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Human Trafficking

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61. The cellular endosomal protein stannin inhibits intracellular trafficking of human papillomavirus during virus entry (PubMed)

The cellular endosomal protein stannin inhibits intracellular trafficking of human papillomavirus during virus entry Human papillomaviruses (HPVs) are the most common sexually transmitted viruses and one of the most important infectious causes of cancers worldwide. While prophylactic vaccines are effective against certain strains of HPV, established infections still cause deadly cancers in both men and women. HPV traffics to the nucleus via the retrograde transport pathway, but the mechanism (...) of intracellular transport of non-enveloped viruses such as HPV is incompletely understood. Using an overexpression screen, we identify several genes that control HPV16 entry. We focused on the mechanism by which one of the screen hits, stannin, blocks HPV16 infection. Stannin has not been previously implicated in virus entry. Overexpression of stannin specifically inhibits infection by several HPV types, but not other viruses tested. Stannin is constitutively expressed in human keratinocytes, and its basal

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2017 The Journal of general virology

62. Phosphorylation of human aquaporin 2 (AQP2) allosterically controls its interaction with the lysosomal trafficking protein LIP5 (PubMed)

Phosphorylation of human aquaporin 2 (AQP2) allosterically controls its interaction with the lysosomal trafficking protein LIP5 The interaction between the renal water channel aquaporin-2 (AQP2) and the lysosomal trafficking regulator-interacting protein LIP5 targets AQP2 to multivesicular bodies and facilitates lysosomal degradation. This interaction is part of a process that controls AQP2 apical membrane abundance in a vasopressin-dependent manner, allowing for urine volume adjustment (...) of AQP2 trafficking by post-translational modifications.© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

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2017 The Journal of biological chemistry

63. Protein trafficking in the mitochondrial intermembrane space: mechanisms and links to human disease (PubMed)

Protein trafficking in the mitochondrial intermembrane space: mechanisms and links to human disease Mitochondria fulfill a diverse range of functions in cells including oxygen metabolism, homeostasis of inorganic ions and execution of apoptosis. Biogenesis of mitochondria relies on protein import pathways that are ensured by dedicated multiprotein translocase complexes localized in all sub-compartments of these organelles. The key components and pathways involved in protein targeting (...) and assembly have been characterized in great detail over the last three decades. This includes the oxidative folding machinery in the intermembrane space, which contributes to the redox-dependent control of proteostasis. Here, we focus on several components of this system and discuss recent evidence suggesting links to human proteopathy.© 2017 The Author(s).

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2017 Biochemical Journal

64. Cell-Free versus Cell-to-Cell Infection by Human Immunodeficiency Virus Type 1 and Human T-Lymphotropic Virus Type 1: Exploring the Link among Viral Source, Viral Trafficking, and Viral Replication (PubMed)

Cell-Free versus Cell-to-Cell Infection by Human Immunodeficiency Virus Type 1 and Human T-Lymphotropic Virus Type 1: Exploring the Link among Viral Source, Viral Trafficking, and Viral Replication Human immunodeficiency virus type 1 (HIV-1) and human T-lymphotropic virus type 1 (HTLV-1) are complex retroviruses mainly infecting CD4(+) T lymphocytes. In addition, antigen-presenting cells such as dendritic cells (DCs) are targeted in vivo by both viruses, although to a lesser extent. Interaction (...) of HIV-1 with DCs plays a key role in viral dissemination from the mucosa to CD4(+) T lymphocytes present in lymphoid organs. While similar mechanisms may occur for HTLV-1 as well, most HTLV-1 data were obtained from T-cell studies, and little is known regarding the trafficking of this virus in DCs. We first compared the efficiency of cell-free versus cell-associated viral sources of both retroviruses at infecting DCs. We showed that both HIV-1 and HTLV-1 cell-free particles are poorly efficient

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2016 Journal of virology

65. Barcoding of GPCR Trafficking and Signaling Through the Various Trafficking Roadmaps by Compartmentalized Signaling Networks (PubMed)

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 β1-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 (...) Barcoding of GPCR Trafficking and Signaling Through the Various Trafficking Roadmaps by Compartmentalized Signaling Networks 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

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2017 Cellular signalling

66. Lysosomal trafficking regulator Lyst links membrane trafficking to toll-like receptor–mediated inflammatory responses (PubMed)

Lysosomal trafficking regulator Lyst links membrane trafficking to toll-like receptor–mediated inflammatory responses Subcellular compartmentalization of receptor signaling is an emerging principle in innate immunity. However, the functional integration of receptor signaling pathways into membrane trafficking routes and its physiological relevance for immune responses is still largely unclear. In this study, using Lyst-mutant beige mice, we show that lysosomal trafficking regulator Lyst links (...) maturation, resulting in a failure to form an activation-induced Rab7+ endosomal/phagosomal compartment. This specific Rab7+ compartment was further demonstrated to serve as a major site for active TRIF signaling events, thus linking phagosomal maturation to specific TLR signaling pathways. The immunoregulatory role of Lyst on TLR signaling pathways was confirmed in human cells by CRISPR/Cas9-mediated gene inactivation. As mutations in LYST cause human Chédiak-Higashi syndrome, a severe immunodeficiency

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2017 The Journal of experimental medicine

67. Hypoxia induced hERG trafficking defect linked to cell cycle arrest in SH-SY5Y cells. (PubMed)

Hypoxia induced hERG trafficking defect linked to cell cycle arrest in SH-SY5Y cells. The alpha subunit of the voltage gated human ether-a-go-go-related (hERG) potassium channel regulates cell excitability in a broad range of cell lines. HERG channels are also expressed in a variety of cancer cells and control cell proliferation and apoptosis. Hypoxia, a common feature of tumors, alters gating properties of hERG currents in SH-SY5Y neuroblastoma cells. In the present study, we examined (...) the molecular mechanisms and physiological significance underlying hypoxia-altered hERG currents in SH-SY5Y neuroblastoma cells. Hypoxia reduced the surface expression of 150kDa form and increased 125kDa form of hERG protein expression in the endoplasmic reticulum (ER). The changes in protein expression were associated with ~50% decrease in hERG potassium conductance. ER retention of hERG 125kDa form by CH was due to defective trafficking and was rescued by exposing cells to hypoxia at low temperatures

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2019 PLoS ONE

68. Caring for trafficked and unidentified patients in the EHR shadows: Shining a light by sharing the data. (PubMed)

Caring for trafficked and unidentified patients in the EHR shadows: Shining a light by sharing the data. Healthcare providers have key roles in the prevention of, detection of, and interventions for human trafficking. Yet caring for trafficked persons is particularly challenging: patients whose identities are unknown, unreliable, or false could receive subpar care from providers delivering care in a vacuum of relevant information. The application of precision medicine principles and integration (...) -structured interviews with key informants, which informed a subsequent broad survey of physicians and registered nurses.Our findings support the perception that trafficked persons obtain care yet remain unnoticed or undocumented in the electronic health record. Our survey findings further reveal that healthcare providers remain largely unaware of human trafficking issues and are inadequately prepared to provide patient-centered care for trafficked and unidentified patients.Meaningful efforts to design

2019 PLoS ONE

69. Trafficking of immune cells across the blood-brain barrier is modulated by neurofibrillary pathology in tauopathies. (PubMed)

Trafficking of immune cells across the blood-brain barrier is modulated by neurofibrillary pathology in tauopathies. Tauopathies represent a heterogeneous group of neurodegenerative disorders characterized by abnormal deposition of the hyperphosphorylated microtubule-associated protein tau. Chronic neuroinflammation in tauopathies is driven by glial cells that potentially trigger the disruption of the blood-brain barrier (BBB). Pro-inflammatory signaling molecules such as cytokines, chemokines (...) , VCAM-1, and selectins. We suggest that the compensation of BBB in the diseased brain represents a crucial factor in neurodegeneration of human tauopathies.

2019 PLoS ONE

70. Human trafficking and health: a cross-sectional survey of NHS professionals' contact with victims of human trafficking. (PubMed)

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

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2015 BMJ open

71. Human T-Lymphotropic Virus Type 1-Induced Overexpression of Activated Leukocyte Cell Adhesion Molecule (ALCAM) Facilitates Trafficking of Infected Lymphocytes through the Blood-Brain Barrier (PubMed)

Human T-Lymphotropic Virus Type 1-Induced Overexpression of Activated Leukocyte Cell Adhesion Molecule (ALCAM) Facilitates Trafficking of Infected Lymphocytes through the Blood-Brain Barrier Human T-lymphotropic virus type 1 (HTLV-1) is the etiological agent of a slowly progressive neurodegenerative disease, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). This disease develops upon infiltration of HTLV-1-infected lymphocytes into the central nervous system, mostly (...) of human BBB endothelial cells. This study suggests a potential role for ALCAM in HAM/TSP pathogenesis.Human T-lymphotropic virus type 1 (HTLV-1) is the etiological agent of a slowly progressive neurodegenerative disease, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). This disease is the consequence of the infiltration of HTLV-1-infected lymphocytes into the central nervous system (CNS), mostly the thoracic spinal cord. The CNS is normally protected by a physiological structure

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2016 Journal of virology

72. Human Immunodeficiency Virus Type 2 (HIV-2) Gag Is Trafficked in an AP-3 and AP-5 Dependent Manner (PubMed)

Human Immunodeficiency Virus Type 2 (HIV-2) Gag Is Trafficked in an AP-3 and AP-5 Dependent Manner Although human immunodeficiency virus (HIV) types 1 and 2 are closely related lentiviruses with similar replication cycles, HIV-2 infection is associated with slower progression to AIDS, a higher proportion of long term non-progressors, and lower rates of transmission than HIV-1, likely as a consequence of a lower viral load during HIV-2 infection. A mechanistic explanation for the differential (...) viral load remains unclear but knowledge of differences in particle production between HIV-1 and HIV-2 may help to shed light on this issue. In contrast to HIV-1, little is known about the assembly of HIV-2 particles, and the trafficking of HIV-2 Gag, the structural component of the virus, within cells. We have established that HIV-2 Gag accumulates in intracellular CD63 positive compartments, from which it may be delivered or recycled to the cell surface, or degraded. HIV-2 particle release

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2016 PloS one

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

Human Sirtuin 2 Localization, Transient Interactions, and Impact on the Proteome Point to Its Role in Intracellular Trafficking 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 (...) interaction partners. Altogether, our study expands the knowledge of SIRT2 cytoplasmic functions to define a previously unrecognized involvement in intracellular trafficking pathways, which may contribute to its roles in cellular homeostasis and human diseases.© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

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2016 Molecular & cellular proteomics : MCP

74. The CD63-Syntenin-1 Complex Controls Post-Endocytic Trafficking of Oncogenic Human Papillomaviruses (PubMed)

The CD63-Syntenin-1 Complex Controls Post-Endocytic Trafficking of Oncogenic Human Papillomaviruses Human papillomaviruses enter host cells via a clathrin-independent endocytic pathway involving tetraspanin proteins. However, post-endocytic trafficking required for virus capsid disassembly remains unclear. Here we demonstrate that the early trafficking pathway of internalised HPV particles involves tetraspanin CD63, syntenin-1 and ESCRT-associated adaptor protein ALIX. Following internalisation (...) present the syntenin-1 interacting protein ALIX as critical for HPV infection and CD63-syntenin-1-ALIX complex formation as a prerequisite for intracellular transport enabling viral capsid disassembly. Thus, our results identify the CD63-syntenin-1-ALIX complex as a key regulatory component in post-endocytic HPV trafficking.

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2016 Scientific reports

75. Vesicular trafficking of immune mediators in human eosinophils revealed by immunoelectron microscopy (PubMed)

Vesicular trafficking of immune mediators in human eosinophils revealed by immunoelectron microscopy Electron microscopy (EM)-based techniques are mostly responsible for our current view of cell morphology at the subcellular level and continue to play an essential role in biological research. In cells from the immune system, such as eosinophils, EM has helped to understand how cells package and release mediators involved in immune responses. Ultrastructural investigations of human eosinophils (...) enabled visualization of secretory processes in detail and identification of a robust, vesicular trafficking essential for the secretion of immune mediators via a non-classical secretory pathway associated with secretory (specific) granules. This vesicular system is mainly organized as large tubular-vesicular carriers (Eosinophil Sombrero Vesicles - EoSVs) actively formed in response to cell activation and provides a sophisticated structural mechanism for delivery of granule-stored mediators

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2016 Experimental cell research

76. Coronary Artery-Bypass-Graft Surgery Increases the Plasma Concentration of Exosomes Carrying a Cargo of Cardiac MicroRNAs: An Example of Exosome Trafficking Out of the Human Heart with Potential for Cardiac Biomarker Discovery (PubMed)

Coronary Artery-Bypass-Graft Surgery Increases the Plasma Concentration of Exosomes Carrying a Cargo of Cardiac MicroRNAs: An Example of Exosome Trafficking Out of the Human Heart with Potential for Cardiac Biomarker Discovery Exosome nanoparticles carry a composite cargo, including microRNAs (miRs). Cultured cardiovascular cells release miR-containing exosomes. The exosomal trafficking of miRNAs from the heart is largely unexplored. Working on clinical samples from coronary-artery by-pass (...) significantly with cTn-I. By contrast cTn-I was positively correlated with the plasma exosome level and the exosomal cardiac miRs.The plasma concentrations of exosomes and their cargo of cardiac miRs increased in patients undergoing CABG and were positively correlated with hs-cTnI. These data provide evidence that CABG induces the trafficking of exosomes from the heart to the peripheral circulation. Future studies are necessary to investigate the potential of circulating exosomes as clinical biomarkers

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2016 PloS one

77. Perceptions of Psychological Coercion and Human Trafficking in the West Midlands of England: Beginning to Know the Unknown (PubMed)

Perceptions of Psychological Coercion and Human Trafficking in the West Midlands of England: Beginning to Know the Unknown Modern slavery is less overt than historical state-sanctioned slavery because psychological abuse is typically used to recruit and then control victims. The recent UK Draft Modern Slavery Bill, and current UK government anti-slavery strategy relies heavily on a shared understanding and public cooperation to tackle this crime. Yet, UK research investigating public (...) understanding of modern slavery is elusive. We report community survey data from 682 residents of the Midlands of England, where modern slavery is known to occur, concerning their understanding of nonphysical coercion and human trafficking (one particular form of modern slavery). Analysis of quantitative data and themed categorization of qualitative data revealed a mismatch between theoretical frameworks and understanding of psychological coercion, and misconceptions concerning the nature of human

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2016 PloS one

78. Distinct functional domains within the acidic cluster of tegument protein pp28 required for trafficking and cytoplasmic envelopment of human cytomegalovirus (PubMed)

Distinct functional domains within the acidic cluster of tegument protein pp28 required for trafficking and cytoplasmic envelopment of human cytomegalovirus Human cytomegalovirus UL99-encoded tegument protein pp28 contains a 16 aa acidic cluster that is required for pp28 trafficking to the assembly compartment (AC) and the virus assembly. However, functional signals within the acidic cluster of pp28 remain undefined. Here, we demonstrated that an acidic cluster rather than specific sorting (...) signals was required for trafficking to the AC. Recombinant viruses with chimeric pp28 proteins expressing non-native acidic clusters exhibited delayed viral growth kinetics and decreased production of infectious virus, indicating that the native acidic cluster of pp28 was essential for wild-type virus assembly. These results suggested that the acidic cluster of pp28 has distinct functional domains required for trafficking and for efficient virus assembly. The first half (aa 44-50) of the acidic

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2016 The Journal of general virology

79. Human Trafficking of Minors and Childhood Adversity in Florida. (PubMed)

Human Trafficking of Minors and Childhood Adversity in Florida. 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

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2016 American Journal of Public Health

80. An incomplete trafficking defect to the cell-surface leads to paradoxical thrombocytosis for human and murine MPL P106L. (PubMed)

An incomplete trafficking defect to the cell-surface leads to paradoxical thrombocytosis for human and murine MPL P106L. The mechanisms behind the hereditary thrombocytosis induced by the thrombopoietin (THPO) receptor MPL P106L mutant remain unknown. A complete trafficking defect to the cell surface has been reported, suggesting either weak constitutive activity or nonconventional THPO-dependent mechanisms. Here, we report that the thrombocytosis phenotype induced by MPL P106L belongs (...) ]-THPO binding. Altogether, these results demonstrate that MPL P106L is a receptor with an incomplete defect in trafficking, which induces a low but not absent localization of the receptor on cell surface and a response to THPO in immature MK cells.© 2016 by The American Society of Hematology.

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2016 Blood

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