WorldWideScience

Sample records for model viral trafficking

  1. Nuclear Export Signal Masking Regulates HIV-1 Rev Trafficking and Viral RNA Nuclear Export.

    Science.gov (United States)

    Behrens, Ryan T; Aligeti, Mounavya; Pocock, Ginger M; Higgins, Christina A; Sherer, Nathan M

    2017-02-01

    HIV-1's Rev protein forms a homo-oligomeric adaptor complex linking viral RNAs to the cellular CRM1/Ran-GTP nuclear export machinery through the activity of Rev's prototypical leucine-rich nuclear export signal (NES). In this study, we used a functional fluorescently tagged Rev fusion protein as a platform to study the effects of modulating Rev NES identity, number, position, or strength on Rev subcellular trafficking, viral RNA nuclear export, and infectious virion production. We found that Rev activity was remarkably tolerant of diverse NES sequences, including supraphysiological NES (SNES) peptides that otherwise arrest CRM1 transport complexes at nuclear pores. Rev's ability to tolerate a SNES was both position and multimerization dependent, an observation consistent with a model wherein Rev self-association acts to transiently mask the NES peptide(s), thereby biasing Rev's trafficking into the nucleus. Combined imaging and functional assays also indicated that NES masking underpins Rev's well-known tendency to accumulate at the nucleolus, as well as Rev's capacity to activate optimal levels of late viral gene expression. We propose that Rev multimerization and NES masking regulates Rev's trafficking to and retention within the nucleus even prior to RNA binding. HIV-1 infects more than 34 million people worldwide causing >1 million deaths per year. Infectious virion production is activated by the essential viral Rev protein that mediates nuclear export of intron-bearing late-stage viral mRNAs. Rev's shuttling into and out of the nucleus is regulated by the antagonistic activities of both a peptide-encoded N-terminal nuclear localization signal and C-terminal nuclear export signal (NES). How Rev and related viral proteins balance strong import and export activities in order to achieve optimal levels of viral gene expression is incompletely understood. We provide evidence that multimerization provides a mechanism by which Rev transiently masks its NES peptide

  2. 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...

  3. 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...

  4. Tyrosine phosphorylation of AAV2 vectors and its consequences on viral intracellular trafficking and transgene expression

    Science.gov (United States)

    Zhong, Li; Li, Baozheng; Jayandharan, Giridhararao; Mah, Cathryn S.; Govindasamy, Lakshmanan; Agbandje-McKenna, Mavis; Herzog, Roland W.; Weigel-Van Aken, Kirsten A.; Hobbs, Jacqueline A.; Zolotukhin, Sergei; Muzyczka, Nicholas; Srivastava, Arun

    2008-01-01

    We have documented that epidermal growth factor receptor protein tyrosine kinase (EGFR-PTK) signaling negatively affects intracellular trafficking and transduction efficiency of recombinant adeno-associated virus 2 (AAV2) vectors. Specifically, inhibition of EGFR-PTK signaling leads to decreased ubiquitination of AAV2 capsid proteins, which in turn, facilitates viral nuclear transport by limiting proteasome-mediated degradation of AAV2 vectors. In the present studies, we observed that AAV capsids can indeed be phosphorylated at tyrosine residues by EGFR-PTK in in vitro phosphorylation assays and that phosphorylated AAV capsids retain their structural integrity. However, although phosphorylated AAV vectors enter cells as efficiently as their unphosphorylated counterparts, their transduction efficiency is significantly reduced. This reduction is not due to impaired viral second-strand DNA synthesis since transduction efficiency of both single-stranded AAV (ssAAV) and self-complementary AAV (scAAV) vectors is decreased by ~68% and ~74%, respectively. We also observed that intracellular trafficking of tyrosine-phosphorylated AAV vectors from cytoplasm to nucleus is significantly decreased, which leads to ubiquitination of AAV capsids followed by proteasome-mediated degradation, although downstream consequences of capsid ubiquitination may also be affected by tyrosine-phosphorylation. These studies provide new insights into the role of tyrosine-phosphorylation of AAV capsids in various steps in the virus life cycle, which has implications in the optimal use of recombinant AAV vectors in human gene therapy. PMID:18834608

  5. Tyrosine-phosphorylation of AAV2 vectors and its consequences on viral intracellular trafficking and transgene expression

    OpenAIRE

    Zhong, Li; Li, Baozheng; Jayandharan, Giridhararao; Mah, Cathryn S.; Govindasamy, Lakshmanan; Agbandje-McKenna, Mavis; Herzog, Roland W.; Weigel-Van Aken, Kirsten A.; Hobbs, Jacqueline A.; Zolotukhin, Sergei; Muzyczka, Nicholas; Srivastava, Arun

    2008-01-01

    We have documented that epidermal growth factor receptor protein tyrosine kinase (EGFR-PTK) signaling negatively affects intracellular trafficking and transduction efficiency of recombinant adeno-associated virus 2 (AAV2) vectors. Specifically, inhibition of EGFR-PTK signaling leads to decreased ubiquitination of AAV2 capsid proteins, which in turn, facilitates viral nuclear transport by limiting proteasome-mediated degradation of AAV2 vectors. In the present studies, we observed that AAV cap...

  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. Tyrosine-phosphorylation of AAV2 vectors and its consequences on viral intracellular trafficking and transgene expression

    International Nuclear Information System (INIS)

    Zhong Li; Li Baozheng; Jayandharan, Giridhararao; Mah, Cathryn S.; Govindasamy, Lakshmanan; Agbandje-McKenna, Mavis; Herzog, Roland W.

    2008-01-01

    We have documented that epidermal growth factor receptor protein tyrosine kinase (EGFR-PTK) signaling negatively affects intracellular trafficking and transduction efficiency of recombinant adeno-associated virus 2 (AAV2) vectors. Specifically, inhibition of EGFR-PTK signaling leads to decreased ubiquitination of AAV2 capsid proteins, which in turn, facilitates viral nuclear transport by limiting proteasome-mediated degradation of AAV2 vectors. In the present studies, we observed that AAV capsids can indeed be phosphorylated at tyrosine residues by EGFR-PTK in in vitro phosphorylation assays and that phosphorylated AAV capsids retain their structural integrity. However, although phosphorylated AAV vectors enter cells as efficiently as their unphosphorylated counterparts, their transduction efficiency is significantly reduced. This reduction is not due to impaired viral second-strand DNA synthesis since transduction efficiency of both single-stranded AAV (ssAAV) and self-complementary AAV (scAAV) vectors is decreased by ∼ 68% and ∼ 74%, respectively. We also observed that intracellular trafficking of tyrosine-phosphorylated AAV vectors from cytoplasm to nucleus is significantly decreased, which results from ubiquitination of AAV capsids followed by proteasome-mediated degradation, although downstream consequences of capsid ubiquitination may also be affected by tyrosine-phosphorylation. These studies provide new insights into the role of tyrosine-phosphorylation of AAV capsids in various steps in the virus life cycle, which has implications in the optimal use of recombinant AAV vectors in human gene therapy

  8. Ubiquitin-regulated nuclear-cytoplasmic trafficking of the Nipah virus matrix protein is important for viral budding.

    Directory of Open Access Journals (Sweden)

    Yao E Wang

    2010-11-01

    Full Text Available Paramyxoviruses are known to replicate in the cytoplasm and bud from the plasma membrane. Matrix is the major structural protein in paramyxoviruses that mediates viral assembly and budding. Curiously, the matrix proteins of a few paramyxoviruses have been found in the nucleus, although the biological function associated with this nuclear localization remains obscure. We report here that the nuclear-cytoplasmic trafficking of the Nipah virus matrix (NiV-M protein and associated post-translational modification play a critical role in matrix-mediated virus budding. Nipah virus (NiV is a highly pathogenic emerging paramyxovirus that causes fatal encephalitis in humans, and is classified as a Biosafety Level 4 (BSL4 pathogen. During live NiV infection, NiV-M was first detected in the nucleus at early stages of infection before subsequent localization to the cytoplasm and the plasma membrane. Mutations in the putative bipartite nuclear localization signal (NLS and the leucine-rich nuclear export signal (NES found in NiV-M impaired its nuclear-cytoplasmic trafficking and also abolished NiV-M budding. A highly conserved lysine residue in the NLS served dual functions: its positive charge was important for mediating nuclear import, and it was also a potential site for monoubiquitination which regulates nuclear export of the protein. Concordantly, overexpression of ubiquitin enhanced NiV-M budding whereas depletion of free ubiquitin in the cell (via proteasome inhibitors resulted in nuclear retention of NiV-M and blocked viral budding. Live Nipah virus budding was exquisitely sensitive to proteasome inhibitors: bortezomib, an FDA-approved proteasome inhibitor for treating multiple myeloma, reduced viral titers with an IC(50 of 2.7 nM, which is 100-fold less than the peak plasma concentration that can be achieved in humans. This opens up the possibility of using an "off-the-shelf" therapeutic against acute NiV infection.

  9. Viral marketing as epidemiological model

    OpenAIRE

    Rodrigues, Helena Sofia; Fonseca, Manuel

    2015-01-01

    In epidemiology, an epidemic is defined as the spread of an infectious disease to a large number of people in a given population within a short period of time. In the marketing context, a message is viral when it is broadly sent and received by the target market through person-to-person transmission. This specific marketing communication strategy is commonly referred as viral marketing. Due to this similarity between an epidemic and the viral marketing process and because the understanding of...

  10. 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.

  11. A model for assessing the risk of human trafficking on a local level

    Science.gov (United States)

    Colegrove, Amanda

    Human trafficking is a human rights violation that is difficult to quantify. Models for estimating the number of victims of trafficking presented by previous researchers depend on inconsistent, poor quality data. As an intermediate step to help current efforts by nonprofits to combat human trafficking, this project presents a model that is not dependent on quantitative data specific to human trafficking, but rather profiles the risk of human trafficking at the local level through causative factors. Businesses, indicated by the literature, were weighted based on the presence of characteristics that increase the likelihood of trafficking in persons. The mean risk was calculated by census tract to reveal the multiplicity of risk levels in both rural and urban settings. Results indicate that labor trafficking may be a more diffuse problem in Missouri than sex trafficking. Additionally, spatial patterns of risk remained largely the same regardless of adjustments made to the model.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. Modeling of Viral Aerosol Transmission and Detection

    KAUST Repository

    Khalid, Maryam; Amin, Osama; Ahmed, Sajid; Alouini, Mohamed-Slim

    2018-01-01

    The objective of this work is to investigate the spread mechanism of diseases in the atmosphere as an engineering problem. Among the viral transmission mechanisms that do not include physical contact, aerosol transmission is the most significant mode of transmission where virus-laden droplets are carried over long distances by wind. In this work, we focus on aerosol transmission of virus and introduce the idea of viewing virus transmission through aerosols and their transport as a molecular communication problem, where one has no control over transmission source but a robust receiver can be designed using nano-biosensors. To investigate this idea, a complete system is presented and end-toend mathematical model for the aerosol transmission channel is derived under certain constraints and boundary conditions. In addition to transmitter and channel, a receiver architecture composed of air sampler and Silicon Nanowire field effect transistor is also discussed. Furthermore, a detection problem is formulated for which maximum likelihood decision rule and the corresponding missed detection probability is discussed. At the end, simulation results are presented to investigate the parameters that affect the performance and justify the feasibility of proposed setup in related applications.

  17. Prostitution and Human Trafficking : A model-based exploration and policy analysis

    NARCIS (Netherlands)

    Kovari, A.; Pruyt, E.

    2012-01-01

    The meeting of the oldest profession with modern slavery is the topic of this paper. After a brief introduction to prostitution and prostitution-related human trafficking, this paper focuses on the Dutch policy debate. A System Dynamics simulation model related to the Dutch situation developed to

  18. The susceptible-infected-recovered (SIR) model for viral marketing

    Science.gov (United States)

    Ismail, Siti Suhaila; Akil, Ku Azlina Ku; Chulan, Majdah; Sharif, Noorzila

    2017-11-01

    Viral marketing is a marketing strategy utilizes social media to spread information about a product or services provided. It is the most powerful way to share information in a short amount of time. The objective of this study is to investigate the dynamic of viral marketing within a time duration in the point of view of mathematics. This study used the epidemiological model known as Susceptible-Infected-Recovered (SIR). The model consists of a system of three differential equations with three state variables namely susceptible (S), infected (I) and recovered (R). It considers a case of SIR model with demography. Numerical experiments have been performed. The results show that viral marketing reaches its peak within two days. The online messages shared will become higher if the initial number of the infected individual has been increased.

  19. Ensemble models of neutrophil trafficking in severe sepsis.

    Directory of Open Access Journals (Sweden)

    Sang Ok Song

    Full Text Available A hallmark of severe sepsis is systemic inflammation which activates leukocytes and can result in their misdirection. This leads to both impaired migration to the locus of infection and increased infiltration into healthy tissues. In order to better understand the pathophysiologic mechanisms involved, we developed a coarse-grained phenomenological model of the acute inflammatory response in CLP (cecal ligation and puncture-induced sepsis in rats. This model incorporates distinct neutrophil kinetic responses to the inflammatory stimulus and the dynamic interactions between components of a compartmentalized inflammatory response. Ensembles of model parameter sets consistent with experimental observations were statistically generated using a Markov-Chain Monte Carlo sampling. Prediction uncertainty in the model states was quantified over the resulting ensemble parameter sets. Forward simulation of the parameter ensembles successfully captured experimental features and predicted that systemically activated circulating neutrophils display impaired migration to the tissue and neutrophil sequestration in the lung, consequently contributing to tissue damage and mortality. Principal component and multiple regression analyses of the parameter ensembles estimated from survivor and non-survivor cohorts provide insight into pathologic mechanisms dictating outcome in sepsis. Furthermore, the model was extended to incorporate hypothetical mechanisms by which immune modulation using extracorporeal blood purification results in improved outcome in septic rats. Simulations identified a sub-population (about 18% of the treated population that benefited from blood purification. Survivors displayed enhanced neutrophil migration to tissue and reduced sequestration of lung neutrophils, contributing to improved outcome. The model ensemble presented herein provides a platform for generating and testing hypotheses in silico, as well as motivating further experimental

  20. Pest control through viral disease: mathematical modeling and analysis.

    Science.gov (United States)

    Bhattacharyya, S; Bhattacharya, D K

    2006-01-07

    This paper deals with the mathematical modeling of pest management under viral infection (i.e. using viral pesticide) and analysis of its essential mathematical features. As the viral infection induces host lysis which releases more virus into the environment, on the average 'kappa' viruses per host, kappain(1,infinity), the 'virus replication parameter' is chosen as the main parameter on which the dynamics of the infection depends. We prove that there exists a threshold value kappa(0) beyond which the endemic equilibrium bifurcates from the free disease one. Still for increasing kappa values, the endemic equilibrium bifurcates towards a periodic solution. We further analyse the orbital stability of the periodic orbits arising from bifurcation by applying Poor's condition. A concluding discussion with numerical simulation of the model is then presented.

  1. A Business Of Security: Applying An Economic Model To Human Trafficking In Oregon

    Science.gov (United States)

    2016-12-01

    restaurants that employ trafficked workers.22 With higher demand, there is supporting evidence of the creation of greater supply, which would allow a...91 This selection bias could stem partially from the fact that most trafficking victims who interact with the judicial system are typically sexually...exploited and trafficked females, which gives the perception that labor trafficking is non-existent or less common.92 The selection pool of

  2. Investigating the thermal dissociation of viral capsid by lattice model

    Science.gov (United States)

    Chen, Jingzhi; Chevreuil, Maelenn; Combet, Sophie; Lansac, Yves; Tresset, Guillaume

    2017-11-01

    The dissociation of icosahedral viral capsids was investigated by a homogeneous and a heterogeneous lattice model. In thermal dissociation experiments with cowpea chlorotic mottle virus and probed by small-angle neutron scattering, we observed a slight shrinkage of viral capsids, which can be related to the strengthening of the hydrophobic interaction between subunits at increasing temperature. By considering the temperature dependence of hydrophobic interaction in the homogeneous lattice model, we were able to give a better estimate of the effective charge. In the heterogeneous lattice model, two sets of lattice sites represented different capsid subunits with asymmetric interaction strengths. In that case, the dissociation of capsids was found to shift from a sharp one-step transition to a gradual two-step transition by weakening the hydrophobic interaction between AB and CC subunits. We anticipate that such lattice models will shed further light on the statistical mechanics underlying virus assembly and disassembly.

  3. Vaccines against viral hemorrhagic fevers: non-human primate models.

    Science.gov (United States)

    Carrion, Ricardo; Patterson, Jean L

    2011-06-01

    Viral hemorrhagic fevers are a group of disease syndromes caused by infection with certain RNA viruses. The disease is marked by a febrile response, malaise, coagulopathy and vascular permeability culminating in death. Case fatality rates can reach 90% depending on the etiologic agent. Currently, there is no approved antiviral treatment. Because of the high case fatality, risk of importation and the potential to use these agents as biological weapons, development of countermeasures to these agents is a high priority. The sporadic nature of disease outbreaks and the ethical issues associated with conducting a human trial for such diseases make human studies impractical; therefore, development of countermeasures must occur in relevant animal models. Non-human primates are superior models to study infectious disease because their immune system is similar to humans and they are good predictors of efficacy in vaccine development and other intervention strategies. This review article summarizes viral hemorrhagic fever non-human primate models.

  4. 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…

  5. What makes a marketing campaing a viral success? : A descriptive model exploring the mechanisms of viral marketing

    OpenAIRE

    Stålnacke Larsson, Richard; Odén, Niklas

    2011-01-01

    What makes some marketing campaigns so immensely big and well known when they are marketed through social media or with a viral approach? How can a company reach out to customers through viral marketing and how can they make use of today’s social media to achieve it? In this article we will try to understand and further explore what a campaign have to accomplish in order to achieve a viral spread, using a descriptive model which uses a number of factors and terms necessary in order to properl...

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

    Science.gov (United States)

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

    2016-02-16

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

  7. 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’.

  8. The anti-human trafficking collaboration model and serving victims: Providers' perspectives on the impact and experience.

    Science.gov (United States)

    Kim, Hea-Won; Park, Taekyung; Quiring, Stephanie; Barrett, Diana

    2018-01-01

    A coalition model is often used to serve victims of human trafficking but little is known about whether the model is adequately meeting the needs of the victims. The purpose of this study was to examine anti-human trafficking collaboration model in terms of its impact and the collaborative experience, including challenges and lessons learned from the service providers' perspective. Mixed methods study was conducted to evaluate the impact of a citywide anti-trafficking coalition model from the providers' perspectives. Web-based survey was administered with service providers (n = 32) and focus groups were conducted with Core Group members (n = 10). Providers reported the coalition model has made important impacts in the community by increasing coordination among the key agencies, law enforcement, and service providers and improving quality of service provision. Providers identified the improved and expanded partnerships among coalition members as the key contributing factor to the success of the coalition model. Several key strategies were suggested to improve the coalition model: improved referral tracking, key partner and protocol development, and information sharing.

  9. The viral G protein-coupled receptor ORF74 hijacks β-arrestins for endocytic trafficking in response to human chemokines

    NARCIS (Netherlands)

    De Munnik, Sabrina M.; Kooistra, Albert J.; Van Offenbeek, Jody; Nijmeijer, Saskia; de Graaf, C.; Smit, Martine J.; Leurs, Rob; Vischer, Henry F.

    2015-01-01

    Kaposi's sarcoma-associated herpesvirus-infected cells express the virally encoded G protein-coupled receptor ORF74. Although ORF74 is constitutively active, it binds human CXC chemokines that modulate this basal activity. ORF74-induced signaling has been demonstrated to underlie the development of

  10. The ANGPTL3-4-8 model, a molecular mechanism for triglyceride trafficking.

    Science.gov (United States)

    Zhang, Ren

    2016-04-01

    Lipoprotein lipase (LPL) is a rate-limiting enzyme for hydrolysing circulating triglycerides (TG) into free fatty acids that are taken up by peripheral tissues. Postprandial LPL activity rises in white adipose tissue (WAT), but declines in the heart and skeletal muscle, thereby directing circulating TG to WAT for storage; the reverse is true during fasting. However, the mechanism for the tissue-specific regulation of LPL activity during the fed-fast cycle has been elusive. Recent identification of lipasin/angiopoietin-like 8 (Angptl8), a feeding-induced hepatokine, together with Angptl3 and Angptl4, provides intriguing, yet puzzling, insights, because all the three Angptl members are LPL inhibitors, and the deficiency (overexpression) of any one causes hypotriglyceridaemia (hypertriglyceridaemia). Then, why does nature need all of the three? Our recent data that Angptl8 negatively regulates LPL activity specifically in cardiac and skeletal muscles suggest an Angptl3-4-8 model: feeding induces Angptl8, activating the Angptl8-Angptl3 pathway, which inhibits LPL in cardiac and skeletal muscles, thereby making circulating TG available for uptake by WAT, in which LPL activity is elevated owing to diminished Angptl4; the reverse is true during fasting, which suppresses Angptl8 but induces Angptl4, thereby directing TG to muscles. The model suggests a general framework for how TG trafficking is regulated. © 2016 The Authors.

  11. Viral infection model with periodic lytic immune response

    International Nuclear Information System (INIS)

    Wang Kaifa; Wang Wendi; Liu Xianning

    2006-01-01

    Dynamical behavior and bifurcation structure of a viral infection model are studied under the assumption that the lytic immune response is periodic in time. The infection-free equilibrium is globally asymptotically stable when the basic reproductive ratio of virus is less than or equal to one. There is a non-constant periodic solution if the basic reproductive ratio of the virus is greater than one. It is found that period doubling bifurcations occur as the amplitude of lytic component is increased. For intermediate birth rates, the period triplication occurs and then period doubling cascades proceed gradually toward chaotic cycles. For large birth rate, the period doubling cascade proceeds gradually toward chaotic cycles without the period triplication, and the inverse period doubling can be observed. These results can be used to explain the oscillation behaviors of virus population, which was observed in chronic HBV or HCV carriers

  12. GLOBAL STABILITY AND PERIODIC SOLUTION OF A VIRAL DYNAMIC MODEL

    Directory of Open Access Journals (Sweden)

    Erhan COŞKUN

    2009-02-01

    Full Text Available Abstract:In this paper, we consider the classical viral dynamic mathematical model. Global dynamics of the model is rigorously established. We prove that, if the basic reproduction number, the HIV infection is cleared from the T-cell population; if , the HIV infection persists. For an open set of parameter values, the chronic-infection equilibrium can be unstable and periodic solutions may exist. We establish parameter regions for which is globally stable. Keywords: Global stability, HIV infection; CD4+ T cells; Periodic solution Mathematics Subject Classifications (2000: 65L10, 34B05 BİR VİRAL DİNAMİK MODELİN GLOBAL KARARLILIĞI VE PERİYODİK ÇÖZÜMÜ Özet: Bu makalede klasik viral dinamik modeli ele aldık. Modelin global dinamikleri oluşturuldu. Eğer temel üretim sayısı olur ise HIV enfeksiyonu T hücre nüfusundan çıkartılır, eğer olursa HIV enfeksiyonu çıkartılamaz. Parametre değerlerinin açık bir kümesi için kronik enfeksiyon dengesi kararsızdır ve periyodik çözüm oluşabilir. ın global kararlı olduğu parametre bölgeleri oluşturuldu. Anahtar Kelimeler: Global Kararlılık, HIV enfeksiyon, CD4+ T hücreler, Periyodik çözüm

  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. Viral persistence, liver disease and host response in Hepatitis C-like virus rat model

    DEFF Research Database (Denmark)

    Trivedi, Sheetal; Murthy, Satyapramod; Sharma, Himanshu

    2018-01-01

    The lack of a relevant, tractable, and immunocompetent animal model for hepatitis C virus (HCV) has severely impeded investigations of viral persistence, immunity and pathogenesis. In the absence of immunocompetent models with robust HCV infection, homolog hepaciviruses in their natural host could...... potentially provide useful surrogate models. We isolated a rodent hepacivirus (RHV) from wild rats (Rattus norvegicus), RHV-rn1, acquired the complete viral genome sequence and developed an infectious reverse genetics system. RHV-rn1 resembles HCV in genomic features including the pattern of polyprotein...... cleavage sites and secondary structures in the viral 5' and 3' UTRs. We used site-directed and random mutagenesis to determine that only the first of the two miR-122 seed sites in viral 5'UTR is required for viral replication and persistence in rats. Next, we used the clone derived virus progeny to infect...

  15. A Viral Branching Model for Predicting the Spread of Electronic Word-of-Mouth

    NARCIS (Netherlands)

    R.J.A. van der Lans (Ralf); G.H. van Bruggen (Gerrit); J. Eliashberg (Jehoshua); B. Wierenga (Berend)

    2009-01-01

    textabstractIn a viral marketing campaign an organization develops a marketing message, and stimulates customers to forward this message to their contacts. Despite its increasing popularity, there are no models yet that help marketers to predict how many customers a viral marketing campaign will

  16. A Probabilistic Model of Illegal Drug Trafficking Operations in the Eastern Pacific and Caribbean Sea

    Science.gov (United States)

    2013-09-01

    production, drug-trafficking, and drug consumption . The South American countries in the Andean region, particularly Colombia, Peru, and Bolivia, are... cocoa production in these three countries at 187,500 hectares in 2010. This is down from a peak in 2007 of 232,500 hectares. Combining the Andean...operations. They tax cocoa farmers and buyers and have controlling interests in various operations of the drug supply chain (Seelke et al., 2011). When the

  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. Use of profile hidden Markov models in viral discovery: current insights

    Directory of Open Access Journals (Sweden)

    Reyes A

    2017-07-01

    Full Text Available Alejandro Reyes,1–3 João Marcelo P Alves,4 Alan Mitchell Durham,5 Arthur Gruber4 1Department of Biological Sciences, Universidad de los Andes, Bogotá, Colombia; 2Department of Pathology and Immunology, Center for Genome Sciences and Systems Biology, Washington University in Saint Louis, St Louis, MO, USA; 3Max Planck Tandem Group in Computational Biology, Universidad de los Andes, Bogotá, Colombia; 4Department of Parasitology, Institute of Biomedical Sciences, 5Department of Computer Science, Institute of Mathematics and Statistics, Universidade de São Paulo, São Paulo, Brazil Abstract: Sequence similarity searches are the bioinformatic cornerstone of molecular sequence analysis for all domains of life. However, large amounts of divergence between organisms, such as those seen among viruses, can significantly hamper analyses. Profile hidden Markov models (profile HMMs are among the most successful approaches for dealing with this problem, which represent an invaluable tool for viral identification efforts. Profile HMMs are statistical models that convert information from a multiple sequence alignment into a set of probability values that reflect position-specific variation levels in all members of evolutionarily related sequences. Since profile HMMs represent a wide spectrum of variation, these models show higher sensitivity than conventional similarity methods such as BLAST for the detection of remote homologs. In recent years, there has been an effort to compile viral sequences from different viral taxonomic groups into integrated databases, such as Prokaryotic Virus Orthlogous Groups (pVOGs and database of profile HMMs (vFam database, which provide functional annotation, multiple sequence alignments, and profile HMMs. Since these databases rely on viral sequences collected from GenBank and RefSeq, they suffer in variable extent from uneven taxonomic sampling, with low sequence representation of many viral groups, which affects the

  20. [Drosophila melanogaster as a model for studying the function of animal viral proteins].

    Science.gov (United States)

    Omelianchuk, L V; Iudina, O S

    2011-07-01

    Studies in which Drosophila melanogaster individuals carrying transgenes of animal viruses were used to analyze the action of animal viral proteins on the cell are reviewed. The data presented suggest that host specificity of viruses is determined by their proteins responsible for the penetration of the virus into the cell, while viral proteins responsible for interactions with the host cell are much less host-specific. Due to this, the model of Drosophila with its developed system of searching for genetic interactions can be used to find intracellular targets for the action of viral proteins of the second group.

  1. Dynamics of a viral infection model with delayed CTL response and immune circadian rhythm

    International Nuclear Information System (INIS)

    Bai Zhenguo; Zhou Yicang

    2012-01-01

    This paper studies the global dynamics of a viral infection model that takes into account circadian rhythm and time delay in the CTL response. It is shown that the basic reproduction numbers, R 0 and R 1 , determine the outcome of viral infection. Numerical simulations demonstrate that the changes in the amplitude of lytic component can generate a variety of dynamical patterns, ranging from simple daily oscillation to multi-day dynamics and eventually chaos, whereas time delay can alter the period of oscillation for the larger level of periodic forcing. These results can help to explain the viral oscillation behaviors, which were observed in chronic HBV and HCV infection patients.

  2. A study of the spreading scheme for viral marketing based on a complex network model

    Science.gov (United States)

    Yang, Jianmei; Yao, Canzhong; Ma, Weicheng; Chen, Guanrong

    2010-02-01

    Buzzword-based viral marketing, known also as digital word-of-mouth marketing, is a marketing mode attached to some carriers on the Internet, which can rapidly copy marketing information at a low cost. Viral marketing actually uses a pre-existing social network where, however, the scale of the pre-existing network is believed to be so large and so random, so that its theoretical analysis is intractable and unmanageable. There are very few reports in the literature on how to design a spreading scheme for viral marketing on real social networks according to the traditional marketing theory or the relatively new network marketing theory. Complex network theory provides a new model for the study of large-scale complex systems, using the latest developments of graph theory and computing techniques. From this perspective, the present paper extends the complex network theory and modeling into the research of general viral marketing and develops a specific spreading scheme for viral marking and an approach to design the scheme based on a real complex network on the QQ instant messaging system. This approach is shown to be rather universal and can be further extended to the design of various spreading schemes for viral marketing based on different instant messaging systems.

  3. How Can Viral Dynamics Models Inform Endpoint Measures in Clinical Trials of Therapies for Acute Viral Infections?

    Directory of Open Access Journals (Sweden)

    Carolin Vegvari

    Full Text Available Acute viral infections pose many practical challenges for the accurate assessment of the impact of novel therapies on viral growth and decay. Using the example of influenza A, we illustrate how the measurement of infection-related quantities that determine the dynamics of viral load within the human host, can inform investigators on the course and severity of infection and the efficacy of a novel treatment. We estimated the values of key infection-related quantities that determine the course of natural infection from viral load data, using Markov Chain Monte Carlo methods. The data were placebo group viral load measurements collected during volunteer challenge studies, conducted by Roche, as part of the oseltamivir trials. We calculated the values of the quantities for each patient and the correlations between the quantities, symptom severity and body temperature. The greatest variation among individuals occurred in the viral load peak and area under the viral load curve. Total symptom severity correlated positively with the basic reproductive number. The most sensitive endpoint for therapeutic trials with the goal to cure patients is the duration of infection. We suggest laboratory experiments to obtain more precise estimates of virological quantities that can supplement clinical endpoint measurements.

  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. Dysplastic hepatocytes develop nuclear inclusions in a mouse model of viral hepatitis.

    Directory of Open Access Journals (Sweden)

    Priyanka Thakur

    Full Text Available Viral hepatitis resulting in chronic liver disease is an important clinical challenge and insight into the cellular processes that drive pathogenesis will be critical in order to develop new diagnostic and therapeutic options. Nuclear inclusions in viral and non-viral hepatitis are well documented and have diagnostic significance in some disease contexts. However, the origins and functional consequences of these nuclear inclusions remain elusive. To date the clinical observation of nuclear inclusions in viral and non-viral hepatitis has not been explored at depth in murine models of liver disease. Herein, we report that in a transgenic model of hepatitis B surface antigen mediated hepatitis, murine hepatocytes exhibit nuclear inclusions. Cells bearing nuclear inclusions were more likely to express markers of cell proliferation. We also established a correlation between these inclusions and oxidative stress. N-acetyl cysteine treatment effectively reduced oxidative stress levels, relieved endoplasmic reticulum (ER stress, and the number of nuclear inclusions we observed in the transgenic mice. Our results suggest that the presence of nuclear inclusions in hepatocytes correlates with oxidative stress and cellular proliferation in a model of antigen mediated hepatitis.

  7. Manipulating 3D-Printed and Paper Models Enhances Student Understanding of Viral Replication

    Science.gov (United States)

    Couper, Lisa; Johannes, Kristen; Powers, Jackie; Silberglitt, Matt; Davenport, Jodi

    2016-01-01

    Understanding key concepts in molecular biology requires reasoning about molecular processes that are not directly observable and, as such, presents a challenge to students and teachers. We ask whether novel interactive physical models and activities can help students understand key processes in viral replication. Our 3D tangible models are…

  8. Rainfall-runoff model for prediction of waterborne viral contamination in a small river catchment

    Science.gov (United States)

    Gelati, E.; Dommar, C.; Lowe, R.; Polcher, J.; Rodó, X.

    2013-12-01

    We present a lumped rainfall-runoff model aimed at providing useful information for the prediction of waterborne viral contamination in small rivers. Viral contamination of water bodies may occur because of the discharge of sewage effluents and of surface runoff over areas affected by animal waste loads. Surface runoff is caused by precipitation that cannot infiltrate due to its intensity and to antecedent soil water content. It may transport animal feces to adjacent water bodies and cause viral contamination. We model streamflow by separating it into two components: subsurface flow, which is produced by infiltrated precipitation; and surface runoff. The model estimates infiltrated and non-infiltrated precipitation and uses impulse-response functions to compute the corresponding fractions of streamflow. The developed methodologies are applied to the Glafkos river, whose catchment extends for 102 km2 and includes the city of Patra. Streamflow and precipitation observations are available at a daily time resolution. Waterborne virus concentration measurements were performed approximately every second week from the beginning of 2011 to mid 2012. Samples were taken at several locations: in river water upstream of Patras and in the urban area; in sea water at the river outlet and approximately 2 km south-west of Patras; in sewage effluents before and after treatment. The rainfall-runoff model was calibrated and validated using observed streamflow and precipitation data. The model contribution to waterborne viral contamination prediction was benchmarked by analyzing the virus concentration measurements together with the estimated surface runoff values. The presented methodology may be a first step towards the development of waterborne viral contamination alert systems. Predicting viral contamination of water bodies would benefit sectors such as water supply and tourism.

  9. Community-driven demand creation for the use of routine viral load testing: a model to scale up routine viral load testing.

    Science.gov (United States)

    Killingo, Bactrin M; Taro, Trisa B; Mosime, Wame N

    2017-11-01

    HIV treatment outcomes are dependent on the use of viral load measurement. Despite global and national guidelines recommending the use of routine viral load testing, these policies alone have not translated into widespread implementation or sufficiently increased access for people living with HIV (PLHIV). Civil society and communities of PLHIV recognize the need to close this gap and to enable the scale up of routine viral load testing. The International Treatment Preparedness Coalition (ITPC) developed an approach to community-led demand creation for the use of routine viral load testing. Using this Community Demand Creation Model, implementers follow a step-wise process to capacitate and empower communities to address their most pressing needs. This includes utlizing a specific toolkit that includes conducting a baseline assessment, developing a treatment education toolkit, organizing mobilization workshops for knowledge building, provision of small grants to support advocacy work and conducting benchmark evaluations. The Community Demand Creation Model to increase demand for routine viral load testing services by PLHIV has been delivered in diverse contexts including in the sub-Saharan African, Asian, Latin American and the Caribbean regions. Between December 2015 and December 2016, ITPC trained more than 240 PLHIV activists, and disbursed US$90,000 to network partners in support of their national advocacy work. The latter efforts informed a regional, community-driven campaign calling for domestic investment in the expeditious implementation of national viral load testing guidelines. HIV treatment education and community mobilization are critical components of demand creation for access to optimal HIV treatment, especially for the use of routine viral load testing. ITPC's Community Demand Creation Model offers a novel approach to achieving this goal. © 2017 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of

  10. A Scalable Heuristic for Viral Marketing Under the Tipping Model

    Science.gov (United States)

    2013-09-01

    Flixster is a social media website that allows users to share reviews and other information about cinema . [35] It was extracted in Dec. 2010. – FourSquare...work of Reichman were developed independently . We also note that Reichman performs no experimental evaluation of the algorithm. A Scalable Heuristic...other dif- fusion models, such as the independent cascade model [21] and evolutionary graph theory [25] as well as probabilistic variants of the

  11. A highly intensified ART regimen induces long-term viral suppression and restriction of the viral reservoir in a simian AIDS model.

    Directory of Open Access Journals (Sweden)

    Iart Luca Shytaj

    Full Text Available Stably suppressed viremia during ART is essential for establishing reliable simian models for HIV/AIDS. We tested the efficacy of a multidrug ART (highly intensified ART in a wide range of viremic conditions (10³-10⁷ viral RNA copies/mL in SIVmac251-infected rhesus macaques, and its impact on the viral reservoir. Eleven macaques in the pre-AIDS stage of the disease were treated with a multidrug combination (highly intensified ART consisting of two nucleosidic/nucleotidic reverse transcriptase inhibitors (emtricitabine and tenofovir, an integrase inhibitor (raltegravir, a protease inhibitor (ritonavir-boosted darunavir and the CCR5 blocker maraviroc. All animals stably displayed viral loads below the limit of detection of the assay (i.e. <40 RNA copies/mL after starting highly intensified ART. By increasing the sensitivity of the assay to 3 RNA copies/mL, viral load was still below the limit of detection in all subjects tested. Importantly, viral DNA resulted below the assay detection limit (<2 copies of DNA/5*10⁵ cells in PBMCs and rectal biopsies of all animals at the end of the follow-up, and in lymph node biopsies from the majority of the study subjects. Moreover, highly intensified ART decreased central/transitional memory, effector memory and activated (HLA-DR⁺ effector memory CD4⁺ T-cells in vivo, in line with the role of these subsets as the main cell subpopulations harbouring the virus. Finally, treatment with highly intensified ART at viral load rebound following suspension of a previous anti-reservoir therapy eventually improved the spontaneous containment of viral load following suspension of the second therapeutic cycle, thus leading to a persistent suppression of viremia in the absence of ART. In conclusion, we show, for the first time, complete suppression of viral load by highly intensified ART and a likely associated restriction of the viral reservoir in the macaque AIDS model, making it a useful platform for testing

  12. First insight into the viral community of the cnidarian model metaorganism Aiptasia using RNA-Seq data

    KAUST Repository

    Brüwer, Jan D.

    2018-03-01

    Current research posits that all multicellular organisms live in symbioses with associated microorganisms and form so-called metaorganisms or holobionts. Cnidarian metaorganisms are of specific interest given that stony corals provide the foundation of the globally threatened coral reef ecosystems. To gain first insight into viruses associated with the coral model system Aiptasia (sensu Exaiptasia pallida), we analyzed an existing RNA-Seq dataset of aposymbiotic, partially populated, and fully symbiotic Aiptasia CC7 anemones with Symbiodinium. Our approach included the selective removal of anemone host and algal endosymbiont sequences and subsequent microbial sequence annotation. Of a total of 297 million raw sequence reads, 8.6 million (∼3%) remained after host and endosymbiont sequence removal. Of these, 3,293 sequences could be assigned as of viral origin. Taxonomic annotation of these sequences suggests that Aiptasia is associated with a diverse viral community, comprising 116 viral taxa covering 40 families. The viral assemblage was dominated by viruses from the families Herpesviridae (12.00%), Partitiviridae (9.93%), and Picornaviridae (9.87%). Despite an overall stable viral assemblage, we found that some viral taxa exhibited significant changes in their relative abundance when Aiptasia engaged in a symbiotic relationship with Symbiodinium. Elucidation of viral taxa consistently present across all conditions revealed a core virome of 15 viral taxa from 11 viral families, encompassing many viruses previously reported as members of coral viromes. Despite the non-random selection of viral genetic material due to the nature of the sequencing data analyzed, our study provides a first insight into the viral community associated with Aiptasia. Similarities of the Aiptasia viral community with those of corals corroborate the application of Aiptasia as a model system to study coral holobionts. Further, the change in abundance of certain viral taxa across different

  13. Modeling the winter-to-summer transition of prokaryotic and viral abundance in the Arctic Ocean.

    Science.gov (United States)

    Winter, Christian; Payet, Jérôme P; Suttle, Curtis A

    2012-01-01

    One of the challenges in oceanography is to understand the influence of environmental factors on the abundances of prokaryotes and viruses. Generally, conventional statistical methods resolve trends well, but more complex relationships are difficult to explore. In such cases, Artificial Neural Networks (ANNs) offer an alternative way for data analysis. Here, we developed ANN-based models of prokaryotic and viral abundances in the Arctic Ocean. The models were used to identify the best predictors for prokaryotic and viral abundances including cytometrically-distinguishable populations of prokaryotes (high and low nucleic acid cells) and viruses (high- and low-fluorescent viruses) among salinity, temperature, depth, day length, and the concentration of Chlorophyll-a. The best performing ANNs to model the abundances of high and low nucleic acid cells used temperature and Chl-a as input parameters, while the abundances of high- and low-fluorescent viruses used depth, Chl-a, and day length as input parameters. Decreasing viral abundance with increasing depth and decreasing system productivity was captured well by the ANNs. Despite identifying the same predictors for the two populations of prokaryotes and viruses, respectively, the structure of the best performing ANNs differed between high and low nucleic acid cells and between high- and low-fluorescent viruses. Also, the two prokaryotic and viral groups responded differently to changes in the predictor parameters; hence, the cytometric distinction between these populations is ecologically relevant. The models imply that temperature is the main factor explaining most of the variation in the abundances of high nucleic acid cells and total prokaryotes and that the mechanisms governing the reaction to changes in the environment are distinctly different among the prokaryotic and viral populations.

  14. Modeling the Winter–to–Summer Transition of Prokaryotic and Viral Abundance in the Arctic Ocean

    Science.gov (United States)

    Winter, Christian; Payet, Jérôme P.; Suttle, Curtis A.

    2012-01-01

    One of the challenges in oceanography is to understand the influence of environmental factors on the abundances of prokaryotes and viruses. Generally, conventional statistical methods resolve trends well, but more complex relationships are difficult to explore. In such cases, Artificial Neural Networks (ANNs) offer an alternative way for data analysis. Here, we developed ANN-based models of prokaryotic and viral abundances in the Arctic Ocean. The models were used to identify the best predictors for prokaryotic and viral abundances including cytometrically-distinguishable populations of prokaryotes (high and low nucleic acid cells) and viruses (high- and low-fluorescent viruses) among salinity, temperature, depth, day length, and the concentration of Chlorophyll-a. The best performing ANNs to model the abundances of high and low nucleic acid cells used temperature and Chl-a as input parameters, while the abundances of high- and low-fluorescent viruses used depth, Chl-a, and day length as input parameters. Decreasing viral abundance with increasing depth and decreasing system productivity was captured well by the ANNs. Despite identifying the same predictors for the two populations of prokaryotes and viruses, respectively, the structure of the best performing ANNs differed between high and low nucleic acid cells and between high- and low-fluorescent viruses. Also, the two prokaryotic and viral groups responded differently to changes in the predictor parameters; hence, the cytometric distinction between these populations is ecologically relevant. The models imply that temperature is the main factor explaining most of the variation in the abundances of high nucleic acid cells and total prokaryotes and that the mechanisms governing the reaction to changes in the environment are distinctly different among the prokaryotic and viral populations. PMID:23285186

  15. Pharmacokinetics and modeling of immune cell trafficking: quantifying differential influences of target tissues versus lymphocytes in SJL and lipopolysaccharide-treated mice

    Directory of Open Access Journals (Sweden)

    Banks William A

    2012-10-01

    Full Text Available Abstract Background Immune cell trafficking into the CNS and other tissues plays important roles in health and disease. Rapid quantitative methods are not available that could be used to study many of the dynamic aspects of immune cell-tissue interactions. Methods We used pharmacokinetics and modeling to quantify and characterize the trafficking of radioactively labeled lymphocytes into brain and peripheral tissues. We used variance from two-way ANOVAs with 2 × 2 experimental designs to model the relative influences of lymphocytes and target tissues in trafficking. Results We found that in male CD-1 mice, about 1 in 5,000 intravenously injected lymphocytes entered each gram of brain. Uptake by brain was 2 to 3 times higher in naïve SJL females, but uptake by spleen and clearance from blood was lower, demonstrating a dichotomy in immune cell distribution. Treatment of CD-1 mice with lipopolysaccharide (LPS increased immune cell uptake into brain but decreased uptake by spleen and axillary nodes. Conclusions Differences in brain uptake and in uptake by spleen between SJL and CD-1 mice were primarily determined by lymphocytes, whereas differences in uptake with LPS were primarily determined by lymphocytes for the brain but by the tissues for the spleen and the axillary lymph node. These results show that immune cells normally enter the CNS and that tissues and immune cells interact in ways that can be quantified by pharmacokinetic models.

  16. Tupaia belangeri as an experimental animal model for viral infection.

    Science.gov (United States)

    Tsukiyama-Kohara, Kyoko; Kohara, Michinori

    2014-01-01

    Tupaias, or tree shrews, are small mammals that are similar in appearance to squirrels. The morphological and behavioral characteristics of the group have been extensively characterized, and despite previously being classified as primates, recent studies have placed the group in its own family, the Tupaiidae. Genomic analysis has revealed that the genus Tupaia is closer to humans than it is to rodents. In addition, tupaias are susceptible to hepatitis B virus and hepatitis C virus. The only other experimental animal that has been demonstrated to be sensitive to both of these viruses is the chimpanzee, but restrictions on animal testing have meant that experiments using chimpanzees have become almost impossible. Consequently, the development of the tupaia for use as an animal infection model could become a powerful tool for hepatitis virus research and in preclinical studies on drug development.

  17. Stochastic simulation modeling to determine time to detect Bovine Viral Diarrhea antibodies in bulk tank milk

    DEFF Research Database (Denmark)

    Foddai, Alessandro; Enøe, Claes; Krogh, Kaspar

    2014-01-01

    A stochastic simulation model was developed to estimate the time from introduction ofBovine Viral Diarrhea Virus (BVDV) in a herd to detection of antibodies in bulk tank milk(BTM) samples using three ELISAs. We assumed that antibodies could be detected, after afixed threshold prevalence of seroco......A stochastic simulation model was developed to estimate the time from introduction ofBovine Viral Diarrhea Virus (BVDV) in a herd to detection of antibodies in bulk tank milk(BTM) samples using three ELISAs. We assumed that antibodies could be detected, after afixed threshold prevalence......, which was the most efficient ELISA, could detect antibodiesin the BTM of a large herd 280 days (95% prediction interval: 218; 568) after a transientlyinfected (TI) milking cow has been introduced into the herd. The estimated time to detectionafter introduction of one PI calf was 111 days (44; 605...

  18. 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.

  19. Support for viral persistence in bats from age-specific serology and models of maternal immunity.

    Science.gov (United States)

    Peel, Alison J; Baker, Kate S; Hayman, David T S; Broder, Christopher C; Cunningham, Andrew A; Fooks, Anthony R; Garnier, Romain; Wood, James L N; Restif, Olivier

    2018-03-01

    Spatiotemporally-localised prediction of virus emergence from wildlife requires focused studies on the ecology and immunology of reservoir hosts in their native habitat. Reliable predictions from mathematical models remain difficult in most systems due to a dearth of appropriate empirical data. Our goal was to study the circulation and immune dynamics of zoonotic viruses in bat populations and investigate the effects of maternally-derived and acquired immunity on viral persistence. Using rare age-specific serological data from wild-caught Eidolon helvum fruit bats as a case study, we estimated viral transmission parameters for a stochastic infection model. We estimated mean durations of around 6 months for maternally-derived immunity to Lagos bat virus and African henipavirus, whereas acquired immunity was long-lasting (Lagos bat virus: mean 12 years, henipavirus: mean 4 years). In the presence of a seasonal birth pulse, the effect of maternally-derived immunity on virus persistence within modelled bat populations was highly dependent on transmission characteristics. To explain previous reports of viral persistence within small natural and captive E. helvum populations, we hypothesise that some bats must experience prolonged infectious periods or within-host latency. By further elucidating plausible mechanisms of virus persistence in bat populations, we contribute to guidance of future field studies.

  20. Modeling viral coevolution: HIV multi-clonal persistence and competition dynamics

    Science.gov (United States)

    Bagnoli, F.; Liò, P.; Sguanci, L.

    2006-07-01

    The coexistence of different viral strains (quasispecies) within the same host are nowadays observed for a growing number of viruses, most notably HIV, Marburg and Ebola, but the conditions for the formation and survival of new strains have not yet been understood. We present a model of HIV quasispecies competition, which describes the conditions of viral quasispecies coexistence under different immune system conditions. Our model incorporates both T and B cells responses, and we show that the role of B cells is important and additive to that of T cells. Simulations of coinfection (simultaneous infection) and superinfection (delayed secondary infection) scenarios in the early stages (days) and in the late stages of the infection (years) are in agreement with emerging molecular biology findings. The immune response induces a competition among similar phenotypes, leading to differentiation (quasispeciation), escape dynamics and complex oscillations of viral strain abundance. We found that the quasispecies dynamics after superinfection or coinfection has time scales of several months and becomes even slower when the immune system response is weak. Our model represents a general framework to study the speed and distribution of HIV quasispecies during disease progression, vaccination and therapy.

  1. 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

  2. Documentation of a Model Action Plan to Deter Illicit Nuclear Trafficking

    International Nuclear Information System (INIS)

    Smith, D; Kristo, M; Niemeyer, S; Dudder, G

    2006-01-01

    Theft, illegal possession, smuggling, or attempted unauthorized sale of nuclear and radiological materials remains a worldwide problem. The Nuclear Smuggling International Technical Working Group (ITWG) has adopted a model action plan to guide investigation of these cases through a systematic approach to nuclear forensics. The model action plan was recently documented and provides recommendations concerning incident response, collection of evidence in conformance with required legal standards, laboratory sampling and distribution of samples, radioactive materials analysis, including categorization and characterization of samples, forensics analysis of conventional evidence, and case development including interpretation of forensic signatures

  3. Documentation of a model action plan to deter illicit nuclear trafficking

    International Nuclear Information System (INIS)

    Smith, D.K.; Kristo, M.J.; Niemeyer, S.; Dudder, G.B.

    2008-01-01

    Theft, illegal possession, smuggling, or attempted unauthorized sale of nuclear and radiological materials remains a worldwide problem. The Nuclear Smuggling International Technical Working Group (ITWG) has adopted a model action plan to guide investigation of these cases through a systematic approach to nuclear forensics. The model action plan was recently documented and provides recommendations concerning incident response, collection of evidence in conformance with required legal standards, laboratory sampling and distribution of samples, radioactive materials analysis, including categorization and characterization of samples, forensics analysis of conventional evidence, and case development including interpretation of forensic signatures. (author)

  4. Increased T cell trafficking as adjunct therapy for HIV-1

    Science.gov (United States)

    Wolinsky, Steven M.; McLean, Angela R.

    2018-01-01

    Although antiretroviral drug therapy suppresses human immunodeficiency virus-type 1 (HIV-1) to undetectable levels in the blood of treated individuals, reservoirs of replication competent HIV-1 endure. Upon cessation of antiretroviral therapy, the reservoir usually allows outgrowth of virus and approaches to targeting the reservoir have had limited success. Ongoing cycles of viral replication in regions with low drug penetration contribute to this persistence. Here, we use a mathematical model to illustrate a new approach to eliminating the part of the reservoir attributable to persistent replication in drug sanctuaries. Reducing the residency time of CD4 T cells in drug sanctuaries renders ongoing replication unsustainable in those sanctuaries. We hypothesize that, in combination with antiretroviral drugs, a strategy to orchestrate CD4 T cell trafficking could contribute to a functional cure for HIV-1 infection. PMID:29499057

  5. Enhancement of epidemic spread by noise and stochastic resonance in spatial network models with viral dynamics.

    Science.gov (United States)

    Tuckwell, H C; Toubiana, L; Vibert, J F

    2000-05-01

    We extend a previous dynamical viral network model to include stochastic effects. The dynamical equations for the viral and immune effector densities within a host population of size n are bilinear, and the noise is white, additive, and Gaussian. The individuals are connected with an n x n transmission matrix, with terms which decay exponentially with distance. In a single individual, for the range of noise parameters considered, it is found that increasing the amplitude of the noise tends to decrease the maximum mean virion level, and slightly accelerate its attainment. Two different spatial dynamical models are employed to ascertain the effects of environmental stochasticity on viral spread. In the first model transmission is unrestricted and there is no threshold within individuals. This model has the advantage that it can be analyzed using a Fokker-Planck approach. The noise is found both to synchronize and uniformize the trajectories of the viral levels across the population of infected individuals, and thus to promote the epidemic spread of the virus. Quantitative measures of the speed of spread and overall amplitude of the epidemic are obtained as functions of the noise and virulence parameters. The mean amplitude increases steadily without threshold effects for a fixed value of the virulence as the noise amplitude sigma is increased, and there is no evidence of a stochastic resonance. However, the speed of transmission, both with respect to its mean and variance, undergoes rapid increases as sigma changes by relatively small amounts. In the second, more realistic, model, there is a threshold for infection and an upper limit to the transmission rate. There may be no spread of infection at all in the absence of noise. With increasing noise level and a low threshold, the mean maximum virion level grows quickly and shows a broad-based stochastic resonance effect. When the threshold within individuals is increased, the mean population virion level increases only

  6. 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...

  7. Viral Hepatitis

    Science.gov (United States)

    ... Home A-Z Health Topics Viral hepatitis Viral hepatitis > A-Z Health Topics Viral hepatitis (PDF, 90 ... liver. Source: National Cancer Institute Learn more about hepatitis Watch a video. Learn who is at risk ...

  8. 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.

  9. 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

  10. Nuclear Trafficking of Retroviral RNAs and Gag Proteins during Late Steps of Replication

    Directory of Open Access Journals (Sweden)

    Matthew S. Stake

    2013-11-01

    Full Text Available Retroviruses exploit nuclear trafficking machinery at several distinct stages in their replication cycles. In this review, we will focus primarily on nucleocytoplasmic trafficking events that occur after the completion of reverse transcription and proviral integration. First, we will discuss nuclear export of unspliced viral RNA transcripts, which serves two essential roles: as the mRNA template for the translation of viral structural proteins and as the genome for encapsidation into virions. These full-length viral RNAs must overcome the cell’s quality control measures to leave the nucleus by co-opting host factors or encoding viral proteins to mediate nuclear export of unspliced viral RNAs. Next, we will summarize the most recent findings on the mechanisms of Gag nuclear trafficking and discuss potential roles for nuclear localization of Gag proteins in retrovirus replication.

  11. 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...

  12. Spatio-temporal dependence of the signaling response in immune-receptor trafficking networks regulated by cell density: a theoretical model.

    Directory of Open Access Journals (Sweden)

    Pilar García-Peñarrubia

    Full Text Available Cell signaling processes involve receptor trafficking through highly connected networks of interacting components. The binding of surface receptors to their specific ligands is a key factor for the control and triggering of signaling pathways. In most experimental systems, ligand concentration and cell density vary within a wide range of values. Dependence of the signal response on cell density is related with the extracellular volume available per cell. This dependence has previously been studied using non-spatial models which assume that signaling components are well mixed and uniformly distributed in a single compartment. In this paper, a mathematical model that shows the influence exerted by cell density on the spatio-temporal evolution of ligands, cell surface receptors, and intracellular signaling molecules is developed. To this end, partial differential equations were used to model ligand and receptor trafficking dynamics through the different domains of the whole system. This enabled us to analyze several interesting features involved with these systems, namely: a how the perturbation caused by the signaling response propagates through the system; b receptor internalization dynamics and how cell density affects the robustness of dose-response curves upon variation of the binding affinity; and c that enhanced correlations between ligand input and system response are obtained under conditions that result in larger perturbations of the equilibrium ligand + surface receptor [Please see text] ligand - receptor complex. Finally, the results are compared with those obtained by considering that the above components are well mixed in a single compartment.

  13. Analysis of stability and Hopf bifurcation for a viral infectious model with delay

    International Nuclear Information System (INIS)

    Sun Chengjun; Cao Zhijie; Lin Yiping

    2007-01-01

    In this paper, a four-dimensional viral infectious model with delay is considered. The stability of the two equilibria and the existence of Hopf bifurcation are investigated. It is found that there are stability switches and Hopf bifurcations occur when the delay τ passes through a sequence of critical values. Using the normal form theory and center manifold argument [Hassard B, Kazarino D, Wan Y. Theory and applications of Hopf bifurcation. Cambridge: Cambridge University Press; 1981], the explicit formulaes which determine the stability, the direction and the period of bifurcating periodic solutions are derived. Numerical simulations are carried out to illustrate the validity of the main results

  14. Structural and Functional Insights into Foamy Viral Integrase

    Directory of Open Access Journals (Sweden)

    Cha-Gyun Shin

    2013-07-01

    Full Text Available Successful integration of retroviral DNA into the host chromosome is an essential step for viral replication. The process is mediated by virally encoded integrase (IN and orchestrated by 3'-end processing and the strand transfer reaction. In vitro reaction conditions, such as substrate specificity, cofactor usage, and cellular binding partners for such reactions by the three distinct domains of prototype foamy viral integrase (PFV-IN have been described well in several reports. Recent studies on the three‑dimensional structure of the interacting complexes between PFV-IN and DNA, cofactors, binding partners, or inhibitors have explored the mechanistic details of such interactions and shown its utilization as an important target to develop anti-retroviral drugs. The presence of a potent, non-transferable nuclear localization signal in the PFV C-terminal domain extends its use as a model for investigating cellular trafficking of large molecular complexes through the nuclear pore complex and also to identify novel cellular targets for such trafficking. This review focuses on recent advancements in the structural analysis and in vitro functional aspects of PFV-IN.

  15. Differential T cell response against BK virus regulatory and structural antigens: A viral dynamics modelling approach.

    Directory of Open Access Journals (Sweden)

    Arturo Blazquez-Navarro

    2018-05-01

    Full Text Available BK virus (BKV associated nephropathy affects 1-10% of kidney transplant recipients, leading to graft failure in about 50% of cases. Immune responses against different BKV antigens have been shown to have a prognostic value for disease development. Data currently suggest that the structural antigens and regulatory antigens of BKV might each trigger a different mode of action of the immune response. To study the influence of different modes of action of the cellular immune response on BKV clearance dynamics, we have analysed the kinetics of BKV plasma load and anti-BKV T cell response (Elispot in six patients with BKV associated nephropathy using ODE modelling. The results show that only a small number of hypotheses on the mode of action are compatible with the empirical data. The hypothesis with the highest empirical support is that structural antigens trigger blocking of virus production from infected cells, whereas regulatory antigens trigger an acceleration of death of infected cells. These differential modes of action could be important for our understanding of BKV resolution, as according to the hypothesis, only regulatory antigens would trigger a fast and continuous clearance of the viral load. Other hypotheses showed a lower degree of empirical support, but could potentially explain the clearing mechanisms of individual patients. Our results highlight the heterogeneity of the dynamics, including the delay between immune response against structural versus regulatory antigens, and its relevance for BKV clearance. Our modelling approach is the first that studies the process of BKV clearance by bringing together viral and immune kinetics and can provide a framework for personalised hypotheses generation on the interrelations between cellular immunity and viral dynamics.

  16. Differential T cell response against BK virus regulatory and structural antigens: A viral dynamics modelling approach.

    Science.gov (United States)

    Blazquez-Navarro, Arturo; Schachtner, Thomas; Stervbo, Ulrik; Sefrin, Anett; Stein, Maik; Westhoff, Timm H; Reinke, Petra; Klipp, Edda; Babel, Nina; Neumann, Avidan U; Or-Guil, Michal

    2018-05-01

    BK virus (BKV) associated nephropathy affects 1-10% of kidney transplant recipients, leading to graft failure in about 50% of cases. Immune responses against different BKV antigens have been shown to have a prognostic value for disease development. Data currently suggest that the structural antigens and regulatory antigens of BKV might each trigger a different mode of action of the immune response. To study the influence of different modes of action of the cellular immune response on BKV clearance dynamics, we have analysed the kinetics of BKV plasma load and anti-BKV T cell response (Elispot) in six patients with BKV associated nephropathy using ODE modelling. The results show that only a small number of hypotheses on the mode of action are compatible with the empirical data. The hypothesis with the highest empirical support is that structural antigens trigger blocking of virus production from infected cells, whereas regulatory antigens trigger an acceleration of death of infected cells. These differential modes of action could be important for our understanding of BKV resolution, as according to the hypothesis, only regulatory antigens would trigger a fast and continuous clearance of the viral load. Other hypotheses showed a lower degree of empirical support, but could potentially explain the clearing mechanisms of individual patients. Our results highlight the heterogeneity of the dynamics, including the delay between immune response against structural versus regulatory antigens, and its relevance for BKV clearance. Our modelling approach is the first that studies the process of BKV clearance by bringing together viral and immune kinetics and can provide a framework for personalised hypotheses generation on the interrelations between cellular immunity and viral dynamics.

  17. Enhanced Metastatic Recurrence Via Lymphatic Trafficking of a High-Metastatic Variant of Human Triple-Negative Breast Cancer After Surgical Resection in Orthotopic Nude Mouse Models.

    Science.gov (United States)

    Yano, Shuya; Takehara, Kiyoto; Tazawa, Hiroshi; Kishimoto, Hiroyuki; Kagawa, Shunsuke; Bouvet, Michael; Fujiwara, Toshiyoshi; Hoffman, Robert M

    2017-03-01

    We previously developed and characterized a highly invasive and metastatic triple-negative breast cancer (TNBC) variant by serial orthotopic implantation of MDA-MB-231 human breast cancer cells in nude mice. Eventually, a highly invasive and metastatic variant of human TNBC was isolated after lymph node metastases was harvested and orthotopically re-implanted into the mammary gland of nude mice for two cycles. The variant thereby isolated is highly invasive in the mammary gland and metastasized to lymph nodes in 10 of 12 mice compared to 2 of 12 of the parental cell line. In the present report, we observed that high-metastatic MDA-MB-231H-RFP cells produced significantly larger subcutaneous tumors compared with parental MDA-MB-231 cells in nude mice. Extensive lymphatic trafficking by high-metastatic MDA-MB-231 cells was also observed. High-metastatic MDA-MB-231 developed larger recurrent tumors 2 weeks after tumor resection compared with tumors that were not resected in orthotopic models. Surgical resection of the MDA-MB-231 high-metastatic variant primary tumor in orthotopic models also resulted in rapid and enhanced lymphatic trafficking of residual cancer cells and extensive lymph node and lung metastasis that did not occur in the non-surgical mice. These results suggest that surgical resection of high metastatic TNBC can greatly increase the malignancy of residual cancer. J. Cell. Biochem. 118: 559-569, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  18. Dynamics of the cytotoxic T cell response to a model of acute viral infection.

    Science.gov (United States)

    DeWitt, William S; Emerson, Ryan O; Lindau, Paul; Vignali, Marissa; Snyder, Thomas M; Desmarais, Cindy; Sanders, Catherine; Utsugi, Heidi; Warren, Edus H; McElrath, Juliana; Makar, Karen W; Wald, Anna; Robins, Harlan S

    2015-04-01

    A detailed characterization of the dynamics and breadth of the immune response to an acute viral infection, as well as the determinants of recruitment to immunological memory, can greatly contribute to our basic understanding of the mechanics of the human immune system and can ultimately guide the design of effective vaccines. In addition to neutralizing antibodies, T cells have been shown to be critical for the effective resolution of acute viral infections. We report the first in-depth analysis of the dynamics of the CD8(+) T cell repertoire at the level of individual T cell clonal lineages upon vaccination of human volunteers with a single dose of YF-17D. This live attenuated yellow fever virus vaccine yields sterile, long-term immunity and has been previously used as a model to understand the immune response to a controlled acute viral infection. We identified and enumerated unique CD8(+) T cell clones specifically induced by this vaccine through a combined experimental and statistical approach that included high-throughput sequencing of the CDR3 variable region of the T cell receptor β-chain and an algorithm that detected significantly expanded T cell clones. This allowed us to establish that (i) on average, ∼ 2,000 CD8(+) T cell clones were induced by YF-17D, (ii) 5 to 6% of the responding clones were recruited to long-term memory 3 months postvaccination, (iii) the most highly expanded effector clones were preferentially recruited to the memory compartment, and (iv) a fraction of the YF-17D-induced clones could be identified from peripheral blood lymphocytes solely by measuring clonal expansion. The exhaustive investigation of pathogen-induced effector T cells is essential to accurately quantify the dynamics of the human immune response. The yellow fever vaccine (YFV) has been broadly used as a model to understand how a controlled, self-resolving acute viral infection induces an effective and long-term protective immune response. Here, we extend this

  19. Hepatitis B virus core antigen determines viral persistence in a C57BL/6 mouse model.

    Science.gov (United States)

    Lin, Yi-Jiun; Huang, Li-Rung; Yang, Hung-Chih; Tzeng, Horng-Tay; Hsu, Ping-Ning; Wu, Hui-Lin; Chen, Pei-Jer; Chen, Ding-Shinn

    2010-05-18

    We recently developed a mouse model of hepatitis B virus (HBV) persistence, in which a single i.v. hydrodynamic injection of HBV DNA to C57BL/6 mice allows HBV replication and induces a partial immune response, so that about 20-30% of the mice carry HBV for more than 6 months. The model was used to identify the viral antigen crucial for HBV persistence. We knocked out individual HBV genes by introducing a premature termination codon to the HBV core, HBeAg, HBx, and polymerase ORFs. The specific-gene-deficient HBV mutants were hydrodynamically injected into mice and the HBV profiles of the mice were monitored. About 90% of the mice that received the HBcAg-mutated HBV plasmid exhibited high levels of hepatitis B surface antigenemia and maintained HBsAg expression for more than 6 months after injection. To map the region of HBcAg essential for viral clearance, we constructed a set of serial HBcAg deletion mutants for hydrodynamic injection. We localized the essential region of HBcAg to the carboxyl terminus, specifically to the 10 terminal amino acids (HBcAg176-185). The majority of mice receiving this HBV mutant DNA did not elicit a proper HBcAg-specific IFN-gamma response and expressed HBV virions for 6 months. These results indicate that the immune response triggered in mice by HBcAg during exposure to HBV is important in determining HBV persistence.

  20. 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

  1. 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

  2. A prototype system dynamic model of nuclear and radiological export controls in Central Asia and the Caucasus; enhancing the effectiveness of preventing illicit nuclear material trafficking

    International Nuclear Information System (INIS)

    Ferguston, C.D.; Ouagrham, S.B.

    2002-01-01

    An urgent need calls out for improved border security and export control systems in the Central Asian and Caucasus regions to prevent illicit nuclear and radioactive materials trafficking. Effective nuclear and radiological exports controls are essential because these regions contain numerous nuclear facilities and radioactive materials as well as lie at the crossroads between seekers and suppliers of technologies that could be employed in nuclear and radiological weapons. Porous and unprotected borders compound these concerns. Moreover, the states within these regions are struggling with forming new regulations and laws, obtaining sufficient portal monitoring equipment, training customs and border security personnel, and coordinating these activities with neighboring states. Building this infrastructure all at once can severely task any government. Thus, unsurprisingly, most of these states have inadequate export control and border security systems. To enable each state in these regions determine how to better prevent illicit nuclear and radiological materials trafficking, the authors have developed a prototype system dynamics model focused on evaluating and improving of effectiveness of export controls. System dynamics modeling, a management tool that grew out of the field of system engineering and nonlinear dynamics, uses two structures: causal loop diagrams and stock and flow diagrams. The former shows how endogenous systematic factors interact with each other to produce feedback mechanisms that results in either balancing or reinforcing loops. A classic example is a arms race, modeled as a vicious cycle or reinforcing loop. In addition to interacting with each other, causal loops influence the flow of stock, which is material concern. In the export control system dynamics model, the stock represents nuclear and radioactive materials. System dynamics modelling is an iterative process that is continually modified by user input. Therefore, export control

  3. A discontinuous RNA platform mediates RNA virus replication: building an integrated model for RNA-based regulation of viral processes.

    Directory of Open Access Journals (Sweden)

    Baodong Wu

    2009-03-01

    Full Text Available Plus-strand RNA viruses contain RNA elements within their genomes that mediate a variety of fundamental viral processes. The traditional view of these elements is that of local RNA structures. This perspective, however, is changing due to increasing discoveries of functional viral RNA elements that are formed by long-range RNA-RNA interactions, often spanning thousands of nucleotides. The plus-strand RNA genomes of tombusviruses exemplify this concept by possessing different long-range RNA-RNA interactions that regulate both viral translation and transcription. Here we report that a third fundamental tombusvirus process, viral genome replication, requires a long-range RNA-based interaction spanning approximately 3000 nts. In vivo and in vitro analyses suggest that the discontinuous RNA platform formed by the interaction facilitates efficient assembly of the viral RNA replicase. This finding has allowed us to build an integrated model for the role of global RNA structure in regulating the reproduction of a eukaryotic RNA virus, and the insights gained have extended our understanding of the multifunctional nature of viral RNA genomes.

  4. Structural equation modelling of viral tropism reveals its impact on achieving viral suppression within 6 months in treatment-naive HIV-1-infected patients after combination antiretroviral therapy.

    Science.gov (United States)

    Mengoli, Carlo; Andreis, Samantha; Scaggiante, Renzo; Cruciani, Mario; Bosco, Oliviero; Ferretto, Roberto; Leoni, Davide; Maffongelli, Gaetano; Basso, Monica; Torti, Carlo; Sarmati, Loredana; Andreoni, Massimo; Palù, Giorgio; Parisi, Saverio Giuseppe

    2017-01-01

    To evaluate the role of pre-treatment co-receptor tropism of plasma HIV on the achievement of viral suppression (plasma HIV RNA 1.69 log 10 copies/mL) at the sixth month of combination antiretroviral therapy (cART) in a cohort of naive patients using, for the first time in this context, a path analysis (PA) approach. Adult patients with chronic infection by subtype B HIV-1 were consecutively enrolled from the start of first-line cART (T0). Genotypic analysis of viral tropism was performed on plasma and interpreted using the bioinformatic tool Geno2pheno, with a false positive rate of 10%. A Bayesian network starting from the viro-immunological data at T0 and at the sixth month of treatment (T1) was set up and this model was evaluated using a PA approach. A total of 262 patients (22.1% bearing an X4 virus) were included; 178 subjects (67.9%) achieved viral suppression. A significant positive indirect effect of bearing X4 virus in plasma at T0 on log 10 HIV RNA at T1 was detected (P = 0.009), the magnitude of this effect was, however, over 10-fold lower than the direct effect of log 10 HIV RNA at T0 on log 10 HIV RNA at T1 (P = 0.000). Moreover, a significant positive indirect effect of bearing an X4 virus on log 10 HIV RNA at T0 (P = 0.003) was apparent. PA overcame the limitations implicit in common multiple regression analysis and showed the possible role of pre-treatment viral tropism at the recommended threshold on the outcome of plasma viraemia in naive patients after 6 months of therapy. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  5. A multi-scale spatial model of hepatitis-B viral dynamics.

    Directory of Open Access Journals (Sweden)

    Quentin Cangelosi

    Full Text Available Chronic hepatitis B viral infection (HBV afflicts around 250 million individuals globally and few options for treatment exist. Once infected, the virus entrenches itself in the liver with a notoriously resilient colonisation of viral DNA (covalently-closed circular DNA, cccDNA. The majority of infections are cleared, yet we do not understand why 5% of adult immune responses fail leading to the chronic state with its collateral morbid effects such as cirrhosis and eventual hepatic carcinoma. The liver environment exhibits particularly complex spatial structures for metabolic processing and corresponding distributions of nutrients and transporters that may influence successful HBV entrenchment. We assembled a multi-scaled mathematical model of the fundamental hepatic processing unit, the sinusoid, into a whole-liver representation to investigate the impact of this intrinsic spatial heterogeneity on the HBV dynamic. Our results suggest HBV may be exploiting spatial aspects of the liver environment. We distributed increased HBV replication rates coincident with elevated levels of nutrients in the sinusoid entry point (the periportal region in tandem with similar distributions of hepatocyte transporters key to HBV invasion (e.g., the sodium-taurocholate cotransporting polypeptide or NTCP, or immune system activity. According to our results, such co-alignment of spatial distributions may contribute to persistence of HBV infections, depending on spatial distributions and intensity of immune response as well. Moreover, inspired by previous HBV models and experimentalist suggestions of extra-hepatic HBV replication, we tested in our model influence of HBV blood replication and observe an overall nominal effect on persistent liver infection. Regardless, we confirm prior results showing a solo cccDNA is sufficient to re-infect an entire liver, with corresponding concerns for transplantation and treatment.

  6. Modeling Zika plasma viral dynamics in non-human primates: insights into viral pathogenesis and antiviral strategies

    Energy Technology Data Exchange (ETDEWEB)

    Best, Katharine [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Guedj, Jeremie [Univ. of Paris (France). IAME; Madelain, Vincent [Univ. of Paris (France); de Lamballerie, Xavier [Aix-Marseille Univ. (France); L, So-Yonim [Harvard Univ., Cambridge, MA (United States). Center for Virology and Vaccine Research; Osuna, Christa E [Harvard Univ., Cambridge, MA (United States). Center for Virology and Vaccine Research; Whitney, James [Harvard Univ., Cambridge, MA (United States). Center for Virology and Vaccine Research; Perelson, Alan S. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-10-24

    The recent outbreak of Zika virus (ZIKV) has been associated with fetal abnormalities and neurological complications, prompting global concern. Here we present the first mathematical analysis of the within-host dynamics of plasma ZiKV burden in a non-human primate model, allowing for characterization of the growth and clearance of ZIKV within an individual macaque.

  7. Modeling Viral Infectious Diseases and Development of Antiviral Therapies Using Human Induced Pluripotent Stem Cell-Derived Systems.

    Science.gov (United States)

    Trevisan, Marta; Sinigaglia, Alessandro; Desole, Giovanna; Berto, Alessandro; Pacenti, Monia; Palù, Giorgio; Barzon, Luisa

    2015-07-13

    The recent biotechnology breakthrough of cell reprogramming and generation of induced pluripotent stem cells (iPSCs), which has revolutionized the approaches to study the mechanisms of human diseases and to test new drugs, can be exploited to generate patient-specific models for the investigation of host-pathogen interactions and to develop new antimicrobial and antiviral therapies. Applications of iPSC technology to the study of viral infections in humans have included in vitro modeling of viral infections of neural, liver, and cardiac cells; modeling of human genetic susceptibility to severe viral infectious diseases, such as encephalitis and severe influenza; genetic engineering and genome editing of patient-specific iPSC-derived cells to confer antiviral resistance.

  8. Modeling Viral Infectious Diseases and Development of Antiviral Therapies Using Human Induced Pluripotent Stem Cell-Derived Systems

    Directory of Open Access Journals (Sweden)

    Marta Trevisan

    2015-07-01

    Full Text Available The recent biotechnology breakthrough of cell reprogramming and generation of induced pluripotent stem cells (iPSCs, which has revolutionized the approaches to study the mechanisms of human diseases and to test new drugs, can be exploited to generate patient-specific models for the investigation of host–pathogen interactions and to develop new antimicrobial and antiviral therapies. Applications of iPSC technology to the study of viral infections in humans have included in vitro modeling of viral infections of neural, liver, and cardiac cells; modeling of human genetic susceptibility to severe viral infectious diseases, such as encephalitis and severe influenza; genetic engineering and genome editing of patient-specific iPSC-derived cells to confer antiviral resistance.

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

    Directory of Open Access Journals (Sweden)

    Samuel K. Campos

    2017-12-01

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

  10. Tailored delivery of analgesic ziconotide across a blood brain barrier model using viral nanocontainers

    Science.gov (United States)

    Anand, Prachi; O'Neil, Alison; Lin, Emily; Douglas, Trevor; Holford, Mandë

    2015-08-01

    The blood brain barrier (BBB) is often an insurmountable obstacle for a large number of candidate drugs, including peptides, antibiotics, and chemotherapeutic agents. Devising an adroit delivery method to cross the BBB is essential to unlocking widespread application of peptide therapeutics. Presented here is an engineered nanocontainer for delivering peptidic drugs across the BBB encapsulating the analgesic marine snail peptide ziconotide (Prialt®). We developed a bi-functional viral nanocontainer based on the Salmonella typhimurium bacteriophage P22 capsid, genetically incorporating ziconotide in the interior cavity, and chemically attaching cell penetrating HIV-Tat peptide on the exterior of the capsid. Virus like particles (VLPs) of P22 containing ziconotide were successfully transported in several BBB models of rat and human brain microvascular endothelial cells (BMVEC) using a recyclable noncytotoxic endocytic pathway. This work demonstrates proof in principle for developing a possible alternative to intrathecal injection of ziconotide using a tunable VLP drug delivery nanocontainer to cross the BBB.

  11. 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.

  12. Viral Meningitis

    Science.gov (United States)

    ... better from treatment such as an antiviral medicine. Antibiotics do not help viral infections, so they are not useful in the treatment of viral meningitis. However, antibiotics do fight bacteria, so they are very important ...

  13. Pharyngitis - viral

    Science.gov (United States)

    ... throat is due to a viral infection. The antibiotics will not help. Using them to treat viral infections helps bacteria become resistant to antibiotics. With some sore throats (such as those caused ...

  14. An Azole-Tolerant Endosomal Trafficking Mutant of Candida albicans Is Susceptible to Azole Treatment in a Mouse Model of Vaginal Candidiasis.

    Science.gov (United States)

    Peters, Brian M; Luna-Tapia, Arturo; Tournu, Hélène; Rybak, Jeffrey M; Rogers, P David; Palmer, Glen E

    2017-06-01

    We recently reported that a Candida albicans endosomal trafficking mutant continues to grow after treatment with the azole antifungals. Herein, we report that the vps21 Δ/Δ mutant does not have a survival advantage over wild-type isolates after fluconazole treatment in a mouse model of vaginal candidiasis. Furthermore, loss of VPS21 does not synergize with established mechanisms of azole resistance, such as overexpression of efflux pumps or of Erg11p, the target enzyme of the azoles. In summary, although loss of VPS21 function enhances C. albicans survival after azole treatment in vitro , it does not seem to affect azole susceptibility in vivo . Copyright © 2017 American Society for Microbiology.

  15. Viral persistence, latent reservoir, and blips: a review on HIV-1 dynamics and modeling during HAART and related treatment implications

    Energy Technology Data Exchange (ETDEWEB)

    Rong, Libin [Los Alamos National Laboratory; Perelson, Alan [Los Alamos National Laboratory

    2008-01-01

    HIV-1 eradication from infected individuals has not been achieved with the use of highly active antiretroviral therapy (HAART) for a prolonged period of time. The cellular reservoir for HIV-1 in resting memory CD4{sup +} T cells remains a major obstacle to viral elimination. The reservoir does not decay significantly over long periods of time as is able to release replication competent HIV-1 upon cell activation. Residual ongoing viral replication may likely occur in many patients because low levels of virus can be detected in plasma by sensitive assays and transient episodes of viremia, or HIV-1 blips, are often observed in patients even with successful viral suppression for many years. Here we review our current knowledge of the factors contributing to viral persistence, the latent reservoir, and blips, and mathematical models developed to explore them and their relationships. We show how mathematical modeling can help improve our understanding of HIV-1 dynamics in patients on HAART and the quantitative events underlying HIV-1 latency, reservoir stability, low-level viremic persistence, and emergence of intermittent viral blips. We also discuss treatment implications related to these studies.

  16. Recycling Endosomes and Viral Infection.

    Science.gov (United States)

    Vale-Costa, Sílvia; Amorim, Maria João

    2016-03-08

    Many viruses exploit specific arms of the endomembrane system. The unique composition of each arm prompts the development of remarkably specific interactions between viruses and sub-organelles. This review focuses on the viral-host interactions occurring on the endocytic recycling compartment (ERC), and mediated by its regulatory Ras-related in brain (Rab) GTPase Rab11. This protein regulates trafficking from the ERC and the trans-Golgi network to the plasma membrane. Such transport comprises intricate networks of proteins/lipids operating sequentially from the membrane of origin up to the cell surface. Rab11 is also emerging as a critical factor in an increasing number of infections by major animal viruses, including pathogens that provoke human disease. Understanding the interplay between the ERC and viruses is a milestone in human health. Rab11 has been associated with several steps of the viral lifecycles by unclear processes that use sophisticated diversified host machinery. For this reason, we first explore the state-of-the-art on processes regulating membrane composition and trafficking. Subsequently, this review outlines viral interactions with the ERC, highlighting current knowledge on viral-host binding partners. Finally, using examples from the few mechanistic studies available we emphasize how ERC functions are adjusted during infection to remodel cytoskeleton dynamics, innate immunity and membrane composition.

  17. Survival of viral pathogens in animal feed ingredients under transboundary shipping models

    Science.gov (United States)

    Bauermann, Fernando V.; Niederwerder, Megan C.; Singrey, Aaron; Clement, Travis; de Lima, Marcelo; Long, Craig; Patterson, Gilbert; Sheahan, Maureen A.; Stoian, Ana M. M.; Petrovan, Vlad; Jones, Cassandra K.; De Jong, Jon; Ji, Ju; Spronk, Gordon D.; Minion, Luke; Christopher-Hennings, Jane; Zimmerman, Jeff J.; Rowland, Raymond R. R.; Nelson, Eric; Sundberg, Paul; Diel, Diego G.

    2018-01-01

    The goal of this study was to evaluate survival of important viral pathogens of livestock in animal feed ingredients imported daily into the United States under simulated transboundary conditions. Eleven viruses were selected based on global significance and impact to the livestock industry, including Foot and Mouth Disease Virus (FMDV), Classical Swine Fever Virus (CSFV), African Swine Fever Virus (ASFV), Influenza A Virus of Swine (IAV-S), Pseudorabies virus (PRV), Nipah Virus (NiV), Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), Swine Vesicular Disease Virus (SVDV), Vesicular Stomatitis Virus (VSV), Porcine Circovirus Type 2 (PCV2) and Vesicular Exanthema of Swine Virus (VESV). Surrogate viruses with similar genetic and physical properties were used for 6 viruses. Surrogates belonged to the same virus families as target pathogens, and included Senecavirus A (SVA) for FMDV, Bovine Viral Diarrhea Virus (BVDV) for CSFV, Bovine Herpesvirus Type 1 (BHV-1) for PRV, Canine Distemper Virus (CDV) for NiV, Porcine Sapelovirus (PSV) for SVDV and Feline Calicivirus (FCV) for VESV. For the remaining target viruses, actual pathogens were used. Virus survival was evaluated using Trans-Pacific or Trans-Atlantic transboundary models involving representative feed ingredients, transport times and environmental conditions, with samples tested by PCR, VI and/or swine bioassay. SVA (representing FMDV), FCV (representing VESV), BHV-1 (representing PRV), PRRSV, PSV (representing SVDV), ASFV and PCV2 maintained infectivity during transport, while BVDV (representing CSFV), VSV, CDV (representing NiV) and IAV-S did not. Notably, more viruses survived in conventional soybean meal, lysine hydrochloride, choline chloride, vitamin D and pork sausage casings. These results support published data on transboundary risk of PEDV in feed, demonstrate survival of certain viruses in specific feed ingredients (“high-risk combinations”) under conditions simulating transport between

  18. Next Generation Respiratory Viral Vaccine System: Advanced and Emerging Bioengineered Human Lung Epithelia Model (HLEM) Organoid Technology

    Science.gov (United States)

    Goodwin, Thomas J.; Schneider, Sandra L.; MacIntosh, Victor; Gibbons, Thomas F.

    2010-01-01

    Acute respiratory infections, including pneumonia and influenza, are the S t" leading cause of United States and worldwide deaths. Newly emerging pathogens signaled the need for an advanced generation of vaccine technology.. Human bronchial-tracheal epithelial tissue was bioengineered to detect, identify, host and study the pathogenesis of acute respiratory viral disease. The 3-dimensional (3D) human lung epithelio-mesechymal tissue-like assemblies (HLEM TLAs) share characteristics with human respiratory epithelium: tight junctions, desmosomes, microvilli, functional markers villin, keratins and production of tissue mucin. Respiratory Syntial Virus (RSV) studies demonstrate viral growth kinetics and membrane bound glycoproteins up to day 20 post infection in the human lung-orgainoid infected cell system. Peak replication of RSV occurred on day 10 at 7 log10 particles forming units per ml/day. HLEM is an advanced virus vaccine model and biosentinel system for emergent viral infectious diseases to support DoD global surveillance and military readiness.

  19. Chromosomally Integrated Human Herpesvirus 6: Models of Viral Genome Release from the Telomere and Impacts on Human Health.

    Science.gov (United States)

    Wood, Michael L; Royle, Nicola J

    2017-07-12

    Human herpesvirus 6A and 6B, alongside some other herpesviruses, have the striking capacity to integrate into telomeres, the terminal repeated regions of chromosomes. The chromosomally integrated forms, ciHHV-6A and ciHHV-6B, are proposed to be a state of latency and it has been shown that they can both be inherited if integration occurs in the germ line. The first step in full viral reactivation must be the release of the integrated viral genome from the telomere and here we propose various models of this release involving transcription of the viral genome, replication fork collapse, and t-circle mediated release. In this review, we also discuss the relationship between ciHHV-6 and the telomere carrying the insertion, particularly how the presence and subsequent partial or complete release of the ciHHV-6 genome may affect telomere dynamics and the risk of disease.

  20. Human Neural Precursor Cells Promote Neurologic Recovery in a Viral Model of Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Lu Chen

    2014-06-01

    Full Text Available Using a viral model of the demyelinating disease multiple sclerosis (MS, we show that intraspinal transplantation of human embryonic stem cell-derived neural precursor cells (hNPCs results in sustained clinical recovery, although hNPCs were not detectable beyond day 8 posttransplantation. Improved motor skills were associated with a reduction in neuroinflammation, decreased demyelination, and enhanced remyelination. Evidence indicates that the reduced neuroinflammation is correlated with an increased number of CD4+CD25+FOXP3+ regulatory T cells (Tregs within the spinal cords. Coculture of hNPCs with activated T cells resulted in reduced T cell proliferation and increased Treg numbers. The hNPCs acted, in part, through secretion of TGF-β1 and TGF-β2. These findings indicate that the transient presence of hNPCs transplanted in an animal model of MS has powerful immunomodulatory effects and mediates recovery. Further investigation of the restorative effects of hNPC transplantation may aid in the development of clinically relevant MS treatments.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. Buccal viral DNA as a trigger for brincidofovir therapy in the mousepox model of smallpox.

    Science.gov (United States)

    Crump, Ryan; Korom, Maria; Buller, R Mark; Parker, Scott

    2017-03-01

    Orthopoxviruses continue to pose a significant threat to the population as potential agents of bioterrorism. An intentional release of natural or engineered variola virus (VARV) or monkeypox viruses would cause mortality and morbidity in the target population. To address this, antivirals have been developed and evaluated in animal models of smallpox and monkeypox. One such antiviral, brincidofovir (BCV, previously CMX001), has demonstrated high levels of efficacy against orthopoxviruses in animal models and is currently under clinical evaluation for prevention and treatment of diseases caused by cytomegaloviruses and adenoviruses. In this study we use the mousepox model of smallpox to evaluate the relationship between the magnitude of the infectious virus dose and an efficacious BCV therapy outcome when treatment is initiated concomitant with detection of ectromelia virus viral DNA (vDNA) in mouse buccal swabs. We found that vDNA could be detected in buccal swabs of some, but not all infected mice over a range of challenge doses by day 3 or 4 postexposure, when initiation of BCV treatment was efficacious, suggesting that detection of vDNA in buccal swabs could be used as a trigger to initiate BCV treatment of an entire potentially exposed population. However, buccal swabs of some mice did not become positive until 5 days postexposure, when initiation of BCV therapy failed to protect mice that received high doses of virus. And finally, the data suggest that the therapeutic window for efficacious BCV treatment decreases as the virus infectious dose increases. Extrapolating these findings to VARV, the data suggest that treatment should be initiated as soon as possible after exposure and not rely on a diagnostic tool such as the measurement of vDNA in buccal cavity swabs; however, consideration should be given to the fact that the behavior/disease-course of VARV in humans is different from that of ectromelia virus in the mouse. Copyright © 2016 Elsevier B.V. All

  6. Quantitative modeling of the dynamics and intracellular trafficking of far-red light-activatable prodrugs: implications in stimuli-responsive drug delivery system.

    Science.gov (United States)

    Li, Mengjie; Thapa, Pritam; Rajaputra, Pallavi; Bio, Moses; Peer, Cody J; Figg, William D; You, Youngjae; Woo, Sukyung

    2017-12-01

    The combination of photodynamic therapy (PDT) with anti-tumor agents is a complimentary strategy to treat local cancers. We developed a unique photosensitizer (PS)-conjugated paclitaxel (PTX) prodrug in which a PS is excited by near-infrared wavelength light to site-specifically release PTX while generating singlet oxygen (SO) to effectively kill cancer cells with both PTX and SO. The aim of the present study was to identify the determinants influencing the combined efficacy of this light-activatable prodrug, especially the bystander killing effects from released PTX. Using PS-conjugated PTX as a model system, we developed a quantitative mathematical model describing the intracellular trafficking. Dynamics of the prodrug and the model predictions were verified with experimental data using human cancer cells in vitro. The sensitivity analysis suggested that parameters related to extracellular concentration of released PTX, prodrug uptake, target engagement, and target abundance are critical in determining the combined killing efficacy of the prodrug. We found that released PTX cytotoxicity was most sensitive to the retention time of the drug in extracellular space. Modulating drug internalization and conjugating the agents targeted to abundant receptors may provide a new strategy for maximizing the killing capacity of the far-red light-activatable prodrug system. These results provide guidance for the design of the PDT combination study in vivo and have implications for other stimuli-responsive drug delivery systems.

  7. 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

  8. Pillbox organizers are associated with improved adherence to HIV antiretroviral therapy and viral suppression: a marginal structural model analysis.

    Science.gov (United States)

    Petersen, Maya L; Wang, Yue; van der Laan, Mark J; Guzman, David; Riley, Elise; Bangsberg, David R

    2007-10-01

    Pillbox organizers are inexpensive and easily used; however, their effect on adherence to antiretroviral medications is unknown. Data were obtained from an observational cohort of 245 human immunodeficiency virus (HIV)-infected subjects who were observed from 1996 through 2000 in San Francisco, California. Adherence was the primary outcome and was measured using unannounced monthly pill counts. Plasma HIV RNA level was considered as a secondary outcome. Marginal structural models were used to estimate the effect of pillbox organizer use on adherence and viral suppression, adjusting for confounding by CD4+ T cell count, viral load, prior adherence, recreational drug use, demographic characteristics, and current and past treatment. Pillbox organizer use was estimated to improve adherence by 4.1%-4.5% and was associated with a decrease in viral load of 0.34-0.37 log10 copies/mL and a 14.2%-15.7% higher probability of achieving a viral load organizers appear to significantly improve adherence to antiretroviral therapy and to improve virologic suppression. We estimate that pillbox organizers may be associated with a cost of approximately $19,000 per quality-adjusted life-year. Pillbox organizers should be a standard intervention to improve adherence to antiretroviral therapy.

  9. 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.

  10. MicroRNA Expression during Viral Infection or PolyI:C Stimulation in a Fish Model

    DEFF Research Database (Denmark)

    Kristensen, Lasse Bøgelund Juel; Schyth, Brian Dall; Lorenzen, Niels

    Fish are important as small vertebrate models for studying various aspects of development and disease. MicroRNA regulation in fish has so far received attention especially in studies of their expression and function during embryonic development. In the studies carried out at the National Veterinary...... Institute in Århus we aim at using fish models for studying microRNA regulation during viral infection. In the studies presented here we make use of a qPCR method to detect miRNAs in fish cells. We present results regarding the expression of the immunologically relevant microRNAs, miR-155, miR-146a and mi......R-146b in fish cells during infection with the fish pathogenic virus viral hemorrhagic septicemia virus (VHSV) and during immune stimulation with double stranded RNA (polyI:C). We highlight the need of finding stable normalization genes for microRNA detection....

  11. Global Analysis of a Model of Viral Infection with Latent Stage and Two Types of Target Cells

    Directory of Open Access Journals (Sweden)

    Shuo Liu

    2013-01-01

    Full Text Available By introducing the probability function describing latency of infected cells, we unify some models of viral infection with latent stage. For the case that the probability function is a step function, which implies that the latency period of the infected cells is constant, the corresponding model is a delay differential system. The model with delay of latency and two types of target cells is investigated, and the obtained results show that when the basic reproduction number is less than or equal to unity, the infection-free equilibrium is globally stable, that is, the in-host free virus will be cleared out finally; when the basic reproduction number is greater than unity, the infection equilibrium is globally stable, that is, the viral infection will be chronic and persist in-host. And by comparing the basic reproduction numbers of ordinary differential system and the associated delayed differential system, we think that it is necessary to elect an appropriate type of probability function for predicting the final outcome of viral infection in-host.

  12. No amelioration of uromodulin maturation and trafficking defect by sodium 4-phenylbutyrate in vivo: studies in mouse models of uromodulin-associated kidney disease.

    Science.gov (United States)

    Kemter, Elisabeth; Sklenak, Stefanie; Rathkolb, Birgit; Hrabě de Angelis, Martin; Wolf, Eckhard; Aigner, Bernhard; Wanke, Ruediger

    2014-04-11

    Uromodulin (UMOD)-associated kidney disease (UAKD) belongs to the hereditary progressive ER storage diseases caused by maturation defects of mutant UMOD protein. Current treatments of UAKD patients are symptomatic and cannot prevent disease progression. Two in vitro studies reported a positive effect of the chemical chaperone sodium 4-phenylbutyrate (4-PBA) on mutant UMOD maturation. Thus, 4-PBA was suggested as a potential treatment for UAKD. This study evaluated the effects of 4-PBA in two mouse models of UAKD. In contrast to previous in vitro studies, treatment with 4-PBA did not increase HSP70 expression or improve maturation and trafficking of mutant UMOD in vivo. Kidney function of UAKD mice was actually deteriorated by 4-PBA treatment. In transfected tubular epithelial cells, 4-PBA did not improve maturation but increased the expression level of both mutant and wild-type UMOD protein. Activation of NF-κB pathway in thick ascending limb of Henle's loop cells of UAKD mice was detected by increased abundance of RelB and phospho-IκB kinase α/β, an indirect activator of NF-κB. Furthermore, the abundance of NF-κB1 p105/p50, NF-κB2 p100/p52, and TRAF2 was increased in UAKD. NF-κB activation was identified as a novel disease mechanism of UAKD and might be a target for therapeutic intervention.

  13. 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.

  14. Viral Marketing

    OpenAIRE

    Sorina Raula Gîrboveanu; Silvia Puiu

    2008-01-01

    With consumers showing increasing resistance to traditional forms of advertising such as TV or newspaper ads, marketers have turned to alternate strategies, including viral marketing. Viral marketing exploits existing social networks by encouraging customers to share product information with their friends.In our study we are able to directly observe the effectiveness of person to person word of mouth advertising for hundreds of thousands of products for the first time

  15. Abca12-mediated lipid transport and Snap29-dependent trafficking of lamellar granules are crucial for epidermal morphogenesis in a zebrafish model of ichthyosis

    Directory of Open Access Journals (Sweden)

    Qiaoli Li

    2011-11-01

    Zebrafish (Danio rerio can serve as a model system to study heritable skin diseases. The skin is rapidly developed during the first 5–6 days of embryonic growth, accompanied by expression of skin-specific genes. Transmission electron microscopy (TEM of wild-type zebrafish at day 5 reveals a two-cell-layer epidermis separated from the underlying collagenous stroma by a basement membrane with fully developed hemidesmosomes. Scanning electron microscopy (SEM reveals an ordered surface contour of keratinocytes with discrete microridges. To gain insight into epidermal morphogenesis, we have employed morpholino-mediated knockdown of the abca12 and snap29 genes, which are crucial for secretion of lipids and intracellular trafficking of lamellar granules, respectively. Morpholinos, when placed on exon-intron junctions, were >90% effective in preventing the corresponding gene expression when injected into one- to four-cell-stage embryos. By day 3, TEM of abca12 morphants showed accumulation of lipid-containing electron-dense lamellar granules, whereas snap29 morphants showed the presence of apparently empty vesicles in the epidermis. Evaluation of epidermal morphogenesis by SEM revealed similar perturbations in both cases in the microridge architecture and the development of spicule-like protrusions on the surface of keratinocytes. These morphological findings are akin to epidermal changes in harlequin ichthyosis and CEDNIK syndrome, autosomal recessive keratinization disorders due to mutations in the ABCA12 and SNAP29 genes, respectively. The results indicate that interference of independent pathways involving lipid transport in the epidermis can result in phenotypically similar perturbations in epidermal morphogenesis, and that these fish mutants can serve as a model to study the pathomechanisms of these keratinization disorders.

  16. Rate-equation modelling and ensemble approach to extraction of parameters for viral infection-induced cell apoptosis and necrosis

    Energy Technology Data Exchange (ETDEWEB)

    Domanskyi, Sergii; Schilling, Joshua E.; Privman, Vladimir, E-mail: privman@clarkson.edu [Department of Physics, Clarkson University, Potsdam, New York 13676 (United States); Gorshkov, Vyacheslav [National Technical University of Ukraine — KPI, Kiev 03056 (Ukraine); Libert, Sergiy, E-mail: libert@cornell.edu [Department of Biomedical Sciences, Cornell University, Ithaca, New York 14853 (United States)

    2016-09-07

    We develop a theoretical approach that uses physiochemical kinetics modelling to describe cell population dynamics upon progression of viral infection in cell culture, which results in cell apoptosis (programmed cell death) and necrosis (direct cell death). Several model parameters necessary for computer simulation were determined by reviewing and analyzing available published experimental data. By comparing experimental data to computer modelling results, we identify the parameters that are the most sensitive to the measured system properties and allow for the best data fitting. Our model allows extraction of parameters from experimental data and also has predictive power. Using the model we describe interesting time-dependent quantities that were not directly measured in the experiment and identify correlations among the fitted parameter values. Numerical simulation of viral infection progression is done by a rate-equation approach resulting in a system of “stiff” equations, which are solved by using a novel variant of the stochastic ensemble modelling approach. The latter was originally developed for coupled chemical reactions.

  17. 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...

  18. 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.

  19. 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

  20. Valuable Virality

    NARCIS (Netherlands)

    Akpinar, E.; Berger, Jonah

    2017-01-01

    Given recent interest in social media, many brands now create content that they hope consumers will view and share with peers. While some campaigns indeed go “viral,” their value to the brand is limited if they do not boost brand evaluation or increase purchase. Consequently, a key question is how

  1. Exposure to electronic cigarettes impairs pulmonary anti-bacterial and anti-viral defenses in a mouse model.

    Directory of Open Access Journals (Sweden)

    Thomas E Sussan

    Full Text Available Electronic cigarettes (E-cigs have experienced sharp increases in popularity over the past five years due to many factors, including aggressive marketing, increased restrictions on conventional cigarettes, and a perception that E-cigs are healthy alternatives to cigarettes. Despite this perception, studies on health effects in humans are extremely limited and in vivo animal models have not been generated. Presently, we determined that E-cig vapor contains 7 x 10(11 free radicals per puff. To determine whether E-cig exposure impacts pulmonary responses in mice, we developed an inhalation chamber for E-cig exposure. Mice that were exposed to E-cig vapor contained serum cotinine concentrations that are comparable to human E-cig users. E-cig exposure for 2 weeks produced a significant increase in oxidative stress and moderate macrophage-mediated inflammation. Since, COPD patients are susceptible to bacterial and viral infections, we tested effects of E-cigs on immune response. Mice that were exposed to E-cig vapor showed significantly impaired pulmonary bacterial clearance, compared to air-exposed mice, following an intranasal infection with Streptococcus pneumonia. This defective bacterial clearance was partially due to reduced phagocytosis by alveolar macrophages from E-cig exposed mice. In response to Influenza A virus infection, E-cig exposed mice displayed increased lung viral titers and enhanced virus-induced illness and mortality. In summary, this study reports a murine model of E-cig exposure and demonstrates that E-cig exposure elicits impaired pulmonary anti-microbial defenses. Hence, E-cig exposure as an alternative to cigarette smoking must be rigorously tested in users for their effects on immune response and susceptibility to bacterial and viral infections.

  2. Activating receptor NKG2D targets RAE-1-expressing allogeneic neural precursor cells in a viral model of multiple sclerosis.

    Science.gov (United States)

    Weinger, Jason G; Plaisted, Warren C; Maciejewski, Sonia M; Lanier, Lewis L; Walsh, Craig M; Lane, Thomas E

    2014-10-01

    Transplantation of major histocompatibility complex-mismatched mouse neural precursor cells (NPCs) into mice persistently infected with the neurotropic JHM strain of mouse hepatitis virus (JHMV) results in rapid rejection that is mediated, in part, by T cells. However, the contribution of the innate immune response to allograft rejection in a model of viral-induced neurological disease has not been well defined. Herein, we demonstrate that the natural killer (NK) cell-expressing-activating receptor NKG2D participates in transplanted allogeneic NPC rejection in mice persistently infected with JHMV. Cultured NPCs derived from C57BL/6 (H-2(b) ) mice express the NKG2D ligand retinoic acid early precursor transcript (RAE)-1 but expression was dramatically reduced upon differentiation into either glia or neurons. RAE-1(+) NPCs were susceptible to NK cell-mediated killing whereas RAE-1(-) cells were resistant to lysis. Transplantation of C57BL/6-derived NPCs into JHMV-infected BALB/c (H-2(d) ) mice resulted in infiltration of NKG2D(+) CD49b(+) NK cells and treatment with blocking antibody specific for NKG2D increased survival of allogeneic NPCs. Furthermore, transplantation of differentiated RAE-1(-) allogeneic NPCs into JHMV-infected BALB/c mice resulted in enhanced survival, highlighting a role for the NKG2D/RAE-1 signaling axis in allograft rejection. We also demonstrate that transplantation of allogeneic NPCs into JHMV-infected mice resulted in infection of the transplanted cells suggesting that these cells may be targets for infection. Viral infection of cultured cells increased RAE-1 expression, resulting in enhanced NK cell-mediated killing through NKG2D recognition. Collectively, these results show that in a viral-induced demyelination model, NK cells contribute to rejection of allogeneic NPCs through an NKG2D signaling pathway. © 2014 AlphaMed Press.

  3. 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

  4. Protocol at the Crossroads: Rethinking anti-trafficking law from an Indian labour law perspective

    Directory of Open Access Journals (Sweden)

    Prabha Kotiswaran

    2015-04-01

    Full Text Available As we approach the fifteenth anniversary of the United Nations Trafficking Protocol, we can discern several phases of its diffusion, materialisation and interpretation in domestic criminal law regimes across the world. Although not exclusively preoccupied with sex work and sex trafficking anymore, the fact remains that the inordinate attention on trafficking in Western industrialised economies is disproportionate to the extent of the problem. Only 7% of the world’s 20.9 million forced labourers are in developed economies while 56% are in Asia Pacific. Yet in BRIC countries like India, with a substantial majority of the world’s trafficked victims and where 90% of all trafficking is domestic, trafficking has gained policy resonance only relatively recently. Even as India remains an active site for sexual humanitarianism with international and local abolitionist groups actively targeting sex workers, the article argues that less developed countries like India can play a crucial role in reorienting international anti-trafficking law and policy. Towards that goal, this article offers India’s bonded, contract and migrant labour laws as a robust labour law model against trafficking in contrast to the criminal justice model propagated by the Trafficking Protocol worldwide.

  5. Viral epidemics in a cell culture: novel high resolution data and their interpretation by a percolation theory based model.

    Directory of Open Access Journals (Sweden)

    Balázs Gönci

    2010-12-01

    Full Text Available Because of its relevance to everyday life, the spreading of viral infections has been of central interest in a variety of scientific communities involved in fighting, preventing and theoretically interpreting epidemic processes. Recent large scale observations have resulted in major discoveries concerning the overall features of the spreading process in systems with highly mobile susceptible units, but virtually no data are available about observations of infection spreading for a very large number of immobile units. Here we present the first detailed quantitative documentation of percolation-type viral epidemics in a highly reproducible in vitro system consisting of tens of thousands of virtually motionless cells. We use a confluent astroglial monolayer in a Petri dish and induce productive infection in a limited number of cells with a genetically modified herpesvirus strain. This approach allows extreme high resolution tracking of the spatio-temporal development of the epidemic. We show that a simple model is capable of reproducing the basic features of our observations, i.e., the observed behaviour is likely to be applicable to many different kinds of systems. Statistical physics inspired approaches to our data, such as fractal dimension of the infected clusters as well as their size distribution, seem to fit into a percolation theory based interpretation. We suggest that our observations may be used to model epidemics in more complex systems, which are difficult to study in isolation.

  6. Viral epidemics in a cell culture: novel high resolution data and their interpretation by a percolation theory based model.

    Science.gov (United States)

    Gönci, Balázs; Németh, Valéria; Balogh, Emeric; Szabó, Bálint; Dénes, Ádám; Környei, Zsuzsanna; Vicsek, Tamás

    2010-12-20

    Because of its relevance to everyday life, the spreading of viral infections has been of central interest in a variety of scientific communities involved in fighting, preventing and theoretically interpreting epidemic processes. Recent large scale observations have resulted in major discoveries concerning the overall features of the spreading process in systems with highly mobile susceptible units, but virtually no data are available about observations of infection spreading for a very large number of immobile units. Here we present the first detailed quantitative documentation of percolation-type viral epidemics in a highly reproducible in vitro system consisting of tens of thousands of virtually motionless cells. We use a confluent astroglial monolayer in a Petri dish and induce productive infection in a limited number of cells with a genetically modified herpesvirus strain. This approach allows extreme high resolution tracking of the spatio-temporal development of the epidemic. We show that a simple model is capable of reproducing the basic features of our observations, i.e., the observed behaviour is likely to be applicable to many different kinds of systems. Statistical physics inspired approaches to our data, such as fractal dimension of the infected clusters as well as their size distribution, seem to fit into a percolation theory based interpretation. We suggest that our observations may be used to model epidemics in more complex systems, which are difficult to study in isolation.

  7. A model for the dynamic nuclear/nucleolar/cytoplasmic trafficking of the porcine reproductive and respiratory syndrome virus (PRRSV) nucleocapsid protein based on live cell imaging

    International Nuclear Information System (INIS)

    You, Jae-Hwan; Howell, Gareth; Pattnaik, Asit K.; Osorio, Fernando A.; Hiscox, Julian A.

    2008-01-01

    Porcine reproductive and respiratory syndrome virus (PRRSV), an arterivirus, in common with many other positive strand RNA viruses, encodes a nucleocapsid (N) protein which can localise not only to the cytoplasm but also to the nucleolus in virus-infected cells and cells over-expressing N protein. The dynamic trafficking of positive strand RNA virus nucleocapsid proteins and PRRSV N protein in particular between the cytoplasm and nucleolus is unknown. In this study live imaging of permissive and non-permissive cell lines, in conjunction with photo-bleaching (FRAP and FLIP), was used to investigate the trafficking of fluorescent labeled (EGFP) PRRSV-N protein. The data indicated that EGFP-PRRSV-N protein was not permanently sequestered to the nucleolus and had equivalent mobility to cellular nucleolar proteins. Further the nuclear import of N protein appeared to occur faster than nuclear export, which may account for the observed relative distribution of N protein between the cytoplasm and the nucleolus

  8. Kupffer cells hasten resolution of liver immunopathology in mouse models of viral hepatitis.

    Directory of Open Access Journals (Sweden)

    Giovanni Sitia

    2011-06-01

    Full Text Available Kupffer cells (KCs are widely considered important contributors to liver injury during viral hepatitis due to their pro-inflammatory activity. Herein we utilized hepatitis B virus (HBV-replication competent transgenic mice and wild-type mice infected with a hepatotropic adenovirus to demonstrate that KCs do not directly induce hepatocellular injury nor do they affect the pathogenic potential of virus-specific CD8 T cells. Instead, KCs limit the severity of liver immunopathology. Mechanistically, our results are most compatible with the hypothesis that KCs contain liver immunopathology by removing apoptotic hepatocytes in a manner largely dependent on scavenger receptors. Apoptotic hepatocytes not readily removed by KCs become secondarily necrotic and release high-mobility group box 1 (HMGB-1 protein, promoting organ infiltration by inflammatory cells, particularly neutrophils. Overall, these results indicate that KCs resolve rather than worsen liver immunopathology.

  9. 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.

  10. Depletion of HPV16 early genes induces autophagy and senescence in a cervical carcinogenesis model, regardless of viral physical state.

    Science.gov (United States)

    Hanning, Jennifer E; Saini, Harpreet K; Murray, Matthew J; Caffarel, Maria M; van Dongen, Stijn; Ward, Dawn; Barker, Emily M; Scarpini, Cinzia G; Groves, Ian J; Stanley, Margaret A; Enright, Anton J; Pett, Mark R; Coleman, Nicholas

    2013-11-01

    In cervical carcinomas, high-risk human papillomavirus (HR-HPV) may be integrated into host chromosomes or remain extra-chromosomal (episomal). We used the W12 cervical keratinocyte model to investigate the effects of HPV16 early gene depletion on in vitro cervical carcinogenesis pathways, particularly effects shared by cells with episomal versus integrated HPV16 DNA. Importantly, we were able to study the specific cellular consequences of viral gene depletion by using short interfering RNAs known not to cause phenotypic or transcriptional off-target effects in keratinocytes. We found that while cervical neoplastic progression in vitro was characterized by dynamic changes in HPV16 transcript levels, viral early gene expression was required for cell survival at all stages of carcinogenesis, regardless of viral physical state, levels of early gene expression or histology in organotypic tissue culture. Moreover, HPV16 early gene depletion induced changes in host gene expression that were common to both episome-containing and integrant-containing cells. In particular, we observed up-regulation of autophagy genes, associated with enrichment of senescence and innate immune-response pathways, including the senescence-associated secretory phenotype (SASP). In keeping with these observations, HPV16 early gene depletion induced autophagy in both episome-containing and integrant-containing W12 cells, as evidenced by the appearance of autophagosomes, punctate expression of the autophagy marker LC3, conversion of LC3B-I to LC3B-II, and reduced levels of the autophagy substrate p62. Consistent with the reported association between autophagy and senescence pathways, HPV16 early gene depletion induced expression of the senescence marker beta-galactosidase and increased secretion of the SASP-related protein IGFBP3. Together, these data indicate that depleting HR-HPV early genes would be of potential therapeutic benefit in all cervical carcinogenesis pathways, regardless of viral

  11. Neuregulin-1/erbB-activation improves cardiac function and survival in models of ischemic, dilated, and viral cardiomyopathy.

    Science.gov (United States)

    Liu, Xifu; Gu, Xinhua; Li, Zhaoming; Li, Xinyan; Li, Hui; Chang, Jianjie; Chen, Ping; Jin, Jing; Xi, Bing; Chen, Denghong; Lai, Donna; Graham, Robert M; Zhou, Mingdong

    2006-10-03

    We evaluated the therapeutic potential of a recombinant 61-residue neuregulin-1 (beta2a isoform) receptor-active peptide (rhNRG-1) in multiple animal models of heart disease. Activation of the erbB family of receptor tyrosine kinases by rhNRG-1 could provide a treatment option for heart failure, because neuregulin-stimulated erbB2/erbB4 heterodimerization is not only critical for myocardium formation in early heart development but prevents severe dysfunction of the adult heart and premature death. Disabled erbB-signaling is also implicated in the transition from compensatory hypertrophy to failure, whereas erbB receptor-activation promotes myocardial cell growth and survival and protects against anthracycline-induced cardiomyopathy. rhNRG-1 was administered IV to animal models of ischemic, dilated, and viral cardiomyopathy, and cardiac function and survival were evaluated. Short-term intravenous administration of rhNRG-1 to normal dogs and rats did not alter hemodynamics or cardiac contractility. In contrast, rhNRG-1 improved cardiac performance, attenuated pathological changes, and prolonged survival in rodent models of ischemic, dilated, and viral cardiomyopathy, with the survival benefits in the ischemic model being additive to those of angiotensin-converting enzyme inhibitor therapy. In addition, despite continued pacing, rhNRG-1 produced global improvements in cardiac function in a canine model of pacing-induced heart failure. These beneficial effects make rhNRG-1 promising as a broad-spectrum therapeutic for the treatment of heart failure due to a variety of common cardiac diseases.

  12. Large Variations in HIV-1 Viral Load Explained by Shifting-Mosaic Metapopulation Dynamics

    Science.gov (United States)

    Lythgoe, Katrina A.; Blanquart, François

    2016-01-01

    The viral population of HIV-1, like many pathogens that cause systemic infection, is structured and differentiated within the body. The dynamics of cellular immune trafficking through the blood and within compartments of the body has also received wide attention. Despite these advances, mathematical models, which are widely used to interpret and predict viral and immune dynamics in infection, typically treat the infected host as a well-mixed homogeneous environment. Here, we present mathematical, analytical, and computational results that demonstrate that consideration of the spatial structure of the viral population within the host radically alters predictions of previous models. We study the dynamics of virus replication and cytotoxic T lymphocytes (CTLs) within a metapopulation of spatially segregated patches, representing T cell areas connected by circulating blood and lymph. The dynamics of the system depend critically on the interaction between CTLs and infected cells at the within-patch level. We show that for a wide range of parameters, the system admits an unexpected outcome called the shifting-mosaic steady state. In this state, the whole body’s viral population is stable over time, but the equilibrium results from an underlying, highly dynamic process of local infection and clearance within T-cell centers. Notably, and in contrast to previous models, this new model can explain the large differences in set-point viral load (SPVL) observed between patients and their distribution, as well as the relatively low proportion of cells infected at any one time, and alters the predicted determinants of viral load variation. PMID:27706164

  13. 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.

  14. The herpes virus Fc receptor gE-gI mediates antibody bipolar bridging to clear viral antigens from the cell surface.

    Directory of Open Access Journals (Sweden)

    Blaise Ndjamen

    2014-03-01

    Full Text Available The Herpes Simplex Virus 1 (HSV-1 glycoprotein gE-gI is a transmembrane Fc receptor found on the surface of infected cells and virions that binds human immunoglobulin G (hIgG. gE-gI can also participate in antibody bipolar bridging (ABB, a process by which the antigen-binding fragments (Fabs of the IgG bind a viral antigen while the Fc binds to gE-gI. IgG Fc binds gE-gI at basic, but not acidic, pH, suggesting that IgG bound at extracellular pH by cell surface gE-gI would dissociate and be degraded in acidic endosomes/lysosomes if endocytosed. The fate of viral antigens associated with gE-gI-bound IgG had been unknown: they could remain at the cell surface or be endocytosed with IgG. Here, we developed an in vitro model system for ABB and investigated the trafficking of ABB complexes using 4-D confocal fluorescence imaging of ABB complexes with transferrin or epidermal growth factor, well-characterized intracellular trafficking markers. Our data showed that cells expressing gE-gI and the viral antigen HSV-1 gD endocytosed anti-gD IgG and gD in a gE-gI-dependent process, resulting in lysosomal localization. These results suggest that gE-gI can mediate clearance of infected cell surfaces of anti-viral host IgG and viral antigens to evade IgG-mediated responses, representing a general mechanism for viral Fc receptors in immune evasion and viral pathogenesis.

  15. 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...

  16. 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...

  17. 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

  18. PDW Index - A Simple Model for the Prediction of Liver Fibrosis in Chronic Viral Hepatitis

    International Nuclear Information System (INIS)

    Ashraf, S.; Ali, N.

    2013-01-01

    Objectives: To assess the accuracy of platelets, platelet morphological parameters, mean platelet volume(MPV) and platelet distribution width, (PDW) to diagnose advanced fibrosis. Study Design: Validation study. Place and Duration of Study: Combined Military Hospital, Malir, from Jun 2008 to Jun 2009. Patients and Methods: Simple laboratory tests, aspartate aminotransferase (AST) alanine aminotransferase (ALT) platelet count and platelet morphological parameters were measured in 91 chronic viral hepatitis patients. All patients had liver biopsy performed. A new index, PDW index was derived to detect the opposing effects of liver fibrosis on platelet count, MPV, and PDW. The predictive value of the index for advanced fibrosis (F3-F4) was assessed through descriptive statistics and area under the ROC curves. Results: Two cut-offs were chosen to qualify different stages of fibrosis. A value of > 8.00 predicted advanced fibrosis, F3-F4, with a specificity of 94% and positive predictive value of 78%. A value of < 6.00 ruled out advanced fibrosis with a negative predictive value of 93% and a sensitivity of 82%. The area under the ROC curve for advanced fibrosis was 0.840. PDW Index values outside of these cut-offs correctly classified 60% of patients. Conclusion: A simple index comprising platelet as only parameters have high diagnostic value for the advanced stages of fibrosis. (author)

  19. Evaluation of disease and viral biomarkers as triggers for therapeutic intervention in respiratory mousepox - an animal model of smallpox.

    Science.gov (United States)

    Parker, Scott; Chen, Nanhai G; Foster, Scott; Hartzler, Hollyce; Hembrador, Ed; Hruby, Dennis; Jordan, Robert; Lanier, Randall; Painter, George; Painter, Wesley; Sagartz, John E; Schriewer, Jill; Mark Buller, R

    2012-04-01

    The human population is currently faced with the potential use of natural or recombinant variola and monkeypox viruses as biological weapons. Furthermore, the emergence of human monkeypox in Africa and its expanding environs poses a significant natural threat. Such occurrences would require therapeutic and prophylactic intervention with antivirals to minimize morbidity and mortality of exposed populations. Two orally-bioavailable antivirals are currently in clinical trials; namely CMX001, an ether-lipid analog of cidofovir with activity at the DNA replication stage and ST-246, a novel viral egress inhibitor. Both of these drugs have previously been evaluated in the ectromelia/mousepox system; however, the trigger for intervention was not linked to a disease biomarker or a specific marker of virus replication. In this study we used lethal, intranasal, ectromelia virus infections of C57BL/6 and hairless SKH1 mice to model human disease and evaluate exanthematous rash (rash) as an indicator to initiate antiviral treatment. We show that significant protection can be provided to C57BL/6 mice by CMX001 or ST-246 when therapy is initiated on day 6 post infection or earlier. We also show that significant protection can be provided to SKH1 mice treated with CMX001 at day 3 post infection or earlier, but this is four or more days before detection of rash (ST-246 not tested). Although in this model rash could not be used as a treatment trigger, viral DNA was detected in blood by day 4 post infection and in the oropharyngeal secretions (saliva) by day 2-3 post infection - thus providing robust and specific markers of virus replication for therapy initiation. These findings are discussed in the context of current respiratory challenge animal models in use for the evaluation of poxvirus antivirals. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Zika Virus Trafficking and Interactions in the Human Male Reproductive Tract.

    Science.gov (United States)

    da Silva, Lucia Regina Cangussu

    2018-05-11

    Sexual transmission of Zika virus (ZIKV) is a matter of great concern. Infectious viral particles can be shed in semen for as long as six months after infection and can be transferred to male and female sexual partners during unprotected sexual intercourse. The virus can be found inside spermatozoa and could be directly transferred to the oocyte during fertilization. Sexual transmission of ZIKV can contribute to the rise in number of infected individuals in endemic areas as well as in countries where the mosquito vector does not thrive. There is also the possibility, as has been demonstrated in mouse models, that the vaginal deposition of ZIKV particles present in semen could lead to congenital syndrome. In this paper, we review the current literature to understand ZIKV trafficking from the bloodstream to the human male reproductive tract and viral interactions with host cells in interstitial spaces, tubule walls, annexed glands and semen. We hope to highlight gaps to be filled by future research and potential routes for vaccine and antiviral development.

  1. 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

  2. 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

  3. 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…

  4. 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 ...

  5. 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.

  6. The CD63-Syntenin-1 Complex Controls Post-Endocytic Trafficking of Oncogenic Human Papillomaviruses.

    Science.gov (United States)

    Gräßel, Linda; Fast, Laura Aline; Scheffer, Konstanze D; Boukhallouk, Fatima; Spoden, Gilles A; Tenzer, Stefan; Boller, Klaus; Bago, Ruzica; Rajesh, Sundaresan; Overduin, Michael; Berditchevski, Fedor; Florin, Luise

    2016-08-31

    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, viral particles are found in CD63-positive endosomes recruiting syntenin-1, a CD63-interacting adaptor protein. Electron microscopy and immunofluorescence experiments indicate that the CD63-syntenin-1 complex controls delivery of internalised viral particles to multivesicular endosomes. Accordingly, infectivity of high-risk HPV types 16, 18 and 31 as well as disassembly and post-uncoating processing of viral particles was markedly suppressed in CD63 or syntenin-1 depleted cells. Our analyses also 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.

  7. 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.

  8. Recombination between Poliovirus and Coxsackie A Viruses of Species C: A Model of Viral Genetic Plasticity and Emergence

    Directory of Open Access Journals (Sweden)

    Francis Delpeyroux

    2011-08-01

    Full Text Available Genetic recombination in RNA viruses was discovered many years ago for poliovirus (PV, an enterovirus of the Picornaviridae family, and studied using PV or other picornaviruses as models. Recently, recombination was shown to be a general phenomenon between different types of enteroviruses of the same species. In particular, the interest for this mechanism of genetic plasticity was renewed with the emergence of pathogenic recombinant circulating vaccine-derived polioviruses (cVDPVs, which were implicated in poliomyelitis outbreaks in several regions of the world with insufficient vaccination coverage. Most of these cVDPVs had mosaic genomes constituted of mutated poliovaccine capsid sequences and part or all of the non-structural sequences from other human enteroviruses of species C (HEV-C, in particular coxsackie A viruses. A study in Madagascar showed that recombinant cVDPVs had been co-circulating in a small population of children with many different HEV-C types. This viral ecosystem showed a surprising and extensive biodiversity associated to several types and recombinant genotypes, indicating that intertypic genetic recombination was not only a mechanism of evolution for HEV-C, but an usual mode of genetic plasticity shaping viral diversity. Results suggested that recombination may be, in conjunction with mutations, implicated in the phenotypic diversity of enterovirus strains and in the emergence of new pathogenic strains. Nevertheless, little is known about the rules and mechanisms which govern genetic exchanges between HEV-C types, as well as about the importance of intertypic recombination in generating phenotypic variation. This review summarizes our current knowledge of the mechanisms of evolution of PV, in particular recombination events leading to the emergence of recombinant cVDPVs.

  9. Recombination between poliovirus and coxsackie A viruses of species C: a model of viral genetic plasticity and emergence.

    Science.gov (United States)

    Combelas, Nicolas; Holmblat, Barbara; Joffret, Marie-Line; Colbère-Garapin, Florence; Delpeyroux, Francis

    2011-08-01

    Genetic recombination in RNA viruses was discovered many years ago for poliovirus (PV), an enterovirus of the Picornaviridae family, and studied using PV or other picornaviruses as models. Recently, recombination was shown to be a general phenomenon between different types of enteroviruses of the same species. In particular, the interest for this mechanism of genetic plasticity was renewed with the emergence of pathogenic recombinant circulating vaccine-derived polioviruses (cVDPVs), which were implicated in poliomyelitis outbreaks in several regions of the world with insufficient vaccination coverage. Most of these cVDPVs had mosaic genomes constituted of mutated poliovaccine capsid sequences and part or all of the non-structural sequences from other human enteroviruses of species C (HEV-C), in particular coxsackie A viruses. A study in Madagascar showed that recombinant cVDPVs had been co-circulating in a small population of children with many different HEV-C types. This viral ecosystem showed a surprising and extensive biodiversity associated to several types and recombinant genotypes, indicating that intertypic genetic recombination was not only a mechanism of evolution for HEV-C, but an usual mode of genetic plasticity shaping viral diversity. Results suggested that recombination may be, in conjunction with mutations, implicated in the phenotypic diversity of enterovirus strains and in the emergence of new pathogenic strains. Nevertheless, little is known about the rules and mechanisms which govern genetic exchanges between HEV-C types, as well as about the importance of intertypic recombination in generating phenotypic variation. This review summarizes our current knowledge of the mechanisms of evolution of PV, in particular recombination events leading to the emergence of recombinant cVDPVs.

  10. Going Multi-viral: Synthedemic Modelling of Internet-based Spreading Phenomena

    Directory of Open Access Journals (Sweden)

    Marily Nika

    2015-02-01

    Full Text Available Epidemics of a biological and technological nature pervade modern life. For centuries, scientific research focused on biological epidemics, with simple compartmental epidemiological models emerging as the dominant explanatory paradigm. Yet there has been limited translation of this effort to explain internet-based spreading phenomena. Indeed, single-epidemic models are inadequate to explain the multimodal nature of complex phenomena. In this paper we propose a novel paradigm for modelling internet-based spreading phenomena based on the composition of multiple compartmental epidemiological models. Our approach is inspired by Fourier analysis, but rather than trigonometric wave forms, our components are compartmental epidemiological models. We show results on simulated multiple epidemic data, swine flu data and BitTorrent downloads of a popular music artist. Our technique can characterise these multimodal data sets utilising a parsimonous number of subepidemic models.

  11. Adult Mouse DRG Explant and Dissociated Cell Models to Investigate Neuroplasticity and Responses to Environmental Insults Including Viral Infection.

    Science.gov (United States)

    Fornaro, Michele; Sharthiya, Harsh; Tiwari, Vaibhav

    2018-03-09

    This protocol describes an ex vivo model of mouse-derived dorsal root ganglia (DRG) explant and in vitro DRG-derived co-culture of dissociated sensory neurons and glial satellite cells. These are useful and versatile models to investigate a variety of biological responses associated with physiological and pathological conditions of the peripheral nervous system (PNS) ranging from neuron-glial interaction, neuroplasticity, neuroinflammation, and viral infection. The usage of DRG explant is scientifically advantageous compared to simplistic single cells models for multiple reasons. For instance, as an organotypic culture, the DRG explant allows ex vivo transfer of an entire neuronal network including the extracellular microenvironment that play a significant role in all the neuronal and glial functions. Further, DRG explants can also be maintained ex vivo for several days and the culture conditions can be perturbed as desired. In addition, the harvested DRG can be further dissociated into an in vitro co-culture of primary sensory neurons and satellite glial cells to investigate neuronal-glial interaction, neuritogenesis, axonal cone interaction with the extracellular microenvironment, and more general, any aspect associated with the neuronal metabolism. Therefore, the DRG-explant system offers a great deal of flexibility to study a wide array of events related to biological, physiological, and pathological conditions in a cost-effective manner.

  12. Modeling the potential risk factors of bovine viral diarrhea prevalence in Egypt using univariable and multivariable logistic regression analyses

    Directory of Open Access Journals (Sweden)

    Abdelfattah M. Selim

    2018-03-01

    Full Text Available Aim: The present cross-sectional study was conducted to determine the seroprevalence and potential risk factors associated with Bovine viral diarrhea virus (BVDV disease in cattle and buffaloes in Egypt, to model the potential risk factors associated with the disease using logistic regression (LR models, and to fit the best predictive model for the current data. Materials and Methods: A total of 740 blood samples were collected within November 2012-March 2013 from animals aged between 6 months and 3 years. The potential risk factors studied were species, age, sex, and herd location. All serum samples were examined with indirect ELIZA test for antibody detection. Data were analyzed with different statistical approaches such as Chi-square test, odds ratios (OR, univariable, and multivariable LR models. Results: Results revealed a non-significant association between being seropositive with BVDV and all risk factors, except for species of animal. Seroprevalence percentages were 40% and 23% for cattle and buffaloes, respectively. OR for all categories were close to one with the highest OR for cattle relative to buffaloes, which was 2.237. Likelihood ratio tests showed a significant drop of the -2LL from univariable LR to multivariable LR models. Conclusion: There was an evidence of high seroprevalence of BVDV among cattle as compared with buffaloes with the possibility of infection in different age groups of animals. In addition, multivariable LR model was proved to provide more information for association and prediction purposes relative to univariable LR models and Chi-square tests if we have more than one predictor.

  13. EVALUATION OF MURINE NOROVIRUS, FELINE CALICIVIRUS, POLIOVIRUS, AND MS2 AS SURROGATES FOR HUMAN NOROVIRUS IN a Model of Viral Persistence in SURFACE Water AND GROUNDWATER

    Science.gov (United States)

    Human noroviruses (NoV) are a significant cause of non bacterial gastroenteritis worldwide with contaminated drinking water a potential transmission route. The absence of a cell culture infectivity model for NoV necessitates the use of molecular methods and/or viral surrogate mod...

  14. 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.

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

    Directory of Open Access Journals (Sweden)

    Williams Alun

    2007-11-01

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

  16. 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

  17. 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.

  18. 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.

  19. Adeno-associated viral vector serotype 5 poorly transduces liver in rat models.

    Directory of Open Access Journals (Sweden)

    Paula S Montenegro-Miranda

    Full Text Available Preclinical studies in mice and non-human primates showed that AAV serotype 5 provides efficient liver transduction and as such seems a promising vector for liver directed gene therapy. An advantage of AAV5 compared to serotype 8 already shown to provide efficient correction in a phase 1 trial in patients suffering from hemophilia B, is its lower seroprevalence in the general population. Our goal is liver directed gene therapy for Crigler-Najjar syndrome type I, inherited severe unconjugated hyperbilirubinemia caused by UGT1A1 deficiency. In a relevant animal model, the Gunn rat, we compared the efficacy of AAV 5 and 8 to that of AAV1 previously shown to be effective. Ferrying a construct driving hepatocyte specific expression of UGT1A1, both AAV8 and AAV1 provided an efficient correction of hyperbilirubinemia. In contrast to these two and to other animal models AAV5 failed to provide any correction. To clarify whether this unexpected finding was due to the rat model used or due to a problem with AAV5, the efficacy of this serotype was compared in a mouse and two additional rat strains. Administration of an AAV5 vector expressing luciferase under the control of a liver specific promoter confirmed that this serotype poorly performed in rat liver, rendering it not suitable for proof of concept studies in this species.

  20. Nuclear trafficking of the HIV-1 pre-integration complex depends on the ADAM10 intracellular domain

    International Nuclear Information System (INIS)

    Endsley, Mark A.; Somasunderam, Anoma D.; Li, Guangyu; Oezguen, Numan; Thiviyanathan, Varatharasa; Murray, James L.; Rubin, Donald H.; Hodge, Thomas W.

    2014-01-01

    Previously, we showed that ADAM10 is necessary for HIV-1 replication in primary human macrophages and immortalized cell lines. Silencing ADAM10 expression interrupted the HIV-1 life cycle prior to nuclear translocation of viral cDNA. Furthermore, our data indicated that HIV-1 replication depends on the expression of ADAM15 and γ-secretase, which proteolytically processes ADAM10. Silencing ADAM15 or γ-secretase expression inhibits HIV-1 replication between reverse transcription and nuclear entry. Here, we show that ADAM10 expression also supports replication in CD4 + T lymphocytes. The intracellular domain (ICD) of ADAM10 associates with the HIV-1 pre-integration complex (PIC) in the cytoplasm and immunoprecipitates and co-localizes with HIV-1 integrase, a key component of PIC. Taken together, our data support a model whereby ADAM15/γ-secretase processing of ADAM10 releases the ICD, which then incorporates into HIV-1 PIC to facilitate nuclear trafficking. Thus, these studies suggest ADAM10 as a novel therapeutic target for inhibiting HIV-1 prior to nuclear entry. - Highlights: • Nuclear trafficking of the HIV-1 pre-integration complex depends on ADAM10. • ADAM10 associates with HIV-1 integrase in the pre-integration complex. • HIV-1 replication depends on the expression of ADAM15 and γ-secretase. • Silencing ADAM15 or γ-secretase expression inhibits nuclear import of viral cDNA. • ADAM10 is important for HIV-1 replication in human macrophages and CD4 + T lymphocytes

  1. Nuclear trafficking of the HIV-1 pre-integration complex depends on the ADAM10 intracellular domain

    Energy Technology Data Exchange (ETDEWEB)

    Endsley, Mark A., E-mail: maendsle@utmb.edu [Department Internal Medicine, Division of Infectious Diseases, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555 (United States); Somasunderam, Anoma D., E-mail: asomasun@utmb.edu [Department Internal Medicine, Division of Infectious Diseases, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555 (United States); Li, Guangyu, E-mail: LIG001@mail.etsu.edu [Department of Internal Medicine, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614 (United States); Oezguen, Numan, E-mail: numan.oezguen@bcm.edu [Department of Pathology and Immunology, Microbiome Center, Texas Children' s Hospital, Houston, TX 77030 (United States); Thiviyanathan, Varatharasa, E-mail: Varatharasa.Thiviyanathan@uth.tmc.edu [Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX 77030 (United States); Murray, James L., E-mail: jmurray100@yahoo.com [GeneTAG Technology, Inc., 3155 Northwoods Place, Norcross, GA 30071 (United States); Rubin, Donald H., E-mail: don.h.rubin@vanderbilt.edu [Research Medicine, VA Tennessee Valley Healthcare System, 1310 24th Ave. South, Nashville, TN 37212 (United States); Departments of Medicine, Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, 1161 21st Ave South, Nashville, TN 37232 (United States); Hodge, Thomas W., E-mail: twhodge3@gmail.com [Pre-clinical and Antiviral Research, Tamir Biotechnology, Inc., 12625 High Bluff Dr., Suite 113, San Diego, CA 92130 (United States); and others

    2014-04-15

    Previously, we showed that ADAM10 is necessary for HIV-1 replication in primary human macrophages and immortalized cell lines. Silencing ADAM10 expression interrupted the HIV-1 life cycle prior to nuclear translocation of viral cDNA. Furthermore, our data indicated that HIV-1 replication depends on the expression of ADAM15 and γ-secretase, which proteolytically processes ADAM10. Silencing ADAM15 or γ-secretase expression inhibits HIV-1 replication between reverse transcription and nuclear entry. Here, we show that ADAM10 expression also supports replication in CD4{sup +} T lymphocytes. The intracellular domain (ICD) of ADAM10 associates with the HIV-1 pre-integration complex (PIC) in the cytoplasm and immunoprecipitates and co-localizes with HIV-1 integrase, a key component of PIC. Taken together, our data support a model whereby ADAM15/γ-secretase processing of ADAM10 releases the ICD, which then incorporates into HIV-1 PIC to facilitate nuclear trafficking. Thus, these studies suggest ADAM10 as a novel therapeutic target for inhibiting HIV-1 prior to nuclear entry. - Highlights: • Nuclear trafficking of the HIV-1 pre-integration complex depends on ADAM10. • ADAM10 associates with HIV-1 integrase in the pre-integration complex. • HIV-1 replication depends on the expression of ADAM15 and γ-secretase. • Silencing ADAM15 or γ-secretase expression inhibits nuclear import of viral cDNA. • ADAM10 is important for HIV-1 replication in human macrophages and CD4{sup +} T lymphocytes.

  2. 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.

  3. 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

  4. 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...

  5. 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...

  6. 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.

  7. Stability of a viral infection model with state-dependent delay, CTL and antibody immune responses

    Czech Academy of Sciences Publication Activity Database

    Rezunenko, Oleksandr

    2017-01-01

    Roč. 22, č. 4 (2017), s. 1547-1563 ISSN 1531-3492 R&D Projects: GA ČR(CZ) GA16-06678S Institutional support: RVO:67985556 Keywords : Evolution equations * Lyapunov stability * state-dependent delay * virus infection model Subject RIV: BC - Control Systems Theory OBOR OECD: Computer sciences, information science, bioinformathics (hardware development to be 2.2, social aspect to be 5.8) Impact factor: 0.994, year: 2016 http://library.utia.cas.cz/separaty/2017/AS/rezunenko-0476128.pdf

  8. 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.

  9. Evaluation of temporal surveillance system sensitivity and freedom from bovine viral diarrhea in Danish dairy herds using scenario tree modelling.

    Science.gov (United States)

    Foddai, Alessandro; Stockmarr, Anders; Boklund, Anette

    2016-06-21

    The temporal sensitivity of the surveillance system (TemSSe) for Bovine Viral Diarrhea (BVD) in Danish dairy herds was evaluated. Currently, the Danish antibody blocking ELISA is used to test quarterly bulk tank milk (BTM). To optimize the surveillance system as an early warning system, we considered the possibility of using the SVANOVIR ELISA, as this test has been shown to detect BVD-positive herds earlier than the blocking ELISA in BTM tests. Information from data (2010) and outputs from two published stochastic models were fed into a stochastic scenario tree to estimate the TemSSe. For that purpose we considered: the risk of BVD introduction into the dairy population, the ELISA used and the high risk period (HRP) from BVD introduction to testing (at 90 or 365 days). The effect of introducing one persistently infected (PI) calf or one transiently infected (TI) milking cow into 1 (or 8) dairy herd(s) was investigated. Additionally we estimated the confidence in low (PLow) herd prevalence (tree methodology, could be applied to optimize early warning surveillance systems of different animal diseases.

  10. Evaluation of bovine viral diarrhoea virus control strategies in dairy herds in Hokkaido, Japan, using stochastic modelling.

    Science.gov (United States)

    Sekiguchi, S; Presi, P; Omori, R; Staerk, K; Schuppers, M; Isoda, N; Yoshikawa, Y; Umemura, T; Nakayama, H; Fujii, Y; Sakoda, Y

    2018-02-01

    Bovine viral diarrhoea virus (BVDV) infection in cattle can result in growth retardation, reduced milk production, reproductive disorders and death. Persistently infected animals are the primary source of infection. In Hokkaido, Japan, all cattle entering shared pastures in summer are vaccinated before movement for disease control. Additionally, these cattle may be tested for BVDV and culled if positive. However, the effectiveness of this control strategy aiming to reduce the number of BVDV-infected animals has not been assessed. The aim of this study was to evaluate the effectiveness of various test-and-cull and/or vaccination strategies on BVDV control in dairy farms in two districts of Hokkaido, Nemuro and Hiyama. A stochastic model was developed to compare the different control strategies over a 10-year period. The model was individual-based and simulated disease dynamics both within and between herds. Parameters included in the model were obtained from the literature, the Hokkaido government and the Japanese Ministry of Agriculture, Forestry and Fisheries. Nine different scenarios were compared as follows: no control, test-and-cull strategies based on antigen testing of either calves or only cattle entering common pastures, vaccination of all adult cattle or only cattle entering shared pastures and combinations thereof. The results indicate that current strategies for BVDV control in Hokkaido slightly reduced the number of BVDV-infected animals; however, alternative strategies such as testing all calves and culling any positives or vaccinating all susceptible adult animals dramatically reduced those. To our knowledge, this is the first report regarding the comparison of the effectiveness between the current strategies in Hokkaido and the alternative strategies for BVDV control measures. © 2017 Blackwell Verlag GmbH.

  11. 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.

  12. Rotavirus Viremia and Extraintestinal Viral Infection in the Neonatal Rat Model

    Science.gov (United States)

    Crawford, Sue E.; Patel, Dinesh G.; Cheng, Elly; Berkova, Zuzana; Hyser, Joseph M.; Ciarlet, Max; Finegold, Milton J.; Conner, Margaret E.; Estes, Mary K.

    2006-01-01

    Rotaviruses infect mature, differentiated enterocytes of the small intestine and, by an unknown mechanism, escape the gastrointestinal tract and cause viremia. The neonatal rat model of rotavirus infection was used to determine the kinetics of viremia, spread, and pathology of rotavirus in extraintestinal organs. Five-day-old rat pups were inoculated intragastrically with an animal (RRV) or human (HAL1166) rotavirus or phosphate-buffered saline. Blood was collected from a subset of rat pups, and following perfusion to remove residual blood, organs were removed and homogenized to analyze rotavirus-specific antigen by enzyme-linked immunosorbent assay and infectious rotavirus by fluorescent focus assay or fixed in formalin for histology and immunohistochemistry. Viremia was detected following rotavirus infection with RRV and HAL1166. The RRV 50% antigenemia dose was 1.8 × 103 PFU, and the 50% diarrhea dose was 7.7 × 105 PFU, indicating that infection and viremia occurred in the absence of diarrhea and that detecting rotavirus antigen in the blood was a more sensitive measure of infection than diarrhea. Rotavirus antigens and infectious virus were detected in multiple organs (stomach, intestines, liver, lungs, spleen, kidneys, pancreas, thymus, and bladder). Histopathological changes due to rotavirus infection included acute inflammation of the portal tract and bile duct, microsteatosis, necrosis, and inflammatory cell infiltrates in the parenchymas of the liver and lungs. Colocalization of structural and nonstructural proteins with histopathology in the liver and lungs indicated that the histological changes observed were due to rotavirus infection and replication. Replicating rotavirus was also detected in macrophages in the lungs and blood vessels, indicating a possible mechanism of rotavirus dissemination. Extraintestinal infectious rotavirus, but not diarrhea, was observed in the presence of passively or actively acquired rotavirus-specific antibody. These

  13. 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

  14. Improving ART programme retention and viral suppression are key to maximising impact of treatment as prevention - a modelling study.

    Science.gov (United States)

    McCreesh, Nicky; Andrianakis, Ioannis; Nsubuga, Rebecca N; Strong, Mark; Vernon, Ian; McKinley, Trevelyan J; Oakley, Jeremy E; Goldstein, Michael; Hayes, Richard; White, Richard G

    2017-08-09

    UNAIDS calls for fewer than 500,000 new HIV infections/year by 2020, with treatment-as-prevention being a key part of their strategy for achieving the target. A better understanding of the contribution to transmission of people at different stages of the care pathway can help focus intervention services at populations where they may have the greatest effect. We investigate this using Uganda as a case study. An individual-based HIV/ART model was fitted using history matching. 100 model fits were generated to account for uncertainties in sexual behaviour, HIV epidemiology, and ART coverage up to 2015 in Uganda. A number of different ART scale-up intervention scenarios were simulated between 2016 and 2030. The incidence and proportion of transmission over time from people with primary infection, post-primary ART-naïve infection, and people currently or previously on ART was calculated. In all scenarios, the proportion of transmission by ART-naïve people decreases, from 70% (61%-79%) in 2015 to between 23% (15%-40%) and 47% (35%-61%) in 2030. The proportion of transmission by people on ART increases from 7.8% (3.5%-13%) to between 14% (7.0%-24%) and 38% (21%-55%). The proportion of transmission by ART dropouts increases from 22% (15%-33%) to between 31% (23%-43%) and 56% (43%-70%). People who are currently or previously on ART are likely to play an increasingly large role in transmission as ART coverage increases in Uganda. Improving retention on ART, and ensuring that people on ART remain virally suppressed, will be key in reducing HIV incidence in Uganda.

  15. The Therapeutic Potential of CRISPR/Cas9 Systems in Oncogene-Addicted Cancer Types: Virally Driven Cancers as a Model System

    Directory of Open Access Journals (Sweden)

    Luqman Jubair

    2017-09-01

    Full Text Available The field of gene editing is undergoing unprecedented growth. The first ex vivo human clinical trial in China started in 2016, more than 1000 US patents have been filed, and there is exponential growth in publications. The ability to edit genes with high fidelity is promising for the development of new treatments for a range of diseases, particularly inherited conditions, infectious diseases, and cancers. For cancer, a major issue is the identification of driver mutations and oncogenes to target for therapeutic effect, and this requires the development of robust models with which to prove their efficacy. The challenge is that there is rarely a single critical gene. However, virally driven cancers, in which cells are addicted to the expression of a single viral oncogene in some cases, may serve as model systems for CRISPR/Cas therapies, as they did for RNAi. These models and systems offer an excellent opportunity to test both preclinical models and clinical conditions to examine the effectiveness of gene editing, and here we review the options and offer a way forward. Keywords: CRISPR/Cas9, virally-driven cancers, cervical cancer, oncogene-addiction

  16. 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.

  17. 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...

  18. 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.

  19. 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

  20. 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

  1. Disruption of Claudin-1 Expression by miRNA-182 Alters the Susceptibility to Viral Infectivity in HCV Cell Models

    Directory of Open Access Journals (Sweden)

    Sarah E. Riad

    2018-03-01

    Full Text Available HCV entry involves a complex interplay between viral and host molecules. During post-binding interactions, the viral E2 complexes with CD81 receptor for delivery to the tight junction proteins CLDN1 and OCLN, which aid in viral internalization. Targeting HCV entry receptors represents an appealing approach to inhibit viral infectivity. This study aimed at investigating the impact of targeting CLDN1 by microRNAs on HCV infectivity. miR-155 was previously shown to target the 3′UTR of CLDN1 mRNA. Therefore, miR-155 was used as a control in this study. In-silico analysis and luciferase reporter assay were utilized to identify potential targeting miRNAs. The impact of the identified miRNAs on CLDN1 mRNA and protein expression was examined by qRT-PCR, indirect immunofluorescence and western blotting, respectively. The role of the selected miRNAs on HCV infectivity was assessed by measuring the viral load following the ectopic expression of the selected miRNAs. miR-182 was identified in-silico and by experimental validation to target CLDN1. Both miR-155 and miR-182 inhibited CLDN1 mRNA and protein expression in infected Huh7 cells. Ectopic expression of miR-155 increased, while miR-182 reduced the viral load. In conclusion, despite repressing CLDN1, the impact of miR-155 and miR-182 on HCV infectivity is contradictory. Ectopic miR-182 expression is suggested as an upstream regulator of the entry factor CLDN1, harnessing HCV infection.

  2. In vivo T2* weighted MRI visualizes cardiac lesions in murine models of acute and chronic viral myocarditis.

    Directory of Open Access Journals (Sweden)

    Xavier Helluy

    Full Text Available Acute and chronic forms of myocarditis are mainly induced by virus infections. As a consequence of myocardial damage and inflammation dilated cardiomyopathy and chronic heart failure may develop. The gold standard for the diagnosis of myocarditis is endomyocardial biopsies which are required to determine the etiopathogenesis of cardiac inflammatory processes. However, new non-invasive MRI techniques hold great potential in visualizing cardiac non-ischemic inflammatory lesions at high spatial resolution, which could improve the investigation of the pathophysiology of viral myocarditis.Here we present the discovery of a novel endogenous T2* MRI contrast of myocardial lesions in murine models of acute and chronic CVB3 myocarditis. The evaluation of infected hearts ex vivo and in vivo by 3D T2w and T2*w MRI allowed direct localization of virus-induced myocardial lesions without any MRI tracer or contrast agent. T2*w weighted MRI is able to detect both small cardiac lesions of acute myocarditis and larger necrotic areas at later stages of chronic myocarditis, which was confirmed by spatial correlation of MRI hypointensity in myocardium with myocardial lesions histologically. Additional in vivo and ex vivo MRI analysis proved that the contrast mechanism was due to a strong paramagnetic tissue alteration in the vicinity of myocardial lesions, effectively pointing towards iron deposits as the primary contributor of contrast. The evaluation of the biological origin of the MR contrast by specific histological staining and transmission electron microscopy revealed that impaired iron metabolism primarily in mitochondria caused iron deposits within necrotic myocytes, which induces strong magnetic susceptibility in myocardial lesions and results in strong T2* contrast.This T2*w MRI technique provides a fast and sensitive diagnostic tool to determine the patterns and the severity of acute and chronic enteroviral myocarditis and the precise localization of

  3. In vivo T2* weighted MRI visualizes cardiac lesions in murine models of acute and chronic viral myocarditis

    Science.gov (United States)

    Helluy, Xavier; Sauter, Martina; Ye, Yu-Xiang; Lykowsky, Gunthard; Kreutner, Jakob; Yilmaz, Ali; Jahns, Roland; Boivin, Valerie; Kandolf, Reinhard; Jakob, Peter M.; Hiller, Karl-Heinz; Klingel, Karin

    2017-01-01

    Objective Acute and chronic forms of myocarditis are mainly induced by virus infections. As a consequence of myocardial damage and inflammation dilated cardiomyopathy and chronic heart failure may develop. The gold standard for the diagnosis of myocarditis is endomyocardial biopsies which are required to determine the etiopathogenesis of cardiac inflammatory processes. However, new non-invasive MRI techniques hold great potential in visualizing cardiac non-ischemic inflammatory lesions at high spatial resolution, which could improve the investigation of the pathophysiology of viral myocarditis. Results Here we present the discovery of a novel endogenous T2* MRI contrast of myocardial lesions in murine models of acute and chronic CVB3 myocarditis. The evaluation of infected hearts ex vivo and in vivo by 3D T2w and T2*w MRI allowed direct localization of virus-induced myocardial lesions without any MRI tracer or contrast agent. T2*w weighted MRI is able to detect both small cardiac lesions of acute myocarditis and larger necrotic areas at later stages of chronic myocarditis, which was confirmed by spatial correlation of MRI hypointensity in myocardium with myocardial lesions histologically. Additional in vivo and ex vivo MRI analysis proved that the contrast mechanism was due to a strong paramagnetic tissue alteration in the vicinity of myocardial lesions, effectively pointing towards iron deposits as the primary contributor of contrast. The evaluation of the biological origin of the MR contrast by specific histological staining and transmission electron microscopy revealed that impaired iron metabolism primarily in mitochondria caused iron deposits within necrotic myocytes, which induces strong magnetic susceptibility in myocardial lesions and results in strong T2* contrast. Conclusion This T2*w MRI technique provides a fast and sensitive diagnostic tool to determine the patterns and the severity of acute and chronic enteroviral myocarditis and the precise

  4. 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.

  5. 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.

  6. An epidemiological model of viral infections in a Varroa-infested bee colony: the case of a bee-dependent mite population size

    OpenAIRE

    Bernardi, Sara; Venturino, Ezio

    2016-01-01

    In recent years the spread of the ectoparasitic mite Varroa destructor has become the most serious threat to worldwide apiculture. In the model presented here we extend the bee population dynamics with mite viral epidemiology examined in an earlier paper by allowing a bee-dependent mite population size. The results of the analysis match field observations well and give a clear explanation of how Varroa affects the epidemiology of certain naturally occurring bee viruses, causing considerable d...

  7. 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.

  8. Psychiatry's Role in the Management of Human Trafficking Victims: An Integrated Care Approach.

    Science.gov (United States)

    Gordon, Mollie; Salami, Temilola; Coverdale, John; Nguyen, Phuong T

    2018-03-01

    Human trafficking is an outrageous human rights violation with potentially devastating consequences to individuals and the public health. Victims are often underrecognized and there are few guidelines for how best to identify, care for, and safely reintegrate victims back into the community. The purpose of this paper is to propose a multifaceted, interdisciplinary, and interprofessional guideline for providing care and services to human trafficking victims. Databases such as PubMed and PsycINFO were searched for papers outlining human trafficking programs with a primary psychiatric focus. No integrated care models that provide decisional guidelines at different points of intervention for human trafficking patients and that highlight the important role of psychiatric consultation were found. Psychiatrists and psychologists are pivotal to an integrated care approach in health care settings. The provision of such a comprehensive and integrated model of care should facilitate the identification of victims, promote their recovery, and reduce the possibility of retraumatization.

  9. Combating Rhino Horn Trafficking: The Need to Disrupt Criminal Networks.

    Directory of Open Access Journals (Sweden)

    Timothy C Haas

    Full Text Available The onslaught on the World's wildlife continues despite numerous initiatives aimed at curbing it. We build a model that integrates rhino horn trade with rhino population dynamics in order to evaluate the impact of various management policies on rhino sustainability. In our model, an agent-based sub-model of horn trade from the poaching event up through a purchase of rhino horn in Asia impacts rhino abundance. A data-validated, individual-based sub-model of the rhino population of South Africa provides these abundance values. We evaluate policies that consist of different combinations of legal trade initiatives, demand reduction marketing campaigns, increased anti-poaching measures within protected areas, and transnational policing initiatives aimed at disrupting those criminal syndicates engaged in horn trafficking. Simulation runs of our model over the next 35 years produces a sustainable rhino population under only one management policy. This policy includes both a transnational policing effort aimed at dismantling those criminal networks engaged in rhino horn trafficking-coupled with increases in legal economic opportunities for people living next to protected areas where rhinos live. This multi-faceted approach should be the focus of the international debate on strategies to combat the current slaughter of rhino rather than the binary debate about whether rhino horn trade should be legalized. This approach to the evaluation of wildlife management policies may be useful to apply to other species threatened by wildlife trafficking.

  10. Effects of State-Level Firearm Seller Accountability Policies on Firearm Trafficking

    OpenAIRE

    Webster, Daniel W.; Vernick, Jon S.; Bulzacchelli, Maria T.

    2009-01-01

    Criminals illegally obtaining firearms represent a great risk to many urban residents. This cross-sectional study of 54 US cities uses data on state laws governing gun sales, a survey of law enforcement agencies’ practices to promote compliance with gun sales laws, and crime gun trace data to examine associations between these policies and practices with gun trafficking indicators. Higher levels of local gun ownership were linked with greater intrastate gun trafficking. Regression models esti...

  11. 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

  12. Human trafficking and severe mental illness: an economic analysis of survivors' use of psychiatric services.

    Science.gov (United States)

    Cary, Maria; Oram, Siân; Howard, Louise M; Trevillion, Kylee; Byford, Sarah

    2016-07-19

    Previous studies have found a high prevalence of depression and post-traumatic stress disorder (PTSD) among survivors of human trafficking. European countries are required to assist trafficked people in their psychological recovery, but there are no rigorous data on the costs of doing so. The objectives of this study were to quantify the use of secondary mental health services by survivors of human trafficking; to estimate the cost of survivors' use of secondary mental health services provided by the UK National Health Service (NHS); and to identify factors that predict higher costs of mental health service provision. Historical cohort study of psychiatric patients who had experienced human trafficking. The South London and Maudsley NHS Trust (SLaM) Biomedical Research Centre Case Register Interactive Search (CRIS) database was used to identify anonymised full patient records of patients who had experienced human trafficking and who had accessed SLaM mental health services between 2007 and 2012. Data were extracted on socio-demographic and trafficking characteristics and contacts with mental health services. Total costs were calculated by multiplying each resource use item by an appropriate unit cost. Factors that predicted high mental health service costs were analysed using regression models. One hundred nineteen patients were included in the analysis. Mean total mental health service costs per patient were £27,293 (sd 80,985) and mean duration of contact with services was 1490 (sd 757) days (approximately 4 years). Regression analysis showed that higher costs were associated with diagnosis of psychotic disorder (p trafficking violence (p = 0.06). Patients diagnosed with psychotic disorders cost approximately £32,635 more than patients with non-psychotic disorders/psychological distress but no formal diagnosis and patients whose clinical notes documented pre-trafficking violence cost £88,633 more than patients for whom pre-trafficking violence was not

  13. A marginal structural model to estimate the causal effect of antidepressant medication treatment on viral suppression among homeless and marginally housed persons with HIV.

    Science.gov (United States)

    Tsai, Alexander C; Weiser, Sheri D; Petersen, Maya L; Ragland, Kathleen; Kushel, Margot B; Bangsberg, David R

    2010-12-01

    Depression strongly predicts nonadherence to human immunodeficiency virus (HIV) antiretroviral therapy, and adherence is essential to maintaining viral suppression. This suggests that pharmacologic treatment of depression may improve virologic outcomes. However, previous longitudinal observational analyses have inadequately adjusted for time-varying confounding by depression severity, which could yield biased estimates of treatment effect. Application of marginal structural modeling to longitudinal observation data can, under certain assumptions, approximate the findings of a randomized controlled trial. To determine whether antidepressant medication treatment increases the probability of HIV viral suppression. Community-based prospective cohort study with assessments conducted every 3 months. Community-based research field site in San Francisco, California. One hundred fifty-eight homeless and marginally housed persons with HIV who met baseline immunologic (CD4+ T-lymphocyte count, 13) inclusion criteria, observed from April 2002 through August 2007. Probability of achieving viral suppression to less than 50 copies/mL. Secondary outcomes of interest were probability of being on an antiretroviral therapy regimen, 7-day self-reported percentage adherence to antiretroviral therapy, and probability of reporting complete (100%) adherence. Marginal structural models estimated a 2.03 greater odds of achieving viral suppression (95% confidence interval [CI], 1.15-3.58; P = .02) resulting from antidepressant medication treatment. In addition, antidepressant medication use increased the probability of antiretroviral uptake (weighted odds ratio, 3.87; 95% CI, 1.98-7.58; P effect is likely attributable to improved adherence to a continuum of HIV care, including increased uptake and adherence to antiretroviral therapy.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. BPIFB6 Regulates Secretory Pathway Trafficking and Enterovirus Replication.

    Science.gov (United States)

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

    2016-05-15

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

  19. BPIFB6 Regulates Secretory Pathway Trafficking and Enterovirus Replication

    Science.gov (United States)

    Morosky, Stefanie; Lennemann, Nicholas J.

    2016-01-01

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

  20. 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

  1. 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.

  2. Anti-respiratory syncytial virus (RSV) G monoclonal antibodies reduce lung inflammation and viral lung titers when delivered therapeutically in a BALB/c mouse model.

    Science.gov (United States)

    Caidi, Hayat; Miao, Congrong; Thornburg, Natalie J; Tripp, Ralph A; Anderson, Larry J; Haynes, Lia M

    2018-06-01

    RSV continues to be a high priority for vaccine and antiviral drug development. Unfortunately, no safe and effective RSV vaccine is available and treatment options are limited. Over the past decade, several studies have focused on the role of RSV G protein on viral entry, viral neutralization, and RSV-mediated pathology. Anti-G murine monoclonal antibody (mAb) 131-2G treatment has been previously shown to reduce weight loss, bronchoalveolar lavage (BAL) cell number, airway reactivity, and Th2-type cytokine production in RSV-infected mice more rapidly than a commercial humanized monoclonal antibody (mAb) against RSV F protein (Palivizumab). In this study, we have tested two human anti-RSV G mAbs, 2B11 and 3D3, by both prophylactic and therapeutic treatment for RSV in the BALB/c mouse model. Both anti-G mAbs reduced viral load, leukocyte infiltration and IFN-γ and IL-4 expression in cell-free BAL supernatants emphasizing the potential of anti-G mAbs as anti-inflammatory and antiviral strategies. Published by Elsevier B.V.

  3. Estimating the timing of mother-to-child transmission of the human immunodeficiency virus type 1 using a viral molecular evolution model.

    Directory of Open Access Journals (Sweden)

    Antoine Chaillon

    Full Text Available Mother-to-child transmission (MTCT is responsible for most pediatric HIV-1 infections worldwide. It can occur during pregnancy, labor, or breastfeeding. Numerous studies have used coalescent and molecular clock methods to understand the epidemic history of HIV-1, but the timing of vertical transmission has not been studied using these methods. Taking advantage of the constant accumulation of HIV genetic variation over time and using longitudinally sampled viral sequences, we used a coalescent approach to investigate the timing of MTCT.Six-hundred and twenty-two clonal env sequences from the RNA and DNA viral population were longitudinally sampled from nine HIV-1 infected mother-and-child pairs [range: 277-1034 days]. For each transmission pair, timing of MTCT was determined using a coalescent-based model within a Bayesian statistical framework. Results were compared with available estimates of MTCT timing obtained with the classic biomedical approach based on serial HIV DNA detection by PCR assays.Four children were infected during pregnancy, whereas the remaining five children were infected at time of delivery. For eight out of nine pairs, results were consistent with the transmission periods assessed by standard PCR-based assay. The discordance in the remaining case was likely confused by co-infection, with simultaneous introduction of multiple maternal viral variants at the time of delivery.The study provided the opportunity to validate the Bayesian coalescent approach that determines the timing of MTCT of HIV-1. It illustrates the power of population genetics approaches to reliably estimate the timing of transmission events and deepens our knowledge about the dynamics of viral evolution in HIV-infected children, accounting for the complexity of multiple transmission events.

  4. 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...

  5. 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

  6. 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...

  7. Bacterial, viral and turbidity removal by intermittent slow sand filtration for household use in developing countries: experimental investigation and modeling.

    Science.gov (United States)

    Jenkins, Marion W; Tiwari, Sangam K; Darby, Jeannie

    2011-11-15

    A two-factor three-block experimental design was developed to permit rigorous evaluation and modeling of the main effects and interactions of sand size (d(10) of 0.17 and 0.52 mm) and hydraulic head (10, 20, and 30 cm) on removal of fecal coliform (FC) bacteria, MS2 bacteriophage virus, and turbidity, under two batch operating modes ('long' and 'short') in intermittent slow sand filters (ISSFs). Long operation involved an overnight pause time between feeding of two successive 20 L batches (16 h average batch residence time (RT)). Short operation involved no pause between two 20 L batch feeds (5h average batch RT). Conditions tested were representative of those encountered in developing country field settings. Over a ten week period, the 18 experimental filters were fed river water augmented with wastewater (influent turbidity of 5.4-58.6 NTU) and maintained with the wet harrowing method. Linear mixed modeling allowed systematic estimates of the independent marginal effects of each independent variable on each performance outcome of interest while controlling for the effects of variations in a batch's actual residence time, days since maintenance, and influent turbidity. This is the first study in which simultaneous measurement of bacteria, viruses and turbidity removal at the batch level over an extended duration has been undertaken with a large number of replicate units to permit rigorous modeling of ISSF performance variability within and across a range of likely filter design configurations and operating conditions. On average, the experimental filters removed 1.40 log fecal coliform CFU (SD 0.40 log, N=249), 0.54 log MS2 PFU (SD 0.42 log, N=245) and 89.0 percent turbidity (SD 6.9 percent, N=263). Effluent turbidity averaged 1.24 NTU (SD 0.53 NTU, N=263) and always remained below 3 NTU. Under the best performing design configuration and operating mode (fine sand, 10 cm head, long operation, initial HLR of 0.01-0.03 m/h), mean 1.82 log removal of bacteria (98

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

    Directory of Open Access Journals (Sweden)

    Nidhi Shrivastava

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

  9. Women and citizenship post-trafficking: the case of Nepal.

    Science.gov (United States)

    Richardson, Diane; Laurie, Nina; Poudel, Meena; Townsend, Janet

    2016-05-01

    This article analyses the relationship between gender, sexuality and citizenship embedded in models of citizenship in the Global South, specifically in South Asia, and the meanings associated with having - or not having - citizenship. It does this through an examination of women's access to citizenship in Nepal in the context of the construction of the emergent nation state in the 'new' Nepal 'post-conflict'. Our analysis explores gendered and sexualized constructions of citizenship in this context through a specific focus on women who have experienced trafficking, and are beginning to organize around rights to sustainable livelihoods and actively lobby for changes in citizenship rules which discriminate against women. Building from this, in the final section we consider important implications of this analysis of post-trafficking experiences for debates about gender, sexuality and citizenship more broadly.

  10. Women and citizenship post‐trafficking: the case of Nepal

    Science.gov (United States)

    Richardson, Diane; Laurie, Nina; Poudel, Meena; Townsend, Janet

    2016-01-01

    Abstract This article analyses the relationship between gender, sexuality and citizenship embedded in models of citizenship in the Global South, specifically in South Asia, and the meanings associated with having – or not having – citizenship. It does this through an examination of women's access to citizenship in Nepal in the context of the construction of the emergent nation state in the ‘new’ Nepal ‘post‐conflict’. Our analysis explores gendered and sexualized constructions of citizenship in this context through a specific focus on women who have experienced trafficking, and are beginning to organize around rights to sustainable livelihoods and actively lobby for changes in citizenship rules which discriminate against women. Building from this, in the final section we consider important implications of this analysis of post‐trafficking experiences for debates about gender, sexuality and citizenship more broadly. PMID:27642193

  11. 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

  12. 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.

  13. Measures for prevention illicit trafficking of nuclear and radioactive materials

    International Nuclear Information System (INIS)

    Strezov, A.

    2002-01-01

    Full text: In the early 1990ies the number of illicit trafficking cases with nuclear material and radioactive sources began to appear in the press more often than before. This fact became of great concern among international organizations and different states that the nuclear material subjected to trafficking might become in possession of rogue states and be implicated in weapons production or that stolen radioactive sources may cause health and safety effects to the population or to the environment. The creation and proposition of a model scheme procedure for the developing countries is important for starting the initial process of preventing and combating the illicit traffic of nuclear materials. Particular efforts have been directed for the protection of fissile materials. The reported incidents for diversion of nuclear materials have raised the problem of potential nuclear terrorism and also for countries of proliferation to take a short cut to the bomb. There is a need of rapid implementation of comprehensive, mutually reinforcing strategy to control the existing stockpiles of fissile material and to lower the future production and use of such materials. The illicit traffic of nuclear materials is a new threat, which requires new efforts, new approaches and coordination of services and institutions and even new legislation. The propositions of a model-procedure will allow better and quicker upgrade of developing countries capabilities for combating illicit nuclear trafficking. (author)

  14. 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...

  15. 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

  16. The influence of value judgments about the existence of free will in prostitution on shaping criminal justice response to human trafficking

    OpenAIRE

    Ristivojević, Branislav

    2015-01-01

    Starting from the unbreakable bond that exists between human trafficking and prostitution, the author explores in the paper the issue of the influence of value judgments about the existence of free will in prostitution on shaping criminal justice responses to human trafficking. Two possible answers to this question also create two models of criminal-political responses to human trafficking. The author criticizes the first one, which does not recognize the freedom of will, because besides the ...

  17. Effects of state-level firearm seller accountability policies on firearm trafficking.

    Science.gov (United States)

    Webster, Daniel W; Vernick, Jon S; Bulzacchelli, Maria T

    2009-07-01

    Criminals illegally obtaining firearms represent a great risk to many urban residents. This cross-sectional study of 54 US cities uses data on state laws governing gun sales, a survey of law enforcement agencies' practices to promote compliance with gun sales laws, and crime gun trace data to examine associations between these policies and practices with gun trafficking indicators. Higher levels of local gun ownership were linked with greater intrastate gun trafficking. Regression models estimate that comprehensive regulation and oversight of gun dealers and state regulation of private sales of handguns were each associated with significantly lower levels of intrastate gun trafficking. Discretionary permit-to-purchase licensing laws' negative association with intrastate trafficking disappeared when local gun ownership is controlled. The effects of these relatively restrictive gun purchase laws on trafficking may be mediated by the laws' lowering of gun ownership. Relatively low prevalence of gun ownership may also be a prerequisite for passage of discretionary purchase. We observed no effect on intrastate trafficking of laws limiting handgun sales to a maximum of one per person per month.

  18. Characterizing Class-Specific Exposure-Viral Load Suppression Response of HIV Antiretrovirals Using A Model-Based Meta-Analysis.

    Science.gov (United States)

    Xu, Y; Li, Y F; Zhang, D; Dockendorf, M; Tetteh, E; Rizk, M L; Grobler, J A; Lai, M-T; Gobburu, J; Ankrom, W

    2016-08-01

    We applied model-based meta-analysis of viral suppression as a function of drug exposure and in vitro potency for short-term monotherapy in human immunodeficiency virus type 1 (HIV-1)-infected treatment-naïve patients to set pharmacokinetic targets for development of nonnucleoside reverse transcriptase inhibitors (NNRTIs) and integrase strand transfer inhibitors (InSTIs). We developed class-specific models relating viral load kinetics from monotherapy studies to potency normalized steady-state trough plasma concentrations. These models were integrated with a literature assessment of doses which demonstrated to have long-term efficacy in combination therapy, in order to set steady-state trough concentration targets of 6.17- and 2.15-fold above potency for NNRTIs and InSTIs, respectively. Both the models developed and the pharmacokinetic targets derived can be used to guide compound selection during preclinical development and to predict the dose-response of new antiretrovirals to inform early clinical trial design. © 2016 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  19. “We have the right not to be ‘rescued’...”*: When Anti-Trafficking Programmes Undermine the Health and Well-Being of Sex Workers

    Directory of Open Access Journals (Sweden)

    Aziza Ahmed

    2012-06-01

    Full Text Available This paper highlights the impact of raid, rescue, and rehabilitation schemes on HIV programmes. It uses a case study of Veshya Anyay Mukti Parishad (VAMP, a sex workers collective in Sangli, India, to explore the impact of anti-trafficking efforts on HIV prevention programmes. The paper begins with an overview of the anti-trafficking movement emerging out of the United States. This U.S. based anti- trafficking movement works in partnership with domestic Indian anti- trafficking organisations to raid brothels to “rescue and rehabilitate” sex workers. Contrary to the purported goal of assisting women, the anti-trafficking projects that employ a raid, rescue, and rehabilitate model often undermine HIV projects at the local level, in turn causing harm to women and girls. We examine the experience of one peer educator in Sangli to demonstrate and highlight some of the negative consequences of these anti-trafficking efforts on HIV prevention programmes.

  20. 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.

  1. Viral pathogen discovery

    Science.gov (United States)

    Chiu, Charles Y

    2015-01-01

    Viral pathogen discovery is of critical importance to clinical microbiology, infectious diseases, and public health. Genomic approaches for pathogen discovery, including consensus polymerase chain reaction (PCR), microarrays, and unbiased next-generation sequencing (NGS), have the capacity to comprehensively identify novel microbes present in clinical samples. Although numerous challenges remain to be addressed, including the bioinformatics analysis and interpretation of large datasets, these technologies have been successful in rapidly identifying emerging outbreak threats, screening vaccines and other biological products for microbial contamination, and discovering novel viruses associated with both acute and chronic illnesses. Downstream studies such as genome assembly, epidemiologic screening, and a culture system or animal model of infection are necessary to establish an association of a candidate pathogen with disease. PMID:23725672

  2. Mobil Viral Pazarlama

    OpenAIRE

    Barutçu, Süleyman

    2011-01-01

    OBJECTIVE: Mobile Viral Marketing, with using mobile phones, is one of the most importantinnovations after Word of Mouth Marketing performed by face to face amongpeople and Viral Marketing performed in the İnternet. The main objective of thisstudy is to call marketing communicators’ and academicians’ attentions whowant to increase the recognition of companies’ products, services and brands tobecome a current issue in the marketplace using Mobile Viral Marketingapplications by reason of techno...

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. Risk factors for mental disorders in women survivors of human trafficking: a historical cohort study

    Science.gov (United States)

    2013-01-01

    Background Previous studies have found high levels of symptoms of depression, anxiety, and post-traumatic stress disorder among women survivors of human trafficking. No previous research has described risk factors for diagnosed mental disorders in this population. Methods A historical cohort study of women survivors of trafficked women aged 18 and over who returned to Moldova and registered for assistance with the International Organisation for Migration (IOM). Women were approached by IOM social workers and, if they gave informed consented to participate in the study, interviewed by the research team. At 2–12 months post-return to Moldova, a psychiatrist assessed DSM-IV mental disorders blind to information about women’s pre-trafficking and post-trafficking experiences using the Structured Clinical Interview for DSM-IV (SCID). A backwards stepwise selection procedure was used to create a multivariable regression model of risk factors for DSM-IV mental disorder measured at an average of 6 months post-return. Results 120/176 (68%) eligible women participated. At an average of 6 months post-return, 54% met criteria for any DSM-IV mental disorder: 35.8% of women had PTSD (alone or co-morbid), 12.5% had depression without PTSD and 5.8% had another anxiety disorder. Multivariable regression analysis found that childhood sexual abuse (Adjusted Odds Ratio [AOR] 4.68, 95% CI 1.04-20.92), increased number of post-trafficking unmet needs (AOR 1.80; 95% CI 1.28-2.52) and post-trafficking social support (AOR 0.64; 95% CI 0.52-0.79) were independent risk factors for mental disorder, and that duration of trafficking showed a borderline association with mental disorder (AOR 1.12, 95% CI 0.98-1.29). Conclusions Assessment for mental disorders should be part of re-integration follow-up care for women survivors of human trafficking. Mental disorders at that time, most commonly PTSD and depression, are likely to be influenced by a range of predisposing, precipitating and

  8. Risk factors for mental disorders in women survivors of human trafficking: a historical cohort study.

    Science.gov (United States)

    Abas, Melanie; Ostrovschi, Nicolae V; Prince, Martin; Gorceag, Viorel I; Trigub, Carolina; Oram, Siân

    2013-08-03

    Previous studies have found high levels of symptoms of depression, anxiety, and post-traumatic stress disorder among women survivors of human trafficking. No previous research has described risk factors for diagnosed mental disorders in this population. A historical cohort study of women survivors of trafficked women aged 18 and over who returned to Moldova and registered for assistance with the International Organisation for Migration (IOM). Women were approached by IOM social workers and, if they gave informed consented to participate in the study, interviewed by the research team. At 2-12 months post-return to Moldova, a psychiatrist assessed DSM-IV mental disorders blind to information about women's pre-trafficking and post-trafficking experiences using the Structured Clinical Interview for DSM-IV (SCID). A backwards stepwise selection procedure was used to create a multivariable regression model of risk factors for DSM-IV mental disorder measured at an average of 6 months post-return. 120/176 (68%) eligible women participated. At an average of 6 months post-return, 54% met criteria for any DSM-IV mental disorder: 35.8% of women had PTSD (alone or co-morbid), 12.5% had depression without PTSD and 5.8% had another anxiety disorder. Multivariable regression analysis found that childhood sexual abuse (Adjusted Odds Ratio [AOR] 4.68, 95% CI 1.04-20.92), increased number of post-trafficking unmet needs (AOR 1.80; 95% CI 1.28-2.52) and post-trafficking social support (AOR 0.64; 95% CI 0.52-0.79) were independent risk factors for mental disorder, and that duration of trafficking showed a borderline association with mental disorder (AOR 1.12, 95% CI 0.98-1.29). Assessment for mental disorders should be part of re-integration follow-up care for women survivors of human trafficking. Mental disorders at that time, most commonly PTSD and depression, are likely to be influenced by a range of predisposing, precipitating and maintaining factors. Care plans for survivors of

  9. The Importance of Justice Restorative to Combat Drug Trafficking

    Directory of Open Access Journals (Sweden)

    Henrique Ribeiro Cardoso

    2016-12-01

    Full Text Available Over the last few decades, the criminal model of retributive justice has been challenged for not being suitable for the prevention and repression of criminality in Brazil. The high incarceration rate has increased with the number of drug trafficking prisoners which leads to, consequently, a formulation of criminal policy on the standard punitive model rather effective alternative forms, or less harmful for solving the problem. Its commercial nature at the same time reveals the importance for the consummation of the crime opening the possibilities for insertion of the extensive restorative practices, which exceeds the legally allowed.

  10. 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.

  11. 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.

  12. 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.

  13. 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...

  14. 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.

  15. 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.

  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. [Emergent viral infections

    NARCIS (Netherlands)

    Galama, J.M.D.

    2001-01-01

    The emergence and re-emergence of viral infections is an ongoing process. Large-scale vaccination programmes led to the eradication or control of some viral infections in the last century, but new viruses are always emerging. Increased travel is leading to a rise in the importation of exotic

  18. Viral Haemorrhagic Septicaemia Virus

    DEFF Research Database (Denmark)

    Olesen, Niels Jørgen; Skall, Helle Frank

    2013-01-01

    This chapter covers the genetics (genotypes and serotypes), clinical signs, host species, transmission, prevalence, diagnosis, control and prevention of viral haemorrhagic septicaemia virus.......This chapter covers the genetics (genotypes and serotypes), clinical signs, host species, transmission, prevalence, diagnosis, control and prevention of viral haemorrhagic septicaemia virus....

  19. 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-viral

  20. A spatio-temporal analysis of forest loss related to cocaine trafficking in Central America

    Science.gov (United States)

    Sesnie, Steven E.; Tellman, Beth; Wrathall, David; McSweeney, Kendra; Nielsen, Erik; Benessaiah, Karina; Wang, Ophelia; Rey, Luis

    2017-05-01

    A growing body of evidence suggests that criminal activities associated with drug trafficking networks are a progressively important driver of forest loss in Central America. However, the scale at which drug trafficking represents a driver of forest loss is not presently known. We estimated the degree to which narcotics trafficking may contribute to forest loss using an unsupervised spatial clustering of 15 spatial and temporal forest loss patch metrics developed from global forest change data. We distinguished anomalous forest loss from background loss patches for each country exhibiting potential ‘narco-capitalized’ signatures which showed a statistically significant dissimilarity from other patches in terms of size, timing, and rate of forest loss. We also compared annual anomalous forest loss with the number of cocaine shipments and volume of cocaine seized, lost, or delivered at country- and department-level. For Honduras, results from linear mixed effects models showed a highly significant relationship between anomalous forest loss and the timing of increased drug trafficking (F = 9.90, p = 0.009) that also differed significantly from temporal patterns of background forest loss (t-ratio = 2.98, p = 0.004). Other locations of high forest loss in Central America showed mixed results. The timing of increased trafficking was not significantly related to anomalous forest loss in Guatemala and Nicaragua, but significantly differed in patch size compared to background losses. We estimated that cocaine trafficking could account for between 15% and 30% of annual national forest loss in these three countries over the past decade, and 30% to 60% of loss occurred within nationally and internationally designated protected areas. Cocaine trafficking is likely to have severe and lasting consequences in terms of maintaining moist tropical forest cover in Central America. Addressing forest loss in these and other tropical locations will require a stronger

  1. Preliminary perspectives on DNA collection in anti-human trafficking efforts.

    Science.gov (United States)

    Katsanis, Sara H; Kim, Joyce; Minear, Mollie A; Chandrasekharan, Subhashini; Wagner, Jennifer K

    2014-01-01

    Forensic DNA methodologies have potential applications in the investigation of human trafficking cases. DNA and relationship testing may be useful for confirmation of biological relationship claims in immigration, identification of trafficked individuals who are missing persons, and family reunification of displaced individuals after mass disasters and conflicts. As these applications rely on the collection of DNA from non-criminals and potentially vulnerable individuals, questions arise as to how to address the ethical challenges of collection, security, and privacy of collected samples and DNA profiles. We administered a survey targeted to victims' advocates to gain preliminary understanding of perspectives regarding human trafficking definitions, DNA and sex workers, and perceived trust of authorities potentially involved in DNA collection. We asked respondents to consider the use of DNA for investigating adoption fraud, sex trafficking, and post-conflict child soldier cases. We found some key differences in perspectives on defining what qualifies as "trafficking." When we varied terminology between "sex worker" and "sex trafficking victim" we detected differences in perception on which authorities can be trusted. Respondents were supportive of the hypothetical models proposed to collect DNA. Most were favorable of DNA specimens being controlled by an authority outside of law enforcement. Participants voiced concerns focused on privacy, misuse of DNA samples and data, unintentional harms, data security, and infrastructure. These preliminary data indicate that while there is perceived value in programs to use DNA for investigating cases of human trafficking, these programs may need to consider levels of trust in authorities as their logistics are developed and implemented.

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. Viral Disease Networks?

    Science.gov (United States)

    Gulbahce, Natali; Yan, Han; Vidal, Marc; Barabasi, Albert-Laszlo

    2010-03-01

    Viral infections induce multiple perturbations that spread along the links of the biological networks of the host cells. Understanding the impact of these cascading perturbations requires an exhaustive knowledge of the cellular machinery as well as a systems biology approach that reveals how individual components of the cellular system function together. Here we describe an integrative method that provides a new approach to studying virus-human interactions and its correlations with diseases. Our method involves the combined utilization of protein - protein interactions, protein -- DNA interactions, metabolomics and gene - disease associations to build a ``viraldiseasome''. By solely using high-throughput data, we map well-known viral associated diseases and predict new candidate viral diseases. We use microarray data of virus-infected tissues and patient medical history data to further test the implications of the viral diseasome. We apply this method to Epstein-Barr virus and Human Papillomavirus and shed light into molecular development of viral diseases and disease pathways.

  8. 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...

  9. 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...

  10. 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.

  11. 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.

  12. 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,…

  13. 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…

  14. 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 ...

  15. Actinobacteria from Termite Mounds Show Antiviral Activity against Bovine Viral Diarrhea Virus, a Surrogate Model for Hepatitis C Virus

    Directory of Open Access Journals (Sweden)

    Marina Aiello Padilla

    2015-01-01

    Full Text Available Extracts from termite-associated bacteria were evaluated for in vitro antiviral activity against bovine viral diarrhea virus (BVDV. Two bacterial strains were identified as active, with percentages of inhibition (IP equal to 98%. Both strains were subjected to functional analysis via the addition of virus and extract at different time points in cell culture; the results showed that they were effective as posttreatments. Moreover, we performed MTT colorimetric assays to identify the CC50, IC50, and SI values of these strains, and strain CDPA27 was considered the most promising. In parallel, the isolates were identified as Streptomyces through 16S rRNA gene sequencing analysis. Specifically, CDPA27 was identified as S. chartreusis. The CDPA27 extract was fractionated on a C18-E SPE cartridge, and the fractions were reevaluated. A 100% methanol fraction was identified to contain the compound(s responsible for antiviral activity, which had an SI of 262.41. GC-MS analysis showed that this activity was likely associated with the compound(s that had a peak retention time of 5 min. Taken together, the results of the present study provide new information for antiviral research using natural sources, demonstrate the antiviral potential of Streptomyces chartreusis compounds isolated from termite mounds against BVDV, and lay the foundation for further studies on the treatment of HCV infection.

  16. Lymphocyte trafficking and HIV infection of human lymphoid tissue in a rotating wall vessel bioreactor

    Science.gov (United States)

    Margolis, L. B.; Fitzgerald, W.; Glushakova, S.; Hatfill, S.; Amichay, N.; Baibakov, B.; Zimmerberg, J.

    1997-01-01

    The pathogenesis of HIV infection involves a complex interplay between both the infected and noninfected cells of human lymphoid tissue, the release of free viral particles, the de novo infection of cells, and the recirculatory trafficking of peripheral blood lymphocytes. To develop an in vitro model for studying these various aspects of HIV pathogenesis we have utilized blocks of surgically excised human tonsils and a rotating wall vessel (RWV) cell culture system. Here we show that (1) fragments of the surgically excised human lymphoid tissue remain viable and retain their gross cytoarchitecture for at least 3 weeks when cultured in the RWV system; (2) such lymphoid tissue gradually shows a loss of both T and B cells to the surrounding growth medium; however, this cellular migration is reversible as demonstrated by repopulation of the tissue by labeled cells from the growth medium; (3) this cellular migration may be partially or completely inhibited by embedding the blocks of lymphoid tissue in either a collagen or agarose gel matrix; these embedded tissue blocks retain most of the basic elements of a normal lymphoid cytoarchitecture; and (4) both embedded and nonembedded RWV-cultured blocks of human lymphoid tissue are capable of productive infection by HIV-1 of at least three various strains of different tropism and phenotype, as shown by an increase in both p24 antigen levels and free virus in the culture medium, and by the demonstration of HIV-1 RNA-positive cells inside the tissue identified by in situ hybridization. It is therefore reasonable to suggest that gel-embedded and nonembedded blocks of human lymphoid tissue, cocultured with a suspension of tonsillar lymphocytes in an RWV culture system, constitute a useful model for simulating normal lymphocyte recirculatory traffic and provide a new tool for testing the various aspects of HIV pathogenesis.

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

    OpenAIRE

    Joy N Ezeilo

    2015-01-01

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

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

    OpenAIRE

    Kruger, H B; Oosthuizen, H

    2012-01-01

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

  19. Nuclear trafficking of proteins from RNA viruses: potential target for antivirals?

    Science.gov (United States)

    Caly, Leon; Wagstaff, Kylie M; Jans, David A

    2012-09-01

    A key aspect of the infectious cycle of many viruses is the transport of specific viral proteins into the host cell nucleus to perturb the antiviral response. Examples include a number of RNA viruses that are significant human pathogens, such as human immunodeficiency virus (HIV)-1, influenza A, dengue, respiratory syncytial virus and rabies, as well agents that predominantly infect livestock, such as Rift valley fever virus and Venezuelan equine encephalitis virus. Inhibiting the nuclear trafficking of viral proteins as a therapeutic strategy offers an attractive possibility, with important recent progress having been made with respect to HIV-1 and dengue. The results validate nuclear protein import as an antiviral target, and suggest the identification and development of nuclear transport inhibitors as a viable therapeutic approach for a range of human and zoonotic pathogenic viruses. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. 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…

  1. Combating human trafficking in the sex trade: can sex workers do it better?

    Science.gov (United States)

    Jana, Smarajit; Dey, Bharati; Reza-Paul, Sushena; Steen, Richard

    2014-12-01

    The dominant anti-trafficking paradigm conflates trafficking and sex work, denying evidence that most sex workers choose their profession and justifying police actions that disrupt communities, drive sex workers underground and increase vulnerability. We review an alternative response to combating human trafficking and child prostitution in the sex trade, the self-regulatory board (SRB) developed by Durbar Mahila Samanwaya Committee (DMSC, Sonagachi). DMSC-led interventions to remove minors and unwilling women from sex work account for over 80% of successful 'rescues' reported in West Bengal. From 2009 through 2011, 2195 women and girls were screened by SRBs: 170 (7.7%) minors and 45 (2.1%) unwilling adult women were assisted and followed up. The remaining 90.2% received counselling, health care and the option to join savings schemes and other community programmes designed to reduce sex worker vulnerability. Between 1992 and 2011 the proportion of minors in sex work in Sonagachi declined from 25 to 2%. With its universal surveillance of sex workers entering the profession, attention to rapid and confidential intervention and case management, and primary prevention of trafficking-including microcredit and educational programmes for children of sex workers-the SRB approach stands as a new model of success in anti-trafficking work. © The Author 2013. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. "The perfect business": human trafficking and Lao-Thai cross-border migration.

    Science.gov (United States)

    Molland, Sverre

    2010-01-01

    Over the past few years some governments and development organizations have increasingly articulated cross-border mobility as "trafficking in persons". The notion of a market where traffickers prey on the "supply" of migrants that flows across international borders to meet the "demand" for labour has become a central trope among anti-trafficking development organizations. This article problematizes such economism by drawing attention to the oscillating cross-border migration of Lao sex workers within a border zone between Laos and Thailand. It illuminates the incongruity between the recruitment of women into the sex industry along the Lao-Thai border and the market models that are employed by the anti-trafficking sector. It discusses the ways in which these cross-border markets are conceived in a context where aid programming is taking on an increasingly important role in the politics of borders. The author concludes that allusions to ideal forms of knowledge (in the guise of classic economic theory) and an emphasis on borders become necessary for anti-trafficking programmes in order to make their object of intervention legible as well as providing post-hoc rationalizations for their continuing operation.

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

    Science.gov (United States)

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

    2018-02-01

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

  4. A theory for aftercare of human trafficking survivors for nursing practice in low resource settings.

    Science.gov (United States)

    Curran, R L; Naidoo, J R; Mchunu, G

    2017-06-01

    Research on aftercare for human trafficking survivors highlights the limited knowledge of the needs of survivors; the evaluation of current aftercare; and the process of recovery navigated by the survivor in aftercare (Oram et al., 2012; Locke, 2010; Hacker & Cohen, 2012). Furthermore there has been a transition in aftercare where the victim or survivor, who before was seen as a passive victim of circumstance of their life and in need of therapeutic intervention, is now seen as having an active role in their recovery, thus facilitating recovery (Hacker & Cohen, 2012). The need for a theory grounded in survivor's voices therefore motivated this grounded theory study underpinned by Freire's (1970) Pedagogy of the oppressed. The aim of the theory is to inform nursing care of human trafficking survivors in low resource settings. The findings elicit a theoretical model of the renewed self, and the conditions that facilitate this process in care of human trafficking survivors. The recommendations of this paper may improve the nursing care provided to human trafficking survivors and equip nurses and other health professionals with the knowledge and skills to promote the renewing of human trafficking survivors. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Human Trafficking and Sexual Servitude: Organised Crime’s Involvement in Australia

    Directory of Open Access Journals (Sweden)

    Mark Langhorn

    2018-03-01

    Full Text Available This study examined the context of organised crime groups that traffic in people for the Australian sex industry. It is a qualitative study of twenty-one cases of human trafficking. The study found that criminal networks preyed on vulnerable females from countries such as Thailand, South Korea, and China. Victims were deceptively recruited with the cost of their travel to Australia held against them as a highly inflated debt. As a result, they find themselves forced into sex work to repay the debt. This study examined the attributes of the organised crime syndicates involved in the people trafficking and discussed the context in which they operate in Australia. The study used the Sleipnir framework to analyse organised crime groups and it is recommended that the Sleipnir model is integrated into future law enforcement activities in respect of human trafficking. The introduction of a standardised data and statistical collection tool in respect of human trafficking would provide law enforcement and intelligence agencies with a conceptual framework and a greater comprehensive description of human trafficking.

  6. 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.

  7. Understanding Image Virality

    Science.gov (United States)

    2015-06-07

    Example non-viral images. Figure 1: Top: Images with high viral scores in our dataset depict internet “celebrity” memes ex. “Grumpy Cat”; Bottom: Images...of images that is most similar to ours is the concurrently introduced viral meme generator of Wang et al., that combines NLP and Computer Vision (low...doing any of our tasks. The test included questions about widely spread Reddit memes and jargon so that anyone familiar with Reddit can easily get a high

  8. 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

  9. 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.

  10. 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.

  11. 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...

  12. 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…

  13. 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.

  14. 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...

  15. 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

  16. Towards a unified biological hypothesis for the BDNF Val66Met-associated memory deficits in humans: a model of impaired dendritic mRNA trafficking

    Directory of Open Access Journals (Sweden)

    Gabriele eBaj

    2013-10-01

    Full Text Available Brain-derived neurotrophic factor (BDNF represents promotesa key molecule for the survival and differentiation of specific populations of neurons in the central nervous system. BDNF also regulates plasticity-related processes underlying memory and learning. A common single nucleotide polymorphism (SNP rs6265 has been identified on the coding sequence of human BDNF located at 11p13. The SNP rs6265 is a single base mutation with an adenine instead of a guanine at position 196 (G196A, resulting in the amino acid substitution Val66Met. This polymorphism only exists in humans and has been associated with a plethora of effects ranging from molecular, cellular and brain structural modifications in association with deficits in social and cognitive functions. To date, the literature on Val66Met polymorphism describes a complex and often conflicting pattern of effects. In this review, we attempt to provide a unifying model of the Val66Met effects. We discuss the clinical evidence of the association between Val66Met and memory deficits, as well as the molecular mechanisms involved including the reduced transport of BDNF mRNA to the dendrites as well as the reduced processing and secretion of BDNF protein through the regulated secretory pathway.

  17. Remyelination Is Correlated with Regulatory T Cell Induction Following Human Embryoid Body-Derived Neural Precursor Cell Transplantation in a Viral Model of Multiple Sclerosis.

    Directory of Open Access Journals (Sweden)

    Warren C Plaisted

    Full Text Available We have recently described sustained clinical recovery associated with dampened neuroinflammation and remyelination following transplantation of neural precursor cells (NPCs derived from human embryonic stem cells (hESCs in a viral model of the human demyelinating disease multiple sclerosis. The hNPCs used in that study were derived by a novel direct differentiation method (direct differentiation, DD-NPCs that resulted in a unique gene expression pattern when compared to hNPCs derived by conventional methods. Since the therapeutic potential of human NPCs may differ greatly depending on the method of derivation and culture, we wanted to determine whether NPCs differentiated using conventional methods would be similarly effective in improving clinical outcome under neuroinflammatory demyelinating conditions. For the current study, we utilized hNPCs differentiated from a human induced pluripotent cell line via an embryoid body intermediate stage (EB-NPCs. Intraspinal transplantation of EB-NPCs into mice infected with the neurotropic JHM strain of mouse hepatitis virus (JHMV resulted in decreased accumulation of CD4+ T cells in the central nervous system that was concomitant with reduced demyelination at the site of injection. Dampened neuroinflammation and remyelination was correlated with a transient increase in CD4+FOXP3+ regulatory T cells (Tregs concentrated within the peripheral lymphatics. However, compared to our earlier study, pathological improvements were modest and did not result in significant clinical recovery. We conclude that the genetic signature of NPCs is critical to their effectiveness in this model of viral-induced neurologic disease. These comparisons will be useful for understanding what factors are critical for the sustained clinical improvement.

  18. Curcumin modulates the inflammatory response and inhibits subsequent fibrosis in a mouse model of viral-induced acute respiratory distress syndrome.

    Science.gov (United States)

    Avasarala, Sreedevi; Zhang, Fangfang; Liu, Guangliang; Wang, Ruixue; London, Steven D; London, Lucille

    2013-01-01

    Acute Respiratory Distress Syndrome (ARDS) is a clinical syndrome characterized by diffuse alveolar damage usually secondary to an intense host inflammatory response of the lung to a pulmonary or extrapulmonary infectious or non-infectious insult often leading to the development of intra-alveolar and interstitial fibrosis. Curcumin, the principal curcumoid of the popular Indian spice turmeric, has been demonstrated as an anti-oxidant and anti-inflammatory agent in a broad spectrum of diseases. Using our well-established model of reovirus 1/L-induced acute viral pneumonia, which displays many of the characteristics of the human ALI/ARDS, we evaluated the anti-inflammatory and anti-fibrotic effects of curcumin. Female CBA/J mice were treated with curcumin (50 mg/kg) 5 days prior to intranasal inoculation with 10(7)pfu reovirus 1/L and daily, thereafter. Mice were evaluated for key features associated with ALI/ARDS. Administration of curcumin significantly modulated inflammation and fibrosis, as revealed by histological and biochemical analysis. The expression of IL-6, IL-10, IFNγ, and MCP-1, key chemokines/cytokines implicated in the development of ALI/ARDS, from both the inflammatory infiltrate and whole lung tissue were modulated by curcumin potentially through a reduction in the phosphorylated form of NFκB p65. While the expression of TGFß1 was not modulated by curcumin, TGFß Receptor II, which is required for TGFß signaling, was significantly reduced. In addition, curcumin also significantly inhibited the expression of α-smooth muscle actin and Tenascin-C, key markers of myofibroblast activation. This data strongly supports a role for curcumin in modulating the pathogenesis of viral-induced ALI/ARDS in a pre-clinical model potentially manifested through the alteration of inflammation and myofibroblast differentiation.

  19. 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.

  20. Training US health care professionals on human trafficking: where do we go from here?

    Science.gov (United States)

    Powell, Clydette; Dickins, Kirsten; Stoklosa, Hanni

    2017-01-01

    Some 21 million adults and children are labor-trafficked or sex-trafficked through force, fraud, or coercion. In recognition of the interface between trafficking victims and the healthcare setting, over the last 10 years there has been a notable increase in training of health care professionals (HCPs) on human trafficking (HT) and its health implications. Many organizations have developed curricula and offered training in various clinical settings. However, methods and content of this education on trafficking vary widely, and there is little evaluation of the impact of the training. The goal of this study was to assess the gaps and strengths in HT education of HCPs in the US. This mixed-method study had two components. The first component consisted of structured interviews with experts in human trafficking HCP education. The second portion of the study involved an analysis of data from HCP calls to the National Human Trafficking Resource Center (NHTRC). The interviews captured trainer-specific data on types of HT training, duration and frequency, key content areas, presence of evaluation approaches and indicators, as well as an assessment of barriers and strengths in HT training for HCP. NHTRC call database analysis demonstrated increasing trends since 2008 in calls by HCPs. Overall findings revealed the need for standardization of HT training content to assure correct information, trauma-informed and patient-centered care, and consistent messaging for HCPs. Evaluation metrics for HT training need to be developed to demonstrate behavior change and impact on service delivery and patient-centered outcomes for HT victims, according to our proposed adapted Kirkpatrick's Pyramid model. HT training and evaluation would benefit from an agency or institution at the national level to provide consistency and standardization of HT training content as well as to guide a process that would develop metrics for evaluation and the building of an evidence base. AAP: American

  1. Training US health care professionals on human trafficking: where do we go from here?

    Science.gov (United States)

    Powell, Clydette; Dickins, Kirsten; Stoklosa, Hanni

    2017-01-01

    ABSTRACT Some 21 million adults and children are labor-trafficked or sex-trafficked through force, fraud, or coercion. In recognition of the interface between trafficking victims and the healthcare setting, over the last 10 years there has been a notable increase in training of health care professionals (HCPs) on human trafficking (HT) and its health implications. Many organizations have developed curricula and offered training in various clinical settings. However, methods and content of this education on trafficking vary widely, and there is little evaluation of the impact of the training. The goal of this study was to assess the gaps and strengths in HT education of HCPs in the US. This mixed-method study had two components. The first component consisted of structured interviews with experts in human trafficking HCP education. The second portion of the study involved an analysis of data from HCP calls to the National Human Trafficking Resource Center (NHTRC). The interviews captured trainer-specific data on types of HT training, duration and frequency, key content areas, presence of evaluation approaches and indicators, as well as an assessment of barriers and strengths in HT training for HCP. NHTRC call database analysis demonstrated increasing trends since 2008 in calls by HCPs. Overall findings revealed the need for standardization of HT training content to assure correct information, trauma-informed and patient-centered care, and consistent messaging for HCPs. Evaluation metrics for HT training need to be developed to demonstrate behavior change and impact on service delivery and patient-centered outcomes for HT victims, according to our proposed adapted Kirkpatrick’s Pyramid model. HT training and evaluation would benefit from an agency or institution at the national level to provide consistency and standardization of HT training content as well as to guide a process that would develop metrics for evaluation and the building of an evidence base

  2. Establishment and validation of a predictive nomogram model for non-small cell lung cancer patients with chronic hepatitis B viral infection.

    Science.gov (United States)

    Chen, Shulin; Lai, Yanzhen; He, Zhengqiang; Li, Jianpei; He, Xia; Shen, Rui; Ding, Qiuying; Chen, Hao; Peng, Songguo; Liu, Wanli

    2018-05-04

    This study aimed to establish an effective predictive nomogram for non-small cell lung cancer (NSCLC) patients with chronic hepatitis B viral (HBV) infection. The nomogram was based on a retrospective study of 230 NSCLC patients with chronic HBV infection. The predictive accuracy and discriminative ability of the nomogram were determined by a concordance index (C-index), calibration plot and decision curve analysis and were compared with the current tumor, node, and metastasis (TNM) staging system. Independent factors derived from Kaplan-Meier analysis of the primary cohort to predict overall survival (OS) were all assembled into a Cox proportional hazards regression model to build the nomogram model. The final model included age, tumor size, TNM stage, treatment, apolipoprotein A-I, apolipoprotein B, glutamyl transpeptidase and lactate dehydrogenase. The calibration curve for the probability of OS showed that the nomogram-based predictions were in good agreement with the actual observations. The C-index of the model for predicting OS had a superior discrimination power compared with the TNM staging system [0.780 (95% CI 0.733-0.827) vs. 0.693 (95% CI 0.640-0.746), P  20.0). The proposed nomogram model resulted in more accurate prognostic prediction for NSCLC patients with chronic HBV infection.

  3. Inhibition of human copper trafficking by a small molecule significantly attenuates cancer cell proliferation

    Science.gov (United States)

    Wang, Jing; Luo, Cheng; Shan, Changliang; You, Qiancheng; Lu, Junyan; Elf, Shannon; Zhou, Yu; Wen, Yi; Vinkenborg, Jan L.; Fan, Jun; Kang, Heebum; Lin, Ruiting; Han, Dali; Xie, Yuxin; Karpus, Jason; Chen, Shijie; Ouyang, Shisheng; Luan, Chihao; Zhang, Naixia; Ding, Hong; Merkx, Maarten; Liu, Hong; Chen, Jing; Jiang, Hualiang; He, Chuan

    2015-12-01

    Copper is a transition metal that plays critical roles in many life processes. Controlling the cellular concentration and trafficking of copper offers a route to disrupt these processes. Here we report small molecules that inhibit the human copper-trafficking proteins Atox1 and CCS, and so provide a selective approach to disrupt cellular copper transport. The knockdown of Atox1 and CCS or their inhibition leads to a significantly reduced proliferation of cancer cells, but not of normal cells, as well as to attenuated tumour growth in mouse models. We show that blocking copper trafficking induces cellular oxidative stress and reduces levels of cellular ATP. The reduced level of ATP results in activation of the AMP-activated protein kinase that leads to reduced lipogenesis. Both effects contribute to the inhibition of cancer cell proliferation. Our results establish copper chaperones as new targets for future developments in anticancer therapies.

  4. Caring for the Trafficked Patient: Ethical Challenges and Recommendations for Health Care Professionals.

    Science.gov (United States)

    Macias-Konstantopoulos, Wendy L

    2017-01-01

    Human trafficking is an egregious human rights violation with profound negative physical and psychological consequences, including communicable diseases, substance use disorders, and mental illnesses. The health needs of this population are multiple, complex, and influenced by past and present experiences of abuse, neglect, and exploitation. Effective health care services for trafficked patients require clinicians to consider individual patients' needs, wishes, goals, priorities, risks, and vulnerabilities as well as public health implications and even resource allocation. Applying the bioethical principles of respect for autonomy, nonmaleficence, beneficence, and justice, this article considers the ethics of care model as a trauma-informed framework for providing health care to human trafficking victims and survivors. © 2017 American Medical Association. All Rights Reserved.

  5. Trafficking of endoplasmic reticulum-retained recombinant proteins is unpredictable in Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Thomas eDe Meyer

    2014-09-01

    Full Text Available A wide variety of recombinant proteins has been produced in the dicot model plant, Arabidopsis thaliana. Many of these proteins are targeted for secretion by means of an N terminal endoplasmic reticulum (ER signal peptide. In addition, they can also be designed for ER retention by adding a C terminal H/KDEL-tag. Despite extensive knowledge of the protein trafficking pathways, the final protein destination, especially of such H/KDEL-tagged recombinant proteins, is unpredictable. In this respect, glycoproteins are ideal study objects. Microscopy experiments reveal their deposition pattern and characterization of their N-glycans aids in elucidating the trafficking. Here, we combine microscopy and N glycosylation data generated in Arabidopsis leaves and seeds, and highlight the lack of a decent understanding of heterologous protein trafficking.

  6. Viral hemorrhagic septicemia

    Science.gov (United States)

    Batts, William N.; Winton, James R.

    2012-01-01

    Viral hemorrhagic septicemia (VHS) is one of the most important viral diseases of finfish worldwide. In the past, VHS was thought to affect mainly rainbow trout Oncorhynchus mykiss reared at freshwater facilities in Western Europe where it was known by various names including Egtved disease and infectious kidney swelling and liver degeneration (Wolf 1988). Today, VHS is known as an important source of mortality for cultured and wild fish in freshwater and marine environments in several regions of the northern hemisphere (Dixon 1999; Gagné et al. 2007; Kim and Faisal 2011; Lumsden et al. 2007; Marty et al. 1998, 2003; Meyers and Winton 1995; Skall et al. 2005b; Smail 1999; Takano et al. 2001). Viral hemorrhagic septicemia is caused by the fish rhabdovirus, viral hemorrhagic septicemia virus (VHSV), a member of the genus Novirhabdovirus of the family Rhabdoviridae

  7. Hepatitis viral aguda

    Directory of Open Access Journals (Sweden)

    Héctor Rubén Hernández Garcés

    1998-10-01

    Full Text Available Se realizó una revisión bibliográfica de las hepatitis virales agudas sobre aspectos vinculados a su etiología. Se tuvieron en cuenta además algunos datos epidemiológicos, las formas clínicas más importantes, los exámenes complementarios con especial énfasis en los marcadores virales y el diagnóstico positivoA bibliographical review of acute viral hepatitis was made taking into account those aspects connected with its etiology. Some epidemiological markers, the most important clinical forms, and the complementary examinations with special emphasis on the viral markers and the positive diagnosis were also considered

  8. Wastewater viral community

    Data.gov (United States)

    U.S. Environmental Protection Agency — The dataset contains the information used to generate the figures in the manuscript. The data describes the viral loss measured at all steps of sample processing,...

  9. Viral pathogenesis in diagrams

    National Research Council Canada - National Science Library

    Tremblay, Michel; Berthiaume, Laurent; Ackermann, Hans-Wolfgang

    2001-01-01

    .... The 268 diagrams in Viral Pathogenesis in Diagrams were selected from over 800 diagrams of English and French virological literature, including one derived from a famous drawing by Leonardo da Vinci...

  10. Metabolism goes viral.

    Science.gov (United States)

    Miyake-Stoner, Shigeki J; O'Shea, Clodagh C

    2014-04-01

    Viral and cellular oncogenes converge in targeting critical protein interaction networks to reprogram the cellular DNA and protein replication machinery for pathological replication. In this issue, Thai et al. (2014) show that adenovirus E4ORF1 activates MYC glycolytic targets to induce a Warburg-like effect that converts glucose into nucleotides for viral replication. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Perturbed cholesterol and vesicular trafficking associated with dengue blocking in Wolbachia-infected Aedes aegypti cells.

    Science.gov (United States)

    Geoghegan, Vincent; Stainton, Kirsty; Rainey, Stephanie M; Ant, Thomas H; Dowle, Adam A; Larson, Tony; Hester, Svenja; Charles, Philip D; Thomas, Benjamin; Sinkins, Steven P

    2017-09-13

    Wolbachia are intracellular maternally inherited bacteria that can spread through insect populations and block virus transmission by mosquitoes, providing an important approach to dengue control. To better understand the mechanisms of virus inhibition, we here perform proteomic quantification of the effects of Wolbachia in Aedes aegypti mosquito cells and midgut. Perturbations are observed in vesicular trafficking, lipid metabolism and in the endoplasmic reticulum that could impact viral entry and replication. Wolbachia-infected cells display a differential cholesterol profile, including elevated levels of esterified cholesterol, that is consistent with perturbed intracellular cholesterol trafficking. Cyclodextrins have been shown to reverse lipid accumulation defects in cells with disrupted cholesterol homeostasis. Treatment of Wolbachia-infected Ae. aegypti cells with 2-hydroxypropyl-β-cyclodextrin restores dengue replication in Wolbachia-carrying cells, suggesting dengue is inhibited in Wolbachia-infected cells by localised cholesterol accumulation. These results demonstrate parallels between the cellular Wolbachia viral inhibition phenotype and lipid storage genetic disorders. Wolbachia infection of mosquitoes can block dengue virus infection and is tested in field trials, but the mechanism of action is unclear. Using proteomics, Geoghegan et al. here identify effects of Wolbachia on cholesterol homeostasis and dengue virus replication in Aedes aegypti.

  12. Financial Capability and Sociodemographic Factors among Survivors of Human Trafficking.

    Science.gov (United States)

    Okech, David; McGarity, Stephen Vandiver; Hansen, Nathan; Burns, Abigail C; Howard, Waylon

    2018-01-01

    Improving the economic well-being of the girls and women is a key to reducing re-trafficking and in providing stability that survivors can use to rebuild their lives. The study looks at how various sociodemographic traits affected the financial capability of n = 144 women and girls who received intervention at a residential care facility in Ghana, West Africa. Three domain of financial capability are assessed in this, i.e., financial risk, financial planning, and financial saving. A scaled likelihood ratio test (chi-square difference test) was used to evaluate the significance of each direct covariate effect(%). Each of the overall goodness-of-fit indices suggested that the initial CFA model fit the data well, χ 2 (19, N = 144)  = 31.45, p = 0.04, RMSEA = 0.067 (90% CI: 0.017-0.108), TLI = 0.923, CFI = 0.948. Older women reported lower levels of financial savings than younger women. We found that women with secondary school education or higher reported significantly higher financial risk than women with less education. Women with children reported lower levels of financial saving than women without children. Married women indicated significantly more financial saving than single women. There was a significant negative effect of time spent in trafficking conditions on financial saving, indicating the highest average level of financial savings at intervention and decreased thereafter. Programs and policies in resource-scarce contexts that aim to assist trafficking survivors must go beyond providing psychosocial counseling and focus also on economic development opportunities.

  13. HCV treatment rates and sustained viral response among people who inject drugs in seven UK sites: real world results and modelling of treatment impact.

    Science.gov (United States)

    Martin, N K; Foster, G R; Vilar, J; Ryder, S; Cramp, M E; Gordon, F; Dillon, J F; Craine, N; Busse, H; Clements, A; Hutchinson, S J; Ustianowski, A; Ramsay, M; Goldberg, D J; Irving, W; Hope, V; De Angelis, D; Lyons, M; Vickerman, P; Hickman, M

    2015-04-01

    Hepatitis C virus (HCV) antiviral treatment for people who inject drugs (PWID) could prevent onwards transmission and reduce chronic prevalence. We assessed current PWID treatment rates in seven UK settings and projected the potential impact of current and scaled-up treatment on HCV chronic prevalence. Data on number of PWID treated and sustained viral response rates (SVR) were collected from seven UK settings: Bristol (37-48% HCV chronic prevalence among PWID), East London (37-48%), Manchester (48-56%), Nottingham (37-44%), Plymouth (30-37%), Dundee (20-27%) and North Wales (27-33%). A model of HCV transmission among PWID projected the 10-year impact of (i) current treatment rates and SVR (ii) scale-up with interferon-free direct acting antivirals (IFN-free DAAs) with 90% SVR. Treatment rates varied from <5 to over 25 per 1000 PWID. Pooled intention-to-treat SVR for PWID were 45% genotypes 1/4 [95%CI 33-57%] and 61% genotypes 2/3 [95%CI 47-76%]. Projections of chronic HCV prevalence among PWID after 10 years of current levels of treatment overlapped substantially with current HCV prevalence estimates. Scaling-up treatment to 26/1000 PWID annually (achieved already in two sites) with IFN-free DAAs could achieve an observable absolute reduction in HCV chronic prevalence of at least 15% among PWID in all sites and greater than a halving in chronic HCV in Plymouth, Dundee and North Wales within a decade. Current treatment rates among PWID are unlikely to achieve observable reductions in HCV chronic prevalence over the next 10 years. Achievable scale-up, however, could lead to substantial reductions in HCV chronic prevalence. © 2014 The Authors Journal of Viral Hepatitis Published by John Wiley & Sons Ltd.

  14. 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.

  15. Human cytomegalovirus gH stability and trafficking are regulated by ER-associated degradation and transmembrane architecture.

    Science.gov (United States)

    Gardner, Thomas J; Hernandez, Rosmel E; Noriega, Vanessa M; Tortorella, Domenico

    2016-03-30

    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. To further define regulatory factors involved in gH/gL trafficking, a CMV gH chimera in which the gH transmembrane and cytoplasmic tail were replaced with that of human CD4 protein permitted cell surface gH expression in absence of gL. We thus demonstrate the ability of distinct cellular processes to regulate the trafficking of viral glycoproteins. Collectively, the data provide insight into the processing and trafficking requirements of CMV envelope protein complexes and provide an example of the co-opting of cellular processes by CMV.

  16. Bile acids for viral hepatitis

    DEFF Research Database (Denmark)

    Chen, Weikeng; Liu, J; Gluud, C

    2003-01-01

    The viral hepatitides are common causes of liver diseases globally. Trials have assessed bile acids for patients with viral hepatitis, but no consensus was reached regarding their usefulness.......The viral hepatitides are common causes of liver diseases globally. Trials have assessed bile acids for patients with viral hepatitis, but no consensus was reached regarding their usefulness....

  17. 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.

  18. 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.

  19. 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.

  20. Nuclear Imprisonment: Viral Strategies to Arrest Host mRNA Nuclear Export

    Science.gov (United States)

    Kuss, Sharon K.; Mata, Miguel A.; Zhang, Liang; Fontoura, Beatriz M. A.

    2013-01-01

    Viruses possess many strategies to impair host cellular responses to infection. Nuclear export of host messenger RNAs (mRNA) that encode antiviral factors is critical for antiviral protein production and control of viral infections. Several viruses have evolved sophisticated strategies to inhibit nuclear export of host mRNAs, including targeting mRNA export factors and nucleoporins to compromise their roles in nucleo-cytoplasmic trafficking of cellular mRNA. Here, we present a review of research focused on suppression of host mRNA nuclear export by viruses, including influenza A virus and vesicular stomatitis virus, and the impact of this viral suppression on host antiviral responses. PMID:23872491

  1. First insight into the viral community of the cnidarian model metaorganism Aiptasia using RNA-Seq data

    KAUST Repository

    Brü wer, Jan D.; Voolstra, Christian R.

    2018-01-01

    of the globally threatened coral reef ecosystems. To gain first insight into viruses associated with the coral model system Aiptasia (sensu Exaiptasia pallida), we analyzed an existing RNA-Seq dataset of aposymbiotic, partially populated, and fully symbiotic

  2. '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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. 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...

  9. Myeloid leukemias and virally induced lymphomas in miniature inbred swine; development of a large animal tumor model

    Directory of Open Access Journals (Sweden)

    RAIMON eDURAN-STRUUCK

    2015-11-01

    Full Text Available The lack of a large animal transplantable tumor model has limited the study of novel therapeutic strategies for the treatment of liquid cancers. Swine as a species provide a natural option based on their similarities with humans and their already extensive use in biomedical research. Specifically, the MGH miniature swine herd retains unique genetic characteristics that facilitate the study of hematopoietic cell and solid organ transplantation. Spontaneously arising liquid cancers in these swine, specifically myeloid leukemias and B cell lymphomas, closely resemble human malignancies. The ability to establish aggressive tumor cell lines in vitro from these naturally occurring malignancies makes a transplantable tumor model a close reality. Here, we discuss our experience with myeloid and lymphoid tumors in MHC characterized miniature swine and future approaches regarding the development of a large animal transplantable tumor model.

  10. 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.

  11. 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".

  12. 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.

  13. 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.

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

    Directory of Open Access Journals (Sweden)

    Lopez-Vergès Sandra

    2006-09-01

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

  15. [Viral hepatitis in travellers].

    Science.gov (United States)

    Abreu, Cândida

    2007-01-01

    Considering the geographical asymmetric distribution of viral hepatitis A, B and E, having a much higher prevalence in the less developed world, travellers from developed countries are exposed to a considerable and often underestimated risk of hepatitis infection. In fact a significant percentage of viral hepatitis occurring in developed countries is travel related. This results from globalization and increased mobility from tourism, international work, humanitarian and religious missions or other travel related activities. Several studies published in Europe and North America shown that more than 50% of reported cases of hepatitis A are travel related. On the other hand frequent outbreaks of hepatitis A and E in specific geographic areas raise the risk of infection in these restricted zones and that should be clearly identified. Selected aspects related with the distribution of hepatitis A, B and E are reviewed, particularly the situation in Portugal according to the published studies, as well as relevant clinical manifestations and differential diagnosis of viral hepatitis. Basic prevention rules considering enteric transmitted hepatitis (hepatitis A and hepatitis E) and parenteral transmitted (hepatitis B) are reviewed as well as hepatitis A and B immunoprophylaxis. Common clinical situations and daily practice "pre travel" advice issues are discussed according to WHO/CDC recommendations and the Portuguese National Vaccination Program. Implications from near future availability of a hepatitis E vaccine, a currently in phase 2 trial, are highlighted. Potential indications for travellers to endemic countries like India, Nepal and some regions of China, where up to 30% of sporadic cases of acute viral hepatitis are caused by hepatitis E virus, are considered. Continued epidemiological surveillance for viral hepatitis is essential to recognize and control possible outbreaks, but also to identify new viral hepatitis agents that may emerge as important global health

  16. Roles of the Picornaviral 3C Proteinase in the Viral Life Cycle and Host Cells

    Directory of Open Access Journals (Sweden)

    Di Sun

    2016-03-01

    Full Text Available The Picornaviridae family comprises a large group of non-enveloped viruses that have a major impact on human and veterinary health. The viral genome contains one open reading frame encoding a single polyprotein that can be processed by viral proteinases. The crucial 3C proteinases (3Cpros of picornaviruses share similar spatial structures and it is becoming apparent that 3Cpro plays a significant role in the viral life cycle and virus host interaction. Importantly, the proteinase and RNA-binding activity of 3Cpro are involved in viral polyprotein processing and the initiation of viral RNA synthesis. In addition, 3Cpro can induce the cleavage of certain cellular factors required for transcription, translation and nucleocytoplasmic trafficking to modulate cell physiology for viral replication. Due to interactions between 3Cpro and these essential factors, 3Cpro is also involved in viral pathogenesis to support efficient infection. Furthermore, based on the structural conservation, the development of irreversible inhibitors and discovery of non-covalent inhibitors for 3Cpro are ongoing and a better understanding of the roles played by 3Cpro may provide insights into the development of potential antiviral treatments. In this review, the current knowledge regarding the structural features, multiple functions in the viral life cycle, pathogen host interaction, and development of antiviral compounds for 3Cpro is summarized.

  17. 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.

  18. 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.

  19. 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.

  20. Nucleolar protein trafficking in response to HIV-1 Tat: rewiring the nucleolus.

    Science.gov (United States)

    Jarboui, Mohamed Ali; Bidoia, Carlo; Woods, Elena; Roe, Barbara; Wynne, Kieran; Elia, Giuliano; Hall, William W; Gautier, Virginie W

    2012-01-01

    The trans-activator Tat protein is a viral regulatory protein essential for HIV-1 replication. Tat trafficks to the nucleoplasm and the nucleolus. The nucleolus, a highly dynamic and structured membrane-less sub-nuclear compartment, is the site of rRNA and ribosome biogenesis and is involved in numerous cellular functions including transcriptional regulation, cell cycle control and viral infection. Importantly, transient nucleolar trafficking of both Tat and HIV-1 viral transcripts are critical in HIV-1 replication, however, the role(s) of the nucleolus in HIV-1 replication remains unclear. To better understand how the interaction of Tat with the nucleolar machinery contributes to HIV-1 pathogenesis, we investigated the quantitative changes in the composition of the nucleolar proteome of Jurkat T-cells stably expressing HIV-1 Tat fused to a TAP tag. Using an organellar proteomic approach based on mass spectrometry, coupled with Stable Isotope Labelling in Cell culture (SILAC), we quantified 520 proteins, including 49 proteins showing significant changes in abundance in Jurkat T-cell nucleolus upon Tat expression. Numerous proteins exhibiting a fold change were well characterised Tat interactors and/or known to be critical for HIV-1 replication. This suggests that the spatial control and subcellular compartimentaliation of these cellular cofactors by Tat provide an additional layer of control for regulating cellular machinery involved in HIV-1 pathogenesis. Pathway analysis and network reconstruction revealed that Tat expression specifically resulted in the nucleolar enrichment of proteins collectively participating in ribosomal biogenesis, protein homeostasis, metabolic pathways including glycolytic, pentose phosphate, nucleotides and amino acids biosynthetic pathways, stress response, T-cell signaling pathways and genome integrity. We present here the first differential profiling of the nucleolar proteome of T-cells expressing HIV-1 Tat. We discuss how these

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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...

  6. 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...

  7. 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

  8. 3,4-Methylenedioxymethamphetamine (MDMA) alters acute gammaherpesvirus burden and limits Interleukin 27 responses in a mouse model of viral infection

    Science.gov (United States)

    Nelson, Daniel A.; Singh, Sam J.; Young, Amy B.; Tolbert, Melanie D.; Bost, Kenneth L.

    2011-01-01

    Aims To test whether 3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”) abuse might increase the susceptibility, or alter the immune response, to murine gammaherpesvirus 68 (HV-68) and/or bacterial lipopolysaccharide. Methods Groups of experimental and control mice were subjected to three day binges of MDMA, and the effect of this drug abuse on acute and latent HV-68 viral burden were assessed. In vitro and in vivo studies were also performed to assess the MDMA effect on IL-27 expression in virally infected or LPS-exposed macrophages and dendritic cells, and latently infected animals, exposed to this drug of abuse. Results Acute viral burden was significantly increased in MDMA-treated mice when compared to controls. However the latent viral burden, and physiological and behavioral responses were not altered in infected mice despite repeated bingeing with MDMA. MDMA could limit the IL-27 response of HV-68 infected or LPS-exposed macrophages and dendritic cells in vitro and in vivo, demonstrating the ability of this drug to alter normal cytokine responses in the context of a viral infection and/or a TLR4 agonist. Conclusion MDMA bingeing could alter the host’s immune response resulting in greater acute viral replication and reductions in the production of the cytokine, IL-27 during immune responses. PMID:21269783

  9. Using the Hepatitis C Virus RNA-Dependent RNA Polymerase as a Model to Understand Viral Polymerase Structure, Function and Dynamics

    Directory of Open Access Journals (Sweden)

    Ester Sesmero

    2015-07-01

    Full Text Available Viral polymerases replicate and transcribe the genomes of several viruses of global health concern such as Hepatitis C virus (HCV, human immunodeficiency virus (HIV and Ebola virus. For this reason they are key targets for therapies to treat viral infections. Although there is little sequence similarity across the different types of viral polymerases, all of them present a right-hand shape and certain structural motifs that are highly conserved. These features allow their functional properties to be compared, with the goal of broadly applying the knowledge acquired from studying specific viral polymerases to other viral polymerases about which less is known. Here we review the structural and functional properties of the HCV RNA-dependent RNA polymerase (NS5B in order to understand the fundamental processes underlying the replication of viral genomes. We discuss recent insights into the process by which RNA replication occurs in NS5B as well as the role that conformational changes play in this process.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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...

  15. Solvent/Detergent Virally Inactivated Serum Eye Drops Restore Healthy Ocular Epithelium in a Rabbit Model of Dry-Eye Syndrome.

    Science.gov (United States)

    Tseng, Ching-Li; Chen, Zhi-Yu; Renn, Ting-Yi; Hsiao, Shun-Hung; Burnouf, Thierry

    2016-01-01

    Application of autologous serum eye drops (SEDs) is a recognized means to treat severe dry-eye syndrome (DES). Due to the inconvenience and difficulty of preparing SEDs from some patients, producing SEDs from allogeneic blood donations is gaining popularity. A major safety concern associated with allogeneic blood is virus transmission. We therefore herein evaluated the possibility of applying a solvent/detergent (S/D) treatment to inactivate viruses and studied the impacts of such treatment of SEDs to resolve DES in a rabbit model. Sera prepared from the blood of five rabbits were pooled and divided into two sub-pools. One was untreated (SEDs), while the other was virally-inactivated with 1% Tri-n-butyl phosphate/1% Triton X-45 at 31°C for 1 h (S/D-SEDs). DES was induced in rabbits using 0.1% benzalkonium chloride (BAC). Rabbits were divided into five groups of two rabbits each. One group was untreated (control), three were treated twice daily for 3 weeks using PBS, SEDs, or S/D-SEDs, and the last received an additional 0.1% BAC (as the negative control). The DES condition was determined by measuring aqueous tear secretion (Schirmer's test), corneal fluorescein staining, a corneal histologic examination, TUNEL stain apoptosis, and corneal inflammatory marker (tumor necrosis factor-α, interleukin (IL)-1β, IL-8, and IL-6) expressions. We first confirmed that SEDs and S/D-SEDs had similar protein profiles and transforming growth factor (TGF)-β contents. Animal experiments showed that tear secretion did not significantly differ between the SED and S/D-SED groups but was significantly higher than in the PBS group. Eye fluorescein staining revealed dramatic improvements in epithelial defects in groups treated with SEDs or S/D-SEDs, and hematoxylin/eosin staining revealed microscopic epithelial layers similar to those of the untreated controls. Inflammatory markers and TUNEL studies showed that healthy epithelium had been restored in groups treated with SEDs or S

  16. Virally mediated Kcnq1 gene replacement therapy in the immature scala media restores hearing in a mouse model of human Jervell and Lange-Nielsen deafness syndrome.

    Science.gov (United States)

    Chang, Qing; Wang, Jianjun; Li, Qi; Kim, Yeunjung; Zhou, Binfei; Wang, Yunfeng; Li, Huawei; Lin, Xi

    2015-08-01

    Mutations in the potassium channel subunit KCNQ1 cause the human severe congenital deafness Jervell and Lange-Nielsen (JLN) syndrome. We applied a gene therapy approach in a mouse model of JLN syndrome (Kcnq1(-/-) mice) to prevent the development of deafness in the adult stage. A modified adeno-associated virus construct carrying a Kcnq1 expression cassette was injected postnatally (P0-P2) into the endolymph, which resulted in Kcnq1 expression in most cochlear marginal cells where native Kcnq1 is exclusively expressed. We also found that extensive ectopic virally mediated Kcnq1 transgene expression did not affect normal cochlear functions. Examination of cochlear morphology showed that the collapse of the Reissner's membrane and degeneration of hair cells (HCs) and cells in the spiral ganglia were corrected in Kcnq1(-/-) mice. Electrophysiological tests showed normal endocochlear potential in treated ears. In addition, auditory brainstem responses showed significant hearing preservation in the injected ears, ranging from 20 dB improvement to complete correction of the deafness phenotype. Our results demonstrate the first successful gene therapy treatment for gene defects specifically affecting the function of the stria vascularis, which is a major site affected by genetic mutations in inherited hearing loss. © 2015 The Authors. Published under the terms of the CC BY 4.0 license.

  17. Treating viral hemorrhagic fever.

    NARCIS (Netherlands)

    Mairuhu, A.T.; Brandjes, D.P.; Gorp, E. van

    2003-01-01

    Viral hemorrhagic fevers are illnesses associated with a number of geographically restricted, mostly tropical areas. Over recent decades a number of new hemorrhagic fever viruses have emerged. Advances in our understanding of the pathophysiology of these diseases have improved our initial supportive

  18. HIV Viral Load

    Science.gov (United States)

    ... PF4 Antibody Hepatitis A Testing Hepatitis B Testing Hepatitis C Testing HER2/neu Herpes Testing High-sensitivity C-reactive Protein (hs-CRP) Histamine Histone Antibody HIV Antibody and HIV Antigen (p24) HIV Antiretroviral Drug Resistance Testing, Genotypic HIV Viral Load HLA Testing HLA- ...

  19. HIV and Viral Hepatitis

    Science.gov (United States)

    ... common causes of viral hepatitis are hepatitis A virus (HAV), hepatitis B virus (HBV), and hepatitis C virus (HCV). HBV and HCV are common ... gov/ mmwr/ preview/ mmwrhtml/ rr5516a1. htm? s_ cid= rr5516a1_ e. The Numbers • • Of people with HIV in the ...

  20. Immigration and viral hepatitis

    NARCIS (Netherlands)

    S. Sharma (Suraj); M. Carballo (Manuel); J.J. Feld (Jordan J.); H.L.A. Janssen (Harry)

    2015-01-01

    textabstractWHO estimates reveal that the global prevalence of viral hepatitis may be as high as 500 million, with an annual mortality rate of up to 1.3 million individuals. The majority of this global burden of disease is borne by nations of the developing world with high rates of vertical and

  1. Characterization of New Zealand White Rabbit Gut-Associated Lymphoid Tissues and Use as Viral Oncology Animal Model.

    Science.gov (United States)

    Haines, Robyn A; Urbiztondo, Rebeccah A; Haynes, Rashade A H; Simpson, Elaine; Niewiesk, Stefan; Lairmore, Michael D

    2016-01-01

    Rabbits have served as a valuable animal model for the pathogenesis of various human diseases, including those related to agents that gain entry through the gastrointestinal tract such as human T cell leukemia virus type 1. However, limited information is available regarding the spatial distribution and phenotypic characterization of major rabbit leukocyte populations in mucosa-associated lymphoid tissues. Herein, we describe the spatial distribution and phenotypic characterization of leukocytes from gut-associated lymphoid tissues (GALT) from 12-week-old New Zealand White rabbits. Our data indicate that rabbits have similar distribution of leukocyte subsets as humans, both in the GALT inductive and effector sites and in mesenteric lymph nodes, spleen, and peripheral blood. GALT inductive sites, including appendix, cecal tonsil, Peyer's patches, and ileocecal plaque, had variable B cell/T cell ratios (ranging from 4.0 to 0.8) with a predominance of CD4 T cells within the T cell population in all four tissues. Intraepithelial and lamina propria compartments contained mostly T cells, with CD4 T cells predominating in the lamina propria compartment and CD8 T cells predominating in the intraepithelial compartment. Mesenteric lymph node, peripheral blood, and splenic samples contained approximately equal percentages of B cells and T cells, with a high proportion of CD4 T cells compared with CD8 T cells. Collectively, our data indicate that New Zealand White rabbits are comparable with humans throughout their GALT and support future studies that use the rabbit model to study human gut-associated disease or infectious agents that gain entry by the oral route. © The Author 2016. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  2. Definitive Management of Oligometastatic Melanoma in a Murine Model Using Combined Ablative Radiation Therapy and Viral Immunotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Blanchard, Miran [Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota (United States); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Shim, Kevin G. [Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota (United States); Department of Immunology, Mayo Clinic, Rochester, Minnesota (United States); Grams, Michael P. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Rajani, Karishma; Diaz, Rosa M. [Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota (United States); Furutani, Keith M. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Thompson, Jill [Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota (United States); Olivier, Kenneth R.; Park, Sean S. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Markovic, Svetomir N. [Department of Immunology, Mayo Clinic, Rochester, Minnesota (United States); Department of Medical Oncology, Mayo Clinic, Rochester, Minnesota (United States); Pandha, Hardev [The Postgraduate Medical School, University of Surrey, Guildford (United Kingdom); Melcher, Alan [Leeds Institute of Cancer Studies and Pathology, University of Leeds, Leeds (United Kingdom); Harrington, Kevin [Targeted Therapy Laboratory, The Institute of Cancer Research, London (United Kingdom); Zaidi, Shane [Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota (United States); Targeted Therapy Laboratory, The Institute of Cancer Research, London (United Kingdom); Vile, Richard, E-mail: vile.richard@mayo.edu [Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota (United States); Department of Immunology, Mayo Clinic, Rochester, Minnesota (United States); Leeds Institute of Cancer Studies and Pathology, University of Leeds, Leeds (United Kingdom)

    2015-11-01

    Purpose: The oligometastatic state is an intermediate state between a malignancy that can be completely eradicated with conventional modalities and one in which a palliative approach is undertaken. Clinically, high rates of local tumor control are possible with stereotactic ablative radiation therapy (SABR), using precisely targeted, high-dose, low-fraction radiation therapy. However, in oligometastatic melanoma, virtually all patients develop progression systemically at sites not initially treated with ablative radiation therapy that cannot be managed with conventional chemotherapy and immunotherapy. We have demonstrated in mice that intravenous administration of vesicular stomatitis virus (VSV) expressing defined tumor-associated antigens (TAAs) generates systemic immune responses capable of clearing established tumors. Therefore, in the present preclinical study, we tested whether the combination of systemic VSV-mediated antigen delivery and SABR would be effective against oligometastatic disease. Methods and Materials: We generated a model of oligometastatic melanoma in C57BL/6 immunocompetent mice and then used a combination of SABR and systemically administered VSV-TAA viral immunotherapy to treat both local and systemic disease. Results: Our data showed that SABR generates excellent control or cure of local, clinically detectable, and accessible tumor through direct cell ablation. Also, the immunotherapeutic activity of systemically administered VSV-TAA generated T-cell responses that cleared subclinical metastatic tumors. We also showed that SABR induced weak T-cell-mediated tumor responses, which, particularly if boosted by VSV-TAA, might contribute to control of local and systemic disease. In addition, VSV-TAA therapy alone had significant effects on control of both local and metastatic tumors. Conclusions: We have shown in the present preliminary murine study using a single tumor model that this approach represents an effective, complementary

  3. Definitive Management of Oligometastatic Melanoma in a Murine Model Using Combined Ablative Radiation Therapy and Viral Immunotherapy

    International Nuclear Information System (INIS)

    Blanchard, Miran; Shim, Kevin G.; Grams, Michael P.; Rajani, Karishma; Diaz, Rosa M.; Furutani, Keith M.; Thompson, Jill; Olivier, Kenneth R.; Park, Sean S.; Markovic, Svetomir N.; Pandha, Hardev; Melcher, Alan; Harrington, Kevin; Zaidi, Shane; Vile, Richard

    2015-01-01

    Purpose: The oligometastatic state is an intermediate state between a malignancy that can be completely eradicated with conventional modalities and one in which a palliative approach is undertaken. Clinically, high rates of local tumor control are possible with stereotactic ablative radiation therapy (SABR), using precisely targeted, high-dose, low-fraction radiation therapy. However, in oligometastatic melanoma, virtually all patients develop progression systemically at sites not initially treated with ablative radiation therapy that cannot be managed with conventional chemotherapy and immunotherapy. We have demonstrated in mice that intravenous administration of vesicular stomatitis virus (VSV) expressing defined tumor-associated antigens (TAAs) generates systemic immune responses capable of clearing established tumors. Therefore, in the present preclinical study, we tested whether the combination of systemic VSV-mediated antigen delivery and SABR would be effective against oligometastatic disease. Methods and Materials: We generated a model of oligometastatic melanoma in C57BL/6 immunocompetent mice and then used a combination of SABR and systemically administered VSV-TAA viral immunotherapy to treat both local and systemic disease. Results: Our data showed that SABR generates excellent control or cure of local, clinically detectable, and accessible tumor through direct cell ablation. Also, the immunotherapeutic activity of systemically administered VSV-TAA generated T-cell responses that cleared subclinical metastatic tumors. We also showed that SABR induced weak T-cell-mediated tumor responses, which, particularly if boosted by VSV-TAA, might contribute to control of local and systemic disease. In addition, VSV-TAA therapy alone had significant effects on control of both local and metastatic tumors. Conclusions: We have shown in the present preliminary murine study using a single tumor model that this approach represents an effective, complementary

  4. 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

  5. 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.

  6. 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.

  7. Aspirin-triggered resolvin D1 reduces pneumococcal lung infection and inflammation in a viral and bacterial coinfection pneumonia model.

    Science.gov (United States)

    Wang, Hao; Anthony, Desiree; Yatmaz, Selcuk; Wijburg, Odilia; Satzke, Catherine; Levy, Bruce; Vlahos, Ross; Bozinovski, Steven

    2017-09-15

    Formyl peptide receptor 2/lipoxin A 4 (LXA 4 ) receptor (Fpr2/ALX) co-ordinates the transition from inflammation to resolution during acute infection by binding to distinct ligands including serum amyloid A (SAA) and Resolvin D1 (RvD1). Here, we evaluated the proresolving actions of aspirin-triggered RvD1 (AT-RvD1) in an acute coinfection pneumonia model. Coinfection with Streptococcus pneumoniae and influenza A virus (IAV) markedly increased pneumococcal lung load and neutrophilic inflammation during the resolution phase. Fpr2/ALX transcript levels were increased in the lungs of coinfected mice, and immunohistochemistry identified prominent Fpr2/ALX immunoreactivity in bronchial epithelial cells and macrophages. Levels of circulating and lung SAA were also highly increased in coinfected mice. Therapeutic treatment with exogenous AT-RvD1 during the acute phase of infection (day 4-6 post-pneumococcal inoculation) significantly reduced the pneumococcal load. AT-RvD1 also significantly reduced neutrophil elastase (NE) activity and restored total antimicrobial activity in bronchoalveolar lavage (BAL) fluid (BALF) of coinfected mice. Pneumonia severity, as measured by quantitating parenchymal inflammation or alveolitis was significantly reduced with AT-RvD1 treatment, which also reduced the number of infiltrating lung neutrophils and monocytes/macrophages as assessed by flow cytometry. The reduction in distal lung inflammation in AT-RvD1-treated mice was not associated with a significant reduction in inflammatory and chemokine mediators. In summary, we demonstrate that in the coinfection setting, SAA levels were persistently increased and exogenous AT-RvD1 facilitated more rapid clearance of pneumococci in the lungs, while concurrently reducing the severity of pneumonia by limiting excessive leukocyte chemotaxis from the infected bronchioles to distal areas of the lungs. © 2017 The Author(s).

  8. Virally inactivated human platelet concentrate lysate induces regulatory T cells and immunosuppressive effect in a murine asthma model.

    Science.gov (United States)

    Lee, Yueh-Lun; Lee, Lin-Wen; Su, Chen-Yao; Hsiao, George; Yang, Yi-Yuan; Leu, Sy-Jye; Shieh, Ying-Hua; Burnouf, Thierry

    2013-09-01

    Platelet concentrate lysates (PCLs) are increasingly used in regenerative medicine. We have developed a solvent/detergent (S/D)-treated PCL. The functional properties of this preparation should be unveiled. We hypothesized that, due to transforming growth factor-β1 (TGF-β1) content, PCLs may exert immunosuppressive and anti-inflammatory functions. PCL was prepared by S/D treatment, oil extraction, and hydrophobic interaction chromatography. The content of TGF-β in PCL was determined by enzyme-linked immunosorbent assay. Cultured CD4+ T cells were used to investigate the effects of PCL on expression of transcription factor forkhead box P3 (Foxp3), the inhibition of T-cell proliferation, and cytokine production. The regulatory function of PCL-converted CD4+ T cells was analyzed by suppressive assay. The BALB/c mice were given PCL-converted CD4+ T cells before ovalbumin (OVA) sensitization and challenge using an asthma model. Inflammatory parameters, such as the level of immunoglobulin E (IgE), airway hyperresponsiveness (AHR), bronchial lavage fluid eosinophils, and cytokines were assayed. Recombinant human (rHu) TGF-β1 was used as control. PCL significantly enhanced the development of CD4+Foxp3+-induced regulatory T cells (iTregs). Converted iTregs produced neither Th1 nor Th2 cytokines and inhibited normal T-cell proliferation. PCL- and rHuTGF-β-converted CD4+ T cells prevented OVA-induced asthma. PCL- and rHuTGF-β-modified T cells both significantly reduced expression levels of OVA-specific IgE and significantly inhibited the development of AHR, airway eosinophilia, and Th2 responses in mice. S/D-treated PCL promotes Foxp3+ iTregs and exerts immunosuppressive and anti-inflammatory properties. This finding may help to understand the clinical properties of platelet lysates. © 2013 American Association of Blood Banks.

  9. A Novel Nuclear Trafficking Module Regulates the Nucleocytoplasmic Localization of the Rabies Virus Interferon Antagonist, P Protein*

    Science.gov (United States)

    Oksayan, Sibil; Wiltzer, Linda; Rowe, Caitlin L.; Blondel, Danielle; Jans, David A.; Moseley, Gregory W.

    2012-01-01

    Regulated nucleocytoplasmic transport of proteins is central to cellular function and dysfunction during processes such as viral infection. Active protein trafficking into and out of the nucleus is dependent on the presence within cargo proteins of intrinsic specific modular signals for nuclear import (nuclear localization signals, NLSs) and export (nuclear export signals, NESs). Rabies virus (RabV) phospho (P) protein, which is largely responsible for antagonising the host anti-viral response, is expressed as five isoforms (P1–P5). The subcellular trafficking of these isoforms is thought to depend on a balance between the activities of a dominant N-terminal NES (N-NES) and a distinct C-terminal NLS (C-NLS). Specifically, the N-NES-containing isoforms P1 and P2 are cytoplasmic, whereas the shorter P3–P5 isoforms, which lack the N-NES, are believed to be nuclear through the activity of the C-NLS. Here, we show for the first time that RabV P contains an additional strong NLS in the N-terminal region (N-NLS), which, intriguingly, overlaps with the N-NES. This arrangement represents a novel nuclear trafficking module where the N-NLS is inactive in P1 but becomes activated in P3, concomitant with truncation of the N-NES, to become the principal targeting signal conferring nuclear accumulation. Understanding this unique switch arrangement of overlapping, co-regulated NES/NLS sequences is vital to delineating the critical role of RabV P protein in viral infection. PMID:22700958

  10. One ring to rule them all: trafficking of heme and heme synthesis intermediates in the metazoans.

    Science.gov (United States)

    Hamza, Iqbal; Dailey, Harry A

    2012-09-01

    The appearance of heme, an organic ring surrounding an iron atom, in evolution forever changed the efficiency with which organisms were able to generate energy, utilize gasses and catalyze numerous reactions. Because of this, heme has become a near ubiquitous compound among living organisms. In this review we have attempted to assess the current state of heme synthesis and trafficking with a goal of identifying crucial missing information, and propose hypotheses related to trafficking that may generate discussion and research. The possibilities of spatially organized supramolecular enzyme complexes and organelle structures that facilitate efficient heme synthesis and subsequent trafficking are discussed and evaluated. Recently identified players in heme transport and trafficking are reviewed and placed in an organismal context. Additionally, older, well established data are reexamined in light of more recent studies on cellular organization and data available from newer model organisms. This article is part of a Special Issue entitled: Cell Biology of Metals. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Bile acids for viral hepatitis

    DEFF Research Database (Denmark)

    Chen, Weikeng; Liu, J; Gluud, C

    2007-01-01

    Trials have assessed bile acids for patients with viral hepatitis, but no consensus has been reached regarding their usefulness.......Trials have assessed bile acids for patients with viral hepatitis, but no consensus has been reached regarding their usefulness....

  12. 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.

  13. Hepatitis A through E (Viral Hepatitis)

    Science.gov (United States)

    ... Treatment Eating, Diet, & Nutrition Clinical Trials Wilson Disease Hepatitis (Viral) View or Print All Sections What is Viral Hepatitis? Viral hepatitis is an infection that causes liver inflammation ...

  14. 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.

  15. A Tool for Investigating Asthma and COPD Exacerbations: A Newly Manufactured and Well Characterised GMP Wild-Type Human Rhinovirus for Use in the Human Viral Challenge Model.

    Directory of Open Access Journals (Sweden)

    Daniel J Fullen

    Full Text Available Human Rhinovirus infection is an important precursor to asthma and chronic obstructive pulmonary disease exacerbations and the Human Viral Challenge model may provide a powerful tool in studying these and other chronic respiratory diseases. In this study we have reported the production and human characterisation of a new Wild-Type HRV-16 challenge virus produced specifically for this purpose.A HRV-16 isolate from an 18 year old experimentally infected healthy female volunteer (University of Virginia Children's Hospital, USA was obtained with appropriate medical history and consent. We manufactured a new HRV-16 stock by minimal passage in a WI-38 cell line under Good Manufacturing Practice conditions. Having first subjected the stock to rigorous adventitious agent testing and determining the virus suitability for human use, we conducted an initial safety and pathogenicity clinical study in adult volunteers in our dedicated clinical quarantine facility in London.In this study we have demonstrated the new Wild-Type HRV-16 Challenge Virus to be both safe and pathogenic, causing an appropriate level of disease in experimentally inoculated healthy adult volunteers. Furthermore, by inoculating volunteers with a range of different inoculum titres, we have established the minimum inoculum titre required to achieve reproducible disease. We have demonstrated that although inoculation titres as low as 1 TCID50 can produce relatively high infection rates, the optimal titre for progression with future HRV challenge model development with this virus stock was 10 TCID50. Studies currently underway are evaluating the use of this virus as a challenge agent in asthmatics.ClinicalTrials.gov NCT02522832.

  16. Value of Sharing: Viral Advertisement

    OpenAIRE

    Duygu Aydın; Aşina Gülerarslan; Süleyman Karaçor; Tarık Doğan

    2013-01-01

    Sharing motivations of viral advertisements by consumers and the impacts of these advertisements on the perceptions for brand will be questioned in this study. Three fundamental questions are answered in the study. These are advertisement watching and sharing motivations of individuals, criteria of liking viral advertisement and the impact of individual attitudes for viral advertisement on brand perception respectively. This study will be carried out via a viral advertise...

  17. Viral Marketing and Academic Institution

    OpenAIRE

    Koktová, Silvie

    2010-01-01

    This bachelor thesis examines modern and constantly developing kind of internet marketing -- the so called viral marketing. It deals with its origin, principle, process, advantages and disadvantages, types of viral marketing and presumptions of creating successful viral campaign. The aim of the theoretical part is especially the understanding of viral marketing as one of the effective instruments of contemporary marketing. In this theoretical part the thesis also elaborates a marketing school...

  18. UGGT1 enhances enterovirus 71 pathogenicity by promoting viral RNA synthesis and viral replication.

    Directory of Open Access Journals (Sweden)

    Peng-Nien Huang

    2017-05-01

    Full Text Available Positive-strand RNA virus infections can induce the stress-related unfolded protein response (UPR in host cells. This study found that enterovirus A71 (EVA71 utilizes host UDP-glucose glycoprotein glucosyltransferase 1 (UGGT1, a key endoplasmic reticulum protein (ER involved in UPR, to enhance viral replication and virulence. EVA71 forms replication complexes (RCs on cellular membranes that contain a mix of host and viral proteins to facilitate viral replication, but the components and processes involved in the assembly and function of RCs are not fully understood. Using EVA71 as a model, this study found that host UGGT1 and viral 3D polymerase co-precipitate along with other factors on membranous replication complexes to enhance viral replication. Increased UGGT1 levels elevated viral growth rates, while viral pathogenicity was observed to be lower in heterozygous knockout mice (Uggt1 +/- mice. These findings provide important insight on the role of UPR and host UGGT1 in regulating RNA virus replication and pathogenicity.

  19. 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.

  20. 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...

  1. 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…

  2. 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. -

  3. 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)

  4. 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…

  5. 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 ...

  6. 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.

  7. 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…

  8. Dengue viral infections

    OpenAIRE

    Malavige, G; Fernando, S; Fernando, D; Seneviratne, S

    2004-01-01

    Dengue viral infections are one of the most important mosquito borne diseases in the world. They may be asymptomatic or may give rise to undifferentiated fever, dengue fever, dengue haemorrhagic fever (DHF), or dengue shock syndrome. Annually, 100 million cases of dengue fever and half a million cases of DHF occur worldwide. Ninety percent of DHF subjects are children less than 15 years of age. At present, dengue is endemic in 112 countries in the world. No vaccine is available for preventing...

  9. Viral membrane fusion

    International Nuclear Information System (INIS)

    Harrison, Stephen C.

    2015-01-01

    Membrane fusion is an essential step when enveloped viruses enter cells. Lipid bilayer fusion requires catalysis to overcome a high kinetic barrier; viral fusion proteins are the agents that fulfill this catalytic function. Despite a variety of molecular architectures, these proteins facilitate fusion by essentially the same generic mechanism. Stimulated by a signal associated with arrival at the cell to be infected (e.g., receptor or co-receptor binding, proton binding in an endosome), they undergo a series of conformational changes. A hydrophobic segment (a “fusion loop” or “fusion peptide”) engages the target-cell membrane and collapse of the bridging intermediate thus formed draws the two membranes (virus and cell) together. We know of three structural classes for viral fusion proteins. Structures for both pre- and postfusion conformations of illustrate the beginning and end points of a process that can be probed by single-virion measurements of fusion kinetics. - Highlights: • Viral fusion proteins overcome the high energy barrier to lipid bilayer merger. • Different molecular structures but the same catalytic mechanism. • Review describes properties of three known fusion-protein structural classes. • Single-virion fusion experiments elucidate mechanism

  10. [History of viral hepatitis].

    Science.gov (United States)

    Fonseca, José Carlos Ferraz da

    2010-01-01

    The history of viral hepatitis goes back thousands of years and is a fascinating one. When humans were first infected by such agents, a natural repetitive cycle began, with the capacity to infect billions of humans, thus decimating the population and causing sequelae in thousands of lives. This article reviews the available scientific information on the history of viral hepatitis. All the information was obtained through extensive bibliographic review, including original and review articles and consultations on the internet. There are reports on outbreaks of jaundice epidemics in China 5,000 years ago and in Babylon more than 2,500 years ago. The catastrophic history of great jaundice epidemics and pandemics is well known and generally associated with major wars. In the American Civil War, 40,000 cases occurred among Union troops. In 1885, an outbreak of catarrhal jaundice affected 191 workers at the Bremen shipyard (Germany) after vaccination against smallpox. In 1942, 28,585 soldiers became infected with hepatitis after inoculation with the yellow fever vaccine. The number of cases of hepatitis during the Second World War was estimated to be 16 million. Only in the twentieth century were the main agents causing viral hepatitis identified. The hepatitis B virus was the first to be discovered. In this paper, through reviewing the history of major epidemics caused by hepatitis viruses and the history of discovery of these agents, singular peculiarities were revealed. Examples of this include the accidental or chance discovery of the hepatitis B and D viruses.

  11. Viral membrane fusion

    Energy Technology Data Exchange (ETDEWEB)

    Harrison, Stephen C., E-mail: harrison@crystal.harvard.edu

    2015-05-15

    Membrane fusion is an essential step when enveloped viruses enter cells. Lipid bilayer fusion requires catalysis to overcome a high kinetic barrier; viral fusion proteins are the agents that fulfill this catalytic function. Despite a variety of molecular architectures, these proteins facilitate fusion by essentially the same generic mechanism. Stimulated by a signal associated with arrival at the cell to be infected (e.g., receptor or co-receptor binding, proton binding in an endosome), they undergo a series of conformational changes. A hydrophobic segment (a “fusion loop” or “fusion peptide”) engages the target-cell membrane and collapse of the bridging intermediate thus formed draws the two membranes (virus and cell) together. We know of three structural classes for viral fusion proteins. Structures for both pre- and postfusion conformations of illustrate the beginning and end points of a process that can be probed by single-virion measurements of fusion kinetics. - Highlights: • Viral fusion proteins overcome the high energy barrier to lipid bilayer merger. • Different molecular structures but the same catalytic mechanism. • Review describes properties of three known fusion-protein structural classes. • Single-virion fusion experiments elucidate mechanism.

  12. Identification of SIV Nef CD8(+) T cell epitopes restricted by a MHC class I haplotype associated with lower viral loads in a macaque AIDS model.

    Science.gov (United States)

    Nomura, Takushi; Yamamoto, Hiroyuki; Takahashi, Naofumi; Naruse, Taeko K; Kimura, Akinori; Matano, Tetsuro

    2014-07-25

    Virus-specific CD8(+) T-cell responses are crucial for the control of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) replication. Multiple studies on HIV-infected individuals and SIV-infected macaques have indicated association of several major histocompatibility complex class I (MHC-I) genotypes with lower viral loads and delayed AIDS progression. Understanding of the viral control mechanism associated with these MHC-I genotypes would contribute to the development of intervention strategy for HIV control. We have previously reported a rhesus MHC-I haplotype, 90-120-Ia, associated with lower viral loads after SIVmac239 infection. Gag206-216 and Gag241-249 epitope-specific CD8(+) T-cell responses have been shown to play a central role in the reduction of viral loads, whereas the effect of Nef-specific CD8(+) T-cell responses induced in all the 90-120-Ia(+) macaques on SIV replication remains unknown. Here, we identified three CD8(+) T-cell epitopes, Nef9-19, Nef89-97, and Nef193-203, associated with 90-120-Ia. Nef9-19 and Nef193-203 epitope-specific CD8(+) T-cell responses frequently selected for mutations resulting in viral escape from recognition by these CD8(+) T cells, indicating that these CD8(+) T cells exert strong suppressive pressure on SIV replication. Results would be useful for elucidation of the viral control mechanism associated with 90-120-Ia. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Construction of a viral T2A-peptide based knock-in mouse model for enhanced Cre recombinase activity and fluorescent labeling of podocytes.

    Science.gov (United States)

    Koehler, Sybille; Brähler, Sebastian; Braun, Fabian; Hagmann, Henning; Rinschen, Markus M; Späth, Martin R; Höhne, Martin; Wunderlich, F Thomas; Schermer, Bernhard; Benzing, Thomas; Brinkkoetter, Paul T

    2017-06-01

    Podocyte injury is a key event in glomerular disease leading to proteinuria and opening the path toward glomerular scarring. As a consequence, glomerular research strives to discover molecular mechanisms and signaling pathways affecting podocyte health. The hNphs2.Cre mouse model has been a valuable tool to manipulate podocyte-specific genes and to label podocytes for lineage tracing and purification. Here we designed a novel podocyte-specific tricistronic Cre mouse model combining codon improved Cre expression and fluorescent cell labeling with mTomato under the control of the endogenous Nphs2 promoter using viral T2A-peptides. Independent expression of endogenous podocin, codon improved Cre, and mTomato was confirmed by immunofluorescence, fluorescent activated cell sorting and protein analyses. Nphs2 pod.T2A.ciCre.T2A.mTomato/wild-type mice developed normally and did not show any signs of glomerular disease or off-target effects under basal conditions and in states of disease. Nphs2 pod.T2A.ciCre.T2A.mTomato/wild-type -mediated gene recombination was superior to conventional hNphs2.Cre mice-mediated gene recombination. Last, we compared Cre efficiency in a disease model by mating Nphs2 pod.T2A.ciCre.T2A.mTomato/wild-type and hNphs2.Cre mice to Phb2 fl/fl mice. The podocyte-specific Phb2 knockout by Nphs2 pod.T2A.ciCre.T2A.mTomato/wild-type mice resulted in an aggravated glomerular injury as compared to a podocyte-specific Phb2 gene deletion triggered by hNphs2.Cre. Thus, we generated the first tricistronic podocyte mouse model combining enhanced Cre recombinase efficiency and fluorescent labeling in podocytes without the need for additional matings with conventional reporter mouse lines. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  14. Nucleocapsid-Independent Specific Viral RNA Packaging via Viral Envelope Protein and Viral RNA Signal

    OpenAIRE

    Narayanan, Krishna; Chen, Chun-Jen; Maeda, Junko; Makino, Shinji

    2003-01-01

    For any of the enveloped RNA viruses studied to date, recognition of a specific RNA packaging signal by the virus's nucleocapsid (N) protein is the first step described in the process of viral RNA packaging. In the murine coronavirus a selective interaction between the viral transmembrane envelope protein M and the viral ribonucleoprotein complex, composed of N protein and viral RNA containing a short cis-acting RNA element, the packaging signal, determines the selective RNA packaging into vi...

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Bicistronic lentiviruses containing a viral 2A cleavage sequence reliably co-express two proteins and restore vision to an animal model of LCA1.

    Directory of Open Access Journals (Sweden)

    Jonathan D Verrier

    Full Text Available The disease processes underlying inherited retinal disease are complex and are not completely understood. Many of the corrective gene therapies designed to treat diseases linked to mutations in genes specifically expressed in photoreceptor cells restore function to these cells but fail to stop progression of the disease. There is growing consensus that effective treatments for these diseases will require delivery of multiple therapeutic proteins that will be selected to treat specific aspects of the disease process. The purpose of this study was to design a lentiviral transgene that reliably expresses all of the proteins it encodes and does so in a consistent manner among infected cells. We show, using both in vitro and in vivo analyses, that bicistronic lentiviral transgenes encoding two fluorescent proteins fused to a viral 2A-like cleavage peptide meet these expression criteria. To determine if this transgene design is suitable for therapeutic applications, we replaced one of the fluorescent protein genes with the gene encoding guanylate cyclase-1 (GC1 and delivered lentivirus carrying this transgene to the retinas of the GUCY1*B avian model of Leber congenital amaurosis-1 (LCA1. GUCY1*B chickens carry a null mutation in the GC1 gene that disrupts photoreceptor function and causes blindness at hatching, a phenotype that closely matches that observed in humans with LCA1. We found that treatment of these animals with the 2A lentivector encoding GC1 restored vision to these animals as evidenced by the presence of optokinetic reflexes. We conclude that 2A-like peptides, with proper optimization, can be successfully incorporated into therapeutic vectors designed to deliver multiple proteins to neural retinal. These results highlight the potential of this vector design to serve as a platform for the development of combination therapies designed to enhance or prolong the benefits of corrective gene therapies.

  7. A simulation model to quantify the value of implementing whole-herd Bovine viral diarrhea virus testing strategies in beef cow-calf herds.

    Science.gov (United States)

    Nickell, Jason S; White, Brad J; Larson, Robert L; Renter, David G; Sanderson, Mike W

    2011-03-01

    Although numerous diagnostic tests are available to identify cattle persistently infected (PI) with Bovine viral diarrhea virus (BVDV) in cow-calf herds, data are sparse when evaluating the economic viability of individual tests or diagnostic strategies. Multiple factors influence BVDV testing in determining if testing should be performed and which strategy to use. A stochastic model was constructed to estimate the value of implementing various whole-herd BVDV cow-calf testing protocols. Three common BVDV tests (immunohistochemistry, antigen-capture enzyme-linked immunosorbent assay, and polymerase chain reaction) performed on skin tissue were evaluated as single- or two-test strategies. The estimated testing value was calculated for each strategy at 3 herd sizes that reflect typical farm sizes in the United States (50, 100, and 500 cows) and 3 probabilities of BVDV-positive herd status (0.077, 0.19, 0.47) based upon the literature. The economic value of testing was the difference in estimated gross revenue between simulated cow-calf herds that either did or did not apply the specific testing strategy. Beneficial economic outcomes were more frequently observed when the probability of a herd being BVDV positive was 0.47. Although the relative value ranking of many testing strategies varied by each scenario, the two-test strategy composed of immunohistochemistry had the highest estimated value in all but one herd size-herd prevalence permutation. These data indicate that the estimated value of applying BVDV whole-herd testing strategies is influenced by the selected strategy, herd size, and the probability of herd BVDV-positive status; therefore, these factors should be considered when designing optimum testing strategies for cow-calf herds.

  8. PINK1 regulates mitochondrial trafficking in dendrites of cortical neurons through mitochondrial PKA.

    Science.gov (United States)

    Das Banerjee, Tania; Dagda, Raul Y; Dagda, Marisela; Chu, Charleen T; Rice, Monica; Vazquez-Mayorga, Emmanuel; Dagda, Ruben K

    2017-08-01

    Mitochondrial Protein Kinase A (PKA) and PTEN-induced kinase 1 (PINK1), which is linked to Parkinson's disease, are two neuroprotective serine/threonine kinases that regulate dendrite remodeling and mitochondrial function. We have previously shown that PINK1 regulates dendrite morphology by enhancing PKA activity. Here, we show the molecular mechanisms by which PINK1 and PKA in the mitochondrion interact to regulate dendrite remodeling, mitochondrial morphology, content, and trafficking in dendrites. PINK1-deficient cortical neurons exhibit impaired mitochondrial trafficking, reduced mitochondrial content, fragmented mitochondria, and a reduction in dendrite outgrowth compared to wild-type neurons. Transient expression of wild-type, but not a PKA-binding-deficient mutant of the PKA-mitochondrial scaffold dual-specificity A Kinase Anchoring Protein 1 (D-AKAP1), restores mitochondrial trafficking, morphology, and content in dendrites of PINK1-deficient cortical neurons suggesting that recruiting PKA to the mitochondrion reverses mitochondrial pathology in dendrites induced by loss of PINK1. Mechanistically, full-length and cleaved forms of PINK1 increase the binding of the regulatory subunit β of PKA (PKA/RIIβ) to D-AKAP1 to enhance the autocatalytic-mediated phosphorylation of PKA/RIIβ and PKA activity. D-AKAP1/PKA governs mitochondrial trafficking in dendrites via the Miro-2/TRAK2 complex and by increasing the phosphorylation of Miro-2. Our study identifies a new role of D-AKAP1 in regulating mitochondrial trafficking through Miro-2, and supports a model in which PINK1 and mitochondrial PKA participate in a similar neuroprotective signaling pathway to maintain dendrite connectivity. © 2017 International Society for Neurochemistry.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  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. Physical protection as the most important part of the national system of combating illicit trafficking

    International Nuclear Information System (INIS)

    Ivanov, P.; Kokhan, V.D.

    2001-01-01

    based on the Convention on Physical Protection, IAEA Guidelines and Recommendations on Physical Protection of Nuclear Materials and Nuclear Installations as well as 'Basic Safety Standards for Ionising Radiation', practical application of which facilitates the development of a national system for combating illicit trafficking of radioactive materials and sources of radiation. These documents will assist in creating basic national legislation. An integrated approach should be provided for the improvement of the System of Physical Protection. These are main provisions of the Concept of Integration of the System of Physical Protection with the System of Accountancy and Control of Nuclear Materials. Goals: earlier detection of theft; improve accuracy of accounts, strengthen objectives and integrity of control; ensure personnel's safety; reduce dependence on human factor; speed-up detection and retrieval of stolen or lost material. The system is based on: national norms and regulations for accountancy, control and physical protection of nuclear materials and installations; existing control and management structure for nuclear materials and nuclear installations; senior officials and companies responsible for organization and quality assurance regarding work on accountancy, control and physical protection; new principles of accountancy and control; methods for supervision of working procedures, response to any abnormal event; model of life circle of nuclear materials; zone classification of nuclear materials etc. Establishment of single integrated system for accountancy, control and physical protection will undoubtedly lead to handling illicit trafficking of nuclear materials more efficiently and to eliminating unauthorized distribution of nuclear materials

  16. 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.

  17. 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

  18. Neural stem cell-derived exosomes mediate viral entry

    Directory of Open Access Journals (Sweden)

    Sims B

    2014-10-01

    Full Text Available Brian Sims,1,2,* Linlin Gu,3,* Alexandre Krendelchtchikov,3 Qiana L Matthews3,4 1Division of Neonatology, Department of Pediatrics, 2Department of Cell, Developmental, and Integrative Biology, 3Division of Infectious Diseases, Department of Medicine, 4Center for AIDS Research, University of Alabama at Birmingham, Birmingham, AL, USA *These authors contributed equally to this work Background: Viruses enter host cells through interactions of viral ligands with cellular receptors. Viruses can also enter cells in a receptor-independent fashion. Mechanisms regarding the receptor-independent viral entry into cells have not been fully elucidated. Exosomal trafficking between cells may offer a mechanism by which viruses can enter cells.Methods: To investigate the role of exosomes on cellular viral entry, we employed neural stem cell-derived exosomes and adenovirus type 5 (Ad5 for the proof-of-principle study. Results: Exosomes significantly enhanced Ad5 entry in Coxsackie virus and adenovirus receptor (CAR-deficient cells, in which Ad5 only had very limited entry. The exosomes were shown to contain T-cell immunoglobulin mucin protein 4 (TIM-4, which binds phosphatidylserine. Treatment with anti-TIM-4 antibody significantly blocked the exosome-mediated Ad5 entry.Conclusion: Neural stem cell-derived exosomes mediated significant cellular entry of Ad5 in a receptor-independent fashion. This mediation may be hampered by an antibody specifically targeting TIM-4 on exosomes. This set of results will benefit further elucidation of virus/exosome pathways, which would contribute to reducing natural viral infection by developing therapeutic agents or vaccines. Keywords: neural stem cell-derived exosomes, adenovirus type 5, TIM-4, viral entry, phospholipids

  19. 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

  20. Hepatitis B virus DNA integration occurs early in the viral life cycle in an in vitro infection model via NTCP-dependent uptake of enveloped virus particles.

    Science.gov (United States)

    Tu, Thomas; Budzinska, Magdalena A; Vondran, Florian W R; Shackel, Nicholas A; Urban, Stephan

    2018-02-07

    Chronic infection by the Hepatitis B Virus (HBV) is the major contributor to liver disease worldwide. Though HBV replicates via a nuclear episomal DNA (cccDNA), integration of HBV DNA into the host cell genome is regularly observed in the liver of infected patients. While reported as a pro-oncogenic alteration, the mechanism(s) and timing of HBV DNA integration are not well-understood, chiefly due to the lack of in vitro infection models that have detectable integration events. Here, we have established an in vitro system in which integration can be reliably detected following HBV infection. We measured HBV DNA integration using inverse nested PCR in primary human hepatocytes, HepaRG-NTCP, HepG2-NTCP, and Huh7-NTCP cells after HBV infection. Integration was detected in all cell types at a rate of >1 per 10000 cells, with the most consistent detection in Huh7-NTCP cells. Integration rate remained stable between 3 and 9 days post-infection. HBV DNA integration was efficiently blocked by treatment with 200nM of the HBV entry inhibitor Myrcludex B, but not with 10μM Tenofovir, 100U Interferon alpha, or 1μM of the capsid assembly inhibitor GLS4. This suggests integration of HBV DNA occurs immediately after infection of hepatocytes and is likely independent of de novo HBV replication in this model. Site analysis revealed that HBV DNA integrations were distributed over the entire human genome. Further, integrated HBV DNA sequences were consistent with double-stranded linear HBV DNA being the major precursor. Thus, we have established an in vitro system to interrogate the mechanisms of HBV DNA integration. Importance Hepatitis B Virus (HBV) is a common blood-borne pathogen and, following a chronic infection, can cause liver cancer and liver cirrhosis. Integration of HBV DNA into the host genome occurs in all known members of the hepadnaviridae family, despite this form not being necessary for viral replication. HBV DNA integration has been reported to drive liver cancer

  1. Contagious Content: Viral Video Ads Identification of Content Characteristics that Help Online Video Advertisements Go Viral

    Directory of Open Access Journals (Sweden)

    Yentl Knossenburg

    2016-12-01

    Full Text Available Why do some online video advertisements go viral while others remain unnoticed? What kind of video content keeps the viewer interested and motivated to share? Many companies have realized the need to innovate their marketing strategies and have embraced the newest ways of using technology, as the Internet, to their advantage as in the example of virality. Yet few marketers actually understand how, and academic literature on this topic is still in development. This study investigated which content characteristics distinguish successful from non-successful online viral video advertisements by analyzing 641 cases using Structural Equation Modeling. Results show that Engagement and Surprise are two main content characteristics that significantly increase the chance of online video advertisements to go viral.  

  2. Cardiovirus Leader proteins bind exportins: Implications for virus replication and nucleocytoplasmic trafficking inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Ciomperlik, Jessica J. [Institute for Molecular Virology and Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706 (United States); Basta, Holly A. [Department of Biology, Rocky Mountain College, Billings, MT (United States); Palmenberg, Ann C., E-mail: acpalmen@wisc.edu [Institute for Molecular Virology and Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706 (United States)

    2016-01-15

    Cardiovirus Leader proteins (L{sub X}) inhibit cellular nucleocytoplasmic trafficking by directing host kinases to phosphorylate Phe/Gly-containing nuclear pore proteins (Nups). Resolution of the Mengovirus L{sub M} structure bound to Ran GTPase, suggested this complex would further recruit specific exportins (karyopherins), which in turn mediate kinase selection. Pull-down experiments and recombinant complex reconstitution now confirm that Crm1 and CAS exportins form stable dimeric complexes with encephalomyocarditis virus L{sub E}, and also larger complexes with L{sub E}:Ran. shRNA knockdown studies support this idea. Similar activities could be demonstrated for recombinant L{sub S} and L{sub T} from Theiloviruses. When mutations were introduced to alter the L{sub E} zinc finger domain, acidic domain, or dual phosphorylation sites, there was reduced exportin selection. These regions are not involved in Ran interactions, so the Ran and Crm1 binding sites on L{sub E} must be non-overlapping. The involvement of exportins in this mechanism is important to viral replication and the observation of trafficking inhibition by L{sub E}.

  3. Intracellular trafficking of VP22 in bovine herpesvirus-1 infected cells

    International Nuclear Information System (INIS)

    Lobanov, Vladislav A.; Babiuk, Lorne A.; Drunen Littel-van den Hurk, Sylvia van

    2010-01-01

    The intracellular trafficking of different VP22-enhanced yellow fluorescent protein (EYFP) fusion proteins expressed by bovine herpesvirus-1 (BHV-1) recombinants was examined by live-cell imaging. Our results demonstrate that (i) the fusion of EYFP to the C terminus of VP22 does not alter the trafficking of the protein in infected cells, (ii) VP22 expressed during BHV-1 infection translocates to the nucleus through three different pathways, namely early mitosis-dependent nuclear translocation, late massive nuclear translocation that follows a prolonged cytoplasmic stage of the protein in non-mitotic cells, and accumulation of a small subset of VP22 in discrete dot-like nuclear domains during its early cytoplasmic stage, (iii) the addition of the SV40 large-T-antigen nuclear localization signal (NLS) to VP22-EYFP abrogates its early cytoplasmic stage, and (iv) the VP22 131 PRPR 134 NLS is not required for the late massive nuclear translocation of the protein, but this motif is essential for the targeting of VP22 to discrete dot-like nuclear domains during the early cytoplasmic stage. These results show that the amount of VP22 in the nucleus is precisely regulated at different stages of BHV-1 infection and suggest that the early pathways of VP22 nuclear accumulation may be more relevant to the infection process as the late massive nuclear influx starts when most of the viral progeny has already emerged from the cell.

  4. Outcomes from monitoring of patients on antiretroviral therapy in resource-limited settings with viral load, CD4 cell count, or clinical observation alone: a computer simulation model

    DEFF Research Database (Denmark)

    Phillips, Andrew N; Pillay, Deenan; Miners, Alec H

    2008-01-01

    BACKGROUND: In lower-income countries, WHO recommends a population-based approach to antiretroviral treatment with standardised regimens and clinical decision making based on clinical status and, where available CD4 cell count, rather than viral load. Our aim was to study the potential consequenc...... laboratory monitoring-is currently the highest priority....

  5. Viral particles of endogenous betaretroviruses are released in the sheep uterus and infect the conceptus trophectoderm in a transspecies embryo transfer model.

    Science.gov (United States)

    Black, Sarah G; Arnaud, Frederick; Burghardt, Robert C; Satterfield, M Carey; Fleming, Jo-Ann G W; Long, Charles R; Hanna, Carol; Murphy, Lita; Biek, Roman; Palmarini, Massimo; Spencer, Thomas E

    2010-09-01

    The sheep genome contains multiple copies of endogenous betaretroviruses highly related to the exogenous and oncogenic jaagsiekte sheep retrovirus (JSRV). The endogenous JSRVs (enJSRVs) are abundantly expressed in the uterine luminal and glandular epithelia as well as in the conceptus trophectoderm and are essential for conceptus elongation and trophectoderm growth and development. Of note, enJSRVs are present in sheep and goats but not cattle. At least 5 of the 27 enJSRV loci cloned to date possess an intact genomic organization and are able to produce viral particles in vitro. In this study, we found that enJSRVs form viral particles that are released into the uterine lumen of sheep. In order to test the infectious potential of enJSRV particles in the uterus, we transferred bovine blastocysts into synchronized ovine recipients and allowed them to develop for 13 days. Analysis of microdissected trophectoderm of the bovine conceptuses revealed the presence of enJSRV RNA and, in some cases, DNA. Interestingly, we found that RNAs belonging to only the most recently integrated enJSRV loci were packaged into viral particles and transmitted to the trophectoderm. Collectively, these results support the hypothesis that intact enJSRV loci expressed in the uterine endometrial epithelia are shed into the uterine lumen and could potentially transduce the conceptus trophectoderm. The essential role played by enJSRVs in sheep reproductive biology could also be played by endometrium-derived viral particles that influence development and differentiation of the trophectoderm.

  6. Viral capsid assembly as a model for protein aggregation diseases: Active processes catalyzed by cellular assembly machines comprising novel drug targets.

    Science.gov (United States)

    Marreiros, Rita; Müller-Schiffmann, Andreas; Bader, Verian; Selvarajah, Suganya; Dey, Debendranath; Lingappa, Vishwanath R; Korth, Carsten

    2015-09-02

    Viruses can be conceptualized as self-replicating multiprotein assemblies, containing coding nucleic acids. Viruses have evolved to exploit host cellular components including enzymes to ensure their replicative life cycle. New findings indicate that also viral capsid proteins recruit host factors to accelerate their assembly. These assembly machines are RNA-containing multiprotein complexes whose composition is governed by allosteric sites. In the event of viral infection, the assembly machines are recruited to support the virus over the host and are modified to achieve that goal. Stress granules and processing bodies may represent collections of such assembly machines, readily visible by microscopy but biochemically labile and difficult to isolate by fractionation. We hypothesize that the assembly of protein multimers such as encountered in neurodegenerative or other protein conformational diseases, is also catalyzed by assembly machines. In the case of viral infection, the assembly machines have been modified by the virus to meet the virus' need for rapid capsid assembly rather than host homeostasis. In the case of the neurodegenerative diseases, it is the monomers and/or low n oligomers of the so-called aggregated proteins that are substrates of assembly machines. Examples for substrates are amyloid β peptide (Aβ) and tau in Alzheimer's disease, α-synuclein in Parkinson's disease, prions in the prion diseases, Disrupted-in-schizophrenia 1 (DISC1) in subsets of chronic mental illnesses, and others. A likely continuum between virus capsid assembly and cell-to-cell transmissibility of aggregated proteins is remarkable. Protein aggregation diseases may represent dysfunction and dysregulation of these assembly machines analogous to the aberrations induced by viral infection in which cellular homeostasis is pathologically reprogrammed. In this view, as for viral infection, reset of assembly machines to normal homeostasis should be the goal of protein aggregation

  7. 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

  8. Homeostatic regulation of T cell trafficking by a B cell derived peptide is impaired in autoimmune and chronic inflammatory disease

    Science.gov (United States)

    Apta, Bonita; Kuravi, Sahithi J.; Yates, Clara M.; Kennedy, Amy; Odedra, Arjun; Alassiri, Mohammed; Harrison, Matthew; Martin, Ashley; Barone, Francesca; Nayar, Saba; Hitchcock, Jessica R.; Cunningham, Adam F.; Raza, Karim; Filer, Andrew; Copland, David A.; Dick, Andrew D.; Robinson, Joseph; Kalia, Neena; Walker, Lucy S. K.; Buckley, Christopher D.; Nash, Gerard B.; Narendran, Parth; Rainger, G. Ed.

    2015-01-01

    During an inflammatory response, lymphocyte recruitment into tissue must be tightly controlled because dysregulated trafficking contributes to the pathogenesis of chronic disease. Here we show that during inflammation and in response to adiponectin, B cells tonically inhibit T cell trafficking by secreting a peptide (PEPITEM) proteolytically derived from 14.3.3.ζδ protein. PEPITEM binds cadherin-15 on endothelial cells, promoting synthesis and release of sphingosine-1 phosphate, which inhibits trafficking of T cells without affecting recruitment of other leukocytes. Expression of adiponectin receptors on B cells and adiponectin induced PEPITEM secretion wanes with age, implying immune senescence of the pathway. Additionally, these changes are evident in individuals with type-1-diabetes or rheumatoid arthritis, and circulating PEPITEM in patient serum is reduced compared to healthy age matched donors. In both diseases, tonic inhibition of T cell trafficking across inflamed endothelium is lost. Importantly, control of patient T cell trafficking is re-established by exogenous PEPITEM. Moreover, in animal models of peritonitis, hepatic I/R injury, Salmonella infection, Uveitis and Sjögren’s Syndrome, PEPITEM could reduce T cell recruitment into inflamed tissues. PMID:25894827

  9. HIV-1 infection, response to treatment and establishment of viral latency in a novel humanized T cell-only mouse (TOM) model.

    Science.gov (United States)

    Honeycutt, Jenna B; Wahl, Angela; Archin, Nancie; Choudhary, Shailesh; Margolis, David; Garcia, J Victor

    2013-10-24

    The major targets of HIV infection in humans are CD4⁺ T cells. CD4⁺ T cell depletion is a hallmark of AIDS. Previously, the SCID-hu thy/liv model was used to study the effect of HIV on thymopoeisis in vivo. However, these mice did not develop high levels of peripheral T cell reconstitution and required invasive surgery for infection and analysis. Here, we describe a novel variant of this model in which thy/liv implantation results in systemic reconstitution with human T cells in the absence of any other human hematopoietic lineages. NOD/SCID-hu thy/liv and NSG-hu thy/liv mice were created by implanting human fetal thymus and liver tissues under the kidney capsule of either NOD/SCID or NSG mice. In contrast to NOD/SCID-hu thy/liv mice that show little or no human cells in peripheral blood or tissues, substantial systemic human reconstitution occurs in NSG-hu thy/liv. These mice are exclusively reconstituted with human T cells (i.e. T-cell only mice or TOM). Despite substantial levels of human T cells no signs of graft-versus-host disease (GVHD) were noted in these mice over a period of 14 months. TOM are readily infected after parenteral exposure to HIV-1. HIV replication is sustained in peripheral blood at high levels and results in modest reduction of CD4⁺ T cells. HIV-1 replication in TOM responds to daily administration of combination antiretroviral therapy (ART) resulting in strong suppression of virus replication as determined by undetectable viral load in plasma. Latently HIV infected resting CD4⁺ T cells can be isolated from suppressed mice that can be induced to express HIV ex-vivo upon activation demonstrating the establishment of latency in vivo. NSG-hu thy/liv mice are systemically reconstituted with human T cells. No other human lymphoid lineages are present in these mice (i.e. monocytes/macrophages, B cells and DC are all absent). These T cell only mice do not develop GVHD, are susceptible to HIV-1 infection and can efficiently maintain virus

  10. Dengue viral infections

    OpenAIRE

    Gurugama Padmalal; Garg Pankaj; Perera Jennifer; Wijewickrama Ananda; Seneviratne Suranjith

    2010-01-01

    Dengue viral infections are one of the most important mosquito-borne diseases in the world. Presently dengue is endemic in 112 countries in the world. It has been estimated that almost 100 million cases of dengue fever and half a million cases of dengue hemorrhagic fever (DHF) occur worldwide. An increasing proportion of DHF is in children less than 15 years of age, especially in South East and South Asia. The unique structure of the dengue virus and the pathophysiologic responses of the host...

  11. Engaging Survivors of Human Trafficking: Complex Health Care Needs and Scarce Resources.

    Science.gov (United States)

    Judge, Abigail M; Murphy, Jennifer A; Hidalgo, Jose; Macias-Konstantopoulos, Wendy

    2018-05-01

    Human trafficking, also known as modern-day slavery, is an egregious human rights violation associated with wide-ranging medical and mental health consequences. Because of the extensive health problems related to trafficking, health care providers play a critical role in identifying survivors and engaging them in ongoing care. Although guidelines for recognizing affected patients and a framework for developing response protocols in health care settings have been described, survivors' ongoing engagement in health care services is very challenging. High rates of disengagement, lost contact, premature termination, and attrition are common outcomes. For interventions to be effective in this marginalized population, challenges in engaging survivors in long-term therapeutic primary and mental health care must be better understood and overcome. This article uses the socioecological model of public health to identify barriers to engagement; offers evidence- and practice-based recommendations for overcoming these barriers; and proposes an interdisciplinary call to action for developing more flexible, adaptable models of care.

  12. 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.

  13. 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.

  14. 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…

  15. 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…

  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. 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.

  19. 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

  20. 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)

  1. 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

  2. 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...

  3. 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 ...

  4. 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.

  5. 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

  6. Role of cellular FKBP52 protein in intracellular trafficking of recombinant adeno-associated virus 2 vectors

    International Nuclear Information System (INIS)

    Zhao Weihong; Zhong Li; Wu Jianqing; Chen Linyuan; Qing Keyun; Weigel-Kelley, Kirsten A.; Larsen, Steven H.; Shou Weinian; Warrington, Kenneth H.; Srivastava, Arun

    2006-01-01

    We have reported that tyrosine-phosphorylated forms of a cellular protein, FKBP52, inhibit the second-strand DNA synthesis of adeno-associated virus 2 (AAV), leading to inefficient transgene expression from recombinant AAV vectors. To further explore the role of FKBP52 in AAV-mediated transduction, we established murine embryo fibroblasts (MEFs) cultures from FKBP52 wild-type (WT), heterozygous (HE), and knockout (KO) mice. Conventional AAV vectors failed to transduce WT MEFs efficiently, and the transduction efficiency was not significantly increased in HE or KO MEFs. AAV vectors failed to traffic efficiently to the nucleus in these cells. Treatment with hydroxyurea (HU) increased the transduction efficiency of conventional AAV vectors by ∼25-fold in WT MEFs, but only by ∼4-fold in KO MEFs. The use of self-complementary AAV (scAAV) vectors, which bypass the requirement of viral second-strand DNA synthesis, revealed that HU treatment increased the transduction efficiency ∼23-fold in WT MEFs, but only ∼4-fold in KO MEFs, indicating that the lack of HU treatment-mediated increase in KO MEFs was not due to failure of AAV to undergo viral second-strand DNA synthesis. Following HU treatment, ∼59% of AAV genomes were present in the nuclear fraction from WT MEFs, but only ∼28% in KO MEFs, indicating that the pathway by which HU treatment mediates nuclear transport of AAV was impaired in KO MEFs. When KO MEFs were stably transfected with an FKBP52 expression plasmid, HU treatment-mediated increase in the transduction efficiency was restored in these cells, which correlated directly with improved intracellular trafficking. Intact AAV particles were also shown to interact with FKBP52 as well as with dynein, a known cellular protein involved in AAV trafficking. These studies suggest that FKBP52, being a cellular chaperone protein, facilitates intracellular trafficking of AAV, which has implications in the optimal use of recombinant AAV vectors in human gene

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

    Directory of Open Access Journals (Sweden)

    Christopher R Bohl

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

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

    Science.gov (United States)

    Seo, Jun-Young; Jeon, Hyejin; Hong, Sookyung; Britt, William J

    2016-10-01

    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 cluster was sufficient for pp28 trafficking, whereas the native acidic cluster consisting of aa 51-59 was required for the assembly of wild-type levels of infectious virus.

  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. 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

  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

    2015-08-20

    (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

  12. Gut-associated lymphoid tissue, T cell trafficking, and chronic intestinal inflammation.

    Science.gov (United States)

    Koboziev, Iurii; Karlsson, Fridrik; Grisham, Matthew B

    2010-10-01

    The etiologies of the inflammatory bowel diseases (IBD; Crohn's disease, ulcerative colitis) have not been fully elucidated. However, there is very good evidence implicating T cell and T cell trafficking to the gut and its associated lymphoid tissue as important components in disease pathogenesis. The objective of this review is to provide an overview of the mechanisms involved in naive and effector T cell trafficking to the gut-associated lymphoid tissue (GALT; Peyer's patches, isolated lymphoid follicles), mesenteric lymph nodes and intestine in response to commensal enteric antigens under physiological conditions as well as during the induction of chronic gut inflammation. In addition, recent data suggests that the GALT may not be required for enteric antigen-driven intestinal inflammation in certain mouse models of IBD. These new data suggest a possible paradigm shift in our understanding of how and where naive T cells become activated to yield disease-producing effector cells. © 2010 New York Academy of Sciences.

  13. Equine viral arteritis

    Directory of Open Access Journals (Sweden)

    Kosec Marjan

    2016-01-01

    Full Text Available Equine viral arteritis (EVA is a contagious disease of equids caused by equine artheritis virus (EAV, widespread in most countries in the world, where patients are diagnosed. The infection usually starts asymptomatic. Clinical signs indicate respiratory infection of different intensity and also abortions are present at different stages of gestation. Large prevalence of this disease in the world has become a growing economic problem. The disease is specific to a particular kind of animals, and it affects only equids (horses, donkeys, mules, mule and zebras. In countries where the infection has been confirmed, the percentage of positive animals differ. Likewise, there is difference in percentage among certain animal kinds. The highest percentage of positive animals has been found in totters and the lowest in cold-blooded.

  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. 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...

  5. 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.

  6. 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.

  7. 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.

  8. 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...

  9. 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...

  10. Viral/Host interaction in viral infections

    International Nuclear Information System (INIS)

    Le Grand, R.

    2006-01-01

    The major objectives of the Neuro-virology Department (SNV for 'Service de Neurovirologie') are related to the study of host/pathogen interactions, particularly during primate lentiviral infections. Various experimental models have been developed such as non-human primates infected with the HIV-related simian immunodeficiency viruses (SIV), as an animal model of human AIDS. The current research programs of the SNV following four main directions: 1) Study of the pathogenesis of primate lentiviral infection, including mucosal transmission of HIV/SIV, primary infection, dissemination to various reservoirs, neuro-pathogenesis and hematopoietic disorders; 2) Prevention of HIV transmission, particularly through vaccination but also by means of microbicides applied to genital mucosa and post-exposure treatment with antiviral drugs; 3) Cellular and molecular pharmacology of new antiviral compounds; 4) Development of new primate models of human hematological disorders like chronic myeloid leukemia cells and development on new gene transfer in hematopoietic cells based on the use of lentiviral vectors Main programs of the SNV will be presented as well as the perspective focused on the use of non invasive in vivo imaging approaches for the exploration of immune and hematopoietic cells

  11. Viral/Host interaction in viral infections

    Energy Technology Data Exchange (ETDEWEB)

    Le Grand, R. [CEA Fontenay-aux-Roses, Service de Neurovirologie, 92 (France)

    2006-07-01

    The major objectives of the Neuro-virology Department (SNV for 'Service de Neurovirologie') are related to the study of host/pathogen interactions, particularly during primate lentiviral infections. Various experimental models have been developed such as non-human primates infected with the HIV-related simian immunodeficiency viruses (SIV), as an animal model of human AIDS. The current research programs of the SNV following four main directions: 1) Study of the pathogenesis of primate lentiviral infection, including mucosal transmission of HIV/SIV, primary infection, dissemination to various reservoirs, neuro-pathogenesis and hematopoietic disorders; 2) Prevention of HIV transmission, particularly through vaccination but also by means of microbicides applied to genital mucosa and post-exposure treatment with antiviral drugs; 3) Cellular and molecular pharmacology of new antiviral compounds; 4) Development of new primate models of human hematological disorders like chronic myeloid leukemia cells and development on new gene transfer in hematopoietic cells based on the use of lentiviral vectors Main programs of the SNV will be presented as well as the perspective focused on the use of non invasive in vivo imaging approaches for the exploration of immune and hematopoietic cells.

  12. Role of proper response schemes, legislation and regional co-operation in combating illicit trafficking of nuclear materials in developing countries

    International Nuclear Information System (INIS)

    Sterzov, A.

    2003-01-01

    Bulgaria's geographical location - between Europe, the former Soviet Union, and the Middle East - exposes it to much illegal trafficking: of people, arms, drugs, etc. The trafficking of nuclear and radioactive materials in Bulgaria can be divided in two main parts - internal and transit. Internal trafficking consists of stolen radioactive sources such as counters and densitometers, irradiation devices, tools for removing static electricity, and smoke detectors, which mainly contain the isotopes 137 Cs, 60 Co, 192 Ir, 226 Ra and 241 Am. The external trafficking of illicit nuclear materials is connected with transfer of raw materials and expensive metals from the former Soviet Union to countries in Western Europe and the Middle East, including aluminium, osmium, caesium, scandium, rare earth elements, red mercury, plutonium and enriched uranium. Detecting internal and external trafficking poses serious problems for the Bulgarian authorities, in terms of equipment and qualified personnel at the borders and inside the country. Developing countries need protocols for detecting and responding to illicit trafficking of nuclear materials, which is a new threat that requires rapid implementation of comprehensive measures and efforts, novel approaches, coordination of services and institutions, and even new legislation. The paper describes a three step model for better and more rapid responses for combating illicit nuclear trafficking in Bulgaria.The steps involve developing first response protocols, using nondestructive analytical means to categorize materials on-site, followed by in-depth analysis. It is also important to initiate contacts with neighbouring countries to foster regional collaboration among law enforcement agencies, customs authorities, analytical laboratories, etc., to improve efficiency in combating illicit trafficking of nuclear materials. (author)

  13. 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.

  14. 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

  15. 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...

  16. Reflecting the real value of health care resources in modelling and cost-effectiveness studies-The example of viral load informed differentiated care.

    Science.gov (United States)

    Revill, Paul; Walker, Simon; Cambiano, Valentina; Phillips, Andrew; Sculpher, Mark J

    2018-01-01

    The WHO HIV Treatment Guidelines suggest routine viral-load monitoring can be used to differentiate antiretroviral therapy (ART) delivery and reduce the frequency of clinic visits for patients stable on ART. This recommendation was informed by economic analysis that showed the approach is very likely to be cost-effective, even in the most resource constrained of settings. The health benefits were shown to be modest but the costs of introducing and scaling up viral load monitoring can be offset by anticipated reductions in the costs of clinic visits, due to these being less frequent for many patients. The cost-effectiveness of introducing viral-load informed differentiated care depends upon whether cost reductions are possible if the number of clinic visits is reduced and/or how freed clinic capacity is used for alternative priorities. Where freed resources, either physical or financial, generate large health gains (e.g. if committed to patients failing ART or to other high value health care interventions), the benefits of differentiated care are expected to be high; if however these freed physical resources are already under-utilized or financial resources are used less efficiently and would not be put to as beneficial an alternative use, the policy may not be cost-effective. The implication is that the use of conventional unit costs to value resources may not well reflect the latter's value in contributing to health improvement. Analyses intended to inform resource allocated decisions in a number of settings may therefore have to be interpreted with due consideration to local context. In this paper we present methods of how economic analyses can reflect the real value of health care resources rather than simply applying their unit costs. The analyses informing the WHO Guidelines are re-estimated by implementing scenarios using this framework, informing how differentiated care can be prioritized to generate greatest gains in population health. The findings have

  17. Reflecting the real value of health care resources in modelling and cost-effectiveness studies—The example of viral load informed differentiated care

    Science.gov (United States)

    Walker, Simon; Cambiano, Valentina; Phillips, Andrew; Sculpher, Mark J.

    2018-01-01

    Background The WHO HIV Treatment Guidelines suggest routine viral-load monitoring can be used to differentiate antiretroviral therapy (ART) delivery and reduce the frequency of clinic visits for patients stable on ART. This recommendation was informed by economic analysis that showed the approach is very likely to be cost-effective, even in the most resource constrained of settings. The health benefits were shown to be modest but the costs of introducing and scaling up viral load monitoring can be offset by anticipated reductions in the costs of clinic visits, due to these being less frequent for many patients. Key issues for economic evaluation The cost-effectiveness of introducing viral-load informed differentiated care depends upon whether cost reductions are possible if the number of clinic visits is reduced and/or how freed clinic capacity is used for alternative priorities. Where freed resources, either physical or financial, generate large health gains (e.g. if committed to patients failing ART or to other high value health care interventions), the benefits of differentiated care are expected to be high; if however these freed physical resources are already under-utilized or financial resources are used less efficiently and would not be put to as beneficial an alternative use, the policy may not be cost-effective. The implication is that the use of conventional unit costs to value resources may not well reflect the latter’s value in contributing to health improvement. Analyses intended to inform resource allocated decisions in a number of settings may therefore have to be interpreted with due consideration to local context. In this paper we present methods of how economic analyses can reflect the real value of health care resources rather than simply applying their unit costs. The analyses informing the WHO Guidelines are re-estimated by implementing scenarios using this framework, informing how differentiated care can be prioritized to generate greatest

  18. 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.

  19. 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.

  20. 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

  1. The Relation of Visual Signs In The Narrative Structure of MTV Exit Human Trafficking Campaign Video

    Directory of Open Access Journals (Sweden)

    Winny Gunarti

    2013-08-01

    Full Text Available Human trafficking is a violation of the human rights. One of the campaign to fight against this crime takes the form of a digital campaign that aired on television and internet.   This study discusses the narrative structure of human trafficking campaign video from non-profit organization MTV Exit in 2012. This video campaign combines art collage and graphic art in its narrative structure. Nonverbal visual elements displayed in the form of a digital photo collage with animated illustrations setting. We consider this video campaign quite interesting as it is visually inform the public about the importance of safe migration through the visual signs in the narrative structure. This study analyzes qualitatively the relation of nonverbal visual signs in the narrative collage and illustration. Denotative and connotative analysis with structural semiotics approach is needed to understand the meaning of visual signs in the context of humans as cultural beings in their communities. This study is expected to be a model example of visual communication campaigns that can foster public awareness of the issue of human trafficking, especially for young women and children as young generation.

  2. Studying illicit drug trafficking on Darknet markets: Structure and organisation from a Canadian perspective.

    Science.gov (United States)

    Broséus, J; Rhumorbarbe, D; Mireault, C; Ouellette, V; Crispino, F; Décary-Hétu, D

    2016-07-01

    Cryptomarkets are online marketplaces that are part of the Dark Web and mainly devoted to the sale of illicit drugs. They combine tools to ensure anonymity of participants with the delivery of products by mail to enable the development of illicit drug trafficking. Using data collected on eight cryptomarkets, this study provides an overview of the Canadian illicit drug market. It seeks to inform about the most prevalent illicit drugs vendors offer for sale and preferred destination countries. Moreover, the research gives an insight into the structure and organisation of distribution networks existing online. In particular, we provide information about how vendors are diversifying and replicating across marketplaces. We inform on the number of listings each vendor manages, the number of cryptomarkets they are active on and the products they offer. This research demonstrates the importance of online marketplaces in the context of illicit drug trafficking. It shows how the analysis of data available online may elicit knowledge on criminal activities. Such knowledge is mandatory to design efficient policy for monitoring or repressive purposes against anonymous marketplaces. Nevertheless, trafficking on Dark Net markets is difficult to analyse based only on digital data. A more holistic approach for investigating this crime problem should be developed. This should rely on a combined use and interpretation of digital and physical data within a single collaborative intelligence model. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Drosophila Vps16A is required for trafficking to lysosomes and biogenesis of pigment granules.

    Science.gov (United States)

    Pulipparacharuvil, Suprabha; Akbar, Mohammed Ali; Ray, Sanchali; Sevrioukov, Evgueny A; Haberman, Adam S; Rohrer, Jack; Krämer, Helmut

    2005-08-15

    Mutations that disrupt trafficking to lysosomes and lysosome-related organelles cause multiple diseases, including Hermansky-Pudlak syndrome. The Drosophila eye is a model system for analyzing such mutations. The eye-color genes carnation and deep orange encode two subunits of the Vps-C protein complex required for endosomal trafficking and pigment-granule biogenesis. Here we demonstrate that dVps16A (CG8454) encodes another Vps-C subunit. Biochemical experiments revealed a specific interaction between the dVps16A C-terminus and the Sec1/Munc18 homolog Carnation but not its closest homolog, dVps33B. Instead, dVps33B interacted with a related protein, dVps16B (CG18112). Deep orange bound both Vps16 homologs. Like a deep orange null mutation, eye-specific RNAi-induced knockdown of dVps16A inhibited lysosomal delivery of internalized ligands and interfered with biogenesis of pigment granules. Ubiquitous knockdown of dVps16A was lethal. Together, these findings demonstrate that Drosophila Vps16A is essential for lysosomal trafficking. Furthermore, metazoans have two types of Vps-C complexes with non-redundant functions.

  4. 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

  5. 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

  6. 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.

  7. Structure, function and physiological consequences of virally encoded chemokine seven transmembrane receptors

    DEFF Research Database (Denmark)

    Rosenkilde, M M; Smit, M J; Waldhoer, M

    2008-01-01

    A number of human and animal herpes viruses encode G-protein coupled receptors with seven transmembrane (7TM) segments-most of which are clearly related to human chemokine receptors. It appears, that these receptors are used by the virus for immune evasion, cellular transformation, tissue targeting...... pathogenesis is still poorly understood. Here we focus on the current knowledge of structure, function and trafficking patterns of virally encoded chemokine receptors and further address the putative roles of these receptors in virus survival and host -cell and/or -immune system modulation. Finally, we...

  8. Viral myositis in children.

    Science.gov (United States)

    Magee, Haley; Goldman, Ran D

    2017-05-01

    Question I recently evaluated a child in my clinic after an emergency department visit where she presented having woken up that morning refusing to walk and was crawling around the house. The parents reported she was getting over a cold, and I recall similar cases of myositis during the H1N1 influenza epidemic a few years ago. What are the key features of myositis that I should recognize? Which investigations are needed to confirm the diagnosis and how should affected patients be managed? Answer Benign acute childhood myositis is a mild and self-limited sudden onset of lower extremity pain during or following recovery from a viral illness. Presentation can include tiptoe gait or refusal to walk, secondary to symmetric bilateral lower extremity pain that resolves quickly, usually within 3 days. In general, no investigation is needed except in severe cases for which screening bloodwork and a urine myoglobin test can confirm the diagnosis and rule out complications. Myoglobinuria and highly elevated creatine phosphokinase levels are rare but should be a consideration for admission to hospital. Prognosis is excellent and management might include rest and analgesia. Copyright© the College of Family Physicians of Canada.

  9. Dengue viral infections

    Directory of Open Access Journals (Sweden)

    Gurugama Padmalal

    2010-01-01

    Full Text Available Dengue viral infections are one of the most important mosquito-borne diseases in the world. Presently dengue is endemic in 112 countries in the world. It has been estimated that almost 100 million cases of dengue fever and half a million cases of dengue hemorrhagic fever (DHF occur worldwide. An increasing proportion of DHF is in children less than 15 years of age, especially in South East and South Asia. The unique structure of the dengue virus and the pathophysiologic responses of the host, different serotypes, and favorable conditions for vector breeding have led to the virulence and spread of the infections. The manifestations of dengue infections are protean from being asymptomatic to undifferentiated fever, severe dengue infections, and unusual complications. Early recognition and prompt initiation of appropriate supportive treatment are often delayed resulting in unnecessarily high morbidity and mortality. Attempts are underway for the development of a vaccine for preventing the burden of this neglected disease. This review outlines the epidemiology, clinical features, pathophysiologic mechanisms, management, and control of dengue infections.

  10. Emerging zoonotic viral diseases.

    Science.gov (United States)

    Wang, L-F; Crameri, G

    2014-08-01

    Zoonotic diseases are infectious diseases that are naturally transmitted from vertebrate animals to humans and vice versa. They are caused by all types of pathogenic agents, including bacteria, parasites, fungi, viruses and prions. Although they have been recognised for many centuries, their impact on public health has increased in the last few decades due to a combination of the success in reducing the spread of human infectious diseases through vaccination and effective therapies and the emergence of novel zoonotic diseases. It is being increasingly recognised that a One Health approach at the human-animal-ecosystem interface is needed for effective investigation, prevention and control of any emerging zoonotic disease. Here, the authors will review the drivers for emergence, highlight some of the high-impact emerging zoonotic diseases of the last two decades and provide examples of novel One Health approaches for disease investigation, prevention and control. Although this review focuses on emerging zoonotic viral diseases, the authors consider that the discussions presented in this paper will be equally applicable to emerging zoonotic diseases of other pathogen types.

  11. Viral Hepatitis: A through E and Beyond

    Science.gov (United States)

    ... National Digestive Diseases Information Clearinghouse What is viral hepatitis? Viral hepatitis is inflammation of the liver caused by ... and serious. Drugs are available to treat chronic hepatitis. 4 Viral Hepatitis: A through E and Beyond What else ...

  12. Requirements within the Ebola Viral Glycoprotein for Tetherin Antagonism

    Directory of Open Access Journals (Sweden)

    Nathan H. Vande Burgt

    2015-10-01

    Full Text Available Tetherin is an interferon-induced, intrinsic cellular response factor that blocks release of numerous viruses, including Ebola virus, from infected cells. As with many viruses targeted by host factors, Ebola virus employs a tetherin antagonist, the viral glycoprotein (EboGP, to counteract restriction and promote virus release. Unlike other tetherin antagonists such as HIV-1 Vpu or KSHV K5, the features within EboGP needed to overcome tetherin are not well characterized. Here, we describe sequences within the EboGP ectodomain and membrane spanning domain (msd as necessary to relieve tetherin restriction of viral particle budding. Fusing the EboGP msd to a normally secreted form of the glycoprotein effectively promotes Ebola virus particle release. Cellular protein or lipid anchors could not substitute for the EboGP msd. The requirement for the EboGP msd was not specific for filovirus budding, as similar results were seen with HIV particles. Furthermore trafficking of chimeric proteins to budding sites did not correlate with an ability to counter tetherin. Additionally, we find that a glycoprotein construct, which mimics the cathepsin-activated species by proteolytic removal of the EboGP glycan cap and mucin domains, is unable to counteract tetherin. Combining these results suggests an important role for the EboGP glycan cap and msd in tetherin antagonism.

  13. KSHV Rta promoter specification and viral reactivation

    Directory of Open Access Journals (Sweden)

    Jonathan eGuito

    2012-02-01

    Full Text Available Viruses are obligate intracellular pathogens whose biological success depends upon replication and packaging of viral genomes, and transmission of progeny viruses to new hosts. The biological success of herpesviruses is enhanced by their ability to reproduce their genomes without producing progeny viruses or killing the host cells, a process called latency. Latency permits a herpesvirus to remain undetected in its animal host for decades while maintaining the potential to reactivate, or switch, to a productive life cycle when host conditions are conducive to generating viral progeny. Direct interactions between many host and viral molecules are implicated in controlling herpesviral reactivation, suggesting complex biological networks that control the decision. One viral protein that is necessary and sufficient to switch latent KSHV into the lytic infection cycle is called K-Rta. Rta is a transcriptional activator that specifies promoters by binding direct DNA directly and interacting with cellular proteins. Among these cellular proteins, binding of K-Rta to RBP-Jk is essential for viral reactivation.. In contrast to the canonical model for Notch signaling, RBP-Jk is not uniformly and constitutively bound to the latent KSHV genome, but rather is recruited to DNA by interactions with K-Rta. Stimulation of RBP-Jk DNA binding requires high affinity binding of Rta to repetitive and palindromic CANT DNA repeats in promoters, and formation of ternary complexes with RBP-Jk. However, while K-Rta expression is necessary for initiating KSHV reactivation, K-Rta’s role as the switch is inefficient. Many factors modulate K-Rta’s function, suggesting that KSHV reactivation can be significantly regulated post-Rta expression and challenging the notion that herpesviral reactivation is bistable. This review analyzes rapidly evolving research on KSHV K-Rta to consider the role of K-Rta promoter specification in regulating the progression of KSHV reactivation.

  14. 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.

  15. 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.

  16. 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.

  17. Application of phase-trafficking methods to natural products research.

    Science.gov (United States)

    Araya, Juan J; Montenegro, Gloria; Mitscher, Lester A; Timmermann, Barbara N

    2010-09-24

    A novel simultaneous phase-trafficking approach using spatially separated solid-supported reagents for rapid separation of neutral, basic, and acidic compounds from organic plant extracts with minimum labor is reported. Acidic and basic ion-exchange resins were physically separated into individual sacks ("tea bags") for trapping basic and acidic compounds, respectively, leaving behind in solution neutral components of the natural mixtures. Trapped compounds were then recovered from solid phase by appropriate suspension in acidic or basic solutions. The feasibility of the proposed separation protocol was demonstrated and optimized with an "artificial mixture" of model compounds. In addition, the utility of this methodology was illustrated with the successful separation of the alkaloid skytanthine from Skytanthus acutus Meyen and the main catechins and caffeine from Camellia sinensis L. (Kuntze). This novel approach offers multiple advantages over traditional extraction methods, as it is not labor intensive, makes use of only small quantities of solvents, produces fractions in adequate quantities for biological assays, and can be easily adapted to field conditions for bioprospecting activities.

  18. Neuroanatomy goes viral!

    Directory of Open Access Journals (Sweden)

    Jonathan eNassi

    2015-07-01

    Full Text Available The nervous system is complex not simply because of the enormous number of neurons it contains but by virtue of the specificity with which they are connected. Unraveling this specificity is the task of neuroanatomy. In this endeavor, neuroanatomists have traditionally exploited an impressive array of tools ranging from the Golgi method to electron microscopy. An ideal method for studying anatomy would label neurons that are interconnected, and, in addition, allow expression of foreign genes in these neurons. Fortuitously, nature has already partially developed such a method in the form of neurotropic viruses, which have evolved to deliver their genetic material between synaptically connected neurons while largely eluding glia and the immune system. While these characteristics make some of these viruses a threat to human health, simple modifications allow them to be used in controlled experimental settings, thus enabling neuroanatomists to trace multi-synaptic connections within and across brain regions. Wild-type neurotropic viruses, such as rabies and alpha-herpes virus, have already contributed greatly to our understanding of brain connectivity, and modern molecular techniques have enabled the construction of recombinant forms of these and other viruses. These newly engineered reagents are particularly useful, as they can target genetically defined populations of neurons, spread only one synapse to either inputs or outputs, and carry instructions by which the targeted neurons can be made to express exogenous proteins, such as calcium sensors or light-sensitive ion channels, that can be used to study neuronal function. In this review, we address these uniquely powerful features of the viruses already in the neuroanatomist's toolbox, as well as the aspects of their biology that currently limit their utility. Based on the latter, we consider strategies for improving viral tracing methods by reducing toxicity, improving control of transsynaptic

  19. Intrinsically disordered region of influenza A NP regulates viral genome packaging via interactions with viral RNA and host PI(4,5)P2.

    Science.gov (United States)

    Kakisaka, Michinori; Yamada, Kazunori; Yamaji-Hasegawa, Akiko; Kobayashi, Toshihide; Aida, Yoko

    2016-09-01

    To be incorporated into progeny virions, the viral genome must be transported to the inner leaflet of the plasma membrane (PM) and accumulate there. Some viruses utilize lipid components to assemble at the PM. For example, simian virus 40 (SV40) targets the ganglioside GM1 and human immunodeficiency virus type 1 (HIV-1) utilizes phosphatidylinositol (4,5) bisphosphate [PI(4,5)P2]. Recent studies clearly indicate that Rab11-mediated recycling endosomes are required for influenza A virus (IAV) trafficking of vRNPs to the PM but it remains unclear how IAV vRNP localized or accumulate underneath the PM for viral genome incorporation into progeny virions. In this study, we found that the second intrinsically disordered region (IDR2) of NP regulates two binding steps involved in viral genome packaging. First, IDR2 facilitates NP oligomer binding to viral RNA to form vRNP. Secondly, vRNP assemble by interacting with PI(4,5)P2 at the PM via IDR2. These findings suggest that PI(4,5)P2 functions as the determinant of vRNP accumulation at the PM. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. 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

  1. Viral Evolution Core | FNLCR Staging

    Science.gov (United States)

    Brandon F. Keele, Ph.D. PI/Senior Principal Investigator, Retroviral Evolution Section Head, Viral Evolution Core Leidos Biomedical Research, Inc. Frederick National Laboratory for Cancer Research Frederick, MD 21702-1201 Tel: 301-846-173

  2. FastStats: Viral Hepatitis

    Science.gov (United States)

    ... Submit What's this? Submit Button NCHS Home Viral Hepatitis Recommend on Facebook Tweet Share Compartir Data are for the U.S. Morbidity Number of new hepatitis A cases: 1,239 (2014) Number of new ...

  3. 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.

  4. 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.

  5. Virus-induced asthma attack: The importance of allergic inflammation in response to viral antigen in an animal model of asthma.

    Science.gov (United States)

    Skappak, Christopher; Ilarraza, Ramses; Wu, Ying-Qi; Drake, Matthew G; Adamko, Darryl J

    2017-01-01

    Asthma exacerbation can be a life-threatening condition, and is most often triggered by common respiratory viruses. Poor asthma control and worsening of respiratory function is associated with increased airway inflammation, including eosinophilia. Prevention of asthma exacerbation relies on treatment with corticosteroids, which preferentially inhibit allergic inflammation like eosinophils. Human studies demonstrate that inactivated virus can trigger eosinophil activation in vitro through antigen presentation and memory CD4+ lymphocytes. We hypothesized that animals with immunologic memory to a respiratory virus would also develop airway hyperresponsiveness in response to a UV-inactivated form of the virus if they have pre-existing allergic airway inflammation. Guinea pigs were ovalbumin-sensitized, infected with live parainfluenza virus (PIV), aerosol-challenged with ovalbumin, and then re-inoculated 60 days later with live or UV-inactivated PIV. Some animals were either treated with dexamethasone prior to the second viral exposure. Lymphocytes were isolated from parabronchial lymph nodes to confirm immunologic memory to the virus. Airway reactivity was measured and inflammation was assessed using bronchoalveolar lavage and lung histology. The induction of viral immunologic memory was confirmed in infected animals. Allergen sensitized and challenged animals developed airway hyperreactivity with eosinophilic airway inflammation when re-exposed to UV-inactivated PIV, while non-sensitized animals did not. Airway hyperreactivity in the sensitized animals was inhibited by pre-treatment with dexamethasone. We suggest that the response of allergic inflammation to virus antigen is a significant factor causing asthma exacerbation. We propose that this is one mechanism explaining how corticosteroids prevent virus-induced asthma attack.

  6. Microbiological diagnostics of viral hepatitis

    OpenAIRE

    HASDEMİR, Ufuk

    2016-01-01

    Viral hepatitis is an infection that primarily affects the liverbut may also have systemic clinical manifestations. The vastmajority of viral hepatitis are caused by one of five hepatotropicviruses: hepatitis A virus (HAV), hepatitis B virus (HBV),hepatitis C virus (HCV), hepatitis D (delta) virus (HDV), andhepatitis E virus (HEV) (Table I) [1]. HBV, HCV, and HDValso cause chronic hepatitis, whereas HAV does not. HEVcauses acute hepatitis in normal hosts but can cause protractedand chronic he...

  7. Viral infections in transplant recipients.

    Science.gov (United States)

    Razonable, R R; Eid, A J

    2009-12-01

    Solid organ and hematopoietic stem cell transplant recipients are uniquely predisposed to develop clinical illness, often with increased severity, due to a variety of common and opportunistic viruses. Patients may acquire viral infections from the donor (donor-derived infections), from reactivation of endogenous latent virus, or from the community. Herpes viruses, most notably cytomegalovirus and Epstein Barr virus, are the most common among opportunistic viral pathogens that cause infection after solid organ and hematopoietic stem cell transplantation. The polyoma BK virus causes opportunistic clinical syndromes predominantly in kidney and allogeneic hematopoietic stem cell transplant recipients. The agents of viral hepatitis B and C present unique challenges particularly among liver transplant recipients. Respiratory viral illnesses due to influenza, respiratory syncytial virus, and parainfluenza virus may affect all types of transplant recipients, although severe clinical disease is observed more commonly among lung and allogeneic hematopoietic stem cell transplant recipients. Less common viral infections affecting transplant recipients include those caused by adenoviruses, parvovirus B19, and West Nile virus. Treatment for viruses with proven effective antiviral drug therapies should be complemented by reduction in the degree of immunosuppression. For others with no proven antiviral drugs for therapy, reduction in the degree of immunosuppression remains as the sole effective strategy for management. Prevention of viral infections is therefore of utmost importance, and this may be accomplished through vaccination, antiviral strategies, and aggressive infection control measures.

  8. Nuclear Imprisonment: Viral Strategies to Arrest Host mRNA Nuclear Export

    Directory of Open Access Journals (Sweden)

    Beatriz M. A. Fontoura

    2013-07-01

    Full Text Available Viruses possess many strategies to impair host cellular responses to infection. Nuclear export of host messenger RNAs (mRNA that encode antiviral factors is critical for antiviral protein production and control of viral infections. Several viruses have evolved sophisticated strategies to inhibit nuclear export of host mRNAs, including targeting mRNA export factors and nucleoporins to compromise their roles in nucleo-cytoplasmic trafficking of cellular mRNA. Here, we present a review of research focused on suppression of host mRNA nuclear export by viruses, including influenza A virus and vesicular stomatitis virus, and the impact of this viral suppression on host antiviral responses.

  9. 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

  10. Immunological features underlying viral hemorrhagic fevers.

    Science.gov (United States)

    Messaoudi, Ilhem; Basler, Christopher F

    2015-10-01

    Several enveloped RNA viruses of the arenavirus, bunyavirus, filovirus and flavivirus families are associated with a syndrome known as viral hemorrhagic fever (VHF). VHF is characterized by fever, vascular leakage, coagulation defects and multi organ system failure. VHF is currently viewed as a disease precipitated by viral suppression of innate immunity, which promotes systemic virus replication and excessive proinflammatory cytokine responses that trigger the manifestations of severe disease. However, the mechanisms by which immune dysregulation contributes to disease remain poorly understood. Infection of nonhuman primates closely recapitulates human VHF, notably Ebola and yellow fever, thereby providing excellent models to better define the immunological basis for this syndrome. Here we review the current state of our knowledge and suggest future directions that will better define the immunological mechanisms underlying VHF. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Identification and Management of Human Trafficking Victims in the Emergency Department.

    Science.gov (United States)

    Hachey, Lisa M; Phillippi, Julia C

    Health care practitioners serve an important role in identification and assistance of human trafficking victims. Advanced practice registered nurses, including certified nurse midwives, clinical nurse specialists, and nurse practitioners, are in a unique position to interact with persons trafficked and seen in the clinical setting, yet they require knowledge to identify the signs of human trafficking. Lack of training and education has been identified as a barrier for health care professionals to recognize human trafficking victims and implement needed health care services (; ). Barriers to identification and management include gap in knowledge about the process to screen for trafficking, to assist victims, and to make referrals. A patient-centered, trauma-informed approach can provide a safe environment to sensitively screen patients for human trafficking. Advanced practice registered nurses should be able to assess for trafficking indicators, collaborate with multidisciplinary service providers, and ensure understanding and availability of federal, state, and local resources to manage the care of victims of trafficking.

  12. Attitudes About Human Trafficking: Individual Differences Related to Belief and Victim Blame.

    Science.gov (United States)

    Cunningham, Katherine C; Cromer, Lisa DeMarni

    2016-01-01

    Human trafficking is believed to oppress millions of people worldwide. Despite increased media attention and public awareness campaigns in recent years, no empirical research has examined public attitudes about human trafficking. The present study examined gender, sexual trauma history, and attitudes about human trafficking as they related to belief of a sex-trafficking scenario and willingness to blame the victim for the situation. Undergraduate students (N = 409) at a large private university in the Northeastern United States completed measures in which they responded to a vignette portraying sex trafficking in the United States. Participants also reported their personal trauma history and completed a Human Trafficking Myths Scale. Results indicated that gender and human trafficking myth acceptance, but not sexual trauma history, were significantly related to participants' belief of the sex-trafficking scenario and their perception of the victim's responsibility. Potential implications and directions for future research are discussed. © The Author(s) 2014.

  13. Social world of organ transplantation, trafficking, and policies.

    Science.gov (United States)

    Yousaf, Farhan Navid; Purkayastha, Bandana

    2016-05-01

    Although success of organ transplants reflects advances in medical procedures, the success has generated debates about the ethical standards and policies that govern transplants, especially the acquisition of organs for transplants. We focus on laws, policies, and organ trafficking to highlight the interdisciplinary perspectives that can shape our understanding of transplantation as a social phenomenon. We discuss international policies and country-specific legislation from Pakistan to point to gaps and their implications for protecting vulnerable people who are exploited for organ removal. International collaboration and the legal framework need to be strengthened to fight the menace globally and to deal with the cases of organ trafficking within the legal ambit of human trafficking so that the rights of victims are upheld by states, justice systems, and ultimately medical establishments and practitioners.

  14. Life after Trafficking in Azerbaijan: Reintegration experiences of survivors

    Directory of Open Access Journals (Sweden)

    Lauren McCarthy

    2018-04-01

    Full Text Available Assisting survivors of trafficking is considered one of the pillars of a human rights-based response Shelter, medical, psychological and legal assistance in the short term and job placement, accommodation and reunification with family and community in the long term are critical steps for helping them recover and feel in control of their lives and futures. This paper examines survivors’ experiences of trafficking and recovery in the Azerbaijani context, using questionnaire responses from 22 women who were trafficked for sexual exploitation between 2006 and 2009 and who were assisted upon their return. It finds that while Azerbaijan has been quite successful at short-term assistance, there are still significant gaps in longer-term assistance, especially with regard to job placement and family reunification. Survivors point to these gaps as significant impediments to full reintegration into society. Looking at their experiences can provide insights into improvements in assistance programmes that can be implemented in both Azerbaijan and elsewhere.

  15. Perspectives on Human Trafficking and Modern Forms of Slavery

    Directory of Open Access Journals (Sweden)

    Siddharth Kara

    2017-06-01

    Full Text Available Migration, technology, law, and measurement are each among the most topical areas of enquiry in the global human trafficking field, with much work remaining to be done in these and other areas. Beneath these particular intersections lies a crucial truth—slavery is a global business that thrives on the callous exploitation of the labor activity of a vast and highly vulnerable subclass of people whose brutalization is tacitly accepted by every participant in the global economy, from corporations to consumers. I am deeply gratified to edit Social Inclusion’s second issue on human trafficking and modern slavery. The level of scholarly interest in these topics continues to grow, and in this issue the authors explore some of the most pressing manifestations of human trafficking around the world.

  16. Terrorism, Drug Trafficking, and the Globalization of Supply

    Directory of Open Access Journals (Sweden)

    Joel Hernández

    2013-08-01

    Full Text Available This case study analyzes the diversification of both terrorist groups and drug traffickers and the convergence between the two types of organizations in recent decades. As financial markets have become globalized, so have opportunities for illicit groups to transact with each other. The article builds on the collapse of Lebanese Canadian Bank in 2011 after its designation by the U.S. Treasury Department as a money-laundering financial institution tied to global drug trafficking and to Hezbollah. It follows the trajectory of two Hezbollah-associated drug kingpins: Ayman Joumaa, who facilitated trade between Hezbollah and the Zetas, and Maroun Saade, who was apprehended attempting to connect Hezbollah to the Taliban. In its analysis of the histories, motivations, and relationships among these three groups, the article reflects on relationships currently in existence between terrorist and drug-trafficking organizations, and on the implications of the possible directions these relationships might take in the future.

  17. 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.

  18. Regulation of dopamine transporter trafficking by intracellular amphetamine

    DEFF Research Database (Denmark)

    Kahlig, Kristopher M; Lute, Brandon J; Wei, Yuqiang

    2006-01-01

    -induced cell surface DAT redistribution may result in long-lasting changes in DA homeostasis. The molecular mechanism by which AMPH induces trafficking is not clear. Because AMPH is a substrate, we do not know whether extracellular AMPH stimulates trafficking through its interaction with DAT and subsequent...... alteration in DAT function, thereby triggering intracellular signaling or whether AMPH must be transported and then act intracellularly. In agreement with our previous studies, extracellular AMPH caused cytosolic redistribution of the wild-type human DAT (WT-hDAT). However, AMPH did not induce cytosolic...... redistribution in an uptake-impaired hDAT (Y335A-hDAT) that still binds AMPH. The divalent cation zinc (Zn(2+)) inhibits WT-hDAT activity, but it restores Y335A-hDAT uptake. Coadministration of Zn(2+) and AMPH consistently reduced WT-hDAT trafficking but stimulated cytosolic redistribution of Y335A...

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

    Science.gov (United States)

    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 scenario: criminal law, with a focus on conspiracy; service provider regulations, with a focus on mandatory reporting laws; and human rights law. In addition to imposing a legal mandate, the law can inform ethical considerations about how health care professionals should respond to human trafficking. © 2017 American Medical Association. All Rights Reserved.

  20. Human Trafficking in Nepal: Post-Earthquake Risk and Response.

    Science.gov (United States)

    Gyawali, Bishal; Keeling, June; Kallestrup, Per

    2017-04-01

    As Nepal mourns the 1-year commemoration of the April 2015 earthquake and its aftershocks that killed more than 8500 people and left thousands injured and displaced, other more hidden repercussions of the resultant chaotic environment need attention: the increased risk of human trafficking. Considering that natural disasters provide a milieu for this illicit trade, there is a need for a robust response from stakeholders such as donors, civil society organizations, and government organizations against human trafficking following disasters such as the Nepal earthquake. Responsibility to prevent and fight trafficking should be explicitly included in the mandate of relief and rehabilitation mechanisms set up at the national level to coordinate the disaster relief response, serving to support populations in both rural and urban areas. (Disaster Med Public Health Preparedness. 2017;11:153-154).