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Human Trafficking

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

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

2016 PloS one PubMed abstract

102. The immune receptor Tim-3 acts as a trafficker in a Tim-3/galectin-9 autocrine loop in human myeloid leukemia cells (Full text)

The immune receptor Tim-3 acts as a trafficker in a Tim-3/galectin-9 autocrine loop in human myeloid leukemia cells The immune receptor Tim-3 is often highly expressed in human acute myeloid leukemia (AML) cells where it acts as a growth factor and inflammatory receptor. Recently, it has been demonstrated that Tim-3 forms an autocrine loop with its natural ligand galectin-9 in human AML cells. However, the pathophysiological functions of Tim-3 in human AML cells remain unclear. Here, we report (...) for the first time that Tim-3 is required for galectin-9 secretion in human AML cells. However, this effect is cell-type specific and was found so far to be applicable only to myeloid (and not, for example, lymphoid) leukemia cells. We concluded that AML cells might use Tim-3 as a trafficker for the secretion of galectin-9 which can then be possibly used to impair the anticancer activities of cytotoxic T cells and natural killer (NK) cells.

2016 Oncoimmunology PubMed abstract

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

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

2016 The Journal of general virology PubMed abstract

104. Small interfering RNA-mediated silencing of nicotinamide phosphoribosyltransferase (NAMPT) and lysosomal trafficking regulator (LYST) induce growth inhibition and apoptosis in human multiple myeloma cells: A preliminary study (Full text)

Small interfering RNA-mediated silencing of nicotinamide phosphoribosyltransferase (NAMPT) and lysosomal trafficking regulator (LYST) induce growth inhibition and apoptosis in human multiple myeloma cells: A preliminary study Multiple myeloma (MM) is a malignancy of B lymphocytes or plasma cells. Our array-based comparative genomic hybridization findings revealed chromosomal gains at 7q22.3 and 1q42.3, where nicotinamide (NAM) phosphoribosyltransferase (NAMPT) and lysosomal trafficking (...) regulator (LYST) genes are localized, respectively. This led us to further study the functions of these genes in myeloma cells. NAMPT is a key enzyme involved in nicotinamide adenine dinucleotide salvage pathway, and it is frequently overexpressed in human cancers. In contrast, little is known about the function of LYST in cancer. The expression of LYST is shown to affect lysosomal size, granule size, and autophagy in human cells. In this study, the effects of small interfering RNA (siRNA)-mediated

2016 Bosnian Journal of Basic Medical Sciences PubMed abstract

105. Analysis of SCAP N-glycosylation and Trafficking in Human Cells (Full text)

Analysis of SCAP N-glycosylation and Trafficking in Human Cells Elevated lipogenesis is a common characteristic of cancer and metabolic diseases. Sterol regulatory element-binding proteins (SREBPs), a family of membrane-bound transcription factors controlling the expression of genes important for the synthesis of cholesterol, fatty acids and phospholipids, are frequently upregulated in these diseases. In the process of SREBP nuclear translocation, SREBP-cleavage activating protein (SCAP) plays (...) a central role in the trafficking of SREBP from the endoplasmic reticulum (ER) to the Golgi and in subsequent proteolysis activation. Recently, we uncovered that glucose-mediated N-glycosylation of SCAP is a prerequisite condition for the exit of SCAP/SREBP from the ER and movement to the Golgi. N-glycosylation stabilizes SCAP and directs SCAP/SREBP trafficking. Here, we describe a protocol for the isolation of membrane fractions in human cells and for the preparation of the samples for the detection

2016 Journal of visualized experiments : JoVE PubMed abstract

106. Human cytomegalovirus gH stability and trafficking are regulated by ER-associated degradation and transmembrane architecture (Full text)

Human cytomegalovirus gH stability and trafficking are regulated by ER-associated degradation and transmembrane architecture The prototypic betaherpesvirus human cytomegalovirus (CMV) establishes life-long persistence within its human host. While benign in healthy individuals, CMV poses a significant threat to the immune compromised, including transplant recipients and neonates. The CMV glycoprotein complex gH/gL/gO mediates infection of fibroblasts, and together with the gH/gL/UL128/130/131 (...) a pentameric complex permits infection of epithelial, endothethial, and myeloid cells. Given the central role of the gH/gL complex during infection, we were interested in studying cellular trafficking of the gH/gL complex through generation of human cells that stably express gH and gL. When expressed alone, CMV gH and gL were degraded through the ER-associated degradation (ERAD) pathway. However, co-expression of these proteins stabilized the polypeptides and enhanced their cell-surface expression

2016 Scientific reports PubMed abstract

107. α-Synuclein–induced lysosomal dysfunction occurs through disruptions in protein trafficking in human midbrain synucleinopathy models (Full text)

α-Synuclein–induced lysosomal dysfunction occurs through disruptions in protein trafficking in human midbrain synucleinopathy models Parkinson's disease (PD) is an age-related neurodegenerative disorder characterized by the accumulation of protein aggregates comprised of α-synuclein (α-syn). A major barrier in treatment discovery for PD is the lack of identifiable therapeutic pathways capable of reducing aggregates in human neuronal model systems. Mutations in key components of protein (...) trafficking and cellular degradation machinery represent important risk factors for PD; however, their precise role in disease progression and interaction with α-syn remains unclear. Here, we find that α-syn accumulation reduced lysosomal degradation capacity in human midbrain dopamine models of synucleinopathies through disrupting hydrolase trafficking. Accumulation of α-syn at the cell body resulted in aberrant association with cis-Golgi-tethering factor GM130 and disrupted the endoplasmic reticulum

2016 Proceedings of the National Academy of Sciences of the United States of America PubMed abstract

108. HIV-tat alters Connexin43 expression and trafficking in human astrocytes: role in NeuroAIDS (Full text)

HIV-tat alters Connexin43 expression and trafficking in human astrocytes: role in NeuroAIDS HIV-associated neurocognitive disorders (HAND) are a major complication in at least half of the infected population despite effective antiretroviral treatment and immune reconstitution. HIV-associated CNS damage is not correlated with active viral replication but instead is associated with mechanisms that regulate inflammation and neuronal compromise. Our data indicate that one of these mechanisms (...) is mediated by gap junction channels and/or hemichannels. Normally, gap junction channels shutdown under inflammatory conditions, including viral diseases. However, HIV infection upregulates Connexin43 (Cx43) expression and maintains gap junctional communication by unknown mechanism(s).Human primary astrocytes were exposed to several HIV proteins as well as to HIV, and expression and function of Connexin43- and Connexin30-containing channels were determined by western blot, immunofluorescence

2016 Journal of neuroinflammation PubMed abstract

109. Trafficking of AAV vectors across a model of the blood-brain barrier; a comparative study of transcytosis and transduction using primary human brain endothelial cells (Full text)

Trafficking of AAV vectors across a model of the blood-brain barrier; a comparative study of transcytosis and transduction using primary human brain endothelial cells Developing therapies for central nervous system (CNS) diseases is exceedingly difficult because of the blood-brain barrier (BBB). Notably, emerging technologies may provide promising new options for the treatment of CNS disorders. Adeno-associated virus serotype 9 (AAV9) has been shown to transduce cells in the CNS following (...) intravascular administration in rodents, cats, pigs, and non-human primates. These results suggest that AAV9 is capable of crossing the BBB. However, mechanisms that govern AAV9 transendothelial trafficking at the BBB remain unknown. Furthermore, possibilities that AAV9 may transduce brain endothelial cells or affect BBB integrity still require investigation. Using primary human brain microvascular endothelial cells as a model of the human BBB, we performed transduction and transendothelial trafficking

2016 Journal of neurochemistry PubMed abstract

110. The CD63-Syntenin-1 Complex Controls Post-Endocytic Trafficking of Oncogenic Human Papillomaviruses (Full text)

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.

2016 Scientific reports PubMed abstract

111. Trafficking Dynamics of PCSK9-Induced LDLR Degradation: Focus on Human PCSK9 Mutations and C-Terminal Domain (Full text)

Trafficking Dynamics of PCSK9-Induced LDLR Degradation: Focus on Human PCSK9 Mutations and C-Terminal Domain PCSK9 is a secreted ligand and negative post-translational regulator of low-density lipoprotein receptor (LDLR) in hepatocytes. Gain-of-function (GOF) or loss-of-function (LOF) mutations in PCSK9 are directly correlated with high or low plasma LDL-cholesterol levels, respectively. Therefore, PCSK9 is a prevailing lipid-lowering target to prevent coronary heart diseases and stroke. Herein (...) , we fused monomeric fluorescent proteins to PCSK9 and LDLR to visualize their intra- and extracellular trafficking dynamics by live confocal microscopy. Fluorescence recovery after photobleaching (FRAP) showed that PCSK9 LOF R46L mutant and GOF mutations S127R and D129G, but not the LDLR high-affinity mutant D374Y, significantly accelerate PCSK9 exit from the endoplasmic reticulum (ER). Quantitative analysis of inverse FRAP revealed that only R46L presented a much slower trafficking from the trans

2016 PloS one PubMed abstract

112. Human Trafficking Identification and Service Provision in the Medical and Social Service Sectors (Full text)

Human Trafficking Identification and Service Provision in the Medical and Social Service Sectors The medical sector presents a unique opportunity for identification and service to victims of human trafficking. In this article, we describe local and site-specific efforts to develop an intervention tool to be used in an urban hospital's emergency department in the midwestern United States. In the development of our tool, we focused on both identification and intervention to assist trafficked (...) by rights-based approaches to anti-trafficking efforts that addresses the practical challenges of human trafficking victim identification while simultaneously working to provide resources and disseminate services to those victims.

2016 Health and human rights PubMed abstract

113. 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 (Full text)

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

2016 Journal of virology PubMed abstract

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

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

2016 PloS one PubMed abstract

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

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.

2016 Molecular & cellular proteomics : MCP PubMed abstract

116. 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 (Full text)

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

2016 PloS one PubMed abstract

117. Modeling leukocyte trafficking at the human blood-nerve barrier in vitro and in vivo geared towards targeted molecular therapies for peripheral neuroinflammation (Full text)

Modeling leukocyte trafficking at the human blood-nerve barrier in vitro and in vivo geared towards targeted molecular therapies for peripheral neuroinflammation Peripheral neuroinflammation is characterized by hematogenous mononuclear leukocyte infiltration into peripheral nerves. Despite significant clinical knowledge, advancements in molecular biology and progress in developing specific drugs for inflammatory disorders such as rheumatoid arthritis, inflammatory bowel disease, and multiple (...) sclerosis, there are currently no specific therapies that modulate pathogenic peripheral nerve inflammation. Modeling leukocyte trafficking at the blood-nerve barrier using a reliable human in vitro model and potential intravital microscopy techniques in representative animal models guided by human observational data should facilitate the targeted modulation of the complex inflammatory cascade needed to develop safe and efficacious therapeutics for immune-mediated neuropathies and chronic neuropathic

2016 Journal of neuroinflammation PubMed abstract

118. The Hague Recommendations: Improving Nonlegislative Responses to Trafficking in Human Beings for the Purpose of Organ Removal (Full text)

The Hague Recommendations: Improving Nonlegislative Responses to Trafficking in Human Beings for the Purpose of Organ Removal Over the years, the trade in human organs has become an object of international concern. Since the 1980s, antiorgan trade initiatives have mainly involved the strengthening of legislative responses. Little attention however is given to nonlegislative responses by law enforcement authorities. The HOTT project is a European Union-funded research project titled "trafficking (...) the ethical and legal obligations of health care providers, the protection of persons trafficked for the purpose of organ removal, strengthening cross-border collaboration in criminal cases, and stimulating partnerships between transplant professionals and law enforcement. These recommendations offer ways in which transplant professionals can contribute to improving the nonlegislative response to trafficking in human beings for the purpose of organ removal.

2016 Transplantation direct PubMed abstract

119. Establishing Trafficking in Human Beings for the Purpose of Organ Removal and Improving Cross-Border Collaboration in Criminal Cases: Recommendations (Full text)

Establishing Trafficking in Human Beings for the Purpose of Organ Removal and Improving Cross-Border Collaboration in Criminal Cases: Recommendations In this short summary report on the legal definition of trafficking in human beings for the purpose of organ removal and improving cross-border collaboration in criminal cases, challenges, and recommendations in the areas of defining the crime, criminal investigation and prosecution, and cross-border cooperation are made. These are the outcomes (...) of a working group discussion during the writers' conference of the HOTT project, a European Union-funded project against trafficking in human beings for the purpose of organ removal.

2016 Transplantation direct PubMed abstract

120. Protection of Human Beings Trafficked for the Purpose of Organ Removal: Recommendations (Full text)

Protection of Human Beings Trafficked for the Purpose of Organ Removal: Recommendations This report presents a comprehensive set of recommendations for protection of human beings who are trafficked for the purpose of organ removal or are targeted for such trafficking. Developed by an interdisciplinary group of international experts under the auspices of the project Trafficking in Human Beings for the Purpose of Organ Removal (also known as the HOTT project), these recommendations are grounded (...) in the view that an individual who parts with an organ for money within an illegal scheme is ipso facto a victim and that the crime of trafficking in human beings for the purpose of organ removal (THBOR) intersects with the crime of trafficking in organs. Consequently, the protection of victims should be a priority for all actors involved in antitrafficking activities: those combating organ-related crimes, such as health organizations and survivor support services, and those combating trafficking in human

2016 Transplantation direct PubMed abstract

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