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Sample records for membrane trafficking heats

  1. 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 ...

  2. 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

  3. 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.

  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. 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-.

  6. 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.

  7. Cellular membrane trafficking of mesoporous silica nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Fang, I-Ju [Iowa State Univ., Ames, IA (United States)

    2012-01-01

    This dissertation mainly focuses on the investigation of the cellular membrane trafficking of mesoporous silica nanoparticles. We are interested in the study of endocytosis and exocytosis behaviors of mesoporous silica nanoparticles with desired surface functionality. The relationship between mesoporous silica nanoparticles and membrane trafficking of cells, either cancerous cells or normal cells was examined. Since mesoporous silica nanoparticles were applied in many drug delivery cases, the endocytotic efficiency of mesoporous silica nanoparticles needs to be investigated in more details in order to design the cellular drug delivery system in the controlled way. It is well known that cells can engulf some molecules outside of the cells through a receptor-ligand associated endocytosis. We are interested to determine if those biomolecules binding to cell surface receptors can be utilized on mesoporous silica nanoparticle materials to improve the uptake efficiency or govern the mechanism of endocytosis of mesoporous silica nanoparticles. Arginine-glycine-aspartate (RGD) is a small peptide recognized by cell integrin receptors and it was reported that avidin internalization was highly promoted by tumor lectin. Both RGD and avidin were linked to the surface of mesoporous silica nanoparticle materials to investigate the effect of receptor-associated biomolecule on cellular endocytosis efficiency. The effect of ligand types, ligand conformation and ligand density were discussed in Chapter 2 and 3. Furthermore, the exocytosis of mesoporous silica nanoparticles is very attractive for biological applications. The cellular protein sequestration study of mesoporous silica nanoparticles was examined for further information of the intracellular pathway of endocytosed mesoporous silica nanoparticle materials. The surface functionality of mesoporous silica nanoparticle materials demonstrated selectivity among the materials and cancer and normal cell lines. We aimed to determine

  8. Endomembrane Cation Transporters and Membrane Trafficking

    Energy Technology Data Exchange (ETDEWEB)

    Sze, Heven [Univ. of Maryland, College Park, MD (United States). Dept. of Cell Biology & Molecular Genetics

    2017-04-01

    fertilization. Based on localization and mutant analyses, we conclude that CHXs modulate the ion balance, pH or both in micro-regions of endoplasmic reticulum, endosomes and prevacuolar compartment (PVC), and so influence membrane trafficking and signaling resulting in proper osmoregulation in guard cells and seed formation. We also demonstrated for the first time that AtKEA2 associates with chloroplasts, especially at the two poles of developing plastids. These results show that AtKEA1 and AtKEA2 transporters in specific microdomains of the inner envelope link local osmotic, ionic, and pH homeostasis to plastid division and thylakoid membrane formation. The first 3-D structure model of AtCHX was generated, and architecture-directed mutagenesis identified critical residues of the transport core giving insights to the transport mode of this family. Thus we have revealed for the first time crucial roles of an unknown K+/H+ transport family on plant growth (KEA), gas exchange, pollen cell wall, and different phases of reproduction (CHXs). The dynamic endomembrane of plant cells is integral to cytokinesis, cell expansion, defense, and cell wall formation, thus these studies are directly relevant to the mission of the Department of Energy and to a better understanding of determinants for enhancing plant biomass and plant tolerance to abiotic stress.

  9. Redefining the essential trafficking pathway for outer membrane lipoproteins

    OpenAIRE

    Grabowicz, Marcin; Silhavy, Thomas J.

    2017-01-01

    In Gram-negative bacteria, most lipoproteins synthesized in the inner membrane (IM) are trafficked to the outer membrane (OM). The Lol pathway is the trafficking paradigm: LolCDE releases lipoproteins from the IM; LolA shuttles them between membranes to LolB in the OM. Several OM lipoproteins are essential for viability. In apparent concordance, the Lol proteins are each essential in wild-type cells. However, we show that Escherichia coli grows well without LolA and LolB in the absence of one...

  10. Roles of membrane trafficking in plant cell wall dynamics

    Directory of Open Access Journals (Sweden)

    Kazuo eEbine

    2015-10-01

    Full Text Available The cell wall is one of the characteristic components of plant cells. The cell wall composition differs among cell types and is modified in response to various environmental conditions. To properly generate and modify the cell wall, many proteins are transported to the plasma membrane or extracellular space through membrane trafficking, which is one of the key protein transport mechanisms in eukaryotic cells. Given the diverse composition and functions of the cell wall in plants, the transport of the cell wall components and proteins that are involved in cell wall-related events could be specialized for each cell type, i.e., the machinery for cell wall biogenesis, modification, and maintenance could be transported via different trafficking pathways. In this review, we summarize the recent progress in the current understanding of the roles and mechanisms of membrane trafficking in plant cells and focus on the biogenesis and regulation of the cell wall.

  11. Cell biology symposium: Membrane trafficking and signal transduction

    Science.gov (United States)

    In general, membrane trafficking is a broad group of processes where proteins and other large molecules are distributed throughout the cell as well as adjacent extracellular spaces. Whereas signal transduction is a process where signals are transmitted through a series of chemical or molecular event...

  12. Membrane domains and polarized trafficking of sphingolipids

    NARCIS (Netherlands)

    Maier, O; Slimane, TA; Hoekstra, D

    The plasma membrane of polarized cells consists of distinct domains, the apical and basolateral membrane that are characterized by a distinct lipid and protein content. Apical protein transport is largely mediated by (glyco)sphingolipid-cholesterol enriched membrane microdomains, so called rafts. In

  13. 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.

  14. Redefining the essential trafficking pathway for outer membrane lipoproteins

    Science.gov (United States)

    Grabowicz, Marcin; Silhavy, Thomas J.

    2017-01-01

    The outer membrane (OM) of Gram-negative bacteria is a permeability barrier and an intrinsic antibiotic resistance factor. Lipoproteins are OM components that function in cell wall synthesis, diverse secretion systems, and antibiotic efflux pumps. Moreover, each of the essential OM machines that assemble the barrier requires one or more lipoproteins. This dependence is thought to explain the essentiality of the periplasmic chaperone LolA and its OM receptor LolB that traffic lipoproteins to the OM. However, we show that in strains lacking substrates that are toxic when mislocalized, both LolA and LolB can be completely bypassed by activating an envelope stress response without compromising trafficking of essential lipoproteins. We identify the Cpx stress response as a monitor of lipoprotein trafficking tasked with protecting the cell from mislocalized lipoproteins. Moreover, our findings reveal that an alternate trafficking pathway exists that can, under certain conditions, bypass the functions of LolA and LolB, implying that these proteins do not perform any truly essential mechanistic steps in lipoprotein trafficking. Instead, these proteins’ key function is to prevent lethal accumulation of mislocalized lipoproteins. PMID:28416660

  15. Redefining the essential trafficking pathway for outer membrane lipoproteins.

    Science.gov (United States)

    Grabowicz, Marcin; Silhavy, Thomas J

    2017-05-02

    The outer membrane (OM) of Gram-negative bacteria is a permeability barrier and an intrinsic antibiotic resistance factor. Lipoproteins are OM components that function in cell wall synthesis, diverse secretion systems, and antibiotic efflux pumps. Moreover, each of the essential OM machines that assemble the barrier requires one or more lipoproteins. This dependence is thought to explain the essentiality of the periplasmic chaperone LolA and its OM receptor LolB that traffic lipoproteins to the OM. However, we show that in strains lacking substrates that are toxic when mislocalized, both LolA and LolB can be completely bypassed by activating an envelope stress response without compromising trafficking of essential lipoproteins. We identify the Cpx stress response as a monitor of lipoprotein trafficking tasked with protecting the cell from mislocalized lipoproteins. Moreover, our findings reveal that an alternate trafficking pathway exists that can, under certain conditions, bypass the functions of LolA and LolB, implying that these proteins do not perform any truly essential mechanistic steps in lipoprotein trafficking. Instead, these proteins' key function is to prevent lethal accumulation of mislocalized lipoproteins.

  16. Membrane trafficking pathways and their roles in plant-microbe interactions.

    Science.gov (United States)

    Inada, Noriko; Ueda, Takashi

    2014-04-01

    Membrane trafficking functions in the delivery of proteins that are newly synthesized in the endoplasmic reticulum (ER) to their final destinations, such as the plasma membrane (PM) and the vacuole, and in the internalization of extracellular components or PM-associated proteins for recycling or degradative regulation. These trafficking pathways play pivotal roles in the rapid responses to environmental stimuli such as challenges by microorganisms. In this review, we provide an overview of the current knowledge of plant membrane trafficking and its roles in plant-microbe interactions. Although there is little information regarding the mechanism of pathogenic modulation of plant membrane trafficking thus far, recent research has identified many membrane trafficking factors as possible targets of microbial modulation.

  17. Membrane Trafficking of Death Receptors: Implications on Signalling

    Directory of Open Access Journals (Sweden)

    Wulf Schneider-Brachert

    2013-07-01

    Full Text Available Death receptors were initially recognised as potent inducers of apoptotic cell death and soon ambitious attempts were made to exploit selective ignition of controlled cellular suicide as therapeutic strategy in malignant diseases. However, the complexity of death receptor signalling has increased substantially during recent years. Beyond activation of the apoptotic cascade, involvement in a variety of cellular processes including inflammation, proliferation and immune response was recognised. Mechanistically, these findings raised the question how multipurpose receptors can ensure selective activation of a particular pathway. A growing body of evidence points to an elegant spatiotemporal regulation of composition and assembly of the receptor-associated signalling complex. Upon ligand binding, receptor recruitment in specialized membrane compartments, formation of receptor-ligand clusters and internalisation processes constitute key regulatory elements. In this review, we will summarise the current concepts of death receptor trafficking and its implications on receptor-associated signalling events.

  18. Exocyst and autophagy-related membrane trafficking in plants.

    Science.gov (United States)

    Pecenková, Tamara; Markovic, Vedrana; Sabol, Peter; Kulich, Ivan; Žárský, Viktor

    2017-12-18

    Endomembrane traffic in eukaryotic cells functions partially as a means of communication; delivery of membrane in one direction has to be balanced with a reduction at the other end. This effect is typically the case during the defence against pathogens. To combat pathogens, cellular growth and differentiation are suppressed, while endomembrane traffic is poised towards limiting the pathogen attack. The octameric exocyst vesicle-tethering complex was originally discovered as a factor facilitating vesicle-targeting and vesicle-plasma membrane (PM) fusion during exocytosis prior to and possibly during SNARE complex formation. Interestingly, it was recently implicated both in animals and plants in autophagy membrane traffic. In animal cells, the exocyst is integrated into the mTOR-regulated energy metabolism stress/starvation pathway, participating in the formation and especially initiation of an autophagosome. In plants, the first functional link was to autophagy-related anthocyanin import to the vacuole and to starvation. In this concise review, we summarize the current knowledge of exocyst functions in autophagy and defence in plants that might involve unconventional secretion and compare it with animal conditions. Formation of different exocyst complexes during undisturbed cell growth, as opposed to periods of cellular stress reactions involving autophagy, might contribute to the coordination of endomembrane trafficking pathways. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  19. Investigation of SNARE-Mediated Membrane Trafficking in Prostate Cancer Cells

    National Research Council Canada - National Science Library

    Li, Xin

    2003-01-01

    In order to better understand how polarized membrane trafficking pathways change during the loss of epithelial cell polarity during cancer progression we have studied syntaxins 3 and 4 in prostate cancer...

  20. Vesicle-associated membrane protein 2 mediates trafficking of α5β1 integrin to the plasma membrane

    International Nuclear Information System (INIS)

    Hasan, Nazarul; Hu, Chuan

    2010-01-01

    Integrins are major receptors for cell adhesion to the extracellular matrix (ECM). As transmembrane proteins, the levels of integrins at the plasma membrane or the cell surface are ultimately determined by the balance between two vesicle trafficking events: endocytosis of integrins at the plasma membrane and exocytosis of the vesicles that transport integrins. Here, we report that vesicle-associated membrane protein 2 (VAMP2), a SNARE protein that mediates vesicle fusion with the plasma membrane, is involved in the trafficking of α5β1 integrin. VAMP2 was present on vesicles containing endocytosed β1 integrin. Small interfering RNA (siRNA) silencing of VAMP2 markedly reduced cell surface α5β1 and inhibited cell adhesion and chemotactic migration to fibronectin, the ECM ligand of α5β1, without altering cell surface expression of α2β1 integrin or α3β1 integrin. By contrast, silencing of VAMP8, another SNARE protein, had no effect on cell surface expression of the integrins or cell adhesion to fibronectin. In addition, VAMP2-mediated trafficking is involved in cell adhesion to collagen but not to laminin. Consistent with disruption of integrin functions in cell proliferation and survival, VAMP2 silencing diminished proliferation and triggered apoptosis. Collectively, these data indicate that VAMP2 mediates the trafficking of α5β1 integrin to the plasma membrane and VAMP2-dependent integrin trafficking is critical in cell adhesion, migration and survival.

  1. Methods of analysis of the membrane trafficking pathway from recycling endosomes to lysosomes.

    Science.gov (United States)

    Matsui, Takahide; Fukuda, Mitsunori

    2014-01-01

    The transferrin receptor (TfR) is responsible for iron uptake through its trafficking between the plasma membrane and recycling endosomes, and as a result it has become a well-known marker for recycling endosomes. Although the molecular basis of the TfR recycling pathway has been thoroughly investigated, the TfR degradation mechanism has been poorly understood. Exposure of cultured cells to two drugs, the protein synthesis inhibitor cycloheximide and the V-ATPase inhibitor bafilomycin A1, recently showed that TfR is not only recycled back to the plasma membrane after endocytosis but is constitutively transported to lysosomes for degradation. The results of genome-wide screening of mouse Rab small GTPases (common regulators of membrane trafficking in all eukaryotes) have indicated that Rab12 regulates TfR trafficking to lysosomes independently of the known membrane trafficking pathways, for example, the conventional endocytic pathway and recycling pathway. This chapter summarizes the methods that the authors used to analyze the membrane trafficking pathway from recycling endosomes to lysosomes that is specifically regulated by Rab12. © 2014 Elsevier Inc. All rights reserved.

  2. 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.

  3. Phosphorylation-dependent trafficking of plasma membrane proteins in animal and plant cells.

    Science.gov (United States)

    Offringa, Remko; Huang, Fang

    2013-09-01

    In both unicellular and multicellular organisms, transmembrane (TM) proteins are sorted to and retained at specific membrane domains by endomembrane trafficking mechanisms that recognize sorting signals in the these proteins. The trafficking and distribution of plasma membrane (PM)-localized TM proteins (PM proteins), especially of those PM proteins that show an asymmetric distribution over the PM, has received much attention, as their proper PM localization is crucial for elementary signaling and transport processes, and defects in their localization often lead to severe disease symptoms or developmental defects. The subcellular localization of PM proteins is dynamically regulated by post-translational modifications, such as phosphorylation and ubiquitination. These modificaitons mostly occur on sorting signals that are located in the larger cytosolic domains of the cargo proteins. Here we review the effects of phosphorylation of PM proteins on their trafficking, and present the key examples from the animal field that have been subject to studies for already several decades, such as that of aquaporin 2 and the epidermal growth factor receptor. Our knowledge on cargo trafficking in plants is largely based on studies of the family of PIN FORMED (PIN) carriers that mediate the efflux of the plant hormone auxin. We will review what is known on the subcellular distribution and trafficking of PIN proteins, with a focus on how this is modulated by phosphorylation, and identify and discuss analogies and differences in trafficking with the well-studied animal examples. © 2013 Institute of Botany, Chinese Academy of Sciences.

  4. Mitochondrial cardiolipin/phospholipid trafficking: the role of membrane contact site complexes and lipid transfer proteins.

    Science.gov (United States)

    Schlattner, Uwe; Tokarska-Schlattner, Malgorzata; Rousseau, Denis; Boissan, Mathieu; Mannella, Carmen; Epand, Richard; Lacombe, Marie-Lise

    2014-04-01

    Historically, cellular trafficking of lipids has received much less attention than protein trafficking, mostly because its biological importance was underestimated, involved sorting and translocation mechanisms were not known, and analytical tools were limiting. This has changed during the last decade, and we discuss here some progress made in respect to mitochondria and the trafficking of phospholipids, in particular cardiolipin. Different membrane contact site or junction complexes and putative lipid transfer proteins for intra- and intermembrane lipid translocation have been described, involving mitochondrial inner and outer membrane, and the adjacent membranes of the endoplasmic reticulum. An image emerges how cardiolipin precursors, remodeling intermediates, mature cardiolipin and its oxidation products could migrate between membranes, and how this trafficking is involved in cardiolipin biosynthesis and cell signaling events. Particular emphasis in this review is given to mitochondrial nucleoside diphosphate kinase D and mitochondrial creatine kinases, which emerge to have roles in both, membrane junction formation and lipid transfer. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  5. Neuron membrane trafficking and protein kinases involved in autism and ADHD.

    Science.gov (United States)

    Kitagishi, Yasuko; Minami, Akari; Nakanishi, Atsuko; Ogura, Yasunori; Matsuda, Satoru

    2015-01-30

    A brain-enriched multi-domain scaffolding protein, neurobeachin has been identified as a candidate gene for autism patients. Mutations in the synaptic adhesion protein cell adhesion molecule 1 (CADM1) are also associated with autism spectrum disorder, a neurodevelopmental disorder of uncertain molecular origin. Potential roles of neurobeachin and CADM1 have been suggested to a function of vesicle transport in endosomal trafficking. It seems that protein kinase B (AKT) and cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) have key roles in the neuron membrane trafficking involved in the pathogenesis of autism. Attention deficit hyperactivity disorder (ADHD) is documented to dopaminergic insufficiencies, which is attributed to synaptic dysfunction of dopamine transporter (DAT). AKT is also essential for the DAT cell-surface redistribution. In the present paper, we summarize and discuss the importance of several protein kinases that regulate the membrane trafficking involved in autism and ADHD, suggesting new targets for therapeutic intervention.

  6. Neuron Membrane Trafficking and Protein Kinases Involved in Autism and ADHD

    Directory of Open Access Journals (Sweden)

    Yasuko Kitagishi

    2015-01-01

    Full Text Available A brain-enriched multi-domain scaffolding protein, neurobeachin has been identified as a candidate gene for autism patients. Mutations in the synaptic adhesion protein cell adhesion molecule 1 (CADM1 are also associated with autism spectrum disorder, a neurodevelopmental disorder of uncertain molecular origin. Potential roles of neurobeachin and CADM1 have been suggested to a function of vesicle transport in endosomal trafficking. It seems that protein kinase B (AKT and cyclic adenosine monophosphate (cAMP-dependent protein kinase A (PKA have key roles in the neuron membrane trafficking involved in the pathogenesis of autism. Attention deficit hyperactivity disorder (ADHD is documented to dopaminergic insufficiencies, which is attributed to synaptic dysfunction of dopamine transporter (DAT. AKT is also essential for the DAT cell-surface redistribution. In the present paper, we summarize and discuss the importance of several protein kinases that regulate the membrane trafficking involved in autism and ADHD, suggesting new targets for therapeutic intervention.

  7. Plasma membrane protein trafficking in plant–microbe interactions: a plant cell point of view

    OpenAIRE

    Nathalie Leborgne-Castel,; Bouhidel, Karim

    2014-01-01

    In order to ensure their physiological and cellular functions, plasma membrane (PM) proteins must be properly conveyed from their site of synthesis, i.e., the endoplasmic reticulum, to their final destination, the PM, through the secretory pathway. PM protein homeostasis also relies on recycling and/or degradation, two processes that are initiated by endocytosis. Vesicular membrane trafficking events to and from the PM have been shown to be altered when plant cells are exposed to mutualistic ...

  8. Functional links between mucolipin-1 and Ca2+-dependent membrane trafficking in mucolipidosis IV

    International Nuclear Information System (INIS)

    LaPlante, Janice M.; Ye, C.P.; Quinn, Stephen J.; Goldin, Ehud; Brown, Edward M.; Slaugenhaupt, Susan A.; Vassilev, Peter M.

    2004-01-01

    Most of the membrane trafficking phenomena including those involving the interactions between endosomes and lysosomes are regulated by changes in intracellular Ca 2+ (Ca i ). These processes are disturbed in some types of mucolipidoses and other lysosomal storage disorders, such as mucolipidosis IV (MLIV), a neurological disorder that usually presents during the first year of life with blindness, cognitive impairment, and psychomotor delays. It is caused by mutations in MCOLN1, the gene encoding mucolipin-1 (MLN1), which we have recently established to represent a Ca 2+ -permeable cation channel that is transiently modulated by changes in Ca i . The cells of MLIV patients contain enlarged lysosomes that are likely associated with abnormal sorting and trafficking of these and related organelles. We studied fibroblasts from MLIV patients and found disturbed Ca 2+ signaling and large acidic organelles such as late endosomes and lysosomes (LEL) with altered cellular localization in these cells. The fusion between LEL vesicles in these cells was defective. This is a Ca 2+ -dependent process related to signaling pathways involved in regulation of Ca 2+ homeostasis and trafficking. The MLN1 channels could play a key role in Ca 2+ release from LEL vesicles, which triggers the fusion and trafficking of these organelles. The characterization of this MLN1-mediated Ca 2+ -dependent process should provide new insights into the pathophysiological mechanisms that lead to the development of MLIV and other mucolipidoses associated with similar disturbances in membrane trafficking

  9. Phosphoinositides, Major Actors in Membrane Trafficking and Lipid Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Johan-Owen De Craene

    2017-03-01

    Full Text Available Phosphoinositides are lipids involved in the vesicular transport of proteins and lipids between the different compartments of eukaryotic cells. They act by recruiting and/or activating effector proteins and thus are involved in regulating various cellular functions, such as vesicular budding, membrane fusion and cytoskeleton dynamics. Although detected in small concentrations in membranes, their role is essential to cell function, since imbalance in their concentrations is a hallmark of many cancers. Their synthesis involves phosphorylating/dephosphorylating positions D3, D4 and/or D5 of their inositol ring by specific lipid kinases and phosphatases. This process is tightly regulated and specific to the different intracellular membranes. Most enzymes involved in phosphoinositide synthesis are conserved between yeast and human, and their loss of function leads to severe diseases (cancer, myopathy, neuropathy and ciliopathy.

  10. Plasma membrane protein trafficking in plant-microbe interactions: a plant cell point of view

    Directory of Open Access Journals (Sweden)

    Nathalie eLeborgne-Castel

    2014-12-01

    Full Text Available In order to ensure their physiological and cellular functions, plasma membrane (PM proteins must be properly conveyed from their site of synthesis, i.e. the endoplasmic reticulum, to their final destination, the PM, through the secretory pathway. PM protein homeostasis also relies on recycling and/or degradation, two processes that are initiated by endocytosis. Vesicular membrane trafficking events to and from the PM have been shown to be altered when plant cells are exposed to mutualistic or pathogenic microbes. In this review, we will describe the fine-tune regulation of such alterations, and their consequence in PM protein activity. We will consider the formation of intracellular perimicrobial compartments, the PM protein trafficking machinery of the host, and the delivery or retrieval of signaling and transport proteins such as pattern-recognition receptors, producers of reactive oxygen species, and sugar transporters.

  11. 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...

  12. Trafficking of plant plasma membrane aquaporins: multiple regulation levels and complex sorting signals.

    Science.gov (United States)

    Chevalier, Adrien S; Chaumont, François

    2015-05-01

    Aquaporins are small channel proteins which facilitate the diffusion of water and small neutral molecules across biological membranes. Compared with animals, plant genomes encode numerous aquaporins, which display a large variety of subcellular localization patterns. More specifically, plant aquaporins of the plasma membrane intrinsic protein (PIP) subfamily were first described as plasma membrane (PM)-resident proteins, but recent research has demonstrated that the trafficking and subcellular localization of these proteins are complex and highly regulated. In the past few years, PIPs emerged as new model proteins to study subcellular sorting and membrane dynamics in plant cells. At least two distinct sorting motifs (one cytosolic, the other buried in the membrane) are required to direct PIPs to the PM. Hetero-oligomerization and interaction with SNAREs (soluble N-ethylmaleimide-sensitive factor protein attachment protein receptors) also influence the subcellular trafficking of PIPs. In addition to these constitutive processes, both the progression of PIPs through the secretory pathway and their dynamics at the PM are responsive to changing environmental conditions. © The Author 2014. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  13. Rab7: roles in membrane trafficking and disease.

    Science.gov (United States)

    Zhang, Ming; Chen, Li; Wang, Shicong; Wang, Tuanlao

    2009-06-01

    The endocytosis pathway controls multiple cellular and physiological events. The lysosome is the destination of newly synthesized lysosomal hydrolytic enzymes. Internalized molecules or particles are delivered to the lysosome for degradation through sequential transport along the endocytic pathway. The endocytic pathway is also emerging as a signalling platform, in addition to the well-known role of the plasma membrane for signalling. Rab7 is a late endosome-/lysosome-associated small GTPase, perhaps the only lysosomal Rab protein identified to date. Rab7 plays critical roles in the endocytic processes. Through interaction with its partners (including upstream regulators and downstream effectors), Rab7 participates in multiple regulation mechanisms in endosomal sorting, biogenesis of lysosome [or LRO (lysosome-related organelle)] and phagocytosis. These processes are closely related to substrates degradation, antigen presentation, cell signalling, cell survival and microbial pathogen infection. Consistently, mutations or dysfunctions of Rab7 result in traffic disorders, which cause various diseases, such as neuropathy, cancer and lipid metabolism disease. Rab7 also plays important roles in microbial pathogen infection and survival, as well as in participating in the life cycle of viruses. Here, we give a brief review on the central role of Rab7 in endosomal traffic and summarize the studies focusing on the participation of Rab7 in disease pathogenesis. The underlying mechanism governed by Rab7 and its partners will also be discussed.

  14. Distinct human and mouse membrane trafficking systems for sweet taste receptors T1r2 and T1r3.

    Science.gov (United States)

    Shimizu, Madoka; Goto, Masao; Kawai, Takayuki; Yamashita, Atsuko; Kusakabe, Yuko

    2014-01-01

    The sweet taste receptors T1r2 and T1r3 are included in the T1r taste receptor family that belongs to class C of the G protein-coupled receptors. Heterodimerization of T1r2 and T1r3 is required for the perception of sweet substances, but little is known about the mechanisms underlying this heterodimerization, including membrane trafficking. We developed tagged mouse T1r2 and T1r3, and human T1R2 and T1R3 and evaluated membrane trafficking in human embryonic kidney 293 (HEK293) cells. We found that human T1R3 surface expression was only observed when human T1R3 was coexpressed with human T1R2, whereas mouse T1r3 was expressed without mouse T1r2 expression. A domain-swapped chimera and truncated human T1R3 mutant showed that the Venus flytrap module and cysteine-rich domain (CRD) of human T1R3 contain a region related to the inhibition of human T1R3 membrane trafficking and coordinated regulation of human T1R3 membrane trafficking. We also found that the Venus flytrap module of both human T1R2 and T1R3 are needed for membrane trafficking, suggesting that the coexpression of human T1R2 and T1R3 is required for this event. These results suggest that the Venus flytrap module and CRD receive taste substances and play roles in membrane trafficking of human T1R2 and T1R3. These features are different from those of mouse receptors, indicating that human T1R2 and T1R3 are likely to have a novel membrane trafficking system.

  15. One-way membrane trafficking of SOS in receptor-triggered Ras activation.

    Science.gov (United States)

    Christensen, Sune M; Tu, Hsiung-Lin; Jun, Jesse E; Alvarez, Steven; Triplet, Meredith G; Iwig, Jeffrey S; Yadav, Kamlesh K; Bar-Sagi, Dafna; Roose, Jeroen P; Groves, Jay T

    2016-09-01

    SOS is a key activator of the small GTPase Ras. In cells, SOS-Ras signaling is thought to be initiated predominantly by membrane recruitment of SOS via the adaptor Grb2 and balanced by rapidly reversible Grb2-SOS binding kinetics. However, SOS has multiple protein and lipid interactions that provide linkage to the membrane. In reconstituted-membrane experiments, these Grb2-independent interactions were sufficient to retain human SOS on the membrane for many minutes, during which a single SOS molecule could processively activate thousands of Ras molecules. These observations raised questions concerning how receptors maintain control of SOS in cells and how membrane-recruited SOS is ultimately released. We addressed these questions in quantitative assays of reconstituted SOS-deficient chicken B-cell signaling systems combined with single-molecule measurements in supported membranes. These studies revealed an essentially one-way trafficking process in which membrane-recruited SOS remains trapped on the membrane and continuously activates Ras until being actively removed via endocytosis.

  16. 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....

  17. The molecular mechanisms of plant plasma membrane intrinsic proteins trafficking and stress response.

    Science.gov (United States)

    Wang, Xing; Zhang, Ji-long; Feng, Xiu-xiu; Li, Hong-jie; Zhang, Gen-fa

    2017-04-20

    Plasma membrane intrinsic proteins (PIPs) are plant channel proteins located on the plasma membrane. PIPs transfer water, CO 2 and small uncharged solutes through the plasma membrane. PIPs have high selectivity to substrates, suggestive of a central role in maintaining cellular water balance. The expression, activity and localization of PIPs are regulated at the transcriptional and post-translational levels, and also affected by environmental factors. Numerous studies indicate that the expression patterns and localizations of PIPs can change in response to abiotic stresses. In this review, we summarize the mechanisms of PIP trafficking, transcriptional and post-translational regulations, and abiotic stress responses. Moreover, we also discuss the current research trends and future directions on PIPs.

  18. HIV-1 matrix dependent membrane targeting is regulated by Gag mRNA trafficking.

    Directory of Open Access Journals (Sweden)

    Jing Jin

    Full Text Available Retroviral Gag polyproteins are necessary and sufficient for virus budding. Productive HIV-1 Gag assembly takes place at the plasma membrane. However, little is known about the mechanisms by which thousands of Gag molecules are targeted to the plasma membrane. Using a bimolecular fluorescence complementation (BiFC assay, we recently reported that the cellular sites and efficiency of HIV-1 Gag assembly depend on the precise pathway of Gag mRNA export from the nucleus, known to be mediated by Rev. Here we describe an assembly deficiency in human cells for HIV Gag whose expression depends on hepatitis B virus (HBV post-transcriptional regulatory element (PRE mediated-mRNA nuclear export. PRE-dependent HIV Gag expressed well in human cells, but assembled with slower kinetics, accumulated intracellularly, and failed to associate with a lipid raft compartment where the wild-type Rev-dependent HIV-1 Gag efficiently assembles. Surprisingly, assembly and budding of PRE-dependent HIV Gag in human cells could be rescued in trans by co-expression of Rev-dependent Gag that provides correct membrane targeting signals, or in cis by replacing HIV matrix (MA with other membrane targeting domains. Taken together, our results demonstrate deficient membrane targeting of PRE-dependent HIV-1 Gag and suggest that HIV MA function is regulated by the trafficking pathway of the encoding mRNA.

  19. 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.

  20. Ion beam heating of thin silicon membranes

    International Nuclear Information System (INIS)

    Tissot, P.E.; Hart, R.R.

    1993-01-01

    For silicon membranes irradiated by an ion beam in a vacuum environment, such as the masks used for ion beam lithography and the membranes used for thin film self-annealing, the heat transfer modes are radiation and limited conduction through the thin membrane. The radiation component depends on the total hemispherical emissivity which varies with the thickness and temperature of the membrane. A semiempirical correlation for the absorption coefficient of high resistivity silicon was derived and the variation of the total emissivity with temperature was computed for membranes with thicknesses between 0.1 and 10 μm. Based on this result, the temperatures reached during exposure to ion beams of varying intensities were computed. A proper modeling of the emissivity is shown to be important for beam heating of thin silicon membranes. (orig.)

  1. Optineurin: A Coordinator of Membrane-Associated Cargo Trafficking and Autophagy

    Directory of Open Access Journals (Sweden)

    Thomas A. Ryan

    2018-05-01

    Full Text Available Optineurin is a multifunctional adaptor protein intimately involved in various vesicular trafficking pathways. Through interactions with an array of proteins, such as myosin VI, huntingtin, Rab8, and Tank-binding kinase 1, as well as via its oligomerisation, optineurin has the ability to act as an adaptor, scaffold, or signal regulator to coordinate many cellular processes associated with the trafficking of membrane-delivered cargo. Due to its diverse interactions and its distinct functions, optineurin is an essential component in a number of homeostatic pathways, such as protein trafficking and organelle maintenance. Through the binding of polyubiquitinated cargoes via its ubiquitin-binding domain, optineurin also serves as a selective autophagic receptor for the removal of a wide range of substrates. Alternatively, it can act in an ubiquitin-independent manner to mediate the clearance of protein aggregates. Regarding its disease associations, mutations in the optineurin gene are associated with glaucoma and have more recently been found to correlate with Paget’s disease of bone and amyotrophic lateral sclerosis (ALS. Indeed, ALS-associated mutations in optineurin result in defects in neuronal vesicular localisation, autophagosome–lysosome fusion, and secretory pathway function. More recent molecular and functional analysis has shown that it also plays a role in mitophagy, thus linking it to a number of other neurodegenerative conditions, such as Parkinson’s. Here, we review the role of optineurin in intracellular membrane trafficking, with a focus on autophagy, and describe how upstream signalling cascades are critical to its regulation. Current data and contradicting reports would suggest that optineurin is an important and selective autophagy receptor under specific conditions, whereby interplay, synergy, and functional redundancy with other receptors occurs. We will also discuss how dysfunction in optineurin-mediated pathways may lead

  2. Wherever I may roam: protein and membrane trafficking in P. falciparum-infected red blood cells.

    Science.gov (United States)

    Deponte, Marcel; Hoppe, Heinrich C; Lee, Marcus C S; Maier, Alexander G; Richard, Dave; Rug, Melanie; Spielmann, Tobias; Przyborski, Jude M

    2012-12-01

    Quite aside from its immense importance as a human pathogen, studies in recent years have brought to light the fact that the malaria parasite Plasmodium falciparum is an interesting eukaryotic model system to study protein trafficking. Studying parasite cell biology often reveals an overrepresentation of atypical cell biological features, possibly driven by the parasites' need to survive in an unusual biological niche. Malaria parasites possess uncommon cellular compartments to which protein traffic must be directed, including secretory organelles such as rhoptries and micronemes, a lysosome-like compartment referred to as the digestive vacuole and a complex (four membrane-bound) plastid, the apicoplast. In addition, the parasite must provide proteins to extracellular compartments and structures including the parasitophorous vacuole, the parasitophorous vacuolar membrane, the Maurer's clefts and both cytosol and plasma membrane of the host cell, the mature human red blood cell. Although some of these unusual destinations are possessed by other cell types, only Plasmodium parasites contain them all within one cell. Here we review what is known about protein and membrane transport in the P. falciparum-infected cell, highlighting novel features of these processes. A growing body of evidence suggests that this parasite is a real "box of tricks" with regards to protein traffic. Possibly, these tricks may be turned against the parasite by exploiting them as novel therapeutic targets. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. EMBO workshop al fin del mundo: a meeting on membrane trafficking and its implication for polarity and diseases.

    Science.gov (United States)

    Marzolo, María-Paz; Faundez, Victor; Galli, Thierry

    2015-07-01

    The EMBO worskhop at the "end of the world'" (al fin del mundo), a meeting on membrane trafficking and its implication for polarity and diseases, took place in the Chilean Patagonia surrounded by the landscapes once witnessed by Charles Darwin. The meeting showcased some of the best membrane trafficking science with an emphasis in neuroscience and disease models. Speakers from Europe, USA, South America and the graduate students behind it; embarked on an enthusiastic and eclectic dialog where a wide range of cell types, model genetic systems, and diseases where discussed. This meeting demonstrated the power of trafficking concepts to integrate diverse biology and to formulate mechanisms of normal and disease cells. © 2015 Société Française des Microscopies and Société de Biologie Cellulaire de France. Published by John Wiley & Sons Ltd.

  4. The formation of endosymbiotic membrane compartments: membrane identity markers and the regulation of vesicle trafficking

    NARCIS (Netherlands)

    Ivanov, S.

    2012-01-01

    In symbiosis of plants and arbuscular mycorrhizal fungi as well as in rhizobium-legume symbiosis the microbes are hosted intracellularly, inside specialized membrane compartments of the host. These membrane compartments are morphologically different but similar in function, since they control

  5. LRRK2 affects vesicle trafficking, neurotransmitter extracellular level and membrane receptor localization.

    Directory of Open Access Journals (Sweden)

    Rossana Migheli

    Full Text Available The leucine-rich repeat kinase 2 (LRRK2 gene was found to play a role in the pathogenesis of both familial and sporadic Parkinson's disease (PD. LRRK2 encodes a large multi-domain protein that is expressed in different tissues. To date, the physiological and pathological functions of LRRK2 are not clearly defined. In this study we have explored the role of LRRK2 in controlling vesicle trafficking in different cellular or animal models and using various readouts. In neuronal cells, the presence of LRRK2(G2019S pathological mutant determines increased extracellular dopamine levels either under basal conditions or upon nicotine stimulation. Moreover, mutant LRRK2 affects the levels of dopamine receptor D1 on the membrane surface in neuronal cells or animal models. Ultrastructural analysis of PC12-derived cells expressing mutant LRRK2(G2019S shows an altered intracellular vesicle distribution. Taken together, our results point to the key role of LRRK2 to control vesicle trafficking in neuronal cells.

  6. Alterations in membrane trafficking and pathophysiological implications in lysosomal storage disorders.

    Science.gov (United States)

    Kuech, Eva-Maria; Brogden, Graham; Naim, Hassan Y

    2016-11-01

    Lysosomal storage disorders are a heterogeneous group of more than 50 distinct inborn metabolic diseases affecting about 1 in 5000 to 7000 live births. The diseases often result from mutations followed by functional deficiencies of enzymes or transporters within the acidic environment of the lysosome, which mediate the degradation of a wide subset of substrates, including glycosphingolipids, glycosaminoglycans, cholesterol, glycogen, oligosaccharides, peptides and glycoproteins, or the export of the respective degradation products from the lysosomes. The progressive accumulation of uncleaved substrates occurs in multiple organs and finally causes a broad spectrum of different pathologies including visceral, neurological, skeletal and hematologic manifestations. Besides deficient lysosomal enzymes and transporters other defects may lead to lysosomal storage disorders, including activator defects, membrane defects or defects in modifier proteins. In this review we concentrate on four different lysosomal storage disorders: Niemann-Pick type C, Fabry disease, Gaucher disease and Pompe disease. While the last three are caused by defective lysosomal hydrolases, Niemann-Pick type C is caused by the inability to export LDL-derived cholesterol out of the lysosome. We want to emphasise potential implications of membrane trafficking defects on the pathology of these diseases, as many mutations interfere with correct lysosomal protein trafficking and alter cellular lipid homeostasis. Current therapeutic strategies are summarised, including substrate reduction therapy as well as pharmacological chaperone therapy which directly aim to improve folding and lysosomal transport of misfolded mutant proteins. Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  7. 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.

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

    Science.gov (United States)

    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.

  9. 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.

  10. 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.

  11. STARD4 knockdown in HepG2 cells disrupts cholesterol trafficking associated with the plasma membrane, ER, and ERC

    DEFF Research Database (Denmark)

    Garbarino, J.; Pan, M. H.; Chin, H. F.

    2012-01-01

    small hairpin RNA knockdown technology to reduce STARD4 expression in HepG2 cells. In a cholesterol-poor environment, we found that a reduction in STARD4 expression leads to retention of cholesterol at the plasma membrane, reduction of endoplasmic reticulum-associated cholesterol, and decreased ACAT...... synthesized cholesteryl esters. Furthermore, D4 KD cells exhibited a reduced rate of sterol transport to the endocytic recycling compartment after cholesterol repletion. Although these cells displayed normal endocytic trafficking in cholesterol-poor and replete conditions, cell surface low density lipoprotein...... membrane and the endocytic recycling compartment to the endoplasmic reticulum and perhaps other intracellular compartments as well. -Garbarino, J., M. Pan, H.F. Chin, F.W. Lund, F.R. Maxfield, and J.L. Breslow. STARD4 knockdown in HepG2 cells disrupts cholesterol trafficking associated with the plasma...

  12. Kinetic imaging of NPC1L1 and sterol trafficking between plasma membrane and recycling endosomes in hepatoma cells

    DEFF Research Database (Denmark)

    Hartwig Petersen, Nicole; Færgeman, Nils J; Yu, Liqing

    2008-01-01

    fluorescent protein (NPC1L1-EGFP) and cholesterol analogues in hepatoma cells. At steady state about 42% of NPC1L1 resided in the transferrin (Tf) positive, sterol enriched endocytic recycling compartment (ERC), while time-lapse microscopy demonstrated NPC1L1 traffic between plasma membrane and ERC...... the ERC to the plasma membrane. NPC1L1-EGFP facilitated transport of fluorescent sterols from the plasma membrane to the ERC. Insulin induced translocation of vesicles containing NPC1L1 and fluorescent sterol from the ERC to the cell membrane. Upon polarization of hepatoma cells NPC1L1 resided almost...... exclusively in the canalicular membrane, where the protein is highly mobile. Our study demonstrates dynamic trafficking of NPC1L1 between cell surface and intracellular compartments and suggests that this transport is involved in NPC1L1 mediated cellular sterol uptake....

  13. Classifying the molecular functions of Rab GTPases in membrane trafficking using deep convolutional neural networks.

    Science.gov (United States)

    Le, Nguyen-Quoc-Khanh; Ho, Quang-Thai; Ou, Yu-Yen

    2018-06-13

    Deep learning has been increasingly used to solve a number of problems with state-of-the-art performance in a wide variety of fields. In biology, deep learning can be applied to reduce feature extraction time and achieve high levels of performance. In our present work, we apply deep learning via two-dimensional convolutional neural networks and position-specific scoring matrices to classify Rab protein molecules, which are main regulators in membrane trafficking for transferring proteins and other macromolecules throughout the cell. The functional loss of specific Rab molecular functions has been implicated in a variety of human diseases, e.g., choroideremia, intellectual disabilities, cancer. Therefore, creating a precise model for classifying Rabs is crucial in helping biologists understand the molecular functions of Rabs and design drug targets according to such specific human disease information. We constructed a robust deep neural network for classifying Rabs that achieved an accuracy of 99%, 99.5%, 96.3%, and 97.6% for each of four specific molecular functions. Our approach demonstrates superior performance to traditional artificial neural networks. Therefore, from our proposed study, we provide both an effective tool for classifying Rab proteins and a basis for further research that can improve the performance of biological modeling using deep neural networks. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. VANGL2 regulates membrane trafficking of MMP14 to control cell polarity and migration.

    Science.gov (United States)

    Williams, B Blairanne; Cantrell, V Ashley; Mundell, Nathan A; Bennett, Andrea C; Quick, Rachel E; Jessen, Jason R

    2012-05-01

    Planar cell polarity (PCP) describes the polarized orientation of cells within the plane of a tissue. Unlike epithelial PCP, the mechanisms underlying PCP signaling in migrating cells remain undefined. Here, the establishment of PCP must be coordinated with dynamic changes in cell adhesion and extracellular matrix (ECM) organization. During gastrulation, the membrane type-1 matrix metalloproteinase (MT1-MMP or MMP14) is required for PCP and convergence and extension cell movements. We report that the PCP protein Vang-like 2 (VANGL2) regulates the endocytosis and cell-surface availability of MMP14 in manner that is dependent on focal adhesion kinase. We demonstrate that zebrafish trilobite/vangl2 mutant embryos exhibit increased Mmp14 activity and decreased ECM. Furthermore, in vivo knockdown of Mmp14 partially rescues the Vangl2 loss-of-function convergence and extension phenotype. This study identifies a mechanism linking VANGL2 with MMP14 trafficking and suggests that establishment of PCP in migrating gastrula cells requires regulated proteolytic degradation or remodeling of the ECM. Our findings implicate matrix metalloproteinases as downstream effectors of PCP and suggest a broadly applicable mechanism whereby VANGL2 affects diverse morphogenetic processes.

  15. Quantification of the Force of Nanoparticle-Cell Membrane Interactions and Its Influence on Intracellular Trafficking of Nanoparticles

    Science.gov (United States)

    Vasir, Jaspreet K.; Labhasetwar, Vinod

    2008-01-01

    Understanding the interaction of nanoparticles (NPs) with the cell membrane and their trafficking through cells is imperative to fully explore the use of NPs for efficient intracellular delivery of therapeutics. Here, we report a novel method of measuring the force of NP-cell membrane interactions using atomic force microscopy (AFM). Poly(dl-lactide co-glycolide, PLGA) NPs functionalized with poly-l-lysine were used as a model system, to demonstrate that this force determines the adhesive interaction of NPs with the cell membrane and in turn the extent of cellular uptake of NPs, and hence that of the encapsulated therapeutic. Cellular uptake of NPs was monitored using AFM imaging, and the dynamics of their intracellular distribution was quantified using confocal microscopy. Results demonstrated that the functionalized NPs have a five-fold greater force of adhesion with the cell membrane and the time-lapse AFM images show their rapid internalization than unmodified NPs. The intracellular trafficking study showed that the functionalized NPs escape more rapidly and efficiently from late endosomes than unmodified NPs and result in 10-fold higher intracellular delivery of the encapsulated model protein. The findings described herein enhance our basic understanding of the NP-cell membrane interaction on the basis of physical phenomena that could have wider applications in developing efficient nanocarrier systems for intracellular delivery of therapeutics. PMID:18692238

  16. P2X7 receptors regulate multiple types of membrane trafficking responses and non-classical secretion pathways.

    Science.gov (United States)

    Qu, Yan; Dubyak, George R

    2009-06-01

    Activation of the P2X7 receptor (P2X7R) triggers a remarkably diverse array of membrane trafficking responses in leukocytes and epithelial cells. These responses result in altered profiles of cell surface lipid and protein composition that can modulate the direct interactions of P2X7R-expressing cells with other cell types in the circulation, in blood vessels, at epithelial barriers, or within sites of immune and inflammatory activation. Additionally, these responses can result in the release of bioactive proteins, lipids, and large membrane complexes into extracellular compartments for remote communication between P2X7R-expressing cells and other cells that amplify or modulate inflammation, immunity, and responses to tissue damages. This review will discuss P2X7R-mediated effects on membrane composition and trafficking in the plasma membrane (PM) and intracellular organelles, as well as actions of P2X7R in controlling various modes of non-classical secretion. It will review P2X7R regulation of: (1) phosphatidylserine distribution in the PM outer leaflet; (2) shedding of PM surface proteins; (3) release of PM-derived microvesicles or microparticles; (4) PM blebbing; (5) cell-cell fusion resulting in formation of multinucleate cells; (6) phagosome maturation and fusion with lysosomes; (7) permeability of endosomes with internalized pathogen-associated molecular patterns; (8) permeability/integrity of mitochondria; (9) exocytosis of secretory lysosomes; and (10) release of exosomes from multivesicular bodies.

  17. Genome comparison implies the role of Wsm2 in membrane trafficking and protein degradation

    Directory of Open Access Journals (Sweden)

    Guorong Zhang

    2018-04-01

    Wsm2 may combat WSMV disease through a molecular mechanism involving protein degradation and/or membrane trafficking. The 93 putative Wsm2 ancestor loci discovered in this study could serve as good candidates for future genetic isolation of the true Wsm2 locus.

  18. Ist2 in the yeast cortical endoplasmic reticulum promotes trafficking of the amino acid transporter Bap2 to the plasma membrane.

    Directory of Open Access Journals (Sweden)

    Wendelin Wolf

    Full Text Available The equipment of the plasma membrane in Saccharomyces cerevisiae with specific nutrient transporters is highly regulated by transcription, translation and protein trafficking allowing growth in changing environments. The activity of these transporters depends on a H(+ gradient across the plasma membrane generated by the H(+-ATPase Pma1. We found that the polytopic membrane protein Ist2 in the cortical endoplasmic reticulum (ER is required for efficient leucine uptake during the transition from fermentation to respiration. Experiments employing tandem fluorescence timer protein tag showed that Ist2 was necessary for efficient trafficking of newly synthesized leucine transporter Bap2 from the ER to the plasma membrane. This finding explains the growth defect of ist2Δ mutants during nutritional challenges and illustrates the important role of physical coupling between cortical ER and plasma membrane.

  19. Fragile X Mental Retardation Protein Regulates Activity-Dependent Membrane Trafficking and Trans-Synaptic Signaling Mediating Synaptic Remodeling

    Science.gov (United States)

    Sears, James C.; Broadie, Kendal

    2018-01-01

    Fragile X syndrome (FXS) is the leading monogenic cause of autism and intellectual disability. The disease arises through loss of fragile X mental retardation protein (FMRP), which normally exhibits peak expression levels in early-use critical periods, and is required for activity-dependent synaptic remodeling during this transient developmental window. FMRP canonically binds mRNA to repress protein translation, with targets that regulate cytoskeleton dynamics, membrane trafficking, and trans-synaptic signaling. We focus here on recent advances emerging in these three areas from the Drosophila disease model. In the well-characterized central brain mushroom body (MB) olfactory learning/memory circuit, FMRP is required for activity-dependent synaptic remodeling of projection neurons innervating the MB calyx, with function tightly restricted to an early-use critical period. FMRP loss is phenocopied by conditional removal of FMRP only during this critical period, and rescued by FMRP conditional expression only during this critical period. Consistent with FXS hyperexcitation, FMRP loss defects are phenocopied by heightened sensory experience and targeted optogenetic hyperexcitation during this critical period. FMRP binds mRNA encoding Drosophila ESCRTIII core component Shrub (human CHMP4 homolog) to restrict Shrub translation in an activity-dependent mechanism only during this same critical period. Shrub mediates endosomal membrane trafficking, and perturbing Shrub expression is known to interfere with neuronal process pruning. Consistently, FMRP loss and Shrub overexpression targeted to projection neurons similarly causes endosomal membrane trafficking defects within synaptic boutons, and genetic reduction of Shrub strikingly rescues Drosophila FXS model defects. In parallel work on the well-characterized giant fiber (GF) circuit, FMRP limits iontophoretic dye loading into central interneurons, demonstrating an FMRP role controlling core neuronal properties through the

  20. 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

  1. 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.

  2. Hydrophobic Light-to-Heat Conversion Membranes with Self-Healing Ability for Interfacial Solar Heating

    KAUST Repository

    Zhang, Lianbin

    2015-07-01

    Self-healing hydrophobic light-to-heat conversion membranes for interfacial solar heating are fabricated by deposition of light-to-heat conversion material of polypyrrole onto porous stainless steel mesh, followed by hydrophobic fluoroalkylsilane modification. The mesh-based membranes spontaneously stay at the water–air interface, collect and convert solar light into heat, and locally heat only the water surface for an enhanced evaporation.

  3. Hydrophobic Light-to-Heat Conversion Membranes with Self-Healing Ability for Interfacial Solar Heating

    KAUST Repository

    Zhang, Lianbin; Tang, Bo; Wu, Jinbo; Li, Renyuan; Wang, Peng

    2015-01-01

    Self-healing hydrophobic light-to-heat conversion membranes for interfacial solar heating are fabricated by deposition of light-to-heat conversion material of polypyrrole onto porous stainless steel mesh, followed by hydrophobic fluoroalkylsilane modification. The mesh-based membranes spontaneously stay at the water–air interface, collect and convert solar light into heat, and locally heat only the water surface for an enhanced evaporation.

  4. On the heat transfer correlation for membrane distillation

    International Nuclear Information System (INIS)

    Wang, Chi-Chuan

    2011-01-01

    Research highlights: → Heat transfer coefficients applicable for membrane distillation. → Data reduction for heat transfer coefficient for membrane distillation method. → Uncertainty of permeate side due to large magnitude of membrane resistance. → Increase accuracy of heat transfer coefficient by modified Wilson plot technique. -- Abstract: The present study examines the heat transfer coefficients applicable for membrane distillation. In the available literatures, researchers often adopt some existing correlations and claim the suitability of these correlations to their test data or models. Unfortunately this approach is quite limited and questionable. This is subject to the influences of boundary conditions, geometrical configurations, entry flow conditions, as well as some influences from spacer or support. The simple way is to obtain the heat transfer coefficients from experimentation. However there is no direct experimental data for heat transfer coefficients being reported directly from the measurements. The main reasons are from the uncertainty of permeate side and of the comparatively large magnitude of membrane resistance. Additional minor influence is the effect of mass transfer on the heat transfer performance. In practice, the mass transfer effect is negligible provided the feed side temperature is low. To increase the accuracy of the measured feed side heat transfer coefficient, it is proposed in this study to exploit a modified Wilson plot technique. Through this approach, one can eliminate the uncertainty from permeate side and reduce the uncertainty in membrane to obtain a more reliable heat transfer coefficients at feed side from the experimentation.

  5. A FRET-Based Approach for Quantitative Evaluation of Forskolin-Induced Pendrin Trafficking at the Plasma Membrane in Bronchial NCI H292 Cells

    Directory of Open Access Journals (Sweden)

    Grazia Tamma

    2013-12-01

    Full Text Available Background: Human pendrin (SLC26A4, PDS is an integral membrane protein acting as an electroneutral anion exchanger. Loss of function mutations in pendrin protein cause Pendred syndrome, a disorder characterized by sensorineural deafness and a partial iodide organification defect that may lead to thyroid goiter. Additionally, pendrin up-regulation could play a role in the pathogenesis of several diseases including bronchial asthma and chronic obstructive pulmonary disease (COPD. Therefore, monitoring the plasma membrane abundance and trafficking of pendrin in the context of a living cell is crucially important. Methods: Trafficking of pendrin to the plasma membrane was monitored by fluorescence resonance energy transfer (FRET, a physical phenomenon occurring between two fluorophores (the FRET donor and acceptor located in close spatial proximity. Because the efficiency of the energy transfer is inversely proportional to the sixth power of the distance between donor and acceptor, FRET is extremely sensitive to small changes in distance between the donor and acceptor and is therefore a powerful tool to determine protein-protein interactions. Results: FRET studies revealed that forskolin-induced cAMP production is associated with a significant increase of pendrin expression at plasma membrane, which is paralleled by a decrease in intracellular pH. Pendrin transposition to the membrane is accompanied with a partial depolymerization of actin cytoskeleton via Rho-GTPase inhibition. Conclusion: Trafficking to the plasma membrane is critical in the regulation of pendrin activity. Therefore, reliable tools for monitoring and quantifying this phenomenon are highly desirable.

  6. A FRET-based approach for quantitative evaluation of forskolin-induced pendrin trafficking at the plasma membrane in bronchial NCI H292 cells.

    Science.gov (United States)

    Tamma, Grazia; Ranieri, Marianna; Dossena, Silvia; Di Mise, Annarita; Nofziger, Charity; Svelto, Maria; Paulmichl, Markus; Valenti, Giovanna

    2013-01-01

    Human pendrin (SLC26A4, PDS) is an integral membrane protein acting as an electroneutral anion exchanger. Loss of function mutations in pendrin protein cause Pendred syndrome, a disorder characterized by sensorineural deafness and a partial iodide organification defect that may lead to thyroid goiter. Additionally, pendrin up-regulation could play a role in the pathogenesis of several diseases including bronchial asthma and chronic obstructive pulmonary disease (COPD). Therefore, monitoring the plasma membrane abundance and trafficking of pendrin in the context of a living cell is crucially important. Trafficking of pendrin to the plasma membrane was monitored by fluorescence resonance energy transfer (FRET), a physical phenomenon occurring between two fluorophores (the FRET donor and acceptor) located in close spatial proximity. Because the efficiency of the energy transfer is inversely proportional to the sixth power of the distance between donor and acceptor, FRET is extremely sensitive to small changes in distance between the donor and acceptor and is therefore a powerful tool to determine protein-protein interactions. FRET studies revealed that forskolin-induced cAMP production is associated with a significant increase of pendrin expression at plasma membrane, which is paralleled by a decrease in intracellular pH. Pendrin transposition to the membrane is accompanied with a partial depolymerization of actin cytoskeleton via Rho-GTPase inhibition. Trafficking to the plasma membrane is critical in the regulation of pendrin activity. Therefore, reliable tools for monitoring and quantifying this phenomenon are highly desirable. © 2014 S. Karger AG, Basel.

  7. STARD4 knockdown in HepG2 cells disrupts cholesterol trafficking associated with the plasma membrane, ER, and ERC.

    Science.gov (United States)

    Garbarino, Jeanne; Pan, Meihui; Chin, Harvey F; Lund, Frederik W; Maxfield, Frederick R; Breslow, Jan L

    2012-12-01

    STARD4, a member of the evolutionarily conserved START gene family, has been implicated in the nonvesicular intracellular transport of cholesterol. However, the direction of transport and the membranes with which this protein interacts are not clear. We present studies of STARD4 function using small hairpin RNA knockdown technology to reduce STARD4 expression in HepG2 cells. In a cholesterol-poor environment, we found that a reduction in STARD4 expression leads to retention of cholesterol at the plasma membrane, reduction of endoplasmic reticulum-associated cholesterol, and decreased ACAT synthesized cholesteryl esters. Furthermore, D4 KD cells exhibited a reduced rate of sterol transport to the endocytic recycling compartment after cholesterol repletion. Although these cells displayed normal endocytic trafficking in cholesterol-poor and replete conditions, cell surface low density lipoprotein receptor (LDLR) levels were increased and decreased, respectively. We also observed a decrease in NPC1 protein expression, suggesting the induction of compensatory pathways to maintain cholesterol balance. These data indicate a role for STARD4 in nonvesicular transport of cholesterol from the plasma membrane and the endocytic recycling compartment to the endoplasmic reticulum and perhaps other intracellular compartments as well.

  8. KSHV Entry and Trafficking in Target Cells—Hijacking of Cell Signal Pathways, Actin and Membrane Dynamics

    Directory of Open Access Journals (Sweden)

    Binod Kumar

    2016-11-01

    Full Text Available Kaposi’s sarcoma associated herpesvirus (KSHV is etiologically associated with human endothelial cell hyperplastic Kaposi’s sarcoma and B-cell primary effusion lymphoma. KSHV infection of adherent endothelial and fibroblast cells are used as in vitro models for infection and KSHV enters these cells by host membrane bleb and actin mediated macropinocytosis or clathrin endocytosis pathways, respectively. Infection in endothelial and fibroblast cells is initiated by the interactions between multiple viral envelope glycoproteins and cell surface associated heparan sulfate (HS, integrins (α3β1, αVβ3 and αVβ5, and EphA2 receptor tyrosine kinase (EphA2R. This review summarizes the accumulated studies demonstrating that KSHV manipulates the host signal pathways to enter and traffic in the cytoplasm of the target cells, to deliver the viral genome into the nucleus, and initiate viral gene expression. KSHV interactions with the cell surface receptors is the key platform for the manipulations of host signal pathways which results in the simultaneous induction of FAK, Src, PI3-K, Rho-GTPase, ROS, Dia-2, PKC ζ, c-Cbl, CIB1, Crk, p130Cas and GEF-C3G signal and adaptor molecules that play critical roles in the modulation of membrane and actin dynamics, and in the various steps of the early stages of infection such as entry and trafficking towards the nucleus. The Endosomal Sorting Complexes Required for Transport (ESCRT proteins are also recruited to assist in viral entry and trafficking. In addition, KSHV interactions with the cell surface receptors also induces the host transcription factors NF-κB, ERK1/2, and Nrf2 early during infection to initiate and modulate viral and host gene expression. Nuclear delivery of the viral dsDNA genome is immediately followed by the host innate responses such as the DNA damage response (DDR, inflammasome and interferon responses. Overall, these studies form the initial framework for further studies of

  9. Cell-autonomous defense, re-organization and trafficking of membranes in plant-microbe interactions.

    Science.gov (United States)

    Dörmann, Peter; Kim, Hyeran; Ott, Thomas; Schulze-Lefert, Paul; Trujillo, Marco; Wewer, Vera; Hückelhoven, Ralph

    2014-12-01

    Plant cells dynamically change their architecture and molecular composition following encounters with beneficial or parasitic microbes, a process referred to as host cell reprogramming. Cell-autonomous defense reactions are typically polarized to the plant cell periphery underneath microbial contact sites, including de novo cell wall biosynthesis. Alternatively, host cell reprogramming converges in the biogenesis of membrane-enveloped compartments for accommodation of beneficial bacteria or invasive infection structures of filamentous microbes. Recent advances have revealed that, in response to microbial encounters, plasma membrane symmetry is broken, membrane tethering and SNARE complexes are recruited, lipid composition changes and plasma membrane-to-cytoskeleton signaling is activated, either for pre-invasive defense or for microbial entry. We provide a critical appraisal on recent studies with a focus on how plant cells re-structure membranes and the associated cytoskeleton in interactions with microbial pathogens, nitrogen-fixing rhizobia and mycorrhiza fungi. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

  10. Desipramine induces disorder in cholesterol-rich membranes: implications for viral trafficking

    Science.gov (United States)

    Pakkanen, Kirsi; Salonen, Emppu; Mäkelä, Anna R.; Oker-Blom, Christian; Vattulainen, Ilpo; Vuento, Matti

    2009-12-01

    In this study, the effect of desipramine (DMI) on phospholipid bilayers and parvoviral entry was elucidated. In atomistic molecular dynamics simulations, DMI was found to introduce disorder in cholesterol-rich phospholipid bilayers. This was manifested by a decrease in the deuterium order parameter SCD as well as an increase in the membrane area. Disordering of the membrane suggested DMI to destabilize cholesterol-rich membrane domains (rafts) in cellular conditions. To relate the raft disrupting ability of DMI with novel biological relevance, we studied the intracellular effect of DMI using canine parvovirus (CPV), a virus known to interact with endosomal membranes and sphingomyelin, as an intracellular probe. DMI was found to cause retention of the virus in intracellular vesicular structures leading to the inhibition of viral proliferation. This implies that DMI has a deleterious effect on the viral traffic. As recycling endosomes and the internal vesicles of multivesicular bodies are known to contain raft components, the effect of desipramine beyond the plasma membrane step could be caused by raft disruption leading to impaired endosomal function and possibly have direct influence on the penetration of the virus through an endosomal membrane.

  11. Desipramine induces disorder in cholesterol-rich membranes: implications for viral trafficking

    International Nuclear Information System (INIS)

    Pakkanen, Kirsi; Mäkelä, Anna R; Oker-Blom, Christian; Vuento, Matti; Salonen, Emppu; Vattulainen, Ilpo

    2009-01-01

    In this study, the effect of desipramine (DMI) on phospholipid bilayers and parvoviral entry was elucidated. In atomistic molecular dynamics simulations, DMI was found to introduce disorder in cholesterol-rich phospholipid bilayers. This was manifested by a decrease in the deuterium order parameter S CD as well as an increase in the membrane area. Disordering of the membrane suggested DMI to destabilize cholesterol-rich membrane domains (rafts) in cellular conditions. To relate the raft disrupting ability of DMI with novel biological relevance, we studied the intracellular effect of DMI using canine parvovirus (CPV), a virus known to interact with endosomal membranes and sphingomyelin, as an intracellular probe. DMI was found to cause retention of the virus in intracellular vesicular structures leading to the inhibition of viral proliferation. This implies that DMI has a deleterious effect on the viral traffic. As recycling endosomes and the internal vesicles of multivesicular bodies are known to contain raft components, the effect of desipramine beyond the plasma membrane step could be caused by raft disruption leading to impaired endosomal function and possibly have direct influence on the penetration of the virus through an endosomal membrane

  12. Control of distributed heat transfer mechanisms in membrane distillation plants

    KAUST Repository

    Laleg-Kirati, Taous-Meriem

    2017-01-05

    Various examples are provided that are related to boundary control in membrane distillation (MD) processes. In one example, a system includes a membrane distillation (MD) process comprising a feed side and a permeate side separated by a membrane boundary layer; and processing circuitry configured to control a water production rate of the MD process based at least in part upon a distributed heat transfer across the membrane boundary layer. In another example, a method includes determining a plurality of estimated temperature states of a membrane boundary layer separating a feed side and a permeate side of a membrane distillation (MD) process; and adjusting inlet flow rate or inlet temperature of at least one of the feed side or the permeate side to maintain a difference temperature along the membrane boundary layer about a defined reference temperature based at least in part upon the plurality of estimated temperature states.

  13. Munc13-4 Is a Rab11-binding Protein That Regulates Rab11-positive Vesicle Trafficking and Docking at the Plasma Membrane.

    Science.gov (United States)

    Johnson, Jennifer L; He, Jing; Ramadass, Mahalakshmi; Pestonjamasp, Kersi; Kiosses, William B; Zhang, Jinzhong; Catz, Sergio D

    2016-02-12

    The small GTPase Rab11 and its effectors control trafficking of recycling endosomes, receptor replenishment and the up-regulation of adhesion and adaptor molecules at the plasma membrane. Despite recent advances in the understanding of Rab11-regulated mechanisms, the final steps mediating docking and fusion of Rab11-positive vesicles at the plasma membrane are not fully understood. Munc13-4 is a docking factor proposed to regulate fusion through interactions with SNAREs. In hematopoietic cells, including neutrophils, Munc13-4 regulates exocytosis in a Rab27a-dependent manner, but its possible regulation of other GTPases has not been explored in detail. Here, we show that Munc13-4 binds to Rab11 and regulates the trafficking of Rab11-containing vesicles. Using a novel Time-resolved Fluorescence Resonance Energy Transfer (TR-FRET) assay, we demonstrate that Munc13-4 binds to Rab11a but not to dominant negative Rab11a. Immunoprecipitation analysis confirmed the specificity of the interaction between Munc13-4 and Rab11, and super-resolution microscopy studies support the interaction of endogenous Munc13-4 with Rab11 at the single molecule level in neutrophils. Vesicular dynamic analysis shows the common spatio-temporal distribution of Munc13-4 and Rab11, while expression of a calcium binding-deficient mutant of Munc13-4 significantly affected Rab11 trafficking. Munc13-4-deficient neutrophils showed normal endocytosis, but the trafficking, up-regulation, and retention of Rab11-positive vesicles at the plasma membrane was significantly impaired. This correlated with deficient NADPH oxidase activation at the plasma membrane in response to Rab11 interference. Our data demonstrate that Munc13-4 is a Rab11-binding partner that regulates the final steps of Rab11-positive vesicle docking at the plasma membrane. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Hypothesis review: are clathrin-mediated endocytosis and clathrin-dependent membrane and protein trafficking core pathophysiological processes in schizophrenia and bipolar disorder?

    LENUS (Irish Health Repository)

    2012-02-01

    Clathrin-mediated endocytosis (CME) is the best-characterized mechanism governing cellular membrane and protein trafficking. In this hypothesis review, we integrate recent evidence implicating CME and related cellular trafficking mechanisms in the pathophysiology of psychotic disorders such as schizophrenia and bipolar disorder. The evidence includes proteomic and genomic findings implicating proteins and genes of the clathrin interactome. Additionally, several important candidate genes for schizophrenia, such as dysbindin, are involved in processes closely linked to CME and membrane trafficking. We discuss that key aspects of psychosis neuropathology such as synaptic dysfunction, white matter changes and aberrant neurodevelopment are all influenced by clathrin-dependent processes, and that other cellular trafficking mechanisms previously linked to psychoses interact with the clathrin interactome in important ways. Furthermore, many antipsychotic drugs have been shown to affect clathrin-interacting proteins. We propose that the targeted pharmacological manipulation of the clathrin interactome may offer fruitful opportunities for novel treatments of schizophrenia.Molecular Psychiatry advance online publication, 11 October 2011; doi:10.1038\\/mp.2011.123.

  15. Multifaceted Roles of ALG-2 in Ca2+-Regulated Membrane Trafficking

    Directory of Open Access Journals (Sweden)

    Masatoshi Maki

    2016-08-01

    Full Text Available ALG-2 (gene name: PDCD6 is a penta-EF-hand Ca2+-binding protein and interacts with a variety of proteins in a Ca2+-dependent fashion. ALG-2 recognizes different types of identified motifs in Pro-rich regions by using different hydrophobic pockets, but other unknown modes of binding are also used for non-Pro-rich proteins. Most ALG-2-interacting proteins associate directly or indirectly with the plasma membrane or organelle membranes involving the endosomal sorting complex required for transport (ESCRT system, coat protein complex II (COPII-dependent ER-to-Golgi vesicular transport, and signal transduction from membrane receptors to downstream players. Binding of ALG-2 to targets may induce conformational change of the proteins. The ALG-2 dimer may also function as a Ca2+-dependent adaptor to bridge different partners and connect the subnetwork of interacting proteins.

  16. Ultrahigh Flux Thin Film Boiling Heat Transfer Through Nanoporous Membranes.

    Science.gov (United States)

    Wang, Qingyang; Chen, Renkun

    2018-05-09

    Phase change heat transfer is fundamentally important for thermal energy conversion and management, such as in electronics with power density over 1 kW/cm 2 . The critical heat flux (CHF) of phase change heat transfer, either evaporation or boiling, is limited by vapor flux from the liquid-vapor interface, known as the upper limit of heat flux. This limit could in theory be greater than 1 kW/cm 2 on a planar surface, but its experimental realization has remained elusive. Here, we utilized nanoporous membranes to realize a new "thin film boiling" regime that resulted in an unprecedentedly high CHF of over 1.2 kW/cm 2 on a planar surface, which is within a factor of 4 of the theoretical limit, and can be increased to a higher value if mechanical strength of the membranes can be improved (demonstrated with 1.85 kW/cm 2 CHF in this work). The liquid supply is achieved through a simple nanoporous membrane that supports the liquid film where its thickness automatically decreases as heat flux increases. The thin film configuration reduces the conductive thermal resistance, leads to high frequency bubble departure, and provides separate liquid-vapor pathways, therefore significantly enhances the heat transfer. Our work provides a new nanostructuring approach to achieve ultrahigh heat flux in phase change heat transfer and will benefit both theoretical understanding and application in thermal management of high power devices of boiling heat transfer.

  17. The cysteines of the extracellular loop are crucial for trafficking of human organic cation transporter 2 to the plasma membrane and are involved in oligomerization.

    Science.gov (United States)

    Brast, Sabine; Grabner, Alexander; Sucic, Sonja; Sitte, Harald H; Hermann, Edwin; Pavenstädt, Hermann; Schlatter, Eberhard; Ciarimboli, Giuliano

    2012-03-01

    Human organic cation transporter 2 (hOCT2) is involved in transport of many endogenous and exogenous organic cations, mainly in kidney and brain cells. Because the quaternary structure of transmembrane proteins plays an essential role for their cellular trafficking and function, we investigated whether hOCT2 forms oligomeric complexes, and if so, which part of the transporter is involved in the oligomerization. A yeast 2-hybrid mating-based split-ubiquitin system (mbSUS), fluorescence resonance energy transfer, Western blot analysis, cross-linking experiments, immunofluorescence, and uptake measurements of the fluorescent organic cation 4-(4-(dimethylamino)styryl)-N-methylpyridinium were applied to human embryonic kidney 293 (HEK293) cells transfected with hOCT2 and partly also to freshly isolated human proximal tubules. The role of cysteines for oligomerization and trafficking of the transporter to the plasma membranes was investigated in cysteine mutants of hOCT2. hOCT2 formed oligomers both in the HEK293 expression system and in native human kidneys. The cysteines of the large extracellular loop are important to enable correct folding, oligomeric assembly, and plasma membrane insertion of hOCT2. Mutation of the first and the last cysteines of the loop at positions 51 and 143 abolished oligomer formation. Thus, the cysteines of the extracellular loop are important for correct trafficking of the transporter to the plasma membrane and for its oligomerization.

  18. Heme in pathophysiology: a matter of scavenging, metabolism and trafficking across cell membranes

    OpenAIRE

    Chiabrando, Deborah; Vinchi, Francesca; Fiorito, Veronica; Mercurio, Sonia; Tolosano, Emanuela

    2014-01-01

    Heme (iron-protoporphyrin IX) is an essential co-factor involved in multiple biological processes: oxygen transport and storage, electron transfer, drug and steroid metabolism, signal transduction, and micro RNA processing. However, excess free-heme is highly toxic due to its ability to promote oxidative stress and lipid peroxidation, thus leading to membrane injury and, ultimately, apoptosis. Thus, heme metabolism needs to be finely regulated. Intracellular heme amount is controlled at multi...

  19. Cholesterol trafficking and raft-like membrane domain composition mediate scavenger receptor class B type 1-dependent lipid sensing in intestinal epithelial cells.

    Science.gov (United States)

    Morel, Etienne; Ghezzal, Sara; Lucchi, Géraldine; Truntzer, Caroline; Pais de Barros, Jean-Paul; Simon-Plas, Françoise; Demignot, Sylvie; Mineo, Chieko; Shaul, Philip W; Leturque, Armelle; Rousset, Monique; Carrière, Véronique

    2018-02-01

    Scavenger receptor Class B type 1 (SR-B1) is a lipid transporter and sensor. In intestinal epithelial cells, SR-B1-dependent lipid sensing is associated with SR-B1 recruitment in raft-like/ detergent-resistant membrane domains and interaction of its C-terminal transmembrane domain with plasma membrane cholesterol. To clarify the initiating events occurring during lipid sensing by SR-B1, we analyzed cholesterol trafficking and raft-like domain composition in intestinal epithelial cells expressing wild-type SR-B1 or the mutated form SR-B1-Q445A, defective in membrane cholesterol binding and signal initiation. These features of SR-B1 were found to influence both apical cholesterol efflux and intracellular cholesterol trafficking from plasma membrane to lipid droplets, and the lipid composition of raft-like domains. Lipidomic analysis revealed likely participation of d18:0/16:0 sphingomyelin and 16:0/0:0 lysophosphatidylethanolamine in lipid sensing by SR-B1. Proteomic analysis identified proteins, whose abundance changed in raft-like domains during lipid sensing, and these included molecules linked to lipid raft dynamics and signal transduction. These findings provide new insights into the role of SR-B1 in cellular cholesterol homeostasis and suggest molecular links between SR-B1-dependent lipid sensing and cell cholesterol and lipid droplet dynamics. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Hydrogen-rich saline controls remifentanil-induced hypernociception and NMDA receptor NR1 subunit membrane trafficking through GSK-3β in the DRG in rats.

    Science.gov (United States)

    Zhang, Linlin; Shu, Ruichen; Wang, Chunyan; Wang, Haiyun; Li, Nan; Wang, Guolin

    2014-07-01

    Although NMDAR trafficking mediated by GSK-3β involvement in transmission of pronociceptive messages in the spinal cord has been confirmed by our previous studies, whether NMDAR trafficking is implicated in peripheral sensitization remains equivocal. It is demonstrated that inflammation is associated with spinal NMDAR-containing nociceptive neurons activation and the maintenance of opioid induced pain hypersensitivity. However, whether and how hydrogen-rich saline, as an effective anti-inflammatory drug, could prevent hyperalgesia through affecting peripheral sensitization caused by NMDAR activation remains to be explored. To test these effects, hydrogen-rich saline (2.5, 5 or 10 ml/kg) was administrated intraperitoneally after remifentanil infusion, NMDAR antagonist MK-801 or GSK-3β inhibitor TDZD-8 was administrated intravenously before remifentanil infusion in rats. We examined time course of hydrogen concentration in blood after hydrogen-rich saline administration. Mechanical and thermal hyperalgesia were evaluated by measuring PWT and PWL for 48 post-infusion hours, respectively. Western blotting and real-time qPCR assay were applied to analyze the NR1 membrane trafficking, GSK-3β expression and activity in DRG. Inflammatory mediators (TNF-α, IL-1β, and IL-6) expressions in DRG were also analyzed. We found that NR1 membrane trafficking in DRG increased, possibly due to GSK-3β activation after remifentanil infusion. We also discovered that hydrogen-rich saline not 2.5 ml/kg but 5 and 10 ml/kg could dose-dependently attenuate mechanical and thermal hyperalgesia without affecting baseline nociceptive threshold, reduce expressions of inflammatory mediators (TNF-α, IL-1β, and IL-6) and decrease NR1 trafficking mediated by GSK-3β, and minimal effective concentration was observed to be higher than 10 μmol/L, namely peak concentration in arterial blood after administration of HRS 2.5 ml/kg without any influence on hyperalgesia. Our results indicated that

  1. Small interference RNA profiling reveals the essential role of human membrane trafficking genes in mediating the infectious entry of dengue virus

    Directory of Open Access Journals (Sweden)

    Chu Justin

    2010-02-01

    Full Text Available Abstract Background Dengue virus (DENV is the causative agent of Dengue fever and the life-threatening Dengue Haemorrhagic fever or Dengue shock syndrome. In the absence of anti-viral agents or vaccine, there is an urgent need to develop an effective anti-viral strategy against this medically important viral pathogen. The initial interplay between DENV and the host cells may represent one of the potential anti-viral targeting sites. Currently the involvements of human membrane trafficking host genes or factors that mediate the infectious cellular entry of dengue virus are not well defined. Results In this study, we have used a targeted small interfering RNA (siRNA library to identify and profile key cellular genes involved in processes of endocytosis, cytoskeletal dynamics and endosome trafficking that are important and essential for DENV infection. The infectious entry of DENV into Huh7 cells was shown to be potently inhibited by siRNAs targeting genes associated with clathrin-mediated endocytosis. The important role of clathrin-mediated endocytosis was confirmed by the expression of well-characterized dominant-negative mutants of genes in this pathway and by using the clathrin endocytosis inhibitor chlorpromazine. Furthermore, DENV infection was shown to be sensitive to the disruption of human genes in regulating the early to late endosomal trafficking as well as the endosomal acidic pH. The importance and involvement of both actin and microtubule dynamics in mediating the infectious entry of DENV was also revealed in this study. Conclusions Together, the findings from this study have provided a detail profiling of the human membrane trafficking cellular genes and the mechanistic insight into the interplay of these host genes with DENV to initiate an infection, hence broadening our understanding on the entry pathway of this medically important viral pathogen. These data may also provide a new potential avenue for development of anti

  2. Ion track membranes providing heat pipe surfaces with capillary structures

    International Nuclear Information System (INIS)

    Akapiev, G.N.; Dmitriev, S.N.; Erler, B.; Shirkova, V.V.; Schulz, A.; Pietsch, H.

    2003-01-01

    The microgalvanic method for metal filling of etched ion tracks in organic foils is of particular interest for the fabrication of microsized structures. Microstructures like copper whiskers with a high aspect ratio produced in ion track membranes are suitable for the generation of high-performance heat transfer surfaces. A surface with good heat transfer characteristics is defined as a surface on which a small temperature difference causes a large heat transfer from the surface material to the liquid. It is well-known that a porous surface layer transfers to an evaporating liquid a given quantity of heat at a smaller temperature difference than does a usual smooth surface. Copper whiskers with high aspect ratio and a density 10 5 per cm 2 form such a porous structure, which produces strong capillary forces and therefore a maximum of heat transfer coefficients

  3. Improving Nanofiber Membrane Characteristics and Membrane Distillation Performance of Heat-Pressed Membranes via Annealing Post-Treatment

    Directory of Open Access Journals (Sweden)

    Minwei Yao

    2017-01-01

    Full Text Available Electrospun membranes are gaining interest for use in membrane distillation (MD due to their high porosity and interconnected pore structure; however, they are still susceptible to wetting during MD operation because of their relatively low liquid entry pressure (LEP. In this study, post-treatment had been applied to improve the LEP, as well as its permeation and salt rejection efficiency. The post-treatment included two continuous procedures: heat-pressing and annealing. In this study, annealing was applied on the membranes that had been heat-pressed. It was found that annealing improved the MD performance as the average flux reached 35 L/m2·h or LMH (>10% improvement of the ones without annealing while still maintaining 99.99% salt rejection. Further tests on LEP, contact angle, and pore size distribution explain the improvement due to annealing well. Fourier transform infrared spectroscopy and X-ray diffraction analyses of the membranes showed that there was an increase in the crystallinity of the polyvinylidene fluoride-co-hexafluoropropylene (PVDF-HFP membrane; also, peaks indicating the α phase of polyvinylidene fluoride (PVDF became noticeable after annealing, indicating some β and amorphous states of polymer were converted into the α phase. The changes were favorable for membrane distillation as the non-polar α phase of PVDF reduces the dipolar attraction force between the membrane and water molecules, and the increase in crystallinity would result in higher thermal stability. The present results indicate the positive effect of the heat-press followed by an annealing post-treatment on the membrane characteristics and MD performance.

  4. Novel role for proteinase-activated receptor 2 (PAR2) in membrane trafficking of proteinase-activated receptor 4 (PAR4).

    Science.gov (United States)

    Cunningham, Margaret R; McIntosh, Kathryn A; Pediani, John D; Robben, Joris; Cooke, Alexandra E; Nilsson, Mary; Gould, Gwyn W; Mundell, Stuart; Milligan, Graeme; Plevin, Robin

    2012-05-11

    Proteinase-activated receptors 4 (PAR(4)) is a class A G protein-coupled receptor (GPCR) recognized through the ability of serine proteases such as thrombin and trypsin to mediate receptor activation. Due to the irreversible nature of activation, a fresh supply of receptor is required to be mobilized to the cell surface for responsiveness to agonist to be sustained. Unlike other PAR subtypes, the mechanisms regulating receptor trafficking of PAR(4) remain unknown. Here, we report novel features of the intracellular trafficking of PAR(4) to the plasma membrane. PAR(4) was poorly expressed at the plasma membrane and largely retained in the endoplasmic reticulum (ER) in a complex with the COPI protein subunit β-COP1. Analysis of the PAR(4) protein sequence identified an arginine-based (RXR) ER retention sequence located within intracellular loop-2 (R(183)AR → A(183)AA), mutation of which allowed efficient membrane delivery of PAR(4). Interestingly, co-expression with PAR(2) facilitated plasma membrane delivery of PAR(4), an effect produced through disruption of β-COP1 binding and facilitation of interaction with the chaperone protein 14-3-3ζ. Intermolecular FRET studies confirmed heterodimerization between PAR(2) and PAR(4). PAR(2) also enhanced glycosylation of PAR(4) and activation of PAR(4) signaling. Our results identify a novel regulatory role for PAR(2) in the anterograde traffic of PAR(4). PAR(2) was shown to both facilitate and abrogate protein interactions with PAR(4), impacting upon receptor localization and cell signal transduction. This work is likely to impact markedly upon the understanding of the receptor pharmacology of PAR(4) in normal physiology and disease.

  5. Heat transfer in a membrane assisted fluidised bed with immersed horizontal tubes

    NARCIS (Netherlands)

    Deshmukh, S.A.R.K.; Volkers, S.; van Sint Annaland, M.; Kuipers, J.A.M.

    2004-01-01

    The effect of gas permeation through horizontally immersed membrane tubes on the heat transfer characteristics in a membrane assisted fluidised bed was investigated experimentally. Local time-averaged heat transfer coefficients from copper tubes arranged in a staggered formation with the membrane

  6. 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…

  7. Loss-of-function of the ciliopathy protein Cc2d2a disorganizes the vesicle fusion machinery at the periciliary membrane and indirectly affects Rab8-trafficking in zebrafish photoreceptors.

    Science.gov (United States)

    Ojeda Naharros, Irene; Gesemann, Matthias; Mateos, José M; Barmettler, Gery; Forbes, Austin; Ziegler, Urs; Neuhauss, Stephan C F; Bachmann-Gagescu, Ruxandra

    2017-12-01

    Ciliopathies are human disorders caused by dysfunction of primary cilia, ubiquitous organelles involved in transduction of environmental signals such as light sensation in photoreceptors. Concentration of signal detection proteins such as opsins in the ciliary membrane is achieved by RabGTPase-regulated polarized vesicle trafficking and by a selective barrier at the ciliary base, the transition zone (TZ). Dysfunction of the TZ protein CC2D2A causes Joubert/Meckel syndromes in humans and loss of ciliary protein localization in animal models, including opsins in retinal photoreceptors. The link between the TZ and upstream vesicle trafficking has been little explored to date. Moreover, the role of the small GTPase Rab8 in opsin-carrier vesicle (OCV) trafficking has been recently questioned in a mouse model. Using correlative light and electron microscopy and live imaging in zebrafish photoreceptors, we provide the first live characterization of Rab8-mediated trafficking in photoreceptors in vivo. Our results support a possibly redundant role for both Rab8a/b paralogs in OCV trafficking, based on co-localization of Rab8 and opsins in vesicular structures, and joint movement of Rab8-tagged particles with opsin. We further investigate the role of the TZ protein Cc2d2a in Rab8-mediated trafficking using cc2d2a zebrafish mutants and identify a requirement for Cc2d2a in the latest step of OCV trafficking, namely vesicle fusion. Progressive accumulation of opsin-containing vesicles in the apical portion of photoreceptors lacking Cc2d2a is caused by disorganization of the vesicle fusion machinery at the periciliary membrane with mislocalization and loss of the t-SNAREs SNAP25 and Syntaxin3 and of the exocyst component Exoc4. We further observe secondary defects on upstream Rab8-trafficking with cytoplasmic accumulation of Rab8. Taken together, our results support participation of Rab8 in OCV trafficking and identify a novel role for the TZ protein Cc2d2a in fusion of incoming

  8. 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

  9. 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’.

  10. Dynamic trafficking and delivery of connexons to the plasma membrane and accretion to gap junctions in living cells

    NARCIS (Netherlands)

    Lauf, Undine; Giepmans, Ben N G; Lopez, Patricia; Braconnot, Sebastien; Chen, Shu-Chih; Falk, Matthias M

    2002-01-01

    Certain membrane channels including acetylcholine receptors, gap junction (GJ) channels, and aquaporins arrange into large clusters in the plasma membrane (PM). However, how these channels are recruited to the clusters is unknown. To address this question, we have investigated delivery of GJ channel

  11. Control of distributed heat transfer mechanisms in membrane distillation plants

    KAUST Repository

    Laleg-Kirati, Taous-Meriem; Eleiwi, Fadi; Karam, Ayman M.

    2017-01-01

    Various examples are provided that are related to boundary control in membrane distillation (MD) processes. In one example, a system includes a membrane distillation (MD) process comprising a feed side and a permeate side separated by a membrane

  12. Heat transfer in a membrane assisted fluidized bed with immersed horizontal tubes

    NARCIS (Netherlands)

    Deshmukh, S.A.R.K.; Volkers, Sander; van Sint Annaland, M.; Kuipers, J.A.M.

    2005-01-01

    The effect of gas permeation through horizontally immersed membrane tubes on the heat transfer characteristics in a membrane assisted fluidized bed operated in the bubbling fluidization regime was investigated experimentally. Local time-averaged heat transfer coefficients from copper tubes arranged

  13. Arabidopsis cortical microtubules position cellulose synthase delivery to the plasma membrane and interact with cellulose synthase trafficking compartments.

    NARCIS (Netherlands)

    Gutierrez, R.; Lindeboom, J.J.; Paredez, A.R.; Emons, A.M.C.; Ehrhardt, D.W.

    2009-01-01

    Plant cell morphogenesis relies on the organization and function of two polymer arrays separated by the plasma membrane: the cortical microtubule cytoskeleton and cellulose microfibrils in the cell wall. Studies using in vivo markers confirmed that one function of the cortical microtubule array is

  14. Not changes in membrane fluidity but proteotoxic stress triggers heat shock protein expression in Chlamydomonas reinhardtii.

    Science.gov (United States)

    Rütgers, Mark; Muranaka, Ligia Segatto; Schulz-Raffelt, Miriam; Thoms, Sylvia; Schurig, Juliane; Willmund, Felix; Schroda, Michael

    2017-12-01

    A conserved reaction of all organisms exposed to heat stress is an increased expression of heat shock proteins (HSPs). Several studies have proposed that HSP expression in heat-stressed plant cells is triggered by an increased fluidity of the plasma membrane. Among the main lines of evidence in support of this model are as follows: (a) the degree of membrane lipid saturation was higher in cells grown at elevated temperatures and correlated with a lower amplitude of HSP expression upon a temperature upshift, (b) membrane fluidizers induce HSP expression at physiological temperatures, and (c) membrane rigidifier dimethylsulfoxide dampens heat-induced HSP expression. Here, we tested whether this holds also for Chlamydomonas reinhardtii. We show that heat-induced HSP expression in cells grown at elevated temperatures was reduced because they already contained elevated levels of cytosolic HSP70A/90A that apparently act as negative regulators of heat shock factor 1. We find that membrane rigidifier dimethylsulfoxide impaired translation under heat stress conditions and that membrane fluidizer benzyl alcohol not only induced HSP expression but also caused protein aggregation. These findings support the classical model for the cytosolic unfolded protein response, according to which HSP expression is induced by the accumulation of unfolded proteins. Hence, the membrane fluidity model should be reconsidered. © 2017 John Wiley & Sons Ltd.

  15. AQP4 plasma membrane trafficking or channel gating is not significantly modulated by phosphorylation at C-terminal serine residues

    DEFF Research Database (Denmark)

    Assentoft, Mette; Larsen, Brian R; Olesen, Emma T B

    2014-01-01

    heterologous expression in Xenopus laevis oocytes (along with serine-to-aspartate mutants of the same residues to mimic a phosphorylation). None of the mutant AQP4 constructs displayed alterations in the unit water permeability. Thus phosphorylation of six different serine residues in the COOH terminus of AQP4....... Phosphorylation of aquaporins can regulate plasma membrane localization and, possibly, the unit water permeability via gating of the AQP channel itself. In vivo phosphorylation of six serine residues in the COOH terminus of AQP4 has been detected by mass spectrometry: Ser(276), Ser(285), Ser(315), Ser(316), Ser...

  16. The coiled-coil domain of MURC/cavin-4 is involved in membrane trafficking of caveolin-3 in cardiomyocytes.

    Science.gov (United States)

    Naito, Daisuke; Ogata, Takehiro; Hamaoka, Tetsuro; Nakanishi, Naohiko; Miyagawa, Kotaro; Maruyama, Naoki; Kasahara, Takeru; Taniguchi, Takuya; Nishi, Masahiro; Matoba, Satoaki; Ueyama, Tomomi

    2015-12-15

    Muscle-restricted coiled-coil protein (MURC), also referred to as cavin-4, is a member of the cavin family that works cooperatively with caveolins in caveola formation and function. Cavins are cytoplasmic proteins with coiled-coil domains and form heteromeric complexes, which are recruited to caveolae in cells expressing caveolins. Among caveolins, caveolin-3 (Cav3) is exclusively expressed in muscle cells, similar to MURC/cavin-4. In the heart, Cav3 overexpression contributes to cardiac protection, and its deficiency leads to progressive cardiomyopathy. Mutations in the MURC/cavin-4 gene have been identified in patients with dilated cardiomyopathy. In the present study, we show the role of MURC/cavin-4 as a caveolar component in the heart. In H9c2 cells, MURC/cavin-4 was localized at the plasma membrane, whereas a MURC/cavin-4 mutant lacking the coiled-coil domain (ΔCC) was primarily localized to the cytoplasm. ΔCC bound to Cav3 and impaired membrane localization of Cav3 in cardiomyocytes. Additionally, although ΔCC did not alter Cav3 mRNA expression, ΔCC decreased the Cav3 protein level. MURC/cavin-4 and ΔCC similarly induced cardiomyocyte hypertrophy; however, ΔCC showed higher hypertrophy-related fetal gene expression than MURC/cavin-4. ΔCC induced ERK activation in cardiomyocytes. Transgenic mice expressing ΔCC in the heart (ΔCC-Tg mice) showed impaired cardiac function accompanied by cardiomyocyte hypertrophy and marked interstitial fibrosis. Hearts from ΔCC-Tg mice showed a reduction of the Cav3 protein level and activation of ERK. These results suggest that MURC/cavin-4 requires its coiled-coil domain to target the plasma membrane and to stabilize Cav3 at the plasma membrane of cardiomyocytes and that MURC/cavin-4 functions as a crucial caveolar component to regulate cardiac function. Copyright © 2015 the American Physiological Society.

  17. Oxygen transport membrane system and method for transferring heat to catalytic/process reactors

    Science.gov (United States)

    Kelly, Sean M; Kromer, Brian R; Litwin, Michael M; Rosen, Lee J; Christie, Gervase Maxwell; Wilson, Jamie R; Kosowski, Lawrence W; Robinson, Charles

    2014-01-07

    A method and apparatus for producing heat used in a synthesis gas production is provided. The disclosed method and apparatus include a plurality of tubular oxygen transport membrane elements adapted to separate oxygen from an oxygen containing stream contacting the retentate side of the membrane elements. The permeated oxygen is combusted with a hydrogen containing synthesis gas stream contacting the permeate side of the tubular oxygen transport membrane elements thereby generating a reaction product stream and radiant heat. The present method and apparatus also includes at least one catalytic reactor containing a catalyst to promote the stream reforming reaction wherein the catalytic reactor is surrounded by the plurality of tubular oxygen transport membrane elements. The view factor between the catalytic reactor and the plurality of tubular oxygen transport membrane elements radiating heat to the catalytic reactor is greater than or equal to 0.5.

  18. Oxygen transport membrane system and method for transferring heat to catalytic/process reactors

    Science.gov (United States)

    Kelly, Sean M.; Kromer, Brian R.; Litwin, Michael M.; Rosen, Lee J.; Christie, Gervase Maxwell; Wilson, Jamie R.; Kosowski, Lawrence W.; Robinson, Charles

    2016-01-19

    A method and apparatus for producing heat used in a synthesis gas production process is provided. The disclosed method and apparatus include a plurality of tubular oxygen transport membrane elements adapted to separate oxygen from an oxygen containing stream contacting the retentate side of the membrane elements. The permeated oxygen is combusted with a hydrogen containing synthesis gas stream contacting the permeate side of the tubular oxygen transport membrane elements thereby generating a reaction product stream and radiant heat. The present method and apparatus also includes at least one catalytic reactor containing a catalyst to promote the steam reforming reaction wherein the catalytic reactor is surrounded by the plurality of tubular oxygen transport membrane elements. The view factor between the catalytic reactor and the plurality of tubular oxygen transport membrane elements radiating heat to the catalytic reactor is greater than or equal to 0.5

  19. Nonlinear observer-based Lyapunov boundary control of distributed heat transfer mechanisms for membrane distillation plant

    KAUST Repository

    Eleiwi, Fadi; Laleg-Kirati, Taous-Meriem

    2016-01-01

    , and seeks to maintain the temperature difference along the membrane boundaries around a sufficient level to promote water production. MD process is modeled with advection diffusion equation model in two dimensions, where the diffusion and convection heat

  20. Nonlinear Lyapunov-based boundary control of distributed heat transfer mechanisms in membrane distillation plant

    KAUST Repository

    Eleiwi, Fadi; Laleg-Kirati, Taous-Meriem

    2015-01-01

    This paper presents a nonlinear Lyapunov-based boundary control for the temperature difference of a membrane distillation boundary layers. The heat transfer mechanisms inside the process are modeled with a 2D advection-diffusion equation. The model

  1. Experimental Evaluation of a Total Heat Recovery Unit with Polymer Membrane Foils

    DEFF Research Database (Denmark)

    Fang, Lei; Yuan, Shu; Nie, Jinzhe

    2014-01-01

    A laboratory experimental study was conducted to investigate the energy performance of a total heat recovery unit using a polymer membranes heat exchanger. The study was conducted in twin climate chambers. One of the chambers simulated outdoor climate conditions and the other simulated the climate...... condition indoors. The airflows taken from the two chambers were connected into the total heat recovery unit and exchange heat in a polymer membrane foil heat exchanger installed inside the unit. The temperature and humidity of the air upstream and downstream of the heat exchanger were measured. Based...... on the measured temperature and humidity values, the temperature, humidity, and enthalpy efficiencies of the total heat recovery unit were calculated. The experiment was conducted in different combinations of outdoor climate conditions simulating warm and humid outdoor climates and air-conditioned indoor climate...

  2. Heat stress causes spatially-distinct membrane re-modelling in K562 leukemia cells.

    Directory of Open Access Journals (Sweden)

    Gábor Balogh

    Full Text Available Cellular membranes respond rapidly to various environmental perturbations. Previously we showed that modulations in membrane fluidity achieved by heat stress (HS resulted in pronounced membrane organization alterations which could be intimately linked to the expression and cellular distribution of heat shock proteins. Here we examine heat-induced membrane changes using several visualisation methods. With Laurdan two-photon microscopy we demonstrate that, in contrast to the enhanced formation of ordered domains in surface membranes, the molecular disorder is significantly elevated within the internal membranes of cells preexposed to mild HS. These results were compared with those obtained by anisotropy, fluorescence lifetime and electron paramagnetic resonance measurements. All probes detected membrane changes upon HS. However, the structurally different probes revealed substantially distinct alterations in membrane heterogeneity. These data call attention to the careful interpretation of results obtained with only a single label. Subtle changes in membrane microstructure in the decision-making of thermal cell killing could have potential application in cancer therapy.

  3. Nano-Pervaporation Membrane with Heat Exchanger Generates Medical-Grade Water

    Science.gov (United States)

    Tsai, Chung-Yi; Alexander, Jerry

    2009-01-01

    A nanoporous membrane is used for the pervaporation process in which potable water is maintained, at atmospheric pressure, on the feed side of the membrane. The water enters the non-pervaporation (NPV) membrane device where it is separated into two streams -- retentate water and permeated water. The permeated pure water is removed by applying low vapor pressure on the permeate side to create water vapor before condensation. This permeated water vapor is subsequently condensed by coming in contact with the cool surface of a heat exchanger with heat being recovered through transfer to the feed water stream.

  4. Membrane heat exchanger in HVAC energy recovery systems, systems energy analysis

    Energy Technology Data Exchange (ETDEWEB)

    Nasif, M. [School of Mechanical and Manufacturing Engineering, The University of New South Wales, Sydney, NSW 2052 (Australia); Opus International Consultants (New Zealand); AL-Waked, R. [Mechanical Engineering Department, Prince Mohammad Bin Fahd University (PMU), P.O. Box 1614, AlKhobar 31952 (Saudi Arabia); Morrison, G. [School of Mechanical and Manufacturing Engineering, The University of New South Wales, Sydney, NSW 2052 (Australia); Behnia, M. [School of Aerospace, Mechanical and Mechatronic Engineering, University of Sydney, NSW 2006 (Australia)

    2010-10-15

    The thermal performance of an enthalpy/membrane heat exchanger is experimentally investigated. The heat exchanger utilizes a 60gsm Kraft paper as the heat and moisture transfer surface for HVAC energy recovery. The heat exchanger sensible, latent and total effectiveness have been determined through temperature and moisture content measurements. The annual energy consumption of an air conditioner coupled with an enthalpy/membrane heat exchanger is also studied and compared with a conventional air conditioning cycle using in-house modified HPRate software. The heat exchanger effectiveness are used as thermal performance indicators and incorporated in the modified software. Energy analysis showed that an air conditioning system coupled with a membrane heat exchanger consumes less energy than a conventional air conditioning system in hot and humid climates where the latent load is high. It has been shown that in humid climate a saving of up to 8% in annual energy consumption can be achieved when membrane heat exchanger is used instead of a conventional HVAC system. (author)

  5. 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.

  6. Mass and Heat Transfer in Ion-Exchange Membranes Applicable to Solid Polymer Fuel Cells

    Energy Technology Data Exchange (ETDEWEB)

    Otteroey, M

    1996-04-01

    In this doctoral thesis, an improved emf method for determination of transference numbers of two counter ions in ion-exchange membranes is presented. Transference numbers were obtained as a continuous function of the composition. The method avoids problems with diffusion by using a stack of membranes. Water transference coefficients in ion-exchange membranes is discussed and reversible and irreversible water transfer is studied by emf methods. Efforts were made to get data relevant to the solid polymer fuel cell. The results support the findings of other researchers that the reversible water transfer is lower than earlier predicted. A chapter on the conductivity of ion-exchange membranes establishes a method to separate the very thin liquid layers surrounding the membranes in a stack. Using the method it was found that the conductivity is obtained with high accuracy and that the liquid layer in a membrane stack can contribute significantly to the total measured resistance. A four point impedance method was tested to measure the conductivity of membranes under fuel cell conditions. Finally, there is a discussion of reversible heat effects and heat transfer in ion-exchange membranes. 155 refs., 45 figs., 13 tabs.

  7. Mass and Heat Transfer Analysis of Membrane Humidifier with a Simple Lumped Mass Model

    International Nuclear Information System (INIS)

    Lee, Young Duk; Bae, Ho June; Ahn, Kook Young; Yu, Sang Seok; Hwang, Joon Young

    2009-01-01

    The performance of proton exchange membrane fuel cell (PEMFC) is seriously changed by the humidification condition which is intrinsic characteristics of the PEMFC. Typically, the humidification of fuel cell is carried out with internal or external humidifier. A membrane humidifier is applied to the external humidification of residential power generation fuel cell due to its convenience and high performance. In this study, a simple static model is constructed to understand the physical phenomena of the membrane humidifier in terms of geometric parameters and operating parameters. The model utilizes the concept of shell and tube heat exchanger but the model is also able to estimate the mass transport through the membrane. Model is constructed with FORTRAN under Matlab/Simulink □ environment to keep consistency with other components model which we already developed. Results shows that the humidity of wet gas and membrane thickness are critical parameters to improve the performance of the humidifier

  8. Membrane-based osmotic heat engine with organic solvent for enhanced power generation from low-grade heat.

    Science.gov (United States)

    Shaulsky, Evyatar; Boo, Chanhee; Lin, Shihong; Elimelech, Menachem

    2015-05-05

    We present a hybrid osmotic heat engine (OHE) system that uses draw solutions with an organic solvent for enhanced thermal separation efficiency. The hybrid OHE system produces sustainable energy by combining pressure-retarded osmosis (PRO) as a power generation stage and membrane distillation (MD) utilizing low-grade heat as a separation stage. While previous OHE systems employed aqueous electrolyte draw solutions, using methanol as a solvent is advantageous because methanol is highly volatile and has a lower heat capacity and enthalpy of vaporization than water. Hence, the thermal separation efficiency of a draw solution with methanol would be higher than that of an aqueous draw solution. In this study, we evaluated the performance of LiCl-methanol as a potential draw solution for a PRO-MD hybrid OHE system. The membrane transport properties as well as performance with LiCl-methanol draw solution were evaluated using thin-film composite (TFC) PRO membranes and compared to the results obtained with a LiCl-water draw solution. Experimental PRO methanol flux and maximum projected power density of 47.1 L m(-2) h(-1) and 72.1 W m(-2), respectively, were achieved with a 3 M LiCl-methanol draw solution. The overall efficiency of the hybrid OHE system was modeled by coupling the mass and energy flows between the thermal separation (MD) and power generation (PRO) stages under conditions with and without heat recovery. The modeling results demonstrate higher OHE energy efficiency with the LiCl-methanol draw solution compared to that with the LiCl-water draw solution under practical operating conditions (i.e., heat recovery<90%). We discuss the implications of the results for converting low-grade heat to power.

  9. Membrane-Based Osmotic Heat Engine with Organic Solvent for Enhanced Power Generation from Low-Grade Heat

    Energy Technology Data Exchange (ETDEWEB)

    Shaulsky, E; Boo, C; Lin, SH; Elimelech, M

    2015-05-05

    We present a hybrid osmotic heat engine (OHE) system that uses draw solutions with an organic solvent for enhanced thermal separation efficiency. The hybrid OHE system produces sustainable energy by combining pressure-retarded osmosis (PRO) as a power generation stage and membrane distillation (MD) utilizing low-grade heat as a separation stage. While previous OHE systems employed aqueous electrolyte draw solutions, using methanol as a solvent is advantageous because methanol is highly volatile and has a lower heat capacity and enthalpy of vaporization than water. Hence, the thermal separation efficiency of a draw solution with methanol would be higher than that of an aqueous draw solution. In this study, we evaluated the performance of LiCl-methanol as a potential draw solution for a PRO-MD hybrid OHE system. The membrane transport properties as well as performance with LiCl methanol draw solution were evaluated using thin-film composite (TFC) PRO membranes and compared to the results obtained with a LiCl water draw solution. Experimental PRO methanol flux and maximum projected power density of 47.1 L m(-2) h(-1) and 72.1 W m(-2), respectively, were achieved with a 3 M LiCl-methanol draw solution. The overall efficiency of the hybrid OHE system was modeled by coupling the mass and energy flows between the thermal separation (MD) and power generation (PRO) stages under conditions with and without heat recovery. The modeling results demonstrate higher ORE energy efficiency with the LiCl methanol draw solution compared to that with the LiCl water draw solution under practical operating conditions (i.e., heat recovery <90%). We discuss the implications of the results for converting low-grade heat to power.

  10. Brain-derived neurotrophic factor (BDNF) enhances GABA transport by modulating the trafficking of GABA transporter-1 (GAT-1) from the plasma membrane of rat cortical astrocytes

    DEFF Research Database (Denmark)

    Vaz, Sandra H; Jørgensen, Trine Nygaard; Cristóvão-Ferreira, Sofia

    2011-01-01

    /MAPK pathway and requires active adenosine A(2A) receptors. Transport through GAT-3 is not affected by BDNF. To elucidate if BDNF affects trafficking of GAT-1 in astrocytes, we generated and infected astrocytes with a functional mutant of the rat GAT-1 (rGAT-1) in which the hemagglutinin (HA) epitope...

  11. Heat-induced reorganization of the structure of photosystem II membranes: role of oxygen evolving complex.

    Science.gov (United States)

    Busheva, Mira; Tzonova, Iren; Stoitchkova, Katerina; Andreeva, Atanaska

    2012-12-05

    The sensitivity of the green plants' photosystem II (PSII) to high temperatures is investigated in PSII enriched membranes and in membranes, from which the oxygen evolving complex is removed. Using steady-state 77 K fluorescence and resonance Raman spectroscopy we analyze the interdependency between the temperature-driven changes in structure and energy distribution in the PSII supercomplex. The results show that the heat treatment induces different reduction of the 77 K fluorescence emission in both types of investigated membranes: (i) an additional considerable decrease of the overall fluorescence emission in Tris-washed membranes as compared to the native membranes; (ii) a transition point at 42°C(,) observed only in native membranes; (iii) a sharp reduction of the PSII core fluorescence in Tris-washed membranes at temperatures higher than 50°C; (iv) a 3 nm red-shift of F700 band's maximum in Tris-washed membranes already at 20°C and its further shift by 1 nm at temperature increase. Both treatments intensified their action by increasing the aggregation and dissociation of the peripheral light harvesting complexes. The oxygen-evolving complex, in addition to its main function to produce O(2), increases the thermal stability of PSII core by strengthening the connection between the core and the peripheral antenna proteins and by keeping their structural integrity. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. 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.

  13. Wettability modified nanoporous ceramic membrane for simultaneous residual heat and condensate recovery

    Science.gov (United States)

    Hu, H. W.; Tang, G. H.; Niu, D.

    2016-06-01

    Recovery of both latent heat and condensate from boiler flue gas is significant for improving boiler efficiency and water conservation. The condensation experiments are carried out to investigate the simultaneous heat and mass transfer across the nanoporous ceramic membranes (NPCMs) which are treated to be hydrophilic and hydrophobic surfaces using the semicontinuous supercritical reactions. The effects of typical parameters including coolant flow rate, vapor/nitrogen gas mixture temperature, water vapor volume fraction and transmembrane pressure on heat and mass transfer performance are studied. The experimental results show that the hydrophilic NPCM exhibits higher performances of condensation heat transfer and condensate recovery. However, the hydrophobic modification results in remarkable degradation of heat and condensate recovery from the mixture. Molecular dynamics simulations are conducted to establish a hydrophilic/hydrophobic nanopore/water liquid system, and the infiltration characteristics of the single hydrophilic/hydrophobic nanopore is revealed.

  14. Wettability modified nanoporous ceramic membrane for simultaneous residual heat and condensate recovery.

    Science.gov (United States)

    Hu, H W; Tang, G H; Niu, D

    2016-06-07

    Recovery of both latent heat and condensate from boiler flue gas is significant for improving boiler efficiency and water conservation. The condensation experiments are carried out to investigate the simultaneous heat and mass transfer across the nanoporous ceramic membranes (NPCMs) which are treated to be hydrophilic and hydrophobic surfaces using the semicontinuous supercritical reactions. The effects of typical parameters including coolant flow rate, vapor/nitrogen gas mixture temperature, water vapor volume fraction and transmembrane pressure on heat and mass transfer performance are studied. The experimental results show that the hydrophilic NPCM exhibits higher performances of condensation heat transfer and condensate recovery. However, the hydrophobic modification results in remarkable degradation of heat and condensate recovery from the mixture. Molecular dynamics simulations are conducted to establish a hydrophilic/hydrophobic nanopore/water liquid system, and the infiltration characteristics of the single hydrophilic/hydrophobic nanopore is revealed.

  15. Spore membrane(s) as the site of damage within heated Clostridium perfringens spores.

    Science.gov (United States)

    Flowers, R S; Adams, D M

    1976-02-01

    Clostridium perfringens spores were injured by ultrahigh-temperature treatment at 105 C for 5 min. Injury was manifested as an increased sensitivity to polymyxin and neomycin. Since many of the survivors could not germinate normally the ultrahigh-temperature-treated spores were sensitized to and germinated by lysozyme. Polymyxin reportedly acts upon the cell membrane. Neomycin may inhibit protein synthesis and has surface-active properties. Injured spores were increasingly sensitive to known surface-active agents, sodium lauryl sulfate, sodium deoxycholate, and Roccal, a quaternary ammonium compound. Injured spores sensitive to polymyxin and neomycin also were osmotically fragile and died during outgrowth in a liquid medium unless the medium was supplemented with 20% sucrose, 10% dextran, or 10% polyvinylpyrrolidone. The results suggested that a spore structure destined to become cell membrane or cell wall was the site of injury. Repair of injury during outgrowth in the presence of protein, deoxyribonucleic acid, ribonucleic acid and cell wall synthesis inhibitors was consistent with this hypothesis.

  16. 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.

  17. Comparative Membrane Proteomics Reveals a Nonannotated E. coli Heat Shock Protein.

    Science.gov (United States)

    Yuan, Peijia; D'Lima, Nadia G; Slavoff, Sarah A

    2018-01-09

    Recent advances in proteomics and genomics have enabled discovery of thousands of previously nonannotated small open reading frames (smORFs) in genomes across evolutionary space. Furthermore, quantitative mass spectrometry has recently been applied to analysis of regulated smORF expression. However, bottom-up proteomics has remained relatively insensitive to membrane proteins, suggesting they may have been underdetected in previous studies. In this report, we add biochemical membrane protein enrichment to our previously developed label-free quantitative proteomics protocol, revealing a never-before-identified heat shock protein in Escherichia coli K12. This putative smORF-encoded heat shock protein, GndA, is likely to be ∼36-55 amino acids in length and contains a predicted transmembrane helix. We validate heat shock-regulated expression of the gndA smORF and demonstrate that a GndA-GFP fusion protein cofractionates with the cell membrane. Quantitative membrane proteomics therefore has the ability to reveal nonannotated small proteins that may play roles in bacterial stress responses.

  18. Stress proteins in lymphocytes: Membrane stabilization does not affect the heat shock response

    International Nuclear Information System (INIS)

    Hughes, C.S.; Repasky, E.A.; Subjeck, J.R.

    1987-01-01

    Temperatures which have been used to induce heat shock proteins (hsps) have been at the upper physiologic limit or well above this limit. In addition, little attention has been given to the effects of physiologic heat exposures on hsp induction in lymphocytes. The author examined temperatures between 39 0 C and 41 0 C on protein synthesis in the following lymphoid cell lines and cells: BDK, EL-4, JM, DO.11, and in dispersed lymph nodes and thymic tissues. In these studies, 39.5 0 appears to be the threshold for hsp induction (as distinguished by gel electrophoresis). At this temperature the induction of the major hsps at 70 and 89 kDa are observed. Hsp 89 appears to be the most strongly induced in all cells examined. In JM cells, a human cell line, heat shock also induces hsp 68, the non-constitutive hsp at this size. These temperatures do not depress normal levels of protein synthesis. When stearic acid or cholesterol was added to lymphocyte cultures prior to heating (which stabilize membranes), hsp induction appears to occur in a manner indistinguishable from cells heated in normal media. This suggests that membrane fluidity (as influenced by these agents) does not affect or depress the heat shock response in these cells. Finally, the authors observed that 2-deoxyglucose and other inducers of glucose regulated proteins in fibroblasts also induce the major glucose regulated proteins in lymphocytes

  19. Analysis of a membrane-based condesate recovery heat exchanger (CRX)

    Science.gov (United States)

    Newbold, D.D.

    1993-01-01

    The development of a temperature and humidity control system that can remove heat and recover water vapor is key to the development of an Environmental Control and Life Support System (ECLSS). Large quantities of water vapor must be removed from air, and this operation has proven difficult in the absense of gravity. This paper presents the modeling results from a program to develop a novel membrane-based heat exchanger known as the condensate recovery heat exchanger (CRX). This device cools and dehumidifies humid air and simultaneously recovers water-vapor condensate. In this paper, the CRX is described and the results of an analysis of the heat- and mass-transfer characteristics of the device are given.

  20. 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.

  1. Influence of high range of mass transfer coefficient and convection heat transfer on direct contact membrane distillation performance

    KAUST Repository

    Lee, Jung Gil

    2017-11-03

    In order to improve water production of membrane distillation (MD), the development of high performance membrane having better mass transfer and enhancement of convection heat transfer in MD module have been continuously investigated. This paper presents the relationship between the heat and mass transfer resistance across the membrane and the performance improvement. Various ranges of mass transfer coefficient (MTC) from normal (0.3×10−6 to 2.1×10−6kg/m2sPa: currently available membranes) to high (>2.1×10−6kg/m2sPa: membranes under development) were simulated using an experimentally validated model at different ranges of convection heat transfer by varying the inlet flow rates and spacer enhancement factor. The effect of mass transfer and convection heat transfer on the MD performance parameters including temperature polarization coefficient (TPC), mean permeate flux, and specific energy consumption were investigated in a direct contact MD (DCMD) configuration. Results showed that improving the MTC at the low ranges is more important than that at the high ranges where the heat transfer resistance becomes dominant and hence the convection heat transfer coefficient must be increased. Therefore, an effort on designing MD modules using feed and permeate spacers and controlling the membrane surface roughness to increase the convection heat transfer and TPC in the channel aiming to enhance the flux is required because the currently developed mass transfer has almost reached the critical point.

  2. Regulation of Trafficking, Membrane Retention and Turnover of the Na+, HCO3- Co-Transporter NBCn1 in Epithelial Cells

    DEFF Research Database (Denmark)

    Olesen, Christina Wilkens

    normal conditions. Furthermore, we found that the small scaffolding protein RACK1 co-localizes with NBCn1 in membrane protrusions and is important for NBCn1 membrane stability. Collectively, the work in this thesis has contributed with new understanding of the mechanisms involved in cisplatin...

  3. 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...

  4. [Change in the lipid composition of the inner mitochondrial membranes in rat organs during adaptation to heat].

    Science.gov (United States)

    Zubareva, E V; Seferova, R I; Denisova, N A

    1991-01-01

    Under conditions of adaptation to heating lipid composition in mitochondrial membranes of rat inner tissues was altered as follows: an increase in relative concentration of plasmalogenous forms of phospholipids (kidney, heart) and in content of saturated fatty acids (liver tissue), a decrease in the index of fatty acids unsaturation and in the ratio of fatty acids omega-3/omega-6. The alterations observed enabled the membranes to keep sufficient amount of liquidity essential for functional activity of mitochondria in heating.

  5. 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...

  6. Nonlinear Lyapunov-based boundary control of distributed heat transfer mechanisms in membrane distillation plant

    KAUST Repository

    Eleiwi, Fadi

    2015-07-01

    This paper presents a nonlinear Lyapunov-based boundary control for the temperature difference of a membrane distillation boundary layers. The heat transfer mechanisms inside the process are modeled with a 2D advection-diffusion equation. The model is semi-descretized in space, and a nonlinear state-space representation is provided. The control is designed to force the temperature difference along the membrane sides to track a desired reference asymptotically, and hence a desired flux would be generated. Certain constraints are put on the control law inputs to be within an economic range of energy supplies. The effect of the controller gain is discussed. Simulations with real process parameters for the model, and the controller are provided. © 2015 American Automatic Control Council.

  7. 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.

  8. A heat pump driven and hollow fiber membrane-based liquid desiccant air dehumidification system: Modeling and experimental validation

    International Nuclear Information System (INIS)

    Zhang, Li-Zhi; Zhang, Ning

    2014-01-01

    A compression heat pump driven and membrane-based liquid desiccant air dehumidification system is presented. The dehumidifier and the regenerator are made of two hollow fiber membrane bundles packed in two shells. Water vapor can permeate through these membranes effectively, while the liquid desiccant droplets are prevented from cross-over. Simultaneous heating and cooling of the salt solution are realized with a heat pump system to improve energy efficiency. In this research, the system is built up and a complete modeling is performed for the system. Heat and mass transfer processes in the membrane modules, as well as in the evaporator, the condenser, and other key components are modeled in detail. The whole model is validated by experiment. The performances of SDP (specific dehumidification power), dehumidification efficiency, EER (energy efficiency ratio) of heat pump, and the COP (coefficient of performance) of the system are investigated numerically and experimentally. The results show that the model can predict the system accurately. The dehumidification capabilities and the energy efficiencies of the system are high. Further, it performs well even under the harsh hot and humid South China weather conditions. - Highlights: • A membrane-based and heat pump driven air dehumidification system is proposed. • A real experimental set up is built and used to validate the model for the whole system. • Performance under design and varying operation conditions is investigated. • The system performs well even under harsh hot and humid conditions

  9. A novel cogeneration system: A proton exchange membrane fuel cell coupled to a heat transformer

    International Nuclear Information System (INIS)

    Huicochea, A.; Romero, R.J.; Rivera, W.; Gutierrez-Urueta, G.; Siqueiros, J.; Pilatowsky, I.

    2013-01-01

    This study focuses on the potential of a novel cogeneration system which consists of a 5 kW proton exchange membrane fuel cell (PEMFC) and an absorption heat transformer (AHT). The dissipation heat resulting from the operation of the PEMFC would be used to feed the absorption heat transformer, which is integrated to a water purification system. Therefore, the products of the proposed cogeneration system are heat, electricity and distilled water. The study includes a simulation for the PEMFC as well as experimental results obtained with an experimental AHT facility. Based on the simulation results, experimental tests were performed in order to estimate the performance parameters of the overall system. This is possible due to the matching in power and temperatures between the outlet conditions of the simulated fuel cell and the inlet requirements of the AHT. Experimental coefficients of performance are reported for the AHT as well as the overall cogeneration efficiency for the integrated system. The results show that experimental values of coefficient of performance of the AHT and the overall cogeneration efficiency, can reach up to 0.256 and 0.571, respectively. This represents an increment in 12.4% of efficiency, compared to the fuel cell efficiency working individually. This study shows that the combined use of AHT systems with a PEMFC is possible and it is a very feasible project to be developed in the Centro de Investigación en Energía (Centre of Energy Research), México.

  10. 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.

  11. Nonlinear observer-based Lyapunov boundary control of distributed heat transfer mechanisms for membrane distillation plant

    KAUST Repository

    Eleiwi, Fadi

    2016-09-19

    This paper presents a nonlinear observer-based Lyapunov control for a membrane distillation (MD) process. The control considers the inlet temperatures of the feed and the permeate solutions as inputs, transforming it to boundary control process, and seeks to maintain the temperature difference along the membrane boundaries around a sufficient level to promote water production. MD process is modeled with advection diffusion equation model in two dimensions, where the diffusion and convection heat transfer mechanisms are best described. Model analysis, effective order reduction and parameters physical interpretation, are provided. Moreover, a nonlinear observer has been designed to provide the control with estimates of the temperature evolution at each time instant. In addition, physical constraints are imposed on the control to have an acceptable range of feasible inputs, and consequently, better energy consumption. Numerical simulations for the complete process with real membrane parameter values are provided, in addition to detailed explanations for the role of the controller and the observer. (C) 2016 Elsevier Ltd. All rights reserved.

  12. Dynamic Modeling and Control of Distributed Heat Transfer Mechanisms: Application to a Membrane Distillation Module

    KAUST Repository

    Eleiwi, Fadi

    2015-12-01

    Sustainable desalination technologies are the smart solution for producing fresh water and preserve the environment and energy by using sustainable renewable energy sources. Membrane distillation (MD) is an emerging technology which can be driven by renewable energy. It is an innovative method for desalinating seawater and brackish water with high quality production, and the gratitude is to its interesting potentials. MD includes a transfer of water vapor from a feed solution to a permeate solution through a micro-porous hydrophobic membrane, rejecting other non-volatile constituents present in the influent water. The process is driven by the temperature difference along the membrane boundaries. Different control applications and supervision techniques would improve the performance and the efficiency of the MD process, however controlling the MD process requires comprehensive mathematical model for the distributed heat transfer mechanisms inside the process. Our objective is to propose a dynamic mathematical model that accounts for the time evolution of the involved heat transfer mechanisms in the process, and to be capable of hosting intermittent energy supplies, besides managing the production rate of the process, and optimizing its energy consumption. Therefore, we propose the 2D Advection-Diffusion Equation model to account for the heat diffusion and the heat convection mechanisms inside the process. Furthermore, experimental validations have proved high agreement between model simulations and experiments with less than 5% relative error. Enhancing the MD production is an anticipated goal, therefore, two main control strategies are proposed. Consequently, we propose a nonlinear controller for a semi-discretized version of the dynamic model to achieve an asymptotic tracking for a desired temperature difference. Similarly, an observer-based feedback control is used to track sufficient temperature difference for better productivity. The second control strategy

  13. Myosins 1 and 6, myosin light chain kinase, actin and microtubules cooperate during antibody-mediated internalisation and trafficking of membrane-expressed viral antigens in feline infectious peritonitis virus infected monocytes.

    Science.gov (United States)

    Dewerchin, Hannah L; Desmarets, Lowiese M; Noppe, Ytse; Nauwynck, Hans J

    2014-02-12

    Monocytes infected with feline infectious peritonitis virus, a coronavirus, express viral proteins in their plasma membranes. Upon binding of antibodies, these proteins are quickly internalised through a new clathrin- and caveolae-independent internalisation pathway. By doing so, the infected monocytes can escape antibody-dependent cell lysis. In the present study, we investigated which kinases and cytoskeletal proteins are of importance during internalisation and subsequent intracellular transport. The experiments showed that myosin light chain kinase (MLCK) and myosin 1 are crucial for the initiation of the internalisation. With co-localisation stainings, it was found that MLCK and myosin 1 co-localise with antigens even before internalisation started. Myosin 6 co-localised with the internalising complexes during passage through the cortical actin, were it might play a role in moving or disintegrating actin filaments, to overcome the actin barrier. One minute after internalisation started, vesicles had passed the cortical actin, co-localised with microtubules and association with myosin 6 was lost. The vesicles were further transported over the microtubules and accumulated at the microtubule organising centre after 10 to 30 min. Intracellular trafficking over microtubules was mediated by MLCK, myosin 1 and a small actin tail. Since inhibiting MLCK with ML-7 was so efficient in blocking the internalisation pathway, this target can be used for the development of a new treatment for FIPV.

  14. 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...

  15. 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.

  16. Plasmonic heating from indium nanoparticles on a floating microporous membrane for enhanced solar seawater desalination.

    Science.gov (United States)

    Zhang, Lulu; Xing, Jun; Wen, Xinglin; Chai, Jianwei; Wang, Shijie; Xiong, Qihua

    2017-09-14

    Passive solar evaporation represents a promising and environmentally benign method of water purification/desalination. Plasmonic nanoparticles have been demonstrated as an effective approach for enhancing solar steam generation through a plasmonic heating effect, nonetheless the efficiency is constrained by unnecessary bulk heating of the entire liquid volume, while the noble metals commonly used are not cost-effective in terms of availability and their sophisticated preparation. Herein, a paper-like plasmonic device consisting of a microporous membrane and indium nanoparticles (In NPs/MPM) is fabricated through a simple thermal evaporation method. Due to the light-weight and porous nature of the device, the broadband light absorption properties, and theoretically the excellent plasmonic heating effect from In NP which could be even higher than gold, silver and aluminium nanoparticles, our device can effectively enhance solar water evaporation by floating on the water surface and its utility has been demonstrated in the solar desalination of a real seawater sample. The durability of the device in solar seawater desalination has also been investigated over multiple cycles with stable performances. This portable device could provide a solution for individuals to do water/seawater purification in under-developed areas with limited/no access to electricity or a centralized drinking water supply.

  17. 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

  18. Study of coupled heat and water transfer in proton exchange membrane fuel cells by the way of internal measurements

    International Nuclear Information System (INIS)

    Thomas, A; Maranzana, G; Didierjean, S; Dillet, J; Lottin, O

    2012-01-01

    Measurements of electrode temperatures within a proton exchange membrane fuel cell were performed using platinum wires. A temperature difference of 7°C between the electrodes and the bipolar plates was observed for a cell operating at a current density of 1.5 A.cm −2 . These measurements show a strong non-uniformity of the temperature profile through membrane electrode assembly (MEA) that future phenomenological models must take into account. In addition, the simultaneous measurements of heat and water flux through the MEA leads to the conclusion that produced water crosses the diffusion layer in vapor phase. A very simple heat transfer model is proposed.

  19. Association and dissociation of Escherichia coli heat-stable enterotoxin from rat brush border membrane receptors

    International Nuclear Information System (INIS)

    Cohen, M.B.; Thompson, M.R.; Overmann, G.J.; Giannella, R.A.

    1987-01-01

    Escherichia coli heat-stable enterotoxin (ST) binds to receptors on rat intestinal cells and brush border membranes (BBM). We devised experiments to examine the reversibility of ST binding. We found that both 125 I-labeled ST and native ST were spontaneously dissociable from the BBM receptor. Radiolabeled ST bound to BBM was also dissociated by the addition of avid goat anti-ST antiserum. Furthermore, using a computer program for analysis of ligand binding, we calculated an apparent Ka of 10(8) liters/mol from competitive inhibition and saturation-binding data. This is significantly lower than the value previously reported by others. Our findings, of a lower Ka and a reversible ST-binding process, suggest that a therapeutic strategy of removing bound ST from its receptor or competing with the enterocyte receptor for unbound ST might be successful in terminating ST-induced secretion

  20. Combinations of physiologic estrogens with xenoestrogens alter calcium and kinase responses, prolactin release, and membrane estrogen receptor trafficking in rat pituitary cells

    Directory of Open Access Journals (Sweden)

    Watson Cheryl S

    2010-10-01

    Full Text Available Abstract Background Xenoestrogens such as alkylphenols and the structurally related plastic byproduct bisphenol A have recently been shown to act potently via nongenomic signaling pathways and the membrane version of estrogen receptor-α. Though the responses to these compounds are typically measured individually, they usually contaminate organisms that already have endogenous estrogens present. Therefore, we used quantitative medium-throughput screening assays to measure the effects of physiologic estrogens in combination with these xenoestrogens. Methods We studied the effects of low concentrations of endogenous estrogens (estradiol, estriol, and estrone at 10 pM (representing pre-development levels, and 1 nM (representing higher cycle-dependent and pregnancy levels in combinations with the same levels of xenoestrogens in GH3/B6/F10 pituitary cells. These levels of xenoestrogens represent extremely low contamination levels. We monitored calcium entry into cells using Fura-2 fluorescence imaging of single cells. Prolactin release was measured by radio-immunoassay. Extracellular-regulated kinase (1 and 2 phospho-activations and the levels of three estrogen receptors in the cell membrane (ERα, ERβ, and GPER were measured using a quantitative plate immunoassay of fixed cells either permeabilized or nonpermeabilized (respectively. Results All xenoestrogens caused responses at these concentrations, and had disruptive effects on the actions of physiologic estrogens. Xenoestrogens reduced the % of cells that responded to estradiol via calcium channel opening. They also inhibited the activation (phosphorylation of extracellular-regulated kinases at some concentrations. They either inhibited or enhanced rapid prolactin release, depending upon concentration. These latter two dose-responses were nonmonotonic, a characteristic of nongenomic estrogenic responses. Conclusions Responses mediated by endogenous estrogens representing different life stages are

  1. 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

  2. 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

  3. Influence of high range of mass transfer coefficient and convection heat transfer on direct contact membrane distillation performance

    KAUST Repository

    Lee, Jung Gil; Jeong, Sanghyun; Alsaadi, Ahmad Salem; Ghaffour, NorEddine

    2017-01-01

    (>2.1×10−6kg/m2sPa: membranes under development) were simulated using an experimentally validated model at different ranges of convection heat transfer by varying the inlet flow rates and spacer enhancement factor. The effect of mass transfer

  4. Modulation of epithelial sodium channel trafficking and function by sodium 4-phenylbutyrate in human nasal epithelial cells.

    Science.gov (United States)

    Prulière-Escabasse, Virginie; Planès, Carole; Escudier, Estelle; Fanen, Pascale; Coste, André; Clerici, Christine

    2007-11-23

    Sodium 4-phenylbutyrate (4-PBA) has been shown to correct the cellular trafficking of several mutant or nonmutant plasma membrane proteins such as cystic fibrosis transmembrane conductance regulator through the expression of 70-kDa heat shock proteins. The objective of the study was to determine whether 4-PBA may influence the functional expression of epithelial sodium channels (ENaC) in human nasal epithelial cells (HNEC). Using primary cultures of HNEC, we demonstrate that 4-PBA (5 mm for 6 h) markedly stimulated amiloride-sensitive sodium channel activity and that this was related to an increased abundance of alpha-, beta-, and gamma-ENaC subunits in the apical membrane. The increase in ENaC cell surface expression (i) was due to insertion of newly ENaC subunits as determined by brefeldin A experiments and (ii) was not associated with cell surface retention of ENaC subunits because endocytosis of ENaC subunits was unchanged. In addition, we find that ENaC co-immunoprecipitated with the heat shock protein constitutively expressed Hsc70, that has been reported to modulate ENaC trafficking, and that 4-PBA decreased Hsc70 protein level. Finally, we report that in cystic fibrosis HNEC obtained from two cystic fibrosis patients, 4-PBA increased functional expression of ENaC as demonstrated by the increase in amiloride-sensitive sodium transport and in alpha-, beta-, and gamma-ENaC subunit expression in the apical membrane. Our results suggest that in HNEC, 4-PBA increases the functional expression of ENaC through the insertion of new alpha-, beta-, and gamma-ENaC subunits into the apical membrane and also suggest that 4-PBA could modify ENaC trafficking by reducing Hsc70 protein expression.

  5. Conversion of Stationary to Invasive Tumor Initiating Cells (TICs): Role of Hypoxia in Membrane Type 1-Matrix Metalloproteinase (MT1-MMP) Trafficking

    Science.gov (United States)

    Li, Jian; Zucker, Stanley; Pulkoski-Gross, Ashleigh; Kuscu, Cem; Karaayvaz, Mihriban; Ju, Jingfang; Yao, Herui; Song, Erwei; Cao, Jian

    2012-01-01

    Emerging evidence has implicated the role of tumor initiating cells (TICs) in the process of cancer metastasis. The mechanism underlying the conversion of TICs from stationary to invasive remains to be characterized. In this report, we employed less invasive breast cancer TICs, SK-3rd, that displays CD44high/CD24low with high mammosphere-forming and tumorigenic capacities, to investigate the mechanism by which stationary TICs are converted to invasive TICs. Invasive ability of SK-3rd TICs was markedly enhanced when the cells were cultured under hypoxic conditions. Given the role of membrane type 1-matrix metalloproteinase (MT1-MMP) in cancer invasion/metastasis, we explored a possible involvement of MT1-MMP in hypoxia-induced TIC invasion. Silencing of MT1-MMP by a shRNA approach resulted in diminution of hypoxia-induced cell invasion in vitro and metastasis in vivo. Under hypoxic conditions, MT1-MMP redistributed from cytoplasmic storage pools to the cell surface of TICs, which coincides with the increased cell invasion. In addition, CD44, a cancer stem-like cell marker, inversely correlated with increased cell surface MT1-MMP. Interestingly, cell surface MT1-MMP gradually disappeared when the hypoxia-treated cells were switched to normoxia, suggesting the plasticity of TICs in response to oxygen content. Furthermore, we dissected the pathways leading to upregulated MT1-MMP in cytoplasmic storage pools under normoxic conditions, by demonstrating a cascade involving Twist1-miR10b-HoxD10 leading to enhanced MT1-MMP expression in SK-3rd TICs. These observations suggest that MT1-MMP is a key molecule capable of executing conversion of stationary TICs to invasive TICs under hypoxic conditions and thereby controlling metastasis. PMID:22679501

  6. Supersymmetry of noncompact MQCD-like membrane instantons and heat kernel asymptotics

    International Nuclear Information System (INIS)

    Belani, Kanishka; Kaura, Payal; Misra, Aalok

    2006-01-01

    We perform a heat kernel asymptotics analysis of the nonperturbative superpotential obtained from wrapping of an M2-brane around a supersymmetric noncompact three-fold embedded in a (noncompact) G 2 -manifold as obtained, the three-fold being the one relevant to domain walls in Witten's MQCD, in the limit of small 'ζ', a complex constant that appears in the Riemann surfaces relevant to defining the boundary conditions for the domain wall in MQCD. The MQCD-like configuration is interpretable, for small but non-zero ζ as a noncompact/'large open membrane instanton, and for vanishing ζ, as the type IIA D0-brane (for vanishing M-theory circle radius). We find that the eta-function Seeley de-Witt coefficients vanish, and we get a perfect match between the zeta-function Seeley de-Witt coefficients (up to terms quadratic in ζ) between the Dirac-type operator and one of the two Laplace-type operators figuring in the superpotential. Given the dissimilar forms of the bosonic and the square of the fermionic operators, this is an extremely nontrivial check, from a spectral analysis point of view, of the expected residual supersymmetry for the nonperturbative configurations in M-theory considered in this work

  7. Response of membrane-bound ATPase of Micrococcus luteus to heat and ultraviolet light

    International Nuclear Information System (INIS)

    Volotovskij, J.; Risi, S.; Dose, K.

    1976-01-01

    It is shown that the properties of ATPase (EC 3.6.1.3) of Micrococcus luteus depend only to some extent on the state of the membrane to which it is attached. Its interaction with the membrane appears to be largely controlled by polar forces. It is shown, however, that the UV-sensitivity of the membrane-bound ATPase is also significantly influenced by the state of membrane lipids. (orig.) [de

  8. Response of membrane-bound ATPase of Micrococcus luteus to heat and ultraviolet light

    Energy Technology Data Exchange (ETDEWEB)

    Volotovskii, J; Risi, S; Dose, K [Mainz Univ. (F.R. Germany). Inst. fuer Biochemie

    1976-03-01

    It is shown that the properties of ATPase (EC 3.6.1.3) of Micrococcus luteus depend only to some extent on the state of the membrane to which it is attached. Its interaction with the membrane appears to be largely controlled by polar forces. It is shown, however, that the UV-sensitivity of the membrane-bound ATPase is also significantly influenced by the state of membrane lipids.

  9. Developing a theoretical model to investigate thermal performance of a thin membrane heat-pipe solar collector

    International Nuclear Information System (INIS)

    Riffat, S.B.; Zhao, X.; Doherty, P.S.

    2005-01-01

    A thin membrane heat-pipe solar collector was designed and constructed to allow heat from solar radiation to be collected at a relatively high efficiency while keeping the capital cost low. A theoretical model incorporating a set of heat balance equations was developed to analyse heat transfer processes occurring in separate regions of the collector, i.e., the top cover, absorber and condenser/manifold areas, and examine their relationship. The thermal performance of the collector was investigated using the theoretical model. The modelling predictions were validated using the experimental data from a referred source. The test efficiency was found to be in the range 40-70%, which is a bitter lower than the values predicted by modelling. The factors influencing these results were investigated

  10. Synergistic production of hydrogen using fossil fuels and nuclear energy application of nuclear-heated membrane reformer

    International Nuclear Information System (INIS)

    Hori, M.; Matsui, K.; Tashimo, M.; Yasuda, I.

    2004-01-01

    Processes and technologies to produce hydrogen synergistically by the steam reforming reaction using fossil fuels and nuclear heat are reviewed. Formulas of chemical reactions, required heats for reactions, saving of fuel consumption or reduction of carbon dioxide emission, possible processes and other prospects are examined for such fossil fuels as natural gas, petroleum and coal. The 'membrane reformer' steam reforming with recirculation of reaction products in a closed loop configuration is considered to be the most advantageous among various synergistic hydrogen production methods. Typical merits of this method are: nuclear heat supply at medium temperature below 600 deg. C, compact plant size and membrane area for hydrogen production, efficient conversion of feed fuel, appreciable reduction of carbon dioxide emission, high purity hydrogen without any additional process, and ease of separating carbon dioxide for future sequestration requirements. With all these benefits, the synergistic production of hydrogen by membrane reformer using fossil fuels and nuclear energy can be an effective solution in this century for the world which has to use. fossil fuels any way to some extent while reducing carbon dioxide emission. For both the fossil fuels industry and the nuclear industry, which are under constraint of resource, environment and economy, this production method will be a viable symbiosis strategy for the coming hydrogen economy era. (author)

  11. Membrane trafficking: ER export encounters dualism.

    Science.gov (United States)

    Barlowe, Charles

    2015-02-16

    Cytoplasmic coat protein complexes perform central roles in sorting protein constituents within the endomembrane system. A new study reveals that the COPII coat operates through dual recognition of signals in a sorting receptor and its bound cargo to promote efficient export from the endoplasmic reticulum. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. 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.

  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. 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.

  15. 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.

  16. Heat-And-Mass Transfer Relationship to Determine Shear Stress in Tubular Membrane Systems

    DEFF Research Database (Denmark)

    Ratkovich, Nicolas Rios; Nopens, Ingmar

    2012-01-01

    The main drawback of Membrane Bioreactors (MBRs) is the fouling of the membrane. One way to reduce this fouling is through controlling the hydrodynamics of the two-phase slug flow near the membrane surface. It has been proven in literature that the slug flow pattern has a higher scouring effect...... to remove particulates due to the high shear rates and high mass transfer between the membrane surface and the bulk region. However, to calculate the mass transfer coefficient in an efficient and accurate way is not straightforward. Indeed, for accurate determination, numerous complex experimental...

  17. 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.

  18. 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.

  19. Analysis of occludin trafficking, demonstrating continuous endocytosis, degradation, recycling and biosynthetic secretory trafficking.

    Directory of Open Access Journals (Sweden)

    Sarah J Fletcher

    Full Text Available Tight junctions (TJs link adjacent cells and are critical for maintenance of apical-basolateral polarity in epithelial monolayers. The TJ protein occludin functions in disparate processes, including wound healing and Hepatitis C Virus infection. Little is known about steady-state occludin trafficking into and out of the plasma membrane. Therefore, we determined the mechanisms responsible for occludin turnover in confluent Madin-Darby canine kidney (MDCK epithelial monolayers. Using various biotin-based trafficking assays we observed continuous and rapid endocytosis of plasma membrane localised occludin (the majority internalised within 30 minutes. By 120 minutes a significant reduction in internalised occludin was observed. Inhibition of lysosomal function attenuated the reduction in occludin signal post-endocytosis and promoted co-localisation with the late endocytic system. Using a similar method we demonstrated that ∼20% of internalised occludin was transported back to the cell surface. Consistent with these findings, significant co-localisation between internalised occludin and recycling endosomal compartments was observed. We then quantified the extent to which occludin synthesis and transport to the plasma membrane contributes to plasma membrane occludin homeostasis, identifying inhibition of protein synthesis led to decreased plasma membrane localised occludin. Significant co-localisation between occludin and the biosynthetic secretory pathway was demonstrated. Thus, under steady-state conditions occludin undergoes turnover via a continuous cycle of endocytosis, recycling and degradation, with degradation compensated for by biosynthetic exocytic trafficking. We developed a mathematical model to describe the endocytosis, recycling and degradation of occludin, utilising experimental data to provide quantitative estimates for the rates of these processes.

  20. 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.

  1. 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...

  2. Estradiol-induced estrogen receptor-alpha trafficking.

    Science.gov (United States)

    Bondar, Galyna; Kuo, John; Hamid, Naheed; Micevych, Paul

    2009-12-02

    Estradiol has rapid actions in the CNS that are mediated by membrane estrogen receptors (ERs) and activate cell signaling pathways through interaction with metabotropic glutamate receptors (mGluRs). Membrane-initiated estradiol signaling increases the free cytoplasmic calcium concentration ([Ca(2+)](i)) that stimulates the synthesis of neuroprogesterone in astrocytes. We used surface biotinylation to demonstrate that ERalpha has an extracellular portion. In addition to the full-length ERalpha [apparent molecular weight (MW), 66 kDa], surface biotinylation labeled an ERalpha-immunoreactive protein (MW, approximately 52 kDa) identified by both COOH- and NH(2)-directed antibodies. Estradiol treatment regulated membrane levels of both proteins in parallel: within 5 min, estradiol significantly increased membrane levels of the 66 and 52 kDa ERalpha. Internalization, a measure of membrane receptor activation, was also increased by estradiol with a similar time course. Continuous treatment with estradiol for 24-48 h reduced ERalpha levels, suggesting receptor downregulation. Estradiol also increased mGluR1a trafficking and internalization, consistent with the proposed ERalpha-mGluR1a interaction. Blocking ER with ICI 182,780 or mGluR1a with LY 367385 prevented ERalpha trafficking to and from the membrane. Estradiol-induced [Ca(2+)](i) flux was also significantly increased at the time of peak ERalpha activation/internalization. These results demonstrate that ERalpha is present in the membrane and has an extracellular portion. Furthermore, membrane levels and internalization of ERalpha are regulated by estradiol and mGluR1a ligands. The pattern of trafficking into and out of the membrane suggests that the changing concentration of estradiol during the estrous cycle regulates ERalpha to augment and then terminate membrane-initiated signaling.

  3. Estradiol-induced estrogen receptor-α trafficking

    Science.gov (United States)

    Bondar, Galyna; Kuo, John; Hamid, Naheed; Micevych, Paul

    2010-01-01

    Estradiol has rapid actions in the central nervous system, which are mediated by membrane estrogen receptors (ERs) and activate cell signaling pathways through interaction with metabotropic glutamate receptors (mGluRs). Membrane-initiated estradiol signaling increases the free cytoplasmic calcium concentration ([Ca2+]i) that stimulates the synthesis of neuroprogesterone in astrocytes. We used surface biotinylation to demonstrate that ERα has an extracellular portion. In addition to the full length ERα (apparent M.W. 66 kDa), surface biotinylation labeled an ERα-immunoreactive protein (M.W. ~ 52 kDa) identified by both COOH- and NH2-directed antibodies. Estradiol treatment regulated membrane levels of both proteins in parallel: within 5 min, estradiol significantly increased membrane levels of the 66 kDa and 52 kDa ERα. Internalization, a measure of membrane receptor activation, was also increased by estradiol with a similar time course. Continuous treatment with estradiol for 24–48 hr reduced ERα levels, suggesting receptor down-regulation. Estradiol also increased mGluR1a trafficking and internalization, consistent with the proposed ERα-mGluR1a interaction. Blocking ER with ICI 182,780 or mGluR1a with LY 367385 prevented ERα trafficking to and from the membrane. Estradiol-induced [Ca2+]i flux was also significantly increased at the time of peak ERα activation/internalization. These results demonstrate that ERα is present in the membrane and has an extracellular portion. Furthermore, membrane levels and internalization of ERα are regulated by estradiol and mGluR1a ligands. The pattern of trafficking into and out of the membrane suggests that the changing concentration of estradiol during the estrous cycle regulates ERα to augment and then terminate membrane-initiated signaling. PMID:19955385

  4. The effects of excessive heat on heat-activated membrane currents in cultured dorsal root ganglia neurons from neonatal rat

    Czech Academy of Sciences Publication Activity Database

    Lyfenko, Alla; Vlachová, Viktorie; Vyklický st., Ladislav; Dittert, Ivan; Kress, M.; Reeh, P. W.

    2002-01-01

    Roč. 95, č. 3 (2002), s. 207-214 ISSN 0304-3959 R&D Projects: GA ČR GA305/00/1639; GA MŠk LN00B122 Institutional research plan: CEZ:AV0Z5011922 Keywords : nociception * noxious heat * capsacin Subject RIV: ED - Physiology Impact factor: 4.829, year: 2002

  5. 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.

  6. Detection of irradiation-induced, membrane heat shock protein 70 (Hsp70) in mouse tumors using Hsp70 Fab fragment

    International Nuclear Information System (INIS)

    Stangl, Stefan; Themelis, George; Friedrich, Lars; Ntziachristos, Vasilis; Sarantopoulos, Athanasios; Molls, Michael; Skerra, Arne; Multhoff, Gabriele

    2011-01-01

    Background and purpose: The major stress-inducible heat shock protein 70 (Hsp70) is frequently overexpressed in highly aggressive tumors, and elevated intracellular Hsp70 levels mediate protection against apoptosis. Following therapeutic intervention, such as ionizing irradiation, translocation of cytosolic Hsp70 to the plasma membrane is selectively increased in tumor cells and therefore, membrane Hsp70 might serve as a therapy-inducible, tumor-specific target structure. Materials and methods: Based on the IgG1 mouse monoclonal antibody (mAb) cmHsp70.1, we produced the Hsp70-specific recombinant Fab fragment (Hsp70 Fab), as an imaging tool for the detection of membrane Hsp70 positive tumor cells in vitro and in vivo. Results: The binding characteristics of Hsp70 Fab towards mouse colon (CT26) and pancreatic (1048) carcinoma cells at 4 deg. C were comparable to that of cmHsp70.1 mAb, as determined by flow cytometry. Following a temperature shift to 37 deg. C, Hsp70 Fab rapidly translocates into subcellular vesicles of mouse tumor cells. Furthermore, in tumor-bearing mice Cy5.5-conjugated Hsp70 Fab, but not unrelated IN-1 control Fab fragment (IN-1 ctrl Fab), gradually accumulates in CT26 tumors between 12 and 55 h after i.v. injection. Conclusions: In summary, the Hsp70 Fab provides an innovative, low immunogenic tool for imaging of membrane Hsp70 positive tumors, in vivo.

  7. Heat shock 70 protein interaction with Turnip mosaic virus RNA-dependent RNA polymerase within virus-induced membrane vesicles

    International Nuclear Information System (INIS)

    Dufresne, Philippe J.; Thivierge, Karine; Cotton, Sophie; Beauchemin, Chantal; Ide, Christine; Ubalijoro, Eliane; Laliberte, Jean-Francois; Fortin, Marc G.

    2008-01-01

    Tandem affinity purification was used in Arabidopsis thaliana to identify cellular interactors of Turnip mosaic virus (TuMV) RNA-dependent RNA polymerase (RdRp). The heat shock cognate 70-3 (Hsc70-3) and poly(A)-binding (PABP) host proteins were recovered and shown to interact with the RdRp in vitro. As previously shown for PABP, Hsc70-3 was redistributed to nuclear and membranous fractions in infected plants and both RdRp interactors were co-immunoprecipitated from a membrane-enriched extract using RdRp-specific antibodies. Fluorescently tagged RdRp and Hsc70-3 localized to the cytoplasm and the nucleus when expressed alone or in combination in Nicotiana benthamiana. However, they were redistributed to large perinuclear ER-derived vesicles when co-expressed with the membrane binding 6K-VPg-Pro protein of TuMV. The association of Hsc70-3 with the RdRp could possibly take place in membrane-derived replication complexes. Thus, Hsc70-3 and PABP2 are potentially integral components of the replicase complex and could have important roles to play in the regulation of potyviral RdRp functions

  8. Effects of heat and water transport on the performance of polymer electrolyte membrane fuel cell under high current density operation

    International Nuclear Information System (INIS)

    Tabuchi, Yuichiro; Shiomi, Takeshi; Aoki, Osamu; Kubo, Norio; Shinohara, Kazuhiko

    2010-01-01

    Key challenges to the acceptance of polymer electrolyte membrane fuel cells (PEMFCs) for automobiles are the cost reduction and improvement in its power density for compactness. In order to get the solution, the further improvement in a fuel cell performance is required. In particular, under higher current density operation, water and heat transport in PEMFCs has considerable effects on the cell performance. In this study, the impact of heat and water transport on the cell performance under high current density was investigated by experimental evaluation of liquid water distribution and numerical validation. Liquid water distribution in MEA between rib and channel area is evaluated by neutron radiography. In order to neglect the effect of liquid water in gas channels and reactant species concentration distribution in the flow direction, the differential cell was used in this study. Experimental results suggested that liquid water under the channel was dramatically changed with rib/channel width. From the numerical study, it is found that the change of liquid water distribution was significantly affected by temperature distribution in MEA between rib and channel area. In addition, not only heat transport but also water transport through the membrane also significantly affected the cell performance under high current density operation.

  9. Sphingolipid trafficking - Sorted out?

    OpenAIRE

    van Meer, G.; Burger, K.N.J.

    1992-01-01

    Studies of intracellular membrane traffic have traditionally focused on the protein components of membranes, but what about lipids? Recent findings have drawn attention to the transport of one type of lipid, the sphingolipids. Their unique physical properties may allow them to aggregate into microdomains in membranes that concentrate sphingolipids into specific transport pathways. Gerrit van Meer and Koert Burger consider here the routes of sphingolipid biosynthesis and transport, and the rol...

  10. Fabrication of Anodic Aluminum Oxide Membrane for High Heat Flux Evaporation

    OpenAIRE

    McGrath, Kristine

    2016-01-01

    As electronics become more powerful and have higher energy densities, it is becoming more and more necessary to find solutions to dissipate these high heat fluxes. One solution to this problem is nanopore evaporative cooling. Based on current literature, the experimental data is far below what is expected from the theoretical calculations.In this thesis, the experimental results produced heat fluxes much closer to the theoretical values. Experimentally, a maximum heat dissipation of 103 W was...

  11. 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.

  12. Sphingolipid trafficking - Sorted out?

    NARCIS (Netherlands)

    van Meer, G.; Burger, K.N.J.

    1992-01-01

    Studies of intracellular membrane traffic have traditionally focused on the protein components of membranes, but what about lipids? Recent findings have drawn attention to the transport of one type of lipid, the sphingolipids. Their unique physical properties may allow them to aggregate into

  13. Internalization and trafficking mechanisms of coxsackievirus B3 in HeLa cells

    International Nuclear Information System (INIS)

    Chung, Sun-Ku; Kim, Joo-Young; Kim, In-Beom; Park, Sang-Ick; Paek, Kyung-Hee; Nam, Jae-Hwan

    2005-01-01

    Coxsackievirus B3 (CVB3) is nonenveloped and has a single-stranded positive-sense RNA genome. CVB3 induces myocarditis and ultimately dilated cardiomyopathy. Although there are mounting evidences of an interaction between CVB3 particles and the cellular receptors, coxsackievirus and adenovirus receptor (CAR) and decay-accelerating factor (DAF), very little is known about the mechanisms of internalization and trafficking. In the present study, we used the CVB3 H3 strain, which is CAR-dependent but DAF-independent Woodruff variant and found that during entry, CVB3 particles were colocalized in clathrin, after interacting primarily with CAR, which was not recycled to the plasma membrane. We also found that CVB3 internalization was dependent on the function of dynamin, a large GTPase that has an essential role in endocytosis. Heat-shock cognate protein, Hsc70, which acts as a chaperone in the release of coat proteins from clathrin-coated vesicles (CCV), played a role in CVB3 trafficking processes. Moreover, endosomal acidification was crucial for CVB3 endocytosis. Finally, CVB3 was colocalized in early endosome autoantigen 1 (EEA1) molecules, which are involved in endosome-endosome tethering and fusion. In conclusion, these data together indicate that CVB3 uses clathrin-mediated endocytosis and is transcytosed to early endosomes

  14. Membrane-bound heat shock proteins facilitate the uptake of dying cells and cross-presentation of cellular antigen.

    Science.gov (United States)

    Zhu, Haiyan; Fang, Xiaoyun; Zhang, Dongmei; Wu, Weicheng; Shao, Miaomiao; Wang, Lan; Gu, Jianxin

    2016-01-01

    Heat shock proteins (HSPs) were originally identified as stress-responsive proteins and serve as molecular chaperones in different intracellular compartments. Translocation of HSPs to the cell surface and release of HSPs into the extracellular space have been observed during the apoptotic process and in response to a variety of cellular stress. Here, we report that UV irradiation and cisplatin treatment rapidly induce the expression of membrane-bound Hsp60, Hsp70, and Hsp90 upstream the phosphatidylserine exposure. Membrane-bound Hsp60, Hsp70 and Hsp90 could promote the release of IL-6 and IL-1β as well as DC maturation by the evaluation of CD80 and CD86 expression. On the other hand, Hsp60, Hsp70 and Hsp90 on cells could facilitate the uptake of dying cells by bone marrow-derived dendritic cells. Lectin-like oxidized LDL receptor-1 (LOX-1), as a common receptor for Hsp60, Hsp70, and Hsp90, is response for their recognition and mediates the uptake of dying cells. Furthermore, membrane-bound Hsp60, Hsp70 and Hsp90 could promote the cross-presentation of OVA antigen from E.G7 cells and inhibition of the uptake of dying cells by LOX-1 decreases the cross-presentation of cellular antigen. Therefore, the rapid exposure of HSPs on dying cells at the early stage allows for the recognition by and confers an activation signal to the immune system.

  15. Development and pilot testing of full-scale membrane distillation modules for deployment of waste heat

    NARCIS (Netherlands)

    Jansen, A.E.; Assink, J.W.; Hanemaaijer, J.H.; Medevoort, J. van; Sonsbeek, E. van

    2013-01-01

    Membrane distillation is an attractive technology for extracting fresh water from seawater. Newly developed modules have been used in pilot tests and bench scale tests to demonstrate the potential of producing excellent product water quality in a single step, little need for water pretreatment and a

  16. Spatio-temporal Remodeling of Functional Membrane Microdomains Organizes the Signaling Networks of a Bacterium

    NARCIS (Netherlands)

    Schneider, Johannes; Klein, Teresa; Mielich-Süss, Benjamin; Koch, Gudrun; Franke, Christian; Kuipers, Oscar P; Kovács, Ákos T; Sauer, Markus; Lopez, Daniel

    Lipid rafts are membrane microdomains specialized in the regulation of numerous cellular processes related to membrane organization, as diverse as signal transduction, protein sorting, membrane trafficking or pathogen invasion. It has been proposed that this functional diversity would require a

  17. 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

  18. 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.

  19. 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...

  20. Evolution of mammalian endothermic metabolism: leaky membranes as a source of heat

    International Nuclear Information System (INIS)

    Else, P.L.; Hulbert, A.J.

    1987-01-01

    O 2 consumption was measured at 37/degrees/C in tissue slices of liver, kidney, and brain from Amphilbolurus vitticeps and Rattus norvegicus (a reptile and mammal with same weight and body temperature) both in the presence and absence of ouabain. O 2 consumption of the mammalian tissues was two to four times that of the reptilian tissues and the mammalian tissues used three to six times the energy for Na + -K + transport than the reptilian tissues. Passive permeability to 42 K + was measured at 37/degrees/C in liver and kidney slices, and passive permeability to 22 Na + was measured at 37/degrees/C in isolated and cultured liver cells from each species. The mammalian cell membrane was severalfold leakier to both these ions than was the reptilian cell membrane, and thus the membrane pumps must use more energy to maintain the transmembrane ion gradients. It is postulated that this is a general difference between the cells of ectotherms and endotherms and thus partly explains the much higher levels of metabolism found in endothermic mammals

  1. The heat-compression technique for the conversion of platelet-rich fibrin preparation to a barrier membrane with a reduced rate of biodegradation.

    Science.gov (United States)

    Kawase, Tomoyuki; Kamiya, Mana; Kobayashi, Mito; Tanaka, Takaaki; Okuda, Kazuhiro; Wolff, Larry F; Yoshie, Hiromasa

    2015-05-01

    Platelet-rich fibrin (PRF) was developed as an advanced form of platelet-rich plasma to eliminate xenofactors, such as bovine thrombin, and it is mainly used as a source of growth factor for tissue regeneration. Furthermore, although a minor application, PRF in a compressed membrane-like form has also been used as a substitute for commercially available barrier membranes in guided-tissue regeneration (GTR) treatment. However, the PRF membrane is resorbed within 2 weeks or less at implantation sites; therefore, it can barely maintain sufficient space for bone regeneration. In this study, we developed and optimized a heat-compression technique and tested the feasibility of the resulting PRF membrane. Freshly prepared human PRF was first compressed with dry gauze and subsequently with a hot iron. Biodegradability was microscopically examined in vitro by treatment with plasmin at 37°C or in vivo by subcutaneous implantation in nude mice. Compared with the control gauze-compressed PRF, the heat-compressed PRF appeared plasmin-resistant and remained stable for longer than 10 days in vitro. Additionally, in animal implantation studies, the heat-compressed PRF was observed at least for 3 weeks postimplantation in vivo whereas the control PRF was completely resorbed within 2 weeks. Therefore, these findings suggest that the heat-compression technique reduces the rate of biodegradation of the PRF membrane without sacrificing its biocompatibility and that the heat-compressed PRF membrane easily could be prepared at chair-side and applied as a barrier membrane in the GTR treatment. © 2014 Wiley Periodicals, Inc.

  2. Modelling and Evaluation of Heating Strategies for High Temperature Polymer Electrolyte Membrane Fuel Cell Stacks

    DEFF Research Database (Denmark)

    Andreasen, Søren Juhl; Kær, Søren Knudsen

    2008-01-01

    Experiments were conducted on two different cathode air cooled high temperature PEM (HTPEM) fuel cell stacks; a 30 cell 400W prototype stack using two bipolar plates per cell, and a 65 cell 1 kW commercial stack using one bipolar plate per cell. The work seeks to examine the use of different...... model to simulate the temperature development of a fuel cell stack during heating can be used for assistance in system and control design. The heating strategies analyzed and tested reduced the startup time of one of the fuel cell stacks from 1 h to about 6 min....

  3. Membrane curvature enables N-Ras lipid anchor sorting to liquid-ordered membrane phases

    DEFF Research Database (Denmark)

    Larsen, Jannik Bruun; Jensen, Martin Borch; Bhatia, Vikram Kjøller

    2015-01-01

    Trafficking and sorting of membrane-anchored Ras GTPases are regulated by partitioning between distinct membrane domains. Here, in vitro experiments and microscopic molecular theory reveal membrane curvature as a new modulator of N-Ras lipid anchor and palmitoyl chain partitioning. Membrane...

  4. 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

  5. Feedback control for distributed heat transfer mechanisms in direct-contact membrane distillation system

    KAUST Repository

    Eleiwi, Fadi; N'Doye, Ibrahima; Laleg-Kirati, Taous-Meriem

    2015-01-01

    In this paper, the problem of stabilization and production rate reference tracking for a Direct-Contact Membrane Distillation (DCMD) system is addressed. Sufficient conditions for the asymptotic and exponential stabilization for DCMD system are presented using the Gronwall-Bellman lemma and Linear Matrix Inequalities (LMIs) approaches, respectively. A nonlinear observer is then proposed to estimate the temperature distribution among the DCMD domain. This contributes to propose a reference production rate control design for the DCMD process via observer-based output control approach. Finally, numerical simulations are given to show the effectiveness of the proposed methods.

  6. Feedback control for distributed heat transfer mechanisms in direct-contact membrane distillation system

    KAUST Repository

    Eleiwi, Fadi

    2015-09-21

    In this paper, the problem of stabilization and production rate reference tracking for a Direct-Contact Membrane Distillation (DCMD) system is addressed. Sufficient conditions for the asymptotic and exponential stabilization for DCMD system are presented using the Gronwall-Bellman lemma and Linear Matrix Inequalities (LMIs) approaches, respectively. A nonlinear observer is then proposed to estimate the temperature distribution among the DCMD domain. This contributes to propose a reference production rate control design for the DCMD process via observer-based output control approach. Finally, numerical simulations are given to show the effectiveness of the proposed methods.

  7. Proton exchange membrane fuel cell for cooperating households: A convenient combined heat and power solution for residential applications

    International Nuclear Information System (INIS)

    Cappa, Francesco; Facci, Andrea Luigi; Ubertini, Stefano

    2015-01-01

    In this paper we compare the technical and economical performances of a high temperature proton exchange membrane fuel cell with those of an internal combustion engine for a 10 kW combined heat and power residential application. In a view of social innovation, this solution will create new partnerships of cooperating families aiming to reduce the energy consumption and costs. The energy system is simulated through a lumped model. We compare, in the Italian context, the total daily operating cost and energy savings of each system with respect to the separate purchase of electricity from the grid and production of the thermal energy through a standard boiler. The analysis is carried out with the energy systems operating with both the standard thermal tracking and an optimized management. The latter is retrieved through an optimization methodology based on the graph theory. We show that the internal combustion engine is much more affected by the choice of the operating strategy with respect to the fuel cell, in terms long term profitability. Then we conduct a net present value analysis with the aim of evidencing the convenience of using a high temperature proton exchange membrane fuel cell for cogeneration in residential applications. - Highlights: • Fuel cells are a feasible and economically convenient solution for residential CHP. • Control strategy is fundamental for the economical performance of a residential CHP. • Flexibility is a major strength of the fuel cell CHP.

  8. Performance study of a heat pump driven and hollow fiber membrane-based two-stage liquid desiccant air dehumidification system

    International Nuclear Information System (INIS)

    Zhang, Ning; Yin, Shao-You; Zhang, Li-Zhi

    2016-01-01

    Graphical abstract: A heat pump driven, hollow fiber membrane-based two-stage liquid desiccant air dehumidification system. - Highlights: • A two-stage hollow fiber membrane based air dehumidification is proposed. • It is heat pump driven liquid desiccant system. • Performance is improved 20% upon single stage system. • The optimal first to second stage dehumidification area ratio is 1.4. - Abstract: A novel compression heat pump driven and hollow fiber membrane-based two-stage liquid desiccant air dehumidification system is presented. The liquid desiccant droplets are prevented from crossing over into the process air by the semi-permeable membranes. The isoenthalpic processes are changed to quasi-isothermal processes by the two-stage dehumidification processes. The system is set up and a model is proposed for simulation. Heat and mass capacities in the system, including the membrane modules, the condenser, the evaporator and the heat exchangers are modeled in detail. The model is also validated experimentally. Compared with a single-stage dehumidification system, the two-stage system has a lower solution concentration exiting from the dehumidifier and a lower condensing temperature. Thus, a better thermodynamic system performance is realized and the COP can be increased by about 20% under the typical hot and humid conditions in Southern China. The allocations of heat and mass transfer areas in the system are also investigated. It is found that the optimal regeneration to dehumidification area ratio is 1.33. The optimal first to second stage dehumidification area ratio is 1.4; and the optimal first to second stage regeneration area ratio is 1.286.

  9. Simultaneous production of high-quality water and electrical power from aqueous feedstock’s and waste heat by high-pressure membrane distillation

    NARCIS (Netherlands)

    Kuipers, N.J.M.; Hanemaaijer, J.H.; Brouwer, H.; Medevoort, J. van; Jansen, A.; Altena, F.; Vleuten, P. van der; Bak, H.

    2015-01-01

    A new membrane distillation (MD) concept (MemPower) has been developed for the simultaneous production of high-quality water from various aqueous feedstocks with cogeneration of mechanical power (electricity). Driven by low-grade heat (waste, solar, geothermal, etc.) a pressurized distillate can be

  10. Ricin Trafficking in Cells

    Directory of Open Access Journals (Sweden)

    Robert A. Spooner

    2015-01-01

    Full Text Available The heterodimeric plant toxin ricin binds exposed galactosyls at the cell surface of target mammalian cells, and, following endocytosis, is transported in vesicular carriers to the endoplasmic reticulum (ER. Subsequently, the cell-binding B chain (RTB and the catalytic A chain (RTA are separated reductively, RTA embeds in the ER membrane and then retrotranslocates (or dislocates across this membrane. The protein conducting channels used by RTA are usually regarded as part of the ER-associated protein degradation system (ERAD that removes misfolded proteins from the ER for destruction by the cytosolic proteasomes. However, unlike ERAD substrates, cytosolic RTA avoids destruction and folds into a catalytic conformation that inactivates its target ribosomes. Protein synthesis ceases, and subsequently the cells die apoptotically. This raises questions about how this protein avoids the pathways that are normally sanctioned for ER-dislocating substrates. In this review we focus on the molecular events that occur with non-tagged ricin and its isolated subunits at the ER–cytosol interface. This focus reveals that intra-membrane interactions of RTA may control its fate, an area that warrants further investigation.

  11. 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.

  12. 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...

  13. 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...

  14. 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

  15. 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

  16. 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…

  17. Intracellular Cholesterol Trafficking and Impact in Neurodegeneration

    Directory of Open Access Journals (Sweden)

    Fabian Arenas

    2017-11-01

    Full Text Available Cholesterol is a critical component of membrane bilayers where it plays key structural and functional roles by regulating the activity of diverse signaling platforms and pathways. Particularly enriched in brain, cholesterol homeostasis in this organ is singular with respect to other tissues and exhibits a heterogeneous regulation in distinct brain cell populations. Due to the key role of cholesterol in brain physiology and function, alterations in cholesterol homeostasis and levels have been linked to brain diseases and neurodegeneration. In the case of Alzheimer disease (AD, however, this association remains unclear with evidence indicating that either increased or decreased total brain cholesterol levels contribute to this major neurodegenerative disease. Here, rather than analyzing the role of total cholesterol levels in neurodegeneration, we focus on the contribution of intracellular cholesterol pools, particularly in endolysosomes and mitochondria through its trafficking via specialized membrane domains delineated by the contacts between endoplasmic reticulum and mitochondria, in the onset of prevalent neurodegenerative diseases such as AD, Parkinson disease, and Huntington disease as well as in lysosomal disorders like Niemann-Pick type C disease. We dissect molecular events associated with intracellular cholesterol accumulation, especially in mitochondria, an event that results in impaired mitochondrial antioxidant defense and function. A better understanding of the mechanisms involved in the distribution of cholesterol in intracellular compartments may shed light on the role of cholesterol homeostasis disruption in neurodegeneration and may pave the way for specific intervention opportunities.

  18. 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.

  19. Quality control of Photosystem II: the mechanisms for avoidance and tolerance of light and heat stresses are closely linked to membrane fluidity of the thylakoids

    Directory of Open Access Journals (Sweden)

    Yasusi Yamamoto

    2016-08-01

    Full Text Available When oxygenic photosynthetic organisms are exposed to excessive light and/or heat, Photosystem II is damaged and electron transport is blocked. In these events, reactive oxygen species, endogenous radicals and lipid peroxidation products generated by photochemical reaction and/or heat cause the damage. Regarding light stress, plants first dissipate excessive light energy captured by light-harvesting chlorophyll protein complexes as heat to avoid the hazards, but once light stress is unavoidable, they tolerate the stress by concentrating damage in a particular protein in photosystem II, i.e. the reaction-center binding D1 protein of Photosystem II. The damaged D1 is removed by specific proteases and replaced with a new copy produced through de novo synthesis (reversible photoinhibition. When light intensity becomes extremely high, irreversible aggregation of D1 occurs and thereby D1 turnover is prevented. Once the aggregated products accumulate in Photosystem II complexes, removal of them by proteases is difficult, and irreversible inhibition of Photosystem II takes place (irreversible photoinhibition. Important is that various aspects of both the reversible and irreversible photoinhibition are highly dependent on the membrane fluidity of the thylakoids. Heat stress-induced inactivation of photosystem II is an irreversible process, which may be also affected by the fluidity of the thylakoid membranes. Here I describe why the membrane fluidity is a key to regulate the avoidance and tolerance of Photosystem II on environmental stresses.

  20. Performance analysis of a direct expansion air dehumidification system combined with membrane-based total heat recovery

    Energy Technology Data Exchange (ETDEWEB)

    Liang, Cai-Hang; Zhang, Li-Zhi; Pei, Li-Xia [Key Laboratory of Enhanced Heat Transfer and Energy Conservation of Education Ministry, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640 (China)

    2010-09-15

    A direct expansion (DX) air dehumidification system is an efficient way to supply fresh and dry air to a built environment. It plays a key role in preventing the spread of respiratory disease like Swine flu (H1N1). To improve the efficiency of a conventional DX system in hot and humid regions, a new system of DX in combination with a membrane-based total heat exchanger is proposed. Air is supplied with dew points. A detailed mathematical modeling is performed. A cell-by-cell simulation technique is used to simulate its performances. A real prototype is built in our laboratory in South China University of Technology to validate the model. The effects of inlet air humidity and temperature, evaporator and condenser sizes on the system performance are investigated. The results indicate that the model can predict the system accurately. Compared to a conventional DX system, the air dehumidification rate (ADR) of the novel system is 0.5 times higher, and the coefficient of performance (COP) is 1 times higher. Furthermore, the system performs well even under harsh hot and humid weather conditions. (author)

  1. A hybrid system using a regenerative electrochemical cycle to harvest waste heat from the proton exchange membrane fuel cell

    International Nuclear Information System (INIS)

    Long, Rui; Li, Baode; Liu, Zhichun; Liu, Wei

    2015-01-01

    A new hybrid system consisting of a PEMFC (proton exchange membrane fuel cell) subsystem and a TREC (thermally regenerative electrochemical cycle) subsystem is proposed to convert the waste heat produced by the PEMFC system into electricity. The performance of the hybrid system and its corresponding subsystems is analyzed. Results reveal that there exists optimal current densities of the PEMFC and TREC systems leading to the maximum power output of the hybrid system. With the maximum power output as the objective function, an optimization of the hybrid system based on genetic algorithm method is conducted under different operating temperatures of the PEMFC subsystem. The power output of the hybrid system is 6.85%–20.59% larger than that of the PEMFC subsystem. And the total electrical efficiency is improved by 2.74%–8.27%. The corresponding electrical efficiency of the TREC is 4.56%–13.81%. The hybrid system proposed in this paper could contribute to utilizing the fuel energy more efficiently and sufficiently. - Highlights: • A hybrid power system consisting of a PEMFC and a TREC subsystems is proposed. • Parameters' impacts on performance of the hybrid system have been analyzed. • The maximum power output of the hybrid system is investigated based on genetic algorithm. • Total power output of the hybrid system is 7.63%–18.84% larger than that of the PEMFC subsystem.

  2. 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...

  3. [The Role of Membrane-Bound Heat Shock Proteins Hsp90 in Migration of Tumor Cells in vitro and Involvement of Cell Surface Heparan Sulfate Proteoglycans in Protein Binding to Plasma Membrane].

    Science.gov (United States)

    Snigireva, A V; Vrublevskaya, V V; Skarga, Y Y; Morenkov, O S

    2016-01-01

    Heat shock protein Hsp90, detected in the extracellular space and on the membrane of cells, plays an important role in cell motility, migration, invasion and metastasis of tumor cells. At present, the functional role and molecular mechanisms of Hsp90 binding to plasma membrane are not elucidated. Using isoform-specific antibodies against Hsp90, Hsp9α and Hsp90β, we showed that membrane-bound Hsp90α and Hsp90β play a significant role in migration of human fibrosarcoma (HT1080) and glioblastoma (A-172) cells in vitro. Disorders of sulfonation of cell heparan sulfates, cleavage of cell heparan. sulfates by heparinase I/III as well as treatment of cells with heparin lead to an abrupt reduction in the expression level of Hsp90 isoforms. Furthermore, heparin significantly inhibits tumor cell migration. The results obtained demonstrate that two isoforms of membrane-bound Hsp90 are involved in migration of tumor cells in vitro and that cell surface heparan sulfate proteoglycans play a pivotal role in the "anchoring" of Hsp90α and Hsp90β to the plasma membrane.

  4. 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.

  5. Modeling and optimization of a heat-pump-assisted high temperature proton exchange membrane fuel cell micro-combined-heat-and-power system for residential applications

    DEFF Research Database (Denmark)

    Arsalis, Alexandros; Kær, Søren Knudsen; Nielsen, Mads Pagh

    2015-01-01

    In this study a micro-combined-heat-and-power (micro-CHP) system is coupled to a vapor-compression heat pump to fulfill the residential needs for heating (space heating and water heating) and electricity in detached single-family households in Denmark. Such a combination is assumed to be attractive...... for application, since both fuel cell technology and electric heat pumps are found to be two of the most efficient technologies for generation/conversion of useful energy. The micro-CHP system is fueled with natural gas and includes a fuel cell stack, a fuel processor and other auxiliary components. The micro......-CHP system assumes heat-led operation, to avoid dumping of heat and the use of complicated thermal energy storage. The overall system is grid-interconnected to allow importing and exporting of electricity as necessary. In this study emphasis is given on the operational characterization of the system...

  6. 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

  7. 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.

  8. Endocytic trafficking from the small intestinal brush border probed with FM dye

    DEFF Research Database (Denmark)

    Hansen, Gert H; Rasmussen, Karina; Niels-Christiansen, Lise-Lotte

    2009-01-01

    -linking galectins/intelectin, but little is known about the dynamic properties of this highly specialized membrane. Here, we probed the endocytic membrane trafficking from the brush border of organ cultured pig intestinal mucosal explants by use of a fixable, lipophilic FM dye. The fluorescent dye readily......, contributes to the overall permeability barrier of the gut. Key words: FM dye, small intestine, brush border, endocytosis....

  9. A fluorescent glycolipid-binding peptide probe traces cholesterol dependent microdomain-derived trafficking pathways.

    Directory of Open Access Journals (Sweden)

    Steffen Steinert

    Full Text Available BACKGROUND: The uptake and intracellular trafficking of sphingolipids, which self-associate into plasma membrane microdomains, is associated with many pathological conditions, including viral and toxin infection, lipid storage disease, and neurodegenerative disease. However, the means available to label the trafficking pathways of sphingolipids in live cells are extremely limited. In order to address this problem, we have developed an exogenous, non-toxic probe consisting of a 25-amino acid sphingolipid binding domain, the SBD, derived from the amyloid peptide Abeta, and conjugated by a neutral linker with an organic fluorophore. The current work presents the characterization of the sphingolipid binding and live cell trafficking of this novel probe, the SBD peptide. SBD was the name given to a motif originally recognized by Fantini et al in a number of glycolipid-associated proteins, and was proposed to interact with sphingolipids in membrane microdomains. METHODOLOGY/PRINCIPAL FINDINGS: In accordance with Fantini's model, optimal SBD binding to membranes depends on the presence of sphingolipids and cholesterol. In synthetic membrane binding assays, SBD interacts preferentially with raft-like lipid mixtures containing sphingomyelin, cholesterol, and complex gangliosides in a pH-dependent manner, but is less glycolipid-specific than Cholera toxin B (CtxB. Using quantitative time-course colocalization in live cells, we show that the uptake and intracellular trafficking route of SBD is unlike that of either the non-raft marker Transferrin or the raft markers CtxB and Flotillin2-GFP. However, SBD traverses an endolysosomal route that partially intersects with raft-associated pathways, with a major portion being diverted at a late time point to rab11-positive recycling endosomes. Trafficking of SBD to acidified compartments is strongly disrupted by cholesterol perturbations, consistent with the regulation of sphingolipid trafficking by cholesterol

  10. Differential trafficking of oxidized LDL and oxidized LDL immune complexes in macrophages: impact on oxidative stress.

    Directory of Open Access Journals (Sweden)

    Mohammed M Al Gadban

    2010-09-01

    Full Text Available Oxidized low-density lipoproteins (oxLDL and oxLDL-containing immune complexes (oxLDL-IC contribute to formation of lipid-laden macrophages (foam cells. It has been shown that oxLDL-IC are considerably more efficient than oxLDL in induction of foam cell formation, inflammatory cytokines secretion, and cell survival promotion. Whereas oxLDL is taken up by several scavenger receptors, oxLDL-IC are predominantly internalized through the FCgamma receptor I (FCgamma RI. This study examined differences in intracellular trafficking of lipid and apolipoprotein moieties of oxLDL and oxLDL-IC and the impact on oxidative stress.Fluorescently labeled lipid and protein moieties of oxLDL co-localized within endosomal and lysosomal compartments in U937 human monocytic cells. In contrast, the lipid moiety of oxLDL-IC was detected in the endosomal compartment, whereas its apolipoprotein moiety advanced to the lysosomal compartment. Cells treated with oxLDL-IC prior to oxLDL demonstrated co-localization of internalized lipid moieties from both oxLDL and oxLDL-IC in the endosomal compartment. This sequential treatment likely inhibited oxLDL lipid moieties from trafficking to the lysosomal compartment. In RAW 264.7 macrophages, oxLDL-IC but not oxLDL induced GFP-tagged heat shock protein 70 (HSP70 and HSP70B', which co-localized with the lipid moiety of oxLDL-IC in the endosomal compartment. This suggests that HSP70 family members might prevent the degradation of the internalized lipid moiety of oxLDL-IC by delaying its advancement to the lysosome. The data also showed that mitochondrial membrane potential was decreased and generation of reactive oxygen and nitrogen species was increased in U937 cell treated with oxLDL compared to oxLDL-IC.Findings suggest that lipid and apolipoprotein moieties of oxLDL-IC traffic to separate cellular compartments, and that HSP70/70B' might sequester the lipid moiety of oxLDL-IC in the endosomal compartment. This mechanism could

  11. 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.

  12. 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

  13. 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...

  14. 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...

  15. 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.

  16. Optimal stochastic coordinated scheduling of proton exchange membrane fuel cell-combined heat and power, wind and photovoltaic units in micro grids considering hydrogen storage

    International Nuclear Information System (INIS)

    Bornapour, Mosayeb; Hooshmand, Rahmat-Allah; Khodabakhshian, Amin; Parastegari, Moein

    2017-01-01

    Highlights: •Stochastic model is proposed for coordinated scheduling of renewable energy sources. •The effect of combined heat and power is considered. •Hydrogen storage is considered for fuel cells. •Maximizing profits of micro grid is considered as objective function. •Considering the uncertainties of problem lead to profit increasing. -- Abstract: Nowadays, renewable energy sources and combined heat and power units are extremely used in micro grids, so it is necessary to schedule these units to improve the performance of the system. In this regard, a stochastic model is proposed in this paper to schedule proton exchange membrane fuel cell-combined heat and power, wind turbines, and photovoltaic units coordinately in a micro grid while considering hydrogen storage. Hydrogen storage strategy is considered for the operation of proton exchange membrane fuel cell-combined heat and power units. To consider stochastic generation of renewable energy source units in this paper, a scenario-based method is used. In this method, the uncertainties of electrical market price, the wind speed, and solar irradiance are considered. This stochastic scheduling problem is a mixed integer- nonlinear programming which considers the proposed objective function and variables of coordinated scheduling of PEMFC-CHP, wind turbines and photovoltaic units. It also considers hydrogen storage strategy and converts it to a mixed integer nonlinear problem. In this study a modified firefly algorithm is used to solve the problem. This method is examined on modified 33-bus distributed network as a MG for its performance.

  17. The effect of non-contact heating (microwave irradiation) and contact heating (annealing process) on properties and performance of polyethersulfone nanofiltration membranes

    International Nuclear Information System (INIS)

    Mansourpanah, Y.; Madaeni, S.S.; Rahimpour, A.; Farhadian, A.

    2009-01-01

    In this work the effect of microwave irradiation on morphology and performance of polyethersulfone (PES) membranes was investigated. The membranes were prepared with 20 wt.% of PES by phase inversion method. N,N-dimethylformamide (DMF) and mixture of water and ethyl alcohol (90/10 vol.%) were employed as solvent and coagulant respectively. Polyvinylpirrolidone (PVP) with the concentration of 2 wt.% was selected as pore former. The effects of irradiation time (10, 30, 60, 90, 120 s) and microwave power (180, 360, 720 and 900 W) on structure and performance of membranes were studied. Increasing the irradiation time and power caused variation in permeate flux and ion rejection. Moreover, the effects of annealing processes (60, 70, 80 deg. C) were studied. Transmembrane pressure was selected around 1.5 MPa for all experiments. Scanning electron microscope (SEM) and atomic force microscope (AFM) were employed to describe the surface morphology of the prepared membranes. The effect of microwave irradiation time in different power revealed alterations in membrane surface morphology and AFM images represented that surface parameters (such as surface roughness) have been changed. The membrane exhibited moderate rejection (47%) and low permeate flux (4.5 kg/m 2 h) at 80 deg. C for NaCl solution. The SEM images indicate that the dense skin layer is formed at 80 deg. C annealing.

  18. Formation and Regulation of Mitochondrial Membranes

    Directory of Open Access Journals (Sweden)

    Laila Cigana Schenkel

    2014-01-01

    Full Text Available Mitochondrial membrane phospholipids are essential for the mitochondrial architecture, the activity of respiratory proteins, and the transport of proteins into the mitochondria. The accumulation of phospholipids within mitochondria depends on a coordinate synthesis, degradation, and trafficking of phospholipids between the endoplasmic reticulum (ER and mitochondria as well as intramitochondrial lipid trafficking. Several studies highlight the contribution of dietary fatty acids to the remodeling of phospholipids and mitochondrial membrane homeostasis. Understanding the role of phospholipids in the mitochondrial membrane and their metabolism will shed light on the molecular mechanisms involved in the regulation of mitochondrial function and in the mitochondrial-related diseases.

  19. 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.

  20. Mass-charge-heat coupled transfers in a single cell of a proton exchange membrane fuel cell; Transferts couples masse-charge-chaleur dans une cellule de pile a combustible a membrane polymere

    Energy Technology Data Exchange (ETDEWEB)

    Ramousse, J

    2005-11-15

    Understanding and modelling of coupled mass, charges and heat transfers phenomena are fundamental to analyze the electrical behaviour of the system. The aim of the present model is to describe electrical performances of a PEFMC according to the fluidic and thermal operating conditions. The water content of the membrane and the water distribution in the single cell are estimated according to the coupled simulations of mass transport in the thickness of the single cell and in the feeding channels of the bipolar plates. A microscopic model of a Gas Diffusion Electrode is built up to describe charges transfer phenomena occurring at the electrodes. Completed by a study of heat transfer in the Membrane Electrode Assembly, conditions and preferential sites of water vapor condensation can be highlighted. A set of measurements of the effective thermal conductivity of carbon felts used in fuel cells as porous backing layers have also been performed. Although the value of this parameter is essential for the study of heat transfer, it is still under investigation because of the strong thermal anisotropy of the medium. (author)

  1. Multivesicular Bodies in Neurons: Distribution, Protein Content, and Trafficking Functions

    Science.gov (United States)

    VON BARTHELD, CHRISTOPHER S.; ALTICK, AMY L.

    2011-01-01

    Summary Multivesicular bodies (MVBs) are intracellular endosomal organelles characterized by multiple internal vesicles that are enclosed within a single outer membrane. MVBs were initially regarded as purely prelysosomal structures along the degradative endosomal pathway of internalized proteins. MVBs are now known to be involved in numerous endocytic and trafficking functions, including protein sorting, recycling, transport, storage, and release. This review of neuronal MVBs summarizes their research history, morphology, distribution, accumulation of cargo and constitutive proteins, transport, and theories of functions of MVBs in neurons and glia. Due to their complex morphologies, neurons have expanded trafficking and signaling needs, beyond those of “geometrically simpler” cells, but it is not known whether neuronal MVBs perform additional transport and signaling functions. This review examines the concept of compartment-specific MVB functions in endosomal protein trafficking and signaling within synapses, axons, dendrites and cell bodies. We critically evaluate reports of the accumulation of neuronal MVBs based on evidence of stress-induced MVB formation. Furthermore, we discuss potential functions of neuronal and glial MVBs in development, in dystrophic neuritic syndromes, injury, disease, and aging. MVBs may play a role in Alzheimer’s, Huntington’s, and Niemann-Pick diseases, some types of frontotemporal dementia, prion and virus trafficking, as well as in adaptive responses of neurons to trauma and toxin or drug exposure. Functions of MVBs in neurons have been much neglected, and major gaps in knowledge currently exist. Developing truly MVB-specific markers would help to elucidate the roles of neuronal MVBs in intra- and intercellular signaling of normal and diseased neurons. PMID:21216273

  2. Hybrid pressure retarded osmosis-membrane distillation system for power generation from low-grade heat: thermodynamic analysis and energy efficiency.

    Science.gov (United States)

    Lin, Shihong; Yip, Ngai Yin; Cath, Tzahi Y; Osuji, Chinedum O; Elimelech, Menachem

    2014-05-06

    We present a novel hybrid membrane system that operates as a heat engine capable of utilizing low-grade thermal energy, which is not readily recoverable with existing technologies. The closed-loop system combines membrane distillation (MD), which generates concentrated and pure water streams by thermal separation, and pressure retarded osmosis (PRO), which converts the energy of mixing to electricity by a hydro-turbine. The PRO-MD system was modeled by coupling the mass and energy flows between the thermal separation (MD) and power generation (PRO) stages for heat source temperatures ranging from 40 to 80 °C and working concentrations of 1.0, 2.0, and 4.0 mol/kg NaCl. The factors controlling the energy efficiency of the heat engine were evaluated for both limited and unlimited mass and heat transfer kinetics in the thermal separation stage. In both cases, the relative flow rate between the MD permeate (distillate) and feed streams is identified as an important operation parameter. There is an optimal relative flow rate that maximizes the overall energy efficiency of the PRO-MD system for given working temperatures and concentration. In the case of unlimited mass and heat transfer kinetics, the energy efficiency of the system can be analytically determined based on thermodynamics. Our assessment indicates that the hybrid PRO-MD system can theoretically achieve an energy efficiency of 9.8% (81.6% of the Carnot efficiency) with hot and cold working temperatures of 60 and 20 °C, respectively, and a working solution of 1.0 M NaCl. When mass and heat transfer kinetics are limited, conditions that more closely represent actual operations, the practical energy efficiency will be lower than the theoretically achievable efficiency. In such practical operations, utilizing a higher working concentration will yield greater energy efficiency. Overall, our study demonstrates the theoretical viability of the PRO-MD system and identifies the key factors for performance

  3. Acetyl salicylic acid and 24-epibrassinolide attenuate decline in photosynthesis, chlorophyll contents and membrane thermo- stability in tomato (lycopersicon esculentum mill.) under heat stress

    International Nuclear Information System (INIS)

    Khan, A.R.; Hui, C.Z.; Ghazanfar, B.

    2015-01-01

    The effect of exogenous application of varying levels of 24-epibrassinolide (0.75, 1.5 and 3 micro M) and acetyl salicylic acid (0.25, 0.75 and 1.25 micro M) for induction of heat tolerance in terms of their effect on photosynthesis, chlorophyll content, membrane integrity and survival in four weeks old tomato (cultivar: Mei Jie Lo) seedlings under high temperature stress (46 degree C/4 h daily) for 21 days was investigated. The daily heat stress treatment had deleterious effects on seedlings but chemical treatments significantly reduced the magnitude of losses to different extents. 24-epibrassinolide (3 micro M) was over all the best treatment to improve survival (86.11%), photosynthesis (39.4%) and chlorophyll contents (26.12%) accompanied with initiation of flower buds and improved vegetative growth. Whereas acetyl salicylic acid (1.25 mM) best improved photosynthetic activity (40.6%) as compared to the untreated heat stressed control seedlings. Moreover, 3 micro M 24-epibrassinolide and 0.75 micro M acetyl salicylic acid reduced cell membrane injury to 8.3 and 6.9% respectively as compared with 22.4% in heat stressed control seedlings. However lower doses of acetyl salicylic acid (0.25 and 0.75 micro M) had slight (5.6 and 12.8%) inhibition effect on the photosynthesis than the heat stressed controls. Overall both acetyl salicylic acid and 24-epibrassinolide up regulated basal heat tolerance in tomato seedlings and studied concentrations demonstrated signature affect upon different parameters. Thus both chemical agents can be potential candidates for further investigations for exogenous application aiming at extension of tomato growth season in summer. (author)

  4. Damage to photosystem II due to heat stress without light-driven electron flow: involvement of enhanced introduction of reducing power into thylakoid membranes.

    Science.gov (United States)

    Marutani, Yoko; Yamauchi, Yasuo; Kimura, Yukihiro; Mizutani, Masaharu; Sugimoto, Yukihiro

    2012-08-01

    Under a moderately heat-stressed condition, the photosystems of higher plants are damaged in the dark more easily than they are in the presence of light. To obtain a better understanding of this heat-derived damage mechanism that occurs in the dark, we focused on the involvement of the light-independent electron flow that occurs at 40 °C during the damage. In various plant species, the maximal photochemical quantum yield of photosystem (PS) II (Fv/Fm) decreased as a result of heat treatment in the dark. In the case of wheat, the most sensitive plant species tested, both Fv/Fm and oxygen evolution rapidly decreased by heat treatment at 40 °C for 30 min in the dark. In the damage, specific degradation of D1 protein was involved, as shown by immunochemical analysis of major proteins in the photosystem. Because light canceled the damage to PSII, the light-driven electron flow may play a protective role against PSII damage without light. Light-independent incorporation of reducing power from stroma was enhanced at 40 °C but not below 35 °C. Arabidopsis mutants that have a deficit of enzymes which mediate the incorporation of stromal reducing power into thylakoid membranes were tolerant against heat treatment at 40 °C in the dark, suggesting that the reduction of the plastoquinone pool may be involved in the damage. In conclusion, the enhanced introduction of reducing power from stroma into thylakoid membranes that occurs around 40 °C causes over-reduction of plastoquinone, resulting in the damage to D1 protein under heat stress without linear electron flow.

  5. 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...

  6. 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

  7. 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.

  8. 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...

  9. 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.

  10. 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

  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. Trafficking and function of the tetraspanin CD63

    Energy Technology Data Exchange (ETDEWEB)

    Pols, Maaike S. [Cell Microscopy Center, Department of Cell Biology and Institute of Biomembranes, University Medical Center Utrecht, Heidelberglaan 100, 3584CX Utrecht (Netherlands); Klumperman, Judith, E-mail: j.klumperman@umcutrecht.nl [Cell Microscopy Center, Department of Cell Biology and Institute of Biomembranes, University Medical Center Utrecht, Heidelberglaan 100, 3584CX Utrecht (Netherlands)

    2009-05-15

    Tetraspanins comprise a large superfamily of cell surface-associated membrane proteins characterized by four transmembrane domains. They participate in a variety of cellular processes, like cell activation, adhesion, differentiation and tumour invasion. At the cell surface, tetraspanins form networks with a wide diversity of proteins called tetraspanin-enriched microdomains (TEMs). CD63 was the first characterized tetraspanin. In addition to its presence in TEMs, CD63 is also abundantly present in late endosomes and lysosomes. CD63 at the cell surface is endocytosed via a clathrin-dependent pathway, although recent studies suggest the involvement of other pathways as well and we here present evidence for a role of caveolae in CD63 endocytosis. In late endosomes, CD63 is enriched on the intraluminal vesicles, which by specialized cells are secreted as exosomes through fusion of endosomes with the plasma membrane. The complex localization pattern of CD63 suggests that its intracellular trafficking and distribution must be tightly regulated. In this review we discuss the latest insights in CD63 trafficking and its emerging function as a transport regulator of its interaction partners. Finally, the involvement of CD63 in cancer will be discussed.

  13. Regulation of AMPA Receptor Trafficking by Protein Ubiquitination

    Directory of Open Access Journals (Sweden)

    Jocelyn Widagdo

    2017-10-01

    Full Text Available The molecular mechanisms underlying plastic changes in the strength and connectivity of excitatory synapses have been studied extensively for the past few decades and remain the most attractive cellular models of learning and memory. One of the major mechanisms that regulate synaptic plasticity is the dynamic adjustment of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA-type glutamate receptor content on the neuronal plasma membrane. The expression of surface AMPA receptors (AMPARs is controlled by the delicate balance between the biosynthesis, dendritic transport, exocytosis, endocytosis, recycling and degradation of the receptors. These processes are dynamically regulated by AMPAR interacting proteins as well as by various post-translational modifications that occur on their cytoplasmic domains. In the last few years, protein ubiquitination has emerged as a major regulator of AMPAR intracellular trafficking. Dysregulation of AMPAR ubiquitination has also been implicated in the pathophysiology of Alzheimer’s disease. Here we review recent advances in the field and provide insights into the role of protein ubiquitination in regulating AMPAR membrane trafficking and function. We also discuss how aberrant ubiquitination of AMPARs contributes to the pathogenesis of various neurological disorders, including Alzheimer’s disease, chronic stress and epilepsy.

  14. Trafficking and function of the tetraspanin CD63

    International Nuclear Information System (INIS)

    Pols, Maaike S.; Klumperman, Judith

    2009-01-01

    Tetraspanins comprise a large superfamily of cell surface-associated membrane proteins characterized by four transmembrane domains. They participate in a variety of cellular processes, like cell activation, adhesion, differentiation and tumour invasion. At the cell surface, tetraspanins form networks with a wide diversity of proteins called tetraspanin-enriched microdomains (TEMs). CD63 was the first characterized tetraspanin. In addition to its presence in TEMs, CD63 is also abundantly present in late endosomes and lysosomes. CD63 at the cell surface is endocytosed via a clathrin-dependent pathway, although recent studies suggest the involvement of other pathways as well and we here present evidence for a role of caveolae in CD63 endocytosis. In late endosomes, CD63 is enriched on the intraluminal vesicles, which by specialized cells are secreted as exosomes through fusion of endosomes with the plasma membrane. The complex localization pattern of CD63 suggests that its intracellular trafficking and distribution must be tightly regulated. In this review we discuss the latest insights in CD63 trafficking and its emerging function as a transport regulator of its interaction partners. Finally, the involvement of CD63 in cancer will be discussed.

  15. 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.

  16. Application of Live-Cell RNA Imaging Techniques to the Study of Retroviral RNA Trafficking

    Directory of Open Access Journals (Sweden)

    Darrin V. Bann

    2012-06-01

    Full Text Available Retroviruses produce full-length RNA that serves both as a genomic RNA (gRNA, which is encapsidated into virus particles, and as an mRNA, which directs the synthesis of viral structural proteins. However, we are only beginning to understand the cellular and viral factors that influence trafficking of retroviral RNA and the selection of the RNA for encapsidation or translation. Live cell imaging studies of retroviral RNA trafficking have provided important insight into many aspects of the retrovirus life cycle including transcription dynamics, nuclear export of viral RNA, translational regulation, membrane targeting, and condensation of the gRNA during virion assembly. Here, we review cutting-edge techniques to visualize single RNA molecules in live cells and discuss the application of these systems to studying retroviral RNA trafficking.

  17. Ion Channel Trafficking: Control of Ion Channel Density as a Target for Arrhythmias?

    Directory of Open Access Journals (Sweden)

    Elise Balse

    2017-10-01

    Full Text Available The shape of the cardiac action potential (AP is determined by the contributions of numerous ion channels. Any dysfunction in the proper function or expression of these ion channels can result in a change in effective refractory period (ERP and lead to arrhythmia. The processes underlying the correct targeting of ion channels to the plasma membrane are complex, and have not been fully characterized in cardiac myocytes. Emerging evidence highlights ion channel trafficking as a potential causative factor in certain acquired and inherited arrhythmias, and therapies which target trafficking as opposed to pore block are starting to receive attention. In this review we present the current evidence for the mechanisms which underlie precise control of cardiac ion channel trafficking and targeting.

  18. A unifying mechanism accounts for sensing of membrane curvature by BAR domains, amphipathic helices and membrane-anchored proteins

    DEFF Research Database (Denmark)

    Bhatia, Vikram Kjøller; Hatzakis, Nikos; Stamou, Dimitrios

    2010-01-01

    itself. We thus anticipate that membrane curvature will promote the redistribution of proteins that are anchored in membranes through any type of hydrophobic moiety, a thesis that broadens tremendously the implications of membrane curvature for protein sorting, trafficking and signaling in cell biology....

  19. 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.

  20. Structural study on Ni nanowires in an anodic alumina membrane by using in situ heating extended x-ray absorption fine structure and x-ray diffraction techniques

    International Nuclear Information System (INIS)

    Cai Quan; Chen Xing; Chen Zhongjun; Wang Wei; Mo Guang; Wu Zhonghua; Zhang Junxi; Zhang Lide; Pan Wei

    2008-01-01

    Polycrystalline Ni nanowires have been prepared by electrochemical deposition in an anodic alumina membrane template with a nanopore size of about 60 nm. In situ heating extended x-ray absorption fine structure and x-ray diffraction techniques are used to probe the atomic structures. The nanowires are identified as being mixtures of nanocrystallites and amorphous phase. The nanocrystallites have the same thermal expansion coefficient, of 1.7 x 10 -5 K -1 , as Ni bulk; however, the amorphous phase has a much larger thermal expansion coefficient of 3.5 x 10 -5 K -1 . Details of the Ni nanowire structures are discussed in this paper

  1. Autoantibodies against Muscarinic Type 3 Receptor in Sjögren's Syndrome Inhibit Aquaporin 5 Trafficking

    Science.gov (United States)

    Lee, Byung Ha; Gauna, Adrienne E.; Perez, Geidys; Park, Yun-jong; Pauley, Kaleb M.; Kawai, Toshihisa; Cha, Seunghee

    2013-01-01

    Sjögren's syndrome (SjS) is a chronic autoimmune disease that mainly targets the salivary and lacrimal glands. It has been controversial whether anti-muscarinic type 3 receptor (α-M3R) autoantibodies in patients with SjS inhibit intracellular trafficking of aquaporin-5 (AQP5), water transport protein, leading to secretory dysfunction. To address this issue, GFP-tagged human AQP5 was overexpressed in human salivary gland cells (HSG-hAQP5) and monitored AQP5 trafficking to the plasma membrane following carbachol (CCh, M3R agonist) stimulation. AQP5 trafficking was indeed mediated by M3R stimulation, shown in partial blockage of trafficking by M3R-antagonist 4-DAMP. HSG-hAQP5 pre-incubated with SjS plasma for 24 hours significantly reduced AQP5 trafficking with CCh, compared with HSG-hAQP5 pre-incubated with healthy control (HC) plasma. This inhibition was confirmed by monoclonal α-M3R antibody and pre-absorbed plasma. Interestingly, HSG-hAQP5 pre-incubated with SjS plasma showed no change in cell volume, compared to the cells incubated with HC plasma showing shrinkage by twenty percent after CCh-stimulation. Our findings clearly indicate that binding of anti-M3R autoantibodies to the receptor, which was verified by immunoprecipitation, suppresses AQP5 trafficking to the membrane and contribute to impaired fluid secretion in SjS. Our current study urges further investigations of clinical associations between SjS symptoms, such as degree of secretory dysfunction, cognitive impairment, and/or bladder irritation, and different profiles (titers, isotypes, and/or specificity) of anti-M3R autoantibodies in individuals with SjS. PMID:23382834

  2. 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

  3. Real-time visualization of HIV-1 GAG trafficking in infected macrophages.

    Directory of Open Access Journals (Sweden)

    Karine Gousset

    2008-03-01

    Full Text Available HIV-1 particle production is driven by the Gag precursor protein Pr55(Gag. Despite significant progress in defining both the viral and cellular determinants of HIV-1 assembly and release, the trafficking pathway used by Gag to reach its site of assembly in the infected cell remains to be elucidated. The Gag trafficking itinerary in primary monocyte-derived macrophages is especially poorly understood. To define the site of assembly and characterize the Gag trafficking pathway in this physiologically relevant cell type, we have made use of the biarsenical-tetracysteine system. A small tetracysteine tag was introduced near the C-terminus of the matrix domain of Gag. The insertion of the tag at this position did not interfere with Gag trafficking, virus assembly or release, particle infectivity, or the kinetics of virus replication. By using this in vivo detection system to visualize Gag trafficking in living macrophages, Gag was observed to accumulate both at the plasma membrane and in an apparently internal compartment that bears markers characteristic of late endosomes or multivesicular bodies. Significantly, the internal Gag rapidly translocated to the junction between the infected macrophages and uninfected T cells following macrophage/T-cell synapse formation. These data indicate that a population of Gag in infected macrophages remains sequestered internally and is presented to uninfected target cells at a virological synapse.

  4. Pharmacological blockade of cholesterol trafficking by cepharanthine in endothelial cells suppresses angiogenesis and tumor growth.

    Science.gov (United States)

    Lyu, Junfang; Yang, Eun Ju; Head, Sarah A; Ai, Nana; Zhang, Baoyuan; Wu, Changjie; Li, Ruo-Jing; Liu, Yifan; Yang, Chen; Dang, Yongjun; Kwon, Ho Jeong; Ge, Wei; Liu, Jun O; Shim, Joong Sup

    2017-11-28

    Cholesterol is an important modulator of membrane protein function and signaling in endothelial cells, thus making it an emerging target for anti-angiogenic agents. In this study, we employed a phenotypic screen that detects intracellular cholesterol distribution in endothelial cells (HUVEC) and identified 13 existing drugs as cholesterol trafficking inhibitors. Cepharanthine, an approved drug for anti-inflammatory and cancer management use, was amongst the candidates, which was selected for in-depth mechanistic studies to link cholesterol trafficking and angiogenesis. Cepharanthine inhibited the endolysosomal trafficking of free-cholesterol and low-density lipoprotein in HUVEC by binding to Niemann-Pick disease, type C1 (NPC1) protein and increasing the lysosomal pH. The blockade of cholesterol trafficking led to a cholesterol-dependent dissociation of mTOR from the lysosomes and inhibition of its downstream signaling. Cepharanthine inhibited angiogenesis in HUVEC and in zebrafish in a cholesterol-dependent manner. Furthermore, cepharanthine suppressed tumor growth in vivo by inhibiting angiogenesis and it enhanced the antitumor activity of the standard chemotherapy cisplatin in lung and breast cancer xenografts in mice. Altogether, these results strongly support the idea that cholesterol trafficking is a viable drug target for anti-angiogenesis and that the inhibitors identified among existing drugs, such as cepharanthine, could be potential anti-angiogenic and antitumor agents. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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. 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. 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.

  9. 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.

  10. 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

  11. 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.

  12. Membrane fusion activity of vesicular stomatitis virus glycoprotein G is induced by low pH but not by heat or denaturant

    International Nuclear Information System (INIS)

    Yao Yi; Ghosh, Kakoli; Epand, Raquel F.; Epand, Richard M.; Ghosh, Hara P.

    2003-01-01

    The fusogenic envelope glycoprotein G of the rhabdovirus vesicular stomatitis virus (VSV) induces membrane fusion at acidic pH. At acidic pH the G protein undergoes a major structural reorganization leading to the fusogenic conformation. However, unlike other viral fusion proteins, the low-pH-induced conformational change of VSV G is completely reversible. As well, the presence of an α-helical coiled-coil motif required for fusion by a number of viral and cellular fusion proteins was not predicted in VSV G protein by using a number of algorithms. Results of pH dependence of the thermal stability of G protein as determined by intrinsic Trp fluorescence and circular dichroism (CD) spectroscopy show that the G protein is equally stable at neutral or acidic pH. Destabilization of G structure at neutral pH with either heat or urea did not induce membrane fusion or conformational change(s) leading to membrane fusion. Taken together, these data suggest that the mechanism of VSV G-induced fusion is distinct from the fusion mechanism of fusion proteins that involve a coiled-coil motif

  13. 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...

  14. 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

  15. 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...

  16. 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

  17. 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.

  18. 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.

  19. Membrane order in the plasma membrane and endocytic recycling compartment.

    Science.gov (United States)

    Iaea, David B; Maxfield, Frederick R

    2017-01-01

    The cholesterol content of membranes plays an important role in organizing membranes for signal transduction and protein trafficking as well as in modulating the biophysical properties of membranes. While the properties of model or isolated membranes have been extensively studied, there has been little evaluation of internal membranes in living cells. Here, we use a Nile Red based probe, NR12S, and ratiometric live cell imaging, to analyze the membrane order of the plasma membrane and endocytic recycling compartment. We find that after a brief incubation to allow endocytosis, NR12S is distributed between the plasma membrane and the endocytic recycling compartment. The NR12S reports that the endocytic recycling compartment is more highly ordered than the plasma membrane. We also find that the plasma membrane and the endocytic recycling compartment are differentially affected by altering cellular cholesterol levels. The membrane order of the plasma membrane, but not the endocytic recycling compartment, is altered significantly when cellular cholesterol content is increased or decreased by 20%. These results demonstrate that changes in cellular cholesterol differentially alter membrane order within different organelles.

  20. 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...

  1. 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

  2. Cell polarity development and protein trafficking in hepatocytes lacking E-cadherin/beta-catenin-based adherens junctions

    NARCIS (Netherlands)

    Theard, Delphine; Steiner, Magdalena; Kalicharan, Dharamdajal; Hoekstra, Dick; van IJzendoorn, Sven C. D.

    Using a mutant hepatocyte cell line in which E-cadherin and ss-catenin are completely depleted from the cell surface, and, consequently, fail to form adherens junctions, we have investigated adherens junction requirement for apical-basolateral polarity development and polarized membrane trafficking.

  3. 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...

  4. 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

  5. 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.

  6. Enthalpy analysis and Heat Exchanger Sizing of an Air-cooled Proton Exchange Membrane Fuel Cell System

    DEFF Research Database (Denmark)

    Gao, Xin; Berning, Torsten; Kær, Søren Knudsen

    below -20 °C in the winter which make liquid-cooled fuel cells impossible. In such cases, air-cooled fuel cell systems are deployed where the air that is fed to the fuel cell serves both as reactant supplier and coolant to remove the waste heat that is generated during fuel cell operation. In some cases...... in order to optimize the operating conditions and the performance of such a system. The adjustable parameters include the fan speed that determines the amount of air that is brought into the system, and the size and rotating speed of the rotating enthalpy wheel. In addition, computational fluid dynamics...... or an ordinary heat exchanger can fulfill the heat recovery demand. Despite the fact that the air enters the stack at a cold temperature, even the forefront of the stack is at a much elevated and desired stack temperature with the help of supplying an acceptable amount of power to an electric stack heater. So...

  7. Endosome-based protein trafficking and Ca2+ homeostasis in the heart

    Directory of Open Access Journals (Sweden)

    Jerry eCurran

    2015-02-01

    Full Text Available The ability to dynamically regulate, traffic, retain, and recycle proteins within the cell membrane is fundamental to life and central to the normal function of the heart and cardiovascular system. In the heart, these systems are essential for the regulation of cardiac calcium, both at the level of the plasma membrane, but also at local domains of the endoplasmic reticulum, sarcoplasmic reticulum, mitochondria, nucleus, and nuclear envelope. One intracellular pathway often overlooked in relation to cardiovascular calcium regulation and signaling is the endosome-based trafficking pathway. Highlighting its importance, this system and its molecular components are evolutionarily conserved across all metazoans. However, remarkably little is known of how endosome-based protein trafficking and recycling functions within mammalian cells systems, especially in the heart. The vast majority of what is known has been derived from heterologous cell systems. However, recently, more appropriate cell and animal models been developed that have allowed researchers to begin to understand how this system functions within the intact physiological environment. All excitable cells, including cardiomyocytes, depend on the proper expression and organization of multiple ion channels, pumps, exchangers, and transporters within the plasma membrane. As the endosomal system acts to regulate the expression and localization of membrane proteins, understanding the in vivo function of this system in the heart is important. This review will focus on endosome-based protein trafficking in the heart in both health and disease. Special emphasis will be given to the role played by the family of endocytic regulatory proteins, C-terminal Eps15 homology domain -containing proteins (EHDs, as recent data demonstrates that this family of proteins is essential for the proper trafficking and localization and of key proteins involved in excitation-contraction coupling.

  8. Cellular Localization and Trafficking of the Human ABCG1 Transporter

    Science.gov (United States)

    Neufeld, Edward B.; O’Brien, Katherine; Walts, Avram D.; Stonik, John A.; Demosky, Steven J.; Malide, Daniela; Combs, Christian A.; Remaley, Alan T.

    2014-01-01

    We have developed a suitable heterologous cell expression system to study the localization, trafficking, and site(s) of function of the human ABCG1 transporter. Increased plasma membrane (PM) and late endosomal (LE) cholesterol generated by ABCG1 was removed by lipoproteins and liposomes, but not apoA-I. Delivery of ABCG1 to the PM and LE was required for ABCG1-mediated cellular cholesterol efflux. ABCG1 LEs frequently contacted the PM, providing a collisional mechanism for transfer of ABCG1-mobilized cholesterol, similar to ABCG1-mediated PM cholesterol efflux to lipoproteins. ABCG1-mobilized LE cholesterol also trafficked to the PM by a non-vesicular pathway. Transfer of ABCG1-mobilized cholesterol from the cytoplasmic face of LEs to the PM and concomitant removal of cholesterol from the outer leaflet of the PM bilayer by extracellular acceptors suggests that ABCG1 mobilizes cholesterol on both sides of the lipid bilayer for removal by acceptors. ABCG1 increased uptake of HDL into LEs, consistent with a potential ABCG1-mediated cholesterol efflux pathway involving HDL resecretion. Thus, ABCG1 at the PM mobilizes PM cholesterol and ABCG1 in LE/LYS generates mobile pools of cholesterol that can traffic by both vesicular and non-vesicular pathways to the PM where it can also be transferred to extracellular acceptors with a lipid surface. PMID:25405320

  9. Complex lipid trafficking in Niemann-Pick disease type C.

    Science.gov (United States)

    Vanier, Marie T

    2015-01-01

    Niemann-Pick disease type C (NPC) is an atypical lysosomal storage disease resulting from mutations in one of two genes, either NPC1 or NPC2. Although a neurovisceral disorder, it is above all a neurodegenerative disease in the vast majority of patients. Not an enzyme deficiency, it is currently conceived as a lipid trafficking disorder. Impaired egress of cholesterol from the late endosomal/lysosomal (LE/L) compartment is a specific and key element of the pathogenesis, but other lipids, more specially sphingolipids, are also involved, and there are indications for further abnormalities. The full function of the NPC1 and NPC2 proteins is still unclear. This review provides a reappraisal of lipid storage and lysosomal enzymes activities in tissues/cells from NPC patients and animal models. It summarizes the current knowledge on the NPC1 and NPC2 proteins and their function in transport of cholesterol within the late endosomal-lysosomal compartment, with emphasis on differences between systemic organs and the brain; it also discusses regulation by membrane lipids of the NPC2-mediated cholesterol trafficking, interplay between cholesterol and sphingomyelin, the metabolic origin of glycosphingolipids stored in brain, and the putative role of free sphingoid bases in pathogenesis. Brief mention is finally made of diseases affecting other genes that were very recently shown to impact the "NPC pathway".

  10. Exocyst and autophagy-related membrane trafficking in plants

    Czech Academy of Sciences Publication Activity Database

    Pečenková, Tamara; Marković, Vedrana; Sabol, P.; Kulich, I.; Žárský, Viktor

    2018-01-01

    Roč. 69, č. 1 (2018), s. 47-57 ISSN 0022-0957 R&D Projects: GA ČR(CZ) GA15-14886S Institutional support: RVO:61389030 Keywords : Autophagy * endomembranes * exocyst * plant defence * secretory transport * ups Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Cell biology Impact factor: 5.830, year: 2016

  11. 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

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

  13. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Spatial separation and bidirectional trafficking of proteins using a multi-functional reporter

    Directory of Open Access Journals (Sweden)

    Klaubert Dieter H

    2008-04-01

    Full Text Available Abstract Background The ability to specifically label proteins within living cells can provide information about their dynamics and function. To study a membrane protein, we fused a multi-functional reporter protein, HaloTag®, to the extracellular domain of a truncated integrin. Results Using the HaloTag technology, we could study the localization, trafficking and processing of an integrin-HaloTag fusion, which we showed had cellular dynamics consistent with native integrins. By labeling live cells with different fluorescent impermeable and permeable ligands, we showed spatial separation of plasma membrane and internal pools of the integrin-HaloTag fusion, and followed these protein pools over time to study bi-directional trafficking. In addition to combining the HaloTag reporter protein with different fluorophores, we also employed an affinity tag to achieve cell capture. Conclusion The HaloTag technology was used successfully to study expression, trafficking, spatial separation and real-time translocation of an integrin-HaloTag fusion, thereby demonstrating that this technology can be a powerful tool to investigate membrane protein biology in live cells.

  16. Neuron specific Rab4 effector GRASP-1 coordinates membrane specialization and maturation of recycling endosomes

    NARCIS (Netherlands)

    C.C. Hoogenraad (Casper); I. Popa (Ioana); K. Futai (Kensuke); E. Sanchez-Martinez (Emma); P. Wulf (Phebe); T. van Vlijmen (Thijs); B.R. Dortland (Bjorn); V. Oorschot (Viola); R. Govers (Robert); M. Monti (Maria); A.J.R. Heck (Albert); M. Sheng (Morgan); J. Klumperman (Judith); H. Rehmann (Holger); D. Jaarsma (Dick); L.C. Kapitein (Lukas); P. van der Sluijs

    2010-01-01

    textabstractThe endosomal pathway in neuronal dendrites is essential for membrane receptor trafficking and proper synaptic function and plasticity. However, the molecular mechanisms that organize specific endocytic trafficking routes are poorly understood. Here, we identify GRIP-associated protein-1

  17. Uncoordinated (UNC)119: coordinating the trafficking of myristoylated proteins.

    Science.gov (United States)

    Constantine, Ryan; Zhang, Houbin; Gerstner, Cecilia D; Frederick, Jeanne M; Baehr, Wolfgang

    2012-12-15

    The mechanism by which myristoylated proteins are targeted to specific subcellular membrane compartments is poorly understood. Two novel acyl-binding proteins, UNC119A and UNC119B, have been shown recently to function as chaperones/co-factors in the transport of myristoylated G protein α-subunits and src-type tyrosine kinases. UNC119 polypeptides feature an immunoglobulin-like β-sandwich fold that forms a hydrophobic pocket capable of binding lauroyl (C12) and myristoyl (C14) side chains. UNC119A in rod photoreceptors facilitates the transfer of transducin α subunits (Tα) from inner segment to outer segment membranes by forming an intermediate diffusible UNC119-Tα complex. Similar complexes are formed in other sensory neurons, as the G proteins ODR-3 and GPA-13 in Caenorhabditis elegans unc-119 mutants traffic inappropriately. UNC119B knockdown in IMCD3 cells prevents trafficking ofmyristoylated nephrocystin-3 (NPHP3), a protein associated with nephronophthisis, to cilia. Further, UNC119A was shown to transport myristoylated src-type tyrosine kinases to cell membranes and to affect T-cell receptor (TCR) and interleukin-5 receptor (IL-5R) activities. These interactions establish UNC119 polypeptides as novel lipid-binding chaperones with specificity for a diverse subset of myristoylated proteins. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. The novel C-terminal KCNQ1 mutation M520R alters protein trafficking

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. HIV-1 Envelope Glycoprotein Trafficking through the Endosomal Recycling Compartment Is Required for Particle Incorporation.

    Science.gov (United States)

    Kirschman, Junghwa; Qi, Mingli; Ding, Lingmei; Hammonds, Jason; Dienger-Stambaugh, Krista; Wang, Jaang-Jiun; Lapierre, Lynne A; Goldenring, James R; Spearman, Paul

    2018-03-01

    The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) encodes specific trafficking signals within its long cytoplasmic tail (CT) that regulate incorporation into HIV-1 particles. Rab11-family interacting protein 1C (FIP1C) and Rab14 are host trafficking factors required for Env particle incorporation, suggesting that Env undergoes sorting from the endosomal recycling compartment (ERC) to the site of particle assembly on the plasma membrane. We disrupted outward sorting from the ERC by expressing a C-terminal fragment of FIP1C (FIP1C 560-649 ) and examined the consequences on Env trafficking and incorporation into particles. FIP1C 560-649 reduced cell surface levels of Env and prevented its incorporation into HIV-1 particles. Remarkably, Env was trapped in an exaggerated perinuclear ERC in a CT-dependent manner. Mutation of either the Yxxϕ endocytic motif or the YW 795 motif in the CT prevented Env trapping in the ERC and restored incorporation into particles. In contrast, simian immunodeficiency virus SIVmac239 Env was not retained in the ERC, while substitution of the HIV-1 CT for the SIV CT resulted in SIV Env retention in this compartment. These results provide the first direct evidence that Env traffics through the ERC and support a model whereby HIV-1 Env is specifically targeted to the ERC prior to FIP1C- and CT-dependent outward sorting to the particle assembly site on the plasma membrane. IMPORTANCE The HIV envelope protein is an essential component of the viral particle. While many aspects of envelope protein structure and function have been established, the pathway it follows in the cell prior to reaching the site of particle assembly is not well understood. The envelope protein has a very long cytoplasmic tail that interacts with the host cell trafficking machinery. Here, we utilized a truncated form of the trafficking adaptor FIP1C protein to arrest the intracellular transport of the envelope protein, demonstrating that it becomes

  4. One dimensional transient numerical study of the mass heat and charge transfer in a proton exchange membrane for PEMFC

    Energy Technology Data Exchange (ETDEWEB)

    Haddad, Djamel; Benmoussa, Hocine [Laboratory (LESEI), Faculty of Engineering, University of Batna (Algeria); Bourmada, Noureddine; Oulmi, Kafia [Laboratory LCCE, Faculty of Science, University of Batna (Algeria); Mahmah, Bouziane; Belhamel, Maiouf [CDER, BP, 62 Avenue-Observatoire, Bouzareah, Alger (Algeria)

    2009-06-15

    The objective of our study is to quantify the mass water transferred by various modes: diffusion, convection and migration. For the water transfer, the principal forces considered in the model are, the convection force, the osmotic force (i.e. diffusion) and the electric force (migration). The first of these forces results from a pressure gradient, the second of a concentration gradient and the third of a protons' migration from the anode to the cathode, which has an effect on the dipole of the water molecules (resistance force to the advancement). The numerical tool used to solve the equations' system is the finite element method. The results obtained numerically considering this method are concentration profiles and concentration variation with time and membrane thickness. These results illustrate the contribution of each mass transfer mode. (author)

  5. The Role of Rab Proteins in Neuronal Cells and in the Trafficking of Neurotrophin Receptors

    Directory of Open Access Journals (Sweden)

    Cecilia Bucci

    2014-10-01

    Full Text Available Neurotrophins are a family of proteins that are important for neuronal development, neuronal survival and neuronal functions. Neurotrophins exert their role by binding to their receptors, the Trk family of receptor tyrosine kinases (TrkA, TrkB, and TrkC and p75NTR, a member of the tumor necrosis factor (TNF receptor superfamily. Binding of neurotrophins to receptors triggers a complex series of signal transduction events, which are able to induce neuronal differentiation but are also responsible for neuronal maintenance and neuronal functions. Rab proteins are small GTPases localized to the cytosolic surface of specific intracellular compartments and are involved in controlling vesicular transport. Rab proteins, acting as master regulators of the membrane trafficking network, play a central role in both trafficking and signaling pathways of neurotrophin receptors. Axonal transport represents the Achilles' heel of neurons, due to the long-range distance that molecules, organelles and, in particular, neurotrophin-receptor complexes have to cover. Indeed, alterations of axonal transport and, specifically, of axonal trafficking of neurotrophin receptors are responsible for several human neurodegenerative diseases, such as Huntington’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis and some forms of Charcot-Marie-Tooth disease. In this review, we will discuss the link between Rab proteins and neurotrophin receptor trafficking and their influence on downstream signaling pathways.

  6. Trafficking regulates the subcellular distribution of voltage-gated sodium channels in primary sensory neurons.

    Science.gov (United States)

    Bao, Lan

    2015-09-30

    Voltage-gated sodium channels (Navs) comprise at least nine pore-forming α subunits. Of these, Nav1.6, Nav1.7, Nav1.8 and Nav1.9 are the most frequently studied in primary sensory neurons located in the dorsal root ganglion and are mainly localized to the cytoplasm. A large pool of intracellular Navs raises the possibility that changes in Nav trafficking could alter channel function. The molecular mediators of Nav trafficking mainly consist of signals within the Navs themselves, interacting proteins and extracellular factors. The surface expression of Navs is achieved by escape from the endoplasmic reticulum and proteasome degradation, forward trafficking and plasma membrane anchoring, and it is also regulated by channel phosphorylation and ubiquitination in primary sensory neurons. Axonal transport and localization of Navs in afferent fibers involves the motor protein KIF5B and scaffold proteins, including contactin and PDZ domain containing 2. Localization of Nav1.6 to the nodes of Ranvier in myelinated fibers of primary sensory neurons requires node formation and the submembrane cytoskeletal protein complex. These findings inform our understanding of the molecular and cellular mechanisms underlying Nav trafficking in primary sensory neurons.

  7. Cystic Fibrosis, Cystic Fibrosis Transmembrane Conductance Regulator and Drugs: Insights from Cellular Trafficking.

    Science.gov (United States)

    Bridges, Robert J; Bradbury, Neil A

    2018-01-01

    The eukaryotic cell is organized into membrane-delineated compartments that are characterized by specific cadres of proteins sustaining biochemically distinct cellular processes. The appropriate subcellular localization of proteins is key to proper organelle function and provides a physiological context for cellular processes. Disruption of normal trafficking pathways for proteins is seen in several genetic diseases, where a protein's absence for a specific subcellular compartment leads to organelle disruption, and in the context of an individual, a disruption of normal physiology. Importantly, several drug therapies can also alter protein trafficking, causing unwanted side effects. Thus, a deeper understanding of trafficking pathways needs to be appreciated as novel therapeutic modalities are proposed. Despite the promising efficacy of novel therapeutic agents, the intracellular bioavailability of these compounds has proved to be a potential barrier, leading to failures in treatments for various diseases and disorders. While endocytosis of drug moieties provides an efficient means of getting material into cells, the subsequent release and endosomal escape of materials into the cytosol where they need to act has been a barrier. An understanding of cellular protein/lipid trafficking pathways has opened up strategies for increasing drug bioavailability. Approaches to enhance endosomal exit have greatly increased the cytosolic bioavailability of drugs and will provide a means of investigating previous drugs that may have been shelved due to their low cytosolic concentration.

  8. The Role of Rab Proteins in Neuronal Cells and in the Trafficking of Neurotrophin Receptors

    Science.gov (United States)

    Bucci, Cecilia; Alifano, Pietro; Cogli, Laura

    2014-01-01

    Neurotrophins are a family of proteins that are important for neuronal development, neuronal survival and neuronal functions. Neurotrophins exert their role by binding to their receptors, the Trk family of receptor tyrosine kinases (TrkA, TrkB, and TrkC) and p75NTR, a member of the tumor necrosis factor (TNF) receptor superfamily. Binding of neurotrophins to receptors triggers a complex series of signal transduction events, which are able to induce neuronal differentiation but are also responsible for neuronal maintenance and neuronal functions. Rab proteins are small GTPases localized to the cytosolic surface of specific intracellular compartments and are involved in controlling vesicular transport. Rab proteins, acting as master regulators of the membrane trafficking network, play a central role in both trafficking and signaling pathways of neurotrophin receptors. Axonal transport represents the Achilles' heel of neurons, due to the long-range distance that molecules, organelles and, in particular, neurotrophin-receptor complexes have to cover. Indeed, alterations of axonal transport and, specifically, of axonal trafficking of neurotrophin receptors are responsible for several human neurodegenerative diseases, such as Huntington’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis and some forms of Charcot-Marie-Tooth disease. In this review, we will discuss the link between Rab proteins and neurotrophin receptor trafficking and their influence on downstream signaling pathways. PMID:25295627

  9. Exosomes derived from human macrophages suppress endothelial cell migration by controlling integrin trafficking.

    Science.gov (United States)

    Lee, Hee Doo; Kim, Yeon Hyang; Kim, Doo-Sik

    2014-04-01

    Integrin trafficking, including internalization, recycling, and lysosomal degradation, is crucial for the regulation of cellular functions. Exosomes, nano-sized extracellular vesicles, are believed to play important roles in intercellular communications. This study demonstrates that exosomes released from human macrophages negatively regulate endothelial cell migration through control of integrin trafficking. Macrophage-derived exosomes promote internalization of integrin β1 in primary HUVECs. The internalized integrin β1 persistently accumulates in the perinuclear region and is not recycled back to the plasma membrane. Experimental results indicate that macrophage-derived exosomes stimulate trafficking of internalized integrin β1 to lysosomal compartments with a corresponding decrease in the integrin destined for recycling endosomes, resulting in proteolytic degradation of the integrin. Moreover, ubiquitination of HUVEC integrin β1 is enhanced by the exosomes, and exosome-mediated integrin degradation is blocked by bafilomycin A, a lysosomal degradation inhibitor. Macrophage-derived exosomes were also shown to effectively suppress collagen-induced activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase signaling pathway and HUVEC migration, which are both dependent on integrin β1. These observations provide new insight into the functional significance of exosomes in the regulation of integrin trafficking. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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...

  16. 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.

  17. Recycling endosomes in apical plasma membrane domain formation and epithelial cell polarity

    NARCIS (Netherlands)

    Golachowska, Magdalena R.; Hoekstra, Dick; van IJzendoorn, Sven C. D.

    2010-01-01

    Recycling endosomes have taken central stage in the intracellular sorting and polarized trafficking of apical and basolateral plasma membrane components. Molecular players in the underlying mechanisms are now emerging, including small GTPases, class V myosins and adaptor proteins. In particular,

  18. Molecular View of Cholesterol Flip-Flop and Chemical Potential in Different Membrane Environments

    NARCIS (Netherlands)

    Bennett, W. F. Drew; MacCallum, Justin L.; Hinner, Marlon J.; Marrink, Siewert J.; Tieleman, D. Peter

    2009-01-01

    The relative stability of cholesterol in cellular membranes and the thermodynamics of fluctuations from equilibrium have important consequences for sterol trafficking and lateral domain formation. We used molecular dynamics computer simulations to investigate the partitioning of cholesterol in a

  19. Rotating bubble membrane radiator

    Science.gov (United States)

    Webb, Brent J.; Coomes, Edmund P.

    1988-12-06

    A heat radiator useful for expelling waste heat from a power generating system aboard a space vehicle is disclosed. Liquid to be cooled is passed to the interior of a rotating bubble membrane radiator, where it is sprayed into the interior of the bubble. Liquid impacting upon the interior surface of the bubble is cooled and the heat radiated from the outer surface of the membrane. Cooled liquid is collected by the action of centrifical force about the equator of the rotating membrane and returned to the power system. Details regarding a complete space power system employing the radiator are given.

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. Manipulation of host membranes by bacterial effectors.

    Science.gov (United States)

    Ham, Hyeilin; Sreelatha, Anju; Orth, Kim

    2011-07-18

    Bacterial pathogens interact with host membranes to trigger a wide range of cellular processes during the course of infection. These processes include alterations to the dynamics between the plasma membrane and the actin cytoskeleton, and subversion of the membrane-associated pathways involved in vesicle trafficking. Such changes facilitate the entry and replication of the pathogen, and prevent its phagocytosis and degradation. In this Review, we describe the manipulation of host membranes by numerous bacterial effectors that target phosphoinositide metabolism, GTPase signalling and autophagy.

  7. 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...

  8. 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.

  9. 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.

  10. 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,…

  11. 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…

  12. 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 ...

  13. 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...

  14. 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...

  15. Dynamic nuclear polarization methods in solids and solutions to explore membrane proteins and membrane systems.

    Science.gov (United States)

    Cheng, Chi-Yuan; Han, Songi

    2013-01-01

    Membrane proteins regulate vital cellular processes, including signaling, ion transport, and vesicular trafficking. Obtaining experimental access to their structures, conformational fluctuations, orientations, locations, and hydration in membrane environments, as well as the lipid membrane properties, is critical to understanding their functions. Dynamic nuclear polarization (DNP) of frozen solids can dramatically boost the sensitivity of current solid-state nuclear magnetic resonance tools to enhance access to membrane protein structures in native membrane environments. Overhauser DNP in the solution state can map out the local and site-specific hydration dynamics landscape of membrane proteins and lipid membranes, critically complementing the structural and dynamics information obtained by electron paramagnetic resonance spectroscopy. Here, we provide an overview of how DNP methods in solids and solutions can significantly increase our understanding of membrane protein structures, dynamics, functions, and hydration in complex biological membrane environments.

  16. Disruption of endolysosomal trafficking pathways in glioma cells by methuosis-inducing indole-based chalcones.

    Science.gov (United States)

    Mbah, Nneka E; Overmeyer, Jean H; Maltese, William A

    2017-06-01

    Methuosis is a form of non-apoptotic cell death involving massive vacuolization of macropinosome-derived endocytic compartments, followed by a decline in metabolic activity and loss of membrane integrity. To explore the induction of methuosis as a potential therapeutic strategy for killing cancer cells, we have developed small molecules (indole-based chalcones) that trigger this form of cell death in glioblastoma and other cancer cell lines. Here, we report that in addition to causing fusion and expansion of macropinosome compartments, the lead compound, 3-(5-methoxy-2-methyl-1H-indol-3-yl)-1-(4-pyridinyl)-2-propen-1-one (MOMIPP), disrupts vesicular trafficking at the lysosomal nexus, manifested by impaired degradation of EGF and LDL receptors, defective processing of procathepsins, and accumulation of autophagosomes. In contrast, secretion of the ectodomain derived from a prototypical type-I membrane glycoprotein, β-amyloid precursor protein, is increased rather than diminished. A closely related MOMIPP analog, which causes substantial vacuolization without reducing cell viability, also impedes cathepsin processing and autophagic flux, but has more modest effects on receptor degradation. A third analog, which causes neither vacuolization nor loss of viability, has no effect on endolysosomal trafficking. The results suggest that differential cytotoxicity of structurally similar indole-based chalcones is related, at least in part, to the severity of their effects on endolysosomal trafficking pathways.

  17. hERG trafficking inhibition in drug-induced lethal cardiac arrhythmia.

    Science.gov (United States)

    Nogawa, Hisashi; Kawai, Tomoyuki

    2014-10-15

    Acquired long QT syndrome induced by non-cardiovascular drugs can cause lethal cardiac arrhythmia called torsades de points and is a significant problem in drug development. The prolongation of QT interval and cardiac action potential duration are mainly due to reduced physiological function of the rapidly activating voltage-dependent potassium channels encoded by human ether-a-go-go-related gene (hERG). Structurally diverse groups of drugs are known to directly inhibit hERG channel conductance. Therefore, the ability of acute hERG inhibition is routinely assessed at the preclinical stages in pharmaceutical testing. Recent findings indicated that chronic treatment with various drugs not only inhibits hERG channels but also decreases hERG channel expression in the plasma membrane of cardiomyocytes, which has become another concern in safety pharmacology. The mechanisms involve the disruption of hERG trafficking to the surface membrane or the acceleration of hERG protein degradation. From this perspective, we present a brief overview of mechanisms of drug-induced trafficking inhibition and pathological regulation. Understanding of drug-induced hERG trafficking inhibition may provide new strategies for predicting drug-induced QT prolongation and lethal cardiac arrhythmia in pharmaceutical drug development. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. LRP1 controls biosynthetic and endocytic trafficking of neuronal prion protein

    DEFF Research Database (Denmark)

    Parkyn, Celia J; Vermeulen, Esmeralda G M; Mootoosamy, Roy C

    2008-01-01

    The trafficking of normal cellular prion protein (PrP(C)) is believed to control its conversion to the altered conformation (designated PrP(Sc)) associated with prion disease. Although anchored to the membrane by means of glycosylphosphatidylinositol (GPI), PrP(C) on neurons is rapidly and consti......The trafficking of normal cellular prion protein (PrP(C)) is believed to control its conversion to the altered conformation (designated PrP(Sc)) associated with prion disease. Although anchored to the membrane by means of glycosylphosphatidylinositol (GPI), PrP(C) on neurons is rapidly...... required for this process. Moreover, sustained inhibition of LRP1 levels by siRNA leads to the accumulation of PrP(C) in biosynthetic compartments, with a concomitant lowering of surface PrP(C), suggesting that LRP1 expedites the trafficking of PrP(C) to the neuronal surface. PrP(C) and LRP1 can be co......-immunoprecipitated from the endoplasmic reticulum in normal neurons. The N-terminal domain of PrP(C) binds to purified human LRP1 with nanomolar affinity, even in the presence of 1 microM of the LRP-specific chaperone, receptor-associated protein (RAP). Taken together, these data argue that LRP1 controls both the surface...

  19. Polyurethane Nanofiber Membranes for Waste Water Treatment by Membrane Distillation

    OpenAIRE

    Jiříček, T.; Komárek, M.; Lederer, T.

    2017-01-01

    Self-sustained electrospun polyurethane nanofiber membranes were manufactured and tested on a direct-contact membrane distillation unit in an effort to find the optimum membrane thickness to maximize flux rate and minimize heat losses across the membrane. Also salt retention and flux at high salinities up to 100 g kg−1 were evaluated. Even though the complex structure of nanofiber layers has extreme specific surface and porosity, membrane performance was surprisingly predictable; the highest ...

  20. Separation membrane development

    Energy Technology Data Exchange (ETDEWEB)

    Lee, M.W. [Savannah River Technology Center, Aiken, SC (United States)

    1998-08-01

    A ceramic membrane has been developed to separate hydrogen from other gases. The method used is a sol-gel process. A thin layer of dense ceramic material is coated on a coarse ceramic filter substrate. The pore size distribution in the thin layer is controlled by a densification of the coating materials by heat treatment. The membrane has been tested by permeation measurement of the hydrogen and other gases. Selectivity of the membrane has been achieved to separate hydrogen from carbon monoxide. The permeation rate of hydrogen through the ceramic membrane was about 20 times larger than Pd-Ag membrane.

  1. Early to Late Endosome Trafficking Controls Secretion and Zymogen Activation in Rodent and Human Pancreatic Acinar Cells.

    Science.gov (United States)

    Messenger, Scott W; Thomas, Diana Dh; Cooley, Michelle M; Jones, Elaina K; Falkowski, Michelle A; August, Benjamin K; Fernandez, Luis A; Gorelick, Fred S; Groblewski, Guy E

    2015-11-01

    Pancreatic acinar cells have an expanded apical endosomal system, the physiological and pathophysiological significance of which is still emerging. Phosphatidylinositol-3,5-bisphosphate (PI(3,5)P 2 ) is an essential phospholipid generated by PIKfyve, which phosphorylates phosphatidylinositol-3-phosphate (PI(3)P). PI(3,5)P 2 is necessary for maturation of early endosomes (EE) to late endosomes (LE). Inhibition of EE to LE trafficking enhances anterograde endosomal trafficking and secretion at the plasma membrane by default through a recycling endosome (RE) intermediate. We assessed the effects of modulating PIKfyve activity on apical trafficking and pancreatitis responses in pancreatic acinar cells. Inhibition of EE to LE trafficking was achieved using pharmacological inhibitors of PIKfyve, expression of dominant negative PIKfyve K1877E, or constitutively active Rab5-GTP Q79L. Anterograde endosomal trafficking was manipulated by expression of constitutively active and dominant negative Rab11a mutants. The effects of these agents on secretion, endolysosomal exocytosis of lysosome associated membrane protein (LAMP1), and trypsinogen activation in response to high-dose CCK-8, bile acids and cigarette toxin was determined. PIKfyve inhibition increased basal and stimulated secretion. Adenoviral overexpression of PIKfyve decreased secretion leading to cellular death. Expression of Rab5-GTP Q79L or Rab11a-GTP Q70L enhanced secretion. Conversely, dominant-negative Rab11a-GDP S25N reduced secretion. High-dose CCK inhibited endolysosomal exocytosis that was reversed by PIKfyve inhibition. PIKfyve inhibition blocked intracellular trypsin accumulation and cellular damage responses to high CCK-8, tobacco toxin, and bile salts in both rodent and human acini. These data demonstrate that EE-LE trafficking acutely controls acinar secretion and the intracellular activation of zymogens leading to the pathogenicity of acute pancreatitis.

  2. 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…

  3. Elongation Factor Tu and Heat Shock Protein 70 Are Membrane-Associated Proteins from Mycoplasma ovipneumoniae Capable of Inducing Strong Immune Response in Mice.

    Directory of Open Access Journals (Sweden)

    Fei Jiang

    Full Text Available Chronic non-progressive pneumonia, a disease that has become a worldwide epidemic has caused considerable loss to sheep industry. Mycoplasma ovipneumoniae (M. ovipneumoniae is the causative agent of interstitial pneumonia in sheep, goat and bighorn. We here have identified by immunogold and immunoblotting that elongation factor Tu (EF-Tu and heat shock protein 70 (HSP 70 are membrane-associated proteins on M. ovipneumonaiea. We have evaluated the humoral and cellular immune responses in vivo by immunizing BALB/c mice with both purified recombinant proteins rEF-Tu and rHSP70. The sera of both rEF-Tu and rHSP70 treated BALB/c mice demonstrated increased levels of IgG, IFN-γ, TNF-α, IL-12(p70, IL-4, IL-5 and IL-6. In addition, ELISPOT assay showed significant increase in IFN-γ+ secreting lymphocytes in the rHSP70 group when compared to other groups. Collectively our study reveals that rHSP70 induces a significantly better cellular immune response in mice, and may act as a Th1 cytokine-like adjuvant in immune response induction. Finally, growth inhibition test (GIT of M. ovipneumoniae strain Y98 showed that sera from rHSP70 or rEF-Tu-immunized mice inhibited in vitro growth of M. ovipneumoniae. Our data strongly suggest that EF-Tu and HSP70 of M. ovipneumoniae are membrane-associated proteins capable of inducing antibody production, and cytokine secretion. Therefore, these two proteins may be potential candidates for vaccine development against M. ovipneumoniae infection in sheep.

  4. 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.

  5. REGULATED VESICULAR TRAFFICKING OF SPECIFIC PCDH15 AND VLGR1 VARIANTS IN AUDITORY HAIR CELLS

    Science.gov (United States)

    Zallocchi, Marisa; Delimont, Duane; Meehan, Daniel T.; Cosgrove, Dominic

    2012-01-01

    Usher syndrome is a genetically heterogeneous disorder characterized by hearing and balance dysfunction and progressive retinitis pigmentosa. Mouse models carrying mutations for the nine Usher-associated genes have splayed stereocilia and some show delayed maturation of ribbon synapses suggesting these proteins may play different roles in terminal differentiation of auditory hair cells. The presence of the Usher proteins at the basal and apical aspects of the neurosensory epithelia suggests the existence of regulated trafficking through specific transport proteins and routes. Immature mouse cochleae and UB/OC-1 cells were used in this work to address whether specific variants of PCDH15 and VLGR1 are being selectively transported to opposite poles of the hair cells. Confocal co-localization studies between apical and basal vesicular markers and the different PCDH15 and VLGR1 variants along with sucrose density gradients and the use of vesicle trafficking inhibitors show the existence of Usher protein complexes in at least two vesicular sub-pools. The apically trafficked pool co-localized with the early endosomal vesicle marker, rab5, while the basally trafficked pool associates with membrane microdomains and SNAP25. Moreover, co-immunoprecipitation experiments between SNAP25 and VLGR1 show a physical interaction of these two proteins in organ of Corti and brain. Collectively, these findings establish the existence of a differential vesicular trafficking mechanism for specific Usher protein variants in mouse cochlear hair cells, with the apical variants playing a potential role in endosomal recycling and stereocilia development/maintenance and the basolateral variants involved in vesicle docking and/or fusion through SNAP25-mediated interactions. PMID:23035094

  6. 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

  7. 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.

  8. 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.

  9. 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...

  10. 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…

  11. 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.

  12. 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...

  13. 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

  14. 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.

  15. Cell polarity and patterning by PIN trafficking through early endosomal compartments in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Hirokazu Tanaka

    2013-05-01

    Full Text Available PIN-FORMED (PIN proteins localize asymmetrically at the plasma membrane and mediate intercellular polar transport of the plant hormone auxin that is crucial for a multitude of developmental processes in plants. PIN localization is under extensive control by environmental or developmental cues, but mechanisms regulating PIN localization are not fully understood. Here we show that early endosomal components ARF GEF BEN1 and newly identified Sec1/Munc18 family protein BEN2 are involved in distinct steps of early endosomal trafficking. BEN1 and BEN2 are collectively required for polar PIN localization, for their dynamic repolarization, and consequently for auxin activity gradient formation and auxin-related developmental processes including embryonic patterning, organogenesis, and vasculature venation patterning. These results show that early endosomal trafficking is crucial for cell polarity and auxin-dependent regulation of plant architecture.

  16. 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.

  17. Heat death in the crayfish Austropotamobius pallipes: thermal inactivation of muscle membrane-bound ATPases in warm and cold adapted animals

    Energy Technology Data Exchange (ETDEWEB)

    Gladwell, R T

    1976-01-01

    The thermal sensitivity of the membrane-bound Mg/sup 2 +/ and Na/sup +/ + K/sup +/ + Mg/sup 2 +/ ATPases from the abdominal flexor muscles of 10 and 25/sup 0/C acclimated animals was investigated. The Mg/sup 2 +/ ATPase was inactivated by milder heat treatments than the Na/sup +/ + K/sup +/ + Mg/sup 2 +/ ATPase. The effect of high lethal temperatures on the Mg/sup 2 +/ ATPase was dependent on the previous thermal history of the animal, the enzyme preparations from 10/sup 0/C acclimated animals being more sensitive than those from 25/sup 0/C acclimated animals. The thermal sensitivity of the Na/sup +/ + K/sup +/ + Mg/sup 2 +/ ATPase was not altered by temperature acclimation. The change in the thermal sensitivity of the Mg/sup 2 +/ ATPase with the acclimation temperature of the whole animal was correlated with the survival times of 10 and 25/sup 0/C acclimated animals. The K/sub m/ and V/sub max/ of the ATPases was investigated and the K/sub m/ of both enzymes was found to decrease with acclimation of the whole animal to lower temperatures, so that enzyme/substrate affinity increased with cold acclimation. It was concluded that the inactivation of the muscle Mg/sup 2 +/ ATPase was the primary lesion of heat death in the crayfish, and that the changes in the kinetic properties of the ATPases were an important mechanism in the process of physiological temperature acclimation.

  18. Performance modeling of direct contact membrane distillation (DCMD) seawater desalination process using a commercial composite membrane

    KAUST Repository

    Lee, Junggil; Kim, Youngdeuk; Kim, Wooseung; Francis, Lijo; Amy, Gary L.; Ghaffour, NorEddine

    2015-01-01

    membrane and the heat transfer across the membrane and through the boundary layers adjacent to the membrane surfaces. Experimental results and model predictions for permeate flux and performance ratio are compared and shown to be in good agreement

  19. P-glycoprotein trafficking as a therapeutic target to optimize CNS drug delivery.

    Science.gov (United States)

    Davis, Thomas P; Sanchez-Covarubias, Lucy; Tome, Margaret E

    2014-01-01

    The primary function of the blood-brain barrier (BBB)/neurovascular unit is to protect the central nervous system (CNS) from potentially harmful xenobiotic substances and maintain CNS homeostasis. Restricted access to the CNS is maintained via a combination of tight junction proteins as well as a variety of efflux and influx transporters that limits the transcellular and paracellular movement of solutes. Of the transporters identified at the BBB, P-glycoprotein (P-gp) has emerged as the transporter that is the greatest obstacle to effective CNS drug delivery. In this chapter, we provide data to support intracellular protein trafficking of P-gp within cerebral capillary microvessels as a potential target for improved drug delivery. We show that pain-induced changes in P-gp trafficking are associated with changes in P-gp's association with caveolin-1, a key scaffolding/trafficking protein that colocalizes with P-gp at the luminal membrane of brain microvessels. Changes in colocalization with the phosphorylated and nonphosphorylated forms of caveolin-1, by pain, are accompanied by dynamic changes in the distribution, relocalization, and activation of P-gp "pools" between microvascular endothelial cell subcellular compartments. Since redox-sensitive processes may be involved in signaling disassembly of higher-order structures of P-gp, we feel that manipulating redox signaling, via specific protein targeting at the BBB, may protect disulfide bond integrity of P-gp reservoirs and control trafficking to the membrane surface, providing improved CNS drug delivery. The advantage of therapeutic drug "relocalization" of a protein is that the physiological impact can be modified, temporarily or long term, despite pathology-induced changes in gene transcription. © 2014 Elsevier Inc. All rights reserved.

  20. Ocean thermocline driven membrane distillation process

    KAUST Repository

    Francis, Lijo

    2017-07-20

    Systems and methods using membrane distillation are provided for desalinating water, for example for the production of potable water, to address freshwater requirements. In an aspect the systems and methods do not require applying an external heat source, or the energy cost of the heating source, to heat the feed stream to the membrane. In an aspect, the sensible heat present in surface seawater is used for the heat energy for the warm stream fed to the membrane, and deep seawater is used as the cold/coolant feed to the membrane to provide the needed temperature gradient or differential across the membrane.

  1. Hydrogen production using the waste heat of Benchmark pressurized Molten carbonate fuel cell system via combination of organic Rankine cycle and proton exchange membrane (PEM) electrolysis

    International Nuclear Information System (INIS)

    Nami, Hossein; Akrami, Ehsan; Ranjbar, Faramarz

    2017-01-01

    Highlights: • Waste heat of the Benchmark system recovered using an ORC. • An integrated system is proposed to produce power and hydrogen. • The effects of some decision parameters on the produced hydrogen have investigated. - Abstract: Energy and exergy analyses are carried out for hydrogen production via combination of Benchmark system and organic Rankine cycle (ORC) coupled with a proton exchange membrane electrolyzer. A parametric study is reported and effects of such organic Rankine cycle significant variables as evaporator temperature, pinch point temperature difference in the evaporator and degree of superheat at the ORC turbine inlet on the rate of produced hydrogen, sustainability index, overall exergy efficiency and organic Rankine cycle net produced power are investigated. It is observed that the rate of produced hydrogen and overall exergy efficiency of the proposed combined system take the maximum value to change in the evaporator temperature. Also, it is revealed that increasing the pinch point temperature difference in the evaporator decreases the rate of produced hydrogen and the overall exergy efficiency of the system. Furthermore, the effects on the rate of produced hydrogen and the overall exergy efficiency of the degree of superheat at the ORC turbine inlet are the same as the effect of pinch point temperature difference.

  2. 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.

  3. Ocean thermocline driven membrane distillation process

    KAUST Repository

    Francis, Lijo; Ghaffour, NorEddine; Alsaadi, Ahmad S.; Abraham, Raju

    2017-01-01

    source, or the energy cost of the heating source, to heat the feed stream to the membrane. In an aspect, the sensible heat present in surface seawater is used for the heat energy for the warm stream fed to the membrane, and deep seawater is used

  4. 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.

  5. 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.

  6. Dominant negative RPW8.2 fusion proteins reveal the importance of haustorium-oriented protein trafficking for resistance against powdery mildew in Arabidopsis.

    Science.gov (United States)

    Zhang, Qiong; Berkey, Robert; Pan, Zhiyong; Wang, Wenming; Zhang, Yi; Ma, Xianfeng; King, Harlan; Xiao, Shunyuan

    2015-01-01

    Powdery mildew fungi form feeding structures called haustoria inside epidermal cells of host plants to extract photosynthates for their epiphytic growth and reproduction. The haustorium is encased by an interfacial membrane termed the extrahaustorial membrane (EHM). The atypical resistance protein RPW8.2 from Arabidopsis is specifically targeted to the EHM where RPW8.2 activates haustorium-targeted (thus broad-spectrum) resistance against powdery mildew fungi. EHM-specific localization of RPW8.2 suggests the existence of an EHM-oriented protein/membrane trafficking pathway during EHM biogenesis. However, the importance of this specific trafficking pathway for host defense has not been evaluated via a genetic approach without affecting other trafficking pathways. Here, we report that expression of EHM-oriented, nonfunctional RPW8.2 chimeric proteins exerts dominant negative effect over functional RPW8.2 and potentially over other EHM-localized defense proteins, thereby compromising both RPW8.2-mediated and basal resistance to powdery mildew. Thus, our results highlight the importance of the EHM-oriented protein/membrane trafficking pathway for host resistance against haustorium-forming pathogens such as powdery mildew fungi.

  7. '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.

  8. 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.

  9. 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

  10. Incorporation of membrane-anchored flagellin or Escherichia coli heat-labile enterotoxin B subunit enhances the immunogenicity of rabies virus-like particles in mice and dogs

    Directory of Open Access Journals (Sweden)

    Yinglin eQi

    2015-03-01

    Full Text Available Rabies remains an important worldwide public health threat, so safe, effective and affordable vaccines are still being sought. Virus-like particle (VLP-based vaccines targeting various viral pathogens have been successfully produced, licensed and commercialized. Here, we designed and constructed two chimeric rabies virus-like particles (cRVLPs containing rabies virus (RABV glycoprotein (G, matrix (M protein, and membrane-anchored flagellin (EVLP-F or Escherichia coli heat-labile enterotoxin B subunit (EVLP-L as molecular adjuvants to enhance the immune response against rabies. The immunogenicity and potential of cRVLPs as novel rabies vaccine were evaluated by intramuscular vaccination in mouse and dog models. Mouse studies demonstrated that both EVLP-F and EVLP-L induced faster and larger virus-neutralizing antibodies (VNA responses and elicited greater numbers of CD4+ and CD8+ T cells secreting IFN-γ or IL-4 compared with a standard rabies VLP (sRVLP containing only G and M. Moreover, cRVLPs recruited and/or activated more B cells and dendritic cells in inguinal lymph nodes. EVLP-F induced a strong, specific IgG2a response but not an IgG1 response, suggesting the activation of Th1 class immunity; in contrast, Th2 class immunity was observed with EVLP-L. The significantly enhanced humoral and cellular immune responses induced by cRVLPs provided complete protection against lethal challenge with RABV. Most importantly, dogs vaccinated with EVLP-F or EVLP-L exhibited increased VNA titers in sera and enhanced IFN-γ and IL-4 secretion from peripheral blood mononuclear cells. Taken together, these results illustrate that when incorporated into sRVLP, membrane-anchored flagellin and LTB possess strong adjuvant activity. EVLP-F and EVLP-L induce significantly enhanced RABV-specific humoral and cellular immune responses in both mouse and dog. Therefore, these cRVLPs may be developed as safe and more efficacious rabies vaccine candidate for animals.

  11. 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.

  12. 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

  13. 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...

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. Investigations on an advanced power system based on a high temperature polymer electrolyte membrane fuel cell and an organic Rankine cycle for heating and power production

    International Nuclear Information System (INIS)

    Perna, Alessandra; Minutillo, Mariagiovanna; Jannelli, Elio

    2015-01-01

    Energy systems based on fuel cells technology can have a strategic role in the range of small-size power generation for the sustainable energy development. In order to enhance their performance, it is possible to recover the “waste heat” from the fuel cells, for producing or thermal power (cogeneration systems) or further electric power by means of a bottoming power cycle (combined systems). In this work an advanced system based on the integration between a HT-PEMFC (high temperature polymer electrolyte membrane fuel cell) power unit and an ORC (organic Rankine cycle) plant, has been proposed and analysed as suitable energy power plant for supplying electric and thermal energies to a stand-alone residential utility. The system can operate both as cogeneration system, in which the electric and thermal loads are satisfied by the HT-PEMFC power unit and as electric generation system, in which the low temperature heat recovered from the fuel cells is used as energy source in the ORC plant for increasing the electric power production. A numerical model, able to characterize the behavior and to predict the performance of the HT-PEMFC/ORC system under different working conditions, has been developed by using the AspenPlus™ code. - Highlights: • The advanced plant can operate both as CHP system and as electric generation system. • The performance prediction of the integrated system is carried out by numerical modeling. • ORC thermodynamic optimization is carried out by a sensitivity analysis. • Thermal coupling between the HT-PEMC system and the ORC plant is analyzed. • Results are very promising in the field of the distributed generation

  20. SNARE-mediated trafficking of α5β1 integrin is required for spreading in CHO cells

    International Nuclear Information System (INIS)

    Skalski, Michael; Coppolino, Marc G.

    2005-01-01

    In this study, the role of SNARE-mediated membrane traffic in regulating integrin localization was examined and the requirement for SNARE function in cellular spreading was quantitatively assessed. Membrane traffic was inhibited with the VAMP-specific catalytic light chain from tetanus toxin (TeTx-LC), a dominant-negative form (E329Q) of N-ethylmaleimide-sensitive fusion protein (NSF), and brefeldin A (BfA). Inhibition of membrane traffic with either E329Q-NSF or TeTx-LC, but not BfA, significantly inhibited spreading of CHO cells on fibronectin. Spreading was rescued in TeTx-LC-expressing cells by co-transfection with a TeTx-resistant cellubrevin/VAMP3. E329Q-NSF, a general inhibitor of SNARE function, was a more potent inhibitor of cell spreading than TeTx-LC, suggesting that tetanus toxin-insensitive SNAREs contribute to adhesion. It was found that E329Q-NSF prevented trafficking of α 5 β 1 integrins from a central Rab11-containing compartment to sites of protrusion during cell adhesion, while TeTx-LC delayed this trafficking. These results are consistent with a model of cellular adhesion that implicates SNARE function as an important component of integrin trafficking during the process of cell spreading

  1. Andrographolide regulates epidermal growth factor receptor and transferrin receptor trafficking in epidermoid carcinoma (A-431) cells

    Science.gov (United States)

    Tan, Y; Chiow, KH; Huang, D; Wong, SH

    2010-01-01

    Background and purpose: Andrographolide is the active component of Andrographis paniculata, a plant used in both Indian and Chinese traditional medicine, and it has been demonstrated to induce apoptosis in different cancer cell lines. However, not much is known about how it may affect the key receptors implicated in cancer. Knowledge of how andrographolide affects receptor trafficking will allow us to better understand new mechanisms by which andrographolide may cause death in cancer cells. Experimental approach: We utilized the well-characterized epidermal growth factor receptor (EGFR) and transferrin receptor (TfR) expressed in epidermoid carcinoma (A-431) cells as a model to study the effect of andrographolide on receptor trafficking. Receptor distribution, the total number of receptors and surface receptors were analysed by immunofluorescence, Western blot as well as flow-cytometry respectively. Key results: Andrographolide treatment inhibited cell growth, down-regulated EGFRs on the cell surface and affected the degradation of EGFRs and TfRs. The EGFR was internalized into the cell at an increased rate, and accumulated in a compartment that co-localizes with the lysosomal-associated membrane protein in the late endosomes. Conclusion and implications: This study sheds light on how andrographolide may affect receptor trafficking by inhibiting receptor movement from the late endosomes to lysosomes. The down-regulation of EGFR from the cell surface also indicates a new mechanism by which andrographolide may induce cancer cell death. PMID:20233216

  2. 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...

  3. 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

  4. 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

  5. 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

  6. 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...

  7. 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...

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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...

  14. 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

  15. Membrane dynamics

    DEFF Research Database (Denmark)

    Bendix, Pól Martin

    2015-01-01

    Current topics include membrane-protein interactions with regard to membrane deformation or curvature sensing by BAR domains. Also, we study the dynamics of membrane tubes of both cells and simple model membrane tubes. Finally, we study membrane phase behavior which has important implications...... for the lateral organization of membranes as wells as for physical properties like bending, permeability and elasticity...

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

    Directory of Open Access Journals (Sweden)

    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

  17. Heme requirement and intracellular trafficking in Trypanosoma cruzi epimastigotes

    International Nuclear Information System (INIS)

    Lara, F.A.; Sant'Anna, C.; Lemos, D.; Laranja, G.A.T.; Coelho, M.G.P.; Reis Salles, I.; Michel, A.; Oliveira, P.L.; Cunha-e-Silva, N.; Salmon, D.; Paes, M.C.

    2007-01-01

    Epimastigotes multiplies in the insect midgut by taking up nutrients present in the blood meal including heme bound to hemoglobin of red blood cell. During blood meal digestion by vector proteases in the posterior midgut, hemoglobin is clipped off into amino acids, peptides, and free heme. In this paper, we compared the heme and hemoglobin uptake kinetics and followed their intracellular trafficking. Addition of heme to culture medium increased epimastigote proliferation in a dose-dependent manner, while medium supplemented with hemoglobin enhanced growth after 3-day lag phase. Medium supplemented with globin-derived peptides stimulated cell proliferation in a dose-independent way. Using Palladium mesoporphyrin IX (Pd-mP) as a fluorescent heme-analog, we observed that heme internalization proceeded much faster than that observed by hemoglobin-rhodamine. Binding experiments showed that parasites accumulated the Pd-mP into the posterior region of the cell whereas hemoglobin-rhodamine stained the anterior region. Finally, using different specific inhibitors of ABC transporters we conclude that a P-glycoprotein homologue transporter is probably involved in heme transport through the plasma membrane

  18. 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.

  19. 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.

  20. Competition between ergosterol and cholesterol in sterol uptake and intracellular trafficking in the yeast Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Valachovic, M.; Hronska, L.; Hapala, I.

    1998-01-01

    The fate of internal cholesterol was evaluated in cells grown under various conditions with respect to the amount and the nature of sterols supplemented to the cells. Steryl esters accumulate in stationary phase-yeast cells and they are rapidly hydrolyzed in cells during exponential growth or ergosterol depletion. Cholesterol and other 'unnatural' sterols are esterified more efficiently that native ergosterol and it was speculated that esterification could protect cellular membranes from accumulation of these less optimal sterols. We tested this idea by monitoring the mobility of 14 C-cholesterol between free and esterified fractions in cell supplemented with cholesterol or ergosterol. It was found that cells grown on cholesterol to the stationary phase accumulated up to 80 % of label in the steryl ester fraction. Subsequent growth in sterol-free media caused sterol-depletion of plasma membrane and induced hydrolysis of 14 C- cholesteryl esters and accumulation of the label in free membranous sterol pool.Supplementation of cells with external sterols resulted in a shift in sterol trafficking and in a new accumulation of 14 C-cholesteryl esters. This indicates that the absence of an efficient proof-reading mechanism in plasma membrane that would be able to remove preferentially cholesterol from the free sterol pool in plasma membrane to steryl esters in lipidic particles. The mobility of cholesterol molecules in non-growing cells wa negligible suggesting that active growth or membrane proliferation are required for shifts of sterol molecules between these pools. (authors)

  1. Changes to cholesterol trafficking in macrophages by Leishmania parasites infection.

    Science.gov (United States)

    Semini, Geo; Paape, Daniel; Paterou, Athina; Schroeder, Juliane; Barrios-Llerena, Martin; Aebischer, Toni

    2017-08-01

    Leishmania spp. are protozoan parasites that are transmitted by sandfly vectors during blood sucking to vertebrate hosts and cause a spectrum of diseases called leishmaniases. It has been demonstrated that host cholesterol plays an important role during Leishmania infection. Nevertheless, little is known about the intracellular distribution of this lipid early after internalization of the parasite. Here, pulse-chase experiments with radiolabeled cholesteryl esterified to fatty acids bound to low-density lipoproteins indicated that retention of this source of cholesterol is increased in parasite-containing subcellular fractions, while uptake is unaffected. This is correlated with a reduction or absence of detectable NPC1 (Niemann-Pick disease, type C1), a protein responsible for cholesterol efflux from endocytic compartments, in the Leishmania mexicana habitat and infected cells. Filipin staining revealed a halo around parasites within parasitophorous vacuoles (PV) likely representing free cholesterol accumulation. Labeling of host cell membranous cholesterol by fluorescent cholesterol species before infection revealed that this pool is also trafficked to the PV but becomes incorporated into the parasites' membranes and seems not to contribute to the halo detected by filipin. This cholesterol sequestration happened early after infection and was functionally significant as it correlated with the upregulation of mRNA-encoding proteins required for cholesterol biosynthesis. Thus, sequestration of cholesterol by Leishmania amastigotes early after infection provides a basis to understand perturbation of cholesterol-dependent processes in macrophages that were shown previously by others to be necessary for their proper function in innate and adaptive immune responses. © 2017 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

  2. 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.

  3. Polyurethane Nanofiber Membranes for Waste Water Treatment by Membrane Distillation

    Directory of Open Access Journals (Sweden)

    T. Jiříček

    2017-01-01

    Full Text Available Self-sustained electrospun polyurethane nanofiber membranes were manufactured and tested on a direct-contact membrane distillation unit in an effort to find the optimum membrane thickness to maximize flux rate and minimize heat losses across the membrane. Also salt retention and flux at high salinities up to 100 g kg−1 were evaluated. Even though the complex structure of nanofiber layers has extreme specific surface and porosity, membrane performance was surprisingly predictable; the highest flux was achieved with the thinnest membranes and the best energy efficiency was achieved with the thickest membranes. All membranes had salt retention above 99%. Nanotechnology offers the potential to find modern solutions for desalination of waste waters, by introducing new materials with revolutionary properties, but new membranes must be developed according to the target application.

  4. 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.

  5. Inter-domain tagging implicates caveolin-1 in insulin receptor trafficking and Erk signaling bias in pancreatic beta-cells

    Directory of Open Access Journals (Sweden)

    Tobias Boothe

    2016-05-01

    Full Text Available Objective: The role and mechanisms of insulin receptor internalization remain incompletely understood. Previous trafficking studies of insulin receptors involved fluorescent protein tagging at their termini, manipulations that may be expected to result in dysfunctional receptors. Our objective was to determine the trafficking route and molecular mechanisms of functional tagged insulin receptors and endogenous insulin receptors in pancreatic beta-cells. Methods: We generated functional insulin receptors tagged with pH-resistant fluorescent proteins between domains. Confocal, TIRF and STED imaging revealed a trafficking pattern of inter-domain tagged insulin receptors and endogenous insulin receptors detected with antibodies. Results: Surprisingly, interdomain-tagged and endogenous insulin receptors in beta-cells bypassed classical Rab5a- or Rab7-mediated endocytic routes. Instead, we found that removal of insulin receptors from the plasma membrane involved tyrosine-phosphorylated caveolin-1, prior to trafficking within flotillin-1-positive structures to lysosomes. Multiple methods of inhibiting caveolin-1 significantly reduced Erk activation in vitro or in vivo, while leaving Akt signaling mostly intact. Conclusions: We conclude that phosphorylated caveolin-1 plays a role in insulin receptor internalization towards lysosomes through flotillin-1-positive structures and that caveolin-1 helps bias physiological beta-cell insulin signaling towards Erk activation. Author Video: Author Video Watch what authors say about their articles Keywords: Insulin receptor internalization, Insulin resistance, Pancreatic islet beta-cells, Autocrine insulin signaling

  6. 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

  7. 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.

  8. 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...

  9. 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…

  10. 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. -

  11. 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)

  12. 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…

  13. 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 ...

  14. 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…

  15. Transport, metabolism, and endosomal trafficking-dependent regulation of intestinal fructose absorption

    Science.gov (United States)

    Patel, Chirag; Douard, Veronique; Yu, Shiyan; Gao, Nan; Ferraris, Ronaldo P.

    2015-01-01

    Dietary fructose that is linked to metabolic abnormalities can up-regulate its own absorption, but the underlying regulatory mechanisms are not known. We hypothesized that glucose transporter (GLUT) protein, member 5 (GLUT5) is the primary fructose transporter and that fructose absorption via GLUT5, metabolism via ketohexokinase (KHK), as well as GLUT5 trafficking to the apical membrane via the Ras-related protein-in-brain 11 (Rab11)a-dependent endosomes are each required for regulation. Introducing fructose but not lysine and glucose solutions into the lumen increased by 2- to 10-fold the heterogeneous nuclear RNA, mRNA, protein, and activity levels of GLUT5 in adult wild-type mice consuming chow. Levels of GLUT5 were >100-fold that of candidate apical fructose transporters GLUTs 7, 8, and 12 whose expression, and that of GLUT 2 and the sodium-dependent glucose transporter protein 1 (SGLT1), was not regulated by luminal fructose. GLUT5-knockout (KO) mice exhibited no facilitative fructose transport and no compensatory increases in activity and expression of SGLT1 and other GLUTs. Fructose could not up-regulate GLUT5 in GLUT5-KO, KHK-KO, and intestinal epithelial cell-specific Rab11a-KO mice. The fructose-specific metabolite glyceraldehyde did not increase GLUT5 expression. GLUT5 is the primary transporter responsible for facilitative absorption of fructose, and its regulation specifically requires fructose uptake and metabolism and normal GLUT5 trafficking to the apical membrane.—Patel, C., Douard, V., Yu, S., Gao, N., Ferraris, R. P. Transport, metabolism, and endosomal trafficking-dependent regulation of intestinal fructose absorption. PMID:26071406

  16. Membrane Curvature and Lipid Composition Synergize To Regulate N-Ras Anchor Recruitment

    DEFF Research Database (Denmark)

    Larsen, Jannik B.; Kennard, Celeste; Pedersen, Søren L.

    2017-01-01

    Proteins anchored to membranes through covalently linked fatty acids and/or isoprenoid groups play crucial roles in all forms of life. Sorting and trafficking of lipidated proteins has traditionally been discussed in the context of partitioning to membrane domains of different lipid composition. We...

  17. Fuel-Cell Structure Prevents Membrane Drying

    Science.gov (United States)

    Mcelroy, J.

    1986-01-01

    Embossed plates direct flows of reactants and coolant. Membrane-type fuel-cell battery has improved reactant flow and heat removal. Compact, lightweight battery produces high current and power without drying of membranes.

  18. Role of amphipathic helix of a herpesviral protein in membrane deformation and T cell receptor downregulation.

    Directory of Open Access Journals (Sweden)

    Chan-Ki Min

    2008-11-01

    Full Text Available Lipid rafts are membrane microdomains that function as platforms for signal transduction and membrane trafficking. Tyrosine kinase interacting protein (Tip of T lymphotropic Herpesvirus saimiri (HVS is targeted to lipid rafts in T cells and downregulates TCR and CD4 surface expression. Here, we report that the membrane-proximal amphipathic helix preceding Tip's transmembrane (TM domain mediates lipid raft localization and membrane deformation. In turn, this motif directs Tip's lysosomal trafficking and selective TCR downregulation. The amphipathic helix binds to the negatively charged lipids and induces liposome tubulation, the TM domain mediates oligomerization, and cooperation of the membrane-proximal helix with the TM domain is sufficient for localization to lipid rafts and lysosomal compartments, especially the mutivesicular bodies. These findings suggest that the membrane-proximal amphipathic helix and TM domain provide HVS Tip with the unique ability to deform the cellular membranes in lipid rafts and to downregulate TCRs potentially through MVB formation.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. An Essential Role of Hrs/Vps27 in Endosomal Cholesterol Trafficking

    Directory of Open Access Journals (Sweden)

    Ximing Du

    2012-01-01

    Full Text Available The endosomal sorting complex required for transport (ESCRT plays a crucial role in the degradation of ubiquitinated endosomal membrane proteins. Here, we report that Hrs, a key protein of the ESCRT-0 complex, is required for the transport of low-density lipoprotein-derived cholesterol from endosomes to the endoplasmic reticulum. This function of Hrs in cholesterol transport is distinct from its previously defined role in lysosomal sorting and downregulation of membrane receptors via the ESCRT pathway. In line with this, knocking down other ESCRT proteins does not cause prominent endosomal cholesterol accumulation. Importantly, the localization and biochemical properties of key cholesterol-sorting proteins, NPC1 and NPC2, appear to be unchanged upon Hrs knockdown. Our data identify Hrs as a regulator of endosomal cholesterol trafficking and provide additional insights into the budding of intralumenal vesicles.

  11. Intracellular trafficking of the β-secretase and processing of amyloid precursor protein.

    Science.gov (United States)

    Zhi, Pei; Chia, Pei Zhi Cheryl; Chia, Cheryl; Gleeson, Paul A

    2011-09-01

    The main component of the amyloid plaques found in the brains of those with Alzheimer's disease (AD) is a polymerized form of the β-amyloid peptide (Aβ) and is considered to play a central role in the pathogenesis of this neurodegenerative disorder. Aβ is derived from the proteolytic processing of the amyloid precursor protein (APP). Beta site APP-cleaving enzyme, BACE1 (also known as β-secretase) is a membrane-bound aspartyl protease responsible for the initial step in the generation of Aβ peptide and is thus a prime target for therapeutic intervention. Substantive evidence now indicates that the processing of APP by BACE1 is regulated by the intracellular sorting of the enzyme and, moreover, perturbations in these intracellular trafficking pathways have been linked to late-onset AD. In this review, we highlight the recent advances in the understanding of the regulation of the intracellular sorting of BACE1 and APP and illustrate why the trafficking of these cargos represent a key issue for understanding the membrane-mediated events associated with the generation of the neurotoxic Aβ products in AD. Copyright © 2011 International Union of Biochemistry and Molecular Biology, Inc.

  12. MUC1 intra-cellular trafficking is clathrin, dynamin, and rab5 dependent

    International Nuclear Information System (INIS)

    Liu Xiaolong; Yuan Zhenglong; Chung, Maureen

    2008-01-01

    MUC1, a transmembrane glycoprotein, is abnormally over-expressed in most human adenocarcinomas. MUC1 association with cytoplasmic cell signal regulators and nuclear accumulation are important for its tumor related activities. Little is known about how MUC1 translocates from the cell membrane to the cytoplasm. In this study, live cell imaging was used to study MUC1 intracellular trafficking. The interaction between EGFR and MUC1 was mapped by FRET analysis and EGF stimulated MUC1 endocytosis was observed directly through live cell imaging. MUC1-CT endocytosis was clathrin and dynamin dependent. Rab5 over-expression resulted in decreased cell membrane localization of MUC1, with accumulation of MUC1 endocytic vesicles in the peri-nuclear region. Conversely, over-expression of a Rab5 dominant negative mutant (S34N) resulted in redistribution of MUC1 from the peri-nuclear region to the cytoplasm. Collectively, these results indicated that MUC1 intra-cellular trafficking occurs through a regulated process that was stimulated by direct EGFR and MUC1 interaction, mediated by clathrin coated pits that were dynamin dependent and regulated by Rab5

  13. A FYVE zinc finger domain protein specifically links mRNA transport to endosome trafficking

    Science.gov (United States)

    Pohlmann, Thomas; Baumann, Sebastian; Haag, Carl; Albrecht, Mario; Feldbrügge, Michael

    2015-01-01

    An emerging theme in cellular logistics is the close connection between mRNA and membrane trafficking. A prominent example is the microtubule-dependent transport of mRNAs and associated ribosomes on endosomes. This coordinated process is crucial for correct septin filamentation and efficient growth of polarised cells, such as fungal hyphae. Despite detailed knowledge on the key RNA-binding protein and the molecular motors involved, it is unclear how mRNAs are connected to membranes during transport. Here, we identify a novel factor containing a FYVE zinc finger domain for interaction with endosomal lipids and a new PAM2-like domain required for interaction with the MLLE domain of the key RNA-binding protein. Consistently, loss of this FYVE domain protein leads to specific defects in mRNA, ribosome, and septin transport without affecting general functions of endosomes or their movement. Hence, this is the first endosomal component specific for mRNP trafficking uncovering a new mechanism to couple mRNPs to endosomes. DOI: http://dx.doi.org/10.7554/eLife.06041.001 PMID:25985087

  14. In silico investigation of ADAM12 effect on TGF-β receptors trafficking

    Directory of Open Access Journals (Sweden)

    LeMeur Nolwenn

    2009-09-01

    Full Text Available Abstract Background The transforming growth factor beta is known to have pleiotropic effects, including differentiation, proliferation and apoptosis. However the underlying mechanisms remain poorly understood. The regulation and effect of TGF-β signaling is complex and highly depends on specific protein context. In liver, we have recently showed that the disintegrin and metalloproteinase ADAM12 interacts with TGF-β receptors and modulates their trafficking among membranes, a crucial point in TGF-β signaling and development of fibrosis. The present study aims to better understand how ADAM12 impacts on TGF-β receptors trafficking and TGF-β signaling. Findings We extracted qualitative biological observations from experimental data and defined a family of models producing a behavior compatible with the presence of ADAM12. We computationally explored the properties of this family of models which allowed us to make novel predictions. We predict that ADAM12 increases TGF-β receptors internalization rate between the cell surface and the endosomal membrane. It also appears that ADAM12 modifies TGF-β signaling shape favoring a permanent response by removing the transient component observed under physiological conditions. Conclusion In this work, confronting differential models with qualitative biological observations, we obtained predictions giving new insights into the role of ADAM12 in TGF-β signaling and hepatic fibrosis process.

  15. VEGF-A isoforms program differential VEGFR2 signal transduction, trafficking and proteolysis

    Directory of Open Access Journals (Sweden)

    Gareth W. Fearnley

    2016-05-01

    Full Text Available Vascular endothelial growth factor A (VEGF-A binding to the receptor tyrosine kinase VEGFR2 triggers multiple signal transduction pathways, which regulate endothelial cell responses that control vascular development. Multiple isoforms of VEGF-A can elicit differential signal transduction and endothelial responses. However, it is unclear how such cellular responses are controlled by isoform-specific VEGF-A–VEGFR2 complexes. Increasingly, there is the realization that the membrane trafficking of receptor–ligand complexes influences signal transduction and protein turnover. By building on these concepts, our study shows for the first time that three different VEGF-A isoforms (VEGF-A165, VEGF-A121 and VEGF-A145 promote distinct patterns of VEGFR2 endocytosis for delivery into early endosomes. This differential VEGFR2 endocytosis and trafficking is linked to VEGF-A isoform-specific signal transduction events. Disruption of clathrin-dependent endocytosis blocked VEGF-A isoform-specific VEGFR2 activation, signal transduction and caused substantial depletion in membrane-bound VEGFR1 and VEGFR2 levels. Furthermore, such VEGF-A isoforms promoted differential patterns of VEGFR2 ubiquitylation, proteolysis and terminal degradation. Our study now provides novel insights into how different VEGF-A isoforms can bind the same receptor tyrosine kinase and elicit diverse cellular outcomes.

  16. VEGF-A isoforms program differential VEGFR2 signal transduction, trafficking and proteolysis.

    Science.gov (United States)

    Fearnley, Gareth W; Smith, Gina A; Abdul-Zani, Izma; Yuldasheva, Nadira; Mughal, Nadeem A; Homer-Vanniasinkam, Shervanthi; Kearney, Mark T; Zachary, Ian C; Tomlinson, Darren C; Harrison, Michael A; Wheatcroft, Stephen B; Ponnambalam, Sreenivasan

    2016-05-15

    Vascular endothelial growth factor A (VEGF-A) binding to the receptor tyrosine kinase VEGFR2 triggers multiple signal transduction pathways, which regulate endothelial cell responses that control vascular development. Multiple isoforms of VEGF-A can elicit differential signal transduction and endothelial responses. However, it is unclear how such cellular responses are controlled by isoform-specific VEGF-A-VEGFR2 complexes. Increasingly, there is the realization that the membrane trafficking of receptor-ligand complexes influences signal transduction and protein turnover. By building on these concepts, our study shows for the first time that three different VEGF-A isoforms (VEGF-A165, VEGF-A121 and VEGF-A145) promote distinct patterns of VEGFR2 endocytosis for delivery into early endosomes. This differential VEGFR2 endocytosis and trafficking is linked to VEGF-A isoform-specific signal transduction events. Disruption of clathrin-dependent endocytosis blocked VEGF-A isoform-specific VEGFR2 activation, signal transduction and caused substantial depletion in membrane-bound VEGFR1 and VEGFR2 levels. Furthermore, such VEGF-A isoforms promoted differential patterns of VEGFR2 ubiquitylation, proteolysis and terminal degradation. Our study now provides novel insights into how different VEGF-A isoforms can bind the same receptor tyrosine kinase and elicit diverse cellular outcomes. © 2016. Published by The Company of Biologists Ltd.

  17. Subcellular trafficking of FGF controls tracheal invasion of Drosophila flight muscle.

    Science.gov (United States)

    Peterson, Soren J; Krasnow, Mark A

    2015-01-15

    To meet the extreme oxygen demand of insect flight muscle, tracheal (respiratory) tubes ramify not only on its surface, as in other tissues, but also within T-tubules and ultimately surrounding every mitochondrion. Although this remarkable physiological specialization has long been recognized, its cellular and molecular basis is unknown. Here, we show that Drosophila tracheoles invade flight muscle T-tubules through transient surface openings. Like other tracheal branching events, invasion requires the Branchless FGF pathway. However, localization of the FGF chemoattractant changes from all muscle membranes to T-tubules as invasion begins. Core regulators of epithelial basolateral membrane identity localize to T-tubules, and knockdown of AP-1γ, required for basolateral trafficking, redirects FGF from T-tubules to surface, increasing tracheal surface ramification and preventing invasion. We propose that tracheal invasion is controlled by an AP-1-dependent switch in FGF trafficking. Thus, subcellular targeting of a chemoattractant can direct outgrowth to specific domains, including inside the cell. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. A FYVE zinc finger domain protein specifically links mRNA transport to endosome trafficking.

    Science.gov (United States)

    Pohlmann, Thomas; Baumann, Sebastian; Haag, Carl; Albrecht, Mario; Feldbrügge, Michael

    2015-05-18

    An emerging theme in cellular logistics is the close connection between mRNA and membrane trafficking. A prominent example is the microtubule-dependent transport of mRNAs and associated ribosomes on endosomes. This coordinated process is crucial for correct septin filamentation and efficient growth of polarised cells, such as fungal hyphae. Despite detailed knowledge on the key RNA-binding protein and the molecular motors involved, it is unclear how mRNAs are connected to membranes during transport. Here, we identify a novel factor containing a FYVE zinc finger domain for interaction with endosomal lipids and a new PAM2-like domain required for interaction with the MLLE domain of the key RNA-binding protein. Consistently, loss of this FYVE domain protein leads to specific defects in mRNA, ribosome, and septin transport without affecting general functions of endosomes or their movement. Hence, this is the first endosomal component specific for mRNP trafficking uncovering a new mechanism to couple mRNPs to endosomes.

  19. 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.

  20. 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.

  1. 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

  2. Emulsification using microporous membranes

    Directory of Open Access Journals (Sweden)

    Goran T. Vladisavljević

    2011-10-01

    Full Text Available Membrane emulsification is a process of injecting a pure dispersed phase or pre-emulsion through a microporous membrane into the continuous phase. As a result of the immiscibility of the two phases, droplets of the dispersed phase are formed at the outlets of membrane pores. The droplets formed in the process are removed from the membrane surface by applying cross-flow or stirring of the continuous phase or using a dynamic (rotating or vibrating membrane. The most commonly used membrane for emulsification is the Shirasu Porous Glass (SPG membrane, fabricated through spinodal decomposition in a melt consisting of Japanese volcanic ash (Shirasu, boric acid and calcium carbonate. Microsieve membranes are increasingly popular as an alternative to highly tortuous glass and ceramic membranes. Microsieves are usually fabricated from nickel by photolithography and electroplating or they can be manufactured from silicon nitride via Reactive Ion Etching (RIE. An advantage of microsieves compared to the SPG membrane is in much higher transmembrane fluxes and higher tolerance to fouling by the emulsion ingredients due to the existence of short, straight through pores. Unlike conventional emulsification devices such as high-pressure valve homogenisers and rotor-stator devices, membrane emulsification devices permit a precise control over the mean pore size over a wide range and during the process insignificant amount of energy is dissipated as heat. The drop size is primarily determined by the pore size, but it depends also on other parameters, such as membrane wettability, emulsion formulation, shear stress on the membrane surface, transmembrane pressure, etc.

  3. 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

  4. Membrane modules for building ventilation

    Energy Technology Data Exchange (ETDEWEB)

    Kistler, K.R.; Cussler, E.L.

    2002-01-01

    Hollow fibre and flat sheet membranes with an interfacially polymerized coating of polyamide have a permeance for water vapour of about 0.16 m sec{sup -1}. These membranes can serve as a basis for building ventilation which provides fresh air while recovering about 70% of the specific heat and 60% of the latent heat. Because these membranes are selective for water vapour, the air is exhausted with internal pollutants like carbon monoxide, formaldehyde, and radon. The expense of the ventilator should be recovered in reduced heating costs in about three years. (Author)

  5. 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

  6. 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

  7. Early to Late Endosome Trafficking Controls Secretion and Zymogen Activation in Rodent and Human Pancreatic Acinar CellsSummary

    Directory of Open Access Journals (Sweden)

    Scott W. Messenger

    2015-11-01

    Full Text Available Background & Aims: Pancreatic acinar cells have an expanded apical endosomal system, the physiologic and pathophysiologic significance of which is still emerging. Phosphatidylinositol-3,5-bisphosphate [PI(3,5P2] is an essential phospholipid generated by phosphatidylinositol 3-phosphate 5-kinase (PIKfyve, which phosphorylates phosphatidylinositol-3-phosphate (PI3P. PI(3,5P2 is necessary for maturation of early endosomes (EE to late endosomes (LE. Inhibition of EE to LE trafficking enhances anterograde endosomal trafficking and secretion at the plasma membrane by default through a recycling endosome (RE intermediate. We assessed the effects of modulating PIKfyve activity on apical trafficking and pancreatitis responses in pancreatic acinar cells. Methods: Inhibition of EE to LE trafficking was achieved using pharmacologic inhibitors of PIKfyve, expression of dominant negative PIKfyve K1877E, or constitutively active Rab5-GTP Q79L. Anterograde endosomal trafficking was manipulated by expression of constitutively active and dominant negative Rab11a mutants. The effects of these agents on secretion, endolysosomal exocytosis of lysosome associated membrane protein (LAMP1, and trypsinogen activation in response to supramaximal cholecystokinin (CCK-8, bile acids, and cigarette toxin was determined. Results: PIKfyve inhibition increased basal and stimulated secretion. Adenoviral overexpression of PIKfyve decreased secretion leading to cellular death. Expression of Rab5-GTP Q79L or Rab11a-GTP Q70L enhanced secretion. Conversely, dominant-negative Rab11a-GDP S25N reduced secretion. High-dose CCK inhibited endolysosomal exocytosis that was reversed by PIKfyve inhibition. PIKfyve inhibition blocked intracellular trypsin accumulation and cellular damage responses to supramaximal CCK-8, tobacco toxin, and bile salts in both rodent and human acini. Conclusions: These data demonstrate that EE-LE trafficking acutely controls acinar secretion and the intracellular

  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. Extracellular anti-angiogenic proteins augment an endosomal protein trafficking pathway to reach mitochondria and execute apoptosis in HUVECs.

    Science.gov (United States)

    Chen, Mo; Qiu, Tao; Wu, Jiajie; Yang, Yang; Wright, Graham D; Wu, Min; Ge, Ruowen

    2018-03-09

    Classic endocytosis destinations include the recycling endosome returning to the plasma membrane or the late endosome (LE) merging with lysosomes for cargo degradation. However, the anti-angiogenic proteins angiostatin and isthmin, are endocytosed and trafficked to mitochondria (Mito) to execute apoptosis of endothelial cells. How these extracellular proteins reach mitochondria remains a mystery. Through confocal and super-resolution fluorescent microscopy, we demonstrate that angiostatin and isthmin are trafficked to mitochondria through the interaction between LE and Mito. Using purified organelles, the LE-Mito interaction is confirmed through in vitro lipid-fusion assay, as well as single vesicle total internal reflection fluorescent microscopy. LE-Mito interaction enables the transfer of not only lipids but also proteins from LE to Mito. Angiostatin and isthmin augment this endosomal protein trafficking pathway and make use of it to reach mitochondria to execute apoptosis. Cell fractionation and biochemical analysis identified that the cytosolic scaffold protein Na+/H+ exchanger regulatory factor 1 (NHERF1) associated with LE and the t-SNARE protein synaptosome-associated protein 25 kDa (SNAP25) associated with Mito form an interaction complex to facilitate LE-Mito interaction. Proximity ligation assay coupled with fluorescent microscopy showed that both NHERF1 and SNAP25 are located at the contacting face between LE and Mito. RNAi knockdown of either NHERF1 or SNAP25 suppressed not only the mitochondrial trafficking of angiostatin and isthmin but also their anti-angiogenic and pro-apoptotic functions. Hence, this study reveals a previously unrealized endosomal protein trafficking pathway from LE to Mito that allows extracellular proteins to reach mitochondria and execute apoptosis.

  10. Identification of a novel trafficking pathway exporting a replication protein, Orc2 to nucleus via classical secretory pathway in Plasmodium falciparum.

    Science.gov (United States)

    Sharma, Rahul; Sharma, Bhumika; Gupta, Ashish; Dhar, Suman Kumar

    2018-05-01

    Malaria parasites use an extensive secretory pathway to traffic a number of proteins within itself and beyond. In higher eukaryotes, Endoplasmic Reticulum (ER) membrane bound transcription factors such as SREBP are reported to get processed en route and migrate to nucleus under the influence of specific cues. However, a protein constitutively trafficked to the nucleus via classical secretory pathway has not been reported. Herein, we report the presence of a novel trafficking pathway in an apicomplexan, Plasmodium falciparum where a homologue of an Origin Recognition Complex 2 (Orc2) goes to the nucleus following its association with the ER. Our work highlights the unconventional role of ER in protein trafficking and reports for the first time an ORC homologue getting trafficked through such a pathway to the nucleus where it may be involved in DNA replication and other ancillary functions. Such trafficking pathways may have a profound impact on the cell biology of a malaria parasite and have significant implications in strategizing new antimalarials. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. 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.

  12. 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.

  13. 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…

  14. 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…

  15. 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.

  16. 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

  17. 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

  18. SLC6A3 coding variant Ala559Val found in two autism probands alters dopamine transporter function and trafficking.

    Science.gov (United States)

    Bowton, E; Saunders, C; Reddy, I A; Campbell, N G; Hamilton, P J; Henry, L K; Coon, H; Sakrikar, D; Veenstra-VanderWeele, J M; Blakely, R D; Sutcliffe, J; Matthies, H J G; Erreger, K; Galli, A

    2014-10-14

    Emerging evidence associates dysfunction in the dopamine (DA) transporter (DAT) with the pathophysiology of autism spectrum disorder (ASD). The human DAT (hDAT; SLC6A3) rare variant with an Ala to Val substitution at amino acid 559 (hDAT A559V) was previously reported in individuals with bipolar disorder or attention-deficit hyperactivity disorder (ADHD). We have demonstrated that this variant is hyper-phosphorylated at the amino (N)-terminal serine (Ser) residues and promotes an anomalous DA efflux phenotype. Here, we report the novel identification of hDAT A559V in two unrelated ASD subjects and provide the first mechanistic description of its impaired trafficking phenotype. DAT surface expression is dynamically regulated by DAT substrates including the psychostimulant amphetamine (AMPH), which causes hDAT trafficking away from the plasma membrane. The integrity of DAT trafficking directly impacts DA transport capacity and therefore dopaminergic neurotransmission. Here, we show that hDAT A559V is resistant to AMPH-induced cell surface redistribution. This unique trafficking phenotype is conferred by altered protein kinase C β (PKCβ) activity. Cells expressing hDAT A559V exhibit constitutively elevated PKCβ activity, inhibition of which restores the AMPH-induced hDAT A559V membrane redistribution. Mechanistically, we link the inability of hDAT A559V to traffic in response to AMPH to the phosphorylation of the five most distal DAT N-terminal Ser. Mutation of these N-terminal Ser to Ala restores AMPH-induced trafficking. Furthermore, hDAT A559V has a diminished ability to transport AMPH, and therefore lacks AMPH-induced DA efflux. Pharmacological inhibition of PKCβ or Ser to Ala substitution in the hDAT A559V background restores AMPH-induced DA efflux while promoting intracellular AMPH accumulation. Although hDAT A559V is a rare variant, it has been found in multiple probands with neuropsychiatric disorders associated with imbalances in DA neurotransmission

  19. 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

  20. 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

  1. Muscle intermediate filaments and their links to membranes and membranous organelles

    International Nuclear Information System (INIS)

    Capetanaki, Yassemi; Bloch, Robert J.; Kouloumenta, Asimina; Mavroidis, Manolis; Psarras, Stelios

    2007-01-01

    Intermediate filaments (IFs) play a key role in the integration of structure and function of striated muscle, primarily by mediating mechanochemical links between the contractile apparatus and mitochondria, myonuclei, the sarcolemma and potentially the vesicle trafficking apparatus. Linkage of all these membranous structures to the contractile apparatus, mainly through the Z-disks, supports the integration and coordination of growth and energy demands of the working myocyte, not only with force transmission, but also with de novo gene expression, energy production and efficient protein and lipid trafficking and targeting. Desmin, the most abundant and intensively studied muscle intermediate filament protein, is linked to proper costamere organization, myoblast and stem cell fusion and differentiation, nuclear shape and positioning, as well as mitochondrial shape, structure, positioning and function. Similar links have been established for lysosomes and lysosome-related organelles, consistent with the presence of widespread links between IFs and membranous structures and the regulation of their fusion, morphology and stabilization necessary for cell survival

  2. 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.

  3. 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

  4. 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)

  5. 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

  6. 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 ...

  7. 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.

  8. The Fight against the Least Visible Form of Human Trafficking: Trafficking for Child Labour Exploitation

    Directory of Open Access Journals (Sweden)

    Luz María Puente Aba

    2018-03-01

    Full Text Available Child trafficking for the purpose of labour exploitation is a difficult phenomenon to detect. It is also not readily definable considering that this specific form of trafficking is closely linked with the phenomenon of forced child labour, and even with the broader occurrence of child labour. A lack of globally reliable data and the convergence of different concepts related to child trafficking for labour exploitation pose significant challenges when trying to regulate the circumstances concerning child work and the criminalisation of trafficking for labour exploitation. This article offers a clear overview of the available data related to all the phenomena, and aims to clarify all the situations involved, defining child work, child labour, forced child labour and child trafficking for the purposes of labour exploitation. Furthermore, this article discusses the possible loopholes and critical issues that could hinder global approaches to resolving these issues. La trata infantil con fines de explotación laboral es un fenómeno difícil de detectar, y tampoco es sencillo definirlo si se tiene en cuenta que esta forma específica de trata está estrechamente relacionada con el fenómeno del trabajo forzado infantil e, incluso, con el fenómeno más general de trabajo infantil. Todo ello supone un desafío a la hora de regular las circunstancias que definen el trabajo realizado por niños y la criminalización de la trata para la explotación laboral. Este artículo ofrece un repaso de los datos disponibles en esta materia y procura aclarar las situaciones que se pueden plantear, así como definir trabajo realizado por niños, trabajo infantil, trabajo infantil forzado y trata infantil con fines de explotación laboral. Por último, profundiza en las posibles deficiencias y en los aspectos críticos que podrían obstaculizar un acercamiento global a esta problemática. DOWNLOAD THIS PAPER FROM SSRN: http://ssrn.com/abstract=3088010

  9. KENYA’S CONSTITUTION AND CHILD TRAFFICKING AS A SECURITY THREAT

    OpenAIRE

    E.O.S. ODHIAMBO; J. KASSILLY; L.T. MAITO; K. ONKWARE; W. A. OBOKA

    2012-01-01

    Human trafficking also referred to as modern-day slavery is seen as a security threat. Traditional security approaches to human trafficking call for analysis of trafficking as a threat to the Kenyan state and to Kenya’s control of its borders. Traditional security analyses of trafficking emphasize border security, migration controls, and international law enforcement cooperation. This article discusses three forms of child trafficking: sexual exploitation, forced labor and child soldiers and ...

  10. Membrane fusion

    DEFF Research Database (Denmark)

    Bendix, Pól Martin

    2015-01-01

    At Stanford University, Boxer lab, I worked on membrane fusion of small unilamellar lipid vesicles to flat membranes tethered to glass surfaces. This geometry closely resembles biological systems in which liposomes fuse to plasma membranes. The fusion mechanism was studied using DNA zippering...... between complementary strands linked to the two apposing membranes closely mimicking the zippering mechanism of SNARE fusion complexes....

  11. Human trafficking and health: a cross-sectional survey of NHS professionals’ contact with victims of human trafficking

    Science.gov (United States)

    Ross, Claire; Dimitrova, Stoyanka; Howard, Louise M; Dewey, Michael; Zimmerman, Cathy; Oram, Siân

    2015-01-01

    Objectives (1) To estimate the proportion of National Health Service (NHS) professionals who have come into contact with trafficked people and (2) to measure NHS professionals’ knowledge and confidence to respond to human trafficking. Design A cross-sectional survey. Setting Face-to-face mandatory child protection and/or vulnerable adults training sessions at 10 secondary healthcare provider organisations in England, and meetings of the UK College of Emergency Medicine. Participants 782/892 (84.4%) NHS professionals participated, including from emergency medicine, maternity, mental health, paediatrics and other clinical disciplines. Measures Self-completed questionnaire developed by an expert panel. Questionnaire asks about prior training and contact with potential victims of trafficking, perceived and actual human trafficking knowledge, confidence in responding to human trafficking, and interest in future human trafficking training. Results 13% participants reported previous contact with a patient they knew or suspected of having been trafficked; among maternity services professionals this was 20.4%. However, 86.8% (n=679) reported lacking knowledge of what questions to ask to identify potential victims and 78.3% (n=613) reported that they had insufficient training to assist trafficked people. 71% (n=556), 67.5% (n=528) and 53.4% (n=418) lacked confidence in making appropriate referrals for men, women and children, respectively, who had been trafficked. 95.3% (n=746) of respondents were unaware of the scale of human trafficking in the UK, and 76.5% (n=598) were unaware that calling the police could put patients in more danger. Psychometric analysis showed that subscales measuring perceived knowledge, actual knowledge and confidence to respond to human trafficking demonstrated good internal consistency (Cronbach's αs 0.93, 0.63 and 0.64, respectively) and internal correlations. Conclusions NHS professionals working in secondary care are in contact with potential

  12. Human trafficking and health: a cross-sectional survey of NHS professionals' contact with victims of human trafficking.

    Science.gov (United States)

    Ross, Claire; Dimitrova, Stoyanka; Howard, Louise M; Dewey, Michael; Zimmerman, Cathy; Oram, Siân

    2015-08-20

    (1) To estimate the proportion of National Health Service (NHS) professionals who have come into contact with trafficked people and (2) to measure NHS professionals' knowledge and confidence to respond to human trafficking. A cross-sectional survey. Face-to-face mandatory child protection and/or vulnerable adults training sessions at 10 secondary healthcare provider organisations in England, and meetings of the UK College of Emergency Medicine. 782/892 (84.4%) NHS professionals participated, including from emergency medicine, maternity, mental health, paediatrics and other clinical disciplines. Self-completed questionnaire developed by an expert panel. Questionnaire asks about prior training and contact with potential victims of trafficking, perceived and actual human trafficking knowledge, confidence in responding to human trafficking, and interest in future human trafficking training. 13% participants reported previous contact with a patient they knew or suspected of having been trafficked; among maternity services professionals this was 20.4%. However, 86.8% (n=679) reported lacking knowledge of what questions to ask to identify potential victims and 78.3% (n=613) reported that they had insufficient training to assist trafficked people. 71% (n=556), 67.5% (n=528) and 53.4% (n=418) lacked confidence in making appropriate referrals for men, women and children, respectively, who had been trafficked. 95.3% (n=746) of respondents were unaware of the scale of human trafficking in the UK, and 76.5% (n=598) were unaware that calling the police could put patients in more danger. Psychometric analysis showed that subscales measuring perceived knowledge, actual knowledge and confidence to respond to human trafficking demonstrated good internal consistency (Cronbach's αs 0.93, 0.63 and 0.64, respectively) and internal correlations. NHS professionals working in secondary care are in contact with potential victims of human trafficking, but lack knowledge and confidence in

  13. 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.

  14. A global bioethical perspective on organ trafficking: Discrimination ...

    African Journals Online (AJOL)

    2017-06-21

    Jun 21, 2017 ... along with other ethical problems, is inherently discriminatory, and in many instances, the ... Although organ trafficking is a global issue and prohibited by most countries ..... Dordrecht: Springer Science and Business. Media ...

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

    National Research Council Canada - National Science Library

    Miko, Francis T

    2006-01-01

    Trafficking in people for prostitution and forced labor is one of the most prolific areas of international criminal activity and is of significant concern to the United States and the international community...

  16. Gender issues in human trafficking in Edo State, Nigeria | Osezua ...

    African Journals Online (AJOL)

    Gender issues in human trafficking in Edo State, Nigeria. ... in order to capture family dynamics and power relations and women status in ... The paper concluded that efforts targeted towards eradicating existing gender inequality in the region ...

  17. Intracellular trafficking of new anticancer therapeutics: antibody–drug conjugates

    Science.gov (United States)

    Kalim, Muhammad; Chen, Jie; Wang, Shenghao; Lin, Caiyao; Ullah, Saif; Liang, Keying; Ding, Qian; Chen, Shuqing; Zhan, Jinbiao

    2017-01-01

    Antibody–drug conjugate (ADC) is a milestone in targeted cancer therapy that comprises of monoclonal antibodies chemically linked to cytotoxic drugs. Internalization of ADC takes place via clathrin-mediated endocytosis, caveolae-mediated endocytosis, and pinocytosis. Conjugation strategies, endocytosis and intracellular trafficking optimization, linkers, and drugs chemistry present a great challenge for researchers to eradicate tumor cells successfully. This inventiveness of endocytosis and intracellular trafficking has given considerable momentum recently to develop specific antibodies and ADCs to treat cancer cells. It is significantly advantageous to emphasize the endocytosis and intracellular trafficking pathways efficiently and to design potent engineered conjugates and biological entities to boost efficient therapies enormously for cancer treatment. Current studies illustrate endocytosis and intracellular trafficking of ADC, protein, and linker strategies in unloading and also concisely evaluate practically applicable ADCs. PMID:28814834

  18. Intracellular trafficking of new anticancer therapeutics: antibody-drug conjugates.

    Science.gov (United States)

    Kalim, Muhammad; Chen, Jie; Wang, Shenghao; Lin, Caiyao; Ullah, Saif; Liang, Keying; Ding, Qian; Chen, Shuqing; Zhan, Jinbiao

    2017-01-01

    Antibody-drug conjugate (ADC) is a milestone in targeted cancer therapy that comprises of monoclonal antibodies chemically linked to cytotoxic drugs. Internalization of ADC takes place via clathrin-mediated endocytosis, caveolae-mediated endocytosis, and pinocytosis. Conjugation strategies, endocytosis and intracellular trafficking optimization, linkers, and drugs chemistry present a great challenge for researchers to eradicate tumor cells successfully. This inventiveness of endocytosis and intracellular trafficking has given considerable momentum recently to develop specific antibodies and ADCs to treat cancer cells. It is significantly advantageous to emphasize the endocytosis and intracellular trafficking pathways efficiently and to design potent engineered conjugates and biological entities to boost efficient therapies enormously for cancer treatment. Current studies illustrate endocytosis and intracellular trafficking of ADC, protein, and linker strategies in unloading and also concisely evaluate practically applicable ADCs.

  19. Recognizing victims of human trafficking in the pediatric emergency department.

    Science.gov (United States)

    Becker, Heather J; Bechtel, Kirsten

    2015-02-01

    Human trafficking is a form of modern-day slavery that is rapidly expanding in the United States and throughout the world. It is a crime under both the United States and international law. The child and adult victims of human trafficking are denied their basic human rights and subjected to unspeakable physical and emotional harm. Traffickers exert complete control over their victims and are proficient at hiding their condition from authorities. Healthcare practitioners may be the only professionals who come into contact with victims if they present for medical care. This article will describe human trafficking and its potential victims, as well as guide medical management and access to services that will ensure their safety and restore their freedom.

  20. Global initiatives to tackle organ trafficking and transplant tourism.

    Science.gov (United States)

    Bagheri, Alireza; Delmonico, Francis L

    2013-11-01

    The increasing gap between organ supply and demand has opened the door for illegal organ sale, trafficking of human organs, tissues and cells, as well as transplant tourism. Currently, underprivileged and vulnerable populations in resource-poor countries are a major source of organs for rich patient-tourists who can afford to purchase organs at home or abroad. This paper presents a summary of international initiatives, such as World Health Organization's Principle Guidelines, The Declaration of Istanbul, Asian Task Force Recommendations, as well as UNESCO's and the United Nation's initiatives against trafficking of human organs, tissues, cells, and transplant tourism. Beyond the summary, it calls for more practical measures to be taken to implement the existing guidelines and recommendations, in order to prevent exploitation of the poor as organ providers. The paper suggests that an international legally binding agreement in criminalizing organ trafficking would be a step forward to bring a change in the global picture of organ trafficking and transplant tourism.

  1. Effectiveness of Counter-Trafficking Response in Albania

    Directory of Open Access Journals (Sweden)

    Meçe Merita H.

    2016-07-01

    Full Text Available Human trafficking is a new phenomenon of Albanian post-socialist society which significantly increased during the difficult years of its transformation from centralized state-led economy to market economy. Both economic and political instability contributed to its size, nature and multiple dynamics. Drawing on a rights-based approach to human trafficking, this paper examines the effectiveness of the counter-trafficking response of the Albanian government with a special emphasis on prevention, protection and prosecution. Using secondary data and reviewing various country strategic documents, it highlights a range of weaknesses and challenges which have hindered its effectiveness over years. It concludes that successful and effective counter-trafficking response requires well rounded and coordinated gender sensitive, victim-centred, holistic and human rights-based efforts. Combined with adequate law enforcement, they will sustainably tackle the full spectrum of this problem.

  2. The Role of Local Authorities in Addressing Human Trafficking

    Directory of Open Access Journals (Sweden)

    Kathryn Rossiter

    2009-05-01

    Full Text Available Worldwide, it is estimated that nearly 4 million people fall victim to people traffickers every year. Trafficking is carried out mainly by Organised Criminal Networks and the victims are forced into prostitution, illegal labour, domestic slavery and petty crime. ROSSITER & BENFIELD: The Role of Local Authorities in Addressing Human Trafficking CJLG May 2009 128 On 1 April 2009, the United Kingdom signed up to the Council of Europe Convention on Action against Trafficking in Human Beings.1 The Convention, which has to date been ratified by 20 European countries, is legally binding and aims to promote and protect the rights of victims who have been tricked or forced into leaving their homes, moved to another country, or within their own country, and then exploited. Whilst it is national governments who are signatories to the Council of Europe Convention, local authorities have a key role to play in its successful implementation.

  3. A global bioethical perspective on organ trafficking: Discrimination ...

    African Journals Online (AJOL)

    A global bioethical perspective on organ trafficking: Discrimination, stigmatisation and the vulnerable. ... South African Journal of Bioethics and Law ... be used as an influential appeal to the world community to combat these activities together.

  4. Rab GTPases Regulate Endothelial Cell Protein C Receptor-Mediated Endocytosis and Trafficking of Factor VIIa

    Science.gov (United States)

    Nayak, Ramesh C.; Keshava, Shiva; Esmon, Charles T.; Pendurthi, Usha R.; Rao, L. Vijaya Mohan

    2013-01-01

    Recent studies have established that factor VIIa (FVIIa) binds to the endothelial cell protein C receptor (EPCR). FVIIa binding to EPCR may promote the endocytosis of this receptor/ligand complex. Rab GTPases are known to play a crucial role in the endocytic and exocytic pathways of receptors or receptor/ligand complexes. The present study was undertaken to investigate the role of Rab GTPases in the intracellular trafficking of EPCR and FVIIa. CHO-EPCR cells and human umbilical vein endothelial cells (HUVEC) were transduced with recombinant adenoviral vectors to express wild-type, constitutively active, or dominant negative mutant of various Rab GTPases. Cells were exposed to FVIIa conjugated with AF488 fluorescent probe (AF488-FVIIa), and intracellular trafficking of FVIIa, EPCR, and Rab proteins was evaluated by immunofluorescence confocal microscopy. In cells expressing wild-type or constitutively active Rab4A, internalized AF488-FVIIa accumulated in early/sorting endosomes and its entry into the recycling endosomal compartment (REC) was inhibited. Expression of constitutively active Rab5A induced large endosomal structures beneath the plasma membrane where EPCR and FVIIa accumulated. Dominant negative Rab5A inhibited the endocytosis of EPCR-FVIIa. Expression of constitutively active Rab11 resulted in retention of accumulated AF488-FVIIa in the REC, whereas expression of a dominant negative form of Rab11 led to accumulation of internalized FVIIa in the cytoplasm and prevented entry of internalized FVIIa into the REC. Expression of dominant negative Rab11 also inhibited the transport of FVIIa across the endothelium. Overall our data show that Rab GTPases regulate the internalization and intracellular trafficking of EPCR-FVIIa. PMID:23555015

  5. Physician Encounters with Human Trafficking: Legal Consequences and Ethical Considerations

    OpenAIRE

    Todres, Jonathan

    2017-01-01

    There is growing recognition and evidence that health care professionals regularly encounter - though they may not identify - victims of human trafficking in a variety of health care settings. Identifying and responding appropriately to trafficking victims or survivors requires not only training in trauma-informed care but also consideration of the legal and ethical issues that arise when serving this vulnerable population. This essay examines three areas of law that are relevant to this case...

  6. Drug Trafficking Organizations and Local Economic Activity in Mexico.

    Science.gov (United States)

    González, Felipe

    2015-01-01

    Little is known about the relationship between illegal firms and local economic activity. In this paper I study changes in satellite night lights across Mexican municipalities after the arrival of large drug trafficking organizations in the period 2000-2010. After accounting for state trends and differences in political regimes, results indicate no significant change in night lights after the arrival of these illegal firms. Estimated coefficients are precise, robust, and similar across different drug trafficking organizations.

  7. Devastating consequences of sex trafficking on women's health.

    Science.gov (United States)

    McTavish, Fr James

    2017-11-01

    Sex trafficking has devastating consequences on the physical and mental well-being of millions of women around the world. These trafficking victims often come in contact with medical personnel, and these encounters with suitably prepared staff can be a step toward healing of the victims. The Catholic Church, especially through Pope Francis, is making strenuous efforts to curb the spread of sex trafficking. Same-sex feelings and behavior may arise post-trafficking in individuals, although this does not appear to be mentioned thus far in the literature. Here, we are most likely dealing with a type of "pseudo-lesbianism" post-trauma. The trafficking survivor can be helped to understand some of the likely roots of her feelings such as anti-male sentiments following abuse. She needs to be patiently, and expertly, accompanied to process the trauma she has experienced, and learn how to meet her genuine needs for female affection and affirmation in healthy, chaste, and non-erotic ways. Around the world, millions of female victims of human trafficking are forced into sex "work," often resulting in serious physical and mental-health problems. Healthcare staff should be alert to spot victims of sex trafficking and be ready to assist them. The Catholic Church, especially through Pope Francis, has been vocal in denouncing this form of modern slavery. Some female victims of sex trafficking may experience same-sex feelings afterward. Healing for such young women involves helping them to process their traumatic experiences, as well as patiently accompanying them as they seek to develop healthy, chaste friendships with other females and males.

  8. Trafficked Women in Denmark—Falling through the cracks

    Directory of Open Access Journals (Sweden)

    Kira West

    2018-05-01

    Full Text Available The policy framework for combating human trafficking and protecting victims in Denmark does not match the reality faced by the majority of the migrant women arriving in the country. Especially in relation to women from African countries, the national legislation and regulations can be a source of frustration for agencies such as Reden International, which helps foreign women working in prostitution in Denmark, particularly victims of trafficking.

  9. Peran End Child Prostitution, Child Pornography And Trafficking Of Children For Sexual Purposes (Ecpat) Internasional dalam Menanggulangi Kasus Child Trafficking di Albania (2007-2012)

    OpenAIRE

    Rani, Faisyal; Rafiqa, Adni Luthfi

    2015-01-01

    This research purpose to explain about the role of End Child Prostitution, Child Pornography and Trafficking of Children for Sexual Purposes (ECPAT) International to solve child trafficking case in Albania (2007-2012). ECPAT International is a non-governmental organization which take focus on solving child trafficking case and ECPAT International has had affiliate in some country in the world, one of them is Albania.Authors analyze and explain about child trafficking condition which is occure...

  10. Fighting Human Trafficking in the European Union: A master’s thesis on the ability of EU law to fight trafficking in women for sexual exploitation

    OpenAIRE

    Nielsen, Stine Piilgaard Porner

    2011-01-01

    Human trafficking is considered to be modern day slavery. The EU continuously seeks to strengthen its fight against this crime, latest with the Directive on Prevention, Combat and Protection adopted in April 2011. But to what extent is the EU able to fight human trafficking through law? Human trafficking is a complex problem which can be assessed from different perspectives. The EU primarily addresses the fight against human trafficking through criminal law, and this thesis investigates the e...

  11. Conjugate heat and mass transfer in heat mass exchanger ducts

    CERN Document Server

    Zhang, Li-Zhi

    2013-01-01

    Conjugate Heat and Mass Transfer in Heat Mass Exchanger Ducts bridges the gap between fundamentals and recent discoveries, making it a valuable tool for anyone looking to expand their knowledge of heat exchangers. The first book on the market to cover conjugate heat and mass transfer in heat exchangers, author Li-Zhi Zhang goes beyond the basics to cover recent advancements in equipment for energy use and environmental control (such as heat and moisture recovery ventilators, hollow fiber membrane modules for humidification/dehumidification, membrane modules for air purification, desi

  12. National Human Trafficking Initiatives: Dimensions of Policy Diffusion.

    Science.gov (United States)

    Yoo, Eun-Hye; Boyle, Elizabeth Heger

    2015-01-01

    The implementation of criminal law involves formal law enforcement, education and public outreach aimed at preventing criminal activity, and providing services for victims. Historically, quantitative research on global trends has tended to focus on a single policy dimension, potentially masking the unique factors that affect the diffusion of each policy dimension independently. Using an ordered-probit model to analyze new human trafficking policy data on national prosecution, prevention, and victim-protection efforts, we find that global ties and domestic interest groups matter more in areas where international law is less defined. While prosecution, officially mandated by the Trafficking Protocol, was relatively impervious to global ties and domestic interest groups, both trafficking prevention and victim protection were associated with these factors. Our findings also suggest that fear of repercussions is not a major driver of state actions to combat trafficking-neither ratification of the Trafficking Protocol nor levels of United States aid were associated with greater implementation of anti-trafficking measures.

  13. 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

  14. The analysis of drug consumption, drug trafficking and the fight against drug trafficking at the present day

    Directory of Open Access Journals (Sweden)

    Borisenko M.V.

    2017-04-01

    Full Text Available the article discusses the current drug situation in Russia, Siberian Federal District and Novosibirsk Region relating to drug consumption and drug trafficking and the main reasons of deaths of drug-dependent people.

  15. Liver ischemia and ischemia-reperfusion induces and trafficks the multi-specific metal transporter Atp7b to bile duct canaliculi: possible preferential transport of iron into bile.

    Science.gov (United States)

    Goss, John A; Barshes, Neal R; Karpen, Saul J; Gao, Feng-Qin; Wyllie, Samuel

    2008-04-01

    Both Atp7b (Wilson disease gene) and Atp7a (Menkes disease gene) have been reported to be trafficked by copper. Atp7b is trafficked to the bile duct canaliculi and Atp7a to the plasma membrane. Whether or not liver ischemia or ischemia-reperfusion modulates Atp7b expression and trafficking has not been reported. In this study, we report for the first time that the multi-specific metal transporter Atp7b is significantly induced and trafficked by both liver ischemia alone and liver ischemia-reperfusion, as judged by immunohistochemistry and Western blot analyses. Although hepatocytes also stained for Atp7b, localized intense staining of Atp7b was found on bile duct canaliculi. Inductive coupled plasma-mass spectrometry analysis of bile copper, iron, zinc, and manganese found a corresponding significant increase in biliary iron. In our attempt to determine if the increased biliary iron transport observed may be a result of altered bile flow, lysosomal trafficking, or glutathione biliary transport, we measured bile flow, bile acid phosphatase activity, and glutathione content. No significant difference was found in bile flow, bile acid phosphatase activity, and glutathione, between control livers and livers subjected to ischemia-reperfusion. Thus, we conclude that liver ischemia and ischemia-reperfusion induction and trafficking Atp7b to the bile duct canaliculi may contribute to preferential iron transport into bile.

  16. Irregular Migration flows and human trafficking in the Western Balkan countries: challenges of the covergence of counter-trafficking response

    OpenAIRE

    Mece, Merita H.

    2016-01-01

    Irregular migration on the Western Balkan route has marked an unprecedented number during the last five years. Evidence indicates that both, non-European nationals and Western Balkan citizens have been involved in this complex migratory flow being exposed to various risks of human trafficking. But Western Balkan countries are source, transit and destination countries of human trafficking while their states are not well organized to implement a comprehensive and well-coordinated regional respo...

  17. The cellular response to vascular endothelial growth factors requires co-ordinated signal transduction, trafficking and proteolysis.

    Science.gov (United States)

    Smith, Gina A; Fearnley, Gareth W; Tomlinson, Darren C; Harrison, Michael A; Ponnambalam, Sreenivasan

    2015-08-18

    VEGFs (vascular endothelial growth factors) are a family of conserved disulfide-linked soluble secretory glycoproteins found in higher eukaryotes. VEGFs mediate a wide range of responses in different tissues including metabolic homoeostasis, cell proliferation, migration and tubulogenesis. Such responses are initiated by VEGF binding to soluble and membrane-bound VEGFRs (VEGF receptor tyrosine kinases) and co-receptors. VEGF and receptor splice isoform diversity further enhances complexity of membrane protein assembly and function in signal transduction pathways that control multiple cellular responses. Different signal transduction pathways are simultaneously activated by VEGFR-VEGF complexes with membrane trafficking along the endosome-lysosome network further modulating signal output from multiple enzymatic events associated with such pathways. Balancing VEGFR-VEGF signal transduction with trafficking and proteolysis is essential in controlling the intensity and duration of different intracellular signalling events. Dysfunction in VEGF-regulated signal transduction is important in chronic disease states including cancer, atherosclerosis and blindness. This family of growth factors and receptors is an important model system for understanding human disease pathology and developing new therapeutics for treating such ailments. © 2015 Authors.

  18. Membrane curvature induction and tubulation are common features of synucleins and apolipoproteins

    DEFF Research Database (Denmark)

    Varkey, Jobin; Isas, Jose Mario; Mizuno, Naoko

    2010-01-01

    Synucleins and apolipoproteins have been implicated in a number of membrane and lipid trafficking events. Lipid interaction for both types of proteins is mediated by 11 amino acid repeats that form amphipathic helices. This similarity suggests that synucleins and apolipoproteins might have...... of amphipathic helices alone. Moreover, we frequently observed that a-synuclein caused membrane structures that had the appearance of nascent budding vesicles. The ability to function as a minimal machinery for vesicle budding agrees well with recent findings that a-synuclein plays a role in vesicle trafficking...

  19. Structures of human folate receptors reveal biological trafficking states and diversity in folate and antifolate recognition.

    Science.gov (United States)

    Wibowo, Ardian S; Singh, Mirage; Reeder, Kristen M; Carter, Joshua J; Kovach, Alexander R; Meng, Wuyi; Ratnam, Manohar; Zhang, Faming; Dann, Charles E

    2013-09-17

    Antifolates, folate analogs that inhibit vitamin B9 (folic acid)-using cellular enzymes, have been used over several decades for the treatment of cancer and inflammatory diseases. Cellular uptake of the antifolates in clinical use occurs primarily via widely expressed facilitative membrane transporters. More recently, human folate receptors (FRs), high affinity receptors that transport folate via endocytosis, have been proposed as targets for the specific delivery of new classes of antifolates or folate conjugates to tumors or sites of inflammation. The development of specific, FR-targeted antifolates would be accelerated if additional biophysical data, particularly structural models of the receptors, were available. Here we describe six distinct crystallographic models that provide insight into biological trafficking of FRs and distinct binding modes of folate and antifolates to these receptors. From comparison of the structures, we delineate discrete structural conformations representative of key stages in the endocytic trafficking of FRs and propose models for pH-dependent conformational changes. Additionally, we describe the molecular details of human FR in complex with three clinically prevalent antifolates, pemetrexed (also Alimta), aminopterin, and methotrexate. On the whole, our data form the basis for rapid design and implementation of unique, FR-targeted, folate-based drugs for the treatment of cancer and inflammatory diseases.

  20. GABA type a receptor trafficking and the architecture of synaptic inhibition.

    Science.gov (United States)

    Lorenz-Guertin, Joshua M; Jacob, Tija C

    2018-03-01

    Ubiquitous expression of GABA type A receptors (GABA A R) in the central nervous system establishes their central role in coordinating most aspects of neural function and development. Dysregulation of GABAergic neurotransmission manifests in a number of human health disorders and conditions that in certain cases can be alleviated by drugs targeting these receptors. Precise changes in the quantity or activity of GABA A Rs localized at the cell surface and at GABAergic postsynaptic sites directly impact the strength of inhibition. The molecular mechanisms constituting receptor trafficking to and from these compartments therefore dictate the efficacy of GABA A R function. Here we review the current understanding of how GABA A Rs traffic through biogenesis, plasma membrane transport, and degradation. Emphasis is placed on discussing novel GABAergic synaptic proteins, receptor and scaffolding post-translational modifications, activity-dependent changes in GABA A R confinement, and neuropeptide and neurosteroid mediated changes. We further highlight modern techniques currently advancing the knowledge of GABA A R trafficking and clinically relevant neurodevelopmental diseases connected to GABAergic dysfunction. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 238-270, 2018. © 2017 Wiley Periodicals, Inc.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. The Anatomy of Human Trafficking: Learning About the Blues: A Healthcare Provider's Guide.

    Science.gov (United States)

    Stevens, Meriam; Berishaj, Kelly

    2016-01-01

    Human trafficking is a major global public health concern. It is a grave crime that violates human rights. Contrary to healthcare providers' perceptions, victims of human trafficking come in contact with the healthcare system while being trafficked, with the emergency department being the most frequented setting for medical treatment. In this article, we explore the anatomy of human trafficking, including the scope of the problem, definitions, and types and elements of human trafficking. The roles of clinicians, particularly emergency department nurses and advanced practice nurses, in screening and identifying those at risk are examined. Clinical practice tools and guidelines that may be used by clinicians to guide the treatment of human trafficking victims are reviewed. Finally, current strategies and resources that address human trafficking are presented. For the purpose of this article, the terms "human trafficking" or "trafficking" will be used throughout.

  3. Human trafficking and health: a conceptual model to inform policy, intervention and research.

    Science.gov (United States)

    Zimmerman, Cathy; Hossain, Mazeda; Watts, Charlotte

    2011-07-01

    Human trafficking is an international crime renowned for extreme forms of violence against women, men and children. Although trafficking-related violence has been well-documented, the health of trafficked persons has been a largely neglected topic. For people who are trafficked, health risks and consequences may begin before they are recruited into the trafficking process, continue throughout the period of exploitation and persist even after individuals are released. Policy-making, service provision and research often focus narrowly on criminal violations that occur during the period of exploitation, regularly overlooking the health implications of trafficking. Similarly, the public health sector has not yet incorporated human trafficking as a health concern. We present a conceptual model that highlights the migratory and exploitative nature of a multi-staged trafficking process, which includes: 'recruitment', travel-transit', 'exploitation' and 'integration' or 'reintegration', and for some trafficked persons, 'detention' and 're-trafficking' stages. Trafficked persons may suffer from physical, sexual and psychological harm, occupational hazards, legal restrictions and difficulties associated with being marginalised or stigmatised. Researchers and decision-makers will benefit from a theoretical approach that conceptualizes trafficking and health as a multi-staged process of cumulative harm. To address a health risk such as trafficking, which spans geographical boundaries and involves multiple sectors, including immigration and law enforcement, labour, social and health services, interventions must be coordinated between nations and across sectors to promote the protection and recovery of people who are trafficked. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Membrane fusion by VAMP3 and plasma membrane t-SNAREs

    International Nuclear Information System (INIS)

    Hu Chuan; Hardee, Deborah; Minnear, Fred

    2007-01-01

    Pairing of SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins on vesicles (v-SNAREs) and SNARE proteins on target membranes (t-SNAREs) mediates intracellular membrane fusion. VAMP3/cellubrevin is a v-SNARE that resides in recycling endosomes and endosome-derived transport vesicles. VAMP3 has been implicated in recycling of transferrin receptors, secretion of α-granules in platelets, and membrane trafficking during cell migration. Using a cell fusion assay, we examined membrane fusion capacity of the ternary complexes formed by VAMP3 and plasma membrane t-SNAREs syntaxin1, syntaxin4, SNAP-23 and SNAP-25. VAMP3 forms fusogenic pairing with t-SNARE complexes syntaxin1/SNAP-25, syntaxin1/SNAP-23 and syntaxin4/SNAP-25, but not with syntaxin4/SNAP-23. Deletion of the N-terminal domain of syntaxin4 enhanced membrane fusion more than two fold, indicating that the N-terminal domain negatively regulates membrane fusion. Differential membrane fusion capacities of the ternary v-/t-SNARE complexes suggest that transport vesicles containing VAMP3 have distinct membrane fusion kinetics with domains of the plasma membrane that present different t-SNARE proteins

  5. Public Discourse on Human Trafficking in International Issue Arenas

    Directory of Open Access Journals (Sweden)

    Niina Meriläinen

    2015-01-01

    Full Text Available The purpose of this study is to better understand how the complex problem of human trafficking is addressed in international debates. How the discussion about human trafficking develops and how it is debated ultimately influences how the decision-making process unfolds. In order to understand the formation of public policy and laws, therefore, it is important to study the debate that occurs prior to decision making. This analysis focuses on the narratives used by major, well-established human rights and political actors that argue for necessary actions to be undertaken—such as the formation of new policies and laws in the European Union—as an attempt to protect citizens of the EU and other regions in the world from becoming victims of trafficking networks. Our research examines how the topic of human trafficking is framed and how this framework is intertwined in the debate with other social problems. We focus on how human trafficking is discussed by two well-established human rights Non-Governmental Organizations (NGOs, Amnesty International (Amnesty and Human Rights Watch (HRW, in addition to the European Parliament (EP. The research questions for this study include: (1 In what context is human trafficking discussed by the three actors? (2 How do these actors frame the definition of human trafficking in their presentations? To answer these questions, we have conducted a systematic content analysis of documents that include official statements and research reports of the NGOs, as well as resolutions and recommendations of the EP. Altogether, 240 documents were analyzed in detail. These findings indicate that the two human rights organizations, Amnesty and Human Rights Watch, along with the European Parliament, all address human trafficking as an important social problem, albeit to varying degrees. Each actor has a different method of correlating human trafficking with many other social problems, thereby emphasizing different causes and

  6. Editorial: How is the money to combat human trafficking spent?

    Directory of Open Access Journals (Sweden)

    Mike Dottridge

    2014-09-01

    This edition of the Anti-Trafficking Review explores what happens to the money that is allocated by governments and private donors to stop human trafficking and to assist people who have been trafficked. It has been an honour to play the role of guest editor, though it has not been easy to steer a route between amazement (at the sums apparently involved, concern (at the lack of real insight into how money is allocated and spent and cynicism (at what appear to be rather modest achievements. It was challenging for potential authors to choose a method of analysing anti-trafficking spending. Should they simply describe what money is available and the drawbacks of the ways which donors make it available to organisations to use? Some authors take this descriptive approach. Should articles be about the efficiency and effectiveness of aid flows in general, in which case the shortcomings in anti-trafficking funding may mirror the generic flaws in aid flows? Only one author (Ucnikova has tackled this. Or, should studies focus on the way the purse strings are controlled by a small number of donors who appear poorly informed about the needs of trafficked persons or the factors that cause them to be trafficked? Several of the articles touch on this (e.g. those of Hoff and Nwogu. Early on, it became apparent to the editorial team that people working for large organisations with anti-trafficking programmes were wary of contributing articles on this topic. In this sense, although the Anti-Trafficking Review aims to promote public debate, we have not yet found the best way of opening up a debate about funding, for practitioners evidently fear that writing about their own sources of funding could result in the tap being turned off! So, it is mainly the Debate section that tackles the question of funding strategies. Even these contributions do not make assessments of the various actors involved (donors and the organisations they fund in as full and frank a way as is needed. The

  7. PICK1 regulates the trafficking of ASIC1a and acidotoxicity in a BAR domain lipid binding-dependent manner

    Directory of Open Access Journals (Sweden)

    Jin Wenying

    2010-12-01

    Full Text Available Abstract Background Acid-sensing ion channel 1a (ASIC1a is the major ASIC subunit determining acid-activated currents in brain neurons. Recent studies show that ASIC1a play critical roles in acid-induced cell toxicity. While these studies raise the importance of ASIC1a in diseases, mechanisms for ASIC1a trafficking are not well understood. Interestingly, ASIC1a interacts with PICK1 (protein interacting with C-kinase 1, an intracellular protein that regulates trafficking of several membrane proteins. However, whether PICK1 regulates ASIC1a surface expression remains unknown. Results Here, we show that PICK1 overexpression increases ASIC1a surface level. A BAR domain mutant of PICK1, which impairs its lipid binding capability, blocks this increase. Lipid binding of PICK1 is also required for PICK1-induced clustering of ASIC1a. Consistent with the effect on ASIC1a surface levels, PICK1 increases ASIC1a-mediated acidotoxicity and this effect requires both the PDZ and BAR domains of PICK1. Conclusions Taken together, our results indicate that PICK1 regulates trafficking and function of ASIC1a in a lipid binding-dependent manner.

  8. 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

  9. Proton exchange membrane fuel cells

    CERN Document Server

    Qi, Zhigang

    2013-01-01

    Preface Proton Exchange Membrane Fuel CellsFuel CellsTypes of Fuel CellsAdvantages of Fuel CellsProton Exchange Membrane Fuel CellsMembraneCatalystCatalyst LayerGas Diffusion MediumMicroporous LayerMembrane Electrode AssemblyPlateSingle CellStackSystemCell Voltage Monitoring Module (CVM)Fuel Supply Module (FSM)Air Supply Module (ASM)Exhaust Management Module (EMM)Heat Management Module (HMM)Water Management Module (WMM)Internal Power Supply Module (IPM)Power Conditioning Module (PCM)Communications Module (COM)Controls Module (CM)SummaryThermodynamics and KineticsTheoretical EfficiencyVoltagePo

  10. Human trafficking: Role of oral health care providers.

    Science.gov (United States)

    Nuzzolese, E

    2014-11-30

    Trafficking in human beings is a modern form of slavery and is a well-known phenomenon throughout the European Union and beyond. After drug dealing and the weapons industry, human trafficking is the second largest criminal activity in the world today and it is a growing crime. The aim of governmental and non-governmental agencies, which are either directly or indirectly involved in combating trafficking in human beings, is the identification and referral of victims of trafficking and also to encourage self-referrals. Identification is the most important step to provide protection and assistance to victims of trafficking. Victims often have a variety of physical and mental health needs, including psychological trauma, injuries from violence, head and neck trauma, sexually transmitted infections and other gynaecological problems, dental/oral problems and have poor nutrition. The author's experience in the field of community dentistry in presented within. Volunteer dental services are offered to non-European Union patients held in a centre for asylum seekers in Bari (Italy). Dental professionals can, in fact, contribute to the identification, assistance and protection of trafficked persons, as well as offering forensic services to assist the police investigation in order to identify crimes and find the criminal organizations behind them. As for domestic violence and child abuse cases, there are ethical concerns involved in the identification and protection of the trafficked persons, as well as the need for interdisciplinary work and awareness. Adequate training in behavioural science and intercultural learning is paramount in order to avoid misunderstandings and increase sensitivity.

  11. KENYA’S CONSTITUTION AND CHILD TRAFFICKING AS A SECURITY THREAT

    Directory of Open Access Journals (Sweden)

    E.O.S. ODHIAMBO

    2012-01-01

    Full Text Available Human trafficking also referred to as modern-day slavery is seen as a security threat. Traditional security approaches to human trafficking call for analysis of trafficking as a threat to the Kenyan state and to Kenya’s control of its borders. Traditional security analyses of trafficking emphasize border security, migration controls, and international law enforcement cooperation. This article discusses three forms of child trafficking: sexual exploitation, forced labor and child soldiers and argues that the newly promulgated Kenyan constitution in chapter three on citizenship has a provision that can be interpreted as encouraging child trafficking.

  12. Human Trafficking in Areas of Conflict: Health Care Professionals' Duty to Act.

    Science.gov (United States)

    Bloem, Christina; Morris, Rikki E; Chisolm-Straker, Makini

    2017-01-01

    Given the significant global burden of human trafficking, the ability of clinicians to identify and provide treatment for trafficked persons is critical. Particularly in conflict settings, health care facilities often serve as the first and sometimes only point of contact for trafficked persons. As such, medical practitioners have a unique opportunity and an ethical imperative to intervene, even in nonclinical roles. With proper training, medical practitioners can assist trafficked persons by documenting human trafficking cases, thereby placing pressure on key stakeholders to enforce legal protections, and by providing adequate services to those trafficked. © 2017 American Medical Association. All Rights Reserved.

  13. 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....

  14. GLUT4 trafficking in a test tube.

    Science.gov (United States)

    Ramm, Georg; James, David E

    2005-09-01

    Insulin regulates glucose transport in muscle and fat cells by stimulating the translocation of GLUT4 from intracellular vesicles to the plasma membrane. In this issue of Cell Metabolism, Holman and colleagues reconstitute this process in vitro, providing a system that promises new breakthroughs in our understanding of this important metabolic process.

  15. Altered TGF-β endocytic trafficking contributes to the increased signaling in Marfan syndrome.

    Science.gov (United States)

    Siegert, Anna-Maria; Serra-Peinado, Carla; Gutiérrez-Martínez, Enric; Rodríguez-Pascual, Fernando; Fabregat, Isabel; Egea, Gustavo

    2018-02-01

    The main cardiovascular alteration in Marfan syndrome (MFS) is the formation of aortic aneurysms in which augmented TGF-β signaling is reported. However, the primary role of TGF-β signaling as a molecular link between the genetic mutation of fibrillin-1 and disease onset is controversial. The compartmentalization of TGF-β endocytic trafficking has been shown to determine a signaling response in which clathrin-dependent internalization leads to TGF-β signal propagation, and caveolin-1 (CAV-1) associated internalization leads to signal abrogation. We here studied the contribution of endocytic trafficking compartmentalization to increased TGF-β signaling in vascular smooth muscle cells (VSMC) from MFS patients. We examined molecular components involved in clathrin- (SARA, SMAD2) and caveolin-1- (SMAD7, SMURF2) dependent endocytosis. Marfan VSMC showed higher recruitment of SARA and SMAD2 to membranes and their increased interaction with TGF-β receptor II, as well as higher colocalization of SARA with the early endosome marker EEA1. We assessed TGF-β internalization using a biotinylated ligand (b-TGF-β), which colocalized equally with either EEA1 or CAV-1 in VSMC from Marfan patients and controls. However, in Marfan cells, colocalization of b-TGF-β with SARA and EEA1 was increased and accompanied by decreased colocalization with CAV-1 at EEA1-positive endosomes. Moreover, Marfan VSMC showed higher transcriptional levels and membrane enrichment of RAB5. Our results indicate that increased RAB5-associated SARA localization to early endosomes facilitates its TGF-β receptor binding and phosphorylation of signaling mediator SMAD2 in Marfan VSMC. This is accompanied by a reduction of TGF-β sorting into multifunctional vesicles containing cargo from both internalization pathways. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Educating health care professionals on human trafficking.

    Science.gov (United States)

    Grace, Aimee M; Lippert, Suzanne; Collins, Kristin; Pineda, Noelle; Tolani, Alisha; Walker, Rebecca; Jeong, Monica; Trounce, Milana Boukhman; Graham-Lamberts, Caroline; Bersamin, Melina; Martinez, Jeremy; Dotzler, Jennifer; Vanek, John; Storfer-Isser, Amy; Chamberlain, Lisa J; Horwitz, Sarah M

    2014-12-01

    The US Department of State estimates that there are between 4 and 27 million individuals worldwide in some form of modern slavery. Recent studies have demonstrated that 28% to 50% of trafficking victims in the United States encountered health care professionals while in captivity, but were not identified and recognized. This study aimed to determine whether an educational presentation increased emergency department (ED) providers' recognition of human trafficking (HT) victims and knowledge of resources to manage cases of HT. The 20 largest San Francisco Bay Area EDs were randomized into intervention (10 EDs) or delayed intervention comparison groups (10 EDs) to receive a standardized educational presentation containing the following: background about HT, relevance of HT to health care, clinical signs in potential victims, and referral options for potential victims. Participants in the delayed intervention group completed a pretest in the period the immediate intervention group received the educational presentation, and all participants were assessed immediately before (pretest) and after (posttest) the intervention. The intervention effect was tested by comparing the pre-post change in the intervention group to the change in 2 pretests in the delayed intervention group adjusted for the effect of clustering within EDs. The 4 primary outcomes were importance of knowledge of HT to the participant's profession (5-point Likert scale), self-rated knowledge of HT (5-point Likert scale), knowledge of who to call for potential HT victims (yes/no), and suspecting that a patient was a victim of HT (yes/no). There were 258 study participants from 14 EDs; 141 from 8 EDs in the intervention group and 117 from 7 EDs in the delayed intervention comparison group, of which 20 served as the delayed intervention comparison group. Participants in the intervention group reported greater increases in their level of knowledge about HT versus those in the delayed intervention comparison

  17. Membrane Biophysics

    CERN Document Server

    Ashrafuzzaman, Mohammad

    2013-01-01

    Physics, mathematics and chemistry all play a vital role in understanding the true nature and functioning of biological membranes, key elements of living processes. Besides simple spectroscopic observations and electrical measurements of membranes we address in this book the phenomena of coexistence and independent existence of different membrane components using various theoretical approaches. This treatment will be helpful for readers who want to understand biological processes by applying both simple observations and fundamental scientific analysis. It provides a deep understanding of the causes and effects of processes inside membranes, and will thus eventually open new doors for high-level pharmaceutical approaches towards fighting membrane- and cell-related diseases.

  18. National Human Trafficking Initiatives: Dimensions of Policy Diffusion1

    Science.gov (United States)

    Yoo, Eun-hye; Boyle, Elizabeth Heger

    2014-01-01

    The implementation of criminal law involves formal law enforcement, education and public outreach aimed at preventing criminal activity, and providing services for victims. Historically, quantitative research on global trends has tended to focus on a single policy dimension, potentially masking the unique factors that affect the diffusion of each policy dimension independently. Using an ordered-probit model to analyze new human trafficking policy data on national prosecution, prevention, and victim-protection efforts, we find that global ties and domestic interest groups matter more in areas where international law is less defined. While prosecution, officially mandated by the Trafficking Protocol, was relatively impervious to global ties and domestic interest groups, both trafficking prevention and victim protection were associated with these factors. Our findings also suggest that fear of repercussions is not a major driver of state actions to combat trafficking—neither ratification of the Trafficking Protocol nor levels of United States aid were associated with greater implementation of anti-trafficking measures. PMID:26538806

  19. Human trafficking: review of educational resources for health professionals.

    Science.gov (United States)

    Ahn, Roy; Alpert, Elaine J; Purcell, Genevieve; Konstantopoulos, Wendy Macias; McGahan, Anita; Cafferty, Elizabeth; Eckardt, Melody; Conn, Kathryn L; Cappetta, Kate; Burke, Thomas F

    2013-03-01

    Human trafficking is an increasingly well-recognized human rights violation that is estimated to involve more than 2 million victims worldwide each year. The health consequences of this issue bring victims into contact with health systems and healthcare providers, thus providing the potential for identification and intervention. A robust healthcare response, however, requires a healthcare workforce that is aware of the health impact of this issue; educated about how to identify and treat affected individuals in a compassionate, culturally aware, and trauma-informed manner; and trained about how to collaborate efficiently with law enforcement, case management, and advocacy partners. This article describes existing educational offerings about human trafficking designed for a healthcare audience and makes recommendations for further curriculum development. A keyword search and structured analysis of peer-reviewed and gray literature, conducted in 2011 and 2012, yielded 27 items that provide basic guidance to health professionals on human trafficking. The 27 resources differed substantially in format, length, scope, and intended audience. Topic areas covered by these resources included trafficking definitions and scope, health consequences, victim identification, appropriate treatment, referral to services, legal issues, and security. None of the educational resources has been rigorously evaluated. There is a clear need to develop, implement, and evaluate high-quality education and training programs that focus on human trafficking for healthcare providers. Copyright © 2013 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  20. Entrepreneurship and Innovation in the Fight Against Human Trafficking

    Directory of Open Access Journals (Sweden)

    Christina Bain

    2017-06-01

    Full Text Available There has been much discussed and written on the benefits of entrepreneurship education, as well as the importance of early access to this type of learning. But how can entrepreneurship education train and inspire the next generation of anti-trafficking leaders? How can entrepreneurship also be a driver for prevention and a source of economic stability for those at-risk and survivors of human trafficking? At present, there are entrepreneurs and entrepreneurs-in-training at multiple age levels coming from a variety of backgrounds, incomes, and circumstances who will develop groundbreaking strategies and solutions in the fight against trafficking. These current and future entrepreneurs can also provide fresh perspectives to those in government and business while building more effective tri-sector coalitions and partnerships that address human trafficking. This article explores how and why entrepreneurship can be a key vehicle for social change and innovations in combating human trafficking, along with providing a multi-ingredient recipe of prosperity for those most vulnerable.