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Human Trafficking

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3421. New naturally occurring missense mutations of the human mineralocorticoid receptor disclose important residues involved in dynamic interactions with deoxyribonucleic acid, intracellular trafficking, and ligand binding. Full Text available with Trip Pro

New naturally occurring missense mutations of the human mineralocorticoid receptor disclose important residues involved in dynamic interactions with deoxyribonucleic acid, intracellular trafficking, and ligand binding. We have investigated the functional consequences of three naturally occurring amino acid substitutions of the human mineralocorticoid receptor (hMR). These mutations are located in the DNA-binding domain and the ligand-binding domain (LBD) and are associated with autosomal

2004 Molecular Endocrinology

3422. The postendocytotic trafficking of the human lutropin receptor is mediated by a transferable motif consisting of the C-terminal cysteine and an upstream leucine. Full Text available with Trip Pro

The postendocytotic trafficking of the human lutropin receptor is mediated by a transferable motif consisting of the C-terminal cysteine and an upstream leucine. Mutants of the human (h) lutropin receptor (LHR) were analyzed using a combination of biochemical and imaging approaches to define motifs that participate in the postendocytotic sorting of this G protein-coupled receptor (GPCR). We show that a substantial portion of the human chorionic gonadotropin internalized by the hLHR sorts (...) to a recycling pathway, and the internalized hLHR accumulates in endosomes because of the C-terminal cysteine (Cys(699)) and an upstream Leu(683) present in the hLHR. The removal or simultaneous mutation of these two residues reroutes the internalized human chorionic gonadotropin to a degradation pathway and the internalized hLHR to lysosomes. We also show that grafting the 17 C-terminal residues of the hLHR into the C-terminal tail of two GPCRs that are routed to a lysosomal/degradation pathway (the rat LHR

2004 Molecular Endocrinology

3423. Mutations in ARFGEF2 implicate vesicle trafficking in neural progenitor proliferation and migration in the human cerebral cortex. Full Text available with Trip Pro

Mutations in ARFGEF2 implicate vesicle trafficking in neural progenitor proliferation and migration in the human cerebral cortex. Disruption of human neural precursor proliferation can give rise to a small brain (microcephaly), and failure of neurons to migrate properly can lead to an abnormal arrest of cerebral cortical neurons in proliferative zones near the lateral ventricles (periventricular heterotopia). Here we show that an autosomal recessive condition characterized by microcephaly (...) protein (BIG2), which is required for vesicle and membrane trafficking from the trans-Golgi network (TGN). Inhibition of BIG2 by BFA, or by a dominant negative ARFGEF2 cDNA, decreases cell proliferation in vitro, suggesting a cell-autonomous regulation of neural expansion. Inhibition of BIG2 also disturbed the intracellular localization of such molecules as E-cadherin and beta-catenin by preventing their transport from the Golgi apparatus to the cell surface. Our findings show that vesicle trafficking

2004 Nature Genetics

3424. An Acidic Cluster of Human Cytomegalovirus UL99 Tegument Protein Is Required for Trafficking and Function Full Text available with Trip Pro

An Acidic Cluster of Human Cytomegalovirus UL99 Tegument Protein Is Required for Trafficking and Function The human cytomegalovirus (HCMV) virion is comprised of a linear double-stranded DNA genome, proteinaceous capsid and tegument, and a lipid envelope containing virus-encoded glycoproteins. Of these components, the tegument is the least well defined in terms of both protein content and function. Several of the major tegument proteins are phosphoproteins (pp), including pp150, pp71, pp65 (...) , and pp28. pp28, encoded by the UL99 open reading frame (ORF), traffics to vacuole-like cytoplasmic structures and was shown recently to be essential for envelopment. To elucidate the UL99 amino acid sequences necessary for its trafficking and function in the HCMV replication cycle, two types of viral mutants were analyzed. Using a series of recombinant viruses expressing various UL99-green fluorescent protein fusions, we demonstrate that myristoylation at glycine 2 and an acidic cluster (AC; amino

2004 Journal of virology

3425. Human Immunodeficiency Virus Type 1 Nef: Adapting to Intracellular Trafficking Pathways Full Text available with Trip Pro

Human Immunodeficiency Virus Type 1 Nef: Adapting to Intracellular Trafficking Pathways The Nef protein of primate lentiviruses is a unique protein that has evolved in several ways to manipulate the biology of an infected cell to support viral replication, immune evasion, pathogenesis, and viral spread. Nef is a small (25- to 34-kDa), myristoylated protein that binds to a collection of cellular factors and acts as an adaptor to generate novel protein interactions to accomplish specific (...) trafficking of several other host molecules has also been reported, and an emerging theory suggests that Nef generates pleiotrophic effects in the secretory and endocytic pathways that reprogram intracellular protein trafficking and may ultimately provide an efficient platform for viral assembly. This review critically discusses some of the major findings regarding the impact of human immunodeficiency virus type 1 Nef on host protein transport and addresses some emerging directions in this area of human

2006 Microbiology and Molecular Biology Reviews

3426. Monocyte/macrophage trafficking in acquired immunodeficiency syndrome encephalitis: Lessons from human and nonhuman primate studies Full Text available with Trip Pro

Monocyte/macrophage trafficking in acquired immunodeficiency syndrome encephalitis: Lessons from human and nonhuman primate studies Here the authors discuss evidence in human and animal models supporting two opposing views regarding the pathogenesis of human immunodeficiency virus (HIV) in the central nervous system (CNS): (1) HIV infection in the CNS is a compartmentalized infection, with the virus-infected macrophages entering the CNS early, infecting resident microglia and astrocytes (...) is normally expressed by perivascular MPhi s but not resident microglia in normal CNS of humans and rhesus macaques. In agreement with other studies, the authors demonstrate expression of CD163 by brain MPhi s in HIVE and simian immunodeficiency virus encephalitis (SIVE). CNS tissues from HIV-sero positive individuals with HIVE or HIV-associated progressive multifocal leukoencephalopathy (PML) were also examined. In HIVE, the authors further demonstrate colocalization of CD163 and CD16 (Fcgamma III

2008 Journal of neurovirology

3427. The Cytoplasmic Tail of Glycoprotein M (gpUL100) Expresses Trafficking Signals Required for Human Cytomegalovirus Assembly and Replication Full Text available with Trip Pro

The Cytoplasmic Tail of Glycoprotein M (gpUL100) Expresses Trafficking Signals Required for Human Cytomegalovirus Assembly and Replication The virion envelope of human cytomegalovirus (HCMV) is complex and consists of an incompletely defined number of glycoproteins. The gM/gN protein complex is the most abundant protein component of the envelope. Studies have indicated that deletion of the viral gene encoding either gM or gN is a lethal mutation. Analysis of the amino acid sequence of gM (...) disclosed a C-terminal acidic cluster of amino acids and a tyrosine-containing trafficking motif, both of which are well-described trafficking/sorting signals in the cellular secretory pathway. To investigate the roles of these signals in the trafficking of the gM/gN complex during virus assembly, we made a series of gM (UL100 open reading frame) mutants in the AD169 strain of HCMV. Mutant viruses that lacked the entire C-terminal cytoplasmic tail of gM were not viable, suggesting that the cytoplasmic

2007 Journal of virology

3428. Intracellular trafficking of a polymorphism in the COOH terminus of the alpha-subunit of the human epithelial sodium channel is modulated by casein kinase 1. Full Text available with Trip Pro

Intracellular trafficking of a polymorphism in the COOH terminus of the alpha-subunit of the human epithelial sodium channel is modulated by casein kinase 1. The A663T polymorphism of the alpha-subunit of the human epithelial sodium channel (hENaC) increases the functional and surface expression of alphabetagamma-hENaC in Xenopus laevis oocytes, and the context of this residue in the COOH terminus of alpha-hENaC is important for this effect. Query of a phosphoprotein database suggested (...) of alpha-T663-hENaC to the oocyte membrane. IC261 also inhibited the functional expression of alpha-T692-mENaC and a chimeric m(1-678)/h(650-669)alpha-T663, mbetagamma ENaC, but not alpha-A692-mENaC or m(1-678)/h(650-669)alpha-A663, mbetagamma ENaC. These data suggest that additional residues outside of the alpha-hENaC COOH terminus are important for modulation of alpha-T663-hENaC trafficking by CK1. Overexpression of CK1alpha did not alter functional expression of alpha-T663-hENaC. In contrast, modest

2007 American Journal of Physiology. Renal physiology

3429. Mental health of female survivors of human trafficking in Nepal. (Abstract)

Mental health of female survivors of human trafficking in Nepal. Little is known about the mental health status of trafficked women, even though international conventions require that it be considered. This study, therefore, aims at exploring the mental health status, including anxiety, depression and post-traumatic stress disorder (PTSD), of female survivors of human trafficking who are currently supported by local non-governmental organizations (NGOs) in Katmandu, the capital of Nepal (...) %). The findings suggest that programs to address human trafficking should include interventions (such as psychosocial support) to improve survivors' mental health status, paying attention to the category of work performed during the trafficking period. In particular, the current efforts of the United Nations and various NGOs that help survivors of human trafficking need to more explicitly focus on mental health and psychosocial support.

2008 Social Science & Medicine

3430. Dynamic regulation of phosphoinositide 3-kinase-gamma activity and beta-adrenergic receptor trafficking in end-stage human heart failure. Full Text available with Trip Pro

Dynamic regulation of phosphoinositide 3-kinase-gamma activity and beta-adrenergic receptor trafficking in end-stage human heart failure. Downregulation of beta-adrenergic receptors (betaARs) under conditions of heart failure requires receptor targeting of phosphoinositide 3-kinase (PI3K)-gamma and redistribution of betaARs into endosomal compartments. Because support with a left ventricular assist device (LVAD) results in significant improvement of cardiac function in humans, we investigated (...) the effects of mechanical unloading on regulation of PI3Kgamma activity and intracellular distribution of betaARs. Additionally, we tested whether displacement of PI3Kgamma from activated betaARs would restore agonist responsiveness in failing human cardiomyocytes.To test the role of PI3K on betaAR endocytosis in failing human hearts, we assayed for PI3K activity in human left ventricular samples before and after mechanical unloading (LVAD). Before LVAD, failing human hearts displayed a marked increase

2007 Circulation

3431. Intracellular localization and trafficking of fluorescein-labeled cisplatin in human ovarian carcinoma cells. (Abstract)

Intracellular localization and trafficking of fluorescein-labeled cisplatin in human ovarian carcinoma cells. We sought to identify the subcellular compartments in which cisplatin [cis-diamminedichloroplatinum (DDP)] accumulates in human ovarian carcinoma cells and define its export pathways.Deconvoluting digital microscopy was used to identify the subcellular location of fluorescein-labeled DDP (F-DDP) in 2008 ovarian carcinoma cells stained with organelle-specific markers. Drugs that block (...) vesicle movement were used to map the traffic pattern.F-DDP accumulated in vesicles and were not detectable in the cytoplasm. F-DDP accumulated in the Golgi, in vesicles belonging to the secretory export pathway, and in lysosomes but not in early endosomes. F-DDP extensively colocalized with vesicles expressing the copper efflux protein, ATP7A, whose expression modulates the cellular pharmacology of DDP. Inhibition of vesicle trafficking with brefeldin A, wortmannin, or H89 increased the F-DDP content

2005 Clinical Cancer Research

3432. Substrate and enzyme trafficking as a means of regulating 1,25-dihydroxyvitamin d synthesis and action: the human innate immune response. Full Text available with Trip Pro

Substrate and enzyme trafficking as a means of regulating 1,25-dihydroxyvitamin d synthesis and action: the human innate immune response. Tissue availability of the active vitamin D metabolite, 1,25-dihydroxyvitamin D [1,25(OH)(2)D] is dependent on expression of the activating enzyme 1alpha-hydroxylase (CYP27b1) and its catabolic counterpart 24-hydroxylase (CYP24). The activity of these two enzymes is in turn controlled by factors including affinity of the serum vitamin D-binding protein (DBP (...) ) for 25-hydroxyvitamin D [25(OH)D]; the availability of enzyme cofactors; and the relative amount of hydroxylase gene product expressed. In recent years, it has become clear that directed trafficking of substrate and enzyme is also a pivotal component of the regulated process of hormone synthesis by both renal and extrarenal tissues expressing the CYP27b1 and CYP24 genes. Extracellular regulatory trafficking events are defined by the quantity of substrate 25(OH)D entering the circulatory pool. Entry

2007 Journal of Bone and Mineral Research

3433. CpG oligodeoxynucleotides alter lymphocyte and dendritic cell trafficking in humans. Full Text available with Trip Pro

CpG oligodeoxynucleotides alter lymphocyte and dendritic cell trafficking in humans. CpG oligodeoxynucleotides (CpG-ODN) are being investigated as cancer vaccine adjuvants because they mature plasmacytoid dendritic cells (PDC) into potent antigen-presenting cells. CpG-ODN also induce PDC to secrete chemokines that alter lymphocyte migration. Whether CpG-ODN TLR signals enhance antigen-specific immunity and/or trafficking in humans is unknown.We conducted a phase I study of CpG-ODN (1018 ISS (...) PDC induced T-cell migration, showing that CpG-ODN stimulation of human PDC was sufficient to chemoattract T cells.Our results show that (a) CpG-ODN with GM-CSF may not be an effective adjuvant strategy for hTERT peptide vaccines but (b) GM-CSF/CpG-ODN causes a PDC-mediated chemokine response that recruits T-cell migration to the peripheral tissues. These findings suggest a novel therapeutic role for targeted injections of CpG-ODN to direct lymphocyte migration to specific sites such as the tumor

2008 Clinical Cancer Research

3434. Liver X receptor activation controls intracellular cholesterol trafficking and esterification in human macrophages. Full Text available with Trip Pro

Liver X receptor activation controls intracellular cholesterol trafficking and esterification in human macrophages. Liver X receptors (LXRs) are nuclear receptors that regulate macrophage cholesterol efflux by inducing ATP-binding cassette transporter A1 (ABCA1) and ABCG1/ABCG4 gene expression. The Niemann-Pick C (NPC) proteins NPC1 and NPC2 are located in the late endosome, where they control cholesterol trafficking to the plasma membrane. The mobilization of cholesterol from intracellular (...) pools to the plasma membrane is a determinant governing its availability for efflux to extracellular acceptors. Here we investigated the influence of LXR activation on intracellular cholesterol trafficking in primary human macrophages. Synthetic LXR activators increase the amount of free cholesterol in the plasma membrane by inducing NPC1 and NPC2 gene expression. Moreover, ABCA1-dependent cholesterol efflux induced by LXR activators was drastically decreased in the presence of progesterone, which

2005 Circulation Research

3435. Trafficking of Shiga toxin/Shiga-like toxin-1 in human glomerular microvascular endothelial cells and human mesangial cells. Full Text available with Trip Pro

Trafficking of Shiga toxin/Shiga-like toxin-1 in human glomerular microvascular endothelial cells and human mesangial cells. This study has determined the intracellular transport route of Shiga-like toxin (Stx) and the highly related Shiga toxin in human glomerular microvascular endothelial cells (GMVECs) and mesangial cells. In addition, the effect of tumor necrosis factor-alpha (TNF-alpha), which contributes to the pathogenesis of hemolytic-uremic syndrome, was evaluated more profound (...) associated and followed the retrograde route. TNF-alpha upregulated Gb3 expression in mesangial cells and GMVECs, without affecting the efficiency of StxB transport to the ER. In conclusion, our study shows that in human GMVECs and mesangial cells, StxB follows the retrograde route to the Golgi apparatus and the ER. TNF-alpha treatment increases the amount of cell-associated StxB, but not retrograde transport as such, making it likely that the strong TNF-alpha-induced sensitization of mesangial cells

2006 Kidney International

3436. Evidence for defects in the trafficking and translocation of GLUT4 glucose transporters in skeletal muscle as a cause of human insulin resistance. Full Text available with Trip Pro

Evidence for defects in the trafficking and translocation of GLUT4 glucose transporters in skeletal muscle as a cause of human insulin resistance. Insulin resistance is instrumental in the pathogenesis of type 2 diabetes mellitus and the Insulin Resistance Syndrome. While insulin resistance involves decreased glucose transport activity in skeletal muscle, its molecular basis is unknown. Since muscle GLUT4 glucose transporter levels are normal in type 2 diabetes, we have tested the hypothesis (...) , the insulin-regulated aminopeptidase (vp165) was redistributed to a dense membrane compartment and did not translocate in response to insulin in insulin-resistant subgroups. In conclusion, insulin alters the subcellular localization of GLUT4 vesicles in human muscle, and this effect is impaired equally in insulin-resistant subjects with and without diabetes. This translocation defect is associated with abnormal accumulation of GLUT4 in a dense membrane compartment demonstrable in basal muscle. We have

1998 Journal of Clinical Investigation

3437. CD8+ T cells in human uterine endometrial lymphoid aggregates: evidence for accumulation of cells by trafficking Full Text available with Trip Pro

CD8+ T cells in human uterine endometrial lymphoid aggregates: evidence for accumulation of cells by trafficking Lymphoid aggregates (LA) develop during the proliferative phase of the menstrual cycle in the human uterine endometrium (EM). They contain mostly CD8+ T cells and B cells. As these LA are absent immediately following menses, they may arise by division of cells resident in the EM, or by division of a limited number of precursor cells that traffic into the EM during the early (...) proliferative phase of the menstrual cycle. Alternatively, they may arise by the continuous trafficking of cells into the EM throughout the proliferative phase of the menstrual cycle. In this study we investigated the distribution and frequency of CD8+ T cells in the aggregates using expression of Vbeta2 or Vbeta8 as markers of clonality and Ki-67 as a marker of dividing cells. Confocal microscopic analysis of endometrial tissues showed the random distribution of CD8+ T cells within aggregates within

2001 Immunology

3438. Agonist-promoted trafficking of human bradykinin receptors: arrestin- and dynamin-independent sequestration of the B2 receptor and bradykinin in HEK293 cells. Full Text available with Trip Pro

Agonist-promoted trafficking of human bradykinin receptors: arrestin- and dynamin-independent sequestration of the B2 receptor and bradykinin in HEK293 cells. In this study, we analysed the agonist-promoted trafficking of human B(2) (B(2)R) and B(1) (B(1)R) bradykinin (BK) receptors using wild-type and green fluorescent protein (GFP)-tagged receptors in HEK293 cells. B(2)R was sequestered to a major extent upon exposure to BK, as determined by the loss of cell-surface B(2)R using radioligand

2001 Biochemical Journal

3439. European parliament tries to stamp out trafficking in human organs Full Text available with Trip Pro

European parliament tries to stamp out trafficking in human organs 14593021 2003 12 03 2012 03 06 1756-1833 327 7422 2003 Nov 01 BMJ (Clinical research ed.) BMJ European parliament tries to stamp out trafficking in human organs. 1009 Watson Rory R eng News England BMJ 8900488 0959-8138 AIM E IM European Union Humans Tissue and Organ Procurement economics legislation & jurisprudence 115745 Health Care and Public Health Legal Approach KIE Bib: organ and tissue donation 2003 11 1 5 0 2003 12 4 5 0

2003 BMJ : British Medical Journal

3440. Impaired trafficking of human kidney anion exchanger (kAE1) caused by hetero-oligomer formation with a truncated mutant associated with distal renal tubular acidosis. Full Text available with Trip Pro

Impaired trafficking of human kidney anion exchanger (kAE1) caused by hetero-oligomer formation with a truncated mutant associated with distal renal tubular acidosis. Autosomal dominant distal renal tubular acidosis (dRTA) has been associated with several mutations in the anion exchanger AE1 gene. The effect of an 11-amino-acid C-terminal dRTA truncation mutation (901 stop) on the expression of kidney AE1 (kAE1) and erythroid AE1 was examined in transiently transfected HEK-293 cells. Unlike (...) the wild-type proteins, kAE1 901 stop and AE1 901 stop mutants exhibited impaired trafficking from the endoplasmic reticulum to the plasma membrane as determined by immunolocalization, cell-surface biotinylation, oligosaccharide processing and pulse-chase experiments. The 901 stop mutants were able to bind to an inhibitor affinity resin, suggesting that these mutant membrane proteins were not grossly misfolded. Co-expression of wild-type and mutant kAE1 or AE1 resulted in intracellular retention

2002 Biochemical Journal

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