work as domestic servants, in factories, restaurants, peddling candy or other goods, or on farms may not automatically elicit suspicion from an outside observer as compared to a child providing sexual services for money. In contrast to sex trafficking, labor trafficking is often tied to formal economies and industries, which often makes it more difficult to distinguish from "legitimate" work, including among adolescents. This article seeks to provide examples of documented cases of child labor trafficking in the United States, and to provide an overview of systemic gaps in law, policy, data collection, research, and practice. These areas are currently overwhelmingly focused on sex trafficking, which undermines the policy intentions of the Trafficking Victims Protection Act (2000, the seminal statute criminalizing sex and labor trafficking in the United States, its subsequent reauthorizations, and international laws and protocols addressing human trafficking.

  8. Prevention of Human Trafficking in Ethiopia: Assessing The Legal Framework

    Directory of Open Access Journals (Sweden)

    Zelalem Shiferaw Woldemichael

    2017-12-01

    Full Text Available Recent findings have indicated that both in-country trafficking (trafficking of individuals from rural areas to relatively affluent towns and cities and external trafficking (trafficking of individuals from a given country to foreign countries are prevalent in Ethiopia. In 2012, the government acceded to the Protocol to Suppress and Punish Trafficking in Persons Especially Women and Children supplementing the United Nations Convention against Transnational Organized Crime (The UN Trafficking Protocol, here after. With a view to giving effect to the requirements of this instrument, the government passed in to law Proclamation No. 909/2015 (The Prevention and Suppression of Trafficking in Persons and Smuggling of Migrants Proclamation, which is the most comprehensive of all laws adopted in Ethiopia to deal with human trafficking. Taking in to account the fact that human trafficking is exacerbated by the absence of regulatory framework on the employment of Ethiopian nationals in foreign countries, the govern-ment has also brought in to practice Proclamation No. 923/2016 (Ethiopia’s Overseas Employment Proclamation. This article has examined whether the above-mentioned laws of Ethiopia comply with international standards in dealing with prevention strategies.

  9. Elided Populations: A Baseline Survey on Human Trafficking in Kenya

    DEFF Research Database (Denmark)

    Owiso, Michael

    2017-01-01

    -regional, as well as inter-regional trafficking, is available. This study seeks to build synergy in the counter-trafficking efforts in Kenya. In so doing it aims to in the overall identify gaps in combating and responding to human trafficking and offer programmatic recommendations/suggestions particularly for IRC......Trafficking in persons is a crime. It is gaining momentum in the continent and particularly in Kenya and also attracting the attention of actors who are working to combat it. This focus shows the multiplicity of actors working together to prosecute, prevent and protect. Evidence of both intra...

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

    Science.gov (United States)

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

    2013-09-01

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

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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.

  13. 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

  14. Pancreas imaging by computed tomography after endoscopic retrograde pancreatography

    International Nuclear Information System (INIS)

    Frick, M.P.; O'Leary, J.F.; Salomonowitz, E.; Stoltenberg, E.; Hutton, S.; Gedgaudas, E.

    1984-01-01

    A method using CT after endoscopic retrograde pancreatography (CT-ERP) is described for pancreatic imaging. When using an ERP technique in the canine model comparable to that used in humans, small amounts of contrast material in peripheral pancreatic radicles resulted in enhancement of the pancreas on CT scans. Nine patients were also studied by CT-ERP images. The main pancreatic duct was seen on delayed images. In cases of chronic pancreatitis (n = 2), pancreatic opacification was patchy and heterogeneous. There was no contrast-material enhancement in areas of pancreatic carcimomas (n = 2). CT-ERP showed the true extent of carcinoma better than ERP alone

  15. Modified Technique of Retrograde Intubation in TMJ Ankylosis

    Directory of Open Access Journals (Sweden)

    Shaila Kamat

    2008-01-01

    Full Text Available We are presenting a case report on the anaesthetic management of a case of ankylosis of temporomandibular joint for corrective surgery in a 7 year old child. Anticipated difficult airway in paediatric population has always been a perplexing problem, awake fibreoptic intubation almost impossible due to obvious difficulties with co-operation. Here we are describing a new approach to this problem, in which the patients were kept under GA with spontaneous ventilation while retrograde intubation was done quite comfortably by the conventional method.

  16. Combined antegrade and retrograde ureteral stenting: the rendezvous technique

    International Nuclear Information System (INIS)

    Macri, A.; Magno, C.; Certo, A.; Basile, A.; Scuderi, G.; Crescenti, F.; Famulari, C.

    2005-01-01

    Ureteral stenting is a routine procedure in endourology. To increase the success rate in difficult cases, it may be helpful to use the rendezvous technique, a combined antegrade and retrograde approach. We performed 16 urological rendezvous in 11 patients with ureteral strictures or urologic lesions. The combined approach was successful in all patients, without morbidity or mortality. In our experience the rendezvous technique increased the success rate of antegrade ureteral stenting from 78.6 to 88.09% (p>0.05). This procedure is a valid option in case of failure of conventional ureteral stenting

  17. Diagnostic and Prevention Approach in Post Endoscopic Retrograde Cholangiopancreatography Pancreatitis

    Directory of Open Access Journals (Sweden)

    Stella Ilone

    2016-12-01

    Full Text Available Obstructive jaundice (icterus was an emergency situation in gastroenterology. Endoscopic retrograde cholangiopancreatography (ERCP was a nonsurgical approach to release obstruction, mostly in common bile duct. Nowadays, this procedure was become frequently used in daily practice, but several complications also emerging. One of the severe complication was Post-ERCP Pancreatitis (PEP. Since it has a high mortality and morbidity, and also reduce patient quality of life, several approaches have been developed to reduce its incidence. In general, approaches consist of patient identification, efficient procedure, until pharmacological agent prevention. Although there were still contradiction among these, careful approach should be considered for each patients for a better outcomes.

  18. Sphingomyelin synthesis in rat liver occurs predominantly at the cis and medial cisternae of the Golgi apparatus

    International Nuclear Information System (INIS)

    Futerman, A.H.; Stieger, B.; Hubbard, A.L.; Pagano, R.E.

    1990-01-01

    The intracellular site of sphingomyelin (SM) synthesis was examined in subcellular fractions from rat liver using a radioactive ceramide analog N-([1-14C]hexanoyl)-D-erythro-sphingosine. This lipid readily transferred from a complex with bovine serum albumin to liver fractions without disrupting the membranes, and was metabolized to radioactive SM. To prevent degradation of the newly synthesized SM to ceramide, all experiments were performed in the presence of EDTA to minimize neutral sphingomyelinase activity and at neutral pH to minimize acid sphingomyelinase activity. An intact Golgi apparatus fraction gave an 85-98-fold enrichment of SM synthesis and a 58-83-fold enrichment of galactosyltransferase activity. Controlled trypsin digestion demonstrated that SM synthesis was localized to the lumen of intact Golgi apparatus vesicles. Although small amounts of SM synthesis were detected in plasma membrane and rough microsome fractions, after accounting for contamination by Golgi apparatus membranes, their combined activity contributed less than 13% of the total SM synthesis in rat liver. Subfractions of the Golgi apparatus were obtained and characterized by immunoblotting and biochemical assays using cis/medial (mannosidase II) and trans (sialyltransferase and galactosyltransferase) Golgi apparatus markers. The specific activity of SM synthesis was highest in enriched cis and medial fractions but far lower in a trans fraction. We conclude that SM synthesis in rat liver occurs predominantly in the cis and medial cisternae of the Golgi apparatus and not at the plasma membrane or endoplasmic reticulum as has been previously suggested

  19. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  1. 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

  2. DMPD: Lipoprotein trafficking in vascular cells. Molecular Trojan horses and cellularsaboteurs. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 9287290 Lipoprotein trafficking in vascular cells. Molecular Trojan horses and cell...ml) Show Lipoprotein trafficking in vascular cells. Molecular Trojan horses and cellularsaboteurs. PubmedID ...9287290 Title Lipoprotein trafficking in vascular cells. Molecular Trojan horses

  3. Trafficking in Persons for Ransom and the Need to Expand the Interpretation of Article 3 of the UN Trafficking Protocol

    Directory of Open Access Journals (Sweden)

    Mogos O Brhane

    2015-04-01

    Full Text Available As the nature of trafficking in persons continues to manifest itself in myriad ways all over the world, interpretation of the UN Protocol to Prevent, Suppress and Punish Trafficking in Persons, Especially Women and Children (Trafficking Protocol, should be broadened to include newly emerging practices that are similar in nature to those it has already embraced under its definition. The Protocol appears to encompass other forms of trafficking which are unnamed or unforeseen by the definition provided under Article 3. It is time to expand its spectrum. Northeast Africa is plagued by a unique form of trafficking in persons—trafficking in persons for ransom. This involves a practice where people are smuggled, abducted, kidnapped and tortured to compel their relatives and families to pay ransom money. Victims are nationals of Eritrea, Ethiopia, Sudan and South Sudan. However, as Northeast Africa hosts particularly high numbers of Eritrean migrants and the largest Eritrean diaspora globally, Eritreans are very vulnerable to being targeted for trafficking for ransom. As trafficking for ransom is an emerging trend, legal ramifications have never been studied in full. Few reports try to address legal issues around the phenomenon, and those that do only give it a few paragraphs of attention. There is need for a closer look at this form of trafficking.

  4. Assisting victims of human trafficking: strategies to facilitate identification, exit from trafficking, and the restoration of wellness.

    Science.gov (United States)

    Hodge, David R

    2014-04-01

    Human trafficking is a pressing social justice concern. Social work is uniquely situated to address this problem. However, despite the profession's commitment to social justice, the scholarship to equip social workers to address this issue has been largely absent from professional discourse. To address this gap, this article helps social work practitioners to assist victims of human trafficking. After orienting readers to the scope and process of human trafficking, the topics of victim identification, exit from trafficking, and the restoration of psychological wellness are discussed. By equipping themselves in these three areas, practitioners can advance social justice on behalf of some of the most exploited people in the world.

  5. Domestic Sex Trafficking of Minors: Medical Student and Physician Awareness.

    Science.gov (United States)

    Titchen, Kanani E; Loo, Dyani; Berdan, Elizabeth; Rysavy, Mary Becker; Ng, Jessica J; Sharif, Iman

    2017-02-01

    Our aim was to assess: (1) medical trainee and practicing physician awareness about domestic sex trafficking of minors; and (2) whether respondents believe that awareness of trafficking is important to their practice. We designed an anonymous electronic survey, and a convenience sample was collected from June through October 2013. Voluntary participants were 1648 medical students, residents, and practicing physicians throughout the United States. Data were analyzed for correlations between study cohort characteristics and: (1) agreement with the statement: "knowing about sex trafficking in my state is important to my profession"; (2) knowledge of national statistics regarding the sex trafficking of minors; and (3) knowledge of appropriate responses to encountering a trafficked victim. More practicing physicians than residents or medical students: (1) agreed or strongly agreed that knowledge about human trafficking was important to their practice (80.6%, 71.1%, and 69.2%, respectively; P = .0008); (2) correctly estimated the number of US trafficked youth according to the US Department of State data (16.1%, 11.7%, and 7.9%, respectively; P = .0011); and (3) were more likely to report an appropriate response to a trafficked victim (40.4%, 20.4%, and 8.9%, respectively; P = .0001). Although most medical trainees and physicians place importance on knowing about human trafficking, they lack knowledge about the scope of the problem, and most would not know where to turn if they encountered a trafficking victim. There exists a need for standardized trafficking education for physicians, residents, and medical students. Copyright © 2015 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  6. Global Trafficking Prevalence Data Distorts Efforts to Stop Patterns of Human Trafficking

    Directory of Open Access Journals (Sweden)

    Mike Dottridge

    2017-04-01

    Full Text Available For everyone engaged in efforts to stop the exploitation and harm associated with human trafficking, it always sounds helpful to know how many people are being exploited in particular places and where they come from. Finding out should help us assess whether efforts to cut down these numbers are effective or not.

  7. Discovery of New Retrograde Substructures: The Shards of ω Centauri?

    Science.gov (United States)

    Myeong, G. C.; Evans, N. W.; Belokurov, V.; Sanders, J. L.; Koposov, S. E.

    2018-06-01

    We use the SDSS-Gaia catalogue to search for substructure in the stellar halo. The sample comprises 62 133 halo stars with full phase space coordinates and extends out to heliocentric distances of ˜10 kpc. As actions are conserved under slow changes of the potential, they permit identification of groups of stars with a common accretion history. We devise a method to identify halo substructures based on their clustering in action space, using metallicity as a secondary check. This is validated against smooth models and numerical constructed stellar halos from the Aquarius simulations. We identify 21 substructures in the SDSS-Gaia catalogue, including 7 high significance, high energy and retrograde ones. We investigate whether the retrograde substructures may be material stripped off the atypical globular cluster ω Centauri. Using a simple model of the accretion of the progenitor of the ω Centauri, we tentatively argue for the possible association of up to 5 of our new substructures (labelled Rg1, Rg3, Rg4, Rg6 and Rg7) with this event. This sets a minimum mass of 5× 108M⊙ for the progenitor, so as to bring ω Centauri to its current location in action - energy space. Our proposal can be tested by high resolution spectroscopy of the candidates to look for the unusual abundance patterns possessed by ω Centauri stars.

  8. Response to Illicit Trafficking of Radioactive Materials

    International Nuclear Information System (INIS)

    2010-01-01

    Two response paths are discussed in the presentation. Reactive response follows when an alarm of a border monitor goes off or a notification is received about an incident involving or suspected to involve radioactive materials. The response can also be the result of the finding of a discrepancy between a customs declaration form and the corresponding actual shipment. Proactive response is undertaken upon receipt of intelligence information suggesting the illicit trafficking of radioactive materials, notification about the discovery of non-compliance with transport regulations or if discrepancies are found in an inventory of radioactive materials.

  9. An indigenous economic technique of positive pressure retrograde urethrography in female patients

    Directory of Open Access Journals (Sweden)

    H Singh

    2001-01-01

    Full Text Available Usually double balloon catheter is required forpositive pressure retrograde urethrography in females. We describe a technique of positive pressure retrograde urethrography using Foley catheter and rubber stopper, inexpensive and could be adopted in any hospital or radiological suite.

  10. Deterioration of cholestasis after endoscopic retrograde cholangiography in advanced primary sclerosing cholangitis

    NARCIS (Netherlands)

    Beuers, U.; Spengler, U.; Sackmann, M.; Paumgartner, G.; Sauerbruch, T.

    1992-01-01

    Complications of endoscopic retrograde cholangiography specific to patients with primary sclerosing cholangitis have not yet been reported. We observed transient rises of serum bilirubin after diagnostic endoscopic retrograde cholangiography in five of 15 patients and persistent rises in three of 15

  11. 78 FR 59950 - Advisory Council on Wildlife Trafficking

    Science.gov (United States)

    2013-09-30

    ... Committee Structure and Organization, the National Strategy to Combat Wildlife Trafficking, and other... will consider: 1. Advisory Council organization and process, 2. The National Strategy to Combat..., through the Secretary of the Interior, on national strategies to combat wildlife trafficking, including...

  12. Domestic Minor Sex Trafficking in the United States

    Science.gov (United States)

    Kotrla, Kimberly

    2010-01-01

    By now, most social workers are familiar with the issue of human trafficking. However, many are likely unfamiliar with research indicating that youths constitute the most vulnerable group in the United States for becoming victims of sex trafficking and that most women in prostitution actually entered as minors. Some experts are now referring to…

  13. Trafficking: Sebuah Masalah Pengiriman Tenaga Kerja Indonesia Ke Malaysia

    OpenAIRE

    Wahyuddin, S.S., M.Hum.

    2013-01-01

    Trafficking atau yang lazim dikenal dengan istilah perdagangan manusia merupakan sebuah fenomena internasional yang terjadi dari masa ke masa. Kalupun terdengar seperti baru, itu karena peristilahan saja. Istilah trafficking dewasa ini kita kenal juga dengan istilah modern slavery. Praktek serupa terjadi juga di masa lampau seperti eksploitasi baik fisik maupun seksual dalam bentuk kerja paksa dan perbudakan. -

  14. Adolescent Black Males' Drug Trafficking and Addiction: Three Theoretical Perspectives.

    Science.gov (United States)

    Moore, Sharon E.

    1995-01-01

    Explains the incidence and nature of drug trafficking and chemical dependency among adolescent black males. The paper also discusses the social science theories of Emile Durkheim, Karl Marx, and Molefi Asante to better understand the behaviors, and the consequences of those behaviors, of young black males who participate in drug trafficking. (GR)

  15. Human Sex Trafficking in America: What Counselors Need to Know

    Science.gov (United States)

    Litam, Stacey Diane A.

    2017-01-01

    The social justice issue of human sex trafficking is a global form of oppression that places men, women and children at risk for sexual exploitation. Although a body of research exists on the topics of human trafficking, literature specific to the mental health implications for counselors working with this population is limited. Counselors should…

  16. South Africa – Safe Haven for Human Traffickers? Employing the ...

    African Journals Online (AJOL)

    Having ratified the Protocol to Prevent, Suppress and Punish Trafficking in Persons, Especially Women and Children, South Africa is obliged to adopt legislative measures that criminalise human trafficking and comply with other standards laid down in this international instrument. However, by mid-2011, South Africa had not ...

  17. Protein kinesis: The dynamics of protein trafficking and stability

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-12-31

    The purpose of this conference is to provide a multidisciplinary forum for exchange of state-of-the-art information on protein kinesis. This volume contains abstracts of papers in the following areas: protein folding and modification in the endoplasmic reticulum; protein trafficking; protein translocation and folding; protein degradation; polarity; nuclear trafficking; membrane dynamics; and protein import into organelles.

  18. Child Trafficking: A Hindrance to the Girl-Child Education

    Science.gov (United States)

    Aibangbe, Mary O.

    2015-01-01

    Child trafficking continues to pose a major hindrance to the freedom and educational development of the girl-child in Nigeria. Most of the girls trafficked are forced into prostitution, forced labour and in some cases as human sacrifice. Some families support this trend because they see it as a means to break the yoke of economic hardship. The…

  19. 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

  20. Shaping the Victim: Borders, security, and human trafficking in Albania

    Directory of Open Access Journals (Sweden)

    James Campbell

    2013-09-01

    Full Text Available Borders are productive sites where knowledge is gathered and migrant populations are formed. The knowledge gathered from victims of trafficking reinforces a victim narrative that represents a perceived threat to society by highlighting violence, criminality, coercion, and naivety. Using Albania as a case in point, the article looks at trafficked people and the narratives of victimhood that surround them. In the case of trafficked people, the border projected out towards other states produces a discursively defined victim of trafficking. When projected back within the national territory, the border essentially produces a criminalised sex worker. To argue this point, the article discusses the role victims of trafficking play in the EU and looks at how international norms espoused by the OSCE and IOM have prepped the Albanian border for EU ascension and created the means for governable populations within Albania.

  1. Health impacts and research ethics in female trafficking.

    Science.gov (United States)

    Dhital, S R; Aro, R A; Sapkota, K

    2011-04-01

    Female trafficking is a social and public health problem, associated with physical and sexual abuse, psychological trauma, injuries from violence, sexually transmitted infections, adverse reproductive outcomes and substance misuse. It faces several challenges ranging from the hidden nature of the problem to ethical and human rights issues. The objectives of this paper are to analyze health impact of trafficking; ethical and research issues and anti-trafficking strategies in the Nepalese context. We collected published and unpublished data assessing the public health, ethical burden and research needs from different sources. Trafficked female involved in sex-industry that face grave situation as depicted and it might a reservoir of sexually transmitted diseases. Ethical issues related to survey of assessing the burden are difficult to carry out. The best ways to prevent and control these problems are to enhance anti- trafficking laws and raise awareness, empower and mobilize females and establish organizational capacity.

  2. At Home: Family reintegration of trafficked Indonesian men

    Directory of Open Access Journals (Sweden)

    Rebecca Surtees

    2018-04-01

    Full Text Available Large numbers of Indonesian men migrate each year for work in construction, in factories and in agriculture, on plantations and on fishing boats. Many of them end up exploited in ways that constitute human trafficking, suffering violence, deprivation, restricted freedom and severe exploitation as well as long periods of separation from their families. This article explores the challenges faced by forty-nine Indonesian men reintegrating into their families and communities after having been trafficked. While many problems with the family were caused by economics, tensions also resulted from long separations, fractured relationships, and frustration and blame over ‘failed’ migration and unfulfilled expectations. Tensions were sometimes exacerbated when men faced recrimination and blame in their communities after return. Understanding the nature of and reasons for the problems that men faced after trafficking is vital in considering how trafficked men and their families can be supported to recover and reintegrate after trafficking.

  3. The role of the nurse in combating human trafficking.

    Science.gov (United States)

    Sabella, Donna

    2011-02-01

    Human trafficking, also called modern slavery, happens worldwide--and the United States is no exception. Within our borders, thousands of foreign nationals and U.S. citizens, many of them children, are forced or coerced into sex work or various forms of labor every year. Nurses and other health care providers who encounter victims of trafficking often don't realize it, and opportunities to intervene are lost. Although no one sign can demonstrate with certainty when someone is being trafficked, there are several indicators that clinicians should know. This article provides an overview of human trafficking, describes how to recognize signs that a person is being trafficked and how to safely intervene, and offers an extensive resource list.

  4. Psychological Coercion in Human Trafficking: An Application of Biderman's Framework.

    Science.gov (United States)

    Baldwin, Susie B; Fehrenbacher, Anne E; Eisenman, David P

    2015-09-01

    This study examined coercive conditions experienced by trafficked persons in the context of Biderman's theory of coercion. We conducted semi-structured interviews with 12 adult women trafficked into Los Angeles County, from 10 countries, for domestic work and/or sex work. Participants described health problems they experienced in relation to their trafficking experience and their perceptions of conditions that caused health problems. Utilizing a framework analysis approach, we analyzed themes using Biderman's framework. Participants reported experiencing the range of nonphysical coercive tactics outlined by Biderman, including isolation, monopolization of perception, induced debility or exhaustion, threats, occasional indulgences, demonstration of omnipotence, degradation, and enforcement of trivial demands. Our analysis demonstrates how these coercion tactics reinforced the submission of trafficked persons to their traffickers even in the absence of physical force or restraints. Such psychological abuse creates extreme stress that can lead to acute and chronic, physical and mental health problems. © The Author(s) 2014.

  5. New insights into how trafficking regulates T cell receptor signaling

    Directory of Open Access Journals (Sweden)

    Jieqiong Lou

    2016-07-01

    Full Text Available AbstractThere is emerging evidence that exocytosis plays an important role in regulating T cell receptor (TCR signaling. The trafficking molecules involved in lytic granule (LG secretion in cytotoxic T lymphocytes (CTL have been well studied due to the immune disorder known as familial hemophagocytic lymphohisiocytosis (FHLH. However, the knowledge of trafficking machineries regulating the exocytosis of receptors and signaling molecules remains quite limited. In this review, we summarize the reported trafficking molecules involved in the transport of the TCR and downstream signaling molecules to the cell surface. By combining this information with the known knowledge of LG exocytosis and general exocytic trafficking machinery, we attempt to draw a more complete picture of how the TCR signaling network and exocytic trafficking matrix are interconnected to facilitate T cell activation. This also highlights how membrane compartmentalization facilitates the spatiotemporal organization of cellular responses that are essential for immune functions.

  6. Domestic minor sex trafficking: what the PNP needs to know.

    Science.gov (United States)

    Hornor, Gail

    2015-01-01

    Human trafficking is a major global public health problem and represents a substantial human rights violation. Human trafficking has been receiving attention in both the lay media and professional literature. Human trafficking can include commercial sex, forced labor, child soldiers, and stealing of human organs. One form of human trafficking represents a significant American pediatric health problem: domestic minor sex trafficking (DMST). DMST is the commercial sexual abuse of children by selling, buying, or trading their sexual service. This continuing education article will define DMST and discuss it in terms of prevalence, risk factors, and practice implications for the pediatric nurse practitioner. Copyright © 2015 National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved.

  7. Providing services to trafficking survivors: Understanding practices across the globe.

    Science.gov (United States)

    Steiner, Jordan J; Kynn, Jamie; Stylianou, Amanda M; Postmus, Judy L

    2018-01-01

    Human trafficking is a global issue, with survivors representing all genders, ages, races, ethnicities, religions, and countries. However, little research exists that identifies effective practices in supporting survivors of human trafficking. The research that does exist is Western-centric. To fill this gap in the literature, the goal of this research was to understand practices used throughout the globe with adult human trafficking survivors. A qualitative approach was utilized. Providers from 26 countries, across six different continents, were interviewed to allow for a comprehensive and multi-faceted understanding of practices in working with survivors. Participants identified utilizing an empowerment-based, survivor, and human life-centered approach to working with survivors, emphasized the importance of engaging in community level interventions, and highlighted the importance of government recognition of human trafficking. Findings provide information from the perspective of advocates on best practices in the field that can be used by agencies to enhance human trafficking programming.

  8. Regulation of vesicular trafficking by Parkinson's disease-associated genes

    Directory of Open Access Journals (Sweden)

    Tsuyoshi Inoshita

    2015-10-01

    Full Text Available The regulatory mechanisms that control intracellular vesicular trafficking play important roles in cellular function and viability. Neurons have specific vesicular trafficking systems for synaptic vesicle formation, release and recycling. Synaptic vesicular trafficking impairments induce neuronal dysfunction and physiological and behavioral disorders. Parkinson's disease (PD is an age-dependent neurodegenerative disorder characterized by dopamine depletion and loss of dopamine neurons in the midbrain. The molecular mechanism responsible for the neurodegeneration that occurs during PD is still not understood; however, recent functional analyses of familial PD causative genes suggest that a number of PD causative genes regulate intracellular vesicular trafficking, including synaptic vesicular dynamics. This review focuses on recent insights regarding the functions of PD causative genes, their relationship with vesicular trafficking and how mutations associated with PD affect vesicular dynamics and neuronal survival.

  9. Entrapment and Enmeshment Schemes Used by Sex Traffickers.

    Science.gov (United States)

    Reid, Joan A

    2016-09-01

    Emerging research suggests that sex traffickers/pimps control the majority of trafficked girls in the United States. The youthfulness of these victims and their lack of psychosocial maturity severely diminish their ability to detect exploitative motives or withstand manipulation of traffickers. A review of 43 cases of sexually exploited girls involving non-relative traffickers and 10 semi-structured interviews with social service providers revealed numerous scripts and schemes used by sex traffickers to entrap and entangle victims including boyfriend/lover scripts, ruses involving debt bondage, friendship or faux-family scripts, threats of forced abortion or to take away children, and coerced co-offending. These findings inform potential prevention efforts and highlight the need for multi-systemic, victim-centered approaches to intervention. © The Author(s) 2014.

  10. Human Trafficking: Fighting the Illicit Economy with the Legitimate Economy

    Directory of Open Access Journals (Sweden)

    Louise Shelley

    2015-02-01

    Full Text Available Since the beginning of research on human trafficking, there has been attention paid to the challenges surrounding the illicit economy. In creating new strategies and initiatives on combatting human trafficking, there needs to be more discussion surrounding the legitimate economy and how the business sector can make an impact in the fight against trafficking. Currently, there is a growing movement of businesses that are looking to address human trafficking through training, education, and leadership initiatives; codes of conduct; supply chain management; and financial analysis. This paper will examine the latest in these strategies and approaches by businesses in the global war against human trafficking, in addition to a discussion of a new initiative engaging the private sector co-led by Dr. Louise Shelley and Christina Bain through the World Economic Forum’s Global Agenda Council Network.

  11. Modeling for Determinants of Human Trafficking: An Empirical Analysis

    Directory of Open Access Journals (Sweden)

    Seo-Young Cho

    2015-02-01

    Full Text Available This study aims to identify robust push and pull factors of human trafficking. I test for the robustness of 70 push and 63 pull factors suggested in the literature. In doing so, I employ an extreme bound analysis, running more than two million regressions with all possible combinations of variables for up to 153 countries during the period of 1995–2010. My results show that crime prevalence robustly explains human trafficking both in destination and origin countries. Income level also has a robust impact, suggesting that the cause of human trafficking shares that of economic migration. Law enforcement matters more in origin countries than destination countries. Interestingly, a very low level of gender equality may have constraining effects on human trafficking outflow, possibly because gender discrimination limits female mobility that is necessary for the occurrence of human trafficking.

  12. Two Cheers for the Trafficking Protocol

    Directory of Open Access Journals (Sweden)

    Anne T Gallagher

    2015-04-01

    Full Text Available The Trafficking Protocol makes an easy target for attack. Its origins lie in an attempt to control a particularly exploitative form of migration that was challenging the ability of States to control their own borders. Its parent instrument is a framework agreement to address transnational organised crime. While paying fleeting attention to the rights of victims, the Protocol, with its emphasis on criminalisation and border protection is nowhere near being a human rights treaty. On top of all that it does not even have a credible enforcement mechanism, allowing states parties wide latitude in interpreting and applying their obligations. Strangely, these seemingly insurmountable flaws have not stopped the Protocol’s emergence as perhaps the single most important development in the fight against human trafficking. Without the Protocol, arguments around definitions would have continued to block the evolution of principles and rules. Without the Protocol it is likely that the human rights system would have continued its shameful tradition of sidelining issues such as forced labour, forced sex, forced marriage and the ritual exploitation of migrant workers through debt. Most critically, the Protocol provided the impetus and template for a series of legal and political developments that, over time, have served to ameliorate some of its greatest weaknesses, including the lack of human rights protections and of a credible oversight mechanism.

  13. Synaptic Control of Secretory Trafficking in Dendrites

    Directory of Open Access Journals (Sweden)

    Cyril Hanus

    2014-06-01

    Full Text Available Localized signaling in neuronal dendrites requires tight spatial control of membrane composition. Upon initial synthesis, nascent secretory cargo in dendrites exits the endoplasmic reticulum (ER from local zones of ER complexity that are spatially coupled to post-ER compartments. Although newly synthesized membrane proteins can be processed locally, the mechanisms that control the spatial range of secretory cargo transport in dendritic segments are unknown. Here, we monitored the dynamics of nascent membrane proteins in dendritic post-ER compartments under regimes of low or increased neuronal activity. In response to activity blockade, post-ER carriers are highly mobile and are transported over long distances. Conversely, increasing synaptic activity dramatically restricts the spatial scale of post-ER trafficking along dendrites. This activity-induced confinement of secretory cargo requires site-specific phosphorylation of the kinesin motor KIF17 by Ca2+/calmodulin-dependent protein kinases (CaMK. Thus, the length scales of early secretory trafficking in dendrites are tuned by activity-dependent regulation of microtubule-dependent transport.

  14. Sex Trafficking, Law Enforcement and Perpetrator Accountability

    Directory of Open Access Journals (Sweden)

    Holly Burkhalter

    2012-06-01

    Full Text Available In theory, everyone – except for criminals involved in their exploitation - agrees that children must not be in the sex industry and further, that those who prey on them must be prosecuted and punished. Virtually every country in the world has adopted national laws prohibiting the commercial sexual exploitation of children. International law is clear on this point, as well. Yet, when governments – and NGOs working with them – take action to extract children from commercial sex venues, common ground on protecting children from abuse can quickly erode with concerns about the efficacy of police intervention, the possibility of collateral harm to consenting adult sex workers or a decrease in access to HIV-prevention and related health services. The author argues that healing this divide must come through the reform of local police – and that, without the participation of law enforcement, there can be no long-term protection for children vulnerable to trafficking and related exploitation. In this article, human rights practitioner Holly Burkhalter argues that healing this divide must be accomplished through the reform of local police – and that human rights advocates, local governments and others seeking to combat trafficking cannot achieve long-term, sustainable protection for children without the involvement of law enforcement.

  15. Epithelial trafficking of Sonic hedgehog by megalin.

    Science.gov (United States)

    Morales, Carlos R; Zeng, Jibin; El Alfy, Mohamed; Barth, Jeremy L; Chintalapudi, Mastan Rao; McCarthy, Robert A; Incardona, John P; Argraves, W Scott

    2006-10-01

    We present here evidence of in vivo epithelial endocytosis and trafficking of non-lipid-modified Sonic hedgehog (ShhN) when infused into rat efferent ducts via microinjection. Initially, exogenous ShhN is detected in endocytic vesicles and early endosomes located near the apical plasma membrane of non-ciliated cells. Within 30-60 min following infusion, ShhN can be detected in lysosomes and at basolateral regions of non-ciliated cells. Basolaterally, ShhN was observed along the extracellular surfaces of interdigitated plasma membranes of adjacent cells and in the extracellular compartment underlying the efferent duct epithelium. Uptake and subcellular trafficking of infused ShhN by non-ciliated cells could be blocked by either anti-megalin IgG or the megalin antagonist, RAP. Ciliated cells, which do not express megalin, displayed little if any apical internalization of ShhN even though they were found to express Patched-1. However, ShhN was found in coated pits of lateral plasma membranes of ciliated cells as well as in underlying endocytic vesicles. We conclude that megalin-mediated endocytosis of ShhN can occur in megalin-expressing epithelia in vivo, and that the internalized ShhN can be targeted to the lysosome or transcytosed in the plane of the epithelium or across the epithelium. These findings highlight the multiple mechanisms by which megalin may influence Shh morphogen gradients in vivo.

  16. Report on combating of illicit trafficking. The Illicit Trafficking Combat Project Group. January 2000

    International Nuclear Information System (INIS)

    2000-01-01

    The objective of this study is to propose improvements of different means and methods for the prevention of illicit trafficking and the proliferation of nuclear weapons. An essential requirement imposed on authorities and operators through basic nuclear legislation is the establishment and implementation of: a) nuclear material accountancy and control; b) physical protection of nuclear material and facilities; and c) export/import control of nuclear material and, so called, dual-use items. The legislation would make it possible for the State nuclear authority to be informed continuously about the location and quantity of nuclear material in the country, and to monitor that it is under satisfactory protection and guard in accordance with the requirements. The introduction of requirements on licensing of practices and activities involving dual-use items, and other products used for nuclear weapons manufacturing, would also give the authority the possibility to prevent unauthorised transfers of such products. The nuclear legislation must clearly stipulate the distribution of responsibilities between nuclear authority, operator and employees. This would give a solid basis for attaining high safety culture, including positive motivation and active commitment among executives and other employees. It would also ensure that nuclear material would not be lost through negligence or internal criminal activities. A further step of improvements on the national level, would be the urgent and firm introduction of modern Quality Assurance and Internal Control Systems into all forms of nuclear activities. In modern, safety related quality control systems, the operator alone is responsible for all activities and operations, and he must establish an internal control that will ensure that the authority's rules and requirements are thoroughly implemented and adhered to. The operator's organisation, including competence and procedures, must be approved by the State authority. By means

  17. Relationships between suspects and victims of sex trafficking. Exploitation of prostitutes and domestic violence parallels in Dutch trafficking cases.

    NARCIS (Netherlands)

    Verhoeven, M.; van Gestel, B.; de Jong, D.; Kleemans, E.R.

    2014-01-01

    This article centres on the hypothesis that human trafficking for sexual exploitation is not only an organised crime activity, but a crime of relational nature as well. Therefore this study explores the relationships that exist between suspects and victims of sex trafficking, and examines to what

  18. Trafficking Dynamics of PCSK9-Induced LDLR Degradation: Focus on Human PCSK9 Mutations and C-Terminal Domain.

    Directory of Open Access Journals (Sweden)

    Steve Poirier

    Full Text Available PCSK9 is a secreted ligand and negative post-translational regulator of low-density lipoprotein receptor (LDLR in hepatocytes. Gain-of-function (GOF or loss-of-function (LOF mutations in PCSK9 are directly correlated with high or low plasma LDL-cholesterol levels, respectively. Therefore, PCSK9 is a prevailing lipid-lowering target to prevent coronary heart diseases and stroke. Herein, we fused monomeric fluorescent proteins to PCSK9 and LDLR to visualize their intra- and extracellular trafficking dynamics by live confocal microscopy. Fluorescence recovery after photobleaching (FRAP showed that PCSK9 LOF R46L mutant and GOF mutations S127R and D129G, but not the LDLR high-affinity mutant D374Y, significantly accelerate PCSK9 exit from the endoplasmic reticulum (ER. Quantitative analysis of inverse FRAP revealed that only R46L presented a much slower trafficking from the trans-Golgi network (TGN to the plasma membrane and a lower mobile fraction likely suggesting accumulation or delayed exit at the TGN as an underlying mechanism. While not primarily involved in LDLR binding, PCSK9 C-terminal domain (CTD was found to be essential to induce LDLR degradation both upon its overexpression in cells or via the extracellular pathway. Our data revealed that PCSK9 CTD is required for the localization of PCSK9 at the TGN and increases its LDLR-mediated endocytosis. Interestingly, intracellular lysosomal targeting of PCSK9-ΔCTD was able to rescue its capacity to induce LDLR degradation emphasizing a role of the CTD in the sorting of PCSK9-LDLR complex towards late endocytic compartments. Finally, we validated our dual fluorescence system as a cell based-assay by preventing PCSK9 internalization using a PCSK9-LDLR blocking antibody, which may be expended to identify protein, peptide or small molecule inhibitors of PCSK9.

  19. Illicit trafficking of radiological and nuclear materials: modeling and analysis of trafficking trends and risks

    International Nuclear Information System (INIS)

    York, David L.; Love, Tracia L.; Rochau, Gary Eugene

    2005-01-01

    Concerns over the illicit trafficking of radiological and nuclear materials were focused originally on the lack of security and accountability of such material throughout the former Soviet states. This is primarily attributed to the frequency of events that have occurred involving the theft and trafficking of critical material components that could be used to construct a Radiological Dispersal Device (RDD) or even a rudimentary nuclear device. However, with the continued expansion of nuclear technology and the deployment of a global nuclear fuel cycle these materials have become increasingly prevalent, affording a more diverse inventory of dangerous materials and dual-use items. To further complicate the matter, the list of nuclear consumers has grown to include: (1) Nation-states that have gone beyond the IAEA agreed framework and additional protocols concerning multiple nuclear fuel cycles and processes that reuse the fuel through reprocessing to exploit technologies previously confined to the more industrialized world; (2) Terrorist organizations seeking to acquire nuclear and radiological material due to the potential devastation and psychological effect of their use; (3) Organized crime, which has discovered a lucrative market in trafficking of illicit material to international actors and/or countries; and (4) Amateur smugglers trying to feed their families in a post-Soviet era. An initial look at trafficking trends of this type seems scattered and erratic, localized primarily to a select group of countries. This is not necessarily the case. The success with which other contraband has been smuggled throughout the world suggests that nuclear trafficking may be carried out with relative ease along the same routes by the same criminals or criminal organizations. Because of the inordinately high threat posed by terrorist or extremist groups acquiring the ingredients for unconventional weapons, it is necessary that illicit trafficking of these materials be better

  20. Endoscopic retrograde cholangiopancreatographic evaluation of patients with obstructive jaundice

    International Nuclear Information System (INIS)

    Khurram, M.; Durrani, A.A.; Butt, A.A.; Ashfaq, S.

    2003-01-01

    Objective: To evaluate the role of endoscopic retrograde cholangiopancreatography (ERCP) in patients with obstructive jaundice. Results: Of the 226 patients, 117 (51.8%) were males, and 109 (48.2%) females, their mean age being 51.8 plus minus 16.6 years. Common bile and pancreatic ducts were visualized in 81.8% and 68.1% patients respectively. Growth/masses and stones were commonest causes of obstructive jaundice. Choledocholithias was common in males, while biliary channel related growth/masses were common in females (p-value = 0.03). Common bile duct stone clearance rate was 88%, stenting was highly successful in patients with growth and strictures. ERCP related complications were noted in 11 (4.8%) patients. Conclusion: ERCP is an important diagnostic and therapeutic modality for evaluation of patients with obstructive jaundice. Growth/masses and stones are common causes of obstructive jaundice, which can be diagnosed and treated with ERCP. (author)

  1. Mitochondrial morphology transitions and functions: implications for retrograde signaling?

    Science.gov (United States)

    Picard, Martin; Shirihai, Orian S.; Gentil, Benoit J.

    2013-01-01

    In response to cellular and environmental stresses, mitochondria undergo morphology transitions regulated by dynamic processes of membrane fusion and fission. These events of mitochondrial dynamics are central regulators of cellular activity, but the mechanisms linking mitochondrial shape to cell function remain unclear. One possibility evaluated in this review is that mitochondrial morphological transitions (from elongated to fragmented, and vice-versa) directly modify canonical aspects of the organelle's function, including susceptibility to mitochondrial permeability transition, respiratory properties of the electron transport chain, and reactive oxygen species production. Because outputs derived from mitochondrial metabolism are linked to defined cellular signaling pathways, fusion/fission morphology transitions could regulate mitochondrial function and retrograde signaling. This is hypothesized to provide a dynamic interface between the cell, its genome, and the fluctuating metabolic environment. PMID:23364527

  2. An interstellar origin for Jupiter's retrograde co-orbital asteroid

    Science.gov (United States)

    Namouni, F.; Morais, M. H. M.

    2018-06-01

    Asteroid (514107) 2015 BZ509 was discovered recently in Jupiter's co-orbital region with a retrograde motion around the Sun. The known chaotic dynamics of the outer Solar system have so far precluded the identification of its origin. Here, we perform a high-resolution statistical search for stable orbits and show that asteroid (514107) 2015 BZ509 has been in its current orbital state since the formation of the Solar system. This result indicates that (514107) 2015 BZ509 was captured from the interstellar medium 4.5 billion years in the past as planet formation models cannot produce such a primordial large-inclination orbit with the planets on nearly coplanar orbits interacting with a coplanar debris disc that must produce the low-inclination small-body reservoirs of the Solar system such as the asteroid and Kuiper belts. This result also implies that more extrasolar asteroids are currently present in the Solar system on nearly polar orbits.

  3. Diagnosis of choledocholithiasis and therapeutic results with endoscopic retrograde cholangiopancreatography

    International Nuclear Information System (INIS)

    Ramos Pachon, Carlos; Gonzalez Cansino, Juan; Fernandez Maderos, Irma

    2009-01-01

    A descriptive, prospective study was carried out on 451 patients that were attended for endoscopic retrograde cholangiopancreatography at CIMEQ's Hospital from January 2004-March 2006. The sample was constituted by 353 patients with choledocholithiasis suspicion. The information was search in the reports of ERCP and the variables were analyzed with the objective of evaluating the diagnostic possibilities and the therapy for choledocholithiasis by ERCP. Choledocholithiasis was detected in 1/4 of the patients with indication of ERCP, and was more frequent in patients of the female sex and in patients older than 40 years. The jaundice was the main clinical condition that motivated the ERCP in the patients with choledocholithiasis. The diagnostic effectiveness of the alkaline phosphatase and the ultrasound was not high. The treatment of the choledocholithiasis by means of ERCP showed good results and low morbidity

  4. Duodenal perforation: after endoscopic retrograde cholangiopancreatography: when to operate?

    International Nuclear Information System (INIS)

    Garcia Navarrete, Aldhem Francisco

    2014-01-01

    The mainly surgical management of duodenal perforation as the iatrogenicity of endoscopic retrograde cholangiopancreatography (ERCP) is defined and protocolized through the exhaustive review of the most conclusive literature available on the subject. Bibliography on the management of post-ERCP duodenal perforation is reviewed in scientific databases, textbooks, publications of medical journals, MD Consult and Medline. A total of 60 bibliographical citations were reviewed; succeeding in defining the protocol on the management of this type of complications, thanks to the appropriate selection of the most conclusive citations and the greatest consensus on the subject. A total of 60 bibliographical citations were reviewed; succeeding in defining the protocol on the management of this type of complications, based on the appropriate selection of the most conclusive citations and the greatest consensus on the subject [es

  5. Retrograde versus Prograde Models of Accreting Black Holes

    Directory of Open Access Journals (Sweden)

    David Garofalo

    2013-01-01

    Full Text Available There is a general consensus that magnetic fields, accretion disks, and rotating black holes are instrumental in the generation of the most powerful sources of energy in the known universe. Nonetheless, because magnetized accretion onto rotating black holes involves both the complications of nonlinear magnetohydrodynamics that currently cannot fully be treated numerically, and uncertainties about the origin of magnetic fields that at present are part of the input, the space of possible solutions remains less constrained. Consequently, the literature still bears witness to the proliferation of rather different black hole engine models. But the accumulated wealth of observational data is now sufficient to meaningfully distinguish between them. It is in this light that this critical paper compares the recent retrograde framework with standard “spin paradigm” prograde models.

  6. Retrograde nailing for distal femur fractures in the elderly

    Directory of Open Access Journals (Sweden)

    Giddie Jasdeep

    2015-01-01

    Full Text Available Introduction: We report the results of treating a series of 56 fractures in 54 elderly patients with a distal femur fracture with a retrograde femoral nail. Methods: Fifty-four of the nails were inserted percutaneously with a closed reduction. After surgery all patients were allowed to weight bear as tolerated. Four fractures were supported in a temporary external splint. Results: The mean age of patients was 80.6 years (range 51–103 years, 52/54 (96% were females. There were no cases of nail related complications and no re-operations were required. One patient was lost to follow up. The 30-day mortality was 5/54 (9.3% and the one year mortality was 17/54 (31.5%. Conclusions: Distal femoral nail fixation provides a good method of fixation allowing immediate mobilisation for this group of patients.

  7. Retrograde Neuroanatomical Tracing of Phrenic Motor Neurons in Mice.

    Science.gov (United States)

    Vandeweerd, Jean-Michel; Hontoir, Fanny; De Knoop, Alexis; De Swert, Kathleen; Nicaise, Charles

    2018-02-22

    Phrenic motor neurons are cervical motor neurons originating from C3 to C6 levels in most mammalian species. Axonal projections converge into phrenic nerves innervating the respiratory diaphragm. In spinal cord slices, phrenic motor neurons cannot be identified from other motor neurons on morphological or biochemical criteria. We provide the description of procedures for visualizing phrenic motor neuron cell bodies in mice, following intrapleural injections of cholera toxin subunit beta (CTB) conjugated to a fluorophore. This fluorescent neuroanatomical tracer has the ability to be caught up at the diaphragm neuromuscular junction, be carried retrogradely along the phrenic axons and reach the phrenic cell bodies. Two methodological approaches of intrapleural CTB delivery are compared: transdiaphragmatic versus transthoracic injections. Both approaches are successful and result in similar number of CTB-labeled phrenic motor neurons. In conclusion, these techniques can be applied to visualize or quantify the phrenic motor neurons in various experimental studies such as those focused on the diaphragm-phrenic circuitry.

  8. Identification of human trafficking victims in health care settings.

    Science.gov (United States)

    Baldwin, Susie B; Eisenman, David P; Sayles, Jennifer N; Ryan, Gery; Chuang, Kenneth S

    2011-07-14

    An estimated 18,000 individuals are trafficked into the United States each year from all over the world, and are forced into hard labor or commercial sex work. Despite their invisibility, some victims are known to have received medical care while under traffickers' control. Our project aimed to characterize trafficking victims' encounters in US health care settings. The study consisted of semi-structured interviews with six Key Informants who work closely with trafficking victims (Phase I) and 12 female trafficking survivors (Phase II). All survivors were recruited through the Coalition to Abolish Slavery and Trafficking, an NGO in Los Angeles, and all were trafficked into Los Angeles. Interviews were conducted in English and six other languages, with the assistance of professional interpreters. Using a framework analysis approach that focused on victims' encounters in health care settings, we assessed interview transcript content and coded for themes. We used an exploratory pile-sorting technique to aggregate similar ideas and identify overarching domains. The survivors came from 10 countries. Eight had experienced domestic servitude, three had survived sex trafficking, and one had experienced both. Half the survivors reported that they had visited a physician while in their traffickers' control, and another worked in a health care facility. All Key Informants described other victims who had received medical care. For domestic servants, medical visits were triggered by injury and respiratory or systemic illness, while sex trafficking victims were seen by health professionals for sexually transmitted infections and abortion. Trafficking victims were prevented from disclosing their status to health care providers by fear, shame, language barriers, and limited interaction with medical personnel, among other obstacles. This exploration of survivors' experiences in health care settings supports anecdotal reports that US health care providers may unwittingly encounter

  9. Glucose-dependent trafficking of 5-HT3 receptors in rat gastrointestinal vagal afferent neurons

    Science.gov (United States)

    Babic, Tanja; Troy, Amanda E; Fortna, Samuel R; Browning, Kirsteen N

    2012-01-01

    Background Intestinal glucose induces gastric relaxation via vagally mediated sensory-motor reflexes. Glucose can alter the activity of gastrointestinal (GI) vagal afferent (sensory) neurons directly, via closure of ATP-sensitive potassium channels, as well as indirectly, via the release of 5-hydroxytryptamine (5-HT) from mucosal enteroendocrine cells. We hypothesized that glucose may also be able to modulate the ability of GI vagal afferent neurons to respond to the released 5-HT, via regulation of neuronal 5-HT3 receptors. Methods Whole cell patch clamp recordings were made from acutely dissociated GI-projecting vagal afferent neurons exposed to equiosmolar Krebs’ solution containing different concentrations of D-glucose (1.25–20mM) and the response to picospritz application of 5-HT assessed. The distribution of 5-HT3 receptors in neurons exposed to different glucose concentrations was also assessed immunohistochemically. Key Results Increasing or decreasing extracellular D-glucose concentration increased or decreased, respectively, the 5-HT-induced inward current as well as the proportion of 5-HT3 receptors associated with the neuronal membrane. These responses were blocked by the Golgi-disrupting agent Brefeldin-A (5µM) suggesting involvement of a protein trafficking pathway. Furthermore, L-glucose did not mimic the response of D-glucose implying that metabolic events downstream of neuronal glucose uptake are required in order to observe the modulation of 5-HT3 receptor mediated responses. Conclusions & Inferences These results suggest that, in addition to inducing the release of 5-HT from enterochromaffin cells, glucose may also increase the ability of GI vagal sensory neurons to respond to the released 5-HT, providing a means by which the vagal afferent signal can be amplified or prolonged. PMID:22845622

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Primary Retrograde Tibiotalocalcaneal Nailing For Fragility Ankle Fractures.

    Science.gov (United States)

    Taylor, Benjamin C; Hansen, Dane C; Harrison, Ryan; Lucas, Douglas E; Degenova, Daniel

    2016-01-01

    Ankle fragility fractures are difficult to treat due to poor bone quality and soft tissues as well as the near ubiquitous presence of comorbidities including diabetes mellitus and peripheral neuropathy. Conventional open reduction and internal fixation in this population has been shown to lead to a significant rate of complications. Given the high rate of complications with contemporary fixation methods, the present study aims to critically evaluate the use of acute hindfoot nailing as a percutaneous fixation technique for high-risk ankle fragility fractures. In this study, we retrospectively evaluated 31 patients treated with primary retrograde tibiotalocalcaneal nail without joint preparation for a mean of 13.6 months postoperatively from an urban Level I trauma center during the years 2006-2012. Overall, there were two superficial infections (6.5%) and three deep infections (9.7%) in the series. There were 28 (90.3%) patients that went on to radiographic union at a mean of 22.2 weeks with maintenance of foot and ankle alignment. There were three cases of asymptomatic screw breakage observed at a mean of 18.3 months postoperatively, which were all treated conservatively.. This study shows that retrograde hindfoot nailing is an acceptable treatment option for treatment of ankle fragility fractures. Hindfoot nailing allows early weightbearing, limited soft tissue injury, and a relatively low rate of complications, all of which are advantages to conventional open reduction internal fixation techniques. Given these findings, larger prospective randomized trials comparing this treatment with conventional open reduction internal fixation techniques are warranted.

  12. 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

  13. 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...

  14. Human Trafficking of Minors and Childhood Adversity in Florida.

    Science.gov (United States)

    Reid, Joan A; Baglivio, Michael T; Piquero, Alex R; Greenwald, Mark A; Epps, Nathan

    2017-02-01

    To examine the link between human trafficking of minors and childhood adversity. We compared the prevalence of adverse childhood experiences (ACEs) and cumulative childhood adversity (ACE score) among a sample of 913 juvenile justice-involved boys and girls in Florida for whom the Florida child abuse hotline accepted human trafficking abuse reports between 2009 and 2015 with those of a matched sample. ACE composite scores were higher and 6 ACEs indicative of child maltreatment were more prevalent among youths who had human trafficking abuse reports. Sexual abuse was the strongest predictor of human trafficking: the odds of human trafficking was 2.52 times greater for girls who experienced sexual abuse, and there was a 8.21 times greater risk for boys who had histories of sexual abuse. Maltreated youths are more susceptible to exploitation in human trafficking. Sexual abuse in connection with high ACE scores may serve as a key predictor of exploitation in human trafficking for both boys and girls.

  15. Normative framework for combating trafficking in human organs

    Directory of Open Access Journals (Sweden)

    Banović Božidar

    2017-01-01

    Full Text Available Trafficking in human organs is a specific and complex criminal phenomenon that takes place in several phases, with the participation of a large number of actors, often covering several jurisdictions. To effectively countering are necessary conceptual and terminological demarcation of organ trafficking from other similar phenomena, fundamental scientifically research of its shape and dynamics, and the construction of an adequate legislative framework, both at the national and international level. This paper first analyses the conceptual - terminological framework in which research of organ trafficking is range, and then presents a review and analysis of the development of ethical and normative international standards aimed at prevention and suppression this phenomenon. In the end, we analysed the current solutions in the domestic legislation. Nowadays, there are two parallel legislative regime that regulate the matter of organ trafficking. The first legislative regime that organ trafficking treated exclusively as a modality of transnational crime of human trafficking, and a second, recent, that organ trafficking treats as forbidden (incriminating activity that violates a regulatory system of organ (tissue cells transplantation.

  16. The Yeast Retrograde Response as a Model of Intracellular Signaling of Mitochondrial Dysfunction

    Directory of Open Access Journals (Sweden)

    S. Michal eJazwinski

    2012-05-01

    Full Text Available Mitochondrial dysfunction activates intracellular signaling pathways that impact yeast longevity, and the best known of these pathways is the retrograde response. More recently, similar responses have been discerned in other systems, from invertebrates to human cells. However, the identity of the signal transducers is either unknown or apparently diverse, contrasting with the well-established signaling module of the yeast retrograde response. On the other hand, it has become equally clear that several other pathways and processes interact with the retrograde response, embedding it in a network responsive to a variety of cellular states. An examination of this network supports the notion that the master regulator NFkB aggregated a variety of mitochondria-related cellular responses at some point in evolution and has become the retrograde transcription factor. This has significant consequences for how we view some of the deficits associated with aging, such as inflammation. The support for NFkB as the retrograde response transcription factor is not only based on functional analyses. It is bolstered by the fact that NFkB can regulate Myc-Max, which is activated in human cells with dysfunctional mitochondria and impacts cellular metabolism. Myc-Max is homologous to the yeast retrograde response transcription factor Rtg1-Rtg3. Further research will be needed to disentangle the pro-aging from the anti-aging effects of NFkB. Interestingly, this is also a challenge for the complete understanding of the yeast retrograde response.

  17. Investigation of the Usability of Retrograded Flour in Meatball Production as A Structure Enhancer.

    Science.gov (United States)

    Dinçer, Elif Aykin; Büyükkurt, Özlem Kiliç; Candal, Cihadiye; Bilgiç, Büşra Fatma; Erbaş, Mustafa

    2018-02-01

    This study aimed to research the possibilities of using retrograded flour produced in the laboratory environment in meatballs and the characteristics of these meatballs. In the use of retrograded flour to produce meatballs, it was ensured that the meatball properties, with respect to chemical, physical and sensorial aspects, were comparable to those of meatballs produced with bread (traditional) and rusk flour (commercial). The cooking loss of meatballs produced with using retrograded flour was similar to that of commercial meatballs. Doses of retrograded flour from 5% to 20% led to a significant decrease in cooking loss, from 21.95% to 6.19%, and in the diameter of meatballs, from 18.60% to 12.74%, but to an increase in the thickness of meatballs, from 28.82% to 41.39% compared to the control. The increase of a * and b * values was shown in that the meatballs were browned on cooking with increasing retrograded flour doses because of non-enzymatic reactions. The springiness of the traditional meatballs was significantly higher than that of the other meatballs. This might have been due to the bread crumbs having a naturally springy structure. Moreover, the addition of retrograded flour in the meatballs significantly ( p meatballs with respect to textural properties. Accordingly, it is considered that the use of 10% retrograded flour is ideal to improve the sensorial values of meatballs and the properties of their structure.

  18. Dynamic Portrait of the Retrograde 1:1 Mean Motion Resonance

    Science.gov (United States)

    Huang, Yukun; Li, Miao; Li, Junfeng; Gong, Shengping

    2018-06-01

    Asteroids in mean motion resonances with giant planets are common in the solar system, but it was not until recently that several asteroids in retrograde mean motion resonances with Jupiter and Saturn were discovered. A retrograde co-orbital asteroid of Jupiter, 2015 BZ509 is confirmed to be in a long-term stable retrograde 1:1 mean motion resonance with Jupiter, which gives rise to our interests in its unique resonant dynamics. In this paper, we investigate the phase-space structure of the retrograde 1:1 resonance in detail within the framework of the circular restricted three-body problem. We construct a simple integrable approximation for the planar retrograde resonance using canonical contact transformation and numerically employ the averaging procedure in closed form. The phase portrait of the retrograde 1:1 resonance is depicted with the level curves of the averaged Hamiltonian. We thoroughly analyze all possible librations in the co-orbital region and uncover a new apocentric libration for the retrograde 1:1 resonance inside the planet’s orbit. We also observe the significant jumps in orbital elements for outer and inner apocentric librations, which are caused by close encounters with the perturber.

  19. Importance of variants in cerebrovascular anatomy for potential retrograde embolization in cryptogenic stroke

    Energy Technology Data Exchange (ETDEWEB)

    Markl, Michael [Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); Northwestern University, Department of Biomedical Engineering, McCormick School of Engineering, Chicago, IL (United States); Semaan, Edouard; Carr, James; Collins, Jeremy [Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); Stromberg, LeRoy [Northwestern University, Department of Neurology, Feinberg School of Medicine, Chicago, IL (United States); Edward Hospital, Department of Radiology, Naperville, IL (United States); Prabhakaran, Shyam [Northwestern University, Department of Neurology, Feinberg School of Medicine, Chicago, IL (United States)

    2017-10-15

    To test the hypothesis that variants in cerebrovascular anatomy will affect the number of patients demonstrating a plausible retrograde embolization mechanism from plaques in the descending aorta (DAo). Thirty-five patients (aged 63 ± 17 years) with cryptogenic stroke underwent 4D flow MRI for the assessment of aortic 3D blood flow and MR angiography for the evaluation of circle of Willis, posterior circulation, and aortic arch architecture. In patients with proven DAo plaque, retrograde embolization was considered a potential mechanism if retrograde flow extended from the DAo to a supra-aortic vessel supplying the cerebral infarct territory. Retrograde embolization with matching cerebral infarct territory was detected in six (17%) patients. Circle of Willis and aortic arch variant anatomy was found in 60% of patients, leading to reclassification of retrograde embolization risk as present in three (9%) additional patients, for a total 26% of cryptogenic stroke patients. 4D flow MRI demonstrated 26% concordance with infarct location on imaging with retrograde diastolic flow into the feeding vessels of the affected cerebral area, identifying a potential etiology for cryptogenic stroke. Our findings further demonstrate the importance of cerebrovascular anatomy when determining concordance of retrograde flow pathways with vascular stroke territory from DAo plaques. (orig.)

  20. Importance of variants in cerebrovascular anatomy for potential retrograde embolization in cryptogenic stroke

    International Nuclear Information System (INIS)

    Markl, Michael; Semaan, Edouard; Carr, James; Collins, Jeremy; Stromberg, LeRoy; Prabhakaran, Shyam

    2017-01-01

    To test the hypothesis that variants in cerebrovascular anatomy will affect the number of patients demonstrating a plausible retrograde embolization mechanism from plaques in the descending aorta (DAo). Thirty-five patients (aged 63 ± 17 years) with cryptogenic stroke underwent 4D flow MRI for the assessment of aortic 3D blood flow and MR angiography for the evaluation of circle of Willis, posterior circulation, and aortic arch architecture. In patients with proven DAo plaque, retrograde embolization was considered a potential mechanism if retrograde flow extended from the DAo to a supra-aortic vessel supplying the cerebral infarct territory. Retrograde embolization with matching cerebral infarct territory was detected in six (17%) patients. Circle of Willis and aortic arch variant anatomy was found in 60% of patients, leading to reclassification of retrograde embolization risk as present in three (9%) additional patients, for a total 26% of cryptogenic stroke patients. 4D flow MRI demonstrated 26% concordance with infarct location on imaging with retrograde diastolic flow into the feeding vessels of the affected cerebral area, identifying a potential etiology for cryptogenic stroke. Our findings further demonstrate the importance of cerebrovascular anatomy when determining concordance of retrograde flow pathways with vascular stroke territory from DAo plaques. (orig.)

  1. Human Trafficking of Children in the United States: A Fact Sheet for Schools

    Science.gov (United States)

    Office of Safe and Healthy Students, US Department of Education, 2013

    2013-01-01

    Human trafficking is a serious federal crime with penalties of up to imprisonment for life. Federal law defines "severe forms of trafficking in persons." In short, human trafficking is a form of modern slavery. Those who recruit minors into commercial sexual exploitation (or prostitution) violate federal anti-trafficking laws, even if there is no…

  2. Human Trafficking of Children in the United States: A Fact Sheet

    Science.gov (United States)

    US Department of Education, 2007

    2007-01-01

    This fact sheet presents questions and answers related to the human trafficking of children in the United States. It describes human trafficking and its extent in the United States, how human traffickers target children for coerced labor and sex exploitation, how to identify victims of human trafficking, how to report a suspected incidence of…

  3. Queering the Support for Trafficked Persons: LGBTQ Communities and Human Trafficking in the Heartland

    Directory of Open Access Journals (Sweden)

    Corinne Schwarz

    2015-02-01

    Full Text Available Human trafficking justice centers on the “Three Ps” model of prevention, protection, and prosecution. While protection and prosecution efforts have been moderately successful, prevention remains elusive, as “upstream” structural fac-tors—class, gender, and sexuality inequalities—remain difficult to target. Individuals who are affected by these factors are not fully served within linear service frameworks. Based on a 12-month study in Kansas City, we find that service providers recognize the limitations of a “one-size-fits all” approach. Using a public health model, our research team con-ducted a public health surveillance, explored risk and protective factors, and facilitated organizational self-assessments of services. Our findings support a prevention approach that supports a survivor-centered model, which creates new, non-linear or queered avenues of agency and community for trafficking survivors. This model allows survivors to make use of services in moments of vulnerability and opt out of others in moments of resilience. Given the systematic cuts in funding that have affected service providers, this research contends that prevention is cheaper, more effective, and more ethical than relying on prosecutions to curb trafficking. Developing a model that fosters survivor empowerment is a key step toward individual justice and survivor resilience for vulnerable and marginalized populations.

  4. Report on combating of illicit trafficking. The Illicit Trafficking Combat Project Group. January 2000

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-01-01

    The objective of this study is to propose improvements of different means and methods for the prevention of illicit trafficking and the proliferation of nuclear weapons. An essential requirement imposed on authorities and operators through basic nuclear legislation is the establishment and implementation of: a) nuclear material accountancy and control; b) physical protection of nuclear material and facilities; and c) export/import control of nuclear material and, so called, dual-use items. The legislation would make it possible for the State nuclear authority to be informed continuously about the location and quantity of nuclear material in the country, and to monitor that it is under satisfactory protection and guard in accordance with the requirements. The introduction of requirements on licensing of practices and activities involving dual-use items, and other products used for nuclear weapons manufacturing, would also give the authority the possibility to prevent unauthorised transfers of such products. The nuclear legislation must clearly stipulate the distribution of responsibilities between nuclear authority, operator and employees. This would give a solid basis for attaining high safety culture, including positive motivation and active commitment among executives and other employees. It would also ensure that nuclear material would not be lost through negligence or internal criminal activities. A further step of improvements on the national level, would be the urgent and firm introduction of modern Quality Assurance and Internal Control Systems into all forms of nuclear activities. In modern, safety related quality control systems, the operator alone is responsible for all activities and operations, and he must establish an internal control that will ensure that the authority's rules and requirements are thoroughly implemented and adhered to. The operator's organisation, including competence and procedures, must be approved by the State authority. By means

  5. Report on combating of illicit trafficking. The Illicit Trafficking Combat Project Group. January 2000

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-01-01

    The objective of this study is to propose improvements of different means and methods for the prevention of illicit trafficking and the proliferation of nuclear weapons. An essential requirement imposed on authorities and operators through basic nuclear legislation is the establishment and implementation of: a) nuclear material accountancy and control; b) physical protection of nuclear material and facilities; and c) export/import control of nuclear material and, so called, dual-use items. The legislation would make it possible for the State nuclear authority to be informed continuously about the location and quantity of nuclear material in the country, and to monitor that it is under satisfactory protection and guard in accordance with the requirements. The introduction of requirements on licensing of practices and activities involving dual-use items, and other products used for nuclear weapons manufacturing, would also give the authority the possibility to prevent unauthorised transfers of such products. The nuclear legislation must clearly stipulate the distribution of responsibilities between nuclear authority, operator and employees. This would give a solid basis for attaining high safety culture, including positive motivation and active commitment among executives and other employees. It would also ensure that nuclear material would not be lost through negligence or internal criminal activities. A further step of improvements on the national level, would be the urgent and firm introduction of modern Quality Assurance and Internal Control Systems into all forms of nuclear activities. In modern, safety related quality control systems, the operator alone is responsible for all activities and operations, and he must establish an internal control that will ensure that the authority's rules and requirements are thoroughly implemented and adhered to. The operator's organisation, including competence and procedures, must be approved by the State authority

  6. 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

    Directory of Open Access Journals (Sweden)

    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.

  7. Insights into plant plasma membrane aquaporin trafficking.

    Science.gov (United States)

    Hachez, Charles; Besserer, Arnaud; Chevalier, Adrien S; Chaumont, François

    2013-06-01

    Plasma membrane intrinsic proteins (PIPs) are plant aquaporins that facilitate the diffusion of water and small uncharged solutes through the cell membrane. Deciphering the network of interacting proteins that modulate PIP trafficking to and activity in the plasma membrane is essential to improve our knowledge about PIP regulation and function. This review highlights the most recent advances related to PIP subcellular routing and dynamic redistribution, identifies some key molecular interacting proteins, and indicates exciting directions for future research in this field. A better understanding of the mechanisms by which plants optimize water movement might help in identifying new molecular players of agronomical relevance involved in the control of cellular water uptake and drought tolerance. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Diagnosis of Acute Appendicitis by Endoscopic Retrograde Appendicitis Therapy (ERAT): Combination of Colonoscopy and Endoscopic Retrograde Appendicography.

    Science.gov (United States)

    Li, Yingchao; Mi, Chen; Li, Weizhi; She, Junjun

    2016-11-01

    Acute appendicitis is the most common abdominal emergency, but the diagnosis of appendicitis remains a challenge. Endoscopic retrograde appendicitis therapy (ERAT) is a new and minimally invasive procedure for the diagnosis and treatment of acute appendicitis. To investigate the diagnostic value of ERAT for acute appendicitis by the combination of colonoscopy and endoscopic retrograde appendicography (ERA). Twenty-one patients with the diagnosis of suspected uncomplicated acute appendicitis who underwent ERAT between November 2014 and January 2015 were included in this study. The main outcomes, imaging findings of acute appendicitis including colonoscopic direct-vision imaging and fluoroscopic ERA imaging, were retrospectively reviewed. Secondary outcomes included mean operative time, mean hospital stay, rate of complication, rate of appendectomy during follow-up period, and other clinical data. The diagnosis of acute appendicitis was established in 20 patients by positive ERA (5 patients) or colonoscopy (1 patient) alone or both (14 patients). The main colonoscopic imaging findings included mucosal inflammation (15/20, 75 %), appendicoliths (14/20, 70 %), and maturation (5/20, 25 %). The key points of ERA for diagnosing acute appendicitis included radiographic changes of appendix (17/20, 85 %), intraluminal appendicoliths (14/20, 70 %), and perforation (1/20, 5 %). Mean operative time of ERAT was 49.7 min, and mean hospital stay was 3.3 days. No patient converted to emergency appendectomy. Perforation occurred in one patient after appendicoliths removal was not severe and did not require invasive procedures. During at least 1-year follow-up period, only one patient underwent laparoscopic appendectomy. ERAT is a valuable procedure of choice providing a precise yield of diagnostic information for patients with suspected acute appendicitis by combination of colonoscopy and ERA.

  9. 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.

  10. 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....

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

    Science.gov (United States)

    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

  12. Molecular nuclear imaging for targeting and trafficking

    International Nuclear Information System (INIS)

    Bom, Hee Seung; Min, Jung Jun; Jeong, Hwan-Jeong

    2006-01-01

    Noninvasive molecular targeting in living subjects is highly demanded for better understanding of such diverse topics as the efficient delivery of drugs, genes, or radionuclides for the diagnosis or treatment of diseases. Progress in molecular biology, genetic engineering and polymer chemistry provides various tools to target molecules and cells in vivo. We used chitosan as a polymer, and 99m Tc as a radionuclide. We developed 99m Tc-galactosylated chitosan to target asialoglycoprotein receptors for nuclear imaging. We also developed 99m Tc-HYNIC-chitosan-transferrin to target inflammatory cells, which was more effective than 67 Ga-citrate for imaging inflammatory lesions. For an effective delivery of molecules, a longer circulation time is needed. We found that around 10% PEGylation was most effective to prolong the circulation time of liposomes for nuclear imaging of 99m Tc-HMPAO-labeled liposomes in rats. Using various characteristics of molecules, we can deliver drugs into targets more effectively. We found that 99m Tc-labeled biodegradable pullulan-derivatives are retained in tumor tissue in response to extracellular ion-strength. For the trafficking of various cells or bacteria in an intact animal, we used optical imaging techniques or radiolabeled cells. We monitored tumor-targeting bacteria by bioluminescent imaging techniques, dentritic cells by radiolabeling and neuronal stem cells by sodium-iodide symporter reporter gene imaging. In summary, we introduced recent achievements of molecular nuclear imaging technologies in targeting receptors for hepatocyte or inflammatory cells and in trafficking bacterial, immune and stem cells using molecular nuclear imaging techniques

  13. ITRAP. Illicit trafficking radiation detection assessment program

    International Nuclear Information System (INIS)

    Beck, P.

    2001-02-01

    Illicit trafficking in nuclear materials (nuclear criminality) has become more and more a problem, due to the circulation of the a high number of radioactive sources and the big amount of nuclear material, particularly, caused by the changes of the organisational infrastructures to supervise these material within the successor states of the former Soviet Union. The IAEA data base counts at present more than 300 verified cases. The endangering cased thereby ranges from possible health defect for the publication to terrorists activities and production of nuclear weapons. In addition to the primary criminal reasons the illegal deposal of radioactive sources as salvage, scrap and others show a further problem, which has lead to severe accidents and lethal effects in the past (e.g. Goiana, Mexiko). As the study ITRAP (Illicit Trafficking Radiation Assessment Program) can show, also in Austria the cases of partly considerable contaminated scrap transports from neighbouring countries exists. Some countries have already under taken countermeasures (e.g. Monitoring at the Finnish-Russian and German-Polish border, border monitoring in Italy). The International Atomic Energy Agency (IAEA) has reacted on this actual problem by setting up a new program to fight against nuclear criminality and has suggested a pilot study for the practical test of border monitoring systems. Aim of the study was to work out the technical requirements and the practicability of an useful monitoring system at border crossings. The results of the study will be offered by the IAEA to the member states as international recommendations for border monitoring systems. (author)

  14. Combating (Child Human Trafficking: Building Capacity

    Directory of Open Access Journals (Sweden)

    John Winterdyk

    2018-03-01

    Full Text Available The presentation/paper focuses on the challenges and necessity of building capacity at local, national, and international levels with a focus of how to more effectively combat trafficking in human beings (THB. Insight from several of initiatives are shared with the aim of illustrating how to capitalize on the vast number of opportunities that already exist at these levels and how they might be coordinated to enable collaborative work in an informed and dynamic manner to combat human trafficking. Information from several recent research projects that focus on some of these same issues is also incorporated into this paper. El artículo se centra en los desafíos de la lucha contra el tráfico de personas y en la necesidad de aumentar la capacidad para ser más eficaces en ese sentido, local, nacional e internacionalmente. Nos hacemos eco de la visión de varias iniciativas, con el fin de ilustrar cómo capitalizar el gran número de oportunidades que ya existen en los ámbitos citados, y la forma en que se podrían coordinar para posibilitar la colaboración de una manera informada y dinámica para combatir la trata de personas. También se incluye en el artículo información emanada de diversos proyectos recientes de investigación sobre el tema que nos ocupa. DOWNLOAD THIS PAPER FROM SSRN: http://ssrn.com/abstract=3086067

  15. Post-translational regulation and trafficking of the granulin-containing protease RD21 of Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Christian Gu

    Full Text Available RD21-like proteases are ubiquitous, plant-specific papain-like proteases typified by carrying a C-terminal granulin domain. RD21-like proteases are involved in immunity and associated with senescence and various types of biotic and abiotic stresses. Here, we interrogated Arabidopsis RD21 regulation and trafficking by site-directed mutagenesis, agroinfiltration, western blotting, protease activity profiling and protein degradation. Using an introduced N-glycan sensor, deglycosylation experiments and glyco-engineered N. benthamiana plants, we show that RD21 passes through the Golgi where it becomes fucosylated. Our studies demonstrate that RD21 is regulated at three post-translational levels. Prodomain removal is not blocked in the catalytic Cys mutant, indicating that RD21 is activated by a proteolytic cascade. However, RD21 activation in Arabidopsis does not require vacuolar processing enzymes (VPEs or aleurain-like protease AALP. In contrast, granulin domain removal requires the catalytic Cys and His residues and is therefore autocatalytic. Furthermore, SDS can (re-activate latent RD21 in Arabidopsis leaf extracts, indicating the existence of a third layer of post-translational regulation, possibly mediated by endogenous inhibitors. RD21 causes a dominant protease activity in Arabidopsis leaf extracts, responsible for SDS-induced proteome degradation.

  16. DKWSLLL, a versatile DXXXLL-type signal with distinct roles in the Cu(+)-regulated trafficking of ATP7B.

    Science.gov (United States)

    Lalioti, Vasiliki; Hernandez-Tiedra, Sonia; Sandoval, Ignacio V

    2014-08-01

    In the liver, the P-type ATPase and membrane pump ATP7B plays a crucial role in Cu(+) donation to cuproenzymes and in the elimination of excess Cu(+). ATP7B is endowed with a COOH-cytoplasmic (DE)XXXLL-type traffic signal. We find that accessory (Lys -3, Trp -2, Ser -1 and Leu +2) and canonical (D -4, Leu 0 and Leu +1) residues confer the DKWSLLL signal with the versatility required for the Cu(+)-regulated cycling of ATP7B between the trans-Golgi network (TGN) and the plasma membrane (PM). The separate mutation of these residues caused a disruption of the signal, resulting in different ATP7B distribution phenotypes. These phenotypes indicate the key roles of specific residues at separate steps of ATP7B trafficking, including sorting at the TGN, transport from the TGN to the PM and its endocytosis, and recycling to the TGN and PM. The distinct roles of ATP7B in the TGN and PM and the variety of phenotypes caused by the mutation of the canonical and accessory residues of the DKWSLLL signal can explain the separate or joined presentation of Wilson's cuprotoxicosis and the dysfunction of the cuproenzymes that accept Cu(+) at the TGN. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Mass spectrometry approaches to study plant endomembrane trafficking

    DEFF Research Database (Denmark)

    Parsons, Harriet Tempé; Lilley, Kathryn S.

    2018-01-01

    . Trafficking of membrane proteins to their correct endomembrane location is especially important to enable them to carry out their function. Although a considerable amount of knowledge about membrane protein trafficking in plants has been delivered by years of dedicated research, there are still significant...... gaps in our understanding of this process. Further knowledge of endomembrane trafficking is dependent on thorough characterization of the subcellular components that constitute the endomembrane system. Such studies are challenging for a number of reasons including the complexity of the plant...

  18. Human trafficking - modern day slavery: Menneskehandel i nutidens samfund

    OpenAIRE

    Holberg, Christina; Wilson, Philippa Rose Lucy; Larsen, Maiken Hollænder; Sennahøj, Cecilie; Søderberg, Ene Alicia

    2014-01-01

    This paper aims to approach the concept of human trafficking from a historical, cultural and philosophical point of view in order to cover the two dimensions: History and Culture and Philosophy and Science. It will be focusing on human trafficking, in the form of the sexual exploitation of women, and it’s existence within Europe. With a focus on human trafficking in the form of sexual exploitation of women, the main intention of this paper is to investigate the modern form of slavery through ...

  19. War Zone Acapulco: Urban Drug Trafficking in the Americas

    Directory of Open Access Journals (Sweden)

    Thiago Rodrigues

    Full Text Available Abstract Acapulco epitomises the (insecurity of urban zones in the Americas whose geographical, political and economic divisions are exacerbated by the political economy and geopolitics of drug trafficking, as well as by militarised attempts to fight it. Various geographic, political, and economic factors in the Acapulco Metropolitan Zone (AMZ have impacted drug trafficking and organised crime and contributed to high levels of violence. As a result, Acapulco now ranks among the 50 most violent cities in the world. This article analyses the trends in drug trafficking and organised crime in the AMZ, and highlights the lessons for scholars and policy-makers.

  20. Right retrograde brachial cerebral angiography with simultaneous compression of the left carotid artery

    International Nuclear Information System (INIS)

    Ericson, K.; Mosskin, M.

    1981-01-01

    Right retrograde brachial angiography with simultaneous compression of the left common carotid artery was performed in 12 patients, invariably resulting in filling of the right vertebral and the basilar artery. In all but one patient, the right carotid artery and its branches were also filled. Retrograde filling of the left internal carotid artery occurred in 8 patients. Furthermore, retrograde filling of the intracranial part of the left vertebral artery was obtained in 5 of 12 patients. A complete four-vessel cranial angiography was thus obtained in one third of the patients. The method may be considered as a safe and valuable adjunct to other angiographic techniques. (Auth.)