Viral Response to Specifically Targeted Antiviral Therapy for Hepatitis C and the Implications for Treatment Success

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Curtis L Cooper

2010-01-01

Full Text Available Currently, hepatitis C virus (HCV antiviral therapy is characterized by long duration, a multitude of side effects, difficult administration and suboptimal success; clearly, alternatives are needed. Collectively, specifically targeted antiviral therapy for HCV (STAT-C molecules achieve rapid viral suppression and very high rapid virological response rates, and improve sustained virological response rates. The attrition rate of agents within this class has been high due to various toxicities. Regardless, several STAT-C molecules are poised to become the standard of care for HCV treatment in the foreseeable future. Optimism must be tempered with concerns related to the rapid development of drug resistance with resulting HCV rebound. Strategies including induction dosing with interferon and ribavirin, use of combination high-potency STAT-C molecules and an intensive emphasis on adherence to HCV antiviral therapy will be critical to the success of this promising advance in HCV therapy.

Effects of Interferon-α/β on HBV Replication Determined by Viral Load

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Tian, Yongjun; Chen, Wen-ling; Ou, Jing-hsiung James

2011-01-01

Interferons α and β (IFN-α/β) are type I interferons produced by the host to control microbial infections. However, the use of IFN-α to treat hepatitis B virus (HBV) patients generated sustained response to only a minority of patients. By using HBV transgenic mice as a model and by using hydrodynamic injection to introduce HBV DNA into the mouse liver, we studied the effect of IFN-α/β on HBV in vivo. Interestingly, our results indicated that IFN-α/β could have opposite effects on HBV: they suppressed HBV replication when viral load was high and enhanced HBV replication when viral load was low. IFN-α/β apparently suppressed HBV replication via transcriptional and post-transcriptional regulations. In contrast, IFN-α/β enhanced viral replication by inducing the transcription factor HNF3γ and activating STAT3, which together stimulated HBV gene expression and replication. Further studies revealed an important role of IFN-α/β in stimulating viral growth and prolonging viremia when viral load is low. This use of an innate immune response to enhance its replication and persistence may represent a novel strategy that HBV uses to enhance its growth and spread in the early stage of viral infection when the viral level is low. PMID:21829354

Rapid host immune response and viral dynamics in herpes simplex virus-2 infection

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Schiffer, Joshua T; Corey, Lawrence

2014-01-01

Herpes Simplex Virus-2 (HSV-2) is episodically shed throughout the human genital tract. While high viral load correlates with development of genital ulcers, shedding also commonly occurs even when ulcers are not present, allowing for silent transmission during coitus and contributing to high seroprevalence of HSV-2 worldwide. Frequent viral reactivation occurs despite diverse and complementary host and viral mechanisms within ganglionic tissue that predispose towards latency, suggesting that viral replication may be constantly occurring in a small minority of neurons within the ganglia. Within genital mucosa, the in vivo expansion and clearance rates of HSV-2 are extremely rapid. Resident dendritic cells and memory HSV-specific T cells persist at prior sites of genital tract reactivation, and in conjunction with prompt innate recognition of infected cells, lead to rapid containment of infected cells. Shedding episodes vary greatly in duration and severity within a single person over time: this heterogeneity appears best explained by variation in the densities of host immunity across the genital tract. The fact that immune responses usually control viral replication in genital skin prior to development of lesions provides optimism that enhancing such responses could lead to effective vaccines and immunotherapies. PMID:23467247

Systems-Biology Approaches to Discover Anti-Viral Effectors of the Human Innate Immune Response

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Andreas F.R. Sommer

2011-07-01

Full Text Available Virus infections elicit an immediate innate response involving antiviral factors. The activities of some of these factors are, in turn, blocked by viral countermeasures. The ensuing battle between the host and the viruses is crucial for determining whether the virus establishes a foothold and/or induces adaptive immune responses. A comprehensive systems-level understanding of the repertoire of anti-viral effectors in the context of these immediate virus-host responses would provide significant advantages in devising novel strategies to interfere with the initial establishment of infections. Recent efforts to identify cellular factors in a comprehensive and unbiased manner, using genome-wide siRNA screens and other systems biology “omics” methodologies, have revealed several potential anti-viral effectors for viruses like Human immunodeficiency virus type 1 (HIV-1, Hepatitis C virus (HCV, West Nile virus (WNV, and influenza virus. This review describes the discovery of novel viral restriction factors and discusses how the integration of different methods in systems biology can be used to more comprehensively identify the intimate interactions of viruses and the cellular innate resistance.

Heterogeneity of HVR-1 quasispecies is predictive of early but not sustained virological response in genotype 1b-infected patients undergoing combined treatment with PEG- or STD-IFN plus RBV.

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Abbate, I; Cappiello, G; Lo Iacono, O; Longo, R; Ferraro, D; Antonucci, G; Di Marco, V; Di Stefano, R; Craxì, A; Solmone, M C; Spanò, A; Ippolito, G; Capobianchi, M R

2003-01-01

ISDR mutation pattern and HVR-1 quasispecies were analyzed in HCV genotype 1b-infected patients treated with either PEG- or STD-IFN plus ribavirin, in order to find virological correlates of therapy outcome. ISDR region analysis, performed at baseline (T0) and at 4 weeks of therapy (T1), indicated that ISDR mutation pattern was not predictive of response to treatment. Moreover, no selection of putative resistant strains in the first month of therapy was observed. Viral load was not correlated with any parameter of HVR-1 heterogeneity. Among the HVR-1 heterogeneity parameters considered, complexity was inversely correlated to viral load decline at T1. In univariate analysis, complexity, proportion of non synonymous substitutions (NS) and NS/S ratio were lower in patients showing virological response at 6 months of treatment. Complexity was the only parameter independently associated with both decline of viral load at T1 and virological response after 6 months, even after adjustment for confounding variables. At the end of treatment or later, these correlations were lost. Evolution pattern of the HVR-1 quasispecies indicated a strong selective pressure in sustained responders, with complete substitution of pre-existing quasispecies, while minor changes occured in non responders. In relapsers both patterns were present at a similar rate. In conclusion, this study shows that HVR-1 heterogeneity may be involved in the early response to combined IFN-RBV therapy. The loss of correlation between viral heterogeneity and therapy outcome at 6 months of therapy, or later, suggests that other factors may play a role in maintaining sustained response to treatment.

Responsible marketing for sustainable tourism

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Jegdić Vaso

2014-01-01

Full Text Available The biggest challenge associated with the concept of sustainable tourism is its operationalisation and perception as a process to be applied through development plans, projects and ongoing activities of tour operators. The traditional approach to marketing, focused on a limited idea of maximising profit businesses, was not able to respond to a number of social and environmental requirements imposed by the concept of sustainable development. This paper discusses the ways in which marketing could play a more important role in the sustainable development of tourism. This refers to the determination of consumer needs and preferences, the formation of certain products and pricing, product information and advertising to consumers of their benefits in a sustainable manner, as well as adequate distribution channels used by businesses to deliver products to consumers. Environmental and social marketing are now being confirmed as important elements of a much broader marketing perspective. In order to develop tourism with sustainable outcomes, responsible marketing can be crucial. The concept of marketing mix for sustainable tourism was used as a starting point to explore the specific role of responsible marketing in tourism.

Staphylococcus aureus α-toxin modulates skin host response to viral infection.

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Bin, Lianghua; Kim, Byung Eui; Brauweiler, Anne; Goleva, Elena; Streib, Joanne; Ji, Yinduo; Schlievert, Patrick M; Leung, Donald Y M

2012-09-01

Patients with atopic dermatitis (AD) with a history of eczema herpeticum have increased staphylococcal colonization and infections. However, whether Staphylococcus aureus alters the outcome of skin viral infection has not been determined. We investigated whether S aureus toxins modulated host response to herpes simplex virus (HSV) 1 and vaccinia virus (VV) infections in normal human keratinocytes (NHKs) and in murine infection models. NHKs were treated with S aureus toxins before incubation of viruses. BALB/c mice were inoculated with S aureus 2 days before VV scarification. Viral loads of HSV-1 and VV were evaluated by using real-time PCR, a viral plaque-forming assay, and immunofluorescence staining. Small interfering RNA duplexes were used to knockdown the gene expression of the cellular receptor of α-toxin, a disintegrin and metalloprotease 10 (ADAM10). ADAM10 protein and α-toxin heptamers were detected by using Western blot assays. We demonstrate that sublytic staphylococcal α-toxin increases viral loads of HSV-1 and VV in NHKs. Furthermore, we demonstrate in vivo that the VV load is significantly greater (P skin inoculated with an α-toxin-producing S aureus strain compared with murine skin inoculated with the isogenic α-toxin-deleted strain. The viral enhancing effect of α-toxin is mediated by ADAM10 and is associated with its pore-forming property. Moreover, we demonstrate that α-toxin promotes viral entry in NHKs. The current study introduces the novel concept that staphylococcal α-toxin promotes viral skin infection and provides a mechanism by which S aureus infection might predispose the host toward disseminated viral infections. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Influenza Virus Induces Inflammatory Response in Mouse Primary Cortical Neurons with Limited Viral Replication

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Gefei Wang

2016-01-01

Full Text Available Unlike stereotypical neurotropic viruses, influenza A viruses have been detected in the brain tissues of human and animal models. To investigate the interaction between neurons and influenza A viruses, mouse cortical neurons were isolated, infected with human H1N1 influenza virus, and then examined for the production of various inflammatory molecules involved in immune response. We found that replication of the influenza virus in neurons was limited, although early viral transcription was not affected. Virus-induced neuron viability decreased at 6 h postinfection (p.i. but increased at 24 h p.i. depending upon the viral strain. Virus-induced apoptosis and cytopathy in primary cortical neurons were not apparent at 24 h p.i. The mRNA levels of inflammatory cytokines, chemokines, and type I interferons were upregulated at 6 h and 24 h p.i. These results indicate that the influenza virus induces inflammatory response in mouse primary cortical neurons with limited viral replication. The cytokines released in viral infection-induced neuroinflammation might play critical roles in influenza encephalopathy, rather than in viral replication-induced cytopathy.

Corporate Social Responsibility for Sustainability

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Wojciech Przychodzeń

2014-06-01

Full Text Available Purpose: The purpose of this paper is to is to provide insights on implementing corporate social responsibility for sustainability (CSRS concept and show how it differs from basic corporate social responsibility (CSR. Methodology: The paper discusses major issues with references to existing literature and real business cases from S&P500 consumer discretionary sector. Findings: The main fi nding of this paper is that CSRS could provide the company with a competitive advantage as a growing number of consumers become more sustainable conscious. It could also help to overcome the increasing consumers’ skepticism towards corporate social responsibility practices. Finally, it can also be seen as a step forward in defi ning what types of corporate activities are associated with desirable social and environmental gains. Research limitations: Our sample was restricted to the U.S. fi rms from the consumer discretionary sector. Therefore, conclusions should not be generalized to other markets. Our study is based on the analysis of environmental and social responsibility statements and assumes that they accurately represent corporate commitment in majority of the cases. Practical implications: CSRS offers corporations the opportunity to use their unique skills, culture, values, resources, and management capabilities to lead social progress by making sustainability part of its internal corporate logic. Originality: The paper raises the importance of the different conditions necessary for making sustainable development concept an important part of corporate strategy.

Sustaining responsible tourism – The case of Kerala.

OpenAIRE

Kokkranikal, Jithendran; Chettiparamb, Angelique

2015-01-01

Responsible tourism is a concept that overlaps significantly with concepts of sustainable tourism, ethical tourism, pro-poor tourism and integrated tourism (Chettiparamb and Kokkranikal, 2012). Responsible tourism emphasises the role of businesses in achieving sustainability and can be seen as yet another concept within the sustainable tourism genre, which comprises many forms of tourism such as ecotourism, ethical tourism, alternative tourism, green tourism, soft tourism, etc. Responsible to...

Treatment response in HCV related chronic hepatitis

International Nuclear Information System (INIS)

Hussain, A.B.; Hussain, T.; Hussain, S.; Masood, A.; Kazmi, Y.; Tariq, W.Z.; Karamat, K.A.

2004-01-01

Objective: To evaluate the virological response to treatment with interferon and ribavirin in-patients with hepatitis C related liver disease. Material and Methods: Two hundred seventy-nine patients were included in the study. These patients had taken interferon and ribavirin treatment for HCV related chronic hepatitis, and were referred to AFIP for HCV RNA testing by polymerase chain reaction (PCR) between January 2002 and September 2002. Out of 279 cases, 229 had taken the treatment for 06 or 12 months and were tested for end-of-treatment response (ETR). Fifty patients had completed there treatment regimens of 6 or 12 months treatment, at least 24 weeks before their PCR test and were having follow-up testing for sustained viral response (SVR). The sera of these patients were tested for HCV RNA by PCR, using a commercial kit of Amplicor (Roche) for qualitative detection of HCV RNA. Results: Out of 229 cases tested for end-of-treatment response, 198 (86.5%) had no detectable HCV RNA (responders) and 31 (13.50%) were PCR positive (non-responders). Thirty-eight out of 50 cases, tested for a sustained viral response, had a negative result for HCV PCR thus showing sustained response rate of 76%. Conclusion: The viral remission/response to interferon and ribavirin combination therapy in our patients was better than that quoted in other regions. (author)

CD4 T Cell Responses in Latent and Chronic Viral Infections

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Walton, Senta; Mandaric, Sanja; Oxenius, Annette

2013-01-01

The spectrum of tasks which is fulfilled by CD4 T cells in the setting of viral infections is large, ranging from support of CD8 T cells and humoral immunity to exertion of direct antiviral effector functions. While our knowledge about the differentiation pathways, plasticity, and memory of CD4 T cell responses upon acute infections or immunizations has significantly increased during the past years, much less is still known about CD4 T cell differentiation and their beneficial or pathological functions during persistent viral infections. In this review we summarize current knowledge about the differentiation, direct or indirect antiviral effector functions, and the regulation of virus-specific CD4 T cells in the setting of persistent latent or active chronic viral infections with a particular emphasis on herpes virus infections for the former and chronic lymphocytic choriomeningitis virus infection for the latter. PMID:23717308

Synthetic sustained gene delivery systems.

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Agarwal, Ankit; Mallapragada, Surya K

2008-01-01

Gene therapy today is hampered by the need of a safe and efficient gene delivery system that can provide a sustained therapeutic effect without cytotoxicity or unwanted immune responses. Bolus gene delivery in solution results in the loss of delivered factors via lymphatic system and may cause undesired effects by the escape of bioactive molecules to distant sites. Controlled gene delivery systems, acting as localized depot of genes, provide an extended sustained release of genes, giving prolonged maintenance of the therapeutic level of encoded proteins. They also limit the DNA degradation in the nuclease rich extra-cellular environment. While attempts have been made to adapt existing controlled drug delivery technologies, more novel approaches are being investigated for controlled gene delivery. DNA encapsulated in nano/micro spheres of polymers have been administered systemically/orally to be taken up by the targeted tissues and provide sustained release once internalized. Alternatively, DNA entrapped in hydrogels or scaffolds have been injected/implanted in tissues/cavities as platforms for gene delivery. The present review examines these different modalities for sustained delivery of viral and non-viral gene-delivery vectors. Design parameters and release mechanisms of different systems made with synthetic or natural polymers are presented along with their prospective applications and opportunities for continuous development.

Consumer Sustainability and Responsibility: Beyond Green and Ethical Consumption

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Maja Hosta

2016-12-01

Full Text Available Purpose – Most literature regarding sustainable behavior is based on the assumption that the reduction of consumption is inherently positive (mainly in the form of positive environmental consequences and based on ethical considerations. However, the issue of the social consequences of this reduction and self-interested intentions in consumption is not generally open to debate. This paper aims to identify dimensions of sustainable and responsible consumer behavior, distinguish between the two concepts, and present consumer obstacles to acting responsibly in all aspects that a sustainability agenda would suggest. Design/Methodology/Approach – The paper includes a literature review, proposes a framework of responsible and sustainable consumption (RSCB, and offers a set of propositions to achieve responsible and sustainable consumption. Insights from personal interviews with consumers are added for the sake of additional understanding of the concepts presented. Findings and implications – Through the RSCB framework, we show the potential trade-off decisions consumers have to make in order to implement sustainability and responsibility issues in everyday consumer decision processes. Struggles between doing what is good for them and what is good for the environment and society could be a reason why consumers have difficulties achieving responsible and sustainable consumption. Limitations – Qualitative study based on a small sample of personal interviews does not allow for generalizations. Originality – A research gap in understanding the dimensions of sustainable and responsible consumer actions in terms of their emphasis (environmental and social and intentions (self-interest and other-interest is addressed. By understanding those two dimensions of behavior, managers and consumers can resolve consumer sustainability and responsibility dilemmas that arise from a one-dimensional view in order to move sustainability research and practice

A patented strain of Bacillus coagulans increased immune response to viral challenge.

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Baron, Mira

2009-03-01

Viral respiratory tract infection is the most common illness among humans. Probiotics have been known to enhance the immune system and, therefore, may represent a significant therapeutic advancement for treating viral respiratory tract infections. A controlled study was conducted to evaluate the effects of the patented GanedenBC30 probiotic (Bacillus coagulans GBI-30, 6086, marketed as Sustenex [Ganeden Biotech, Inc., Mayfield Heights, OH]) on the immune system when exposed to adenovirus and influenza in otherwise healthy adults. Ten healthy men and women (average age, 44 years) were instructed to consume 1 capsule of GanedenBC30 with water once a day for 30 days. At baseline and after completion of the 30-day treatment, blood levels of cytokines were measured in vitro after T-cell exposure to adenovirus and influenza A. Each participant served as his/her own control with baseline blood draw. The use of GanedenBC30 significantly increased T-cell production of TNF-alpha in response to adenovirus exposure (P = 0.027) and influenza A (H3N2 Texas strain) exposure (P = 0.004), but it did not have a significant effect on the response to other strains of influenza. No serious adverse events were reported throughout the study. The patented GanedenBC30 probiotic may be a safe and effective therapeutic option for enhancing T-cell response to certain viral respiratory tract infections.

Economics, Corporate Sustainability and Social Responsibility

OpenAIRE

Tisdell, Clement A.

2008-01-01

It is often argued that corporate sustainability requires a corporation to make a profit, to act in a socially responsible manner and to engage in policies that are environmentally sustainable. This is sometimes called the corporation’s triple bottom line. In this paper it is argued that in practice profitability or more general maintaining economic variability constitutes a corporation’s bottom line and that it is limited by this consideration in showing social responsibility and in acting w...

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

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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

Recent Advances in Non-viral Vectors for Gene Delivery

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Guo, Xia; Huang, Leaf

2011-01-01

membrane/core nanoparticles for nucleic acid delivery and ultrasound-responsive nucleic acid vectors. The systemic delivery studies are highlighted. Finally, we bring forward the prospect for nucleic acid delivery. We think a better understandings of the fate of the nanoparticles inside the cell and of the interactions between the parts of hybrid particles will lead to a delivery system suitable for clinical use. We also underscore the value of sustained release of nucleic acid and presume making vectors targeted to cells with sustained release in vivo should be an interesting research challenge. PMID:21870813

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.

Contribution of herpesvirus specific CD8 T cells to anti-viral T cell response in humans.

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Elena Sandalova

Full Text Available Herpesviruses infect most humans. Their infections can be associated with pathological conditions and significant changes in T cell repertoire but evidences of symbiotic effects of herpesvirus latency have never been demonstrated. We tested the hypothesis that HCMV and EBV-specific CD8 T cells contribute to the heterologous anti-viral immune response. Volume of activated/proliferating virus-specific and total CD8 T cells was evaluated in 50 patients with acute viral infections: 20 with HBV, 12 with Dengue, 12 with Influenza, 3 with Adenovirus infection and 3 with fevers of unknown etiology. Virus-specific (EBV, HCMV, Influenza pentamer+ and total CD8 T cells were analyzed for activation (CD38/HLA-DR, proliferation (Ki-67/Bcl-2(low and cytokine production. We observed that all acute viral infections trigger an expansion of activated/proliferating CD8 T cells, which differs in size depending on the infection but is invariably inflated by CD8 T cells specific for persistent herpesviruses (HCMV/EBV. CD8 T cells specific for other non-related non persistent viral infection (i.e. Influenza were not activated. IL-15, which is produced during acute viral infections, is the likely contributing mechanism driving the selective activation of herpesvirus specific CD8 T cells. In addition we were able to show that herpesvirus specific CD8 T cells displayed an increased ability to produce the anti-viral cytokine interferon-gamma during the acute phase of heterologous viral infection. Taken together, these data demonstrated that activated herpesvirus specific CD8 T cells inflate the activated/proliferating CD8 T cells population present during acute viral infections in human and can contribute to the heterologous anti-viral T cell response.

The Viral Transcription Group Determines the HLA Class I Cellular Immune Response Against Human Respiratory Syncytial Virus*

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Johnstone, Carolina; Lorente, Elena; Barriga, Alejandro; Barnea, Eilon; Infantes, Susana; Lemonnier, François A.; David, Chella S.; Admon, Arie; López, Daniel

2015-01-01

The cytotoxic T-lymphocyte-mediated killing of virus-infected cells requires previous recognition of short viral antigenic peptides bound to human leukocyte antigen class I molecules that are exposed on the surface of infected cells. The cytotoxic T-lymphocyte response is critical for the clearance of human respiratory syncytial virus infection. In this study, naturally processed viral human leukocyte antigen class I ligands were identified with mass spectrometry analysis of complex human leukocyte antigen-bound peptide pools isolated from large amounts of human respiratory syncytial virus-infected cells. Acute antiviral T-cell response characterization showed that viral transcription determines both the immunoprevalence and immunodominance of the human leukocyte antigen class I response to human respiratory syncytial virus. These findings have clear implications for antiviral vaccine design. PMID:25635267

Inhibition of viral replication reduces regulatory T cells and enhances the antiviral immune response in chronic hepatitis B

International Nuclear Information System (INIS)

Stoop, Jeroen N.; Molen, Renate G. van der; Kuipers, Ernst J.; Kusters, Johannes G.; Janssen, Harry L.A.

2007-01-01

Regulatory T cells (Treg) play a key role in the impaired immune response that is typical for a chronic Hepatitis B virus (HBV) infection. To gain more insight in the mechanism that is responsible for this impaired immune response, the effect of viral load reduction resulting from treatment with the nucleotide analogue adefovir dipivoxil on the percentages of Treg and HBV-specific T-cell responses was analyzed. Peripheral blood mononuclear cells (PBMC) of 12 patients were collected at baseline and during treatment. In parallel to the decline in viral load, we found a decline in circulating Treg, combined with an increase in HBV core antigen-specific IFN-γ production and proliferation. The production of IL10 did not decrease during therapy. In conclusion, adefovir induced viral load reduction results in a decline of circulating Treg together with a partial recovery of the immune response

Interferon Response and Viral Evasion by Members of the Family Rhabdoviridae

OpenAIRE

Matthias J. Schnell; Elizabeth J. Faul; Douglas S. Lyles

2009-01-01

Like many animal viruses, those of the Rhabdoviridae family, are able to antagonize the type I interferon response and cause disease in mammalian hosts. Though these negative-stranded RNA viruses are very simple and code for as few as five proteins, they have been seen to completely abrogate the type I interferon response early in infection. In this review, we will discuss the viral organization and type I interferon evasion of rhabdoviruses, focusing on vesicular stomatitis virus (VSV) and r...

Rapid virological response assessment by Abbott RealTime hepatitis C virus assay for predicting sustained virological responses in patients with hepatitis C virus genotype 1 treated with pegylated-interferon and ribavirin

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Pei-yuan Su

2016-07-01

Full Text Available The lower limits of virus detection of hepatitis C virus (HCV RNA detection assays are continuously improving. We aimed to assess the utility of more precise definition of 4th week viral load [rapid virological response (RVR] in predicting sustained virological response (SVR in HCV genotype 1 patients treated with pegylated-interferon (PEG-IFN and ribavirin. Clinical data of treatment-naïve HCV genotype 1 patients were retrospectively collected from 2009 to 2014. Patients were grouped according to 4th week viral load as follows: undetectable (n = 90 and detectable but not quantifiable (< 12 IU/mL, n = 27. All patients received PEG-IFNα-2a or -2b and ribavirin for 24 weeks. Serum HCV RNA levels were measured by Abbott RealTime (ART; Abbott Molecular, Abbott Park, IL, USA HCV assay. SVR was 95.5% and 63% in the undetectable group and < 12 IU/mL group of 4th week viral load, respectively. The between-group difference in SVR was significant (p < 0.001. We determined 4th week viral load was independently associated with SVR (odds ratio = 19.28; p = 0.002 and a good predictor of SVR [area under the curve (AUC = 0.775; p = 0.001]. ART HCV assays had a stronger SVR predictive value in HCV genotype 1 patients, indicating that only the undetectable group of 4th week viral load patients measured by ART HCV assay should be considered for shorter treatment time (24 weeks with PEG-IFN and ribavirin.

Practices of corporate social responsibility and sustainable systems work in Peruvian companies issuing sustainability reports

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María Angela Prialé

2015-12-01

Full Text Available Through a literature review, this exploratory study seeks to determine whether the practices related to its colaborators, who report as part of its action responsible Peruvian companies issuing sustainability reports can be considered sustainable management practices of human resources. To this end, it was used the approach of sustainable work systems as a general approach. It was found that some of the practices of responsible management of human resources that implement the analyzed companies address the human dimensions of sustainability, although not all dimensions are considered equally or similar depth.

The viral transcription group determines the HLA class I cellular immune response against human respiratory syncytial virus.

Science.gov (United States)

Johnstone, Carolina; Lorente, Elena; Barriga, Alejandro; Barnea, Eilon; Infantes, Susana; Lemonnier, François A; David, Chella S; Admon, Arie; López, Daniel

2015-04-01

The cytotoxic T-lymphocyte-mediated killing of virus-infected cells requires previous recognition of short viral antigenic peptides bound to human leukocyte antigen class I molecules that are exposed on the surface of infected cells. The cytotoxic T-lymphocyte response is critical for the clearance of human respiratory syncytial virus infection. In this study, naturally processed viral human leukocyte antigen class I ligands were identified with mass spectrometry analysis of complex human leukocyte antigen-bound peptide pools isolated from large amounts of human respiratory syncytial virus-infected cells. Acute antiviral T-cell response characterization showed that viral transcription determines both the immunoprevalence and immunodominance of the human leukocyte antigen class I response to human respiratory syncytial virus. These findings have clear implications for antiviral vaccine design. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Parallel epigenomic and transcriptomic responses to viral infection in honey bees (Apis mellifera).

Science.gov (United States)

Galbraith, David A; Yang, Xingyu; Niño, Elina Lastro; Yi, Soojin; Grozinger, Christina

2015-03-01

Populations of honey bees are declining throughout the world, with US beekeepers losing 30% of their colonies each winter. Though multiple factors are driving these colony losses, it is increasingly clear that viruses play a major role. However, information about the molecular mechanisms mediating antiviral immunity in honey bees is surprisingly limited. Here, we examined the transcriptional and epigenetic (DNA methylation) responses to viral infection in honey bee workers. One-day old worker honey bees were fed solutions containing Israeli Acute Paralysis Virus (IAPV), a virus which causes muscle paralysis and death and has previously been associated with colony loss. Uninfected control and infected, symptomatic bees were collected within 20-24 hours after infection. Worker fat bodies, the primary tissue involved in metabolism, detoxification and immune responses, were collected for analysis. We performed transcriptome- and bisulfite-sequencing of the worker fat bodies to identify genome-wide gene expression and DNA methylation patterns associated with viral infection. There were 753 differentially expressed genes (FDR<0.05) in infected versus control bees, including several genes involved in epigenetic and antiviral pathways. DNA methylation status of 156 genes (FDR<0.1) changed significantly as a result of the infection, including those involved in antiviral responses in humans. There was no significant overlap between the significantly differentially expressed and significantly differentially methylated genes, and indeed, the genomic characteristics of these sets of genes were quite distinct. Our results indicate that honey bees have two distinct molecular pathways, mediated by transcription and methylation, that modulate protein levels and/or function in response to viral infections.

Parallel epigenomic and transcriptomic responses to viral infection in honey bees (Apis mellifera.

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David A Galbraith

2015-03-01

Full Text Available Populations of honey bees are declining throughout the world, with US beekeepers losing 30% of their colonies each winter. Though multiple factors are driving these colony losses, it is increasingly clear that viruses play a major role. However, information about the molecular mechanisms mediating antiviral immunity in honey bees is surprisingly limited. Here, we examined the transcriptional and epigenetic (DNA methylation responses to viral infection in honey bee workers. One-day old worker honey bees were fed solutions containing Israeli Acute Paralysis Virus (IAPV, a virus which causes muscle paralysis and death and has previously been associated with colony loss. Uninfected control and infected, symptomatic bees were collected within 20-24 hours after infection. Worker fat bodies, the primary tissue involved in metabolism, detoxification and immune responses, were collected for analysis. We performed transcriptome- and bisulfite-sequencing of the worker fat bodies to identify genome-wide gene expression and DNA methylation patterns associated with viral infection. There were 753 differentially expressed genes (FDR<0.05 in infected versus control bees, including several genes involved in epigenetic and antiviral pathways. DNA methylation status of 156 genes (FDR<0.1 changed significantly as a result of the infection, including those involved in antiviral responses in humans. There was no significant overlap between the significantly differentially expressed and significantly differentially methylated genes, and indeed, the genomic characteristics of these sets of genes were quite distinct. Our results indicate that honey bees have two distinct molecular pathways, mediated by transcription and methylation, that modulate protein levels and/or function in response to viral infections.

Partiality of Responsibility: Ethics in Sustainability Consulting

NARCIS (Netherlands)

Earhart, R.S.

2011-01-01

Sustainability, Socially Responsible Investment (SRI) and Corporate Social Responsibility (CSR) are both highly normative fields of professional practice, framed by various narratives: capitalist versus environmentalist, waste versus respect for the planet, consumerism versus responsibility;

Innate immune responses of calves during transient infection with a noncytopathic strain of bovine viral diarrhea virus

DEFF Research Database (Denmark)

Muller-Doblies, D.; Arquint, A.; Schaller, P.

2004-01-01

In this study, six immunocompetent calves were experimentally infected with a noncytopathic strain of bovine viral diarrhea virus (BVDV), and the effects of the viral infection on parameters of the innate immune response of the host were analyzed. Clinical and virological data were compared...

From Corporate Social Responsibility to Corporate Sustainability: Features of Financing Sustainable Development

Directory of Open Access Journals (Sweden)

Vasylchuk Irуna P.

2018-03-01

Full Text Available The theoretical basis of the concepts of corporate social responsibility and sustainable development are studied. It is revealed that scientists mainly distinguish two main stages in the evolution of the concept of corporate social responsibility. There argued the expediency of singling out the third stage of the development of the concept (version CSR 2.0, which is characterized by the integration of the theoretical and practical foundations of the concepts of CSR and sustainable development as well as by their implementation into activities of corporations. The presence of the necessary prerequisites for singling out the new stage in the evolution of these concepts (version CSR 3.0, which is based on the provisions of the collaborative theory and provides for the cooperation of social enterprises and sustainable corporations in achieving the goals of sustainable development, is revealed, its expediency is justified. The determinant of the stage is the use of opportunities for sustainable development, the dominant is the social orientation, and its content is characterized by the slogan “doing common good to do common well”. Using generalization, there identified the features of the established models of sustainable development of corporations by key aspects (goals, principles, methods. On this basis, the features of approaches to financing sustainable development at the macro and micro levels are determined, and the principles for financing the activities of corporations in the new conditions are defined. It is concluded that achieving sustainability requires an effective system of financing corporate measures aimed at sustainable development, for the creation of which in Ukraine it is necessary to use the experience of “best practices” at the national, local and corporate levels.

Viral oncogene-induced DNA damage response is activated in Kaposi sarcoma tumorigenesis.

Directory of Open Access Journals (Sweden)

Sonja Koopal

2007-09-01

Full Text Available Kaposi sarcoma is a tumor consisting of Kaposi sarcoma herpesvirus (KSHV-infected tumor cells that express endothelial cell (EC markers and viral genes like v-cyclin, vFLIP, and LANA. Despite a strong link between KSHV infection and certain neoplasms, de novo virus infection of human primary cells does not readily lead to cellular transformation. We have studied the consequences of expression of v-cyclin in primary and immortalized human dermal microvascular ECs. We show that v-cyclin, which is a homolog of cellular D-type cyclins, induces replicative stress in ECs, which leads to senescence and activation of the DNA damage response. We find that antiproliferative checkpoints are activated upon KSHV infection of ECs, and in early-stage but not late-stage lesions of clinical Kaposi sarcoma specimens. These are some of the first results suggesting that DNA damage checkpoint response also functions as an anticancer barrier in virally induced cancers.

End-of-Treatment-Response in Patients Treated for Hepatitis C Virus with Standard Interferon and Ribavirin Based on Viral Load

International Nuclear Information System (INIS)

Rathore, M. A.; Hussain, A. B.; Ghani, E.

2015-01-01

Objective: To determine the End-of-Treatment-Response (ETR) to standard interferon and ribavirin based regimen in patients of chronic hepatitis C and to compare the ETR response in low and high viral load groups. Study Design: Descriptive study. Place and Duration of Study: Virology Department, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from March 2012 to May 2013. Methodology: Patients with chronic hepatitis C virus infection were included in the study. Pre-treatment viral load was determined by RoboGene Quantification kit. Based on viral load, the 400 patients were divided into two equal groups of low viral load (< 800,000 IU/ml) and high viral load (> 800,000 IU/ml). The patients were treated with standard interferon alpha (3 million units subcutaneously thrice weekly) and ribavirin (10.6 mg/kg body weight) for 6 months. ETR was measured using Sacace Biotechnologies Qualitative kit. Chi-square test was used to compare the ETR in the two viral load groups. P-value < 0.05 was considered as significant. Results: Out of 400 patients, 206 (51.5%) were males and 194 (48.5%) were females. Two hundred seventy (67.5%) patients achieved ETR and 130 (35.5%) failed to do so. In low viral load group, 145 (72.5%) patients achieved and 55 (27.5%) patients did not achieve ETR. In high viral load group, 123 (61.5%) patients achieved and 77 (38.5%) did not achieve ETR. The difference in ETR between low and high viral load groups was statistically significant (p=0.019). Conclusion: End-of-treatment-response in patients treated for hepatitis C virus with standard interferon and ribavirin was greater in patients with low viral load as compared to patients with high viral load. (author)

Practices of corporate social responsibility and sustainable systems work in Peruvian companies issuing sustainability reports

OpenAIRE

Prialé, María Angela; Fuchs, Rosa María; Sáenz, Manuel

2014-01-01

Through a literature review, this exploratory study seeks to determine whether the practices related to its colaborators, who report as part of its action responsible Peruvian companies issuing sustainability reports can be considered sustainable management practices of human resources. To this end, it was used the approach of sustainable work systems as a general approach. It was found that some of the practices of responsible management of human resources that implement the analyzed compani...

Gene Expression Profiles Link Respiratory Viral Infection, Platelet Response to Aspirin, and Acute Myocardial Infarction

Science.gov (United States)

Cyr, Derek D.; Lucas, Joseph E.; Zaas, Aimee K.; Woods, Christopher W.; Newby, L. Kristin; Kraus, William E.; Ginsburg, Geoffrey S.

2015-01-01

Background Influenza infection is associated with myocardial infarction (MI), suggesting that respiratory viral infection may induce biologic pathways that contribute to MI. We tested the hypotheses that 1) a validated blood gene expression signature of respiratory viral infection (viral GES) was associated with MI and 2) respiratory viral exposure changes levels of a validated platelet gene expression signature (platelet GES) of platelet function in response to aspirin that is associated with MI. Methods A previously defined viral GES was projected into blood RNA data from 594 patients undergoing elective cardiac catheterization and used to classify patients as having evidence of viral infection or not and tested for association with acute MI using logistic regression. A previously defined platelet GES was projected into blood RNA data from 81 healthy subjects before and after exposure to four respiratory viruses: Respiratory Syncytial Virus (RSV) (n=20), Human Rhinovirus (HRV) (n=20), Influenza A virus subtype H1N1 (H1N1) (n=24), Influenza A Virus subtype H3N2 (H3N2) (n=17). We tested for the change in platelet GES with viral exposure using linear mixed-effects regression and by symptom status. Results In the catheterization cohort, 32 patients had evidence of viral infection based upon the viral GES, of which 25% (8/32) had MI versus 12.2% (69/567) among those without evidence of viral infection (OR 2.3; CI [1.03-5.5], p=0.04). In the infection cohorts, only H1N1 exposure increased platelet GES over time (time course p-value = 1e-04). Conclusions A viral GES of non-specific, respiratory viral infection was associated with acute MI; 18% of the top 49 genes in the viral GES are involved with hemostasis and/or platelet aggregation. Separately, H1N1 exposure, but not exposure to other respiratory viruses, increased a platelet GES previously shown to be associated with MI. Together, these results highlight specific genes and pathways that link viral infection

DNA/MVA Vaccination of HIV-1 Infected Participants with Viral Suppression on Antiretroviral Therapy, followed by Treatment Interruption: Elicitation of Immune Responses without Control of Re-Emergent Virus.

Directory of Open Access Journals (Sweden)

Melanie Thompson

Full Text Available GV-TH-01, a Phase 1 open-label trial of a DNA prime—Modified Vaccinia Ankara (MVA boost vaccine (GOVX-B11, was undertaken in HIV infected participants on antiretroviral treatment (ART to evaluate safety and vaccine-elicited T cell responses, and explore the ability of elicited CD8+ T cells to control viral rebound during analytical treatment interruption (TI. Nine men who began antiretroviral therapy (ART within 18 months of seroconversion and had sustained plasma HIV-1 RNA <50 copies/mL for at least 6 months were enrolled. Median age was 38 years, median pre-ART HIV-1 RNA was 140,000 copies/ml and mean baseline CD4 count was 755/μl. Two DNA, followed by 2 MVA, inoculations were given 8 weeks apart. Eight subjects completed all vaccinations and TI. Clinical and laboratory adverse events were generally mild, with no serious or grade 4 events. Only reactogenicity events were considered related to study drug. No treatment emergent viral resistance was seen. The vaccinations did not reduce viral reservoirs and virus re-emerged in all participants during TI, with a median time to re-emergence of 4 weeks. Eight of 9 participants had CD8+ T cells that could be stimulated by vaccine-matched Gag peptides prior to vaccination. Vaccinations boosted these responses as well as eliciting previously undetected CD8+ responses. Elicited T cells did not display signs of exhaustion. During TI, temporal patterns of viral re-emergence and Gag-specific CD8+ T cell expansion suggested that vaccine-specific CD8+ T cells had been stimulated by re-emergent virus in only 2 of 8 participants. In these 2, transient decreases in viremia were associated with Gag selection in known CD8+ T cell epitopes. We hypothesize that escape mutations, already archived in the viral reservoir, plus a poor ability of CD8+ T cells to traffic to and control virus at sites of re-emergence, limited the therapeutic efficacy of the DNA/MVA vaccine.clinicaltrials.gov NCT01378156.

DNA/MVA Vaccination of HIV-1 Infected Participants with Viral Suppression on Antiretroviral Therapy, followed by Treatment Interruption: Elicitation of Immune Responses without Control of Re-Emergent Virus.

Science.gov (United States)

Thompson, Melanie; Heath, Sonya L; Sweeton, Bentley; Williams, Kathy; Cunningham, Pamela; Keele, Brandon F; Sen, Sharon; Palmer, Brent E; Chomont, Nicolas; Xu, Yongxian; Basu, Rahul; Hellerstein, Michael S; Kwa, Suefen; Robinson, Harriet L

2016-01-01

GV-TH-01, a Phase 1 open-label trial of a DNA prime—Modified Vaccinia Ankara (MVA) boost vaccine (GOVX-B11), was undertaken in HIV infected participants on antiretroviral treatment (ART) to evaluate safety and vaccine-elicited T cell responses, and explore the ability of elicited CD8+ T cells to control viral rebound during analytical treatment interruption (TI). Nine men who began antiretroviral therapy (ART) within 18 months of seroconversion and had sustained plasma HIV-1 RNA HIV-1 RNA was 140,000 copies/ml and mean baseline CD4 count was 755/μl. Two DNA, followed by 2 MVA, inoculations were given 8 weeks apart. Eight subjects completed all vaccinations and TI. Clinical and laboratory adverse events were generally mild, with no serious or grade 4 events. Only reactogenicity events were considered related to study drug. No treatment emergent viral resistance was seen. The vaccinations did not reduce viral reservoirs and virus re-emerged in all participants during TI, with a median time to re-emergence of 4 weeks. Eight of 9 participants had CD8+ T cells that could be stimulated by vaccine-matched Gag peptides prior to vaccination. Vaccinations boosted these responses as well as eliciting previously undetected CD8+ responses. Elicited T cells did not display signs of exhaustion. During TI, temporal patterns of viral re-emergence and Gag-specific CD8+ T cell expansion suggested that vaccine-specific CD8+ T cells had been stimulated by re-emergent virus in only 2 of 8 participants. In these 2, transient decreases in viremia were associated with Gag selection in known CD8+ T cell epitopes. We hypothesize that escape mutations, already archived in the viral reservoir, plus a poor ability of CD8+ T cells to traffic to and control virus at sites of re-emergence, limited the therapeutic efficacy of the DNA/MVA vaccine. clinicaltrials.gov NCT01378156.

Corporate Social Responsibility and Sustainability: Tourist Enterprises of Cantabria

OpenAIRE

Garrido Palacio, Fernando

2011-01-01

Currently, corporate social responsibility is seen as a factor to take into account for the sustainable development of the enterprises. This research provides an approach on this matter, defining the socially responsible activities developed in the tourism industry through sustainable development theory and stakeholder's theory. This study is made on a qualitative research methodology, based on case study. The analysis shows that corporate social responsibility is a multidimensional const...

Conditions for Viral Influence Spreading through Multiplex Correlated Social Networks

Science.gov (United States)

Hu, Yanqing; Havlin, Shlomo; Makse, Hernán A.

2014-04-01

A fundamental problem in network science is to predict how certain individuals are able to initiate new networks to spring up "new ideas." Frequently, these changes in trends are triggered by a few innovators who rapidly impose their ideas through "viral" influence spreading, producing cascades of followers and fragmenting an old network to create a new one. Typical examples include the rise of scientific ideas or abrupt changes in social media, like the rise of Facebook to the detriment of Myspace. How this process arises in practice has not been conclusively demonstrated. Here, we show that a condition for sustaining a viral spreading process is the existence of a multiplex-correlated graph with hidden "influence links." Analytical solutions predict percolation-phase transitions, either abrupt or continuous, where networks are disintegrated through viral cascades of followers, as in empirical data. Our modeling predicts the strict conditions to sustain a large viral spreading via a scaling form of the local correlation function between multilayers, which we also confirm empirically. Ultimately, the theory predicts the conditions for viral cascading in a large class of multiplex networks ranging from social to financial systems and markets.

Viral-Associated GN: Hepatitis C and HIV.

Science.gov (United States)

Kupin, Warren L

2017-08-07

Viruses are capable of inducing a wide spectrum of glomerular disorders that can be categorized on the basis of the duration of active viremia: acute, subacute, or chronic. The variable responses of the adaptive immune system to each time period of viral infection results mechanistically in different histologic forms of glomerular injury. The unique presence of a chronic viremic carrier state with either hepatitis C (HCV) or HIV has led to the opportunity to study in detail various pathogenic mechanisms of viral-induced glomerular injury, including direct viral infection of renal tissue and the development of circulating immune complexes composed of viral antigens that deposit along the glomerular basement membrane. Epidemiologic data show that approximately 25%-30% of all HIV patients are coinfected with HCV and 5%-10% of all HCV patients are coinfected with HIV. This situation can often lead to a challenging differential diagnosis when glomerular disease occurs in this dual-infected population and requires the clinician to be familiar with the clinical presentation, laboratory workup, and pathophysiology behind the development of renal disease for both HCV and HIV. Both of these viruses can be categorized under the new classification of infection-associated GN as opposed to being listed as causes of postinfectious GN as has previously been applied to them. Neither of these viruses lead to renal injury after a latent period of controlled and inactive viremia. The geneses of HCV- and HIV-associated glomerular diseases share a total dependence on the presence of active viral replication to sustain renal injury so the renal disease cannot be listed under "postinfectious" GN. With the new availability of direct-acting antivirals for HCV and more effective combined antiretroviral therapy for HIV, successful remission and even regression of glomerular lesions can be achieved if initiated at an early stage. Copyright © 2017 by the American Society of Nephrology.

Responsible and sustainable business in the context of sustainable development

Directory of Open Access Journals (Sweden)

Gheorghe Săvoiu

2013-11-01

Full Text Available Businesses in the contemporary world, detached from the classic entrepreneurial paradigm in keeping with which a business appears, grows and matures, are undergoing a process of adjustment to the new concept of sustainability, focusing on reconciling global, regional, national and local economic development and the quality of the environment. The practical organization of a responsible and sustainable business, the results of which are ever new products and services, which creates new jobs, and contributes, by aggregating systematically, to assessing new macroeconomic results, from GDP or NDP to import and export, and especially to sustainable economic development, requires the presence of both the three classical factors, i.e., capital, labour and location (land, and the other three essential new factors, which are called technology, information and the specific skills of the business owner, or simply of the entrepreneur.

Viral DNA Sensors IFI16 and Cyclic GMP-AMP Synthase Possess Distinct Functions in Regulating Viral Gene Expression, Immune Defenses, and Apoptotic Responses during Herpesvirus Infection.

Science.gov (United States)

Diner, Benjamin A; Lum, Krystal K; Toettcher, Jared E; Cristea, Ileana M

2016-11-15

The human interferon-inducible protein IFI16 is an important antiviral factor that binds nuclear viral DNA and promotes antiviral responses. Here, we define IFI16 dynamics in space and time and its distinct functions from the DNA sensor cyclic dinucleotide GMP-AMP synthase (cGAS). Live-cell imaging reveals a multiphasic IFI16 redistribution, first to viral entry sites at the nuclear periphery and then to nucleoplasmic puncta upon herpes simplex virus 1 (HSV-1) and human cytomegalovirus (HCMV) infections. Optogenetics and live-cell microscopy establish the IFI16 pyrin domain as required for nuclear periphery localization and oligomerization. Furthermore, using proteomics, we define the signature protein interactions of the IFI16 pyrin and HIN200 domains and demonstrate the necessity of pyrin for IFI16 interactions with antiviral proteins PML and cGAS. We probe signaling pathways engaged by IFI16, cGAS, and PML using clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9-mediated knockouts in primary fibroblasts. While IFI16 induces cytokines, only cGAS activates STING/TBK-1/IRF3 and apoptotic responses upon HSV-1 and HCMV infections. cGAS-dependent apoptosis upon DNA stimulation requires both the enzymatic production of cyclic dinucleotides and STING. We show that IFI16, not cGAS or PML, represses HSV-1 gene expression, reducing virus titers. This indicates that regulation of viral gene expression may function as a greater barrier to viral replication than the induction of antiviral cytokines. Altogether, our findings establish coordinated and distinct antiviral functions for IFI16 and cGAS against herpesviruses. How mammalian cells detect and respond to DNA viruses that replicate in the nucleus is poorly understood. Here, we decipher the distinct functions of two viral DNA sensors, IFI16 and cGAS, during active immune signaling upon infection with two herpesviruses, herpes simplex virus 1 (HSV-1) and human cytomegalovirus (HCMV). We show that IFI16

Association of coral algal symbionts with a diverse viral community responsive to heat shock

KAUST Repository

Brüwer, Jan D.

2017-08-17

Stony corals provide the structural foundation of coral reef ecosystems and are termed holobionts given they engage in symbioses, in particular with photosynthetic dinoflagellates of the genus Symbiodinium. Besides Symbiodinium, corals also engage with bacteria affecting metabolism, immunity, and resilience of the coral holobiont, but the role of associated viruses is largely unknown. In this regard, the increase of studies using RNA sequencing (RNA-Seq) to assess gene expression provides an opportunity to elucidate viral signatures encompassed within the data via careful delineation of sequence reads and their source of origin.Here, we re-analyzed an RNA-Seq dataset from a cultured coral symbiont (Symbiodinium microadriaticum, Clade A1) across four experimental treatments (control, cold shock, heat shock, dark shock) to characterize associated viral diversity, abundance, and gene expression. Our approach comprised the filtering and removal of host sequence reads, subsequent phylogenetic assignment of sequence reads of putative viral origin, and the assembly and analysis of differentially expressed viral genes. About 15.46% (123 million) of all sequence reads were non-host-related, of which <1% could be classified as archaea, bacteria, or virus. Of these, 18.78% were annotated as virus and comprised a diverse community consistent across experimental treatments. Further, non-host related sequence reads assembled into 56,064 contigs, including 4856 contigs of putative viral origin that featured 43 differentially expressed genes during heat shock. The differentially expressed genes included viral kinases, ubiquitin, and ankyrin repeat proteins (amongst others), which are suggested to help the virus proliferate and inhibit the algal host\\'s antiviral response.Our results suggest that a diverse viral community is associated with coral algal endosymbionts of the genus Symbiodinium, which prompts further research on their ecological role in coral health and resilience.

Contribution of viral recombinants to the study of the immune response against the Epstein-Barr virus.

Science.gov (United States)

Delecluse, Henri-Jacques; Feederle, Regina; Behrends, Uta; Mautner, Josef

2008-12-01

Over the past two decades, Epstein-Barr virus (EBV) mutants have become valuable tools for the analysis of viral functions. Several experimental strategies are currently used to generate recombinant mutant genomes that carry alterations in one or several viral genes. The probably most versatile approach utilizes bacterial artificial chromosomes (BAC) carrying parts or the whole EBV genome, which permits extensive genetic manipulations in Escherichia coli cells. The 'mini-EBVs', for example, which contain roughly half of the wild type viral information, efficiently transform primary B cells and have been used as gene vectors for foreign antigens. After expression in lymphoblastoid cell lines (LCLs), these antigens are efficiently presented on MHC molecules and recognized by antigen-specific T cells. These vectors, however, cannot undergo lytic replication and require a helper cell line for efficient replication and DNA packaging. Further experimental systems include the complete viral genome cloned onto a BAC. These mutants can typically be complemented by expression plasmids, some of which are expressed on EBV-derived vectors and can be propagated without requirement of a helper cell line. Over the last years, these viral recombinants have been utilized increasingly to analyse different aspects of the immune response against EBV. Immunological applications are manifold and steadily growing and include crude screening of T cell clones for their specificity towards latent versus lytic antigens, or more detailed analyses in which the exact specificity of T cells is determined using EBV mutants that lack a single viral antigen. Other applications include detailed analysis of protein domains important for immune recognition, e.g. Gly-Ala repeats in the EBV nuclear antigen 1 (EBNA1) protein, expansion of T cell clones directed against virion structures using virus-like particles and phenotypic analysis of virus mutants defective in infection. Future developments might

PAR-1 contributes to the innate immune response during viral infection

Science.gov (United States)

Antoniak, Silvio; Owens, A. Phillip; Baunacke, Martin; Williams, Julie C.; Lee, Rebecca D.; Weithäuser, Alice; Sheridan, Patricia A.; Malz, Ronny; Luyendyk, James P.; Esserman, Denise A.; Trejo, JoAnn; Kirchhofer, Daniel; Blaxall, Burns C.; Pawlinski, Rafal; Beck, Melinda A.; Rauch, Ursula; Mackman, Nigel

2013-01-01

Coagulation is a host defense system that limits the spread of pathogens. Coagulation proteases, such as thrombin, also activate cells by cleaving PARs. In this study, we analyzed the role of PAR-1 in coxsackievirus B3–induced (CVB3-induced) myocarditis and influenza A infection. CVB3-infected Par1–/– mice expressed reduced levels of IFN-β and CXCL10 during the early phase of infection compared with Par1+/+ mice that resulted in higher viral loads and cardiac injury at day 8 after infection. Inhibition of either tissue factor or thrombin in WT mice also significantly increased CVB3 levels in the heart and cardiac injury compared with controls. BM transplantation experiments demonstrated that PAR-1 in nonhematopoietic cells protected mice from CVB3 infection. Transgenic mice overexpressing PAR-1 in cardiomyocytes had reduced CVB3-induced myocarditis. We found that cooperative signaling between PAR-1 and TLR3 in mouse cardiac fibroblasts enhanced activation of p38 and induction of IFN-β and CXCL10 expression. Par1–/– mice also had decreased CXCL10 expression and increased viral levels in the lung after influenza A infection compared with Par1+/+ mice. Our results indicate that the tissue factor/thrombin/PAR-1 pathway enhances IFN-β expression and contributes to the innate immune response during single-stranded RNA viral infection. PMID:23391721

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

Astrocytes sustain long-term productive HIV-1 infection without establishment of reactivable viral latency.

Science.gov (United States)

Barat, Corinne; Proust, Alizé; Deshiere, Alexandre; Leboeuf, Mathieu; Drouin, Jean; Tremblay, Michel J

2018-02-21

The "shock and kill" HIV-1 cure strategy proposes eradication of stable cellular reservoirs by clinical treatment with latency-reversing agents (LRAs). Although resting CD4 + T cells latently infected with HIV-1 constitute the main reservoir that is targeted by these approaches, their consequences on other reservoirs such as the central nervous system are still unknown and should be taken into consideration. We performed experiments aimed at defining the possible role of astrocytes in HIV-1 persistence in the brain and the effect of LRA treatments on this viral sanctuary. We first demonstrate that the diminished HIV-1 production in a proliferating astrocyte culture is due to a reduced proliferative capacity of virus-infected cells compared with uninfected astrocytes. In contrast, infection of non-proliferating astrocytes led to a robust HIV-1 infection that was sustained for over 60 days. To identify astrocytes latently infected with HIV-1, we designed a new dual-color reporter virus called NL4.3 eGFP-IRES-Crimson that is fully infectious and encodes for all viral proteins. Although we detected a small fraction of astrocytes carrying silent HIV-1 proviruses, we did not observe any reactivation using various LRAs and even strong inducers such as tumor necrosis factor, thus suggesting that these proviruses were either not transcriptionally competent or in a state of deep latency. Our findings imply that astrocytes might not constitute a latent reservoir per se but that relentless virus production by this brain cell population could contribute to the neurological disorders seen in HIV-1-infected persons subjected to combination antiretroviral therapy. © 2018 Wiley Periodicals, Inc.

Bridging basic science and clinical research: the EASL Monothematic Conference on Translational Research in Viral Hepatitis.

Science.gov (United States)

Boettler, Tobias; Moradpour, Darius; Thimme, Robert; Zoulim, Fabien

2014-09-01

The EASL Monothematic Conference on Translational Research in Viral Hepatitis brought together a group of leading scientists and clinicians working on both, basic and clinical aspects of viral hepatitis, thereby building bridges from bench to bedside. This report recapitulates the presentations and discussions at the conference held in Lyon, France on November 29-30, 2013. In recent years, great advances have been made in the field of viral hepatitis, particularly in hepatitis C virus (HCV) infection. The identification of IL28B genetic polymorphisms as a major determinant for spontaneous and treatment-induced HCV clearance was a seminal discovery. Currently, hepatologists are at the doorstep of even greater advances, with the advent of a wealth of directly acting antivirals (DAAs) against HCV. Indeed, promising results have accumulated over the last months and few years, showing sustained virological response (SVR) rates of up to 100% with interferon-free DAA combination therapies. Thus, less than 25 years after its identification, HCV infection may soon be curable in the vast majority of patients, highlighting the great success of HCV research over the last decades. However, viral hepatitis and its clinical complications such as liver cirrhosis and hepatocellular carcinoma (HCC) remain major global challenges. New therapeutic strategies to tackle hepatitis B virus (HBV) and hepatitis D virus (HDV) infection are needed, as current therapies have undeniable limitations. Nucleoside/nucleotide analogues (NUC) can efficiently control HBV replication and reduce or even reverse liver damage. However, these drugs have to be given for indefinite periods in most patients to maintain virological and biochemical responses. Although sustained responses off treatment can be achieved by treatment with (pegylated) interferon-α, only about 10-30% of patients effectively resolve chronic hepatitis B. It was the goal of this conference to review the progress made over the last

Viral evasion of DNA-stimulated innate immune responses.

Science.gov (United States)

Christensen, Maria H; Paludan, Søren R

2017-01-01

Cellular sensing of virus-derived nucleic acids is essential for early defenses against virus infections. In recent years, the discovery of DNA sensing proteins, including cyclic GMP-AMP synthase (cGAS) and gamma-interferon-inducible protein (IFI16), has led to understanding of how cells evoke strong innate immune responses against incoming pathogens carrying DNA genomes. The signaling stimulated by DNA sensors depends on the adaptor protein STING (stimulator of interferon genes), to enable expression of antiviral proteins, including type I interferon. To facilitate efficient infections, viruses have evolved a wide range of evasion strategies, targeting host DNA sensors, adaptor proteins and transcription factors. In this review, the current literature on virus-induced activation of the STING pathway is presented and we discuss recently identified viral evasion mechanisms targeting different steps in this antiviral pathway.

Mechanisms of Hepatitis C Viral Resistance to Direct Acting Antivirals.

Science.gov (United States)

Ahmed, Asma; Felmlee, Daniel J

2015-12-18

There has been a remarkable transformation in the treatment of chronic hepatitis C in recent years with the development of direct acting antiviral agents targeting virus encoded proteins important for viral replication including NS3/4A, NS5A and NS5B. These agents have shown high sustained viral response (SVR) rates of more than 90% in phase 2 and phase 3 clinical trials; however, this is slightly lower in real-life cohorts. Hepatitis C virus resistant variants are seen in most patients who do not achieve SVR due to selection and outgrowth of resistant hepatitis C virus variants within a given host. These resistance associated mutations depend on the class of direct-acting antiviral drugs used and also vary between hepatitis C virus genotypes and subtypes. The understanding of these mutations has a clear clinical implication in terms of choice and combination of drugs used. In this review, we describe mechanism of action of currently available drugs and summarize clinically relevant resistance data.

Viral kinetics of hepatitis C virus RNA in patients with chronic hepatitis C treated with 18 MU of interferon alpha daily

NARCIS (Netherlands)

Sentjens, Roel E.; Weegink, Christine J.; Beld, Marcel G.; Cooreman, Michel C.; Reesink, Henk W.

2002-01-01

BACKGROUND: A rapid decrease of hepatitis C virus (HCV) RNA is interferon (IFN) dose-dependent, and a 3-log decline of HCV-RNA is a strong predictor of sustained virological response. In this study, viral kinetics of HCV RNA in patients treated with 18 MU interferon alpha (IFN-alpha) daily for 2

Viral DNA Sensors IFI16 and Cyclic GMP-AMP Synthase Possess Distinct Functions in Regulating Viral Gene Expression, Immune Defenses, and Apoptotic Responses during Herpesvirus Infection

Directory of Open Access Journals (Sweden)

Benjamin A. Diner

2016-11-01

Full Text Available The human interferon-inducible protein IFI16 is an important antiviral factor that binds nuclear viral DNA and promotes antiviral responses. Here, we define IFI16 dynamics in space and time and its distinct functions from the DNA sensor cyclic dinucleotide GMP-AMP synthase (cGAS. Live-cell imaging reveals a multiphasic IFI16 redistribution, first to viral entry sites at the nuclear periphery and then to nucleoplasmic puncta upon herpes simplex virus 1 (HSV-1 and human cytomegalovirus (HCMV infections. Optogenetics and live-cell microscopy establish the IFI16 pyrin domain as required for nuclear periphery localization and oligomerization. Furthermore, using proteomics, we define the signature protein interactions of the IFI16 pyrin and HIN200 domains and demonstrate the necessity of pyrin for IFI16 interactions with antiviral proteins PML and cGAS. We probe signaling pathways engaged by IFI16, cGAS, and PML using clustered regularly interspaced short palindromic repeat (CRISPR/Cas9-mediated knockouts in primary fibroblasts. While IFI16 induces cytokines, only cGAS activates STING/TBK-1/IRF3 and apoptotic responses upon HSV-1 and HCMV infections. cGAS-dependent apoptosis upon DNA stimulation requires both the enzymatic production of cyclic dinucleotides and STING. We show that IFI16, not cGAS or PML, represses HSV-1 gene expression, reducing virus titers. This indicates that regulation of viral gene expression may function as a greater barrier to viral replication than the induction of antiviral cytokines. Altogether, our findings establish coordinated and distinct antiviral functions for IFI16 and cGAS against herpesviruses.

IPNV with high and low virulence: host immune responses and viral mutations during infection

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Skjesol Astrid

2011-08-01

Full Text Available Abstract Background Infectious pancreatic necrosis virus (IPNV is an aquatic member of the Birnaviridae family that causes widespread disease in salmonids. IPNV is represented by multiple strains with markedly different virulence. Comparison of isolates reveals hyper variable regions (HVR, which are presumably associated with pathogenicity. However little is known about the rates and modes of sequence divergence and molecular mechanisms that determine virulence. Also how the host response may influence IPNV virulence is poorly described. Methods In this study we compared two field isolates of IPNV (NFH-Ar and NFH-El. The sequence changes, replication and mortality were assessed following experimental challenge of Atlantic salmon. Gene expression analyses with qPCR and microarray were applied to examine the immune responses in head kidney. Results Significant differences in mortality were observed between the two isolates, and viral load in the pancreas at 13 days post infection (d p.i. was more than 4 orders of magnitude greater for NFH-Ar in comparison with NFH-El. Sequence comparison of five viral genes from the IPNV isolates revealed different mutation rates and Ka/Ks ratios. A strong tendency towards non-synonymous mutations was found in the HRV of VP2 and in VP3. All mutations in VP5 produced precocious stop codons. Prior to the challenge, NFH-Ar and NFH-El possessed high and low virulence motifs in VP2, respectively. Nucleotide substitutions were noticed already during passage of viruses in CHSE-214 cells and their accumulation continued in the challenged fish. The sequence changes were notably directed towards low virulence. Co-ordinated activation of anti-viral genes with diverse functions (IFN-a1 and c, sensors - Rig-I, MDA-5, TLR8 and 9, signal transducers - Srk2, MyD88, effectors - Mx, galectin 9, galectin binding protein, antigen presentation - b2-microglobulin was observed at 13 d p.i. (NFH-Ar and 29 d p.i. (both isolates

Sustainable Development and Corporate Social Responsibility: Linking Goals to Standards

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Radostina Bakardjieva

2016-12-01

Full Text Available Corporate social responsibility (CSR is the core of sustainable development of companies. On one hand, the corporate social responsibility of companies is a prerequisite for sustainable business, on the other - sustainable development sets specific requirements for the development of businesses in the context of increasing requirements to the degree of quality and reliability of financial information. In recent years, sustainable development has become a strategic issue for companies and this trend applies to Bulgarian companies too. Development of non-financial reporting is a very dynamic process, whose peak is the establishment of an integrated system of accountability. Current paper makes analyses of advantages of CSR linking it to the implementation of sustainable development goals through the integrated reporting following the requirements of the standards of the Global Reporting Initiative (GRI.

Slower Fibrosis Progression Among Liver Transplant Recipients With Sustained Virological Response After Hepatitis C Treatment

Science.gov (United States)

Habib, Shahid; Meister, Edward; Habib, Sana; Murakami, Traci; Walker, Courtney; Rana, Abbas; Shaikh, Obaid S.

2015-01-01

Background The natural course of hepatic fibrosis in HCV allograft recipients with sustained virological response (SVR) after anti-HCV therapy remains debatable. The aim of this study was to examine the progression of fibrosis in a cohort of patients who achieved SVR compared with those without treatment. Methods The 167 patients who met the inclusion and exclusion criteria were chosen from a transplant database. All patients were required to have histological evidence of recurrent HCV infection post-liver transplantation and a follow-up biopsy. The 140 of these patients had received anti-viral therapy. Twenty-seven patients were identified as controls and were matched with the treatment group in all respects. The patients were categorized into four groups based on treatment response: 1) no treatment (control) (n = 27); 2) non-responders (n = 81); 3) relapsers (n = 32); and 4) SVR (n = 27). The endpoint was the stage of fibrosis on the follow-up liver biopsy. Results The treated and untreated groups were similar in clinical characteristics at the time of transplantation and prior to the initiation of treatment. The 72% of the cohort showed a fibrosis progression of ≥ 1 stage; this change did not significantly differ between the patient groups. Nonetheless, the fibrosis progression rate was the highest in the untreated group and lowest in the patients who achieved SVR. A coefficient of determination was used. Improvements in fibrosis scores were found with greater treatment duration. These improvements were most evident with the achievement of SVR. Conclusions In conclusion, SVR after anti-viral therapy for recurrent hepatitis C infection post-transplantation was associated with slower fibrosis progression and significantly improved graft survival. PMID:27785303

IL-10 and IL-28B gene variants as predictors of sustained response to peginterferon and ribavirin therapy in chronic HCV infection.

Science.gov (United States)

Sghaier, Ikram; Mouelhi, Leila; Rabia, Noor A; Ghazoueni, Ezzedine; Almawi, Wassim Y; Loueslati, Besma Yacoubi

2017-04-05

Interleukin-10 (IL-10) plays an important role in the immunity to hepatitis C virus (HCV). Insofar as IL-10 variants are associated with altered levels of IL-10, previous studies that examined the association of IL-10 polymorphisms with the susceptibility to and progression of chronic HCV, and response to anti-viral treatment were inconsistent. We investigated the association between common IL-10 variants in the intron and the promotor region with HCV and associated features. Study subjects comprised 120 patients infected with HCV-1b, and treated with Peg-IFN/RBV. Genotyping of six IL-10 promoter variants in the intron region (rs1878672, rs1554286, rs1518111) and promotor region (rs1800872, rs1800871, rs1800896) were done by real-time PCR. Compared to G/G, carriage of IL-10 rs1800896 (-1082A/G) A/A genotype was more frequent in patients with sustained virological response (SVR). The decline in viral load over the first 12weeks of treatment was more pronounced in rs1800896 A/A genotype carriers, compared to G/G genotype carriers, and was irrespective of the treatment dosage. Carriage of rs1800896 A/A genotype was positively associated with improvement in viral load decline, which was simultaneous, with and without carriage of the common favourable IL-28B variant. Carriage of both IL-10 rs1800896 G/G and IL-28B non-favourable genotype was associated with twice the risk of getting slow decline of viral load during treatment. Haploview analysis identified ACGCTA and CCGCTG haplotypes to be linked with excellent PegIFN/RBV cure rate, and complete HCV eradication. On the other hand, ACGCTG and CCGCTA haplotypes were associated with resistance to PegIFN/RBV treatment. IL-10 rs1800896 variant markedly influences the clinical outcome of HCV infection, and is a determinant of the response to HCV treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sustainable Ergonomic Program - Basic Condition for Implementation of Corporate Social Responsibility

Science.gov (United States)

Marková, Petra; Beňo, Rastislav; Hatiar, Karol

2012-12-01

Gradually increasing pressure on companies to start to behave socially responsible is a response to social, environmental and economic requirements. The society faces a period of changes that have occurred since the beginning of the crisis and revealing weaknesses in the economy. We become witnesses of rapid changes and challenges posed by globalization, lack of resources, demographic structure and innovation. Objective necessity becomes a corporate social responsibility (CSR) already at the companies’ level, which is supported by the approach of the EU institutions and the Slovak Republic. One of the possible appliance through which we can contribute to the sustainability of CSR are sustainable ergonomic programs. When we want to talk about sustainable ergonomic program is important to focus on three key areas. The first area is the Impact of technic and technology to employees at work, the second area is the Importance and impact of socially responsible HR in ergonomics and last area is the Creation of the work environment in relation to environmental sustainability. Ergonomic programs sustainability requires to apply appropriate methods for evaluation of their cost benefit and health effect.

Cell-mediated immune responses in rainbow trout after DNA immunization against the viral hemorrhagic septicemia virus

DEFF Research Database (Denmark)

Utke, Katrin; Kock, Holger; Schuetze, Heike

2008-01-01

injection site rather than to injection sites of heterologous vaccines, suggesting the antigen specificity of homing. By demonstrating CMC responses to distinct viral proteins and homing in rainbow trout, these results substantially contribute to the understanding of the teleost immune system.......To identify viral proteins that induce cell-mediated cytotoxicity (CMC) against viral hemorrhagic septicemia virus (VHSV)-infected cells, rainbow trout were immunized with DNA vectors encoding the glycoprotein G or the nucleocapsid protein N of VHSV. The G protein was a more potent trigger...... of cytotoxic cells than the N protein. Peripheral blood leukocytes (PBL) isolated from trout immunized against the G protein killed both VHSV-infected MHC class I matched (RTG-2) and VHSV-infected xenogeneic (EPC) target cells, suggesting the involvement of both cytotoxic T lymphocytes (CTL) and NK cells...

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

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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.

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.

Viral evasion of DNA-stimulated innate immune responses

Science.gov (United States)

Christensen, Maria H; Paludan, Søren R

2017-01-01

Cellular sensing of virus-derived nucleic acids is essential for early defenses against virus infections. In recent years, the discovery of DNA sensing proteins, including cyclic GMP–AMP synthase (cGAS) and gamma-interferon-inducible protein (IFI16), has led to understanding of how cells evoke strong innate immune responses against incoming pathogens carrying DNA genomes. The signaling stimulated by DNA sensors depends on the adaptor protein STING (stimulator of interferon genes), to enable expression of antiviral proteins, including type I interferon. To facilitate efficient infections, viruses have evolved a wide range of evasion strategies, targeting host DNA sensors, adaptor proteins and transcription factors. In this review, the current literature on virus-induced activation of the STING pathway is presented and we discuss recently identified viral evasion mechanisms targeting different steps in this antiviral pathway. PMID:26972769

Biodegradable nanoparticle-entrapped vaccine induces cross-protective immune response against a virulent heterologous respiratory viral infection in pigs.

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Varun Dwivedi

Full Text Available Biodegradable nanoparticle-based vaccine development research is unexplored in large animals and humans. In this study, we illustrated the efficacy of nanoparticle-entrapped UV-killed virus vaccine against an economically important respiratory viral disease of pigs called porcine reproductive and respiratory syndrome virus (PRRSV. We entrapped PLGA [poly (lactide-co-glycolides] nanoparticles with killed PRRSV antigens (Nano-KAg and detected its phagocytosis by pig alveolar macrophages. Single doses of Nano-KAg vaccine administered intranasally to pigs upregulated innate and PRRSV specific adaptive responses. In a virulent heterologous PRRSV challenge study, Nano-KAg vaccine significantly reduced the lung pathology and viremia, and the viral load in the lungs. Immunologically, enhanced innate and adaptive immune cell population and associated cytokines with decreased secretion of immunosuppressive mediators were observed at both mucosal sites and blood. In summary, we demonstrated the benefits of intranasal delivery of nanoparticle-based viral vaccine in eliciting cross-protective immune response in pigs, a potential large animal model.

Exercise Improves Host Response to Influenza Viral Infection in Obese and Non-Obese Mice through Different Mechanisms

Science.gov (United States)

Warren, Kristi J.; Olson, Molly M.; Thompson, Nicholas J.; Cahill, Mackenzie L.; Wyatt, Todd A.; Yoon, Kyoungjin J.; Loiacono, Christina M.; Kohut, Marian L.

2015-01-01

Obesity has been associated with greater severity of influenza virus infection and impaired host defense. Exercise may confer health benefits even when weight loss is not achieved, but it has not been determined if regular exercise improves immune defense against influenza A virus (IAV) in the obese condition. In this study, diet-induced obese mice and lean control mice exercised for eight weeks followed by influenza viral infection. Exercise reduced disease severity in both obese and non-obese mice, but the mechanisms differed. Exercise reversed the obesity-associated delay in bronchoalveolar-lavage (BAL) cell infiltration, restored BAL cytokine and chemokine production, and increased ciliary beat frequency and IFNα-related gene expression. In non-obese mice, exercise treatment reduced lung viral load, increased Type-I-IFN-related gene expression early during infection, but reduced BAL inflammatory cytokines and chemokines. In both obese and non-obese mice, exercise increased serum anti-influenza virus specific IgG2c antibody, increased CD8+ T cell percentage in BAL, and reduced TNFα by influenza viral NP-peptide-responding CD8+ T cells. Overall, the results suggest that exercise “restores” the immune response of obese mice to a phenotype similar to non-obese mice by improving the delay in immune activation. In contrast, in non-obese mice exercise treatment results in an early reduction in lung viral load and limited inflammatory response. PMID:26110868

Corporate social responsibility, a strategy to create and consolidate sustainable businesses

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Mariana Cristina GANESCU

2012-11-01

Full Text Available To highlight the strategic importance of CSR, this paper starts with a study of specialized literature in order to identify the role of these strategies in the creation and strengthening of sustainable business. Using Dunphy's model as a start point, we attempted to draft typologies for social responsibility strategies that support organizations in creating and strengthening sustainable business. An empirical study of the European automobile industry has sought to highlight the impact CSR strategies have on sustainable business. Selection and implementation of appropriate social responsibility strategies are important in achieving added value through the creation and strengthening of sustainable business.

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

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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.

WHERE DOES CORPORATE SOCIAL RESPONSIBILITY STAND IN RELATION TO SUSTAINABILITY?

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Nancy Diana Panta

2018-03-01

Full Text Available The business competitive landscape of today is shaped by new challenges. In order to outperform their peers, companies seek to seize opportunities and manage the risks associated with the challenges that arise. To this adds the pressure of societies on organizations to be more transparent, ethical and responsible. Corporate Social Responsibility (CSR and sustainability come in response to this increasing demand of societies by being a pivotal tool in the business area. Organizations of the 21st century can no longer ignore CSR and sustainability and should follow the steps of integrating them across all departments as part of their strategic policy. Sustainable organizations are required to direct their interest beyond the economical factor and extend their goals towards environmental and social aspects. By integrating environmental and social concerns in the daily operations of a company, new models of doing business emerge and a synergy with various stakeholder groups takes place. Although a significant amount of attention has been headed towards the conceptualisation of CSR and sustainability, they both remain contested concepts. Therefore, the present paper depicts the effort to follow the emergence and conceptualization of CSR and sustainability from their origins, to introduce the changing meaning of CSR and to bridge the gap between the two concepts. Through literature review, the paper will provide relevant theoretical underpinnings that link CSR and sustainability.

Constrained pattern of viral evolution in acute and early HCV infection limits viral plasticity.

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Katja Pfafferott

2011-02-01

Full Text Available Cellular immune responses during acute Hepatitis C virus (HCV and HIV infection are a known correlate of infection outcome. Viral adaptation to these responses via mutation(s within CD8+ T-cell epitopes allows these viruses to subvert host immune control. This study examined HCV evolution in 21 HCV genotype 1-infected subjects to characterise the level of viral adaptation during acute and early HCV infection. Of the total mutations observed 25% were within described CD8+ T-cell epitopes or at viral adaptation sites. Most mutations were maintained into the chronic phase of HCV infection (75%. The lack of reversion of adaptations and high proportion of silent substitutions suggests that HCV has structural and functional limitations that constrain evolution. These results were compared to the pattern of viral evolution observed in 98 subjects during a similar phase in HIV infection from a previous study. In contrast to HCV, evolution during acute HIV infection is marked by high levels of amino acid change relative to silent substitutions, including a higher proportion of adaptations, likely reflecting strong and continued CD8+ T-cell pressure combined with greater plasticity of the virus. Understanding viral escape dynamics for these two viruses is important for effective T cell vaccine design.

Spliceosome SNRNP200 Promotes Viral RNA Sensing and IRF3 Activation of Antiviral Response.

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Nicolas Tremblay

2016-07-01

Full Text Available Spliceosomal SNRNP200 is a Ski2-like RNA helicase that is associated with retinitis pigmentosa 33 (RP33. Here we found that SNRNP200 promotes viral RNA sensing and IRF3 activation through the ability of its amino-terminal Sec63 domain (Sec63-1 to bind RNA and to interact with TBK1. We show that SNRNP200 relocalizes into TBK1-containing cytoplasmic structures upon infection, in contrast to the RP33-associated S1087L mutant, which is also unable to rescue antiviral response of SNRNP200 knockdown cells. This functional rescue correlates with the Sec63-1-mediated binding of viral RNA. The hindered IFN-β production of knockdown cells was further confirmed in peripheral blood cells of RP33 patients bearing missense mutation in SNRNP200 upon infection with Sendai virus (SeV. This work identifies a novel immunoregulatory role of the spliceosomal SNRNP200 helicase as an RNA sensor and TBK1 adaptor for the activation of IRF3-mediated antiviral innate response.

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

Impact of sex steroid ablation on viral, tumour and vaccine responses in aged mice.

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Tracy S P Heng

Full Text Available Recent evidence suggests that the decline in resistance to viral infections with age occurs predominantly as a result of a gradual loss of naïve antigen-specific T cells. As such, restoration of the naïve T cell repertoire to levels seen in young healthy adults may improve defence against infection in the aged. We have previously shown that sex steroid ablation (SSA rejuvenates the ageing thymus and increases thymic export of naïve T cells, but it remains unclear whether T cell responses are improved. Using mouse models of clinically relevant diseases, we now demonstrate that SSA increases the number of naïve T cells able to respond to antigen, thereby enhancing effector responses in aged mice. Specifically, aged mice exhibit a delay in clearing influenza A virus, which correlates with diminished specific cytotoxic activity. This is due to a decreased magnitude of response and not an intrinsic defect in effector T cell function. Upon SSA, aged mice exhibit increased T cell responsiveness that restores efficient viral clearance. We further demonstrate that SSA decreases the incidence of an inducible tumour in aged mice and can potentially increase their responsiveness to a low-dose human papillomavirus vaccine in clearing pre-formed tumours. As thymectomy abrogates the increase in T cell numbers and responsiveness following SSA, we propose that the T cell effects of SSA are dependent on thymic reactivation and subsequent replenishment of the peripheral T cell pool with newly emigrated naïve T cells. These findings have important implications for strategies to improve protection from infection and responsiveness to vaccination in the aged.

Mechanisms of Hepatitis C Viral Resistance to Direct Acting Antivirals

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Asma Ahmed

2015-12-01

Full Text Available There has been a remarkable transformation in the treatment of chronic hepatitis C in recent years with the development of direct acting antiviral agents targeting virus encoded proteins important for viral replication including NS3/4A, NS5A and NS5B. These agents have shown high sustained viral response (SVR rates of more than 90% in phase 2 and phase 3 clinical trials; however, this is slightly lower in real-life cohorts. Hepatitis C virus resistant variants are seen in most patients who do not achieve SVR due to selection and outgrowth of resistant hepatitis C virus variants within a given host. These resistance associated mutations depend on the class of direct-acting antiviral drugs used and also vary between hepatitis C virus genotypes and subtypes. The understanding of these mutations has a clear clinical implication in terms of choice and combination of drugs used. In this review, we describe mechanism of action of currently available drugs and summarize clinically relevant resistance data.

Antibody-independent control of gamma-herpesvirus latency via B cell induction of anti-viral T cell responses.

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Kelly B McClellan

2006-06-01

Full Text Available B cells can use antibody-dependent mechanisms to control latent viral infections. It is unknown whether this represents the sole function of B cells during chronic viral infection. We report here that hen egg lysozyme (HEL-specific B cells can contribute to the control of murine gamma-herpesvirus 68 (gammaHV68 latency without producing anti-viral antibody. HEL-specific B cells normalized defects in T cell numbers and proliferation observed in B cell-/- mice during the early phase of gammaHV68 latency. HEL-specific B cells also reversed defects in CD8 and CD4 T cell cytokine production observed in B cell-/- mice, generating CD8 and CD4 T cells necessary for control of latency. Furthermore, HEL-specific B cells were able to present virally encoded antigen to CD8 T cells. Therefore, B cells have antibody independent functions, including antigen presentation, that are important for control of gamma-herpesvirus latency. Exploitation of this property of B cells may allow enhanced vaccine responses to chronic virus infection.

Corporate Social Responsibility and Sustainability in Danish Public Procurement

DEFF Research Database (Denmark)

Andrecka, Marta

2017-01-01

understand the continuously developing concepts of SPP, as well as to identify the drivers and barriers that promote or hinder its further implementation. This article firstly deals with the relationship between the concepts of sustainability, Corporate Social Responsibility (CSR) and public procurement....... Secondly, as Denmark has been known as a pioneer in sustainable development, including implementation of it in public purchasing this article focuses on recent developments in the areas of CSR and sustainable public procurement in Denmark, and analyses relevant Danish Public Procurement Complaints Board...

Sustainable and responsible supply chain governance: challenges and opportunities

NARCIS (Netherlands)

Boström, M.; Jönsson, A.M.; Lockie, S.; Mol, A.P.J.; Oosterveer, P.J.M.

2015-01-01

This paper introduces the Special Volume on sustainable and responsible supply chain governance. As globalized supply chains cross multiple regulatory borders, the firms involved in these chains come under increasing pressure from consumers, NGOs and governments to accept responsibility for social

Hepatitis C treatment response kinetics and impact of baseline predictors

DEFF Research Database (Denmark)

Lindh, M; Arnholm, B; Eilard, A

2011-01-01

Summary. The optimal duration of treatment for hepatitis C virus (HCV) infections is highly variable but critical for achieving cure (sustained virological response, SVR). We prospectively investigated the impact of age, fibrosis, baseline viraemia and genotype on the early viral kinetics...... above 400 000 IU/mL were strongly associated with slower second phase declines of HCV RNA. Genotype 2/3 infections responded more rapidly than genotype 1, reaching week 4 negativity (RVR) in 59%vs 22%. We conclude that baseline response predictors such as age, fibrosis and viral load were well reflected...... by the early viral kinetics as assessed by repeated HCV RNA quantifications. The kinetic patterns and the high relapse rate in genotype 2/3 patients without RVR suggest that this group might benefit from treatment durations longer than 24 weeks....

TREX1 Knockdown Induces an Interferon Response to HIV that Delays Viral Infection in Humanized Mice

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Lee Adam Wheeler

2016-05-01

Full Text Available Despite their antiviral effect, the in vivo effect of interferons on HIV transmission is difficult to predict, because interferons also activate and recruit HIV-susceptible cells to sites of infection. HIV does not normally induce type I interferons in infected cells, but does if TREX1 is knocked down. Here, we investigated the effect of topical TREX1 knockdown and local interferon production on HIV transmission in human cervicovaginal explants and humanized mice. In explants in which TREX1 was knocked down, HIV induced interferons, which blocked infection. In humanized mice, even though TREX1 knockdown increased infiltrating immune cells, it delayed viral replication for 3–4 weeks. Similarly intravaginal application of type I interferons the day before HIV infection induced interferon responsive genes, reduced inflammation, and decreased viral replication. However, intravenous interferon enhanced inflammation and infection. Thus, in models of human sexual transmission, a localized interferon response inhibits HIV transmission but systemic interferons do not.

Four weeks of paritaprevir/ritonavir/ombitasvir plus dasabuvir encountering dengue fever resulted in sustained virological response in an HCV patient: A case report.

Science.gov (United States)

Huang, Chung-Feng; Jang, Tyng-Yuan; Lu, Po-Liang; Yu, Ming-Lung

2016-11-01

Direct antiviral agent (DAA) has been the standard of care for patients with hepatitis C virus (HCV) infection. Twelve weeks of paritaprevir/ritonavir/ombitasvir plus dasabuvir (PROD) with or without ribavirin has shown to have a sustained virological response at post-treatment 12 weeks (SVR12) rate of >90% in HCV genotype 1 (HCV-1) patients. We report a HCV-1b patient who received only 25 days of PROD treatment. The patient early terminated treatment due to dengue fever but eventually achieved SVR12. It may attribute to low baseline viral loads and extraordinarily rapid suppression of HCV after treatment day1. The finding may shed light for possible response-guided-therapy for so-called ultra-super-responders in the DAA era. Whether the dengue virus, the Flaviviridae family as with HCV, enhanced the HCV clearance remains unclear and needs further exploration.

Responsible and Sustainable Tourism : Strengthening Small-Scale ...

International Development Research Centre (IDRC) Digital Library (Canada)

Responsible and Sustainable Tourism : Strengthening Small-Scale ... to work with the Costa Rican association of small and medium tourism enterprises of the ... as the hub of a network of small service providers operating within the model. ... marketing and outreach, distance learning, and the integration of services that are ...

SUSTAINABILITY AS A STRATEGY OF RESPONSIBLE AND COMPETITIVE DEVELOPMENT

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José G. Vargas-Hernández

2012-12-01

Full Text Available The aim of this paper is to analyze a competitiveness strategy based on sustainability to lead the way to a model of responsible and competitive development. The analysis takes as its starting point the assumption that the maturity of a sustainable business strategy positively affects competitiveness. The used method is the critical analysis. Among other results of this analysis concludes that the current business strategy seeks a system ecologically appropriate, economically viable and socially fair to reach sustainable equilibrium. This strategy based on sustainability must be promoted by the institutions and strengthened by the capabilities and resources that each company counts on to develop advantages to foster the overall development and achieve the maximization of benefits from the tangible and intangible perspectives

THE STRATEGIC IMPORTANCE OF CORPORATE RESPONSIBILITY AND SUSTAINABILITY IN BANKING

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DRĂGAN (SÂNTĂMARIAN OANA RALUCA

2013-02-01

Full Text Available The paper aims to highlight the strategic implication of corporate social responsibility (CSR and sustainable development for the banking sector. A few years ago, banks did not give much importance to the social and environmental problems. Recently, the banks began to realize the major impact of the sustainable development over the way of ulterior development of the society and, implicitly over the banking system. In this context, the development of a bank management system based on sustainable principles is one of the current challenges. For this purpose this paper focuses on issues such as the importance and advantages of implementing sustainability bank management, international standards regarding sustainable banking management such as: Equator Principles for sustainable investment projects’ financing or GRI principles for sustainable reporting. In addition, we have developed a practical case study about the implementation of sustainable banking management; the case study presents Romanian Commercial Bank as an example of good practice in the Romanian banking sector.

APOBEC3G inhibits HIV-1 RNA elongation by inactivating the viral trans-activation response element.

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Nowarski, Roni; Prabhu, Ponnandy; Kenig, Edan; Smith, Yoav; Britan-Rosich, Elena; Kotler, Moshe

2014-07-29

Deamination of cytidine residues in viral DNA is a major mechanism by which APOBEC3G (A3G) inhibits vif-deficient human immunodeficiency virus type 1 (HIV-1) replication. dC-to-dU transition following RNase-H activity leads to viral cDNA degradation, production of non-functional proteins, formation of undesired stop codons and decreased viral protein synthesis. Here, we demonstrate that A3G provides an additional layer of defense against HIV-1 infection dependent on inhibition of proviral transcription. HIV-1 transcription elongation is regulated by the trans-activation response (TAR) element, a short stem-loop RNA structure required for elongation factors binding. Vif-deficient HIV-1-infected cells accumulate short viral transcripts and produce lower amounts of full-length HIV-1 transcripts due to A3G deamination of the TAR apical loop cytidine, highlighting the requirement for TAR loop integrity in HIV-1 transcription. We further show that free single-stranded DNA (ssDNA) termini are not essential for A3G activity and a gap of CCC motif blocked with juxtaposed DNA or RNA on either or 3'+5' ends is sufficient for A3G deamination. These results identify A3G as an efficient mutator and that deamination of (-)SSDNA results in an early block of HIV-1 transcription. Copyright © 2014 Elsevier Ltd. All rights reserved.

APOBEC3 Interference during Replication of Viral Genomes

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Luc Willems

2015-06-01

Full Text Available Co-evolution of viruses and their hosts has reached a fragile and dynamic equilibrium that allows viral persistence, replication and transmission. In response, infected hosts have developed strategies of defense that counteract the deleterious effects of viral infections. In particular, single-strand DNA editing by Apolipoprotein B Editing Catalytic subunits proteins 3 (APOBEC3s is a well-conserved mechanism of mammalian innate immunity that mutates and inactivates viral genomes. In this review, we describe the mechanisms of APOBEC3 editing during viral replication, the viral strategies that prevent APOBEC3 activity and the consequences of APOBEC3 modulation on viral fitness and host genome integrity. Understanding the mechanisms involved reveals new prospects for therapeutic intervention.

Anti-metastatic effects of viral and non-viral mediated Nk4 delivery to tumours.

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Buhles, Alexandra; Collins, Sara A; van Pijkeren, Jan P; Rajendran, Simon; Miles, Michelle; O'Sullivan, Gerald C; O'Hanlon, Deirdre M; Tangney, Mark

2009-03-09

The most common cause of death of cancer sufferers is through the occurrence of metastases. The metastatic behaviour of tumour cells is regulated by extracellular growth factors such as hepatocyte growth factor (HGF), a ligand for the c-Met receptor tyrosine kinase, and aberrant expression/activation of the c-Met receptor is closely associated with metastatic progression. Nk4 (also known as Interleukin (IL)32b) is a competitive antagonist of the HGF c-Met system and inhibits c-Met signalling and tumour metastasis. Nk4 has an additional anti-angiogenic activity independent of its HGF-antagonist function. Angiogenesis-inhibitory as well as cancer-specific apoptosis inducing effects make the Nk4 sequence an attractive candidate for gene therapy of cancer. This study investigates the inhibition of tumour metastasis by gene therapy mediated production of Nk4 by the primary tumour. Optimal delivery of anti-cancer genes is vital in order to achieve the highest therapeutic responses. Non-viral plasmid delivery methods have the advantage of safety and ease of production, providing immediate transgene expression, albeit short-lived in most tumours. Sustained presence of anti-angiogenic molecules is preferable with anti-angiogenic therapies, and the long-term expression mediated by Adeno-associated Virus (AAV) might represent a more appropriate delivery in this respect. However, the incubation time required by AAV vectors to reach appropriate gene expression levels hampers efficacy in many fast-growing murine tumour models. Here, we describe murine trials assessing the effects of Nk4 on the spontaneously metastatic Lewis Lung Carcinoma (LLC) model when delivered to primary tumour via plasmid lipofection or AAV2 vector. Intratumoural AAV-Nk4 administration produced the highest therapeutic response with significant reduction in both primary tumour growth and incidence of lung metastases. Plasmid-mediated therapy also significantly reduced metastatic growth, but with moderate

Zinc source and concentration altered physiological responses of beef heifers during a combined viral-bacterial respiratory challenge

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Three treatments were evaluated in feedlot heifers to determine the effects of zinc supplementation on the immune response to a combined viral-bacterial respiratory disease challenge. Thirty-two beef heifers (255+/-15 kg) were subjected to a 30d period of Zn depletion, then randomly assigned to one ...

Hepatitis B and hepatitis C viruses: a review of viral genomes, viral induced host immune responses, genotypic distributions and worldwide epidemiology

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Umar Saeed

2014-04-01

Full Text Available Hepatitis B and hepatitis C viruses (HCV are frequently propagating blood borne pathogens in global community. Viral hepatitis is primarily associated with severe health complications, such as liver cirrhosis, hepatocellular carcinoma, hepatic fibrosis and steatosis. A literature review was conducted on hepatitis B virus (HBV, HBV genome, genotypic distribution and global epidemiology of HBV, HCV, HCV genome, HCV and host immune responses, HCV genotypic distribution and global epidemiology. The valued information was subjected for review. HBV has strict tissue tropism to liver. The virus infecting hepatocytes produces large amount of hepatitis B surface antigen particles which lack the DNA. It has capability to integrate into host genome. It has been found that genotype C is most emerging genotype associated with more severe liver diseases (cirrhosis. The approximate prevalence rate of genotype C is 27.7% which represents a major threat to future generations. Approximately 8% of population is chronic carrier of HBV in developing countries. The chronic carrier rate of HBV is 2%-7% in Middle East, Eastern and Southern Europe, South America and Japan. Among HCV infected individuals, 15% usually have natural tendency to overcome acute viral infection, where as 85% of individuals were unable to control HCV infection. The internal ribosomal entry site contains highly conserved structures important for binding and appropriate positioning of viral genome inside the host cell. HCV infects only in 1%-10% of hepatocytes, but production of tumor necrosis factor alpha (from CD8+ cells and interferon-gamma cause destruction of both infected cells and non-infected surrounding cells. Almost 11 genotypes and above 100 subtypes of HCV exists worldwide with different geographical distribution. Many efforts are still needed to minimize global burden of these infections. For the complete eradication of HBV (just like small pox and polio via vaccination strategies

Predictors of sustained response to rivastigmine in patients with Alzheimer's disease: a retrospective analysis.

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Sadowsky, Carl H; Grossberg, George T; Somogyi, Monique; Meng, Xiangyi

2011-01-01

The cholinesterase inhibitor rivastigmine is approved for the treatment of mild to moderate Alzheimer's disease. However, it is not possible to predict which individuals will benefit from treatment. This retrospective analysis of an international, 24-week, randomized, double-blind trial aimed to identify the percentage of persons with Alzheimer's disease who have a sustained response with rivastigmine patch, rivastigmine capsules, or placebo; to determine the magnitude of the sustained treatment response; and to investigate baseline patient characteristics predictive of the observed sustained response. Patients who improved on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and Alzheimer's Disease Cooperative Study-Activities of Daily Living scale (ADCS-ADL) at week 16 and maintained at least the week 16 improvement at week 24 were identified as sustained responders. Treatment differences and baseline predictive factors were assessed in patients demonstrating a 1-, 2-, 3-, 4-, or 5-point sustained improvement. The first patient was screened in November 2003 and the last patient completed the study in January 2006. More persons with Alzheimer's disease had sustained improvements on the ADAS-cog and ADCS-ADL with rivastigmine versus placebo. Sustained improvements of 4 or 5 points on the ADAS-cog or ADCS-ADL were demonstrated in the 9.5-mg/24-h rivastigmine patch (24% and 36% of patients, respectively) and 12-mg/d capsule groups (28% on both outcome measures). Factors predictive of a sustained response to treatment included baseline Mini-Mental State Examination, ADAS-cog, and ADCS-ADL scores and treatment, country of treatment, and time since first symptom was diagnosed by a physician. Understanding factors predictive of sustained cholinesterase inhibitor treatment response should help to optimize Alzheimer's disease management and encourage compliance by allowing more realistic expectations of treatment effects.

Viral Inhibition of PRR-Mediated Innate Immune Response: Learning from KSHV Evasion Strategies.

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Lee, Hye-Ra; Choi, Un Yung; Hwang, Sung-Woo; Kim, Stephanie; Jung, Jae U

2016-11-30

The innate immune system has evolved to detect and destroy invading pathogens before they can establish systemic infection. To successfully eradicate pathogens, including viruses, host innate immunity is activated through diverse pattern recognition receptors (PRRs) which detect conserved viral signatures and trigger the production of type I interferon (IFN) and pro-inflammatory cytokines to mediate viral clearance. Viral persistence requires that viruses co-opt cellular pathways and activities for their benefit. In particular, due to the potent antiviral activities of IFN and cytokines, viruses have developed various strategies to meticulously modulate intracellular innate immune sensing mechanisms to facilitate efficient viral replication and persistence. In this review, we highlight recent advances in the study of viral immune evasion strategies with a specific focus on how Kaposi's sarcoma-associated herpesvirus (KSHV) effectively targets host PRR signaling pathways.

THE ROLE OF SOCIAL RESPONSIBILITY STRATEGIES EMPLOYED BY EUROPEAN AUTOMOTIVE CORPORATIONS IN DEVELOPING SUSTAINABLE BUSINESSES

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Cristina Gănescu

2013-01-01

Full Text Available Corporate social responsibility strategies are a topic of great interest for both researchers and practitioners, and require the development of interdisciplinary approaches: economic, ethical and social. The paper analyses the social responsibility strategies employed by European automotive businesses and highlights their impact on business sustainability. From a theoretical perspective, applying the content analysis method on sustainability or social responsibility reports revealed a variety of social responsibility strategies. The utility of the research is supported by formulating a typology of social responsibility strategies, based on objectives of sustainable development and by establishing arguments concerning the impact of these strategies on automotive businesses’ sustainability in the following areas: social and societal, ecological and environmental, distribution chains and suppliers, corporate image, position in relation to competitors and financial performance.

Acute hepatitis A virus infection is associated with a limited type I interferon response and persistence of intrahepatic viral RNA.

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Lanford, Robert E; Feng, Zongdi; Chavez, Deborah; Guerra, Bernadette; Brasky, Kathleen M; Zhou, Yan; Yamane, Daisuke; Perelson, Alan S; Walker, Christopher M; Lemon, Stanley M

2011-07-05

Hepatitis A virus (HAV) is an hepatotropic human picornavirus that is associated only with acute infection. Its pathogenesis is not well understood because there are few studies in animal models using modern methodologies. We characterized HAV infections in three chimpanzees, quantifying viral RNA by quantitative RT-PCR and examining critical aspects of the innate immune response including intrahepatic IFN-stimulated gene expression. We compared these infection profiles with similar studies of chimpanzees infected with hepatitis C virus (HCV), an hepatotropic flavivirus that frequently causes persistent infection. Surprisingly, HAV-infected animals exhibited very limited induction of type I IFN-stimulated genes in the liver compared with chimpanzees with acute resolving HCV infection, despite similar levels of viremia and 100-fold greater quantities of viral RNA in the liver. Minimal IFN-stimulated gene 15 and IFIT1 responses peaked 1-2 wk after HAV challenge and then subsided despite continuing high hepatic viral RNA. An acute inflammatory response at 3-4 wk correlated with the appearance of virus-specific antibodies and apoptosis and proliferation of hepatocytes. Despite this, HAV RNA persisted in the liver for months, remaining present long after clearance from serum and feces and revealing dramatic differences in the kinetics of clearance in the three compartments. Viral RNA was detected in the liver for significantly longer (35 to >48 wk) than HCV RNA in animals with acute resolving HCV infection (10-20 wk). Collectively, these findings indicate that HAV is far stealthier than HCV early in the course of acute resolving infection. HAV infections represent a distinctly different paradigm in virus-host interactions within the liver.

Value Creation in the Context of Sustainable Corporate Social Responsibility

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Šmida, Ľubomír; Sakál, Peter

2014-12-01

Under the influence of the new rules of the economy and the society, companies are achieving a notional line of a necessary change in the approach to creating new value, wealth. Implementation of changes in the system of wealth creation requires a review of existing assumptions of unlimited growth of the global economy and wealth creation in the environment accepting economic interests, society and the environment as a holistic unit. The main purpose of this paper is the clarification of a new requirements for business, presentation of the questionnaire survey Sustainable Corporate Social Responsibility and inform on value creation in the context of Sustainable Corporate Social Responsibility.

Value Creation in the Context of Sustainable Corporate Social Responsibility

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Šmida Ľubomír

2014-12-01

Full Text Available Under the influence of the new rules of the economy and the society, companies are achieving a notional line of a necessary change in the approach to creating new value, wealth. Implementation of changes in the system of wealth creation requires a review of existing assumptions of unlimited growth of the global economy and wealth creation in the environment accepting economic interests, society and the environment as a holistic unit. The main purpose of this paper is the clarification of a new requirements for business, presentation of the questionnaire survey Sustainable Corporate Social Responsibility and inform on value creation in the context of Sustainable Corporate Social Responsibility.

Effect of Lopinavir and Nevirapine Concentrations on Viral Outcomes in Protease Inhibitor-experienced HIV-infected Children.

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Moholisa, Retsilisitsoe R; Schomaker, Michael; Kuhn, Louise; Castel, Sandra; Wiesner, Lubbe; Coovadia, Ashraf; Strehlau, Renate; Patel, Faeezah; Pinillos, Francoise; Abrams, Elaine J; Maartens, Gary; McIlleron, Helen

2016-12-01

Adequate exposure to antiretroviral drugs is necessary to achieve and sustain viral suppression. However, the target antiretroviral concentrations associated with long-term viral suppression have not been adequately defined in children. We assessed the relationship between plasma lopinavir or nevirapine concentrations and the risk of subsequent viremia in children initially suppressed on antiretroviral therapy. After an induction phase of antiretroviral treatment, 195 children with viral suppression (viral load ≤400 copies/mL) were randomized to continue a lopinavir/ritonavir-based regimen or to switch to a nevirapine-based regimen (together with lamivudine and stavudine). Viral load and lopinavir or nevirapine concentrations were measured at clinic visits 4, 8, 12, 16, 20, 24, 36, 52, 64 and 76 weeks post randomization. Cox multiple failure event models were used to estimate the effects of drug concentrations on the hazard of viremia (viral load >50 copies/mL) RESULTS:: At randomization, the median (interquartile range) age, CD4 T-Lymphocyte percentage, weight-for-age and weight-for-height z scores were 19 (16-24) months, 29% (23-37), -0.6 (-1.3 to 0.2) and -3.2 (-4.1 to -2.1), respectively. The proportion of children with viral load 51-400 copies/mL at randomization was 43%. The hazard of subsequent viremia during follow-up was increased for lopinavir concentrations <1 versus ≥1 mg/L [adjusted hazard ratio 0.62 (95% confidence interval, 0.40-0.94)] and for children with viral loads 51-400 copies/mL at randomization. Nevirapine concentrations were not significantly associated with subsequent viremia. Plasma lopinavir concentrations predicted viral outcomes in children receiving lopinavir-based antiretroviral therapy. Our findings support a minimum target concentration of ≥1 mg/L of lopinavir to ensure sustained viral suppression.

Reading the viral signature by Toll-like receptors and other pattern recognition receptors.

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Mogensen, Trine H; Paludan, Søren R

2005-03-01

Successful host defense against viral infections relies on early production of type I interferon (IFN) and subsequent activation of a cellular cytotoxic response. The acute IFN and inflammatory response against virus infections is mediated by cellular pattern-recognition receptors (PRRs) that recognize specific molecular structures on viral particles or products of viral replication. Toll-like receptors (TLRs) constitute a class of membrane-bound PRRs capable of detecting microbial infections. While TLR2 and TLR4, which were first identified to recognize Gram-positive and Gram-negative bacteria, respectively, sense specific viral proteins on the cell surface, TLRs 3, 7, 8, and 9 serve as receptors for viral nucleic acids in endosomic compartments. In addition to TLRs, cells express cytoplasmic PRRs such as the RNA helicase retinoic acid inducible gene I and the kinase double-stranded RNA-activated protein kinase R, both of which sense dsRNA, a characteristic signature of viral replication, and initiate a protective cellular response. Here we review the recent progress in our understanding of PRRs and viral infections and discuss the molecular and cellular responses evoked by virus-activated PRRs. Finally, we look into what is currently known about the role of PRRs in viral infections in vivo.

Understanding the Innate Immune Response in Viral Hepatitis : Interferons and NK Cells

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R.A. de Groen (Rik)

2017-01-01

textabstractHBV and HCV infection are the two leading causes of chronic liver inflammation worldwide, affecting an approximate 370–390 million people. Currently, the viral and immunological mechanisms that underlie either the resolution or persistence of viral hepatitis infections are not fully

A Collaborative Programme in Sustainability and Social Responsibility

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Albareda Tiana, Silvia; Alférez Villarreal, Azul

2016-01-01

Purpose: The purpose of this paper is to collect methodological strategies used in the training of future teachers to develop competences in sustainability and social responsibility (SSR). The proposal in this paper is to show how students learn and develop competences by performing practical activities and through a collaborative experience,…

Influential Factors and Strategy of Sustainable Product Development under Corporate Social Responsibility in Taiwan

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Jui-Che Tu

2013-01-01

Full Text Available This study aimed to adopt the perspective of corporate social responsibility (CSR to explore the intention of sustainable product development in Taiwan, as well as leading to the creation of influential factors that affect corporate sustainable product development intention. In this research, the induction analysis was conducted to understand the implementation of sustainable product development, and this was supplemented with questionnaire surveys and in-depth interviews to evaluate developmental intention. In addition, principal component analysis was used for factor analysis and content analysis in the 6 W expression method, leading to the creation of the influential factors. The research results have demonstrated that the factors affecting the intention of corporate sustainable product development include having a sustainable design and a development purpose, a corporate development purpose, sustainable development concepts, a sustainable design value, a sustainability concept, and a manufacturing process quality. For sustainable product development, corporate social responsibility needs to be most concerned with the added value of products, regulation requirements, and accommodation of the industrial chain, costs, and quality.

Eco-innovation, Responsible Leadership and Organizational Change for Corporate Sustainability

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Dorel Mihai Paraschiv

2012-06-01

Full Text Available Creating a sustainable development strategy is essential for organizations that seek to reduce risks associated with tightening legislation, increased energy prices and natural resources and growing customer demands. Sustainability requires the full integration of social and environmental aspects into the vision, culture and operations of an organization, a profound process of organizational change being essential. The purpose of this paper is to present the main drivers of corporate sustainability, illustrating – after a thorough literature review – the link between the following elements: corporate sustainability – a necessity in the current global context; eco-innovation – as a way to implement sustainability in an organization; responsible leadership – as the art of building and maintaining strong and moral relationships with all stakeholders; organizational culture and organizational change – the basic elements through which organizations continuously renew their processes and products, adapting them to the new context. Furthermore, the paper provides an overview of organizations active in Romania in terms of sustainability practices, in general, and the ecological component of sustainable development, in particular, by presenting the results of an exploratory questionnaire-based research. The research reflects the importance of visionary management in adopting and implementing sustainability in the responding organizations.

Corporate Sustainable Development Assessment Base on the Corporate Social Responsibility

OpenAIRE

Sun Mei; Nagata Katsuya; Onoda Hiroshi

2011-01-01

With the resource exhaustion, bad affections of human activities and the awakening of the human rights, the corporate social responsibility became popular corporate strategy achieving sustainable development of both corporation and society. The issue of Guideline of Chinese Corporate Social Responsibility Report promotes greatly corporation to take social responsibility. This paper built the index system according to this guideline and takes the textile industry as an exa...

The aryl hydrocarbon receptor is a modulator of anti-viral immunity

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Head, Jennifer L.; Lawrence, B. Paige

2009-01-01

Although immune modulation by AhR ligands has been studied for many years, the impact of AhR activation on host defenses against viral infection has not, until recently, garnered much attention. The development of novel reagents and model systems, new information regarding antiviral immunity, and a growing appreciation for the global health threat posed by viruses have invigorated interest in understanding how environmental signals affect susceptibility to and pathological consequences of viral infection. Using influenza A virus as a model of respiratory viral infection, recent studies show that AhR activation cues signaling events in both leukocytes and non-immune cells. Functional alterations include suppressed lymphocyte responses and increased inflammation in the infected lung. AhR-mediated events within and extrinsic to hematopoietic cells has been investigated using bone marrow chimeras, which show that AhR alters different elements of the immune response by affecting different tissue targets. In particular, suppressed CD8+ T cell responses are due to deregulated events within leukocytes themselves, whereas increased neutrophil recruitment to and IFN-γ levels in the lung result from AhR-regulated events extrinsic to bone marrow-derived cells. This latter discovery suggests that epithelial and endothelial cells are overlooked targets of AhR-mediated changes in immune function. Further support that AhR influences host cell responses to viral infection are provided by several studies demonstrating that AhR interacts directly with viral proteins and affects viral latency. While AhR clearly modulates host responses to viral infection, we still have much to understand about the complex interactions between immune cells, viruses, and the host environment. PMID:19027719

Wolbachia Blocks Viral Genome Replication Early in Infection without a Transcriptional Response by the Endosymbiont or Host Small RNA Pathways.

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Stephanie M Rainey

2016-04-01

Full Text Available The intracellular endosymbiotic bacterium Wolbachia can protect insects against viral infection, and is being introduced into mosquito populations in the wild to block the transmission of arboviruses that infect humans and are a major public health concern. To investigate the mechanisms underlying this antiviral protection, we have developed a new model system combining Wolbachia-infected Drosophila melanogaster cell culture with the model mosquito-borne Semliki Forest virus (SFV; Togaviridae, Alphavirus. Wolbachia provides strong antiviral protection rapidly after infection, suggesting that an early stage post-infection is being blocked. Wolbachia does appear to have major effects on events distinct from entry, assembly or exit as it inhibits the replication of an SFV replicon transfected into the cells. Furthermore, it causes a far greater reduction in the expression of proteins from the 3' open reading frame than the 5' non-structural protein open reading frame, indicating that it is blocking the replication of viral RNA. Further to this separation of the replicase proteins and viral RNA in transreplication assays shows that uncoupling of viral RNA and replicase proteins does not overcome Wolbachia's antiviral activity. This further suggests that replicative processes are disrupted, such as translation or replication, by Wolbachia infection. This may occur by Wolbachia mounting an active antiviral response, but the virus did not cause any transcriptional response by the bacterium, suggesting that this is not the case. Host microRNAs (miRNAs have been implicated in protection, but again we found that host cell miRNA expression was unaffected by the bacterium and neither do our findings suggest any involvement of the antiviral siRNA pathway. We conclude that Wolbachia may directly interfere with early events in virus replication such as translation of incoming viral RNA or RNA transcription, and this likely involves an intrinsic (as opposed to

Effects of TLR agonists and viral infection on cytokine and TLR expression in Atlantic salmon (Salmo salar).

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Arnemo, Marianne; Kavaliauskis, Arturas; Gjøen, Tor

2014-10-01

The development of efficient and cheap vaccines against several aquatic viruses is necessary for a sustainable fish farming industry. Toll-like receptor (TLR) ligands have already been used as good adjuvants in human vaccines. With more understanding of TLR expression, function, and ligand specificity in fish, more efficient adjuvants for fish viral vaccines can be developed. In this paper, we examine all known TLRs in Atlantic salmon (Salmo salar) and demonstrate that head kidney and spleen are the main organs expressing TLRs in salmon. We also show that adherent head kidney leucocytes from salmon are able to respond to many of the known agonists for human TLRs, and that viral infection can induce up-regulation of several TLRs. These findings substantiate these receptors' role in immune responses to pathogens in salmonids making their ligands attractive as vaccine adjuvant candidates. Copyright © 2014 Elsevier Ltd. All rights reserved.

Who Regulates Whom? An Overview of RNA Granules and Viral Infections

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Natalia Poblete-Durán

2016-06-01

Full Text Available After viral infection, host cells respond by mounting an anti-viral stress response in order to create a hostile atmosphere for viral replication, leading to the shut-off of mRNA translation (protein synthesis and the assembly of RNA granules. Two of these RNA granules have been well characterized in yeast and mammalian cells, stress granules (SGs, which are translationally silent sites of RNA triage and processing bodies (PBs, which are involved in mRNA degradation. This review discusses the role of these RNA granules in the evasion of anti-viral stress responses through virus-induced remodeling of cellular ribonucleoproteins (RNPs.

Recombinant viruses as vaccines against viral diseases

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A.P.D. Souza

2005-04-01

Full Text Available Vaccine approaches to infectious diseases are widely applied and appreciated. Amongst them, vectors based on recombinant viruses have shown great promise and play an important role in the development of new vaccines. Many viruses have been investigated for their ability to express proteins from foreign pathogens and induce specific immunological responses against these antigens in vivo. Generally, gene-based vaccines can stimulate potent humoral and cellular immune responses and viral vectors might be an effective strategy for both the delivery of antigen-encoding genes and the facilitation and enhancement of antigen presentation. In order to be utilized as a vaccine carrier, the ideal viral vector should be safe and enable efficient presentation of required pathogen-specific antigens to the immune system. It should also exhibit low intrinsic immunogenicity to allow for its re-administration in order to boost relevant specific immune responses. Furthermore, the vector system must meet criteria that enable its production on a large-scale basis. Several viral vaccine vectors have thus emerged to date, all of them having relative advantages and limits depending on the proposed application, and thus far none of them have proven to be ideal vaccine carriers. In this review we describe the potential, as well as some of the foreseeable obstacles associated with viral vaccine vectors and their use in preventive medicine.

Viral vector-based influenza vaccines

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de Vries, Rory D.; Rimmelzwaan, Guus F.

2016-01-01

ABSTRACT Antigenic drift of seasonal influenza viruses and the occasional introduction of influenza viruses of novel subtypes into the human population complicate the timely production of effective vaccines that antigenically match the virus strains that cause epidemic or pandemic outbreaks. The development of game-changing vaccines that induce broadly protective immunity against a wide variety of influenza viruses is an unmet need, in which recombinant viral vectors may provide. Use of viral vectors allows the delivery of any influenza virus antigen, or derivative thereof, to the immune system, resulting in the optimal induction of virus-specific B- and T-cell responses against this antigen of choice. This systematic review discusses results obtained with vectored influenza virus vaccines and advantages and disadvantages of the currently available viral vectors. PMID:27455345

SUSTAINABLE DEVELOPMENT AND ECOLOGICAL RESPONSIBILITY OF BUSINESS

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Viktoria Krykun

2016-11-01

Full Text Available Today sustainable development is a widely used term, which has been increasingly influential in recent years. Debates about sustainability no longer consider sustainability solely as an environmental concern, but also incorporate economic and social dimensions. However, while a social and economic dimensions of sustainable development are widely discussed, environmental degradation becomes more and more crucial each year and is likely to reduce human well-being all across the world within the next few decades. The purpose of the paper is to analyse ecological ‘pillar’ of sustainable development, its historical background, main steps towards implementation of ‘new global environmental rules for society. Methodology. The paper is based on statistical information from public sources, reports of different international organizations and institutions, which are used to stress and underline main crucial points of research. Results of the survey show, that environmental quality, economic development and social well-being are interdependent and the main aim of international institutions, independent countries, businesses and society is to achieve environmentally sustainable development. Environmental issues make strong impact on modern economy. Responsible global strategy of development provides the whole society with rules, how ‘wise’ technological changes and economic policy can make industrial production processes less polluting and less resource intensive but yet more productive and profitable. Practical implications. Strategy of sustainable development and it’s three basic dimensions have found practical implication in one complex model, which illustrates the level of development of each country – the Human Development Index, which is focusing on three basic dimensions of human development: life expectancy at birth, mean years of schooling and expected years of schooling and gross national income per capita. Another data, which is

Pulmonary vascular responses during acute and sustained respiratory alkalosis or acidosis in intact newborn piglets.

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Gordon, J B; Rehorst-Paea, L A; Hoffman, G M; Nelin, L D

1999-12-01

Acute alkalosis-induced pulmonary vasodilation and acidosis-induced pulmonary vasoconstriction have been well described, but responses were generally measured within 5-30 min of changing pH. In contrast, several in vitro studies have found that relatively brief periods of sustained alkalosis can enhance, and sustained acidosis can decrease, vascular reactivity. In this study of intact newborn piglets, effects of acute (20 min) and sustained (60-80 min) alkalosis or acidosis on baseline (35% O2) and hypoxic (12% O2) pulmonary vascular resistance (PVR) were compared with control piglets exposed only to eucapnia. Acute alkalosis decreased hypoxic PVR, but sustained alkalosis failed to attenuate either baseline PVR or the subsequent hypoxic response. Acute acidosis did not significantly increase hypoxic PVR, but sustained acidosis markedly increased both baseline PVR and the subsequent hypoxic response. Baseline PVR was similar in all piglets after resumption of eucapnic ventilation, but the final hypoxic response was greater in piglets previously exposed to alkalosis than in controls. Thus, hypoxic pulmonary vasoconstriction was not attenuated during sustained alkalosis, but was accentuated during sustained acidosis and after the resumption of eucapnia in alkalosis-treated piglets. Although extrapolation of data from normal piglets to infants and children with pulmonary hypertension must be done with caution, this study suggests that sustained alkalosis may be of limited efficacy in treating acute hypoxia-induced pulmonary hypertension and the risks of pulmonary hypertension must be considered when using ventilator strategies resulting in permissive hypercapnic acidosis.

Mast cells in viral infections

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Piotr Witczak

2012-04-01

Full Text Available  There are some premises suggesting that mast cells are involved in the mechanisms of anti-virus defense and in viral disease pathomechanisms. Mast cells are particularly numerous at the portals of infections and thus may have immediate and easy contact with the external environment and invading pathogens. These cells express receptors responsible for recognition of virus-derived PAMP molecules, mainly Toll-like receptors (TLR3, TLR7/8 and TLR9, but also RIG-I-like and NOD-like molecules. Furthermore, mast cells generate various mediators, cytokines and chemokines which modulate the intensity of inflammation and regulate the course of innate and adaptive anti-viral immunity. Indirect evidence for the role of mast cells in viral infections is also provided by clinical observations and results of animal studies. Currently, more and more data indicate that mast cells can be infected by some viruses (dengue virus, adenoviruses, hantaviruses, cytomegaloviruses, reoviruses, HIV-1 virus. It is also demonstrated that mast cells can release pre formed mediators as well as synthesize de novo eicosanoids in response to stimulation by viruses. Several data indicate that virus-stimulated mast cells secrete cytokines and chemokines, including interferons as well as chemokines with a key role in NK and Tc lymphocyte influx. Moreover, some information indicates that mast cell stimulation via TLR3, TLR7/8 and TLR9 can affect their adhesion to extracellular matrix proteins and chemotaxis, and influence expression of some membrane molecules. Critical analysis of current data leads to the conclusion that it is not yet possible to make definitive statements about the role of mast cells in innate and acquired defense mechanisms developing in the course of viral infection and/or pathomechanisms of viral diseases.

Clinical outcome of HIV-infected patients with sustained virologic response to antiretroviral therapy: long-term follow-up of a multicenter cohort.

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Félix Gutierrez

Full Text Available BACKGROUND: Limited information exists on long-term prognosis of patients with sustained virologic response to antiretroviral therapy. We aimed to assess predictors of unfavorable clinical outcome in patients who maintain viral suppression with HAART. METHODS: Using data collected from ten clinic-based cohorts in Spain, we selected all antiretroviral-naive adults who initiated HAART and maintained plasma HIV-1 RNA levels <500 copies/mL throughout follow-up. Factors associated with disease progression were determined by Cox proportional-hazards models. RESULTS: Of 2,613 patients who started HAART, 757 fulfilled the inclusion criteria. 61% of them initiated a protease inhibitor-based HAART regimen, 29.7% a nonnucleoside reverse-transcriptase inhibitor-based regimen, and 7.8% a triple-nucleoside regimen. During 2,556 person-years of follow-up, 22 (2.9% patients died (mortality rate 0.86 per 100 person-years, and 40 (5.3% died or developed a new AIDS-defining event. The most common causes of death were neoplasias and liver failure. Mortality was independently associated with a CD4-T cell response <50 cells/L after 12 months of HAART (adjusted hazard ratio [AHR], 4.26 [95% confidence interval {CI}, 1.68-10.83]; P = .002, and age at initiation of HAART (AHR, 1.06 per year; 95% CI, 1.02-1.09; P = .001. Initial antiretroviral regimen chosen was not associated with different risk of clinical progression. CONCLUSIONS: Patients with sustained virologic response on HAART have a low mortality rate over time. Long-term outcome of these patients is driven by immunologic response at the end of the first year of therapy and age at the time of HAART initiation, but not by the initial antiretroviral regimen selected.

Haemangioma with coagulopathy: sustained response to prednisone.

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Evans, J; Batchelor, A D; Stark, G; Uttley, W S

1975-01-01

Two cases of giant haemangioma with thrombocytopenia are described. A satisfactory and sustained response to prednisone was achieved in respect of both coagulation abnormalities and tumour size. It is proposed that prednisone is effective by enhancement of thrombosis and reduction of fibrinolysis within the tumour, thus promoting a natural form of resolution. It is suggested that prednisone therapy should be first-choice treatment of complicated haemangiomas. Images Fig. 1 Fig. 3 PMID:147646

Why pass on viral messages? Because they connect emotionally

NARCIS (Netherlands)

Dobele, A.; Lindgreen, A.; Beverland, M.; Vanhamme, J.; Wijk, van R.

2007-01-01

In this article, we identify that successful viral marketing campaigns trigger an emotional response in recipients. Working under this premise, we examine the effects of viral messages containing the six primary emotions (surprise, joy, sadness, anger, fear, and disgust) on recipients' emotional

Alcohol intake alters immune responses and promotes CNS viral persistence in mice.

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Loftis, Jennifer M; Taylor, Jonathan; Raué, Hans-Peter; Slifka, Mark K; Huang, Elaine

2016-10-01

Chronic hepatitis C virus (HCV) infection leads to progressive liver disease and is associated with a variety of extrahepatic effects, including central nervous system (CNS) damage and neuropsychiatric impairments. Alcohol abuse can exacerbate these adverse effects on brain and behavior, but the molecular mechanisms are not well understood. This study investigated the role of alcohol in regulating viral persistence and CNS immunopathology in mice infected with lymphocytic choriomeningitis virus (LCMV), a model for HCV infections in humans. Female and male BALB/c mice (n=94) were exposed to alcohol (ethanol; EtOH) and water (or water only) using a two-bottle choice paradigm, followed one week later by infection with either LCMV clone 13 (causes chronic infection similar to chronic HCV), LCMV Armstrong (causes acute infection), or vehicle. Mice were monitored for 60days post-infection and continued to receive 24-h access to EtOH and water. Animals infected with LCMV clone 13 drank more EtOH, as compared to those with an acute or no viral infection. Six weeks after infection with LCMV clone 13, mice with EtOH exposure evidenced higher serum viral titers, as compared to mice without EtOH exposure. EtOH intake was also associated with reductions in virus-specific CD8(+) T cell frequencies (particularly CD11a(hi) subsets) and evidence of persistent CNS viremia in chronically infected mice. These findings support the hypothesis that EtOH use and chronic viral infection can result in combined toxic effects accelerating CNS damage and neuropsychiatric dysfunction and suggest that examining the role of EtOH in regulating viral persistence and CNS immunopathology in mice infected with LCMV can lead to a more comprehensive understanding of comorbid alcohol use disorder and chronic viral infection. Published by Elsevier B.V.

Accessory factors of cytoplasmic viral RNA sensors required for antiviral innate immune response

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Hiroyuki eOshiumi

2016-05-01

Full Text Available Type I interferon (IFN induces many antiviral factors in host cells. RIG-I-like receptors (RLRs are cytoplasmic viral RNA sensors that trigger the signal to induce the innate immune response that includes type I IFN production. RIG-I and MDA5 are RLRs that form nucleoprotein filaments along viral double-stranded RNA, resulting in the activation of MAVS adaptor molecule. The MAVS protein forms a prion-like aggregation structure, leading to type I IFN production. RIG-I and MDA5 undergo post-translational modification. TRIM25 and Riplet ubiquitin ligases deliver a K63-linked polyubiquitin moiety to the RIG-I N-terminal caspase activation and recruitment domains (CARDs and C-terminal region; the polyubiquitin chain then stabilizes the two-CARD tetramer structure required for MAVS assembly. MDA5 activation is regulated by phosphorylation. RIOK3 is a protein kinase that phosphorylates the MDA5 protein in a steady state, and PP1α/γ dephosphorylate this protein, resulting in its activation. RIG-I and MDA5 require cytoplasmic RNA helicases for their efficient activation. LGP2, another RLR, is an RNA helicase involved in RLR signaling. This protein does not possess N-terminal CARDs and thus cannot trigger downstream signaling by itself. Recent studies have revealed that this protein modulates MDA5 filament formation, resulting in enhanced type I IFN production. Several other cytoplasmic RNA helicases are involved in RLR signaling. DDX3, DHX29, DHX36, and DDX60 RNA helicases have been reported to be involved in RLR-mediated type I IFN production after viral infection. However, the underlying mechanism is largely unknown. Future studies are required to reveal the role of RNA helicases in the RLR signaling pathway.

MicroRNAs in the host response to viral infections of veterinary importance

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Mohamed Samir Ahmed

2016-10-01

Full Text Available The discovery of small regulatory non-coding RNAs has been an exciting advance in the field of genomics. MicroRNAs (miRNAs are endogenous RNA molecules, approximately 22 nucleotides in length that regulate gene expression, mostly at the post-transcriptional level. MiRNA profiling technologies have made it possible to identify and quantify novel miRNAs and to study their regulation and potential roles in disease pathogenesis. Although miRNAs have been extensively investigated in viral infections of humans, their implications in viral diseases affecting animals of veterinary importance are much less understood. The number of annotated miRNAs in different animal species is growing continuously, and novel roles in regulating host-pathogen interactions are being discovered, for instance miRNA-mediated augmentation of viral transcription and replication. In this review, we present an overview of synthesis and function of miRNAs and an update on the current state of research on host-encoded miRNAs in the genesis of viral infectious diseases in their natural animal host as well as in selected in vivo and in vitro laboratory models.

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...

Factors predictive of sustained virological response following 72 weeks of combination therapy for genotype 1b hepatitis C.

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Chayama, Kazuaki; Hayes, C Nelson; Yoshioka, Kentaro; Moriwaki, Hisataka; Okanoue, Takashi; Sakisaka, Shotaro; Takehara, Tetsuo; Oketani, Makoto; Toyota, Joji; Izumi, Namiki; Hiasa, Yoichi; Matsumoto, Akihiro; Nomura, Hideyuki; Seike, Masataka; Ueno, Yoshiyuki; Yotsuyanagi, Hiroshi; Kumada, Hiromitsu

2011-04-01

Treatment of genotype 1b chronic hepatitis C virus (HCV) infection has been improved by extending peg-interferon plus ribavirin combination therapy to 72 weeks, but predictive factors are needed to identify those patients who are likely to respond to long-term therapy. We analyzed amino acid (aa) substitutions in the core protein and the interferon sensitivity determining region (ISDR) of nonstructural protein (NS) 5A in 840 genotype 1b chronic hepatitis C patients with high viral load. We used logistic regression and classification and regression tree (CART) analysis to identify predictive factors for sustained virological response (SVR) for patients undergoing 72 weeks of treatment. When patients were separately analyzed by treatment duration using multivariate logistic regression, several factors, including sex, age, viral load, and core aa70 and ISDR substitutions (P = 0.0003, P = 0.02, P = 0.01, P = 0.0001, and P = 0.0004, respectively) were significant predictive factors for SVR with 48 weeks of treatment, whereas age, previous interferon treatment history, and ISDR substitutions (P = 0.03, P = 0.01, and P = 0.02, respectively) were the only significant predictive factors with 72 weeks of treatment. Using CART analysis, a decision tree was generated that identified age, cholesterol, sex, treatment length, and aa70 and ISDR substitutions as the most important predictive factors. The CART model had a sensitivity of 69.2% and specificity of 60%, with a positive predictive value of 68.4%. Complementary statistical and data mining approaches were used to identify a subgroup of patients likely to benefit from 72 weeks of therapy.

Sustainable palm oil as a public responsibility? : On the governance capacity of Indonesian standard for sustainable palm oil (ISPO)

NARCIS (Netherlands)

Hidayat, Nia; Offermans, Astrid; Glasbergen, Pieter

2017-01-01

This paper is motivated by the observation that Southern governments start to take responsibility for a more sustainable production of agricultural commodities as a response to earlier private initiatives by businesses and non-governmental organizations (NGOs). Indonesia is one of the leading

Development of improved low-cost ceramic water filters for viral removal in the Haitian context

OpenAIRE

Guerrero Latorre, Laura; Rusiñol Arantegui, Marta; Hundesa Gonfa, Ayalkibet; Garcia Vallès, Maite; Martínez Manent, Salvador; Joseph, Osnick; Bofill Mas, Silvia; Gironès Llop, Rosina

2015-01-01

Household-based water treatment (HWT) is increasingly being promoted to improve water quality and, therefore, health status in low-income countries. Ceramic water filters (CWFs) are used in many regions as sustainable HWT and have been proven to meet World Health Organization (WHO) microbiological performance targets for bacterial removal (24 log); however, the described viral removal efficiencies are insufficient to significantly reduce the associated risk of viral infection. With the object...

Kinetics of viral shedding provide insights into the epidemiology of viral hemorrhagic septicemia in Pacific herring

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Hershberger, Paul K.; Gregg, Jacob L.; Winton, James R.; Grady, Courtney; Collins, Rachael

2010-01-01

Losses from infectious diseases are an important component of natural mortality among marine fish species, but factors controlling the ecology of these diseases and their potential responses to anthropogenic changes are poorly understood. We used viral hemorrhagic septicemia virus (VHSV) and a laboratory stock of Pacific herring Clupea pallasii to investigate the kinetics of viral shedding and its effect on disease transmission and host mortality. Outbreaks of acute disease, accompanied by mortality and viral shedding, were initiated after waterborne exposure of herring to concentrations of VHSV as low as 101 plaque-forming units (pfu) ml–1. Shed virus in flow-through tanks was first detected 4 to 5 d post-exposure, peaked after 6 to 10 d, and was no longer detected after 16 d. Shedding rates, calculated from density, flow and waterborne virus titer reached 1.8 to 5.0 × 108 pfu fish–1 d–1. Onset of viral shedding was dose-dependent and preceded initial mortality by 2 d. At 21 d, cumulative mortality in treatment groups ranged from 81 to 100% and was dependent not on challenge dose, but on the kinetics and level of viral shedding by infected fish in the tank. Possible consequences of the viral shedding and disease kinetics are discussed in the context of epizootic initiation and perpetuation among populations of wild Pacific herring.

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...

The Immunoproteasome and Viral Infection: A Complex Regulator of Inflammation

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Mary Katherine McCarthy

2015-01-01

Full Text Available During viral infection, proper regulation of immune responses is necessary to ensure successful viral clearance with minimal host tissue damage. Proteasomes play a crucial role in the generation of antigenic peptides for presentation on MHC class I molecules, and thus activation of CD8 T cells, as well as activation of the NF-kB pathway. A specialized type of proteasome called the immunoproteasome is constitutively expressed in hematopoietic cells and induced in nonimmune cells during viral infection by interferon (IFN signaling. The immunoproteasome regulates CD8 T cell responses to many viral epitopes during infection. Accumulating evidence suggests that the immunoproteasome may also contribute to regulation of proinflammatory cytokine production, activation of the NF-kB pathway, and management of oxidative stress. Many viruses have mechanisms of interfering with immunoproteasome function, including prevention of transcriptional upregulation of immunoproteasome components as well as direct interaction of viral proteins with immunoproteasome subunits. A better understanding of the role of the immunoproteasome in different cell types, tissues, and hosts has the potential to improve vaccine design and facilitate the development of effective treatment strategies for viral infections.

What does sustainability mean in the HIV and AIDS response?

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Oberth, Gemma; Whiteside, Alan

2016-01-01

Immense progress has been made in the fight against HIV and AIDS. Achieving and exceeding the AIDS targets for the Millennium Development Goals (MDGs) was accomplished, in large part, due to an unprecedented financial investment from the international community. Following an $800 million dip in donor disbursements in 2010, the discourse has since shifted to the need for greater sustainability of funding. But what does sustainability mean? Current efforts focus heavily on fiscal imperatives such as increasing domestic funding. This is important - needs are increasing at a faster rate than donor funding, especially with increased treatment coverage. The problem is that measures of financial sustainability tell very little about the actual sustainability of specific programmes, disease trajectories or enabling environments. Recognising that current definitions of sustainability lack clarity and depth, we offer a new six-tenet conceptualisation of what sustainability means in the HIV and AIDS response: (1) financial, (2) epidemiological, (3) political, (4) structural, (5) programmatic, and (6) human rights. Based on these, we examine examples of donor transitions for their approach to sustainability, including PEPFAR in South Africa, the Global Fund in Eastern Europe, and the Bill and Melinda Gates Foundation in India (Avahan). We conclude that sustainability must be understood within a broader framework beyond funding stability. We also recommend that certain interventions, such as programming for key populations, may have to continue to receive external support even if affected countries can afford to pay.

Viral Evasion of Natural Killer Cell Activation

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Yi Ma

2016-04-01

Full Text Available Natural killer (NK cells play a key role in antiviral innate defenses because of their abilities to kill infected cells and secrete regulatory cytokines. Additionally, NK cells exhibit adaptive memory-like antigen-specific responses, which represent a novel antiviral NK cell defense mechanism. Viruses have evolved various strategies to evade the recognition and destruction by NK cells through the downregulation of the NK cell activating receptors. Here, we review the recent findings on viral evasion of NK cells via the impairment of NK cell-activating receptors and ligands, which provide new insights on the relationship between NK cells and viral actions during persistent viral infections.

Viral Evasion of Natural Killer Cell Activation.

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Ma, Yi; Li, Xiaojuan; Kuang, Ersheng

2016-04-12

Natural killer (NK) cells play a key role in antiviral innate defenses because of their abilities to kill infected cells and secrete regulatory cytokines. Additionally, NK cells exhibit adaptive memory-like antigen-specific responses, which represent a novel antiviral NK cell defense mechanism. Viruses have evolved various strategies to evade the recognition and destruction by NK cells through the downregulation of the NK cell activating receptors. Here, we review the recent findings on viral evasion of NK cells via the impairment of NK cell-activating receptors and ligands, which provide new insights on the relationship between NK cells and viral actions during persistent viral infections.

Genetics and Molecular Biology of Epstein-Barr Virus-Encoded BART MicroRNA: A Paradigm for Viral Modulation of Host Immune Response Genes and Genome Stability

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David H. Dreyfus

2017-01-01

Full Text Available Epstein-Barr virus, a ubiquitous human herpesvirus, is associated through epidemiologic evidence with common autoimmune syndromes and cancers. However, specific genetic mechanisms of pathogenesis have been difficult to identify. In this review, the author summarizes evidence that recently discovered noncoding RNAs termed microRNA encoded by Epstein-Barr virus BARF (BamHI A right frame termed BART (BamHI A right transcripts are modulators of human immune response genes and genome stability in infected and bystander cells. BART expression is apparently regulated by complex feedback loops with the host immune response regulatory NF-κB transcription factors. EBV-encoded BZLF-1 (ZEBRA protein could also regulate BART since ZEBRA contains a terminal region similar to ankyrin proteins such as IκBα that regulate host NF-κB. BALF-2 (BamHI A left frame transcript, a viral homologue of the immunoglobulin and T cell receptor gene recombinase RAG-1 (recombination-activating gene-1, may also be coregulated with BART since BALF-2 regulatory sequences are located near the BART locus. Viral-encoded microRNA and viral mRNA transferred to bystander cells through vesicles, defective viral particles, or other mechanisms suggest a new paradigm in which bystander or hit-and-run mechanisms enable the virus to transiently or chronically alter human immune response genes as well as the stability of the human genome.

HLA-Driven Convergence of HIV-1 Viral Subtypes B and F Toward the Adaptation to Immune Responses in Human Populations

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Dilernia, Dario Alberto; Jones, Leandro; Rodriguez, Sabrina; Turk, Gabriela; Rubio, Andrea E.; Pampuro, Sandra; Gomez-Carrillo, Manuel; Bautista, Christian; Deluchi, Gabriel; Benetucci, Jorge; Lasala, María Beatriz; Lourtau, Leonardo; Losso, Marcelo Horacio; Perez, Héctor; Cahn, Pedro; Salomón, Horacio

2008-01-01

Background Cytotoxic T-Lymphocyte (CTL) response drives the evolution of HIV-1 at a host-level by selecting HLA-restricted escape mutations. Dissecting the dynamics of these escape mutations at a population-level would help to understand how HLA-mediated selection drives the evolution of HIV-1. Methodology/Principal Findings We undertook a study of the dynamics of HIV-1 CTL-escape mutations by analyzing through statistical approaches and phylogenetic methods the viral gene gag sequenced in plasma samples collected between the years 1987 and 2006 from 302 drug-naïve HIV-positive patients. By applying logistic regression models and after performing correction for multiple test, we identified 22 potential CTL-escape mutations (p-value<0.05; q-value<0.2); 10 of these associations were confirmed in samples biologically independent by a Bayesian Markov Chain Monte-Carlo method. Analyzing their prevalence back in time we found that escape mutations that are the consensus residue in samples collected after 2003 have actually significantly increased in time in one of either B or F subtype until becoming the most frequent residue, while dominating the other viral subtype. Their estimated prevalence in the viral subtype they did not dominate was lower than 30% for the majority of samples collected at the end of the 80's. In addition, when screening the entire viral region, we found that the 75% of positions significantly changing in time (p<0.05) were located within known CTL epitopes. Conclusions Across HIV Gag protein, the rise of polymorphisms from independent origin during the last twenty years of epidemic in our setting was related to an association with an HLA allele. The fact that these mutations accumulated in one of either B or F subtypes have also dominated the other subtype shows how this selection might be causing a convergence of viral subtypes to variants which are more likely to evade the immune response of the population where they circulate. PMID:18941505

Viral Hepatitis

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... 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 ...

Challenges, responses and partnership for achieving sustainable tourism and heritage preservation

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Maksin Marija

2010-01-01

Full Text Available The process of globalization has created the situation where the expectations of tourists are the same both with respect to the quality of services in all destinations and with respect to the authencity based on local attractions and experiences, which should be unique and different for each destination. The key element in maintaining destination attractiveness is the protection and presentation of natural and cultural heritage and its sustainable utilization for tourism development. The sustainability concept is of equal importance for long-term tourism development, destination competitiveness and heritage protection. The paper deals with the main challenges to achieving sustainable tourism and points to some key responses to them. Participation, cooperation and partnership should be a vital prerequisite for the implementation and performance of sustainable tourism and heritage protection. This attitude has been tested on several examples of good practice in heritage protection and the sustainable development of tourism destinations in Serbia. .

Benefit of Hepatitis C Virus Core Antigen Assay in Prediction of Therapeutic Response to Interferon and Ribavirin Combination Therapy

OpenAIRE

Takahashi, Masahiko; Saito, Hidetsugu; Higashimoto, Makiko; Atsukawa, Kazuhiro; Ishii, Hiromasa

2005-01-01

A highly sensitive second-generation hepatitis C virus (HCV) core antigen assay has recently been developed. We compared viral disappearance and first-phase kinetics between commercially available core antigen (Ag) assays, Lumipulse Ortho HCV Ag (Lumipulse-Ag), and a quantitative HCV RNA PCR assay, Cobas Amplicor HCV Monitor test, version 2 (Amplicor M), to estimate the predictive benefit of a sustained viral response (SVR) and non-SVR in 44 genotype 1b patients treated with interferon (IFN) ...

The Response of Heterotrophic Prokaryote and Viral Communities to Labile Organic Carbon Inputs Is Controlled by the Predator Food Chain Structure.

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Sandaa, Ruth-Anne; Pree, Bernadette; Larsen, Aud; Våge, Selina; Töpper, Birte; Töpper, Joachim P; Thyrhaug, Runar; Thingstad, Tron Frede

2017-08-23

Factors controlling the community composition of marine heterotrophic prokaryotes include organic-C, mineral nutrients, predation, and viral lysis. Two mesocosm experiments, performed at an Arctic location and bottom-up manipulated with organic-C, had very different results in community composition for both prokaryotes and viruses. Previously, we showed how a simple mathematical model could reproduce food web level dynamics observed in these mesocosms, demonstrating strong top-down control through the predator chain from copepods via ciliates and heterotrophic nanoflagellates. Here, we use a steady-state analysis to connect ciliate biomass to bacterial carbon demand. This gives a coupling of top-down and bottom-up factors whereby low initial densities of ciliates are associated with mineral nutrient-limited heterotrophic prokaryotes that do not respond to external supply of labile organic-C. In contrast, high initial densities of ciliates give carbon-limited growth and high responsiveness to organic-C. The differences observed in ciliate abundance, and in prokaryote abundance and community composition in the two experiments were in accordance with these predictions. Responsiveness in the viral community followed a pattern similar to that of prokaryotes. Our study provides a unique link between the structure of the predator chain in the microbial food web and viral abundance and diversity.

Special issue on"social responsibility accounting and reporting in times of ‘sustainability Downturn/crisis

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Carmen Correa-ruiz

2011-08-01

Full Text Available At a time when sustainability performance does not seem to match the expectations raised by the sustainable development concept and, moreover, when the economic downturn and crisis could be further eroding social and environmental concerns and values, the notion of sustainability crisis provides an interesting starting point to reflect on the role of Social and Environmental Accounting Research. Lack of humanity and values, short term economic approach, institutional capture and misunderstanding and misuse of democracy, have all served as catalysts of sustainability downturn and crisis. Thus, this editorial attempts to advance public interest accounting by discussing the controversy around Sustainability and Corporate Social Responsibility, expecting that the constitutive effects of researchers’ words in this special issue and in future research agendas, will result in more transformative power relations able to enhance a healthy democracy inspired by the capacity to do things and to transform individuals’ attitudes and behaviours, as well as the institutional response to the sustainability crisis.

Budesonide and formoterol reduce early innate anti-viral immune responses in vitro.

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Janet M Davies

Full Text Available Asthma is a chronic inflammatory airways disease in which respiratory viral infections frequently trigger exacerbations. Current treatment of asthma with combinations of inhaled corticosteroids and long acting beta2 agonists improves asthma control and reduces exacerbations but what impact this might have on innate anti-viral immunity is unclear. We investigated the in vitro effects of asthma drugs on innate anti-viral immunity. Peripheral blood mononuclear cells (PBMC from healthy and asthmatic donors were cultured for 24 hours with the Toll-like receptor 7 agonist, imiquimod, or rhinovirus 16 (RV16 in the presence of budesonide and/or formoterol. Production of proinflammatory cytokines and expression of anti-viral intracellular signalling molecules were measured by ELISA and RT-PCR respectively. In PBMC from healthy donors, budesonide alone inhibited IP-10 and IL-6 production induced by imiquimod in a concentration-dependent manner and the degree of inhibition was amplified when budesonide and formoterol were used in combination. Formoterol alone had little effect on these parameters, except at high concentrations (10⁻⁶ M when IL-6 production increased. In RV16 stimulated PBMC, the combination of budesonide and formoterol inhibited IFNα and IP-10 production in asthmatic as well as healthy donors. Combination of budesonide and formoterol also inhibited RV16-stimulated expression of the type I IFN induced genes myxovirus protein A and 2', 5' oligoadenylate synthetise. Notably, RV16 stimulated lower levels of type Myxovirus A and oligoadenylate synthase in PBMC of asthmatics than control donors. These in vitro studies demonstrate that combinations of drugs commonly used in asthma therapy inhibit both early pro-inflammatory cytokines and key aspects of the type I IFN pathway. These findings suggest that budesonide and formoterol curtail excessive inflammation induced by rhinovirus infections in patients with asthma, but whether this inhibits

Lesion Neuroanatomy of the Sustained Attention to Response Task

Science.gov (United States)

Molenberghs, Pascal; Gillebert, Celine R.; Schoofs, Hanne; Dupont, Patrick; Peeters, Ronald; Vandenberghe, Rik

2009-01-01

The Sustained Attention to Response task is a classical neuropsychological test that has been used by many centres to characterize the attentional deficits in traumatic brain injury, ADHD, autism and other disorders. During the SART a random series of digits 1-9 is presented repeatedly and subjects have to respond to each digit (go trial) except…

Viral Interference and Persistence in Mosquito-Borne Flaviviruses

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Juan Santiago Salas-Benito

2015-01-01

Full Text Available Mosquito-borne flaviviruses are important pathogens for humans, and the detection of two or more flaviviruses cocirculating in the same geographic area has often been reported. However, the epidemiological impact remains to be determined. Mosquito-borne flaviviruses are primarily transmitted through Aedes and Culex mosquitoes; these viruses establish a life-long or persistent infection without apparent pathological effects. This establishment requires a balance between virus replication and the antiviral host response. Viral interference is a phenomenon whereby one virus inhibits the replication of other viruses, and this condition is frequently associated with persistent infections. Viral interference and persistent infection are determined by several factors, such as defective interfering particles, competition for cellular factors required for translation/replication, and the host antiviral response. The interaction between two flaviviruses typically results in viral interference, indicating that these viruses share common features during the replicative cycle in the vector. The potential mechanisms involved in these processes are reviewed here.

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

Science.gov (United States)

Xu, Y; Li, YF; Zhang, D; Dockendorf, M; Tetteh, E; Rizk, ML; Grobler, JA; Lai, M‐T; Gobburu, J

2016-01-01

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. PMID:27171172

Bovine Viral Diarrhea Virus Type 2 Impairs Macrophage Responsiveness to Toll-Like Receptor Ligation with the Exception of Toll-Like Receptor 7.

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Robert G Schaut

Full Text Available Bovine viral diarrhea virus (BVDV is a member of the Flaviviridae family. BVDV isolates are classified into two biotypes based on the development of cytopathic (cp or non-cytopathic (ncp effects in epithelial cell culture. BVDV isolates are further separated into species, BVDV1 and 2, based on genetic differences. Symptoms of BVDV infection range from subclinical to severe, depending on strain virulence, and may involve multiple organ systems and induction of a generalized immunosuppression. During BVDV-induced immune suppression, macrophages, critical to innate immunity, may have altered pathogen recognition receptor (PRR signaling, including signaling through toll-like receptors (TLRs. Comparison of BVDV 2 strains with different biotypes and virulence levels is valuable to determining if there are differences in host macrophage cellular responses between viral phenotypes. The current study demonstrates that cytopathic (cp, noncytopathic (ncp, high (hv or low virulence (lv BVDV2 infection of bovine monocyte-derived macrophages (MDMΦ result in differential expression of pro-inflammatory cytokines compared to uninfected MDMΦ. A hallmark of cp BVDV2 infection is IL-6 production. In response to TLR2 or 4 ligation, as might be observed during secondary bacterial infection, cytokine secretion was markedly decreased in BVDV2-infected MDMΦ, compared to non-infected MDMΦ. Macrophages were hyporesponsive to viral TLR3 or TLR8 ligation. However, TLR7 stimulation of BVDV2-infected MDMΦ induced cytokine secretion, unlike results observed for other TLRs. Together, these data suggest that BVDV2 infection modulated mRNA responses and induced a suppression of proinflammatory cytokine protein responses to TLR ligation in MDMΦ with the exception of TLR7 ligation. It is likely that there are distinct differences in TLR pathways modulated following BVDV2 infection, which have implications for macrophage responses to secondary infections.

FREEDOM CHOICE OF THE ROMANIAN ENTERPRISES TO CORPORATE RESPONSIBILITY & SUSTAINABILITY COMPETITIVENESS

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Lucretia Mariana Constantinescu

2013-12-01

Full Text Available The declared aim of this paper is to be an attempt to analyze the opinions regarding the corporate sustainability and responsibility that’s providing to formulate a combination of diagnosis and prognosis, assessing the past and present conditions of corporate responsibility and the way ahead by the investors of the Romanian economy during the last economic recession crisis years.

The double-stranded RNA-activated protein kinase mediates viral-induced encephalitis

International Nuclear Information System (INIS)

Scheuner, Donalyn; Gromeier, Matthias; Davies, Monique V.; Dorner, Andrew J.; Song Benbo; Patel, Rupali V.; Wimmer, Eckard J.; McLendon, Roger E.; Kaufman, Randal J.

2003-01-01

The double-stranded (ds) RNA-activated protein kinase (PKR) plays an important role in control of viral infections and cell growth. We have studied the role of PKR in viral infection in mice that are defective in the PKR signaling pathway. Transgenic mice were derived that constitutively express a trans-dominant-negative kinase-defective mutant PKR under control of the β-actin promoter. The trans-dominant-negative PKR mutant expressing transgenic mice do not have a detectable phenotype, similar to observations with PKR knock-out mice. The requirement for PKR in viral pathogenesis was studied by intracerebral infection of mice with a mouse-adapted poliovirus. Histopathological analysis revealed diffuse encephalomyelitis with severe inflammatory lesions throughout the central nervous system (CNS) in infected wild-type mice. In contrast, histopathological evaluation of virus-injected trans-dominant-negative PKR transgenic mice as well as PKR knock-out mice yielded no signs of tissue damage associated with inflammatory host responses. However, the virus did replicate in both models of PKR-deficient mice at a level equal to that observed in wild-type infected mice. Although the results indicate a clear difference in susceptibility to poliovirus-induced encephalitis, this difference manifests clinically as a slight delay in fatal neuropathy in trans-dominant-negative PKR transgenic and PKR knock-out animals. Our observations support the finding that viral-induced PKR activation may play a significant role in pathogenesis by mediating the host response to viral CNS infection. They support PKR to be an effective target to control tissue damage due to deleterious host responses to viral infection

Targeting of non-dominant antigens as a vaccine strategy to broaden T-cell responses during chronic viral infection

DEFF Research Database (Denmark)

Holst, Peter Johannes; Jensen, Benjamin Anderschou Holbech; Ragonnaud, Emeline

2015-01-01

In this study, we compared adenoviral vaccine vectors with the capacity to induce equally potent immune responses against non-dominant and immunodominant epitopes of murine lymphocytic choriomeningitis virus (LCMV). Our results demonstrate that vaccination targeting non-dominant epitopes facilita......In this study, we compared adenoviral vaccine vectors with the capacity to induce equally potent immune responses against non-dominant and immunodominant epitopes of murine lymphocytic choriomeningitis virus (LCMV). Our results demonstrate that vaccination targeting non-dominant epitopes...... was lost over time in T cells specific for the dominant T cell epitopes, and these cells were fully capable of expanding in response to a new viral challenge. Overall, our data suggests a potential for broadening of the antiviral CD8+ T-cell response by selecting non-dominant antigens to be targeted...

The proteasomal Rpn11 metalloprotease suppresses tombusvirus RNA recombination and promotes viral replication via facilitating assembly of the viral replicase complex.

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Prasanth, K Reddisiva; Barajas, Daniel; Nagy, Peter D

2015-03-01

RNA viruses co-opt a large number of cellular proteins that affect virus replication and, in some cases, viral genetic recombination. RNA recombination helps viruses in an evolutionary arms race with the host's antiviral responses and adaptation of viruses to new hosts. Tombusviruses and a yeast model host are used to identify cellular factors affecting RNA virus replication and RNA recombination. In this study, we have examined the role of the conserved Rpn11p metalloprotease subunit of the proteasome, which couples deubiquitination and degradation of proteasome substrates, in tombusvirus replication and recombination in Saccharomyces cerevisiae and plants. Depletion or mutations of Rpn11p lead to the rapid formation of viral RNA recombinants in combination with reduced levels of viral RNA replication in yeast or in vitro based on cell extracts. Rpn11p interacts with the viral replication proteins and is recruited to the viral replicase complex (VRC). Analysis of the multifunctional Rpn11p has revealed that the primary role of Rpn11p is to act as a "matchmaker" that brings the viral p92(pol) replication protein and the DDX3-like Ded1p/RH20 DEAD box helicases into VRCs. Overexpression of Ded1p can complement the defect observed in rpn11 mutant yeast by reducing TBSV recombination. This suggests that Rpn11p can suppress tombusvirus recombination via facilitating the recruitment of the cellular Ded1p helicase, which is a strong suppressor of viral recombination, into VRCs. Overall, this work demonstrates that the co-opted Rpn11p, which is involved in the assembly of the functional proteasome, also functions in the proper assembly of the tombusvirus VRCs. RNA viruses evolve rapidly due to genetic changes based on mutations and RNA recombination. Viral genetic recombination helps viruses in an evolutionary arms race with the host's antiviral responses and facilitates adaptation of viruses to new hosts. Cellular factors affect viral RNA recombination, although the role

Simultaneous assessment of cytotoxic T lymphocyte responses against multiple viral infections by combined usage of optimal epitope matrices, anti- CD3 mAb T-cell expansion and "RecycleSpot"

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Wong Johnson T

2005-05-01

Full Text Available Abstract The assessment of cellular anti-viral immunity is often hampered by the limited availability of adequate samples, especially when attempting simultaneous, high-resolution determination of T cell responses against multiple viral infections. Thus, the development of assay systems, which optimize cell usage, while still allowing for the detailed determination of breadth and magnitude of virus-specific cytotoxic T lymphocyte (CTL responses, is urgently needed. This study provides an up-to-date listing of currently known, well-defined viral CTL epitopes for HIV, EBV, CMV, HCV and HBV and describes an approach that overcomes some of the above limitations through the use of peptide matrices of optimally defined viral CTL epitopes in combination with anti-CD3 in vitro T cell expansion and re-use of cells from negative ELISpot wells. The data show that, when compared to direct ex vivo cell preparations, antigen-unspecific in vitro T cell expansion maintains the breadth of detectable T cell responses and demonstrates that harvesting cells from negative ELISpot wells for re-use in subsequent ELISpot assays (RecycleSpot, further maximized the use of available cells. Furthermore when combining T cell expansion and RecycleSpot with the use of rationally designed peptide matrices, antiviral immunity against more than 400 different CTL epitopes from five different viruses can be reproducibly assessed from samples of less than 10 milliliters of blood without compromising information on the breadth and magnitude of these responses. Together, these data support an approach that facilitates the assessment of cellular immunity against multiple viral co-infections in settings where sample availability is severely limited.

Hepatitis C Virus Infection Induces Autophagy as a Prosurvival Mechanism to Alleviate Hepatic ER-Stress Response

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Dash, Srikanta; Chava, Srinivas; Aydin, Yucel; Chandra, Partha K.; Ferraris, Pauline; Chen, Weina; Balart, Luis A.; Wu, Tong; Garry, Robert F.

2016-01-01

Hepatitis C virus (HCV) infection frequently leads to chronic liver disease, liver cirrhosis and hepatocellular carcinoma (HCC). The molecular mechanisms by which HCV infection leads to chronic liver disease and HCC are not well understood. The infection cycle of HCV is initiated by the attachment and entry of virus particles into a hepatocyte. Replication of the HCV genome inside hepatocytes leads to accumulation of large amounts of viral proteins and RNA replication intermediates in the endoplasmic reticulum (ER), resulting in production of thousands of new virus particles. HCV-infected hepatocytes mount a substantial stress response. How the infected hepatocyte integrates the viral-induced stress response with chronic infection is unknown. The unfolded protein response (UPR), an ER-associated cellular transcriptional response, is activated in HCV infected hepatocytes. Over the past several years, research performed by a number of laboratories, including ours, has shown that HCV induced UPR robustly activates autophagy to sustain viral replication in the infected hepatocyte. Induction of the cellular autophagy response is required to improve survival of infected cells by inhibition of cellular apoptosis. The autophagy response also inhibits the cellular innate antiviral program that usually inhibits HCV replication. In this review, we discuss the physiological implications of the HCV-induced chronic ER-stress response in the liver disease progression. PMID:27223299

Translational Implication of Galectin-9 in the Pathogenesis and Treatment of Viral Infection

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Jenn-Haung Lai

2017-10-01

Full Text Available The interaction between galectin-9 and its receptor, Tim-3, triggers a series of signaling events that regulate immune responses. The expression of galectin-9 has been shown to be increased in a variety of target cells of many different viruses, such as hepatitis C virus (HCV, hepatitis B virus (HBV, herpes simplex virus (HSV, influenza virus, dengue virus (DENV, and human immunodeficiency virus (HIV. This enhanced expression of galectin-9 following viral infection promotes significant changes in the behaviors of the virus-infected cells, and the resulting events tightly correlate with the immunopathogenesis of the viral disease. Because the human immune response to different viral infections can vary, and the lack of appropriate treatment can have potentially fatal consequences, understanding the implications of galectin-9 is crucial for developing better methods for monitoring and treating viral infections. This review seeks to address how we can apply the current understanding of galectin-9 function to better understand the pathogenesis of viral infection and better treat viral diseases.

Host immune responses to a viral immune modulating protein: immunogenicity of viral interleukin-10 in rhesus cytomegalovirus-infected rhesus macaques.

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Meghan K Eberhardt

Full Text Available Considerable evidence has accumulated that multiple viruses, bacteria, and protozoa manipulate interleukin-10 (IL-10-mediated signaling through the IL-10 receptor (IL-10R in ways that could enable establishment of a persistent microbial infection. This suggests that inhibition of pathogen targeting of IL-10/IL-10R signaling could prevent microbial persistence. Human cytomegalovirus (HCMV and rhesus cytomegalovirus (RhCMV express a viral interleukin-10 (cmvIL-10 and rhcmvIL-10, respectively with comparable immune modulating properties in vitro to that of their host's cellular IL-10 (cIL-10. A prior study noted that rhcmvIL-10 alters innate and adaptive immunity to RhCMV in vivo, consistent with a central role for rhcmvIL-10 during acute virus-host interactions. Since cmvIL-10 and rhcmvIL-10 are extremely divergent from the cIL-10 of their respective hosts, vaccine-mediated neutralization of their function could inhibit establishment of viral persistence without inhibition of cIL-10.As a prelude to evaluating cmvIL-10-based vaccines in humans, the rhesus macaque model of HCMV was used to interrogate peripheral and mucosal immune responses to rhcmvIL-10 in RhCMV-infected animals. ELISA were used to detect rhcmvIL-10-binding antibodies in plasma and saliva, and an IL-12-based bioassay was used to quantify plasma antibodies that neutralized rhcmvIL-10 function. rhcmvIL-10 is highly immunogenic during RhCMV infection, stimulating high avidity rhcmvIL-10-binding antibodies in the plasma of all infected animals. Most infected animals also exhibited plasma antibodies that partially neutralized rhcmvIL-10 function but did not cross-neutralize the function of rhesus cIL-10. Notably, minimally detectable rhcmvIL-10-binding antibodies were detected in saliva.This study demonstrates that rhcmvIL-10, as a surrogate for cmvIL-10, is a viable vaccine candidate because (1 it is highly immunogenic during natural RhCMV infection, and (2 neutralizing antibodies to

Transmission of innate immune signaling by packaging of cGAMP in viral particles.

Science.gov (United States)

Gentili, Matteo; Kowal, Joanna; Tkach, Mercedes; Satoh, Takeshi; Lahaye, Xavier; Conrad, Cécile; Boyron, Marilyn; Lombard, Bérangère; Durand, Sylvère; Kroemer, Guido; Loew, Damarys; Dalod, Marc; Théry, Clotilde; Manel, Nicolas

2015-09-11

Infected cells detect viruses through a variety of receptors that initiate cell-intrinsic innate defense responses. Cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase (cGAS) is a cytosolic sensor for many DNA viruses and HIV-1. In response to cytosolic viral DNA, cGAS synthesizes the second messenger 2'3'-cyclic GMP-AMP (cGAMP), which activates antiviral signaling pathways. We show that in cells producing virus, cGAS-synthesized cGAMP can be packaged in viral particles and extracellular vesicles. Viral particles efficiently delivered cGAMP to target cells. cGAMP transfer by viral particles to dendritic cells activated innate immunity and antiviral defenses. Finally, we show that cell-free murine cytomegalovirus and Modified Vaccinia Ankara virus contained cGAMP. Thus, transfer of cGAMP by viruses may represent a defense mechanism to propagate immune responses to uninfected target cells. Copyright © 2015, American Association for the Advancement of Science.

Viral infections as controlling factors for the deep biosphere? (Invited)

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Engelen, B.; Engelhardt, T.; Sahlberg, M.; Cypionka, H.

2009-12-01

biogeography? Can viral infections tell us something about the physiological state of indigenous microorganisms? Finally, we will obtain estimates for the viral shunt as an important factor for sustaining the deep biosphere. References: Batzke A, Engelen B, Sass H, Cypionka H (2007) Phylogenetic and physiological diversity of cultured deep-biosphere bacteria from Equatorial Pacific Ocean and Peru Margin sediments. Geomicrobiology J 24:261-273 Danovaro R, Dell'Anno A, Corinaldesi C, Magagnini M, Noble R, Tamburini C, Weinbauer M (2008) Major viral impact on the functioning of benthic deep-sea ecosystems. Nature 454: 1084-U1027.

Weight loss, leukopenia and thrombocytopenia associated with sustained virologic response to Hepatitis C treatment

Science.gov (United States)

Suwantarat, Nuntra; Tice, Alan D.; Khawcharoenporn, Thana; Chow, Dominic C.

2010-01-01

OBJECTIVE: To identify apparent adverse effects of treatment of chronic hepatitis C and their relationship to sustained virologic response (SVR). METHODS: A retrospective study was conducted of all Hepatitis C virus (HCV)-infected patients treated with pegylated interferon and ribavirin in an academic ambulatory infectious disease practice. Clinical and laboratory characteristics were compared between patients with SVR and without SVR. RESULTS: Fifty-four patients completed therapy with the overall SVR rate of 76%. SVR was associated with genotype non-1 (P=0.01), weight loss more than 5 kilograms (P=0.04), end of treatment leukopenia (P=0.02) and thrombocytopenia (P=0.05). In multivariate analysis, SVR was significant associated with HCV genotype non-1 (Adjusted Odd Ratio [AOR] 15.22; CI 1.55 to 149.72; P=0.02), weight loss more than 5 kilograms, (AOR 5.74; CI 1.24 to 26.32; P=0.04), and end of treatment white blood cell count level less than 3 X 103 cells/µl (AOR 9.09; CI 1.59 to 52.63; P=0.02). Thrombocytopenia was not significant after adjustment. Other factors including age, gender, ethnicity, injection drug use, viral load, anemia, alanine transaminase level, and liver histology did not reach statistical significance. CONCLUSION: Besides non-1 genotype, SVR was found to be independently associated with weight loss during therapy, and leukopenia at the end of HCV treatment. These correlations suggest continuation of therapy despite adverse effects, may be of benefit. PMID:20107528

SUSTAINABILITY AND COMPANY’S CORPORATE SOCIAL RESPONSIBILITY NEED

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MONICA VIOLETA ACHIM

2012-05-01

Full Text Available The company is a living organism, is an entity and its analysis should be made taking into account the whole system. The company is a dynamic environment, which has as a mainly aims to add value for all participants in the economic life. In the organizations, the achievement of the concept of sustainable development is achieved through the concept of societal responsibility of the organizations. For this scope we need to use the term introduced by Elkington namely “The Triple Bottom Line” which involve economic prosperity, environmental compliance and improve social cohesion. [11]. So, “The Triple Bottom Line” can be defined as an approach for measuring the overall performance of an organization according to its triple contribution to the three aspects mentioned above. The new conceptual framework change radically the final aim of a company because it is not anymore maximizing the value of shares held by shareholders, but it is maximizing value for all stakeholders, where shareholders are just another category of stakeholders. Sustainable development and globalization require new performance standards that exceed the economic field, for both national company and international ones. As a consequence, these standards must be integrated into the company's development strategy, to ensure sustainability of activities carried, by the harmonization of economic, social and environmental objectives.

The impact of luminance on tonic and phasic pupillary responses to sustained cognitive load.

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Peysakhovich, Vsevolod; Vachon, François; Dehais, Frédéric

2017-02-01

Pupillary reactions independent of light conditions have been linked to cognition for a long time. However, the light conditions can impact the cognitive pupillary reaction. Previous studies underlined the impact of luminance on pupillary reaction, but it is still unclear how luminance modulates the sustained and transient components of pupillary reaction - tonic pupil diameter and phasic pupil response. In the present study, we investigated the impact of the luminance on these two components under sustained cognitive load. Fourteen participants performed a novel working memory task combining mathematical computations with a classic n-back task. We studied both tonic pupil diameter and phasic pupil response under low (1-back) and high (2-back) working memory load and two luminance levels (gray and white). We found that the impact of working memory load on the tonic pupil diameter was modulated by the level of luminance, the increase in tonic pupil diameter with the load being larger under lower luminance. In contrast, the smaller phasic pupil response found under high load remained unaffected by luminance. These results showed that luminance impacts the cognitive pupillary reaction - tonic pupil diameter (phasic pupil response) being modulated under sustained (respectively, transient) cognitive load. These findings also support the relationship between the locus-coeruleus system, presumably functioning in two firing modes - tonic and phasic - and the pupil diameter. We suggest that the tonic pupil diameter tracks the tonic activity of the locus-coeruleus while phasic pupil response reflects its phasic activity. Besides, the designed novel cognitive paradigm allows the simultaneous manipulation of sustained and transient components of the cognitive load and is useful for dissociating the effects on the tonic pupil diameter and phasic pupil response. Copyright © 2016 Elsevier B.V. All rights reserved.

Responsible software: A research agenda to help enterprises become more sustainable

NARCIS (Netherlands)

Espana Cubillo, S.; Brinkkemper, S.

[BACKGROUND] Responsible enterprises are key to reaching a sustainable economy that cares about the people and the planet. Their spectrum is wide and it encompasses, among others, non-profit non-governmental organisations, social economy enterprises and companies with a committed corporate social

Emerging viral diseases from a vaccinology perspective: preparing for the next pandemic.

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Graham, Barney S; Sullivan, Nancy J

2018-01-01

Emerging infectious diseases will continue to threaten public health and are sustained by global commerce, travel and disruption of ecological systems. Most pandemic threats are caused by viruses from either zoonotic sources or vector-borne sources. Developing better ways to anticipate and manage the ongoing microbial challenge will be critical for achieving the United Nations Sustainable Development Goals and, conversely, each such goal will affect the ability to control infectious diseases. Here we discuss how technology can be applied effectively to better prepare for and respond to new viral diseases with a focus on new paradigms for vaccine development.

[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.

Regulation of Viral Replication, Apoptosis and Pro-Inflammatory Responses by 17-AAG during Chikungunya Virus Infection in Macrophages

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Tapas K. Nayak

2017-01-01

Full Text Available Chikungunya virus (CHIKV infection has re-emerged as a major public health concern due to its recent worldwide epidemics and lack of control measures. Although CHIKV is known to infect macrophages, regulation of CHIKV replication, apoptosis and immune responses towards macrophages are not well understood. Accordingly, the Raw264.7 cells, a mouse macrophage cell line, were infected with CHIKV and viral replication as well as new viral progeny release was assessed by flow cytometry and plaque assay, respectively. Moreover, host immune modulation and apoptosis were studied through flow cytometry, Western blot and ELISA. Our current findings suggest that expression of CHIKV proteins were maximum at 8 hpi and the release of new viral progenies were remarkably increased around 12 hpi. The induction of Annexin V binding, cleaved caspase-3, cleaved caspase-9 and cleaved caspase-8 in CHIKV infected macrophages suggests activation of apoptosis through both intrinsic and extrinsic pathways. The pro-inflammatory mediators (TNF and IL-6 MHC-I/II and B7.2 (CD86 were also up-regulated during infection over time. Further, 17-AAG, a potential HSP90 inhibitor, was found to regulate CHIKV infection, apoptosis and pro-inflammatory cytokine/chemokine productions of host macrophages significantly. Hence, the present findings might bring new insight into the therapeutic implication in CHIKV disease biology.

Regulation of Viral Replication, Apoptosis and Pro-Inflammatory Responses by 17-AAG during Chikungunya Virus Infection in Macrophages.

Science.gov (United States)

Nayak, Tapas K; Mamidi, Prabhudutta; Kumar, Abhishek; Singh, Laishram Pradeep K; Sahoo, Subhransu S; Chattopadhyay, Soma; Chattopadhyay, Subhasis

2017-01-06

Chikungunya virus (CHIKV) infection has re-emerged as a major public health concern due to its recent worldwide epidemics and lack of control measures. Although CHIKV is known to infect macrophages, regulation of CHIKV replication, apoptosis and immune responses towards macrophages are not well understood. Accordingly, the Raw264.7 cells, a mouse macrophage cell line, were infected with CHIKV and viral replication as well as new viral progeny release was assessed by flow cytometry and plaque assay, respectively. Moreover, host immune modulation and apoptosis were studied through flow cytometry, Western blot and ELISA. Our current findings suggest that expression of CHIKV proteins were maximum at 8 hpi and the release of new viral progenies were remarkably increased around 12 hpi. The induction of Annexin V binding, cleaved caspase-3, cleaved caspase-9 and cleaved caspase-8 in CHIKV infected macrophages suggests activation of apoptosis through both intrinsic and extrinsic pathways. The pro-inflammatory mediators (TNF and IL-6) MHC-I/II and B7.2 (CD86) were also up-regulated during infection over time. Further, 17-AAG, a potential HSP90 inhibitor, was found to regulate CHIKV infection, apoptosis and pro-inflammatory cytokine/chemokine productions of host macrophages significantly. Hence, the present findings might bring new insight into the therapeutic implication in CHIKV disease biology.

Differential responses of Africanized and European honey bees (Apis mellifera) to viral replication following mechanical transmission or Varroa destructor parasitism.

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Hamiduzzaman, Mollah Md; Guzman-Novoa, Ernesto; Goodwin, Paul H; Reyes-Quintana, Mariana; Koleoglu, Gun; Correa-Benítez, Adriana; Petukhova, Tatiana

2015-03-01

For the first time, adults and brood of Africanized and European honey bees (Apis mellifera) were compared for relative virus levels over 48 h following Varroa destructor parasitism or injection of V. destructor homogenate. Rates of increase of deformed wing virus (DWV) for Africanized versus European bees were temporarily lowered for 12h with parasitism and sustainably lowered over the entire experiment (48 h) with homogenate injection in adults. The rates were also temporarily lowered for 24h with parasitism but were not affected by homogenate injection in brood. Rates of increase of black queen cell virus (BQCV) for Africanized versus European bees were similar with parasitism but sustainably lowered over the entire experiment with homogenate injection in adults and were similar for parasitism and homogenate injection in brood. Analyses of sac brood bee virus and Israeli acute paralysis virus were limited as detection did not occur after both homogenate injection and parasitism treatment, or levels were not significantly higher than those following control buffer injection. Lower rates of replication of DWV and BQCV in Africanized bees shows that they may have greater viral resistance, at least early after treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

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

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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.

Embryonic exposure to lead: comparison of immune and cellular responses in unchallenged and virally stressed chickens

Energy Technology Data Exchange (ETDEWEB)

Lee, Ji-Eun; Kao, Elizabeth; Dietert, Rodney R. [Institute for Comparative and Environmental Toxicology, College of Veterinary Medicine, Cornell University, Ithaca, NY (United States); Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY (United States); Naqi, Syed A. [Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY (United States)

2002-01-01

Lead, a ubiquitous environmental contaminant, has been shown to modulate various functions of the immune system and decrease host resistance to infectious disease. However, limited information is available concerning the direct effects of lead on the host immune response to an infectious agent after developmental exposure. The current study utilized chickens to examine the effect of embryonic lead exposure on immune and cellular responses during viral challenge. Sublethal doses of lead were introduced into fertilized Cornell K Strain White Leghorn chicken eggs via the air sac at day 5 or day 12 of embryonic development (designated as E5 and E12, respectively). Four-week-old female chickens were inoculated with infectious bronchitis virus (IBV) strain M41. Antibody titer to IBV, delayed-type hypersensitivity (DTH) response against bovine serum albumin (BSA), the absolute number and percentage of leukocyte subpopulations, and interferon-{gamma} (IFN-{gamma})-like cytokine production by splenocytes were evaluated at 5-6 weeks of age. While antibody response to IBV in juvenile chicks was unaffected by the in ovo lead exposure, IFN-{gamma}-like cytokine production by splenocytes was significantly depressed following lead exposure at both developmental stages. In contrast with this pattern, the DTH response against BSA was unaffected following E5 exposure, but was significantly decreased after E12 exposure to lead. These changes were similar to those previously reported in chickens not exposed to IBV. While lead exposure at E5 induced significant changes in the percentage of circulating heterophils at 1 day postinfection (dpi), lead did not cause any change in relative leukocyte counts after E12 exposure. At 7 dpi, E5 lead exposure resulted in decreased absolute number and percentage of circulating lymphocytes, while total leukocyte counts, and the absolute number and percentage of circulating monocytes and heterophils were significantly reduced in E12 lead

Sustainable Development and Corporate Social Responsibility in Sub-Saharan Africa: Evidence from Industries in Cameroon

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Oyewole Simon Oginni

2016-05-01

Full Text Available Present technological innovations and social organizations continue to impose risks and limitations on the efficient performance of the biosphere. Human activities have increasingly short-lived sustainable natural endowments, to the extent that, the multiplier effects have ripples beyond the traditional benefits of economic production and consumption. Therefore, this study addressed practical concerns on how industries in Sub-Saharan Africa promote sustainable development in their corporate social responsibility models, using industries in Cameroon as a case study; it examined economic, social, and environmental components of sustainable development and corporate social responsibility (CSR. Our sample consists of 335 business enterprises from the last Censure Survey of Enterprises in Cameroon. The study adopted a systematic analysis through the Adjusted Residual Test, and the Phi and Cramer’s V tests. Findings revealed that industries in Cameroon prioritize environmental and social dimensions over economic dimensions. However, a few large enterprises implement a broad CSR that promotes sustainable business practices, whereas smaller ones do not; industries in Cameroon implement environmental dimensions of CSR as a safe buffer and a social dimension as philanthropy. Hence, there is no concrete evidence that industries promote sustainable development via CSR in Cameroon. The implementation of a sustainable business model is a precondition for promoting sustainable development via CSR. Industries should realize the concrete value in implementing a sustainable business model that helps to adjust to the complex and increasingly changing business environment.

Improving laboratory efficiencies to scale-up HIV viral load testing.

Science.gov (United States)

Alemnji, George; Onyebujoh, Philip; Nkengasong, John N

2017-03-01

Viral load measurement is a key indicator that determines patients' response to treatment and risk for disease progression. Efforts are ongoing in different countries to scale-up access to viral load testing to meet the Joint United Nations Programme on HIV and AIDS target of achieving 90% viral suppression among HIV-infected patients receiving antiretroviral therapy. However, the impact of these initiatives may be challenged by increased inefficiencies along the viral load testing spectrum. This will translate to increased costs and ineffectiveness of scale-up approaches. This review describes different parameters that could be addressed across the viral load testing spectrum aimed at improving efficiencies and utilizing test results for patient management. Though progress is being made in some countries to scale-up viral load, many others still face numerous challenges that may affect scale-up efficiencies: weak demand creation, ineffective supply chain management systems; poor specimen referral systems; inadequate data and quality management systems; and weak laboratory-clinical interface leading to diminished uptake of test results. In scaling up access to viral load testing, there should be a renewed focus to address efficiencies across the entire spectrum, including factors related to access, uptake, and impact of test results.

Pharyngitis - viral

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... 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 ...

Viral Management as a New Type of Enterprise Management in Coal Industry

Science.gov (United States)

Garafonova, Olga; Grigashkina, Svetlana; Zhosan, Anna

2017-11-01

The article considers the evolution of the concept of "management". The Internet analysis of the concept of "viral management" was conducted, the results of which testify to the positive trend, the growing interest in scientific circles, the relevance of the chosen direction for further research and the increasing popularity of the viral management among business leaders. The indices of coal and brown coal extraction in Ukraine and Russia for 2010-2016 are analyzed. Among the problems that exist in the coal industry are the following: mine assets have a high degree of deterioration; the equipment is rather obsolete and does not correspond to the world level; among the existing face equipment, the specific weight of longwall mining equipment, road headers, loading machines, and belt conveyors of the new generation is only several percent. Five steps of introduction of the virus management at the enterprise are identified: opening, development, participation, diffusion, sustainability. The principles of introduction of the viral management in the enterprises of the coal industry are offered. It is established that the main idea of the viral management is to "infect" the organization and, mainly, employees with one or another "virus" in the form of a common idea or goal. It is indicated that the viral management assumes a certain automaticity of changes, internal "obsession" with this or other innovation, involvement of an informal personal factor.

Virus del dengue: estructura y ciclo viral Dengue virus: structure and viral cycle

Directory of Open Access Journals (Sweden)

Myriam L Velandia

2011-03-01

Full Text Available El virus del dengue (DENV es el agente causal de la enfermedad conocida como dengue, que es la principal enfermedad viral transmitida por artrópodos en el mundo. El DENV es un flavivirus que ingresa por endocitosis y se replica en el citoplasma de la célula infectada, originando tres proteínas estructurales y siete proteínas no estructurales, sobre las cuales se conocen sólo algunas de sus funciones en la replicación viral o en la infección. El ciclo viral que ocurre en las células infectadas hasta ahora está comenzando a aclararse y su conocimiento permitirá en el futuro próximo diseñar racionalmente moléculas que lo intervengan y eviten la replicación del virus. Durante la infección, el individuo puede presentar fiebre indiferenciada o, en otros casos, puede presentar un proceso generalizado de activación de la respuesta inmunitaria innata y adquirida, lo cual provoca la liberación de factores inflamatorios solubles que alteran la fisiología de los tejidos, principalmente el endotelio, conllevando al desarrollo de manifestaciones clínicas graves. Aunque se ha identificado un gran número de factores del individuo asociados al desarrollo de la enfermedad por DENV, queda por identificar el papel de las diferentes proteínas virales en la patogenia de la enfermedad. En la presente revisión, se presenta una breve actualización sobre la estructura y biología del DENV, de su ciclo viral intracelular y, finalmente, se introducen algunos conceptos sobre la inmunopatogenia de la enfermedad producida por este agente.Dengue virus (DENV is responsible for the clinical entity known as dengue that is a great concern for economy and public health of tropical countries. This flavivirus is a single strand RNA virus that after their translation and replication in host cells produces three structural and seven non-structural proteins with specific function in replication or cell binding process that we will describe here. Intracellular

Variant allele frequency enrichment analysis in vitro reveals sonic hedgehog pathway to impede sustained temozolomide response in GBM.

Science.gov (United States)

Biswas, Nidhan K; Chandra, Vikas; Sarkar-Roy, Neeta; Das, Tapojyoti; Bhattacharya, Rabindra N; Tripathy, Laxmi N; Basu, Sunandan K; Kumar, Shantanu; Das, Subrata; Chatterjee, Ankita; Mukherjee, Ankur; Basu, Pryiadarshi; Maitra, Arindam; Chattopadhyay, Ansuman; Basu, Analabha; Dhara, Surajit

2015-01-21

Neoplastic cells of Glioblastoma multiforme (GBM) may or may not show sustained response to temozolomide (TMZ) chemotherapy. We hypothesize that TMZ chemotherapy response in GBM is predetermined in its neoplastic clones via a specific set of mutations that alter relevant pathways. We describe exome-wide enrichment of variant allele frequencies (VAFs) in neurospheres displaying contrasting phenotypes of sustained versus reversible TMZ-responses in vitro. Enrichment of VAFs was found on genes ST5, RP6KA1 and PRKDC in cells showing sustained TMZ-effect whereas on genes FREM2, AASDH and STK36, in cells showing reversible TMZ-effect. Ingenuity pathway analysis (IPA) revealed that these genes alter cell-cycle, G2/M-checkpoint-regulation and NHEJ pathways in sustained TMZ-effect cells whereas the lysine-II&V/phenylalanine degradation and sonic hedgehog (Hh) pathways in reversible TMZ-effect cells. Next, we validated the likely involvement of the Hh-pathway in TMZ-response on additional GBM neurospheres as well as on GBM patients, by extracting RNA-sequencing-based gene expression data from the TCGA-GBM database. Finally, we demonstrated TMZ-sensitization of a TMZ non-responder neurosphere in vitro by treating them with the FDA-approved pharmacological Hh-pathway inhibitor vismodegib. Altogether, our results indicate that the Hh-pathway impedes sustained TMZ-response in GBM and could be a potential therapeutic target to enhance TMZ-response in this malignancy.

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...

[Immunotherapy for refractory viral infections].

Science.gov (United States)

Morio, Tomohiro; Fujita, Yuriko; Takahashi, Satoshi

Various antiviral agents have been developed, which are sometimes associated with toxicity, development of virus-resistant strain, and high cost. Virus-specific T-cell (VST) therapy provides an alternative curative therapy that can be effective for a prolonged time without eliciting drug resistance. VSTs can be directly separated using several types of capture devices and can be obtained by stimulating peripheral blood mononuclear cells with viral antigens (virus, protein, or peptide) loaded on antigen-presenting cells (APC). APC can be transduced with virus-antigen coding plasmid or pulsed with overlapping peptides. VST therapy has been studied in drug non-responsive viral infections after hematopoietic cell transplantation (HCT). Several previous studies have demonstrated the efficacy of VST therapy without significant severe GVHD. In addition, VSTs from a third-party donor have been prepared and administered for post-HCT viral infection. Although target viruses of VSTs include herpes virus species and polyomavirus species, a wide variety of pathogens, such as papillomavirus, intracellular bacteria, and fungi, can be treated by pathogen-specific T-cells. Perhaps, these specific T-cells could be used for opportunistic infections in other immunocompromised hosts in the near future.

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 ...

Anti-viral RNA silencing: do we look like plants ?

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Lecellier Charles-Henri

2006-01-01

Full Text Available Abstract The anti-viral function of RNA silencing was first discovered in plants as a natural manifestation of the artificial 'co-suppression', which refers to the extinction of endogenous gene induced by homologous transgene. Because silencing components are conserved among most, if not all, eukaryotes, the question rapidly arose as to determine whether this process fulfils anti-viral functions in animals, such as insects and mammals. It appears that, whereas the anti-viral process seems to be similarly conserved from plants to insects, even in worms, RNA silencing does influence the replication of mammalian viruses but in a particular mode: micro(miRNAs, endogenous small RNAs naturally implicated in translational control, rather than virus-derived small interfering (siRNAs like in other organisms, are involved. In fact, these recent studies even suggest that RNA silencing may be beneficial for viral replication. Accordingly, several large DNA mammalian viruses have been shown to encode their own miRNAs. Here, we summarize the seminal studies that have implicated RNA silencing in viral infection and compare the different eukaryotic responses.

Rabies Virus Infection Induces the Formation of Stress Granules Closely Connected to the Viral Factories.

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Jovan Nikolic

2016-10-01

Full Text Available Stress granules (SGs are membrane-less dynamic structures consisting of mRNA and protein aggregates that form rapidly in response to a wide range of environmental cellular stresses and viral infections. They act as storage sites for translationally silenced mRNAs under stress conditions. During viral infection, SG formation results in the modulation of innate antiviral immune responses, and several viruses have the ability to either promote or prevent SG assembly. Here, we show that rabies virus (RABV induces SG formation in infected cells, as revealed by the detection of SG-marker proteins Ras GTPase-activating protein-binding protein 1 (G3BP1, T-cell intracellular antigen 1 (TIA-1 and poly(A-binding protein (PABP in the RNA granules formed during viral infection. As shown by live cell imaging, RABV-induced SGs are highly dynamic structures that increase in number, grow in size by fusion events, and undergo assembly/disassembly cycles. Some SGs localize in close proximity to cytoplasmic viral factories, known as Negri bodies (NBs. Three dimensional reconstructions reveal that both structures remain distinct even when they are in close contact. In addition, viral mRNAs synthesized in NBs accumulate in the SGs during viral infection, revealing material exchange between both compartments. Although RABV-induced SG formation is not affected in MEFs lacking TIA-1, TIA-1 depletion promotes viral translation which results in an increase of viral replication indicating that TIA-1 has an antiviral effect. Inhibition of PKR expression significantly prevents RABV-SG formation and favors viral replication by increasing viral translation. This is correlated with a drastic inhibition of IFN-B gene expression indicating that SGs likely mediate an antiviral response which is however not sufficient to fully counteract RABV infection.

Distribution of T Cells in Rainbow Trout (Oncorhynchus mykiss) Skin and Responsiveness to Viral Infection

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Leal, Esther; Granja, Aitor G.; Zarza, Carlos; Tafalla, Carolina

2016-01-01

Although the skin constitutes the first line of defense against waterborne pathogens, there is a great lack of information regarding the skin associated lymphoid tissue (SALT) and whether immune components of the skin are homogeneously distributed through the surface of the fish is still unknown. In the current work, we have analyzed the transcription of several immune genes throughout different rainbow trout (Oncorhynchus mykiss) skin areas. We found that immunoglobulin and chemokine gene transcription levels were higher in a skin area close to the gills. Furthermore, this skin area as well as other anterior sections also transcribed significantly higher levels of many different immune genes related to T cell immunity such as T cell receptor α (TCRα), TCRγ, CD3, CD4, CD8, perforin, GATA3, Tbet, FoxP3, interferon γ (IFNγ), CD40L and Eomes in comparison to posterior skin sections. In agreement with these results, immunohistochemical analysis revealed that anterior skin areas had a higher concentration of CD3+ T cells and flow cytometry analysis confirmed that the percentage of CD8+ T lymphocytes was also higher in anterior skin sections. These results demonstrate for the first time that T cells are not homogeneously distributed throughout the teleost skin. Additionally, we studied the transcriptional regulation of these and additional T cell markers in response to a bath infection with viral hemorrhagic septicemia virus (VHSV). We found that VHSV regulated the transcription of several of these T cell markers in both the skin and the spleen; with some differences between anterior and posterior skin sections. Altogether, our results point to skin T cells as major players of teleost skin immunity in response to waterborne viral infections. PMID:26808410

Cytotoxic CD4 T Cells—Friend or Foe during Viral Infection?

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Juno, Jennifer A.; van Bockel, David; Kent, Stephen J.; Kelleher, Anthony D.; Zaunders, John J.; Munier, C. Mee Ling

2017-01-01

CD4 T cells with cytotoxic function were once thought to be an artifact due to long-term in vitro cultures but have in more recent years become accepted and reported in the literature in response to a number of viral infections. In this review, we focus on cytotoxic CD4 T cells in the context of human viral infections and in some infections that affect mice and non-human primates. We examine the effector mechanisms used by cytotoxic CD4 cells, the phenotypes that describe this population, and the transcription factors and pathways that lead to their induction following infection. We further consider the cells that are the predominant targets of this effector subset and describe the viral infections in which CD4 cytotoxic T lymphocytes have been shown to play a protective or pathologic role. Cytotoxic CD4 T cells are detected in the circulation at much higher levels than previously realized and are now recognized to have an important role in the immune response to viral infections. PMID:28167943

Responsible marketing for sustainable tourism

OpenAIRE

Jegdić Vaso

2014-01-01

The biggest challenge associated with the concept of sustainable tourism is its operationalisation and perception as a process to be applied through development plans, projects and ongoing activities of tour operators. The traditional approach to marketing, focused on a limited idea of maximising profit businesses, was not able to respond to a number of social and environmental requirements imposed by the concept of sustainable development. This paper discusses the ways in which marketing cou...

Multiparametric analysis of host response to murine cytomegalovirus in MHC class I-disparate mice reveals primacy of Dk-licensed Ly49G2+ NK cells in viral control.

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Prince, Jessica; Lundgren, Alyssa; Stadnisky, Michael D; Nash, William T; Beeber, Amira; Turner, Stephen D; Brown, Michael G

2013-11-01

MHC class I D(k) and Ly49G2 (G2) inhibitory receptor-expressing NK cells are essential to murine CMV (MCMV) resistance in MA/My mice. Without D(k), G2(+) NK cells in C57L mice fail to protect against MCMV infection. As a cognate ligand of G2, D(k) licenses G2(+) NK cells for effector activity. These data suggested that D(k)-licensed G2(+) NK cells might recognize and control MCMV infection. However, a role for licensed NK cells in viral immunity is uncertain. We combined classical genetics with flow cytometry to visualize the host response to MCMV. Immune cells collected from individuals of a diverse cohort of MA/My × C57L offspring segregating D(k) were examined before infection and postinfection, including Ly49(+) NK subsets, receptor expression features, and other phenotypic traits. To identify critical NK cell features, automated analysis of 110 traits was performed in R using the Pearson correlation, followed with a Bonferroni correction for multiple tests. Hierarchical clustering of trait associations and principal component analyses were used to discern shared immune response and genetic relationships. The results demonstrate that G2 expression on naive blood NK cells was predictive of MCMV resistance. However, rapid G2(+) NK cell expansion following viral exposure occurred selectively in D(k) offspring; this response was more highly correlated with MCMV control than all other immune cell features. We infer that D(k)-licensed G2(+) NK cells efficiently detected missing-self MHC cues on viral targets, which elicited cellular expansion and target cell killing. Therefore, MHC polymorphism regulates licensing and detection of viral targets by distinct subsets of NK cells required in innate viral control.

Transcriptomic responses in rainbow trout gills upon infection with viral hemorrhagic septicemia virus (VHSV).

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Aquilino, Carolina; Castro, Rosario; Fischer, Uwe; Tafalla, Carolina

2014-05-01

It has been previously demonstrated that even though the fin bases constitute the main portal of entry of viral hemorrhagic septicemia virus (VHSV) in rainbow trout (Oncorhynchus mykiss), an important number of chemokine genes are up-regulated in the gills upon bath exposure to the virus. Because chemokines mediate the recruitment of leukocytes through the action of specific chemokine receptors, in the current study, we have studied the transcription of several immune genes in response to a VHSV bath infection in the gills, focusing both on chemokine receptor genes and on genes characteristic of distinct leukocyte populations such as IgM, IgD, IgT, CD4, CD8, perforin and MHC-II. We have studied the response to the virus in naïve fish as well as in fish that had been previously intramuscularly (i.m.) injected with a VHSV DNA vaccine. Additionally, we have sorted both IgM(+) and CD8(+) cells from the gills of naïve and infected animals to study some of these up-regulated genes in specific leukocyte populations. Our results indicate that despite the low replication level, VHSV provokes an up-regulation of IgM, IgT, CD3 and perforin transcription together with the up-regulation of CCR7, CCR9, CXCR3B and CXCR4 mRNA levels. Interestingly, MHC-II mRNA was up-regulated and CCR7 was down-modulated in IgM(+) cells from infected gills, whereas perforin, CCR7 and CXCR4 mRNA levels were higher in sorted CD8(+) cells from infected animals. Surprisingly, when fish had been previously injected with either the empty plasmid or the VHSV DNA vaccine, these up-regulations in immune gene transcription were no longer observed. Our results point to the gills as an important site for innate and acquired viral defense. Copyright © 2013 Elsevier Ltd. All rights reserved.

Linking public sector corporate social responsibility with sustainable development: lessons from India

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Subhasis Ray

2013-12-01

Full Text Available Economic think tanks predict India to be the world’s largest economy by 2050. This would require India to accelerate its industrial and infrastructure development. Industrialization based economic development will have a negative impact on the environment and hence sustainable development. Such steps could affect the social and environmental bottom line of the national economy. In recent years, a number of regulatory measures have been proposed by the Indian government to ensure corporate support to the goals of sustainable and inclusive development. The objective of these regulations is to achieve triple bottom line based growth. Notable among them is the mandatory Corporate Social Responsibility (CSR guidelines for public sector undertakings, first issued in April, 2010. I study the possibility and problems created by this effort by analyzing the policy documents and interviewing managers responsible for implementing CSR programmers in Indian public sector. Managers interviewed came from hydropower, coal, power distribution and shipping industries. Based on the study, four areas are identified that requires attention for effective linking between sustainable development and CSR; stakeholder engagement, institutional mechanisms, capacity building and knowledge management. Both government-public sector and public sector-community engagements have to be more streamlined. Institutional mechanisms have to be developed to see that CSR projects are effective and delivering. Importantly, managers at all levels need a better understanding of CSR and sustainable development. Since most projects are in rural areas, understanding of rural issues and sustainability is very important. Finally, such a large scale exercise in CSR should have a knowledge management mechanism to learn from the achievements and mistakes of the early years. I discuss the implication of the findings on India and other emerging economies many of which are struggling to balance

Viral infection affects sucrose responsiveness and homing ability of forager honey bees, Apis mellifera L.

Science.gov (United States)

Li, Zhiguo; Chen, Yanping; Zhang, Shaowu; Chen, Shenglu; Li, Wenfeng; Yan, Limin; Shi, Liangen; Wu, Lyman; Sohr, Alex; Su, Songkun

2013-01-01

Honey bee health is mainly affected by Varroa destructor, viruses, Nosema spp., pesticide residues and poor nutrition. Interactions between these proposed factors may be responsible for the colony losses reported worldwide in recent years. In the present study, the effects of a honey bee virus, Israeli acute paralysis virus (IAPV), on the foraging behaviors and homing ability of European honey bees (Apis mellifera L.) were investigated based on proboscis extension response (PER) assays and radio frequency identification (RFID) systems. The pollen forager honey bees originated from colonies that had no detectable level of honey bee viruses and were manually inoculated with IAPV to induce the viral infection. The results showed that IAPV-inoculated honey bees were more responsive to low sucrose solutions compared to that of non-infected foragers. After two days of infection, around 10⁷ copies of IAPV were detected in the heads of these honey bees. The homing ability of IAPV-infected foragers was depressed significantly in comparison to the homing ability of uninfected foragers. The data provided evidence that IAPV infection in the heads may enable the virus to disorder foraging roles of honey bees and to interfere with brain functions that are responsible for learning, navigation, and orientation in the honey bees, thus, making honey bees have a lower response threshold to sucrose and lose their way back to the hive.

Viral infection affects sucrose responsiveness and homing ability of forager honey bees, Apis mellifera L.

Directory of Open Access Journals (Sweden)

Zhiguo Li

Full Text Available Honey bee health is mainly affected by Varroa destructor, viruses, Nosema spp., pesticide residues and poor nutrition. Interactions between these proposed factors may be responsible for the colony losses reported worldwide in recent years. In the present study, the effects of a honey bee virus, Israeli acute paralysis virus (IAPV, on the foraging behaviors and homing ability of European honey bees (Apis mellifera L. were investigated based on proboscis extension response (PER assays and radio frequency identification (RFID systems. The pollen forager honey bees originated from colonies that had no detectable level of honey bee viruses and were manually inoculated with IAPV to induce the viral infection. The results showed that IAPV-inoculated honey bees were more responsive to low sucrose solutions compared to that of non-infected foragers. After two days of infection, around 10⁷ copies of IAPV were detected in the heads of these honey bees. The homing ability of IAPV-infected foragers was depressed significantly in comparison to the homing ability of uninfected foragers. The data provided evidence that IAPV infection in the heads may enable the virus to disorder foraging roles of honey bees and to interfere with brain functions that are responsible for learning, navigation, and orientation in the honey bees, thus, making honey bees have a lower response threshold to sucrose and lose their way back to the hive.

Viral Infection Affects Sucrose Responsiveness and Homing Ability of Forager Honey Bees, Apis mellifera L.

Science.gov (United States)

Li, Zhiguo; Chen, Yanping; Zhang, Shaowu; Chen, Shenglu; Li, Wenfeng; Yan, Limin; Shi, Liangen; Wu, Lyman; Sohr, Alex; Su, Songkun

2013-01-01

Honey bee health is mainly affected by Varroa destructor, viruses, Nosema spp., pesticide residues and poor nutrition. Interactions between these proposed factors may be responsible for the colony losses reported worldwide in recent years. In the present study, the effects of a honey bee virus, Israeli acute paralysis virus (IAPV), on the foraging behaviors and homing ability of European honey bees (Apis mellifera L.) were investigated based on proboscis extension response (PER) assays and radio frequency identification (RFID) systems. The pollen forager honey bees originated from colonies that had no detectable level of honey bee viruses and were manually inoculated with IAPV to induce the viral infection. The results showed that IAPV-inoculated honey bees were more responsive to low sucrose solutions compared to that of non-infected foragers. After two days of infection, around 107 copies of IAPV were detected in the heads of these honey bees. The homing ability of IAPV-infected foragers was depressed significantly in comparison to the homing ability of uninfected foragers. The data provided evidence that IAPV infection in the heads may enable the virus to disorder foraging roles of honey bees and to interfere with brain functions that are responsible for learning, navigation, and orientation in the honey bees, thus, making honey bees have a lower response threshold to sucrose and lose their way back to the hive. PMID:24130876

Virally encoded chemokines and chemokine receptors in the role of viral infections

DEFF Research Database (Denmark)

Holst, Peter J; Lüttichau, Hans R; Schwartz, Thue W

2003-01-01

of these or potent ways to alter an efficient antiviral response to a weak Th2-driven response. Examples here are the chemokine scavenging by US28, attractance of Th2 cells and regulatory cells by vMIP1-3 and the selective engaging of CCR8 by MC148. Important insights into viral pathology and possible targets...... for antiviral therapies have been provided by UL33, UL78 and in particular ORF74 and the chances are that many more will follow. In HHV8 vMIP-2 and the chemokine-binding proteins potent anti-inflammatory agents have been provided. These have already had their potential demonstrated in animal models and may...

Responsibility and Sustainability in a Food Chain: A Priority Matrix Analysis

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Francesco Caracciolo

2011-12-01

Full Text Available  This paper shows the results of empirical research conducted to assess the sustainability of a typical food supply chain, suggesting feasible solutions to satisfy inter-dimensional requisites of durable development. The analysis was conducted with reference to the supply chain of the San Marzano tomato (SMZ, a typical local food. The product is endowed with an origin certification label (PDO, meeting demand within high-value market niches. The SMZ is a flagship product in the Italian region of Campania and has benefited from several regionally funded interventions, such as genetic research and support for the application for EU certification of origin. Two key findings emerged from the research. First, the results allowed us to define a Stakeholder Priority and Responsibilities’ Matrix (SPRM, and monitor the sustainability trend of SMZ food supply chains. Second, the consistency between the adoption of quality strategy (brand of origin and sustainable development of the sector was evaluated. Despite its intrinsic characteristics and its organized, well-defined structure, the SMZ food supply chain is unable to address sustainable objectives without considerable public intervention and support. In terms of sustainability, to be able to show desirable food chain characteristics, the existence of a fully collaborative relationship between the actors has to be ascertained. Identifying shared goals is essential to assign and implement coordinated actions, pooling responsibility for product quality into social and environmental dimensions.

Human Parvovirus B19 Utilizes Cellular DNA Replication Machinery for Viral DNA Replication.

Science.gov (United States)

Zou, Wei; Wang, Zekun; Xiong, Min; Chen, Aaron Yun; Xu, Peng; Ganaie, Safder S; Badawi, Yomna; Kleiboeker, Steve; Nishimune, Hiroshi; Ye, Shui Qing; Qiu, Jianming

2018-03-01

Human parvovirus B19 (B19V) infection of human erythroid progenitor cells (EPCs) induces a DNA damage response and cell cycle arrest at late S phase, which facilitates viral DNA replication. However, it is not clear exactly which cellular factors are employed by this single-stranded DNA virus. Here, we used microarrays to systematically analyze the dynamic transcriptome of EPCs infected with B19V. We found that DNA metabolism, DNA replication, DNA repair, DNA damage response, cell cycle, and cell cycle arrest pathways were significantly regulated after B19V infection. Confocal microscopy analyses revealed that most cellular DNA replication proteins were recruited to the centers of viral DNA replication, but not the DNA repair DNA polymerases. Our results suggest that DNA replication polymerase δ and polymerase α are responsible for B19V DNA replication by knocking down its expression in EPCs. We further showed that although RPA32 is essential for B19V DNA replication and the phosphorylated forms of RPA32 colocalized with the replicating viral genomes, RPA32 phosphorylation was not necessary for B19V DNA replication. Thus, this report provides evidence that B19V uses the cellular DNA replication machinery for viral DNA replication. IMPORTANCE Human parvovirus B19 (B19V) infection can cause transient aplastic crisis, persistent viremia, and pure red cell aplasia. In fetuses, B19V infection can result in nonimmune hydrops fetalis and fetal death. These clinical manifestations of B19V infection are a direct outcome of the death of human erythroid progenitors that host B19V replication. B19V infection induces a DNA damage response that is important for cell cycle arrest at late S phase. Here, we analyzed dynamic changes in cellular gene expression and found that DNA metabolic processes are tightly regulated during B19V infection. Although genes involved in cellular DNA replication were downregulated overall, the cellular DNA replication machinery was tightly

Information Overload and Viral Marketing: Countermeasures and Strategies

Science.gov (United States)

Cheng, Jiesi; Sun, Aaron; Zeng, Daniel

Studying information diffusion through social networks has become an active research topic with important implications in viral marketing applications. One of the fundamental algorithmic problems related to viral marketing is the Influence Maximization (IM) problem: given an social network, which set of nodes should be considered by the viral marketer as the initial targets, in order to maximize the influence of the advertising message. In this work, we study the IM problem in an information-overloaded online social network. Information overload occurs when individuals receive more information than they can process, which can cause negative impacts on the overall marketing effectiveness. Many practical countermeasures have been proposed for alleviating the load of information on recipients. However, how these approaches can benefit viral marketers is not well understood. In our work, we have adapted the classic Information Cascade Model to incorporate information overload and study its countermeasures. Our results suggest that effective control of information overload has the potential to improve marketing effectiveness, but the targeting strategy should be re-designed in response to these countermeasures.

Social Responsibility as a Means for the Sustainable Development in the Lower Danube River Basin

Directory of Open Access Journals (Sweden)

Tzvetelin Gueorguiev

2014-08-01

Full Text Available Sustainable development of the world and the EU in particular is a priority outlined in a number of strategic documents. Social responsibility is an important topic covered by standards such as SA 8000:2001 and ISO 26000:2010. This paper presents a case study of the practical implementation of corporate social responsibility activities in a Bulgarian company. Several key initiatives have been undertaken to prove the company‘s commitment to all interested parties including local communities as well. Social responsibility is where the interests and benefits for all stakeholders meet, namely employers, employees, contractors, academics, authorities and society as a whole. This paper presents a critical and original point of view on the advantages of using standards for social responsibility as a means for sustainable development.

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.

Structural and Nonstructural Viral Proteins Are Targets of T-Helper Immune Response against Human Respiratory Syncytial Virus.

Science.gov (United States)

Lorente, Elena; Barriga, Alejandro; Barnea, Eilon; Mir, Carmen; Gebe, John A; Admon, Arie; López, Daniel

2016-06-01

Proper antiviral humoral and cellular immune responses require previous recognition of viral antigenic peptides that are bound to HLA class II molecules, which are exposed on the surface of antigen-presenting cells. The helper immune response is critical for the control and the clearance of human respiratory syncytial virus (HRSV) infection, a virus with severe health risk in infected pediatric, immunocompromised, and elderly populations. In this study, using a mass spectrometry analysis of complex HLA class II-bound peptide pools that were isolated from large amounts of HRSV-infected cells, 19 naturally processed HLA-DR ligands, most of them included in a complex nested set of peptides, were identified. Both the immunoprevalence and the immunodominance of the HLA class II response to HRSV were focused on one nonstructural (NS1) and two structural (matrix and mainly fusion) proteins of the infective virus. These findings have clear implications for analysis of the helper immune response as well as for antiviral vaccine design. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

NaVirCept - Nucleic Acid-Based Anti-Viral Project

International Nuclear Information System (INIS)

Stephen, E. R.; Wong, J.; Van Loon, D.

2007-01-01

Vaccines are generally considered to be the most effective countermeasures to bacterial and viral diseases, however, licensed vaccines against many disease agents are either not available or their efficacies have not been demonstrated. Vaccines are generally agent specific in terms of treatment spectrum and are subject to defeat through natural mutation or through directed efforts. With respect to viral therapeutics, one of the major limitations associated with antiviral drugs is acquired drug resistance caused by antigenic shift or drift. A number of next-generation prophylactic and/or therapeutic measures are on the horizon. Of these, nucleic acid-based drugs are showing great antiviral potential. These drugs elicit long-lasting, broad spectrum protective immune responses, especially to respiratory viral pathogens. The Nucleic Acid-Based Antiviral (NaVirCept) project provides the opportunity to demonstrate the effectiveness of novel medical countermeasures against military-significant endemic and other viral threat agents. This project expands existing DRDC drug delivery capability development, in the form of proprietary liposome intellectual property, by coupling it with leading-edge nucleic acid-based technology to deliver effective medical countermeasures that will protect deployed personnel and the warfighter against a spectrum of viral disease agents. The technology pathway will offer a means to combat emerging viral diseases or modified threat agents such as the bird flu or reconstructed Spanish flu without going down the laborious, time-consuming and expensive paths to develop countermeasures for each new and/or emerging viral disease organism.(author)

Viral Management as a New Type of Enterprise Management in Coal Industry

Directory of Open Access Journals (Sweden)

Garafonova Olga

2017-01-01

Full Text Available The article considers the evolution of the concept of “management”. The Internet analysis of the concept of “viral management” was conducted, the results of which testify to the positive trend, the growing interest in scientific circles, the relevance of the chosen direction for further research and the increasing popularity of the viral management among business leaders. The indices of coal and brown coal extraction in Ukraine and Russia for 2010-2016 are analyzed. Among the problems that exist in the coal industry are the following: mine assets have a high degree of deterioration; the equipment is rather obsolete and does not correspond to the world level; among the existing face equipment, the specific weight of longwall mining equipment, road headers, loading machines, and belt conveyors of the new generation is only several percent. Five steps of introduction of the virus management at the enterprise are identified: opening, development, participation, diffusion, sustainability. The principles of introduction of the viral management in the enterprises of the coal industry are offered. It is established that the main idea of the viral management is to “infect” the organization and, mainly, employees with one or another “virus” in the form of a common idea or goal. It is indicated that the viral management assumes a certain automaticity of changes, internal “obsession” with this or other innovation, involvement of an informal personal factor.

Associations between national viral hepatitis policies/programmes and country-level socioeconomic factors

DEFF Research Database (Denmark)

Lazarus, Jeffrey V; Sperle, Ida; Safreed-Harmon, Kelly

2017-01-01

BACKGROUND: As more countries worldwide develop national viral hepatitis strategies, it is important to ask whether context-specific factors affect their decision-making. This study aimed to determine whether country-level socioeconomic factors are associated with viral hepatitis programmes...... and policy responses across WHO Member States (MS). METHODS: WHO MS focal points completed a questionnaire on national viral hepatitis policies. This secondary analysis of data reported in the 2013 Global Policy Report on the Prevention and Control of Viral Hepatitis in WHO Member States used logistic...... regression to examine associations between four survey questions and four socioeconomic factors: country income level, Human Development Index (HDI), health expenditure and physician density. RESULTS: This analysis included 119 MS. MS were more likely to have routine viral hepatitis surveillance and to have...

Hatchery Vaccination Against Poultry Viral Diseases: Potential Mechanisms and Limitations.

Science.gov (United States)

Abdul-Cader, Mohamed Sarjoon; Palomino-Tapia, Victor; Amarasinghe, Aruna; Ahmed-Hassan, Hanaa; De Silva Senapathi, Upasama; Abdul-Careem, Mohamed Faizal

Commercial broiler and layer chickens are heavily vaccinated against economically important viral diseases with a view of preventing morbidity, mortality, and production impacts encountered during short production cycles. Hatchery vaccination is performed through in ovo embryo vaccination prehatch or spray and subcutaneous vaccinations performed at the day of hatch before the day-old chickens are being placed in barns with potentially contaminated environments. Commercially, multiple vaccines (e.g., live, live attenuated, and viral vectored vaccines) are available to administer through these routes within a short period (embryo day 18 prehatch to day 1 posthatch). Although the ability to mount immune response, especially the adaptive immune response, is not optimal around the hatch, it is possible that the efficacy of these vaccines depends partly on innate host responses elicited in response to replicating vaccine viruses. This review focuses on the current knowledge of hatchery vaccination in poultry and potential mechanisms of hatchery vaccine-mediated protective responses and limitations.

Human Lectins and Their Roles in Viral Infections

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Christopher P. Mason

2015-01-01

Full Text Available Innate recognition of virus proteins is an important component of the immune response to viral pathogens. A component of this immune recognition is the family of lectins; pattern recognition receptors (PRRs that recognise viral pathogen-associated molecular patterns (PAMPs including viral glycoproteins. In this review we discuss the contribution of soluble and membrane-associated PRRs to immunity against virus pathogens, and the potential role of these molecules in facilitating virus replication. These processes are illustrated with examples of viruses including human immunodeficiency virus (HIV, hepatitis C virus (HCV and Ebola virus (EBOV. We focus on the structure, function and genetics of the well-characterised C-type lectin mannose-binding lectin, the ficolins, and the membrane-bound CD209 proteins expressed on dendritic cells. The potential for lectin-based antiviral therapies is also discussed.

Hepatitis viral aguda

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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

Virale commercials: de consument als marketeer. Onderzoek naar de redenen waarom consumenten virale commercials doorsturen: hun motieven, de inhoudskenmerken van viral commercials en de mediumcontext waarin virale commercials verschijnen

NARCIS (Netherlands)

Ketelaar, P.E.; Lucassen, P.; Kregting, G.H.J.

2010-01-01

Research into the reasons why consumers pass along viral commercials: their motives, the content characteristics of viral commercials and the medium context in which viral commercials appear. Based on the uses and gratifications perspective this study has determined which motives of consumers,

Viral infection of human lung macrophages increases PDL1 expression via IFNβ.

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Karl J Staples

Full Text Available Lung macrophages are an important defence against respiratory viral infection and recent work has demonstrated that influenza-induced macrophage PDL1 expression in the murine lung leads to rapid modulation of CD8+ T cell responses via the PD1 receptor. This PD1/PDL1 pathway may downregulate acute inflammatory responses to prevent tissue damage. The aim of this study was to investigate the mechanisms of PDL1 regulation by human macrophages in response to viral infection. Ex-vivo viral infection models using influenza and RSV were established in human lung explants, isolated lung macrophages and monocyte-derived macrophages (MDM and analysed by flow cytometry and RT-PCR. Incubation of lung explants, lung macrophages and MDM with X31 resulted in mean cellular infection rates of 18%, 18% and 29% respectively. Viral infection significantly increased cell surface expression of PDL1 on explant macrophages, lung macrophages and MDM but not explant epithelial cells. Infected MDM induced IFNγ release from autologous CD8+ T cells, an effect enhanced by PDL1 blockade. We observed increases in PDL1 mRNA and IFNβ mRNA and protein release by MDM in response to influenza infection. Knockdown of IFNβ by siRNA, resulted in a 37.5% reduction in IFNβ gene expression in response to infection, and a significant decrease in PDL1 mRNA. Furthermore, when MDM were incubated with IFNβ, this cytokine caused increased expression of PDL1 mRNA. These data indicate that human macrophage PDL1 expression modulates CD8+ cell IFNγ release in response to virus and that this expression is regulated by autologous IFNβ production.

Plant response-based sensing for control starategies in sustainable greenhouse production

International Nuclear Information System (INIS)

Kacira, M.; Sase, S.; Okushima, L.; Ling, P.P.

2005-01-01

The effect of environmental variability is one of the major concerns in experimental design for both research in plant systems and greenhouse plant production. Microclimates surrounding plants are not usually uniform. Therefore, many samples and sensors are required to obtain a true representation of the plant population. A plant monitoring system capable of reducing the required number of samples by reducing environmental variability would be more advantageous. To better understand plant-environment interaction, it is essential to study plants, microclimate surrounding the plants and the growth media. To achieve this, the monitoring system must be equipped with proper instrumentation. To achieve proper management practices and sustainable greenhouse production, it is essential first to understand plants and their interactions with their surroundings and then establish plant response-based sensing and control strategies for greenhouse processes. Therefore, an effort was conducted to review and discuss current sensing and control strategies in greenhouse research and plant production and provide recommendations on plant response-based sensing and control strategies for sustainable greenhouse production

Dynamic Changes in Host Gene Expression following In Vitro Viral Mimic Stimulation in Crocodile Cells

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Subir Sarker

2017-11-01

Full Text Available The initial control of viral infection in a host is dominated by a very well orchestrated early innate immune system; however, very little is known about the ability of a host to control viral infection outside of mammals. The reptiles offer an evolutionary bridge between the fish and mammals, with the crocodile having evolved from the archosauria clade that included the dinosaurs, and being the largest living reptile species. Using an RNA-seq approach, we have defined the dynamic changes of a passaged primary crocodile cell line to stimulation with both RNA and DNA viral mimics. Cells displayed a marked upregulation of many genes known to be involved in the mammalian response to viral infection, including viperin, Mx1, IRF7, IRF1, and RIG-I with approximately 10% of the genes being uncharacterized transcripts. Both pathway and genome analysis suggested that the crocodile may utilize the main known mammalian TLR and cytosolic antiviral RNA signaling pathways, with the pathways being responsible for sensing DNA viruses less clear. Viral mimic stimulation upregulated the type I interferon, IFN-Omega, with many known antiviral interferon-stimulated genes also being upregulated. This work demonstrates for the first time that reptiles show functional regulation of many known and unknown antiviral pathways and effector genes. An enhanced knowledge of these ancient antiviral pathways will not only add to our understanding of the host antiviral innate response in non-mammalian species, but is critical to fully comprehend the complexity of the mammalian innate immune response to viral infection.

Two doses of bovine viral diarrhea virus DNA vaccine delivered by electroporation induce long-term protective immune responses.

Science.gov (United States)

van Drunen Littel-van den Hurk, Sylvia; Lawman, Zoe; Snider, Marlene; Wilson, Don; van den Hurk, Jan V; Ellefsen, Barry; Hannaman, Drew

2013-02-01

Bovine viral diarrhea virus (BVDV) is a pathogen of major importance in cattle, so there is a need for new effective vaccines. DNA vaccines induce balanced immune responses and are relatively inexpensive and thus promising for both human and veterinary applications. In this study, newborn calves with maternal antibodies were vaccinated intramuscularly (i.m.) with a BVDV E2 DNA vaccine with the TriGrid Delivery System for i.m. delivery (TDS-IM). Two doses of this vaccine spaced 6 or 12 weeks apart were sufficient to induce significant virus-neutralizing antibody titers, numbers of activated T cells, and reduction in viral shedding and clinical presentations after BVDV-2 challenge. In contrast to the placebo-treated animals, the vaccinated calves did not lose any weight, which is an excellent indicator of the well-being of an animal and has a significant economic impact. Furthermore, the interval between the two vaccinations did not influence the magnitude of the immune responses or degree of clinical protection, and a third immunization was not necessary or beneficial. Since electroporation may enhance not only the magnitude but also the duration of immunity after DNA immunization, the interval between vaccination and challenge was extended in a second trial, which showed that two doses of this E2 DNA vaccine again significantly reduced clinical disease against BVDV for several months. These results are promising and support this technology for use against infectious diseases in cattle and large species, including humans, in general.

When Legitimacy Shapes Environmentally Responsible Behaviors: Considering Exposure to University Sustainability Initiatives

Science.gov (United States)

Watson, Lesley; Hegtvedt, Karen A.; Johnson, Cathryn; Parris, Christie L.; Subramanyam, Shruthi

2017-01-01

This study examines how perceptions of the legitimacy of university sustainability efforts--support by the administration (authorization) or from students' peers (endorsement)--as well as the physical context in which students live, matter in shaping students' environmentally responsible behaviors (ERBs). Using survey data collected from…

Microneedle-mediated delivery of viral vectored vaccines.

Science.gov (United States)

Zaric, Marija; Ibarzo Yus, Bárbara; Kalcheva, Petya Petrova; Klavinskis, Linda Sylvia

2017-10-01

Microneedle array platforms are a promising technology for vaccine delivery, due to their ease of administration with no sharp waste generated, small size, possibility of targeted delivery to the specified skin depth and efficacious delivery of different vaccine formulations, including viral vectors. Areas covered: Attributes and challenges of the most promising viral vector candidates that have advanced to the clinic and that have been leveraged for skin delivery by microneedles; The importance of understanding the immunobiology of antigen-presenting cells in the skin, in particular dendritic cells, in order to generate further improved skin vaccination strategies; recent studies where viral vectors expressing various antigens have been coupled with microneedle technology to examine their potential for improved vaccination. Expert opinion: Simple, economic and efficacious vaccine delivery methods are needed to improve health outcomes and manage possible outbreaks of new emerging viruses. Understanding what innate/inflammatory signals are required to induce both immediate and long-term responses remains a major hurdle in the development of the effective vaccines. One approach to meet these needs is microneedle-mediated viral vector vaccination. In order for this technology to fulfil this potential the industry must invest significantly to further develop its design, production, biosafety, delivery and large-scale manufacturing.

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.

Immune Response to Recombinant Adenovirus in Humans: Capsid Components from Viral Input Are Targets for Vector-Specific Cytotoxic T Lymphocytes

Science.gov (United States)

Molinier-Frenkel, Valérie; Gahery-Segard, Hanne; Mehtali, Majid; Le Boulaire, Christophe; Ribault, Sébastien; Boulanger, Pierre; Tursz, Thomas; Guillet, Jean-Gérard; Farace, Françoise

2000-01-01

We previously demonstrated that a single injection of 109 PFU of recombinant adenovirus into patients induces strong vector-specific immune responses (H. Gahéry-Ségard, V. Molinier-Frenkel, C. Le Boulaire, P. Saulnier, P. Opolon, R. Lengagne, E. Gautier, A. Le Cesne, L. Zitvogel, A. Venet, C. Schatz, M. Courtney, T. Le Chevalier, T. Tursz, J.-G. Guillet, and F. Farace, J. Clin. Investig. 100:2218–2226, 1997). In the present study we analyzed the mechanism of vector recognition by cytotoxic T lymphocytes (CTL). CD8+ CTL lines were derived from two patients and maintained in long-term cultures. Target cell infections with E1-deleted and E1-plus E2-deleted adenoviruses, as well as transcription-blocking experiments with actinomycin D, revealed that host T-cell recognition did not require viral gene transcription. Target cells treated with brefeldin A were not lysed, indicating that viral input protein-derived peptides are associated with HLA class I molecules. Using recombinant capsid component-loaded targets, we observed that the three major proteins could be recognized. These results raise the question of the use of multideleted adenoviruses for gene therapy in the quest to diminish antivector CTL responses. PMID:10906225

Viral Infections in Pregnancy: A Focus on Ebola Virus.

Science.gov (United States)

Olgun, Nicole S

2018-01-30

During gestation, the immune response of the placenta to viruses and other pathogens plays an important role in determining a pregnant woman's vulnerability toward infectious diseases. Located at the maternal- fetal interface, trophoblast cells serve to minimize the spread of viruses between the host and developing fetus through an intricate system of innate antiviral immune signaling. Adverse pregnancy outcomes, ranging from learning disabilities to preterm birth and fetal death, are all documented results of a viral breach in the placental barrier. Viral infections during pregnancy can also be spread through blood and vaginal secretions, and during the post-natal period, via breast milk. Thus, even in the absence of vertical transmission of viral infection to the fetus, maternal health can still be compromised and threaten the pregnancy. The most common viral DNA isolates found in gestation are adenovirus, cytomegalovirus, and enterovirus. However, with the recent pandemic of Ebola virus, and the first documented case of a neonate to survive due to experimental therapies in 2017, it is becoming increasingly apparent that the changing roles and impacts of viral infection during pregnancy needs to be better understood, while strategies to minimize adverse pregnancy outcomes need to be identified. This review focuses on the adverse impacts of viral infection during gestation, with an emphasis on Ebola virus. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

APLASTIC ANEMIA AND VIRAL HEPATITIS

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Laura Cudillo

2009-11-01

Liver histology is characterized by T cell infiltrating the parenchyma as reported in acute hepatitis. Recently in HAA it has been demonstrated intrahepatic  and blood lymphocytes with  T cell repertoire similar to that of confirmed viral acute hepatitis. The expanded T cell clones return to a normal distribution after response to immunosuppressive treatment, suggesting the antigen or T cell clearance. Therapeutic options are the same as acquired aplastic anemia.

Tracking of peptide-specific CD4+ T-cell responses after an acute resolving viral infection: a study of parvovirus B19

DEFF Research Database (Denmark)

Kasprowicz, Victoria; Isa, Adiba; Tolfvenstam, Thomas

2006-01-01

The evolution of peptide-specific CD4(+) T-cell responses to acute viral infections of humans is poorly understood. We analyzed the response to parvovirus B19 (B19), a ubiquitous and clinically significant pathogen with a compact and conserved genome. The magnitude and breadth of the CD4(+) T......-cell response to the two B19 capsid proteins were investigated using a set of overlapping peptides and gamma interferon-specific enzyme-linked immunospot assays of peripheral blood mononuclear cells (PBMCs) from a cohort of acutely infected individuals who presented with acute arthropathy. These were compared...... to those for a cohort of B19-specific immunoglobulin M-negative (IgM(-)), IgG(+) remotely infected individuals. Both cohorts of individuals were found to make broad CD4(+) responses. However, while the responses following acute infection were detectable ex vivo, responses in remotely infected individuals...

Policy responses to viral hepatitis B and C among people who inject drugs in Member States of the WHO European region

DEFF Research Database (Denmark)

Spina, Alexander; Eramova, Irina; Lazarus, Jeffrey V

2014-01-01

BACKGROUND: Unsafe injections, through infectious bodily fluids, are a major route of transmission for hepatitis B and C. Viral hepatitis burden among people who inject drugs is particularly high in many Member States of central and Eastern Europe while national capacity and willingness to address......, with less than one-third reportedly conducting regular serosurveys among people who inject drugs. CONCLUSIONS: Findings highlight key gaps requiring attention in order to improve national policies and programmes in the region and ensure an adequate response to injection drug use-associated viral hepatitis...... of a national policy for hepatitis prevention and control; however less than one-third (27%) reported having written national strategies. Under half of the responding Member States reported holding events for World Hepatitis Day 2012. One-fifth reported offering hepatitis B and C testing free of charge...

Oncolytic Viral Therapy and the Immune System: A Double-Edged Sword Against Cancer.

Science.gov (United States)

Marelli, Giulia; Howells, Anwen; Lemoine, Nicholas R; Wang, Yaohe

2018-01-01

Oncolytic viral therapy is a new promising strategy against cancer. Oncolytic viruses (OVs) can replicate in cancer cells but not in normal cells, leading to lysis of the tumor mass. Beside this primary effect, OVs can also stimulate the immune system. Tumors are an immuno-suppressive environment in which the immune system is silenced in order to avoid the immune response against cancer cells. The delivery of OVs into the tumor wakes up the immune system so that it can facilitate a strong and durable response against the tumor itself. Both innate and adaptive immune responses contribute to this process, producing an immune response against tumor antigens and facilitating immunological memory. However, viruses are recognized by the immune system as pathogens and the consequent anti-viral response could represent a big hurdle for OVs. Finding a balance between anti-tumor and anti-viral immunity is, under this new light, a priority for researchers. In this review, we provide an overview of the various ways in which different components of the immune system can be allied with OVs. We have analyzed the different immune responses in order to highlight the new and promising perspectives leading to increased anti-tumor response and decreased immune reaction to the OVs.

Prediction of fibrosis progression in chronic viral hepatitis

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Grace Lai-Hung Wong

2014-09-01

Full Text Available Prediction of liver fibrosis progression has a key role in the management of chronic viral hepatitis, as it will be translated into the future risk of cirrhosis and its various complications including hepatocellular carcinoma. Both hepatitis B and C viruses mainly lead to fibrogenesis induced by chronic inflammation and a continuous wound healing response. At the same time direct and indirect profibrogenic responses are also elicited by the viral infection. There are a handful of well-established risk factors for fibrosis progression including older age, male gender, alcohol use, high viral load and co-infection with other viruses. Metabolic syndrome is an evolving risk factor of fibrosis progression. The new notion of regression of advanced fibrosis or even cirrhosis is now strongly supported various clinical studies. Even liver biopsy retains its important role in the assessment of fibrosis progression, various non-invasive assessments have been adopted widely because of their non-invasiveness, which facilitates serial applications in large cohorts of subjects. Transient elastography is one of the most validated tools which has both diagnostic and prognostic role. As there is no single perfect test for liver fibrosis assessment, algorithms combining the most validated noninvasive methods should be considered as initial screening tools.

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...

PIWIs Go Viral: Arbovirus-Derived piRNAs in Vector Mosquitoes.

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Pascal Miesen

2016-12-01

Full Text Available Vector mosquitoes are responsible for transmission of the majority of arthropod-borne (arbo- viruses. Virus replication in these vectors needs to be sufficiently high to permit efficient virus transfer to vertebrate hosts. The mosquito immune response therefore is a key determinant for arbovirus transmission. Mosquito antiviral immunity is primarily mediated by the small interfering RNA pathway. Besides this well-established antiviral machinery, the PIWI-interacting RNA (piRNA pathway processes viral RNA into piRNAs. In recent years, significant progress has been made in characterizing the biogenesis and function of these viral piRNAs. In this review, we discuss these developments, identify knowledge gaps, and suggest directions for future research.

Cognitive-behavioral therapy as continuation treatment to sustain response after electroconvulsive therapy in depression: a randomized controlled trial.

Science.gov (United States)

Brakemeier, Eva-Lotta; Merkl, Angela; Wilbertz, Gregor; Quante, Arnim; Regen, Francesca; Bührsch, Nicole; van Hall, Franziska; Kischkel, Eva; Danker-Hopfe, Heidi; Anghelescu, Ion; Heuser, Isabella; Kathmann, Norbert; Bajbouj, Malek

2014-08-01

Although electroconvulsive therapy (ECT) is the most effective acute antidepressant intervention, sustained response rates are low. It has never been systematically assessed whether psychotherapy, continuation ECT, or antidepressant medication is the most efficacious intervention to maintain initial treatment response. In a prospective, randomized clinical trial, 90 inpatients with major depressive disorder (MDD) were treated with right unilateral ultra-brief acute ECT. Electroconvulsive therapy responders received 6 months guideline-based antidepressant medication (MED) and were randomly assigned to add-on therapy with cognitive-behavioral group therapy (CBT-arm), add-on therapy with ultra-brief pulse continuation electroconvulsive therapy (ECT-arm), or no add-on therapy (MED-arm). After the 6 months of continuation treatment, patients were followed-up for another 6 months. The primary outcome parameter was the proportion of patients who remained well after 12 months. Of 90 MDD patients starting the acute phase, 70% responded and 47% remitted to acute ECT. After 6 months of continuation treatment, significant differences were observed in the three treatment arms with sustained response rates of 77% in the CBT-arm, 40% in the ECT-arm, and 44% in the MED-arm. After 12 months, these differences remained stable with sustained response rates of 65% in the CBT-arm, 28% in the ECT-arm, and 33% in the MED-arm. These results suggest that ultra-brief pulse ECT as a continuation treatment correlates with low sustained response rates. However, the main finding implicates cognitive-behavioral group therapy in combination with antidepressants might be an effective continuation treatment to sustain response after successful ECT in MDD patients. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

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

Integrated Platform for Automated Sustainable Demand Response in Smart Grids

Energy Technology Data Exchange (ETDEWEB)

Zois, Vassilis [Univ. of Southern California, Los Angeles, CA (United States). Dept. of Computer Science; Frincu, Marc [Univ. of Southern California, Los Angeles, CA (United States). Dept. of Electrical Engineering; Prasanna, Viktor K. [Univ. of Southern California, Los Angeles, CA (United States). Dept. of Electrical Engineering

2014-10-08

Demand Response(DR) is a common practice used by utility providers to regulate energy demand. It is used at periods of high demand to minimize the peak to average consumption ratio. Several methods have been Demand Response(DR) is a common praon using information about the baseline consumption and the consumption during DR. Our goal is to provide a sustainable reduction to ensure the elimination of peaks in demand. The proposed system includes an adaptation mechanism for when the provided solution does not meet the DR requirements. We conducted a series of experiments using consumption data from a real life micro grid to evaluate the efficiency as well as the robustness of our solution.

Increased cellular immune responses and CD4+ T-cell proliferation correlate with reduced plasma viral load in SIV challenged recombinant simian varicella virus - simian immunodeficiency virus (rSVV-SIV vaccinated rhesus macaques

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Pahar Bapi

2012-08-01

Full Text Available Abstract Background An effective AIDS vaccine remains one of the highest priorities in HIV-research. Our recent study showed that vaccination of rhesus macaques with recombinant simian varicella virus (rSVV vector – simian immunodeficiency virus (SIV envelope and gag genes, induced neutralizing antibodies and cellular immune responses to SIV and also significantly reduced plasma viral loads following intravenous pathogenic challenge with SIVMAC251/CX1. Findings The purpose of this study was to define cellular immunological correlates of protection in rSVV-SIV vaccinated and SIV challenged animals. Immunofluorescent staining and multifunctional assessment of SIV-specific T-cell responses were evaluated in both Experimental and Control vaccinated animal groups. Significant increases in the proliferating CD4+ T-cell population and polyfunctional T-cell responses were observed in all Experimental-vaccinated animals compared with the Control-vaccinated animals. Conclusions Increased CD4+ T-cell proliferation was significantly and inversely correlated with plasma viral load. Increased SIV-specific polyfunctional cytokine responses and increased proliferation of CD4+ T-cell may be crucial to control plasma viral loads in vaccinated and SIVMAC251/CX1 challenged macaques.

Dengue E Protein Domain III-Based DNA Immunisation Induces Strong Antibody Responses to All Four Viral Serotypes.

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Monica Poggianella

Full Text Available Dengue virus (DENV infection is a major emerging disease widely distributed throughout the tropical and subtropical regions of the world affecting several millions of people. Despite constants efforts, no specific treatment or effective vaccine is yet available. Here we show a novel design of a DNA immunisation strategy that resulted in the induction of strong antibody responses with high neutralisation titres in mice against all four viral serotypes. The immunogenic molecule is an engineered version of the domain III (DIII of the virus E protein fused to the dimerising CH3 domain of the IgG immunoglobulin H chain. The DIII sequences were also codon-optimised for expression in mammalian cells. While DIII alone is very poorly secreted, the codon-optimised fusion protein is rightly expressed, folded and secreted at high levels, thus inducing strong antibody responses. Mice were immunised using gene-gun technology, an efficient way of intradermal delivery of the plasmid DNA, and the vaccine was able to induce neutralising titres against all serotypes. Additionally, all sera showed reactivity to a recombinant DIII version and the recombinant E protein produced and secreted from mammalian cells in a mono-biotinylated form when tested in a conformational ELISA. Sera were also highly reactive to infective viral particles in a virus-capture ELISA and specific for each serotype as revealed by the low cross-reactive and cross-neutralising activities. The serotype specific sera did not induce antibody dependent enhancement of infection (ADE in non-homologous virus serotypes. A tetravalent immunisation protocol in mice showed induction of neutralising antibodies against all four dengue serotypes as well.

Social responsibility and sustainability in Spanish university libraries: questioning the discourse from critical analysis perspectives

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M. Engracia Martin Valdunciel

2018-03-01

Full Text Available The paper focus on a critical analysis of a discursive formation in Spanish academic libraries: social responsibility and sustainability. The concepts that make up the discourse are historically contextualized in order to clarify their origin and social affiliation. Although the enunciation of social responsibility and sustainability content is formulated ambiguously, its articulation as a discursive practice within the framework of the new corporate management university libraries leads us to infer bias in their rhetorical formulation. We consider that, from a fuzzy concept and its integration into technocratic practices, the discourse can be used as a tool for legitimizing the deregulation of public educational institutions.

Global Avian Influenza Surveillance in Wild Birds: A Strategy to Capture Viral Diversity

Science.gov (United States)

Machalaba, Catherine C.; Elwood, Sarah E.; Forcella, Simona; Smith, Kristine M.; Hamilton, Keith; Jebara, Karim B.; Swayne, David E.; Webby, Richard J.; Mumford, Elizabeth; Mazet, Jonna A.K.; Gaidet, Nicolas; Daszak, Peter

2015-01-01

Wild birds play a major role in the evolution, maintenance, and spread of avian influenza viruses. However, surveillance for these viruses in wild birds is sporadic, geographically biased, and often limited to the last outbreak virus. To identify opportunities to optimize wild bird surveillance for understanding viral diversity, we reviewed responses to a World Organisation for Animal Health–administered survey, government reports to this organization, articles on Web of Knowledge, and the Influenza Research Database. At least 119 countries conducted avian influenza virus surveillance in wild birds during 2008–2013, but coordination and standardization was lacking among surveillance efforts, and most focused on limited subsets of influenza viruses. Given high financial and public health burdens of recent avian influenza outbreaks, we call for sustained, cost-effective investments in locations with high avian influenza diversity in wild birds and efforts to promote standardized sampling, testing, and reporting methods, including full-genome sequencing and sharing of isolates with the scientific community. PMID:25811221

Nuclear Imprisonment: Viral Strategies to Arrest Host mRNA Nuclear Export

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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.

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

Sustainable Eco Coastal Development Through Corporate Social Responsibility (CSR) Program

Science.gov (United States)

Rakhmanissazly, Arsi; Mursito Ardy, Yong; Abdullah

2017-02-01

Besides technical problems the company’s operational constraints that may effect high deficiency for the company is the company - community conflicts. Company - community conflict can also arise depends on the geographic conditions and characteristics of the community itself. Some studies has show that coastal community have higher level of social risk when compared to non-coastal community. Also, the coastal community ussually only rely on what sea provides as their main livelihood. Because of the level of education still contemtible the community couldn’t optimized the potential of their own area. Corporate Social Responsibility (CSR) har emerged as an important approach for addressing the social and environmental impact of company activities. Through CSR program, PT Pertamina EP Asset 3 Tambun Field (PEP) try to form value integration by utilizing resources from the community and the company by making sustainable eco - coastal living in Desa Tambaksari, Karawang, one of PEP working area. Using sustainable livelihood approach begin with compiling data by doing social mapping PEP has initiate the area to becoming Fish Processing Industry Centre. By implementing PDCA in every steps of the program, PEP has multiplied some other programs such as Organic Fish Feed Processing, Seaweed Farming and Waste Bank for Green Coastal Village. These program is PEP’s effort to create a sustainability environment by enhancing the community’s potentials as well as resolving social problems around Tambaksari. The most important result besides getting our license to operate from the community, is the community itself can grow into an eco coastal sustainable system.

Poor CD4 response despite viral suppression is associated with increased non-AIDS related mortality among HIV patients and their parents

DEFF Research Database (Denmark)

Helleberg, Marie; Kronborg, Gitte; Larsen, Carsten S

2012-01-01

association between poor CD4 response and increased risk of cardiovascular disease and cancer (IRR 1.6 (95%CI 0.8-3.2) and 1.6 (95%CI 0.6-4.8)). CONCLUSIONS:: poor CD4 increase after HAART is associated with adverse prognosis even in absence of severe immunosuppression. CD4 response in HIV patients......INTRODUCTION:: poor CD4 response to antiretroviral treatment (HAART) is associated with increased mortality. We analyzed the impact of CD4 increase on non-AIDS related morbidity and on mortality in HIV patients and their parents. METHODS:: mortality rates were estimated among 1,758 virally...... is associated with mortality among their parents, thus poor CD4 response may be caused by genetic factors, which might also affect morbidity and mortality in the HIV negative population....

From Sustainability-as-usual to Sustainability Excellence in Local Bioenergy Business

Directory of Open Access Journals (Sweden)

Heli Kasurinen

2017-06-01

Full Text Available Bioenergy business operators can significantly contribute to the sustainability of bioenergy systems. While research has addressed the maturity of corporate responsibility for sustainability, the maturity levels of bioenergy business have not been determined. The objectives of this research were to characterise the maturity levels of bioenergy corporate responsibility for sustainability and outline an approach by which companies can operate at the most mature sustainability excellence level. Literature, three workshops attended by bioenergy experts and a case study on biobutanol production in Brazil were used to develop the maturity model and approach. The results characterise the profitability, acceptability, and sustainability orientation maturity levels through sustainability questions and methods, and list the components of a systemic, holistic approach. Although the shift of business mindset from sustainability-as-usual to sustainability excellence is challenging, a systemic approach is necessary to broadly identify sustainability questions and a multitude of methods by which they can be answered.

Viral infections stimulate the metabolism and shape prokaryotic assemblages in submarine mud volcanoes.

Science.gov (United States)

Corinaldesi, Cinzia; Dell'Anno, Antonio; Danovaro, Roberto

2012-06-01

Mud volcanoes are geological structures in the oceans that have key roles in the functioning of the global ecosystem. Information on the dynamics of benthic viruses and their interactions with prokaryotes in mud volcano ecosystems is still completely lacking. We investigated the impact of viral infection on the mortality and assemblage structure of benthic prokaryotes of five mud volcanoes in the Mediterranean Sea. Mud volcano sediments promote high rates of viral production (1.65-7.89 × 10(9) viruses g(-1) d(-1)), viral-induced prokaryotic mortality (VIPM) (33% cells killed per day) and heterotrophic prokaryotic production (3.0-8.3 μgC g(-1) d(-1)) when compared with sediments outside the mud volcano area. The viral shunt (that is, the microbial biomass converted into dissolved organic matter as a result of viral infection, and thus diverted away from higher trophic levels) provides 49 mgC m(-2) d(-1), thus fuelling the metabolism of uninfected prokaryotes and contributing to the total C budget. Bacteria are the dominant components of prokaryotic assemblages in surface sediments of mud volcanoes, whereas archaea dominate the subsurface sediment layers. Multivariate multiple regression analyses show that prokaryotic assemblage composition is not only dependant on the geochemical features and processes of mud volcano ecosystems but also on synergistic interactions between bottom-up (that is, trophic resources) and top-down (that is, VIPM) controlling factors. Overall, these findings highlight the significant role of the viral shunt in sustaining the metabolism of prokaryotes and shaping their assemblage structure in mud volcano sediments, and they provide new clues for our understanding of the functioning of cold-seep ecosystems.

Company, Sustainability and Social Responsibility: Origins, Motivations, Critical and Practical Aspects.

Directory of Open Access Journals (Sweden)

Mariana Ribeiro Santiago

2015-12-01

Full Text Available The present paper analyzes the sustainability and its historical aspects, the emergence of global concern about the subject, with sustainable economic development and its major initiatives, from the effective involvement of the States in the discussions in the search for consensus in the quality of life on the planet, rationality in the exploitation of natural resources and concern for future generations. We research also the context of social responsibility (business, starting at historical aspect to following analyze its interrelationship as an instrument to combat the problem of social inequality and poverty, was discoursing on the possibility of state action while inducing corporate behavior on this theme, describing the concrete experience revealed in the actions of the Federal Public Ministry, through award-winning design that became known as "Green Cities / Meat Legal".

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.

Acute mucosal pathogenesis of feline immunodeficiency virus is independent of viral dose in vaginally infected cats

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Egan Erin A

2010-01-01

Full Text Available Abstract Background The mucosal pathogenesis of HIV has been shown to be an important feature of infection and disease progression. HIV-1 infection causes depletion of intestinal lamina propria CD4+ T cells (LPL, therefore, intestinal CD4+ T cell preservation may be a useful correlate of protection in evaluating vaccine candidates. Vaccine studies employing the cat/FIV and macaque/SIV models frequently use high doses of parenterally administered challenge virus to ensure high plasma viremia in control animals. However, it is unclear if loss of mucosal T cells would occur regardless of initial viral inoculum dose. The objective of this study was to determine the acute effect of viral dose on mucosal leukocytes and associated innate and adaptive immune responses. Results Cats were vaginally inoculated with a high, middle or low dose of cell-associated and cell-free FIV. PBMC, serum and plasma were assessed every two weeks with tissues assessed eight weeks following infection. We found that irrespective of mucosally administered viral dose, FIV infection was induced in all cats. However, viremia was present in only half of the cats, and viral dose was unrelated to the development of viremia. Importantly, regardless of viral dose, all cats experienced significant losses of intestinal CD4+ LPL and CD8+ intraepithelial lymphocytes (IEL. Innate immune responses by CD56+CD3- NK cells correlated with aviremia and apparent occult infection but did not protect mucosal T cells. CD4+ and CD8+ T cells in viremic cats were more likely to produce cytokines in response to Gag stimulation, whereas aviremic cats T cells tended to produce cytokines in response to Env stimulation. However, while cell-mediated immune responses in aviremic cats may have helped reduce viral replication, they could not be correlated to the levels of viremia. Robust production of anti-FIV antibodies was positively correlated with the magnitude of viremia. Conclusions Our results indicate

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....

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

Deciphering emerging Zika and dengue viral epidemics: Implications for global maternal–child health burden

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Ernest Tambo

2016-05-01

Full Text Available Summary: Since its discovery in 1947 in Uganda and control and eradication efforts have aimed at its vectors (Aedes mosquitoes in Latin America in the 1950s, an absolute neglect of Zika programs and interventions has been documented in Aedes endemic and epidemic-prone countries. The current unprecedented Zika viral epidemics and rapid spread in the Western hemisphere pose a substantial global threat, with associated anxiety and consequences. The lack of safe and effective drugs and vaccines against Zika or dengue epidemics further buttresses the realization from the West Africa Ebola outbreak that most emerging disease-prone countries are still poorly prepared for an emergency response. This paper examines knowledge gaps in both emerging and neglected arthropod-borne flavivirus infectious diseases associated with poverty and their implications for fostering local, national and regional emerging disease preparedness, effective and robust surveillance–response systems, sustained control and eventual elimination. Strengthening the regional and Global Health Flavivirus Surveillance-Response Network (GHFV-SRN with other models of socio-economic, climatic, environmental and ecological mitigation and adaptation strategies will be necessary to improve evidence-based national and global maternal–child health agenda and action plans. Keywords: Zika virus, Epidemics, Health, Preparedness, Surveillance, Maternal–child

ViralORFeome: an integrated database to generate a versatile collection of viral ORFs.

Science.gov (United States)

Pellet, J; Tafforeau, L; Lucas-Hourani, M; Navratil, V; Meyniel, L; Achaz, G; Guironnet-Paquet, A; Aublin-Gex, A; Caignard, G; Cassonnet, P; Chaboud, A; Chantier, T; Deloire, A; Demeret, C; Le Breton, M; Neveu, G; Jacotot, L; Vaglio, P; Delmotte, S; Gautier, C; Combet, C; Deleage, G; Favre, M; Tangy, F; Jacob, Y; Andre, P; Lotteau, V; Rabourdin-Combe, C; Vidalain, P O

2010-01-01

Large collections of protein-encoding open reading frames (ORFs) established in a versatile recombination-based cloning system have been instrumental to study protein functions in high-throughput assays. Such 'ORFeome' resources have been developed for several organisms but in virology, plasmid collections covering a significant fraction of the virosphere are still needed. In this perspective, we present ViralORFeome 1.0 (http://www.viralorfeome.com), an open-access database and management system that provides an integrated set of bioinformatic tools to clone viral ORFs in the Gateway(R) system. ViralORFeome provides a convenient interface to navigate through virus genome sequences, to design ORF-specific cloning primers, to validate the sequence of generated constructs and to browse established collections of virus ORFs. Most importantly, ViralORFeome has been designed to manage all possible variants or mutants of a given ORF so that the cloning procedure can be applied to any emerging virus strain. A subset of plasmid constructs generated with ViralORFeome platform has been tested with success for heterologous protein expression in different expression systems at proteome scale. ViralORFeome should provide our community with a framework to establish a large collection of virus ORF clones, an instrumental resource to determine functions, activities and binding partners of viral proteins.

How and When Retailers’ Sustainability Efforts Translate into Positive Consumer Responses: The Interplay Between Personal and Social Factors

NARCIS (Netherlands)

Hofenk, D.; Birgelen, M.J.H. van; Bloemer, J.M.M.; Semeijn, J.

2017-01-01

This study aims to address how (through which mechanisms) and when (under which conditions) retailers’ sustainability efforts translate into positive consumer responses. Hypotheses are developed and tested through a scenario-based experiment among 672 consumers. Retailers’ assortment sustainability

Sustainability Ethics Emergency and Media Responsibility in the Consumption Society

Directory of Open Access Journals (Sweden)

Rogério Bianchi de Araujo

2008-08-01

Full Text Available In this article, it is discussed the sustainable development and the importance of the environmental cause, in order to create models of development that consider the sustainability and environmental preservation for the future generations. The participation of all society is essential in this debate. The establishment of new habits that do not compromise the subsistence and the conscience of the real self-destruction possibility must be studied and analysed; they consist in challenging intentions, which detach the relevance and the moral duty of the media to restore a new ethics and a new way to understand the reality, as well as to divulge the impact of this different perception in the human life. Therefore occurs the requirement of a responsible compromise relating to the development, by way of understanding the biosphere as the social life basis, considering that, in these ecosystems, the human being is only one of the many species that live in an interdependence relationship.

Efficient Customer Selection for Sustainable Demand Response in Smart Grids

Energy Technology Data Exchange (ETDEWEB)

Zois, Vasileios; Frincu, Marc; Chelmis, Charalambos; Saeed, Muhammad Rizwan; Prasanna, Viktor K.

2014-11-03

Regulating the power consumption to avoid peaks in demand is a common practice. Demand Response(DR) is being used by utility providers to minimize costs or ensure system reliability. Although it has been used extensively there is a shortage of solutions dealing with dynamic DR. Past attempts focus on minimizing the load demand without considering the sustainability of the reduced energy. In this paper an efficient algorithm is presented which solves the problem of dynamic DR scheduling. Data from the USC campus micro grid were used to evaluate the efficiency as well as the robustness of the proposed solution. The targeted energy reduction is achieved with a maximum average approximation error of ≈ 0.7%. Sustainability of the reduced energy is achieved with respect to the optimal available solution providing a maximum average error less than 0.6%. It is also shown that a solution is provided with a low computational cost fulfilling the requirements of dynamic DR.

Viral capsid is a pathogen-associated molecular pattern in adenovirus keratitis.

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Ashish V Chintakuntlawar

2010-04-01

Full Text Available Human adenovirus (HAdV infection of the human eye, in particular serotypes 8, 19 and 37, induces the formation of corneal subepithelial leukocytic infiltrates. Using a unique mouse model of adenovirus keratitis, we studied the role of various virus-associated molecular patterns in subsequent innate immune responses of resident corneal cells to HAdV-37 infection. We found that neither viral DNA, viral gene expression, or viral replication was necessary for the development of keratitis. In contrast, empty viral capsid induced keratitis and a chemokine profile similar to intact virus. Transfected viral DNA did not induce leukocyte infiltration despite CCL2 expression similar to levels in virus infected corneas. Mice without toll-like receptor 9 (Tlr9 signaling developed clinical keratitis upon HAdV-37 infection similar to wild type mice, although the absolute numbers of activated monocytes in the cornea were less in Tlr9(-/- mice. Virus induced leukocytic infiltrates and chemokine expression in mouse cornea could be blocked by treatment with a peptide containing arginine glycine aspartic acid (RGD. These results demonstrate that adenovirus infection of the cornea induces chemokine expression and subsequent infiltration by leukocytes principally through RGD contact between viral capsid and the host cell, possibly through direct interaction between the viral capsid penton base and host cell integrins.

Granulomatous cheilitis: sustained response to combination of intralesional steroids, metronidazole and minocycline

International Nuclear Information System (INIS)

Dar, N.R.; Raza, N.; Nadeem, A.; Manzoor, A.

2007-01-01

Various conservative methods for treatment of labial swelling in patients with granulomatous cheilitis have been attempted, often with only moderate success. We report a case of granulomatous cheilitis who showed excellent sustained response to combination of intralesional steroids, metronidazole and minocycline for initial one month followed by prolonged maintenance treatment with minocycline alone. (author)

Comparison of the cross-antibody response induced in sheep by inactivated bovine viral diarrhoea virus 1 and Hobi-like pestivirus.

Science.gov (United States)

Decaro, Nicola; Mari, Viviana; Sciarretta, Rossana; Lucente, Maria Stella; Camero, Michele; Losurdo, Michele; Larocca, Vittorio; Colao, Valeriana; Cavaliere, Nicola; Lovero, Angela; Lorusso, Eleonora; Buonavoglia, Canio

2013-06-01

Hobi-like pestivirus, a new tentative species within genus Pestivirus, was firstly detected in foetal bovine serum batches and later associated to respiratory distress and reproductive failures in cattle. In the present study, the cross-antibody response between bovine viral diarrhoea virus 1 (BVDV-1) and the emerging pestivirus was evaluated in the sheep model. Ten sheep were immunised against BVDV-1 or Hobi-like pestivirus using inactivated preparations and the induced antibody responses were evaluated against the homologous and heterologous viruses. The results showed that heterologous antibody titres were significantly lower than the homologous ones, thus suggesting the need to develop specific vaccines against the emerging pestiviral species. Copyright © 2012 Elsevier Ltd. All rights reserved.

Counteracting Educational Injustice with Applied Critical Leadership: Culturally Responsive Practices Promoting Sustainable Change

Science.gov (United States)

Santamaría, Lorri J.; Santamaría, Andrés P.

2015-01-01

This contribution considers educational leadership practice to promote and sustain diversity. Comparative case studies are presented featuring educational leaders in the United States and New Zealand who counter injustice in their practice. The leaders' leadership practices responsive to the diversity presented in their schools offer…

Novel use of surveillance data to detect HIV-infected persons with sustained high viral load and durable virologic suppression in New York City.

Directory of Open Access Journals (Sweden)

Arpi S Terzian

Full Text Available Monitoring of the uptake and efficacy of ART in a population often relies on cross-sectional data, providing limited information that could be used to design specific targeted intervention programs. Using repeated measures of viral load (VL surveillance data, we aimed to estimate and characterize the proportion of persons living with HIV/AIDS (PLWHA in New York City (NYC with sustained high VL (SHVL and durably suppressed VL (DSVL.Retrospective cohort study of all persons reported to the NYC HIV Surveillance Registry who were alive and ≥12 years old by the end of 2005 and who had ≥2 VL tests in 2006 and 2007. SHVL and DSVL were defined as PLWHA with 2 consecutive VLs ≥100,000 copies/mL and PLWHA with all VLs ≤400 copies/mL, respectively. Logistic regression models using generalized estimating equations were used to model the association between SHVL and covariates. There were 56,836 PLWHA, of whom 7% had SHVL and 38% had DSVL. Compared to those without SHVL, persons with SHVL were more likely to be younger, black and have injection drug use (IDU risk. PLWHA with SHVL were more likely to die by 2007 and be younger by nearly ten years, on average.Nearly 60% of PLWHA in 2005 had multiple VLs, of whom almost 40% had DSVL, suggesting successful ART uptake. A small proportion had SHVL, representing groups known to have suboptimal engagement in care. This group should be targeted for additional outreach to reduce morbidity and secondary transmission. Measures based on longitudinal analyses of surveillance data in conjunction with cross-sectional measures such as community viral load represent more precise and powerful tools for monitoring ART effectiveness and potential impact on disease transmission than cross-sectional measures alone.

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

Corporate Social Responsibility as a tool to ensure sustainability and competitiveness of the monotowns

Directory of Open Access Journals (Sweden)

Sechina Asya

2016-01-01

Full Text Available Learning the basics and trends of the development of corporate social responsibility is connected with the need to identify the reasons for its humanization and globalization in today’s business environment. Sustainability and competitiveness is one of the important characteristics of the company today. The characteristic of the Russian practice of corporate social responsibility highlights its features, levels and forms of development. Monotowns are a highly vulnerable category of Russian communities; they are in constant risk due to their specific characteristics and largely the underdeveloped economic base. The problems of monoprofile towns usually do not have simple solutions. They require a comprehensive approach and taking account of the existence and development of each monotown. The article deals with the concept of a monoprofile town, stages of formation and evolution of this phenomenon in the Russian economy. There is the problem of application of corporate social responsibility in the practice of Russian monotowns. There is the characteristic advantage of social responsibility in the monotowns. There is the influence of the organizations activities operating in a monotown on the quality of life of the population. There is the necessity of the use of corporate social responsibility in monotowns to enhance their sustainability and improve competitiveness.

Chemokines cooperate with TNF to provide protective anti-viral immunity and to enhance inflammation.

Science.gov (United States)

Alejo, Alí; Ruiz-Argüello, M Begoña; Pontejo, Sergio M; Fernández de Marco, María Del Mar; Saraiva, Margarida; Hernáez, Bruno; Alcamí, Antonio

2018-05-03

The role of cytokines and chemokines in anti-viral defense has been demonstrated, but their relative contribution to protective anti-viral responses in vivo is not fully understood. Cytokine response modifier D (CrmD) is a secreted receptor for TNF and lymphotoxin containing the smallpox virus-encoded chemokine receptor (SECRET) domain and is expressed by ectromelia virus, the causative agent of the smallpox-like disease mousepox. Here we show that CrmD is an essential virulence factor that controls natural killer cell activation and allows progression of fatal mousepox, and demonstrate that both SECRET and TNF binding domains are required for full CrmD activity. Vaccination with recombinant CrmD protects animals from lethal mousepox. These results indicate that a specific set of chemokines enhance the inflammatory and protective anti-viral responses mediated by TNF and lymphotoxin, and illustrate how viruses optimize anti-TNF strategies with the addition of a chemokine binding domain as soluble decoy receptors.

Ex vivo screening for immunodominant viral epitopes by quantitative real time polymerase chain reaction (qRT-PCR

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Nagorsen Dirk

2003-12-01

Full Text Available Abstract The identification and characterization of viral epitopes across the Human Leukocyte Antigen (HLA polymorphism is critical for the development of actives-specific or adoptive immunotherapy of virally-mediated diseases. This work investigates whether cytokine mRNA transcripts could be used to identify epitope-specific HLA-restricted memory T lymphocytes reactivity directly in fresh peripheral blood mononuclear cells (PBMCs from viral-seropositive individuals in response to ex vivo antigen recall. PBMCs from HLA-A*0201 healthy donors, seropositive for Cytomegalovirus (CMV and Influenza (Flu, were exposed for different periods and at different cell concentrations to the HLA-A*0201-restricted viral FluM158–66 and CMVpp65495–503 peptides. Quantitative real time PCR (qRT-PCR was employed to evaluate memory T lymphocyte immune reactivation by measuring the production of mRNA encoding four cytokines: Interferon-γ (IFN-γ, Interleukin-2 (IL-2, Interleukin-4 (IL-4, and Interleukin-10 (IL-10. We could characterize cytokine expression kinetics that illustrated how cytokine mRNA levels could be used as ex vivo indicators of T cell reactivity. Particularly, IFN-γ mRNA transcripts could be consistently detected within 3 to 12 hours of short-term stimulation in levels sufficient to screen for HLA-restricted viral immune responses in seropositive subjects. This strategy will enhance the efficiency of the identification of viral epitopes independently of the individual HLA phenotype and could be used to follow the intensity of immune responses during disease progression or in response to in vivo antigen-specific immunization.

Ex vivo screening for immunodominant viral epitopes by quantitative real time polymerase chain reaction (qRT-PCR)

Science.gov (United States)

Provenzano, Maurizio; Mocellin, Simone; Bonginelli, Paola; Nagorsen, Dirk; Kwon, Seog-Woon; Stroncek, David

2003-01-01

The identification and characterization of viral epitopes across the Human Leukocyte Antigen (HLA) polymorphism is critical for the development of actives-specific or adoptive immunotherapy of virally-mediated diseases. This work investigates whether cytokine mRNA transcripts could be used to identify epitope-specific HLA-restricted memory T lymphocytes reactivity directly in fresh peripheral blood mononuclear cells (PBMCs) from viral-seropositive individuals in response to ex vivo antigen recall. PBMCs from HLA-A*0201 healthy donors, seropositive for Cytomegalovirus (CMV) and Influenza (Flu), were exposed for different periods and at different cell concentrations to the HLA-A*0201-restricted viral FluM158–66 and CMVpp65495–503 peptides. Quantitative real time PCR (qRT-PCR) was employed to evaluate memory T lymphocyte immune reactivation by measuring the production of mRNA encoding four cytokines: Interferon-γ (IFN-γ), Interleukin-2 (IL-2), Interleukin-4 (IL-4), and Interleukin-10 (IL-10). We could characterize cytokine expression kinetics that illustrated how cytokine mRNA levels could be used as ex vivo indicators of T cell reactivity. Particularly, IFN-γ mRNA transcripts could be consistently detected within 3 to 12 hours of short-term stimulation in levels sufficient to screen for HLA-restricted viral immune responses in seropositive subjects. This strategy will enhance the efficiency of the identification of viral epitopes independently of the individual HLA phenotype and could be used to follow the intensity of immune responses during disease progression or in response to in vivo antigen-specific immunization. PMID:14675481

Treatment of Decompensated Cirrhosis Secondary to Hepatitis C with Antiviral Therapy

International Nuclear Information System (INIS)

Khokhar, N.; Qureshi, M.O.; Niazi, T.K.

2013-01-01

Objective: To treat decompensated hepatitis C patient with interferon, ribavirin and amantidine to ascertain the sustained viral response. Study Design: Descriptive study. Place and Duration of Study: Shifa International Hospital, Islamabad, from January 2007 to January 2012. Methodology: HCV PCR patients with decompensated hepatitis C, who had developed a complication like ascites, encephalopathy or variceal bleeding were included in the study. Those with uncontrolled ascites or other complications were excluded. Treatment with standard interferon 3 miU subcutaneously three times a week along with ribavirin 800 mg to 1200 mg and amantidine 100 mg b.i.d. was administered for 12 months. Patients were followed every month with CBC and ALT and HCV PCR was performed after 3 months to document early viral response. They had HCV PCR at the end of the treatment to document end of treatment response. All were further followed for another 6 months at monthly intervals and HCV PCR was performed at the end of this period to document sustained viral response. Results: In all, 165 patients were treated. Treatment had to be discontinued in 42 (26%) patients. Out of these, 16 patients died. Thus, 123 completed treatment. Sustained viral response was documented in 58 out of the 123 (47%) patients. Hepatic encephalopathy, gastrointestinal bleeding, sepsis and development of ascites were the major complications during treatment. Conclusion: Forty seven percent of patients with decompensated hepatitis C cirrhosis were able to achieve sustained viral response after one year treatment with anti-viral therapy. However, complications developed during treatment and, therefore, frequent and close monitoring is necessary in these patients. (author)

Responsible tourism as an agent of sustainable and socially-conscious development

Directory of Open Access Journals (Sweden)

Pierluigi Musarò

2014-10-01

Full Text Available Despite the variety of banalities that are often associated with trips and vacations as mass consumption, the study of tourism – due to the commitment of social, economic, political and cultural energy - remains one of the predominant inputs for understanding contemporary society and the new social hierarchies that distinguish it. Tourism, which is  increasingly seen as a process that has become integral to social and cultural life, also plays an essential role in the social and spatial dialectic that gives meaning to the places. Focusing tourism through the lens of "productive consumption" developed by Cultural Studies, the paper moves from the assumption that responsible tourism can be analyzed in the broader paradigm of relational goods to explore the role of responsible tourism as a possible way of sustainable and responsible development.

Non-oncogenic Acute Viral Infections Disrupt Anti-cancer Responses and Lead to Accelerated Cancer-Specific Host Death

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Frederick J. Kohlhapp

2016-10-01

Full Text Available In light of increased cancer prevalence and cancer-specific deaths in patients with infections, we investigated whether infections alter anti-tumor immune responses. We report that acute influenza infection of the lung promotes distal melanoma growth in the dermis and leads to accelerated cancer-specific host death. Furthermore, we show that during influenza infection, anti-melanoma CD8+ T cells are shunted from the tumor to the infection site, where they express high levels of the inhibitory receptor programmed cell death protein 1 (PD-1. Immunotherapy to block PD-1 reverses this loss of anti-tumor CD8+ T cells from the tumor and decreases infection-induced tumor growth. Our findings show that acute non-oncogenic infection can promote cancer growth, raising concerns regarding acute viral illness sequelae. They also suggest an unexpected role for PD-1 blockade in cancer immunotherapy and provide insight into the immune response when faced with concomitant challenges.

The role of biochemical variations and genotype testing in determining the virological response of patients infected with hepatitis C virus

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Abid Shoukat

2018-01-01

Full Text Available Background: In hepatitis C virus (HCV, infection viral and IL28B genotype along with many clinical and biochemical factors can influence response rates to pegylated interferon plus ribavirin (Peg-IFN-a/R therapy and progression to chronic hepatitis C (CHC. Aims: The present study was conducted to determine the effect of biochemical and risk factors on treatment outcome in CHC patients in relation to their viral and host genotype. Settings and Design: The present study was a prospective Pe- IFN efficacy study consisting of Peg-IFN-a/R therapy for 24–48 weeks including 250 HCV infected patients. Materials and Methods: Biochemical parameters were determined by Beckman Coulter AU680 automated analyzer. HCV and Interleukin 28B (IL28B genotyping were carried out by polymerase chain reaction-restriction fragment length polymorphism and viral load was determined by quantitative real-time PCR. Results: Wild outnumbered the variant genotypes in rs 12979860, rs 12980275, and rs 8099917 SNP of IL28B gene. Sustained virological response (SVR SVR and viral genotype were significantly associated with age, hepatic steatosis, low-grade varices, and serum aspartate transaminase levels (at the end of treatment (P < 0.05. In addition, SVR was significantly influenced by body mass index (BMI, insulin resistance, serum low-density lipoprotein , and ferritin levels (P < 0.05. Viral genotype 1 infected patients had higher serum cholesterol and triglyceride levels (P < 0.05. Conclusions: Although the IL28B sequence variation is the major factor that can influence response rates to antiviral therapy, viral and biochemical factors also have a definite role to play in the diagnosis, etiology, and treatment outcome in HCV-infected patients.

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...

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...

Viral Hepatitis Strategic Information to Achieve Elimination by 2030: Key Elements for HIV Program Managers.

Science.gov (United States)

Hutin, Yvan; Low-Beer, Daniel; Bergeri, Isabel; Hess, Sarah; Garcia-Calleja, Jesus Maria; Hayashi, Chika; Mozalevskis, Antons; Rinder Stengaard, Annemarie; Sabin, Keith; Harmanci, Hande; Bulterys, Marc

2017-12-15

Evidence documenting the global burden of disease from viral hepatitis was essential for the World Health Assembly to endorse the first Global Health Sector Strategy (GHSS) on viral hepatitis in May 2016. The GHSS on viral hepatitis proposes to eliminate viral hepatitis as a public health threat by 2030. The GHSS on viral hepatitis is in line with targets for HIV infection and tuberculosis as part of the Sustainable Development Goals. As coordination between hepatitis and HIV programs aims to optimize the use of resources, guidance is also needed to align the strategic information components of the 2 programs. The World Health Organization monitoring and evaluation framework for viral hepatitis B and C follows an approach similar to the one of HIV, including components on the following: (1) context (prevalence of infection), (2) input, (3) output and outcome, including the cascade of prevention and treatment, and (4) impact (incidence and mortality). Data systems that are needed to inform this framework include (1) surveillance for acute hepatitis, chronic infections, and sequelae and (2) program data documenting prevention and treatment, which for the latter includes a database of patients. Overall, the commonalities between HIV and hepatitis at the strategic, policy, technical, and implementation levels justify coordination, strategic linkage, or integration, depending on the type of HIV and viral hepatitis epidemics. Strategic information is a critical area of this alignment under the principle of what gets measured gets done. It is facilitated because the monitoring and evaluation frameworks for HIV and viral hepatitis were constructed using a similar approach. However, for areas where elimination of viral hepatitis requires data that cannot be collected through the HIV program, collaborations are needed with immunization, communicable disease control, tuberculosis, and hepatology centers to ensure collection of information for the remaining indicators. �

Withholding and withdrawing life-sustaining treatment: criminal responsibility for established medical practice?

Science.gov (United States)

White, Ben; Willmott, Lindy; Allen, John

2010-05-01

The law recognises the right of a competent adult to refuse medical treatment even if this will lead to death. Guardianship and other legislation also facilitates the making of decisions to withhold or withdraw life-sustaining treatment in certain circumstances. Despite this apparent endorsement that such decisions can be lawful, doubts have been raised in Queensland about whether decisions to withhold or withdraw life-sustaining treatment would contravene the criminal law, and particularly the duty imposed by the Criminal Code (Qld) to provide the "necessaries of life". This article considers this tension in the law and examines various arguments that might allow for such decisions to be made lawfully. It ultimately concludes, however, that criminal responsibility may still arise and so reform is needed.

P53-mediated rapid induction of apoptosis conveys resistance to viral infection in Drosophila melanogaster.

Directory of Open Access Journals (Sweden)

Bo Liu

2013-02-01

Full Text Available Arthropod-borne pathogens account for millions of deaths each year. Understanding the genetic mechanisms controlling vector susceptibility to pathogens has profound implications for developing novel strategies for controlling insect-transmitted infectious diseases. The fact that many viruses carry genes that have anti-apoptotic activity has long led to the hypothesis that induction of apoptosis could be a fundamental innate immune response. However, the cellular mechanisms mediating the induction of apoptosis following viral infection remained enigmatic, which has prevented experimental verification of the functional significance of apoptosis in limiting viral infection in insects. In addition, studies with cultured insect cells have shown that there is sometimes a lack of apoptosis, or the pro-apoptotic response happens relatively late, thus casting doubt on the functional significance of apoptosis as an innate immunity. Using in vivo mosquito models and the native route of infection, we found that there is a rapid induction of reaper-like pro-apoptotic genes within a few hours following exposure to DNA or RNA viruses. Recapitulating a similar response in Drosophila, we found that this rapid induction of apoptosis requires the function of P53 and is mediated by a stress-responsive regulatory region upstream of reaper. More importantly, we showed that the rapid induction of apoptosis is responsible for preventing the expression of viral genes and blocking the infection. Genetic changes influencing this rapid induction of reaper-like pro-apoptotic genes led to significant differences in susceptibility to viral infection.

[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

Association between Leptin and Complement in Hepatitis C Patients with Viral Clearance: Homeostasis of Metabolism and Immunity.

Science.gov (United States)

Chang, Ming-Ling; Kuo, Chia-Jung; Huang, Hsin-Chih; Chu, Yin-Yi; Chiu, Cheng-Tang

2016-01-01

The association between leptin and complement in hepatitis C virus (HCV) infection remains unknown. A prospective study was conducted including 474 (250 genotype 1, 224 genotype 2) consecutive chronic hepatitis C (CHC) patients who had completed an anti-HCV therapy course and undergone pre-therapy and 24-week post-therapy assessments of interferon λ3-rs12979860 and HCV RNA/genotypes, anthropometric measurements, metabolic and liver profiles, and complement component 3 (C3), C4, and leptin levels. Of the 474 patients, 395 had a sustained virological response (SVR). Pre-therapy leptin levels did not differ between patients with and without an SVR. Univariate and multivariate analyses showed that sex (pre- and post-therapy, pimmune and metabolic homeostasis through association with C4 and TC. Positive alterations in C4 and TC levels reflect viral clearance after therapy in CHC patients.

The Impacts of Social Responsibility and Ownership Structure on Sustainable Financial Development of China’s Energy Industry

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Ye Feng

2018-01-01

Full Text Available In the analysis, we integrated stakeholder and agency theories to explore the connection between corporate social responsibility (CSR and sustainable financial development by considering the moderating effect of ownership structure. After empirical analysis, we found the following conclusions. First, the short-term and long-term economic performance is positively affected by CSR, which leads to sustainable financial development. Second, ownership circulation has a positive relationship with economic performance in the short run, which short-term profit increases as ownership circulation strengthens. Third, the effect of CSR on short-term economic performance is moderated by ownership structure. Excessive concentrated ownership may lead to decisions that do not satisfy all key stakeholders and may reduce the positive effect of CSR on economic performance. Finally, we suggest that Chinese energy companies should pay more attention to improving corporate social responsibility to maintain good economic performance and develop sustainable competitive advantage. Meanwhile, companies should optimize ownership concentration to avoid weakening the positive effects of social responsibility on short-term economic performance.

Impact of corporate social responsibility on sustainable enterprise development

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Danubianu Mirela

2017-06-01

Top management endorsement and nomination of a complex CSR teamDeveloping formal company CSR policy documentsSelecting and engaging the company’s stakeholders as early as possible.Building a Project Advisory Board – useful in every modern managerial tool application should guide the progress toward CSR.An external facilitator would help solve internal conflicts.An audit of what CSR represents for the Company, what are the CSR options, e.g., promoting a “green company” profile, what would be the best impact of philanthropy and community volunteering, etc.Generate a CSR portfolio of actions, setting deadlines, responsibilities and allocating resources, establishing communication, reporting, monitoring and corrective proceduresupgrading the sustainable enterprise strategy.

Sustainable Entrepreneurship Orientation: A Reflection on Status-Quo Research on Factors Facilitating Responsible Managerial Practices

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Sascha Kraus

2018-02-01

Full Text Available With the global financial system having undergone vast changes since the financial crisis of 2007, scientific research concerning the investor’s point of view on sustainable investments has drastically increased. However, there remains a lack of research focused on the entrepreneur’s angle regarding sustainable oriented investments. The aim of this paper is to contribute to the understanding of sustainable financial markets by bringing together entrepreneurial and financial research. This paper provides a structured literature review, based on which the authors identify three relevant levels that they believe have an effect on the successful implementation of managerial sustainable practices; these are the individual, the firm, and the contextual levels. The results show that on the individual level sustainable entrepreneurs tend to derive their will to act more sustainably from their personal values or traits. On the organizational level, though, it can be concluded that an small and medium sized enterprise’s internal culture and the reconfiguration of resources are critical determinants for adopting a sustainable entrepreneurial orientation. Finally, on the contextual level, researchers have focused on a better understanding of how entrepreneurs can help society and the environment through sustainable entrepreneurship, and how they can act as role models or change agents in light of the fact that the choice of investing or financing based on sustainability is still in its infancy. By providing an overview on facilitating factors for responsible managerial practices on the entrepreneur’s side, this research contributes to a better understanding for both theory and practice on how sustainable practices can be implemented and facilitated.

Changes in human dendritic cell number and function in severe obesity may contribute to increased susceptibility to viral infection.

LENUS (Irish Health Repository)

O'Shea, D

2013-02-26

Dendritic cells (DCs) are key immune sentinels linking the innate and adaptive immune systems. DCs recognise danger signals and initiate T-cell tolerance, memory and polarisation. They are critical cells in responding to a viral illness. Obese individuals have been shown to have an impaired response to vaccinations against virally mediated conditions and to have an increased susceptibility to multi-organ failure in response to viral illness. We investigated if DCs are altered in an obese cohort (mean body mass index 51.7±7.3 kg m(-2)), ultimately resulting in differential T-cell responses. Circulating DCs were found to be significantly decreased in the obese compared with the lean cohort (0.82% vs 2.53%). Following Toll-like receptor stimulation, compared with lean controls, DCs generated from the obese cohort upregulated significantly less CD83 (40% vs 17% mean fluorescence intensity), a molecule implicated in the elicitation of T-cell responses, particularly viral responses. Obese DCs produced twofold more of the immunosuppressive cytokine interleukin (IL)-10 than lean controls, and in turn stimulated fourfold more IL-4-production from allogenic naive T cells. We conclude that obesity negatively impacts the ability of DCs to mature and elicit appropriate T-cell responses to a general stimulus. This may contribute to the increased susceptibility to viral infection observed in severe obesity.International Journal of Obesity advance online publication, 26 February 2013; doi:10.1038\\/ijo.2013.16.

Associations between national viral hepatitis policies/programmes and country-level socioeconomic factors: a sub-analysis of data from the 2013 WHO viral hepatitis policy report.

Science.gov (United States)

Lazarus, Jeffrey V; Sperle, Ida; Safreed-Harmon, Kelly; Gore, Charles; Cebolla, Beatriz; Spina, Alexander

2017-07-26

As more countries worldwide develop national viral hepatitis strategies, it is important to ask whether context-specific factors affect their decision-making. This study aimed to determine whether country-level socioeconomic factors are associated with viral hepatitis programmes and policy responses across WHO Member States (MS). WHO MS focal points completed a questionnaire on national viral hepatitis policies. This secondary analysis of data reported in the 2013 Global Policy Report on the Prevention and Control of Viral Hepatitis in WHO Member States used logistic regression to examine associations between four survey questions and four socioeconomic factors: country income level, Human Development Index (HDI), health expenditure and physician density. This analysis included 119 MS. MS were more likely to have routine viral hepatitis surveillance and to have a national strategy and/or policy/guidelines for preventing infection in healthcare settings if they were in the higher binary categories for income level, HDI, health expenditure and physician density. In multivariable analyses, the only significant finding was a positive association between having routine surveillance and being in the higher binary HDI category (adjusted odds ratio 26; 95% confidence interval 2.0-340). Countries with differing socioeconomic status indicators did not appear to differ greatly regarding the existence of key national policies and programmes. A more nuanced understanding of the multifaceted interactions of socioeconomic factors, health policy, service delivery and health outcomes is needed to support country-level efforts to eliminate viral hepatitis.

Hypothesis for heritable, anti-viral immunity in crustaceans and insects

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Flegel Timothy W

2009-09-01

Full Text Available Abstract Background It is known that crustaceans and insects can persistently carry one or more viral pathogens at low levels, without signs of disease. They may transmit them to their offspring or to naïve individuals, often with lethal consequences. The underlying molecular mechanisms have not been elucidated, but the process has been called viral accommodation. Since tolerance to one virus does not confer tolerance to another, tolerance is pathogen-specific, so the requirement for a specific pathogen response mechanism (memory was included in the original viral accommodation concept. Later, it was hypothesized that specific responses were based on the presence of viruses in persistent infections. However, recent developments suggest that specific responses may be based on viral sequences inserted into the host genome. Presentation of the hypothesis Non-retroviral fragments of both RNA and DNA viruses have been found in insect and crustacean genomes. In addition, reverse-transcriptase (RT and integrase (IN sequences are also common in their genomes. It is hypothesized that shrimp and other arthropods use these RT to recognize "foreign" mRNA of both RNA and DNA viruses and use the integrases (IN to randomly insert short cDNA sequences into their genomes. By chance, some of these sequences result in production of immunospecific RNA (imRNA capable of stimulating RNAi that suppresses viral propagation. Individuals with protective inserts would pass these on to the next generation, together with similar protective inserts for other viruses that could be amalgamated rapidly in individual offspring by random assortment of chromosomes. The most successful individuals would be environmentally selected from billions of offspring. Conclusion This hypothesis for immunity based on an imRNA generation mechanism fits with the general principle of invertebrate immunity based on a non-host, "pattern recognition" process. If proven correct, understanding the

Social responsibility and sustainable development: a strategy to be practice; Responsabilidade social e desenvolvimento sustentavel - estrategias que conduzem a pratica

Energy Technology Data Exchange (ETDEWEB)

Santos, Marcia Amaral Estevao dos [PETROBRAS, Rio de Janeiro, RJ (Brazil); Said, Nagib Albuquerque [Fundacao Gorceix, Ouro Preto, MG (Brazil)

2004-07-01

This work presents the strategy adopted by the Research and Development Center of PETROBRAS - CENPES to disseminate the culture of social responsibility and sustainable development. It is associated to the strategic objectives of the company and is based on the integration of diagnosis, sensibility and training actions of CENPES manpower. The objective is to promote appropriate postures toward sustainability which will be manifested from individual attitudes in daily actions inside the company - as for instance the responsible consumption of paper and water - until the election of sustainability criteria, with emphasis in the social and environmental variables that will contribute to research and basic engineer projects evaluation. The diagnosis phase considers two fundamental actions: to check the 'state of the art' of the internal culture and to map the several relationship groups or stakeholders. In the sensibility stage, the objective is to offer knowledge and information about the theme using different approaches some times continued, other times segmented, through specific and appropriate media. Finally, the training of the researchers and sustainability concepts promoter and multiplier agents will close the virtuous cycle that will lead to practice the values proposed in the social responsibility and sustainable development agenda. (author)

Long-term correction of canine hemophilia B by gene transfer of blood coagulation factor IX mediated by adeno-associated viral vector.

Science.gov (United States)

Herzog, R W; Yang, E Y; Couto, L B; Hagstrom, J N; Elwell, D; Fields, P A; Burton, M; Bellinger, D A; Read, M S; Brinkhous, K M; Podsakoff, G M; Nichols, T C; Kurtzman, G J; High, K A

1999-01-01

Hemophilia B is a severe X-linked bleeding diathesis caused by the absence of functional blood coagulation factor IX, and is an excellent candidate for treatment of a genetic disease by gene therapy. Using an adeno-associated viral vector, we demonstrate sustained expression (>17 months) of factor IX in a large-animal model at levels that would have a therapeutic effect in humans (up to 70 ng/ml, adequate to achieve phenotypic correction, in an animal injected with 8.5x10(12) vector particles/kg). The five hemophilia B dogs treated showed stable, vector dose-dependent partial correction of the whole blood clotting time and, at higher doses, of the activated partial thromboplastin time. In contrast to other viral gene delivery systems, this minimally invasive procedure, consisting of a series of percutaneous intramuscular injections at a single timepoint, was not associated with local or systemic toxicity. Efficient gene transfer to muscle was shown by immunofluorescence staining and DNA analysis of biopsied tissue. Immune responses against factor IX were either absent or transient. These data provide strong support for the feasibility of the approach for therapy of human subjects.

Response to standard interferon A2b and ribavirin combination therapy in chronic hepatitis C treatment naive patients

International Nuclear Information System (INIS)

Jadoon, S.M.K.; Muhammad, I.

2010-01-01

Background: Treatment of Chronic Hepatitis C is now well established with conventional interferon or pegylated interferon in combination with ribavirin. Peginterferon Alfa and Ribavirin for 6 to 12 months is currently approved initial therapy, which is expensive. Response of our patients to standard Interferon-alpha-2b and ribavirin for 24 weeks have been studied. The objective of this study was to asses Sustained Viral Response (SVR) with standard Interferon A2b and Ribavirin combination treatment in chronic Hepatitis C patients. Methods: This quasi-experimental study was conducted at Combined Military Hospital, Quetta from Jan 2006 to Jun 2007. One hundred and three patients, with 20-60 years of age suffering from chronic Hepatitis C were selected on the basis of raised ALT, positive anti-HCV antibodies, evidence of viraemia by quantitative PCR for HCV RNA and liver biopsy. All patients were started on same brand of Interferon alpha-2b, 3 MIU subcutaneously, thrice weekly and oral Ribavirin (1,000-1,200 mg/day) for 24 weeks. End treatment response (ETR) after completion of treatment and SVR six months after ETR were recorded. Results: The 103 patients, 85 males and 18 females with mean age of 21-48 years completed the treatment for 24 weeks. Mean ALT was 96.17 (SD +- 49.98). End treatment response (ETR) was 89.3% (p=0.032). Sustained Viral Response after 6 months of treatment was 86.4% (p=0.034). Conclusion: Standard Interferon and Ribavirin had excellent SVR. It is effective as well as economical treatment in Chronic Hepatitis C patients. (author)

Improved osteogenic vector for non-viral gene therapy

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ARA Hacobian

2016-03-01

Full Text Available Therapeutic compensation of deficient bone regeneration is a challenging task and a topic of on-going search for novel treatment strategies. One promising approach for improvement involves non-viral gene delivery using the bone morphogenetic protein-2 (BMP-2 gene to provide transient, local and sustained expression of the growth factor. However, since efficiency of non-viral gene delivery is low, this study focused on the improvement of a BMP-2 gene expression system, aiming for compensation of poor transfection efficiency. First, the native BMP-2 gene sequence was modified by codon optimisation and altered by inserting a highly truncated artificial intron (96 bp. Transfection of multiple cell lines and rat adipose-derived mesenchymal stem cells with plasmids harbouring the improved BMP-2 sequence led to a several fold increased expression rate and subsequent osteogenic differentiation. Additionally, comparing expression kinetics of elongation factor 1 alpha (EF1α promoter with a state of the art CMV promoter revealed significantly higher BMP-2 expression when under the influence of the EF1α promoter. Results obtained by quantification of bone markers as well as osteogenic assays showed reduced sensitivity to promoter silencing effects of the EF1α promoter in rat adipose-derived mesenchymal stem cells. Finally, screening of several protein secretion signals using either luciferase or BMP-2 as reporter protein revealed no superior candidates for potential replacement of the native BMP-2 secretion signal. Taken together, by enhancing the exogenous BMP-2 expression system, low transfection efficiencies in therapeutic applications can be compensated, making safe non-viral systems even more suitable for tissue regeneration approaches.

Chronic viral hepatitis: policy, regulation, and strategies for its control and elimination in Ethiopia

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Fassil Shiferaw

2016-08-01

Full Text Available Abstract Background Hepatitis B and C are silent killers not yet recognized as major public health challenges in many developing countries with huge disease burden. In Ethiopia, Hepatitis B is endemic with an average prevalence of 10.8 %, and the prevalence of Hepatitis C is 2 %. The prevalence of both infections, however, is likely to be underreported due to the lack of diagnostic facilities and appropriate surveillance systems. Ethiopia is also among the many Sub-Sahara African countries lacking a coordinated and systematic national response to chronic viral hepatitis. The objective of this study is to examine the current level of response to viral Hepatitis B & C in Ethiopia with the aim to bring identified gaps to the attention of relevant stakeholders and policy makers. Methods This cross-sectional qualitative study was based on semi-structured in-depth interviews with 21 key informants from health facilities, health offices, pharmaceutical companies, regulatory bodies, professional association and blood bank units. Participants were selected purposively based on their role in the national hepatitis response. The investigators also reviewed available policy and strategy documents, standards of practice and surveys, and paid visits to pharmaceutical premises to check the availability of antiviral drugs. Thematic analysis was employed to make sense of the data. During the data analysis process, all the authors critically read the materials, and data was triangulated by source, interpreter view and thematic perspective to ensure accurate representation and comprehensiveness, and validation of the interviewees’ responses. Once each investigator reviewed the data independently, the team reached a common understanding of the scope and contexts of the information attained. Data were subsequently reduced to key concepts, and case stories were taken with successive revisions. The key concepts were later coded into most basic meaningful

Chronic viral hepatitis: policy, regulation, and strategies for its control and elimination in Ethiopia.

Science.gov (United States)

Shiferaw, Fassil; Letebo, Mekitew; Bane, Abate

2016-08-11

Hepatitis B and C are silent killers not yet recognized as major public health challenges in many developing countries with huge disease burden. In Ethiopia, Hepatitis B is endemic with an average prevalence of 10.8 %, and the prevalence of Hepatitis C is 2 %. The prevalence of both infections, however, is likely to be underreported due to the lack of diagnostic facilities and appropriate surveillance systems. Ethiopia is also among the many Sub-Sahara African countries lacking a coordinated and systematic national response to chronic viral hepatitis. The objective of this study is to examine the current level of response to viral Hepatitis B & C in Ethiopia with the aim to bring identified gaps to the attention of relevant stakeholders and policy makers. This cross-sectional qualitative study was based on semi-structured in-depth interviews with 21 key informants from health facilities, health offices, pharmaceutical companies, regulatory bodies, professional association and blood bank units. Participants were selected purposively based on their role in the national hepatitis response. The investigators also reviewed available policy and strategy documents, standards of practice and surveys, and paid visits to pharmaceutical premises to check the availability of antiviral drugs. Thematic analysis was employed to make sense of the data. During the data analysis process, all the authors critically read the materials, and data was triangulated by source, interpreter view and thematic perspective to ensure accurate representation and comprehensiveness, and validation of the interviewees' responses. Once each investigator reviewed the data independently, the team reached a common understanding of the scope and contexts of the information attained. Data were subsequently reduced to key concepts, and case stories were taken with successive revisions. The key concepts were later coded into most basic meaningful categories. The World Health Organization (WHO) global

Incorporating Corporate Social Responsibility and Sustainability into a Business Course: A Shared Experience

Science.gov (United States)

Persons, Obeua

2012-01-01

The author discusses how corporate social responsibility (CSR) and sustainability were incorporated into a business course by using 4 assignments, a project with a CSR question, 7 ethics cases, and 17 ethics scenarios tied to a corporate code of ethics. The author also discusses student evaluation of CSR learning experience, strengths and…

Viral (hepatitis C virus, hepatitis B virus, HIV) persistence and immune homeostasis

Science.gov (United States)

Zhou, Yun; Zhang, Ying; Moorman, Jonathan P; Yao, Zhi Q; Jia, Zhan S

2014-01-01

Immune homeostasis is a host characteristic that maintains biological balance within a host. Humans have evolved many host defence mechanisms that ensure the survival of individuals upon encountering a pathogenic infection, with recovery or persistence from a viral infection being determined by both viral factors and host immunity. Chronic viral infections, such as hepatitis B virus, hepatitis C virus and HIV, often result in chronic fluctuating viraemia in the face of host cellular and humoral immune responses, which are dysregulated by multi-faceted mechanisms that are incompletely understood. This review attempts to illuminate the mechanisms involved in this process, focusing on immune homeostasis in the setting of persistent viral infection from the aspects of host defence mechanism, including interferon-stimulated genes, apolipoprotein B mRNA editing enzyme catalytic polypeptide 3 (APOBEC3), autophagy and interactions of various immune cells, cytokines and regulatory molecules. PMID:24965611

Incorporating Human Rights into the Sustainability Agenda: A Commentary on "Corporate Responsibility to Respect Human Rights and Business Schools' Responsibility to Teach It"

Science.gov (United States)

Andrew, Jane

2013-01-01

In her commentary of McPhail's 2013 article "Corporate Responsibility to Respect Human Rights and Business Schools' Responsibility to Teach It: Incorporating Human Rights into the Sustainability Agenda," Jane Andrew begins by highlighting a number of McPhail's primary arguments. She points out that McPhail sets out to achieve two things…

Introductory analysis of sustainable consumption and production : Factors of corporate social responsibility management in Japan

OpenAIRE

八木, 迪幸; 國部, 克彦

2017-01-01

As an introductory analysis of sustainable consumption and production, this paper examines what factors influence corporate social responsibility management in Japan. Following some underlying theories (management control system; the neo-institutional theory; performance measurement systems; the stakeholder theory; the resource dependence theory), this paper conducts empirical studies using firm-level data. The first three studies examine what factors encourage corporate social responsibility...

Sustainable Enterprise Excellence and the Continuously Relevant and Responsible Organization

DEFF Research Database (Denmark)

Edgeman, Rick; Bøllingtoft, Anne; Eskildsen, Jacob Kjær

2013-01-01

Innovation and sustainability are critical to the design, activities, results, and financial viability of organizations. These support one another, with “sustainable innovation” addressing economic sustainability, and “innovating for sustainability” addressing societal and environmental...... sustainability. Both sustainable innovation and innovation for sustainability have gained traction as partial means of confronting economic, environmental and societal challenges. Although garnering footholds is promising, the growth rate of these challenges has thus far exceeded trajectory, scale, and velocity...... issues surrounding enterprise innovation and sustainability efforts and capabilities. Innovation and sustainability of the necessary trajectory, scale, and velocity are strategically integrated to deliver what we refer to as innovating sustainability. This provides an accelerated means path toward...

Selective expansion of viral variants following experimental transmission of a reconstituted feline immunodeficiency virus quasispecies.

Directory of Open Access Journals (Sweden)

Brian J Willett

Full Text Available Following long-term infection with virus derived from the pathogenic GL8 molecular clone of feline immunodeficiency virus (FIV, a range of viral variants emerged with distinct modes of interaction with the viral receptors CD134 and CXCR4, and sensitivities to neutralizing antibodies. In order to assess whether this viral diversity would be maintained following subsequent transmission, a synthetic quasispecies was reconstituted comprising molecular clones bearing envs from six viral variants and its replicative capacity compared in vivo with a clonal preparation of the parent virus. Infection with either clonal (Group 1 or diverse (Group 2 challenge viruses, resulted in a reduction in CD4+ lymphocytes and an increase in CD8+ lymphocytes. Proviral loads were similar in both study groups, peaking by 10 weeks post-infection, a higher plateau (set-point being achieved and maintained in study Group 1. Marked differences in the ability of individual viral variants to replicate were noted in Group 2; those most similar to GL8 achieved higher viral loads while variants such as the chimaeras bearing the B14 and B28 Envs grew less well. The defective replication of these variants was not due to suppression by the humoral immune response as virus neutralising antibodies were not elicited within the study period. Similarly, although potent cellular immune responses were detected against determinants in Env, no qualitative differences were revealed between animals infected with either the clonal or the diverse inocula. However, in vitro studies indicated that the reduced replicative capacity of variants B14 and B28 in vivo was associated with altered interactions between the viruses and the viral receptor and co-receptor. The data suggest that viral variants with GL8-like characteristics have an early, replicative advantage and should provide the focus for future vaccine development.

Analysis of host genetic diversity and viral entry as sources of between-host variation in viral load

Science.gov (United States)

Wargo, Andrew R.; Kell, Alison M.; Scott, Robert J.; Thorgaard, Gary H.; Kurath, Gael

2012-01-01

Little is known about the factors that drive the high levels of between-host variation in pathogen burden that are frequently observed in viral infections. Here, two factors thought to impact viral load variability, host genetic diversity and stochastic processes linked with viral entry into the host, were examined. This work was conducted with the aquatic vertebrate virus, Infectious hematopoietic necrosis virus (IHNV), in its natural host, rainbow trout. It was found that in controlled in vivo infections of IHNV, a suggestive trend of reduced between-fish viral load variation was observed in a clonal population of isogenic trout compared to a genetically diverse population of out-bred trout. However, this trend was not statistically significant for any of the four viral genotypes examined, and high levels of fish-to-fish variation persisted even in the isogenic trout population. A decrease in fish-to-fish viral load variation was also observed in virus injection challenges that bypassed the host entry step, compared to fish exposed to the virus through the natural water-borne immersion route of infection. This trend was significant for three of the four virus genotypes examined and suggests host entry may play a role in viral load variability. However, high levels of viral load variation also remained in the injection challenges. Together, these results indicate that although host genetic diversity and viral entry may play some role in between-fish viral load variation, they are not major factors. Other biological and non-biological parameters that may influence viral load variation are discussed.

Laboratory procedures to generate viral metagenomes.

Science.gov (United States)

Thurber, Rebecca V; Haynes, Matthew; Breitbart, Mya; Wegley, Linda; Rohwer, Forest

2009-01-01

This collection of laboratory protocols describes the steps to collect viruses from various samples with the specific aim of generating viral metagenome sequence libraries (viromes). Viral metagenomics, the study of uncultured viral nucleic acid sequences from different biomes, relies on several concentration, purification, extraction, sequencing and heuristic bioinformatic methods. No single technique can provide an all-inclusive approach, and therefore the protocols presented here will be discussed in terms of hypothetical projects. However, care must be taken to individualize each step depending on the source and type of viral-particles. This protocol is a description of the processes we have successfully used to: (i) concentrate viral particles from various types of samples, (ii) eliminate contaminating cells and free nucleic acids and (iii) extract, amplify and purify viral nucleic acids. Overall, a sample can be processed to isolate viral nucleic acids suitable for high-throughput sequencing in approximately 1 week.

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 ...

Highly-Immunogenic Virally-Vectored T-cell Vaccines Cannot Overcome Subversion of the T-cell Response by HCV during Chronic Infection

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Leo Swadling

2016-08-01

Full Text Available An effective therapeutic vaccine for the treatment of chronic hepatitis C virus (HCV infection, as an adjunct to newly developed directly-acting antivirals (DAA, or for the prevention of reinfection, would significantly reduce the global burden of disease associated with chronic HCV infection. A recombinant chimpanzee adenoviral (ChAd3 vector and a modified vaccinia Ankara (MVA, encoding the non-structural proteins of HCV (NSmut, used in a heterologous prime/boost regimen induced multi-specific, high-magnitude, durable HCV-specific CD4+ and CD8+ T-cell responses in healthy volunteers, and was more immunogenic than a heterologous Ad regimen. We now assess the immunogenicity of this vaccine regimen in HCV infected patients (including patients with a low viral load suppressed with interferon/ribavirin therapy, determine T-cell cross-reactivity to endogenous virus, and compare immunogenicity with that observed previously in both healthy volunteers and in HCV infected patients vaccinated with the heterologous Ad regimen. Vaccination of HCV infected patients with ChAd3-NSmut/MVA-NSmut was well tolerated. Vaccine-induced HCV-specific T-cell responses were detected in 8/12 patients; however, CD4+ T-cell responses were rarely detected, and the overall magnitude of HCV-specific T-cell responses was markedly reduced when compared to vaccinated healthy volunteers. Furthermore, HCV-specific cells had a distinct partially-functional phenotype (lower expression of activation markers, granzyme B, and TNFα production, weaker in vitro proliferation, and higher Tim3 expression, with comparable Tbet and Eomes expression compared to healthy volunteers. Robust anti-vector T-cells and antibodies were induced, showing that there is no global defect in immunity. The level of viremia at the time of vaccination did not correlate with the magnitude of the vaccine-induced T-cell response. Full-length, next-generation sequencing of the circulating virus demonstrated that T

Adsorption of viral particles from the blood plasma of patients with viral hepatitis on nanodiamonds.

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Baron, A V; Osipov, N V; Yashchenko, S V; Kokotukha, Yu A; Baron, I J; Puzyr, A P; Olkhovskiy, I A; Bondar, V S

2016-07-01

Adsorption of viral particles from the blood plasma of patients with viral hepatitis B and C on modified nanodiamonds (MNDs) was shown in the in vitro experiments. PCR method showed the treatment of plasma with MNDs leads to a decrease in the viral load by 2-3 orders of magnitude or more in both cases studied. These results make it possible to predict the applicability of MNDs for the development of new technologies of hemodialysis and plasmapheresis for binding and removal of viral particles from the blood of infected patients.

"Omics" of maize stress response for sustainable food production: opportunities and challenges.

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Gong, Fangping; Yang, Le; Tai, Fuju; Hu, Xiuli; Wang, Wei

2014-12-01

Maize originated in the highlands of Mexico approximately 8700 years ago and is one of the most commonly grown cereal crops worldwide, followed by wheat and rice. Abiotic stresses (primarily drought, salinity, and high and low temperatures), together with biotic stresses (primarily fungi, viruses, and pests), negatively affect maize growth, development, and eventually production. To understand the response of maize to abiotic and biotic stresses and its mechanism of stress tolerance, high-throughput omics approaches have been used in maize stress studies. Integrated omics approaches are crucial for dissecting the temporal and spatial system-level changes that occur in maize under various stresses. In this comprehensive analysis, we review the primary types of stresses that threaten sustainable maize production; underscore the recent advances in maize stress omics, especially proteomics; and discuss the opportunities, challenges, and future directions of maize stress omics, with a view to sustainable food production. The knowledge gained from studying maize stress omics is instrumental for improving maize to cope with various stresses and to meet the food demands of the exponentially growing global population. Omics systems science offers actionable potential solutions for sustainable food production, and we present maize as a notable case study.

Analysis of hepatitis C viral dynamics using Latin hypercube sampling

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Pachpute, Gaurav; Chakrabarty, Siddhartha P.

2012-12-01

We consider a mathematical model comprising four coupled ordinary differential equations (ODEs) to study hepatitis C viral dynamics. The model includes the efficacies of a combination therapy of interferon and ribavirin. There are two main objectives of this paper. The first one is to approximate the percentage of cases in which there is a viral clearance in absence of treatment as well as percentage of response to treatment for various efficacy levels. The other is to better understand and identify the parameters that play a key role in the decline of viral load and can be estimated in a clinical setting. A condition for the stability of the uninfected and the infected steady states is presented. A large number of sample points for the model parameters (which are physiologically feasible) are generated using Latin hypercube sampling. An analysis of the simulated values identifies that, approximately 29.85% cases result in clearance of the virus during the early phase of the infection. Results from the χ2 and the Spearman's tests done on the samples, indicate a distinctly different distribution for certain parameters for the cases exhibiting viral clearance under the combination therapy.

Associations between national viral hepatitis policies/programmes and country-level socioeconomic factors: a sub-analysis of data from the 2013 WHO viral hepatitis policy report

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Jeffrey V Lazarus

2017-07-01

Full Text Available Abstract Background As more countries worldwide develop national viral hepatitis strategies, it is important to ask whether context-specific factors affect their decision-making. This study aimed to determine whether country-level socioeconomic factors are associated with viral hepatitis programmes and policy responses across WHO Member States (MS. Methods WHO MS focal points completed a questionnaire on national viral hepatitis policies. This secondary analysis of data reported in the 2013 Global Policy Report on the Prevention and Control of Viral Hepatitis in WHO Member States used logistic regression to examine associations between four survey questions and four socioeconomic factors: country income level, Human Development Index (HDI, health expenditure and physician density. Results This analysis included 119 MS. MS were more likely to have routine viral hepatitis surveillance and to have a national strategy and/or policy/guidelines for preventing infection in healthcare settings if they were in the higher binary categories for income level, HDI, health expenditure and physician density. In multivariable analyses, the only significant finding was a positive association between having routine surveillance and being in the higher binary HDI category (adjusted odds ratio 26; 95% confidence interval 2.0–340. Conclusion Countries with differing socioeconomic status indicators did not appear to differ greatly regarding the existence of key national policies and programmes. A more nuanced understanding of the multifaceted interactions of socioeconomic factors, health policy, service delivery and health outcomes is needed to support country-level efforts to eliminate viral hepatitis.

Corporate social responsibility in China: an analysis of domestic and foreign retailers' sustainability dimensions

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Kolk, A.; Hong, P.; van Dolen, W.

2010-01-01

In the past decade, a sizeable body of literature has built up on the concept and characteristics of corporate social responsibility (CSR) in Western countries, where it has also been referred to as sustainability. More recently, attention has grown for CSR in emerging countries. Remarkably, China

Bacterial–viral load and the immune response in stable and exacerbated COPD: significance and therapeutic prospects

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D’Anna SE

2016-03-01

Full Text Available Silvestro Ennio D’Anna,1 Bruno Balbi,2 Francesco Cappello,3,4 Mauro Carone,2 Antonino Di Stefano21Department of Rehabilitation, Cardiorespiratory Unit, Fondazione Istituto G. Giglio di Cefalù, 2Pneumology Unit and Laboratory of Cytoimmunopathology of Heart and Lung, Fondazione Salvatore Maugeri, IRCCS, Veruno (NO and Cassano delle Murge (BA, 3Human Anatomy Section, Department of Experimental Biomedicine and Clinical Neuroscience, University of Palermo, Palermo, Italy; 4Euro-Mediterranean Institute of Science and Technology, Palermo, ItalyAbstract: Chronic obstructive pulmonary disease (COPD is characterized by persistent airflow limitation and an abnormal inflammatory response of the lung. Bacteria and viruses are a major cause of COPD exacerbations and may contribute to COPD progression by perpetuating the inflammatory response in the airways. Bacterial variety diminishes with increasing COPD severity. Respiratory viruses can colonize the lower respiratory tract in stable COPD, altering the respiratory microbiome and facilitating secondary bacterial infections. In this review, we present the most updated information about the role of bacteria and viruses in stable and exacerbated COPD. In our opinion, to optimize therapeutic strategies, the dynamic events involving bacterial–viral infections and related immune response in COPD phenotypes need to be better clarified. Our paper would address these points that we consider of great importance for the clinical management of COPD.Keywords: COPD phenotype, biomarkers, exacerbations, severity of COPD, microbiome

Responsible tourism: A guide for tourism and sustainability in small-scale fisheries and agri-food

OpenAIRE

Ford, Adriana; Acott, Timothy

2015-01-01

‘Responsible Tourism: a guide for tourism and sustainability in small-scale fisheries and agri-food’ is a product of TourFish, a project funded by the EU INTERREG IVA 2 Seas programme. The aim of TourFish was to explore opportunities for coastal areas through developing responsible tourism that draws together food, small-scale inshore fisheries, regional branding and place-based marketing opportunities.

Sustainability Management in Agribusiness: Challenges, Concepts, Responsibilities and Performance

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Nina Friedrich

2012-12-01

Full Text Available The idea of sustainable management has recently gained growing attention in the agribusiness sector. This is mainly due to a widespread discontent with the industrialization of agricultural production and food processing and growing public pressure on agribusiness firms to implement more sustainable management practices. In this paper we present the results of an explorative empirical study of sustainability management in German agribusiness firms. The study shows that agribusiness firms have developed a broad understanding of sustainability management and perceive a multi-facetted spectrum of societal demands they have to meet. The most important arguments for implementing more sustainable management practices are that companies have to make sure that they are trusted by society in the long run and that the perception of a company by external stakeholders has become more and more important. The companies surveyed know quite a number of sustainability programmes and standards, but the number of companies that actually participate in these initiatives is much smaller. Nonetheless, the majority of the respondents feels that their company is more successful with regard to sustainability management than industry average.

When Legitimacy Shapes Environmentally Responsible Behaviors: Considering Exposure to University Sustainability Initiatives

OpenAIRE

Lesley Watson; Karen A. Hegtvedt; Cathryn Johnson; Christie L. Parris; Shruthi Subramanyam

2017-01-01

This study examines how perceptions of the legitimacy of university sustainability efforts—support by the administration (authorization) or from students’ peers (endorsement)—as well as the physical context in which students live, matter in shaping students’ environmentally responsible behaviors (ERBs). Using survey data collected from fourth-year students at a university in the Southeastern US, we employ Seeming Unrelated Regression to analyze the impact of perceived legitimacy and context o...

CORPORATE SOCIAL RESPONSIBILITY AS AN INSTRUMENT OF SUSTAINABLE DEVELOPMENT OF PRODUCTION ENTERPRISES

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Ewelina GAWEŁ

2015-07-01

Full Text Available The paper deals with the issue of corporate social responsibility as an instrument of operationalising the paradigm of sustainable development on the microeconomic level in the sector of production enterprises. It presents a genesis and importance of CSR and indicates the most relevant essential instruments of CSR implementation on an enterprise level. The paper also analyses endogenous and exogenous benefits from implementing CSR into the business practice.

Managing Supplier Sustainability Risk

OpenAIRE

Harilainen, Hanna-Riitta

2014-01-01

Supply chains are increasingly global, often reaching to developing regions. The media pressure brand owners to be responsible, but a product is only as sustainable as the practices of all the companies involved in manufacturing it are. It’s not enough that the brand owner acts responsibly; sustainable practices have to reach component and raw material suppliers upstream. Image risk has often been recognized as reason for investing in sustainability. In the supply chain context, supplier m...

From Customer to Stakeholder Management: Quality Managers perceptions of Sustainability and Social Responsibility concepts, motivations and impacts

OpenAIRE

Fonseca, Luis

2013-01-01

57Th EOQ Congress, Quality Renaissance - Co-creating a Viable Future" The research proves that under certain conditions: The economic, environmental and social dimensions are key to organizational sustainable success; Stakeholder satisfaction is significantly higher when a Social Responsibility program is present and it is relevant for the organizational sustainable success and competitive position, as suggested by Freeman (1984) Stakeholder Theory and in line with ISO...

Neonatal bronchial hyperresponsiveness precedes acute severe viral bronchiolitis in infants

DEFF Research Database (Denmark)

Chawes, Bo L K; Poorisrisak, Porntiva; Johnston, Sebastian L

2012-01-01

Respiratory syncytial virus and other respiratory tract viruses lead to common colds in most infants, whereas a minority develop acute severe bronchiolitis often requiring hospitalization. We hypothesized that such an excessive response to respiratory tract viral infection is caused by host factors...

Transient nephritis during resolution phase of acute virale hepatitis E

OpenAIRE

Arden, Amir David

2009-01-01

Hepatitis E Virus is a causative agent of hepatitis. Viral E hepatitis is responsible for various clinical manifestations. However, immune reactions due to hepatitis E virus are rarely encountered. A case of membranoproliferative glomerulonephritis associated with hepatitis E virus is reported her.

Sustainable Logistics Responses to a Global Challenge

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Bretzke, Wolf-Rüdiger

2013-01-01

Currently the notion of "sustainability" is used in an inflationary manner. Therefore the authors start with a definition which is stable to serve as an anchor for further research as well as for discussions among scientists, managers and politicians, ideally across different disciplines. The character of this book is purely conceptual. The argumentation is based on comparison of new and demanding requisites with existing models (process and network architectures in the field of logistics). Formerly neglected impacts on the environment will be included. Main features of a new approach will be developed which are capable to avoid these impacts and to align logistics with the requirements of sustainability. In order to make logistics sustainable large parts will have to be reinvented. The focus needs to be on decoupling transportation activities from economic growth rates.

Faktor Risiko Non Viral Pada Karsinoma Nasofaring

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Sukri Rahman

2015-09-01

Full Text Available Abstrak           Latar belakang: Karsinoma nasofaring adalah tumor ganas epitel nasofaring yang sampai saat ini penyebabnya belum diketahui, infeksi virus Epstein Barr dilaporkan sebagai faktor dominan terjadinya karsinoma nasofaring tetapi faktor non viral juga berperan untuk timbulnya keganasan nasofaring. Tujuan: Untuk mengetahui faktor non viral  yang dapat meningkatkan kejadian karsinoma nasofaring sehingga dapat mencegah dan menghindari faktor-faktor non viral tersebut. Tinjauan Pustaka: Karsinoma nasofaring merupakan tumor ganas epitel nasofaring yang penyebabnya berhubungan dengan faktor viral dan non viral diantaranya asap rokok, ikan asin, formaldehid, genetik, asap kayu bakar , debu kayu, infeksi kronik telinga hidung tenggorok, alkohol dan obat tradisional. Kesimpulan: Pembuktian secara klinis dan ilmiah terhadap faktor non viral sebagai penyebab timbulnya karsinoma nasofaring masih belum dapat dijelaskan secara pasti. Faktor non viral merupakan salah satu faktor risiko yang dapat meningkatkan angka kejadian timbulnya keganasan nasofaring Kata kunci: karsinoma nasofaring, faktor risiko, non viral AbstractBackground: Nasopharyngeal carcinoma is a malignant epithelial nasopharyngeal tumor that until now the cause still unknown, Epstein barr virus infection had reported as predominant occurance of nasopharyngeal carcinoma but non viral factors may also contribute to the onset of the incidence of nasopharyngeal malignancy. Purpose: To find non viral factors that may increase the incidence of nasopharyngel carcinoma in order to prevent and avoid non-viral factors Literature: Nasopharyngeal carcinoma is a malignant tumor that causes nasopharyngeal epithelium associated with viral and non-viral factors such as cigarette smoke, salt fish, formaldehyde, genetic, wood smoke ,wood dust, ear nose throat chronic infections, alcohol, and traditional medicine. Conclusion: Clinically and scientifically proving the non-viral factors as

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

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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.

Optimization of sustained release aceclofenac microspheres using response surface methodology

Energy Technology Data Exchange (ETDEWEB)

Deshmukh, Rameshwar K.; Naik, Jitendra B., E-mail: jitunaik@gmail.com

2015-03-01

Polymeric microspheres containing aceclofenac were prepared by single emulsion (oil-in-water) solvent evaporation method using response surface methodology (RSM). Microspheres were prepared by changing formulation variables such as the amount of Eudragit® RS100 and the amount of polyvinyl alcohol (PVA) by statistical experimental design in order to enhance the encapsulation efficiency (E.E.) of the microspheres. The resultant microspheres were evaluated for their size, morphology, E.E., and in vitro drug release. The amount of Eudragit® RS100 and the amount of PVA were found to be significant factors respectively for determining the E.E. of the microspheres. A linear mathematical model equation fitted to the data was used to predict the E.E. in the optimal region. Optimized formulation of microspheres was prepared using optimal process variables setting in order to evaluate the optimization capability of the models generated according to IV-optimal design. The microspheres showed high E.E. (74.14 ± 0.015% to 85.34 ± 0.011%) and suitably sustained drug release (minimum; 40% to 60%; maximum) over a period of 12 h. The optimized microspheres formulation showed E.E. of 84.87 ± 0.005 with small error value (1.39). The low magnitudes of error and the significant value of R{sup 2} in the present investigation prove the high prognostic ability of the design. The absence of interactions between drug and polymers was confirmed by Fourier transform infrared (FTIR) spectroscopy. Differential scanning calorimetry (DSC) and X-ray powder diffractometry (XRPD) revealed the dispersion of drug within microspheres formulation. The microspheres were found to be discrete, spherical with smooth surface. The results demonstrate that these microspheres could be promising delivery system to sustain the drug release and improve the E.E. thus prolong drug action and achieve the highest healing effect with minimal gastrointestinal side effects. - Highlights: • Aceclofenac microspheres

Metabolism goes viral.

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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.

[Results of treatment with peginterferon plus ribavirin in patients with chronic hepatitis C].

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Pizarro, Carolina; Venegas, Mauricio; Hola, Karen; Smok, Gladys; Brahm, Javier

2011-06-01

The current treatment recommendation for chronic hepatitis C virus infection is the combination of peginterferon and ribavirin for 24 or 48 weeks, depending on the viral genotype. The aim of the therapy is to obtain a sustained virological response. To report our experience in the treatment of chronic hepatitis C. Analysis of 52 patients treated between September 2000 and June 2009. Patients with genotype 1 or 5 were treated with peginterferon alpha 2a (180 ug/week) and ribavirin (1000 mg/day for those weighing less than 75 kg and 1200 mg/day for those weighing more than 75 kg) during 48 weeks. Patients with genotypes 2 and 3 were treated for 24 weeks with the same dose of peginterferon and ribavirin 800 mg/day. Viral genotypes 1, 2, 3 and 5 were present in 81, 4, 11 and 4% of patients, respectively. Twenty four patients (46 %), 18 with genotype 1, achieved a sustained viral response. Age was the only variable that influenced the response to treatment. Approximately half of the patients with chronic hepatitis C, achieve a sustained viral response with peginterferon and ribavirin.

Sustainability strategies for real-estates. Thinking long-term and shoulder entrepreneurial responsibility; Nachhaltigkeitsstrategien fuer Immobilien. Langfristig denken und unternehmerische Verantwortung wahrnehmen

Energy Technology Data Exchange (ETDEWEB)

Kaeding, Uta; Sigg, Rene [Intep - Integrale Planung GmbH, Hamburg (Germany); Intep - Integrale Planung GmbH, Muenchen (Germany)

2011-07-01

On the basis of their corporate strategy and sustainability strategy responsible companies set suitable objectives for their real-estate portfolio. The companies recognized that sustainable real-estates offer long-term economic advantages and reduced risks. For the development and conversion of a sustainability strategy for real-estates innovative tools and aids are available today which make the life cycle costs or the surplus value of sustainable real-estates transparent.

Role of pentraxin 3 in shaping arthritogenic alphaviral disease: from enhanced viral replication to immunomodulation.

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Suan-Sin Foo

2015-02-01

Full Text Available The rising prevalence of arthritogenic alphavirus infections, including chikungunya virus (CHIKV and Ross River virus (RRV, and the lack of antiviral treatments highlight the potential threat of a global alphavirus pandemic. The immune responses underlying alphavirus virulence remain enigmatic. We found that pentraxin 3 (PTX3 was highly expressed in CHIKV and RRV patients during acute disease. Overt expression of PTX3 in CHIKV patients was associated with increased viral load and disease severity. PTX3-deficient (PTX3(-/- mice acutely infected with RRV exhibited delayed disease progression and rapid recovery through diminished inflammatory responses and viral replication. Furthermore, binding of the N-terminal domain of PTX3 to RRV facilitated viral entry and replication. Thus, our study demonstrates the pivotal role of PTX3 in shaping alphavirus-triggered immunity and disease and provides new insights into alphavirus pathogenesis.

A holistic approach to corporate social responsibility as a prerequisite for sustainable development: Empirical evidence

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Zlatanović Dejana

2015-01-01

Full Text Available The growing importance of sustainable development and corporate social responsibility (CSR for contemporary organizations demands appropriate holistic tools. The paper highlights how Soft Systems Methodology (SSM, a relevant holistic, i.e., soft systems approach, supports the conceptualization and management of the complex issues of CSR and sustainable development. The SSM’s key methodological tools are used: rich picture, root definitions, and conceptual models. Empirical research compares a selected sample of enterprises in the automotive industry in the Republic of Serbia, to identify possible systemically desirable and culturally feasible changes to improve their CSR behaviour through promoting their sustainable development. Some limitations of this research and of SSM application are discussed. Combining SSM with some other systems approaches, such as System Dynamics or Critical Systems Heuristics, is recommended for future research.

The Incubation Period of Primary Epstein-Barr Virus Infection: Viral Dynamics and Immunologic Events.

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Samantha K Dunmire

2015-12-01

Full Text Available Epstein-Barr virus (EBV is a human herpesvirus that causes acute infectious mononucleosis and is associated with cancer and autoimmune disease. While many studies have been performed examining acute disease in adults following primary infection, little is known about the virological and immunological events during EBV's lengthy 6 week incubation period owing to the challenge of collecting samples from this stage of infection. We conducted a prospective study in college students with special emphasis on frequent screening to capture blood and oral wash samples during the incubation period. Here we describe the viral dissemination and immune response in the 6 weeks prior to onset of acute infectious mononucleosis symptoms. While virus is presumed to be present in the oral cavity from time of transmission, we did not detect viral genomes in the oral wash until one week before symptom onset, at which time viral genomes were present in high copy numbers, suggesting loss of initial viral replication control. In contrast, using a sensitive nested PCR method, we detected viral genomes at low levels in blood about 3 weeks before symptoms. However, high levels of EBV in the blood were only observed close to symptom onset-coincident with or just after increased viral detection in the oral cavity. These data imply that B cells are the major reservoir of virus in the oral cavity prior to infectious mononucleosis. The early presence of viral genomes in the blood, even at low levels, correlated with a striking decrease in the number of circulating plasmacytoid dendritic cells well before symptom onset, which remained depressed throughout convalescence. On the other hand, natural killer cells expanded only after symptom onset. Likewise, CD4+ Foxp3+ regulatory T cells decreased two fold, but only after symptom onset. We observed no substantial virus specific CD8 T cell expansion during the incubation period, although polyclonal CD8 activation was detected in

Viral Causes of Hearing Loss: A Review for Hearing Health Professionals

Science.gov (United States)

Cohen, Brandon E.; Durstenfeld, Anne

2014-01-01

A number of viral infections can cause hearing loss. Hearing loss induced by these viruses can be congenital or acquired, unilateral or bilateral. Certain viral infections can directly damage inner ear structures, others can induce inflammatory responses which then cause this damage, and still others can increase susceptibility or bacterial or fungal infection, leading to hearing loss. Typically, virus-induced hearing loss is sensorineural, although conductive and mixed hearing losses can be seen following infection with certain viruses. Occasionally, recovery of hearing after these infections can occur spontaneously. Most importantly, some of these viral infections can be prevented or treated. For many of these viruses, guidelines for their treatment or prevention have recently been revised. In this review, we outline many of the viruses that cause hearing loss, their epidemiology, course, prevention, and treatment. PMID:25080364

Shrimp miR-10a Is Co-opted by White Spot Syndrome Virus to Increase Viral Gene Expression and Viral Replication

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Jiun-Yan Huang

2017-09-01

Full Text Available Members of the microRNA miR-10 family are highly conserved and play many important roles in diverse biological mechanisms, including immune-related responses and cancer-related processes in certain types of cancer. In this study, we found the most highly upregulated shrimp microRNA from Penaeus vannamei during white spot syndrome virus (WSSV infection was miR-10a. After confirming the expression level of miR-10a by northern blot and quantitative RT-PCR, an in vivo experiment showed that the viral copy number was decreased in miR-10a-inhibited shrimp. We found that miR-10a targeted the 5′ untranslated region (UTR of at least three viral genes (vp26, vp28, and wssv102, and plasmids that were controlled by the 5′ UTR of these genes produced enhanced luciferase signals in transfected SF9 cells. These results suggest a previously unreported role for shrimp miR-10a and even a new type of host–virus interaction, whereby a co-opts the key cellular regulator miR-10a to globally enhance the translation of viral proteins.

Shrimp miR-10a Is Co-opted by White Spot Syndrome Virus to Increase Viral Gene Expression and Viral Replication.

Science.gov (United States)

Huang, Jiun-Yan; Kang, Shih-Ting; Chen, I-Tung; Chang, Li-Kwan; Lin, Shih-Shun; Kou, Guang-Hsiung; Chu, Chia-Ying; Lo, Chu-Fang

2017-01-01

Members of the microRNA miR-10 family are highly conserved and play many important roles in diverse biological mechanisms, including immune-related responses and cancer-related processes in certain types of cancer. In this study, we found the most highly upregulated shrimp microRNA from Penaeus vannamei during white spot syndrome virus (WSSV) infection was miR-10a. After confirming the expression level of miR-10a by northern blot and quantitative RT-PCR, an in vivo experiment showed that the viral copy number was decreased in miR-10a-inhibited shrimp. We found that miR-10a targeted the 5' untranslated region (UTR) of at least three viral genes ( vp26, vp28 , and wssv102 ), and plasmids that were controlled by the 5' UTR of these genes produced enhanced luciferase signals in transfected SF9 cells. These results suggest a previously unreported role for shrimp miR-10a and even a new type of host-virus interaction, whereby a co-opts the key cellular regulator miR-10a to globally enhance the translation of viral proteins.

A Viral RNA Structural Element Alters Host Recognition of Nonself RNA

Energy Technology Data Exchange (ETDEWEB)

Hyde, J. L.; Gardner, C. L.; Kimura, T.; White, J. P.; Liu, G.; Trobaugh, D. W.; Huang, C.; Tonelli, M.; Paessler, S.; Takeda, K.; Klimstra, W. B.; Amarasinghe, G. K.; Diamond, M. S.

2014-01-30

Although interferon (IFN) signaling induces genes that limit viral infection, many pathogenic viruses overcome this host response. As an example, 2'-O methylation of the 5' cap of viral RNA subverts mammalian antiviral responses by evading restriction of Ifit1, an IFN-stimulated gene that regulates protein synthesis. However, alphaviruses replicate efficiently in cells expressing Ifit1 even though their genomic RNA has a 5' cap lacking 2'-O methylation. We show that pathogenic alphaviruses use secondary structural motifs within the 5' untranslated region (UTR) of their RNA to alter Ifit1 binding and function. Mutations within the 5'-UTR affecting RNA structural elements enabled restriction by or antagonism of Ifit1 in vitro and in vivo. These results identify an evasion mechanism by which viruses use RNA structural motifs to avoid immune restriction.

Cytokine responses in acute and persistent human parvovirus B19 infection

DEFF Research Database (Denmark)

Isa, A; Lundqvist, A; Lindblom, A

2007-01-01

The aim of this study was to characterize the proinflammatory and T helper (Th)1/Th2 cytokine responses during acute parvovirus B19 (B19) infection and determine whether an imbalance of the Th1/Th2 cytokine pattern is related to persistent B19 infection. Cytokines were quantified by multiplex beads...... immunoassay in serum from B19-infected patients and controls. The cytokine responses were correlated with B19 serology, quantitative B19 DNA levels and clinical symptoms. In addition to a proinflammatory response, elevated levels of the Th1 type of cytokines interleukin (IL)-2, IL-12 and IL-15 were evident...... at time of the initial peak of B19 viral load in a few patients during acute infection. This pattern was seen in the absence of an interferon (IFN)-gamma response. During follow-up (20-130 weeks post-acute infection) some of these patients had a sustained Th1 cytokine response. The Th1 cytokine response...

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....

Assembly of viral genomes from metagenomes

NARCIS (Netherlands)

S.L. Smits (Saskia); R. Bodewes (Rogier); A. Ruiz-Gonzalez (Aritz); V. Baumgärtner (Volkmar); M.P.G. Koopmans D.V.M. (Marion); A.D.M.E. Osterhaus (Albert); A. Schürch (Anita)

2014-01-01

textabstractViral infections remain a serious global health issue. Metagenomic approaches are increasingly used in the detection of novel viral pathogens but also to generate complete genomes of uncultivated viruses. In silico identification of complete viral genomes from sequence data would allow

Viral commercials: the consumer as marketeer

NARCIS (Netherlands)

Ketelaar, P.E.; Lucassen, P.; Kregting, G.H.J.

2010-01-01

Research into the reasons why consumers pass along viral commercials: their motives, the content characteristics of viral commercials and the medium context in which viral commercials appear. Based on the uses and gratifications perspective this study has determined which motives of consumers,

The stress granule component TIA-1 binds tick-borne encephalitis virus RNA and is recruited to perinuclear sites of viral replication to inhibit viral translation.

Science.gov (United States)

Albornoz, Amelina; Carletti, Tea; Corazza, Gianmarco; Marcello, Alessandro

2014-06-01

Flaviviruses are a major cause of disease in humans and animals worldwide. Tick-borne encephalitis virus (TBEV) is the most important arthropod-borne flavivirus endemic in Europe and is the etiological agent of tick-borne encephalitis, a potentially fatal infection of the central nervous system. However, the contributions of host proteins during TBEV infection are poorly understood. In this work, we investigate the cellular protein TIA-1 and its cognate factor TIAR, which are stress-induced RNA-binding proteins involved in the repression of initiation of translation of cellular mRNAs and in the formation of stress granules. We show that TIA-1 and TIAR interact with viral RNA in TBEV-infected cells. During TBEV infection, cytoplasmic TIA-1 and TIAR are recruited at sites of viral replication with concomitant depletion from stress granules. This effect is specific, since G3BP1, another component of these cytoplasmic structures, remains localized to stress granules. Moreover, heat shock induction of stress granules containing TIA-1, but not G3BP1, is inhibited in TBEV-infected cells. Infection of cells depleted of TIA-1 or TIAR by small interfering RNA (siRNA) or TIA-1(-/-) mouse fibroblasts, leads to a significant increase in TBEV extracellular infectivity. Interestingly, TIAR(-/-) fibroblasts show the opposite effect on TBEV infection, and this phenotype appears to be related to an excess of TIA-1 in these cells. Taking advantage of a TBE-luciferase replicon system, we also observed increased luciferase activity in TIA-1(-/-) mouse fibroblasts at early time points, consistent with TIA-1-mediated inhibition at the level of the first round of viral translation. These results indicate that, in response to TBEV infection, TIA-1 is recruited to sites of virus replication to bind TBEV RNA and modulate viral translation independently of stress granule (SG) formation. This study (i) extends previous work that showed TIA-1/TIAR recruitment at sites of flavivirus replication

Apolipoprotein B-associated cholesterol is a determinant of treatment outcome in patients with chronic hepatitis C virus infection receiving anti-viral agents interferon-alpha and ribavirin.

Science.gov (United States)

Sheridan, D A; Price, D A; Schmid, M L; Toms, G L; Donaldson, P; Neely, D; Bassendine, M F

2009-06-15

Hepatitis C virus (HCV) co-opts very-low-density lipoprotein (VLDL) pathways for replication, secretion and entry into hepatocytes and associates with apolipoprotein B (apoB) in plasma. Each VLDL contains apoB-100 and variable amounts of apolipoproteins E and C, cholesterol and triglycerides. To determine whether baseline lipid levels predicted treatment outcome. Retrospective analysis was performed of 250 chronic hepatitis C (CHC) patients who had received anti-viral agents interferon-alpha and ribavirin; 165 had a sustained virological response (SVR). Pre- and post-treatment nonfasting lipid profiles were measured and non-high-density lipoprotein (non-HDL) cholesterol (i.e. apoB-associated) was calculated. Binary logistic regression analysis assessed factors independently associated with treatment outcome. There was an independent association between higher apoB-associated cholesterol (non-HDL-C) and increased odds of SVR (odds ratio 2.09, P = 0.042). In multivariate analysis, non-HDL-C was significantly lower in HCV genotype 3 (g3) than genotype 1 (P = 0.007); this was reversible upon eradication of HCVg3 (pre-treatment non-HDL-C = 2.8 mmol/L, SVR = 3.6 mmol/L, P < 0.001). Higher apoB-associated cholesterol is positively associated with treatment outcome in CHC patients receiving anti-viral therapy, possibly due to competition between apoB-containing lipoproteins and infectious low-density HCV lipo-viral particles for hepatocyte entry via shared lipoprotein receptors.

Viral Infection in Renal Transplant Recipients

Directory of Open Access Journals (Sweden)

Jovana Cukuranovic

2012-01-01

Full Text Available Viruses are among the most common causes of opportunistic infection after transplantation. The risk for viral infection is a function of the specific virus encountered, the intensity of immune suppression used to prevent graft rejection, and other host factors governing susceptibility. Although cytomegalovirus is the most common opportunistic pathogen seen in transplant recipients, numerous other viruses have also affected outcomes. In some cases, preventive measures such as pretransplant screening, prophylactic antiviral therapy, or posttransplant viral monitoring may limit the impact of these infections. Recent advances in laboratory monitoring and antiviral therapy have improved outcomes. Studies of viral latency, reactivation, and the cellular effects of viral infection will provide clues for future strategies in prevention and treatment of viral infections. This paper will summarize the major viral infections seen following transplant and discuss strategies for prevention and management of these potential pathogens.

Immunological changes in response to herpesvirus infection in abalone Haliotis laevigata and Haliotis rubra hybrids.

Science.gov (United States)

Dang, Vinh T; Benkendorff, Kirsten; Corbeil, Serge; Williams, Lynette M; Hoad, John; Crane, Mark St J; Speck, Peter

2013-02-01

Australian abalone production has been affected by outbreaks of abalone viral ganglioneuritis (AVG) caused by a herpesvirus (AbHV). In this study, we undertook experimental transmission trials by immersion to study the abalone immune response to infection with AbHV. Representative cellular and humoural immune parameters of abalone, including total haemocyte count (THC), superoxide anion (SO) and antiviral activity against herpes simplex virus type 1 (HSV-1), were examined in apparently healthy (sub-clinical) and moribund abalone after challenge. In the early infection, sub-clinical stage (days 1-3), THC was found to increase significantly in infected abalone. TaqMan qPCR confirmed 20.5% higher viral load in moribund abalone compared to apparently healthy abalone, indicating that the abundance of AbHV within abalone is linked to their clinical signs. At the clinical stage of infection, THC was significantly lower in moribund abalone, but increased in AbHV-exposed but apparently healthy abalone, in comparison to non-infected controls. SO was reduced in all abalone that were PCR-positive for AbHV. THC and SO level were found to be negatively correlated with the presence of AbHV in abalone, but no effect of AbVH exposure was observed on the haemolymph antiviral activity. These results suggest that abalone mount an initial cellular immune response to AbHV infection, but this response cannot be sustained under high viral loads, leading to mortality. Copyright © 2012 Elsevier Ltd. All rights reserved.

Viral Metagenomics: MetaView Software

Energy Technology Data Exchange (ETDEWEB)

Zhou, C; Smith, J

2007-10-22

The purpose of this report is to design and develop a tool for analysis of raw sequence read data from viral metagenomics experiments. The tool should compare read sequences of known viral nucleic acid sequence data and enable a user to attempt to determine, with some degree of confidence, what virus groups may be present in the sample. This project was conducted in two phases. In phase 1 we surveyed the literature and examined existing metagenomics tools to educate ourselves and to more precisely define the problem of analyzing raw read data from viral metagenomic experiments. In phase 2 we devised an approach and built a prototype code and database. This code takes viral metagenomic read data in fasta format as input and accesses all complete viral genomes from Kpath for sequence comparison. The system executes at the UNIX command line, producing output that is stored in an Oracle relational database. We provide here a description of the approach we came up with for handling un-assembled, short read data sets from viral metagenomics experiments. We include a discussion of the current MetaView code capabilities and additional functionality that we believe should be added, should additional funding be acquired to continue the work.

Acute Pancreatitis in acute viral hepatitis

Directory of Open Access Journals (Sweden)

S K.C.

2011-03-01

Full Text Available Introduction: The association of acute viral hepatitis and acute pancreatitis is well described. This study was conducted to find out the frequency of pancreatic involvement in acute viral hepatitis in the Nepalese population. Methods: Consecutive patients of acute viral hepatitis presenting with severe abdominal pain between January 2005 and April 2010 were studied. Patients with history of significant alcohol consumption and gall stones were excluded. Acute viral hepatitis was diagnosed by clinical examination, liver function test, ultrasound examination and confirmed by viral serology. Pancreatitis was diagnosed by clinical presentation, biochemistry, ultrasound examination and CT scan. Results: Severe abdominal pain was present in 38 of 382 serologically-confirmed acute viral hepatitis patients. Twenty five patients were diagnosed to have acute pancreatitis. The pancreatitis was mild in 14 and severe in 11 patients. The etiology of pancreatitis was hepatitis E virus in 18 and hepatitis A virus in 7 patients. Two patients died of complications secondary to shock. The remaining patients recovered from both pancreatitis and hepatitis on conservative treatment. Conclusions: Acute pancreatitis occurred in 6.5 % of patients with acute viral hepatitis. Cholelithiasis and gastric ulcers are the other causes of severe abdominal pain. The majority of the patients recover with conservative management. Keywords: acute viral hepatitis, acute pancreatitis, pain abdomen, hepatitis E, hepatitis A, endemic zone

Effect of HFE gene polymorphism on sustained virological response in patients with chronic hepatitis C and elevated serum ferritin.

Science.gov (United States)

Coelho-Borges, Silvia; Cheinquer, Hugo; Wolff, Fernando Herz; Cheinquer, Nelson; Krug, Luciano; Ashton-Prolla, Patricia

2012-01-01

Abnormal serum ferritin levels are found in approximately 20%-30% of the patients with chronic hepatitis C and are associated with a lower response rate to interferon therapy. To determine if the presence of HFE gene mutations had any effect on the sustained virological response rate to interferon based therapy in chronic hepatitis C patients with elevated serum ferritin. A total of 44 treatment naÏve patients with histologically demonstrated chronic hepatitis C, all infected with hepatitis C virus genotype non-1 (38 genotype 3; 6 genotype 2) and serum ferritin above 500 ng/mL were treated with interferon (3 MU, 3 times a week) and ribavirin (1.000 mg, daily) for 24 weeks. Sustained virological response was defined as negative qualitative HCV-RNA more than 24 weeks after the end of treatment. Serum HCV-RNA was measured by qualitative in house polymerase chain reaction with a limit of detection of 200 IU/mL. HFE gene mutation was detected using restriction-enzyme digestion with RsaI (C282Y mutation analysis) and BclI (H63D mutation analysis) in 16 (37%) patients, all heterozygous (11 H63D, 2 C282Y and 3 both). Sustained virological response was achieved in 0 of 16 patients with HFE gene mutations and 11 (41%) of 27 patients without HFE gene mutations (P = 0.002; exact Fisher test). Heterozigozity for H63D and/or C282Y HFE gene mutation predicts absence of sustained virological response to combination treatment with interferon and ribavirin in patients with chronic hepatitis C, non-1 genotype and serum ferritin levels above 500 ng/mL.

Human leukocyte antigen and cytokine receptor gene polymorphisms associated with heterogeneous immune responses to mumps viral vaccine.

Science.gov (United States)

Ovsyannikova, Inna G; Jacobson, Robert M; Dhiman, Neelam; Vierkant, Robert A; Pankratz, V Shane; Poland, Gregory A

2008-05-01

Mumps outbreaks continue to occur throughout the world, including in highly vaccinated populations. Vaccination against mumps has been successful; however, humoral and cellular immune responses to mumps vaccines vary significantly from person to person. We set out to assess whether HLA and cytokine gene polymorphisms are associated with variations in the immune response to mumps viral vaccine. To identify genetic factors that might contribute to variations in mumps vaccine-induced immune responses, we performed HLA genotyping in a group of 346 healthy schoolchildren (12-18 years of age) who previously received 2 doses of live mumps vaccine. Single-nucleotide polymorphisms (minor allele frequency of >5%) in cytokine and cytokine receptor genes were genotyped for a subset of 118 children. Median values for mumps-specific antibody titers and lymphoproliferative stimulation indices were 729 IU/mL and 4.8, respectively. Girls demonstrated significantly higher mumps antibody titers than boys, indicating gender-linked genetic differences in humoral immune response. Significant associations were found between the HLA-DQB1*0303 alleles and lower mumps-specific antibody titers. An interesting finding was the association of several HLA class II alleles with mumps-specific lymphoproliferation. Alleles of the DRB1 (*0101, *0301, *0801, *1001, *1201, and *1302), DQA1 (*0101, *0105, *0401, and *0501), and DQB1 (*0201, *0402, and *0501) loci were associated with significant variations in lymphoproliferative immune responses to mumps vaccine. Additional associations were observed with single-nucleotide polymorphisms in the interleukin-10RA, interleukin-12RB1, and interleukin-12RB2 cytokine receptor genes. Minor alleles for 4 single-nucleotide polymorphisms within interleukin-10RA and interleukin-12RB genes were associated with variations in humoral and cellular immune responses to mumps vaccination. These data suggest the important role of HLA and immunoregulatory cytokine receptor

iNKT Cells and Their potential Lipid Ligands during Viral Infection

Directory of Open Access Journals (Sweden)

Anunya eOpasawatchai

2015-07-01

Full Text Available Invariant natural killer T (iNKT cells are a unique population of lipid reactive CD1d restricted innate-like T lymphocytes. Despite being a minor population, they serve as an early source of cytokines and promote immunological crosstalk thus bridging innate and adaptive immunity. Diseases ranging from allergy, autoimmunity, and cancer as well as infectious diseases, including viral infection, have been reported to be influenced by iNKT cells. However, it remains unclear how iNKT cells are activated during viral infection, as virus derived lipid antigens have not been reported. Cytokines may activate iNKT cells during infections from influenza and murine cytomegalovirus (MCMV, although CD1d dependent activation is evident in other viral infections. Several viruses, such as dengue virus (DENV, induce CD1d upregulation which correlates with iNKT cell activation. In contrast, Herpes simplex virus type 1 (HSV-1, Human immunodeficiency virus (HIV, Epstein-Barr virus (EBV and Human papiloma virus (HPV promote CD1d downregulation as a strategy to evade iNKT cell recognition. These observations suggest the participation of a CD1d-dependent process in the activation of iNKT cells in response to viral infection. Endogenous lipid ligands, including phospholipids as well as glycosphingolipids, such as glucosylceramide have been proposed to mediate iNKT cell activation. Pro-inflammatory signals produced during viral infection may stimulate iNKT cells through enhanced CD1d dependent endogenous lipid presentation. Furthermore, viral infection may alter lipid composition and inhibit endogenous lipid degradation. Recent advances in this field are reviewed.

Viral infections in allergy and immunology: How allergic inflammation influences viral infections and illness.

Science.gov (United States)

Edwards, Michael R; Strong, Katherine; Cameron, Aoife; Walton, Ross P; Jackson, David J; Johnston, Sebastian L

2017-10-01

Viral respiratory tract infections are associated with asthma inception in early life and asthma exacerbations in older children and adults. Although how viruses influence asthma inception is poorly understood, much research has focused on the host response to respiratory viruses and how viruses can promote; or how the host response is affected by subsequent allergen sensitization and exposure. This review focuses on the innate interferon-mediated host response to respiratory viruses and discusses and summarizes the available evidence that this response is impaired or suboptimal. In addition, the ability of respiratory viruses to act in a synergistic or additive manner with T H 2 pathways will be discussed. In this review we argue that these 2 outcomes are likely linked and discuss the available evidence that shows reciprocal negative regulation between innate interferons and T H 2 mediators. With the renewed interest in anti-T H 2 biologics, we propose a rationale for why they are particularly successful in controlling asthma exacerbations and suggest ways in which future clinical studies could be used to find direct evidence for this hypothesis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

When not every response to climate change is a good one: identifying principles for sustainable adaptation

CSIR Research Space (South Africa)

Eriksen, S

2011-01-01

Full Text Available to the need for sustainable adaptation strategies and measures that contribute to social justice and environmental integrity. This paper presents four normative principles to guide responses to climate change and illustrates the significance...

Viral O-GalNAc peptide epitopes

DEFF Research Database (Denmark)

Olofsson, Sigvard; Blixt, Klas Ola; Bergström, Tomas

2016-01-01

Viral envelope glycoproteins are major targets for antibodies that bind to and inactivate viral particles. The capacity of a viral vaccine to induce virus-neutralizing antibodies is often used as a marker for vaccine efficacy. Yet the number of known neutralization target epitopes is restricted o...

[Viral encephalitis virus, a new bioterrorist menace].

Science.gov (United States)

Rigaudeau, Sophie; Micol, Romain; Bricaire, François; Bossi, Philippe

2005-01-29

Often responsible for little known infections, today viral encephalitis viruses appear as a new bioterrorist menace, because of their easy production and their great pathogenic potential. Spraying is the best way to permit the rapid diffusion of certain encephalitis viruses. Diagnosis of viral encephalitis, predominating in tropical surroundings, is difficult. In the majority of cases, symptoms differ little from those of common flu. With supplementary examinations, the biological abnormalities are usually non-specific. There are no characteristic images on scans or MRI. Identification of the virus in the nasopharynx, blood or cerebrospinal fluid, in serology, PCR or RT-PCR permits confirmation of the virus. Treatment is essentially symptomatic and relies on appropriate reanimation measures. Ribavirin can be indicated in some cases such as the Rift Valley fever, but is formally contraindicated in West Nile encephalitis. The aim of terrorist groups who would use this type of weapon is more to provoke panic and disorganisation than to kill as many people as possible.

HVR-1 quasispecies modifications occur early and are correlated to initial but not sustained response in HCV-infected patients treated with pegylated- or standard-interferon and ribavirin.

Science.gov (United States)

Abbate, Isabella; Lo Iacono, Oreste; Di Stefano, Rosa; Cappiello, Giuseppina; Girardi, Enrico; Longo, Roberta; Ferraro, Donatella; Antonucci, Giorgio; Di Marco, Vito; Solmone, Mariacarmela; Craxì, Antonio; Ippolito, Giuseppe; Capobianchi, Maria R

2004-05-01

HVR-1 quasispecies composition and evolution were investigated in patients chronically infected with genotype 1b HCV, treated with PEG-IFN alpha 2b or STD-IFN alpha 2b plus RBV. HVR-1 heterogeneity was assessed by calculating nucleotidic complexity, diversity, synonymous (S) and non-synonymous (NS) substitutions at baseline, after 4 weeks of therapy (T1) and at follow-up (T18). Evolution of viral quasispecies was analysed by constructing phylogenetic trees. No correlation of baseline viremia with heterogeneity was observed. Nucleotidic complexity was lower in patients showing early virological response, and tended to be inversely correlated to viral load decline at 4 weeks of treatment. In the majority of SR, profound changes of quasispecies composition occurred during 4 weeks of treatment, while in NR virtually no major changes of pre-therapy variants were observed. Relapse showed both patterns of quasispecies evolution. Virus quasispecies after follow-up was similar to that found at T1 in both Relapsers and NR patients. Baseline parameters of HVR-1 heterogeneity seem to be involved in the early response to treatment, and early response is associated with profound variations in the HVR-1 quasispecies. Viral quasispecies surviving early therapeutic pressure are most likely able to give rise to either virus rebound or persistence at T18.

Viral infection upregulates myostatin promoter activity in orange-spotted grouper (Epinephelus coioides).

Science.gov (United States)

Chen, Yi-Tien; Lin, Chao-Fen; Chen, Young-Mao; Lo, Chih-En; Chen, Wan-Erh; Chen, Tzong-Yueh

2017-01-01

Myostatin is a negative regulator of myogenesis and has been suggested to be an important factor in the development of muscle wasting during viral infection. The objective of this study was to characterize the main regulatory element of the grouper myostatin promoter and to study changes in promoter activity due to viral stimulation. In vitro and in vivo experiments indicated that the E-box E6 is a positive cis-and trans-regulation motif, and an essential binding site for MyoD. In contrast, the E-box E5 is a dominant negative cis-regulatory. The characteristics of grouper myostatin promoter are similar in regulation of muscle growth to that of other species, but mainly through specific regulatory elements. According to these results, we conducted a study to investigate the effect of viral infection on myostatin promoter activity and its regulation. The nervous necrosis virus (NNV) treatment significantly induced myostatin promoter activity. The present study is the first report describing that specific myostatin motifs regulate promoter activity and response to viral infection.

Viral infection upregulates myostatin promoter activity in orange-spotted grouper (Epinephelus coioides.

Directory of Open Access Journals (Sweden)

Yi-Tien Chen

Full Text Available Myostatin is a negative regulator of myogenesis and has been suggested to be an important factor in the development of muscle wasting during viral infection. The objective of this study was to characterize the main regulatory element of the grouper myostatin promoter and to study changes in promoter activity due to viral stimulation. In vitro and in vivo experiments indicated that the E-box E6 is a positive cis-and trans-regulation motif, and an essential binding site for MyoD. In contrast, the E-box E5 is a dominant negative cis-regulatory. The characteristics of grouper myostatin promoter are similar in regulation of muscle growth to that of other species, but mainly through specific regulatory elements. According to these results, we conducted a study to investigate the effect of viral infection on myostatin promoter activity and its regulation. The nervous necrosis virus (NNV treatment significantly induced myostatin promoter activity. The present study is the first report describing that specific myostatin motifs regulate promoter activity and response to viral infection.

36 CFR 219.20 - Ecological sustainability.

Science.gov (United States)

2010-07-01

... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Ecological sustainability... Sustainability § 219.20 Ecological sustainability. To achieve ecological sustainability, the responsible official... diversity and species diversity are components of ecological sustainability. The planning process must...

Corporate sustainability, social responsibility and environmental management : an introduction to theory and practice with case studies

OpenAIRE

Camilleri, Mark Anthony

2017-01-01

Responsible behaviours are increasingly being embedded into new business models and strategies that are designed to meet environmental, societal and governance deficits. Therefore, the notions of Corporate Sustainability, Social Responsibility and Environmental Management have become very popular among academia as corporations are moving beyond transparency, business ethics and stakeholder engagement. This book provides business students and scholars with a broad analysis on the subject ...

Treatment-Induced Viral Cure of Hepatitis C Virus-Infected Patients Involves a Dynamic Interplay among three Important Molecular Players in Lipid Homeostasis: Circulating microRNA (miR)-24, miR-223, and Proprotein Convertase Subtilisin/Kexin Type 9.

Science.gov (United States)

Hyrina, Anastasia; Olmstead, Andrea D; Steven, Paul; Krajden, Mel; Tam, Edward; Jean, François

2017-09-01

In patients with chronic hepatitis C virus (HCV) infection, viral hijacking of the host-cell biosynthetic pathways is associated with altered lipid metabolism, which contributes to disease progression and may influence antiviral response. We investigated the molecular interplay among four key regulators of lipid homeostasis [microRNA (miR)-122, miR-24, miR-223, and proprotein convertase subtilisin/kexin type 9 (PCSK9)] in HCV-infected patients (n=72) who achieved a treatment-based viral cure after interferon-based therapy with first-generation direct-acting antivirals. Real-time PCR was used to quantify microRNA plasma levels, and ELISA assays were used to determine plasma concentrations of PCSK9. We report that levels of miR-24 and miR-223 significantly increased in patients achieving sustained virologic response (SVR), whereas the levels of miR-122, a liver-specific cofactor for HCV infection, decreased in these patients. PCSK9 concentrations were significantly increased in SVRs, suggesting that PCSK9 may help impede viral infection. The modulatory effect of PCSK9 on HCV infection was also demonstrated in the context of HCV-infected Huh-7.5.1 cells employing recombinant human PCSK9 mutants. Together, these results provide insights into a novel coordinated interplay among three important molecular players in lipid homeostasis - circulating miR-24, miR-223 and PCSK9 - whose regulation is affected by HCV infection and treatment-based viral cure. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Prediction of therapy response to interferon-alpha in chronic viral hepatitis-B by liver and hepatobiliary scintigraphy

International Nuclear Information System (INIS)

Caglar, M.; Sari, O.; Akcan, Y.

2002-01-01

Interferon (IFN) provides effective treatment in some patients with chronic hepatitis. The clarification of factors predictive of therapy response would be helpful in identifying patients who would benefit from treatment. In this study, we evaluated the potential utility of Tc-99m sulfur colloid liver/spleen and Tc-99m-disofenin hepatobiliary scintigraphy to predict therapy response to IFN in patients with chronic active hepatitis. The study group consisted of ten patients with chronic viral hepatitis B who were treated with 4.5 units of interferon alpha for 12 months. Prior to the start of the therapy, sulfur colloid scintigraphy was obtained by which the liver/spleen ratios were derived. Hepatobiliary scintigraphy was performed on a separate day and time-activity curves were generated from regions of interest drawn over the liver, heart and gall-bladder. The index of blood and liver clearance time was calculated. Histological grading and laboratory values were obtained for clinical correlation. Responders (n=6) to IFN were defined as those who improved clinically with normalized transaminase levels and had hepatitis B envelope antigen (HBeAg) seroconversion. On sulfur colloid (SC) scintigraphy, the liver/spleen ratio of non-responders was significantly lower than responders (median values: 0.69 vs. 1.16, p=0.01) but on hepatobiliary scintigraphy no statistically significant parameters were found to predict response to interferon therapy. (author)

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.

[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

Assembly of viral genomes from metagenomes

Directory of Open Access Journals (Sweden)

Saskia L Smits

2014-12-01

Full Text Available Viral infections remain a serious global health issue. Metagenomic approaches are increasingly used in the detection of novel viral pathogens but also to generate complete genomes of uncultivated viruses. In silico identification of complete viral genomes from sequence data would allow rapid phylogenetic characterization of these new viruses. Often, however, complete viral genomes are not recovered, but rather several distinct contigs derived from a single entity, some of which have no sequence homology to any known proteins. De novo assembly of single viruses from a metagenome is challenging, not only because of the lack of a reference genome, but also because of intrapopulation variation and uneven or insufficient coverage. Here we explored different assembly algorithms, remote homology searches, genome-specific sequence motifs, k-mer frequency ranking, and coverage profile binning to detect and obtain viral target genomes from metagenomes. All methods were tested on 454-generated sequencing datasets containing three recently described RNA viruses with a relatively large genome which were divergent to previously known viruses from the viral families Rhabdoviridae and Coronaviridae. Depending on specific characteristics of the target virus and the metagenomic community, different assembly and in silico gap closure strategies were successful in obtaining near complete viral genomes.

A temporal gate for viral enhancers to co-opt Toll-like-receptor transcriptional activation pathways upon acute infection.

Directory of Open Access Journals (Sweden)

Kai A Kropp

2015-04-01

Full Text Available Viral engagement with macrophages activates Toll-Like-Receptors (TLRs and viruses must contend with the ensuing inflammatory responses to successfully complete their replication cycle. To date, known counter-strategies involve the use of viral-encoded proteins that often employ mimicry mechanisms to block or redirect the host response to benefit the virus. Whether viral regulatory DNA sequences provide an opportunistic strategy by which viral enhancer elements functionally mimic innate immune enhancers is unknown. Here we find that host innate immune genes and the prototypical viral enhancer of cytomegalovirus (CMV have comparable expression kinetics, and positively respond to common TLR agonists. In macrophages but not fibroblasts we show that activation of NFκB at immediate-early times of infection is independent of virion-associated protein, M45. We find upon virus infection or transfection of viral genomic DNA the TLR-agonist treatment results in significant enhancement of the virus transcription-replication cycle. In macrophage time-course infection experiments we demonstrate that TLR-agonist stimulation of the viral enhancer and replication cycle is strictly delimited by a temporal gate with a determined half-maximal time for enhancer-activation of 6 h; after which TLR-activation blocks the viral transcription-replication cycle. By performing a systematic siRNA screen of 149 innate immune regulatory factors we identify not only anticipated anti-viral and pro-viral contributions but also new factors involved in the CMV transcription-replication cycle. We identify a central convergent NFκB-SP1-RXR-IRF axis downstream of TLR-signalling. Activation of the RXR component potentiated direct and indirect TLR-induced activation of CMV transcription-replication cycle; whereas chromatin binding experiments using wild-type and enhancer-deletion virus revealed IRF3 and 5 as new pro-viral host transcription factor interactions with the CMV enhancer in

A Rapid Blood Test To Determine the Active Status and Duration of Acute Viral Infection.

Science.gov (United States)

Zheng, Tianyu; Finn, Caroline; Parrett, Christopher J; Dhume, Kunal; Hwang, Ji Hae; Sidhom, David; Strutt, Tara M; Li Sip, Yuen Yee; McKinstry, Karl K; Huo, Qun

2017-11-10

The ability to rapidly detect and diagnose acute viral infections is crucial for infectious disease control and management. Serology testing for the presence of virus-elicited antibodies in blood is one of the methods used commonly for clinical diagnosis of viral infections. However, standard serology-based tests have a significant limitation: they cannot easily distinguish active from past, historical infections. As a result, it is difficult to determine whether a patient is currently infected with a virus or not, and on an optimal course of action, based off of positive serology testing responses. Here, we report a nanoparticle-enabled blood test that can help overcome this major challenge. The new test is based on the analysis of virus-elicited immunoglobulin G (IgG) antibody present in the protein corona of a gold nanoparticle surface upon mixing the gold nanoparticles with blood sera. Studies conducted on mouse models of influenza A virus infection show that the test gives positive responses only in the presence of a recent acute viral infection, approximately between day 14 and day 21 following the infection, and becomes negative thereafter. When used together with the traditional serology testing, the nanoparticle test can determine clearly whether a positive serology response is due to a recent or historical viral infection. This new blood test can provide critical clinical information needed to optimize further treatment and/or to determine if further quarantining should be continued.

Viral Small-RNA Analysis of Bombyx mori Larval Midgut during Persistent and Pathogenic Cytoplasmic Polyhedrosis Virus Infection.

Science.gov (United States)

Zografidis, Aris; Van Nieuwerburgh, Filip; Kolliopoulou, Anna; Apostolou-Karampelis, Konstantinos; Head, Steven R; Deforce, Dieter; Smagghe, Guy; Swevers, Luc

2015-11-01

The lepidopteran innate immune response against RNA viruses remains poorly understood, while in other insects several studies have highlighted an essential role for the exo-RNAi pathway in combating viral infection. Here, by using deep-sequencing technology for viral small-RNA (vsRNA) assessment, we provide evidence that exo-RNAi is operative in the silkworm Bombyx mori against both persistent and pathogenic infection of B. mori cytoplasmic polyhedrosis virus (BmCPV) which is characterized by a segmented double-stranded RNA (dsRNA) genome. Further, we show that Dicer-2 predominantly targets viral dsRNA and produces 20-nucleotide (nt) vsRNAs, whereas an additional pathway is responsive to viral mRNA derived from segment 10. Importantly, vsRNA distributions, which define specific hot and cold spot profiles for each viral segment, to a considerable degree overlap between Dicer-2-related (19 to 21 nt) and Dicer-2-unrelated vsRNAs, suggesting a common origin for these profiles. We found a degenerate motif significantly enriched at the cut sites of vsRNAs of various lengths which link an unknown RNase to the origins of vsRNAs biogenesis and distribution. Accordingly, the indicated RNase activity may be an important early factor for the host's antiviral defense in Lepidoptera. This work contributes to the elucidation of the lepidopteran antiviral response against infection of segmented double-stranded RNA (dsRNA) virus (CPV; Reoviridae) and highlights the importance of viral small-RNA (vsRNA) analysis for getting insights into host-pathogen interactions. Three vsRNA pathways are implicated in antiviral defense. For dsRNA, two pathways are proposed, either based on Dicer-2 cleavage to generate 20-nucleotide vsRNAs or based on the activity of an uncharacterized endo-RNase that cleaves the viral RNA substrate at a degenerate motif. The analysis also indicates the existence of a degradation pathway that targets the positive strand of segment 10. Copyright © 2015, American

CONCEPTUAL DELIMITATIONS ON SUSTAINABLE DEVELOPMENT

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Ienciu Ionel-Alin

2013-07-01

Full Text Available Sustainable development is a model for resource use meant to satisfy human needs, without polluting the environment, so that these needs can be satisfied not only in the present, but in the future as well. It is a concept of nowadays with no generally accepted definition, placing environment first and foremost, aiming at implementing the environmental policies in all structures and at all economic levels. Within the present study we have aimed at creating a conceptual delimitation on sustainable development, sustainability and socialresponsibility, concepts of present interest, that tend to become a mystery for the academic community and practitioners by their variety and complexity of approaches. During our scientific endeavor we believe that social responsibility is the foundation of sustainable development. Sustainable development is a concept used especially at macro-economic level, while social responsibility is used at entity level and incorporates the economic, environmental and social dimension, which has a voluntary character and tries to respond to the information needs of the society and other stakeholders. Sustainability at the entity\\'s level is the goal or final objective of sustainable development – satisfaction of present needs without compromising the possibility for future generations to satisfy their own needs, while social responsibility is an intermediate phase of sustainability wherein entities try to balance the economic, social and environmental dimension. Thus, we can state we include ourselves within social corporatism, slightly close to social institutionalism, which is characteristic to developed countries, giving a particular importance to social contract and relations between entity and society. We believe that in Romania, a POSDRU funded project should be regarded as a legal person with social values, which must be based on sustainable development and to promote, besides legal liability of automatically deriving

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...

Pivotal role of cardiomyocyte TGF-β signaling in the murine pathological response to sustained pressure overload

NARCIS (Netherlands)

Koitabashi, Norimichi; Danner, Thomas; Zaiman, Ari L.; Pinto, Yigal M.; Rowell, Janelle; Mankowski, Joseph; Zhang, Dou; Nakamura, Taishi; Takimoto, Eiki; Kass, David A.

2011-01-01

The cardiac pathological response to sustained pressure overload involves myocyte hypertrophy and dysfunction along with interstitial changes such as fibrosis and reduced capillary density. These changes are orchestrated by mechanical forces and factors secreted between cells. One such secreted

Ethical Considerations in Research Participation Virality.

Science.gov (United States)

Ellis-Barton, Carol

2016-07-01

This article seeks to commence and encourage discussion around the upcoming ethical challenges of virality in network structures. When the call for participation in a research project on lupus in Ireland went from an advertisement in a newsletter to a meme (unit of transmissible information) on a closed Facebook page, the ethical considerations of virality were raised. The article analyzes the Association of Internet Researchers guidelines, Facebook policies, and the context of privacy in relation to virality. Virality creates the leverage for methodological pluralism. The nature of the inquiry can determine the method rather than the other way around. Viral ethical considerations are evolving due to the cyber world becoming the primary meme of communication, with flexibility in the researcher's protocol providing opportunities for efficient, cost-effective, and diverse recruitment. © The Author(s) 2016.

The N-Terminal of Aquareovirus NS80 Is Required for Interacting with Viral Proteins and Viral Replication.

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Jie Zhang

Full Text Available Reovirus replication and assembly occurs within viral inclusion bodies that formed in specific intracellular compartments of cytoplasm in infected cells. Previous study indicated that aquareovirus NS80 is able to form inclusion bodies, and also can retain viral proteins within its inclusions. To better understand how NS80 performed in viral replication and assembly, the functional regions of NS80 associated with other viral proteins in aquareovirus replication were investigated in this study. Deletion mutational analysis and rotavirus NSP5-based protein association platform were used to detect association regions. Immunofluorescence images indicated that different N-terminal regions of NS80 could associate with viral proteins VP1, VP4, VP6 and NS38. Further co-immunoprecipitation analysis confirmed the interaction between VP1, VP4, VP6 or NS38 with different regions covering the N-terminal amino acid (aa, 1-471 of NS80, respectively. Moreover, removal of NS80 N-terminal sequences required for interaction with proteins VP1, VP4, VP6 or NS38 not only prevented the capacity of NS80 to support viral replication in NS80 shRNA-based replication complementation assays, but also inhibited the expression of aquareovirus proteins, suggesting that N-terminal regions of NS80 are necessary for viral replication. These results provided a foundational basis for further understanding the role of NS80 in viral replication and assembly during aquareovirus infection.

Viral MicroRNAs Repress the Cholesterol Pathway, and 25-Hydroxycholesterol Inhibits Infection.

Science.gov (United States)

Serquiña, Anna K P; Kambach, Diane M; Sarker, Ontara; Ziegelbauer, Joseph M

2017-07-11

From various screens, we found that Kaposi's sarcoma-associated herpesvirus (KSHV) viral microRNAs (miRNAs) target several enzymes in the mevalonate/cholesterol pathway. 3-Hydroxy-3-methylglutaryl-coenzyme A (CoA) synthase 1 (HMGCS1), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR [a rate-limiting step in the mevalonate pathway]), and farnesyl-diphosphate farnesyltransferase 1 (FDFT1 [a committed step in the cholesterol branch]) are repressed by multiple KSHV miRNAs. Transfection of viral miRNA mimics in primary endothelial cells (human umbilical vein endothelial cells [HUVECs]) is sufficient to reduce intracellular cholesterol levels; however, small interfering RNAs (siRNAs) targeting only HMGCS1 did not reduce cholesterol levels. This suggests that multiple targets are needed to perturb this tightly regulated pathway. We also report here that cholesterol levels were decreased in de novo -infected HUVECs after 7 days. This reduction is at least partially due to viral miRNAs, since the mutant form of KSHV lacking 10 of the 12 miRNA genes had increased cholesterol compared to wild-type infections. We hypothesized that KSHV is downregulating cholesterol to suppress the antiviral response by a modified form of cholesterol, 25-hydroxycholesterol (25HC). We found that the cholesterol 25-hydroxylase (CH25H) gene, which is responsible for generating 25HC, had increased expression in de novo -infected HUVECs but was strongly suppressed in long-term latently infected cell lines. We found that 25HC inhibits KSHV infection when added exogenously prior to de novo infection. In conclusion, we found that multiple KSHV viral miRNAs target enzymes in the mevalonate pathway to modulate cholesterol in infected cells during latency. This repression of cholesterol levels could potentially be beneficial to viral infection by decreasing the levels of 25HC. IMPORTANCE A subset of viruses express unique microRNAs (miRNAs), which act like cellular miRNAs to generally repress host gene

Encefalitis virales en la infancia

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Monserrat Téllez de Meneses

2013-09-01

Full Text Available La encefalitis viral es una enfermedad grave que implica el compromiso inflamatorio del parénquima cerebral. Las infecciones virales del SNC ocurren con frecuencia como complicación de infecciones virales sistémicas. Más de 100 virus están implicados como agentes causales, entre los cuales el virus Herpes simplex tipo I, es el agente causal más frecuente de encefalitis no epidémica en todos los grupos poblacionales del mundo; es el responsable de los casos más graves en todas las edades. Muchos de los virus para los cuales existe vacunas también pueden causar encefalitis como: sarampión, paperas, polio, rabia, rubéola, varicela. El virus produce una inflamación del tejido cerebral, la cual puede evolucionar a una destrucción de neuronas, provocar hemorragia y daño cerebral, dando lugar a encefalitis graves, como la encefalitis necrotizante o hemorrágica, con mucho peor pronóstico, produciendo secuelas graves, incluso la muerte. El cuadro clínico, incluye la presencia de cefalea, fiebre y alteración de la conciencia, de rápida progresión. El pronóstico de las encefalitis víricas es variable, algunos casos son leves, con recuperación completa, sin embargo existen casos graves que pueden ocasionar secuelas importantes a nivel cerebral. Es fundamental realizar un diagnóstico lo antes posible, a través de pruebas de laboratorio (bioquímica, PCR, cultivos y de neuroimagen (TAC, RM y ante todo, la instauración de un tratamiento precoz para evitar la evolución del proceso y sus posibles complicaciones. El pronóstico empeora si se retrasa la instauración del tratamiento.

Effect of HFE gene polymorphism on sustained virological response in patients with chronic hepatitis C and elevated serum ferritin

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Silvia Coelho-Borges

2012-03-01

Full Text Available CONTEXT: Abnormal serum ferritin levels are found in approximately 20%-30% of the patients with chronic hepatitis C and are associated with a lower response rate to interferon therapy. OBJECTIVE: To determine if the presence of HFE gene mutations had any effect on the sustained virological response rate to interferon based therapy in chronic hepatitis C patients with elevated serum ferritin. METHODS: A total of 44 treatment naÏve patients with histologically demonstrated chronic hepatitis C, all infected with hepatitis C virus genotype non-1 (38 genotype 3; 6 genotype 2 and serum ferritin above 500 ng/mL were treated with interferon (3 MU, 3 times a week and ribavirin (1.000 mg, daily for 24 weeks. RESULTS: Sustained virological response was defined as negative qualitative HCV-RNA more than 24 weeks after the end of treatment. Serum HCV-RNA was measured by qualitative in house polymerase chain reaction with a limit of detection of 200 IU/mL. HFE gene mutation was detected using restriction-enzyme digestion with RsaI (C282Y mutation analysis and BclI (H63D mutation analysis in 16 (37% patients, all heterozygous (11 H63D, 2 C282Y and 3 both. Sustained virological response was achieved in 0 of 16 patients with HFE gene mutations and 11 (41% of 27 patients without HFE gene mutations (P = 0.002; exact Fisher test. CONCLUSION: Heterozigozity for H63D and/or C282Y HFE gene mutation predicts absence of sustained virological response to combination treatment with interferon and ribavirin in patients with chronic hepatitis C, non-1 genotype and serum ferritin levels above 500 ng/mL.

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

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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.

Sustainable Transportation

DEFF Research Database (Denmark)

Hall, Ralph P.; Gudmundsson, Henrik; Marsden, Greg

2014-01-01

The transportation system is the backbone of economic and social progress and the means by which humans access goods and services and connect with one another. Yet, as the scale of transportation activities has grown worldwide, so too have the negative environmental, social, and economic impacts...... that relate to the construction and maintenance of transportation infrastructure and the operation or use of the different transportation modes. The concept of sustainable transportation emerged in response to these concerns as part of the broader notion of sustainable development. Given the transportation...... sector’s significant contribution to global challenges such as climate change, it is often said that sustainable development cannot be achieved without sustainable transportation....

Lymphocyte subset contents in cerebrospinal fluid of children with viral encephalitis

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An-Ran Xu

2016-06-01

Full Text Available Objective: To study the lymphocyte subset contents in cerebrospinal fluid of children with viral encephalitis and their correlation with disease. Methods: Children with viral encephalitis were selected as VE group, children excluded of central nervous system infection by lumbar puncture or children without central nervous system diseases but receiving surgery with spinal anesthesia were selected as control group, and then cerebrospinal fluid and serum were collected to detect lymphocyte subset contents, nerve injury molecule contents as well as inflammatory response indicators and oxidative stress response indicators. Results: CD3+, CD3+CD4+, CD4/CD8 and CD16+CD56+ in cerebrospinal fluid of VE group were lower than those of control group, and both CD3+CD8+ and CD19+ were higher than those of control group; CD3+, CD3+CD4+, CD4/CD8 and CD16+CD56+ in cerebrospinal fluid of children with abnormal MRI were lower than those of children with normal MRI, and both CD3+CD8+ and CD19+ were higher than those of children with normal MRI; NSE, MBP, S-100 and NPT contents in cerebrospinal fluid and serum of VE group were significantly higher than those of control group and had good correlation with lymphocyte subset contents; MMP9, TNF-α and IL-6 contents in cerebrospinal fluid of VE group were significantly higher than those of control group, and SOD and GSH-Px contents were significantly lower than those of control group and had good correlation with lymphocyte subset contents. Conclusions: CD4+/CD8+T lymphocyte ratio and NK cell content decrease, and B lymphocyte content increases in cerebrospinal fluid of children with viral encephalitis, and lymphocyte subset contents have inhibitory effect on MRI manifestation, degree of inflammatory response and oxidative stress response.

Final Technical Report: Viral Infection of Subsurface Microorganisms and Metal/Radionuclide Transport

Energy Technology Data Exchange (ETDEWEB)

Weber, Karrie A.; Bender, Kelly S.; Li, Yusong

2013-09-28

Microbially mediated metabolisms have been identified as a significant factor either directly or indirectly impacting the fate and transport of heavy metal/radionuclide contaminants. To date microorganisms have been isolated from contaminated environments. Examination of annotated finished genome sequences of many of these subsurface isolates from DOE sites, revealed evidence of prior viral infection. To date the role that viruses play influencing microbial mortality and the resulting community structure which directly influences biogeochemical cycling in soils and sedimentary environments remains poorly understood. The objective of this exploratory study was to investigate the role of viral infection of subsurface bacteria and the formation of contaminant-bearing viral particles. This objective was approached by examining the following working hypotheses: (i) subsurface microorganisms are susceptible to viral infections by the indigenous subsurface viral community, and (ii) viral surfaces will adsorb heavy metals and radionuclides. Our results have addressed basic research needed to accomplish the BER Long Term Measure to provide sufficient scientific understanding such that DOE sites would be able to incorporate coupled physical, chemical and biological processes into decision making for environmental remediation or natural attenuation and long-term stewardship by establishing viral-microbial relationships on the subsequent fate and transport of heavy metals and radionuclides. Here we demonstrated that viruses play a significant role in microbial mortality and community structure in terrestrial subsurface sedimentary systems. The production of viral-like particles within subsurface sediments in response to biostimulation with dissolved organic carbon and a terminal electron acceptor resulted in the production of viral-like particles. Organic carbon alone did not result in significant viral production and required the addition of a terminal electron acceptor

Appeals to consumer responsibility and improving structural conditions as means to promote sustainable consumer behavior

DEFF Research Database (Denmark)

Thøgersen, John

for their acts or (b) structural conditions determined by governments? In field experiments with large samples of ordinary consumers, the behavioral effects of perceptions of responsibility/personal moral norms and of altering an important structural condition are quantified by measuring a relevant behavior......-developed public transit service. The results suggest that there is often more to gain from changing structural conditions to be more facilitating for the desired behavior than from a campaign targeting consumer feelings of responsibility.......Environmental policy-makers increasingly emphasize consumers' responsibility for environmental side effects of their acts, but is this justified? This paper investigates which is the most important limiting factor for sustainable consumption: (a) the extent to which consumers assume responsibility...

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....

HIV-1 viral escape in cerebrospinal fluid of subjects on suppressive antiretroviral treatment.

Science.gov (United States)

Edén, Arvid; Fuchs, Dietmar; Hagberg, Lars; Nilsson, Staffan; Spudich, Serena; Svennerholm, Bo; Price, Richard W; Gisslén, Magnus

2010-12-15

Occasional cases of viral escape in cerebrospinal fluid (CSF) despite suppression of plasma human immunodeficiency virus type 1 (HIV-1) RNA have been reported. We investigated CSF viral escape in subjects treated with commonly used antiretroviral therapy regimens in relation to intrathecal immune activation and central nervous system penetration effectiveness (CPE) rank. Sixty-nine neurologically asymptomatic subjects treated with antiretroviral therapy >6 months and plasma HIV-1 RNA penetration effectiveness rank was not a significant predictor of detectable CSF virus or CSF neopterin levels. Viral escape in CSF is more common than previously reported, suggesting that low-grade central nervous system infection may continue in treated patients. Although these findings need extension in longitudinal studies, they suggest the utility of monitoring CSF responses, as new treatment combinations and strategies modify clinical practice.

Reactive or proactive approach towards sustainability? A conceptual framework based on sustainable business models to increase stakeholders' sustainable value capture

DEFF Research Database (Denmark)

Rosati, Francesco; Morioka, Sandra; Monteiro de Carvalho, Marly

2016-01-01

and challenging companies to seek for business opportunities with an entrepreneurial attitude to help solving sustainable development challenges. By combining both approaches, organizations have the opportunity to increase sustainable value capture by its stakeholders, acting on their institutional responsibility...... as instrument to help companies describe, analyze, manage and communicate their sustainable value proposition, creation, delivery and capture mechanism. In particular, this research focuses on value capture dynamics, aiming to explore how companies can increase their contribution to sustainable development...... sustainability. In this sense, a proactive approach to foster sustainable value capture can complement the reactive approach by delivering value beyond stakeholders' expectations. In this case, companies use their capabilities to identify opportunities to create and deliver sustainable value that stakeholders...

Honeybee (Apis mellifera Venom Reinforces Viral Clearance during the Early Stage of Infection with Porcine Reproductive and Respiratory Syndrome Virus through the Up-Regulation of Th1-Specific Immune Responses

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Jin-A Lee

2015-05-01

Full Text Available Porcine reproductive and respiratory syndrome (PRRS is a chronic and immunosuppressive viral disease that is responsible for substantial economic losses for the swine industry. Honeybee venom (HBV is known to possess several beneficial biological properties, particularly, immunomodulatory effects. Therefore, this study aimed at evaluating the effects of HBV on the immune response and viral clearance during the early stage of infection with porcine reproductive and respiratory syndrome virus (PRRSV in pigs. HBV was administered via three routes of nasal, neck, and rectal and then the pigs were inoculated with PRRSV intranasally. The CD4+/CD8+ cell ratio and levels of interferon (IFN-γ and interleukin (IL-12 were significantly increased in the HBV-administered healthy pigs via nasal and rectal administration. In experimentally PRRSV-challenged pigs with virus, the viral genome load in the serum, lung, bronchial lymph nodes and tonsil was significantly decreased, as was the severity of interstitial pneumonia, in the nasal and rectal administration group. Furthermore, the levels of Th1 cytokines (IFN-γ and IL-12 were significantly increased, along with up-regulation of pro-inflammatory cytokines (TNF-α and IL-1β with HBV administration. Thus, HBV administration—especially via the nasal or rectal route—could be a suitable strategy for immune enhancement and prevention of PRRSV infection in pigs.

Tip60 degradation by adenovirus relieves transcriptional repression of viral transcriptional activator EIA.

Science.gov (United States)

Gupta, A; Jha, S; Engel, D A; Ornelles, D A; Dutta, A

2013-10-17

Adenoviruses are linear double-stranded DNA viruses that infect human and rodent cell lines, occasionally transform them and cause tumors in animal models. The host cell challenges the virus in multifaceted ways to restrain viral gene expression and DNA replication, and sometimes even eliminates the infected cells by programmed cell death. To combat these challenges, adenoviruses abrogate the cellular DNA damage response pathway. Tip60 is a lysine acetyltransferase that acetylates histones and other proteins to regulate gene expression, DNA damage response, apoptosis and cell cycle regulation. Tip60 is a bona fide tumor suppressor as mice that are haploid for Tip60 are predisposed to tumors. We have discovered that Tip60 is degraded by adenovirus oncoproteins EIB55K and E4orf6 by a proteasome-mediated pathway. Tip60 binds to the immediate early adenovirus promoter and suppresses adenovirus EIA gene expression, which is a master regulator of adenovirus transcription, at least partly through retention of the virally encoded repressor pVII on this promoter. Thus, degradation of Tip60 by the adenoviral early proteins is important for efficient viral early gene transcription and for changes in expression of cellular genes.

Sustainable IT and IT for Sustainability

Science.gov (United States)

Liu, Zhenhua

industry's first Net-zero Energy Data Center. The second thrust of this thesis is to use IT systems to improve the sustainability and efficiency of our energy infrastructure through data center demand response. The main challenges as we integrate more renewable sources to the existing power grid come from the fluctuation and unpredictability of renewable generation. Although energy storage and reserves can potentially solve the issues, they are very costly. One promising alternative is to make the cloud data centers demand responsive. The potential of such an approach is huge. To realize this potential, we need adaptive and distributed control of cloud data centers and new electricity market designs for distributed electricity resources. My work is progressing in both directions. In particular, I have designed online algorithms with theoretically guaranteed performance for data center operators to deal with uncertainties under popular demand response programs. Based on local control rules of customers, I have further designed new pricing schemes for demand response to align the interests of customers, utility companies, and the society to improve social welfare.

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 ...

Irreversible inactivation of ISG15 by a viral leader protease enables alternative infection detection strategies

NARCIS (Netherlands)

Swatek, Kirby N; Aumayr, Martina; Pruneda, Jonathan N; Visser, Linda J; Berryman, Stephen; Kueck, Anja F; Geurink, Paul P; Ovaa, Huib; van Kuppeveld, Frank J M; Tuthill, Tobias J; Skern, Tim; Komander, David

2018-01-01

In response to viral infection, cells mount a potent inflammatory response that relies on ISG15 and ubiquitin posttranslational modifications. Many viruses use deubiquitinases and deISGylases that reverse these modifications and antagonize host signaling processes. We here reveal that the leader

Viral Hepatitis: Information for Gay and Bisexual Men

Science.gov (United States)

VIRAL HEPATITIS Information for Gay and Bisexual Men What is viral hepatitis? Viral hepatitis is an infection of the liver caused by one of several ... each virus is spread in different ways. Are gay and bisexual men at risk for viral hepatitis? ...

Association between insulin resistance and sustained virologic response in hepatitis C treatment, genotypes 1 versus 2 and 3: systematic literature review and meta-analysis.

Science.gov (United States)

Laurito, Marcela Pezzoto; Parise, Edison Roberto

2013-01-01

Controversial results have been found in literature for the association between insulin resistance and sustained virologic response to standard chronic hepatitis C treatment. This study aims to provide a systematic literature review with meta-analysis, in order to evaluate if insulin resistance interferes with sustained virologic response in patients infected by the HCV genotype 1 versus HCV genotypes 2 and 3, undergoing treatment with interferon and ribavirin or pegylated interferon and ribavarin. Systematic search was performed on main electronic databases until May 2012. Primary outcome was sustained virologic response, defined as undetectable levels of HCV-RNA six months after the end of treatment. Meta-analytic measure was estimated using Dersimonian and Laird's method, using Stata software. Thirteen studies involving 2238 infected patients were included. There was a statistically significant association between insulin resistance and lower sustained virologic response rate, and this difference occurred in HCV genotype G1 (OR: 2.23; 95% CI: 1.59-3.13) and G2/G3 (OR: 4.45; 95% CI: 1.59-12.49). In addition, a difference was seen in the cut-offs used for defining insulin resistance by Homeostasis Model Assessment of Insulin Resistance. To minimize this limitation, sub-analysis that excluded the studies that did not use 2 as a cut-off value was performed and the results still demonstrated association between insulin resistance and sustained virologic response, for both genotypic groups. This meta-analysis provides evidence that elevated Homeostasis Model Assessment of Insulin Resistance is associated with a lower sustained virologic response rate in patients with hepatitis C treated with interferon and ribavirin or pegylated interferon and ribavarin, regardless of their genotype. Copyright © 2013 Elsevier Editora Ltda. All rights reserved.

Validation of Sustainable Development Practices Scale Using the Bayesian Approach to Item Response Theory

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Martin Hernani Merino

2014-12-01

Full Text Available There has been growing recognition of the importance of creating performance measurement tools for the economic, social and environmental management of micro and small enterprise (MSE. In this context, this study aims to validate an instrument to assess perceptions of sustainable development practices by MSEs by means of a Graded Response Model (GRM with a Bayesian approach to Item Response Theory (IRT. The results based on a sample of 506 university students in Peru, suggest that a valid measurement instrument was achieved. At the end of the paper, methodological and managerial contributions are presented.

Corporate social responsibility: a real options approach to the challenge of financial sustainability.

Science.gov (United States)

Bosch-Badia, Maria-Teresa; Montllor-Serrats, Joan; Tarrazon-Rodon, Maria-Antonia

2015-01-01

In contemporary complex societies, social values like ethics, corporate social responsibility, and being respectful with the environment, among others, are becoming social requirements. Corporations are expected to fulfill them and, according to empirical evidence, an overwhelming majority aspires to good social valuation. At the same time, the maximization of market share value in the long run continues to be the central corporate goal. Making environmental and social expenses compatible with value creation is a central challenge for corporations since it implies the financial sustainability of Corporate Social Responsibility (CSR). The value creation capacity of CSR projects, mainly through innovation, is widely acknowledged in economic literature and corporate practice. This fact arouses the need of having a quantitative framework capable of summarizing the value creation capacity of the variables involved in CSR projects. With this aim we build up a sensitivity analysis of real option ratios that studies and quantifies the value creation capacity of CSR projects connected with innovation. Ratio analysis has the advantage of being scale independent. Hence, it furnishes a homogeneous framework to express the interaction of value creation variables and, thus, supports strategic thinking quantitatively. Often, CSR expenses can be regarded as preliminary projects that create the opportunity to undertake a full future project. For them, we obtain the minimum expectations scenario that makes financially sustainable a preliminary project that can be interpreted as a call option. We propose a classification of CSR projects from the decision analysis perspective following a two-fold approach: Their relationship with value creation and their links with existing corporate activities. This classification of CSR projects aims at contributing to choose the best capital budgeting method to study the financial sustainability of the project and identifying those CSR projects

Corporate social responsibility: a real options approach to the challenge of financial sustainability.

Directory of Open Access Journals (Sweden)

Maria-Teresa Bosch-Badia

Full Text Available In contemporary complex societies, social values like ethics, corporate social responsibility, and being respectful with the environment, among others, are becoming social requirements. Corporations are expected to fulfill them and, according to empirical evidence, an overwhelming majority aspires to good social valuation. At the same time, the maximization of market share value in the long run continues to be the central corporate goal. Making environmental and social expenses compatible with value creation is a central challenge for corporations since it implies the financial sustainability of Corporate Social Responsibility (CSR.The value creation capacity of CSR projects, mainly through innovation, is widely acknowledged in economic literature and corporate practice. This fact arouses the need of having a quantitative framework capable of summarizing the value creation capacity of the variables involved in CSR projects. With this aim we build up a sensitivity analysis of real option ratios that studies and quantifies the value creation capacity of CSR projects connected with innovation. Ratio analysis has the advantage of being scale independent. Hence, it furnishes a homogeneous framework to express the interaction of value creation variables and, thus, supports strategic thinking quantitatively. Often, CSR expenses can be regarded as preliminary projects that create the opportunity to undertake a full future project. For them, we obtain the minimum expectations scenario that makes financially sustainable a preliminary project that can be interpreted as a call option. We propose a classification of CSR projects from the decision analysis perspective following a two-fold approach: Their relationship with value creation and their links with existing corporate activities. This classification of CSR projects aims at contributing to choose the best capital budgeting method to study the financial sustainability of the project and identifying

Viral asthma: implications for clinical practice

Directory of Open Access Journals (Sweden)

Roger Menendez

2010-07-01

Full Text Available Roger Menendez1, Michael D Goldman21Allergy and Asthma Center of El Paso, El Paso, TX, USA; 2Pulmonary Division, UCLA Gaffen School of Medicine, Los Angeles, CA, USAAbstract: The natural history of asthma appears to be driven primarily by the timing and duration of viral respiratory infections. From the very high rate of infections in childhood, to the more sporadic pattern seen in adults, the cycle of acute injury followed by an inefficient repair process helps explain the clinical patterns of asthma severity currently recognized by asthma guidelines. Why the asthmatic host responds to viral injury in a particular way is largely a mystery and the subject of intense investigation. The role of viruses in asthma extends not just to intermittent but to persistent disease, and to both the atopic as well as nonatopic phenotypes. Future therapeutic strategies should include primary prevention via the development of antiviral innate immunity-enhancing vaccines, as well as secondary prevention via the use of antiviral agents, or immunomodulators designed to boost the antiviral response or interrupt the proinflammatory cascade.Keywords: asthma, rhinoviruses, exacerbations, epidemiology, phenotypes, clinical trials

Evaluation of early recognition of viral infections in man. [using specific gravity of lymphocytes

Science.gov (United States)

Kelton, A. A.; Lawton, M. B.

1975-01-01

The potential of Lymphocyte Specific Gravity Distribution (LSGD) as a non-specific procedure for early diagnosis of viral disease in astronauts is considered. Results of experiments and a literature search show that several virus diseases result in distinctive changes in the specific gravity distribution of peripheral blood lymphocytes as a result of disease process and associated immune response. A tentative model is proposed which relates the shape of LSGD to the identity of subpopulations of peripheral lymphocytes in a preclinical viral disease situation.

T cells for viral infections after allogeneic hematopoietic stem cell transplant.

Science.gov (United States)

Bollard, Catherine M; Heslop, Helen E

2016-06-30

Despite recent advances in the field of allogeneic hematopoietic stem cell transplantation (HSCT), viral infections are still a major complication during the period of immune suppression that follows the procedure. Adoptive transfer of donor-derived virus-specific cytotoxic T cells (VSTs) is a strategy to rapidly restore virus-specific immunity to prevent or treat viral diseases after HSCT. Early proof of principle studies demonstrated that the administration of donor-derived T cells specific for cytomegalovirus or Epstein-Barr virus (EBV) could effectively restore virus-specific immunity and control viral infections. Subsequent studies using different expansion or direct selection techniques have shown that donor-derived VSTs confer protection in vivo after adoptive transfer in 70% to 90% of recipients. Because a major cause of failure is lack of immunity to the infecting virus in a naïve donor, more recent studies have infused closely matched third-party VSTs and reported response rates of 60% to 70%. Current efforts have focused on broadening the applicability of this approach by: (1) extending the number of viral antigens being targeted, (2) simplifying manufacture, (3) exploring strategies for recipients of virus-naïve donor grafts, and (4) developing and optimizing "off the shelf" approaches. © 2016 by The American Society of Hematology.

Tools of Realization of Social Responsibility of Industrial Business for Sustainable Socio-economic Development of Mining Region's Rural Territory

Science.gov (United States)

Jurzina, Tatyana; Egorova, Natalia; Zaruba, Natalia; Kosinskij, Peter

2017-11-01

Modern conditions of the Russian economy do especially relevant questions of social responsibility of industrial business of the mining region for sustainable social and economic development of rural territories that demands search of the new strategy, tools, ways for positioning and increase in competitiveness of the enterprises, which are carrying out the entrepreneurial activity in this territory. The article opens problems of an influence of the industrial enterprises on the territory of presence, reasons the theoretical base directed to the formation of practical tools (mechanism) providing realization of social responsibility of business for sustainable social and economic development of rural territories of the mining region.

Tools of Realization of Social Responsibility of Industrial Business for Sustainable Socio-economic Development of Mining Region's Rural Territory

Directory of Open Access Journals (Sweden)

Jurzina Tatyana

2017-01-01

Full Text Available Modern conditions of the Russian economy do especially relevant questions of social responsibility of industrial business of the mining region for sustainable social and economic development of rural territories that demands search of the new strategy, tools, ways for positioning and increase in competitiveness of the enterprises, which are carrying out the entrepreneurial activity in this territory. The article opens problems of an influence of the industrial enterprises on the territory of presence, reasons the theoretical base directed to the formation of practical tools (mechanism providing realization of social responsibility of business for sustainable social and economic development of rural territories of the mining region.

Clay Nanoparticles Elicit Long-Term Immune Responses by Forming Biodegradable Depots for Sustained Antigen Stimulation.

Science.gov (United States)

Chen, Weiyu; Zuo, Huali; Li, Bei; Duan, Chengcheng; Rolfe, Barbara; Zhang, Bing; Mahony, Timothy J; Xu, Zhi Ping

2018-05-01

Nanomaterials have been widely tested as new generation vaccine adjuvants, but few evoke efficient immunoreactions. Clay nanoparticles, for example, layered double hydroxide (LDH) and hectorite (HEC) nanoparticles, have shown their potent adjuvanticity in generating effective and durable immune responses. However, the mechanism by which clay nanoadjuvants stimulate the immune system is not well understood. Here, it is demonstrated that LDH and HEC-antigen complexes form loose agglomerates in culture medium/serum. They also form nodules with loose structures in tissue after subcutaneous injection, where they act as a depot for up to 35 d. More importantly, clay nanoparticles actively and continuously recruit immune cells into the depot for up to one month, and stimulate stronger immune responses than FDA-approved adjuvants, Alum and QuilA. Sustained antigen release is also observed in clay nanoparticle depots, with 50-60% antigen released after 35 d. In contrast, Alum-antigen complexes show minimal antigen release from the depot. Importantly, LDH and HEC are more effective than QuilA and Alum in promoting memory T-cell proliferation. These findings suggest that both clay nanoadjuvants can serve as active vaccine platforms for sustained and potent immune responses. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Hepatitis C viral infection among prisoners.

Science.gov (United States)

Kostić, Velimir; Radović, Jelena; Djordjević, Jovana; Vujić, Stevan

2013-11-01

Hepatitis C virus (HCV) infection is an important sociomedical problem worldwide because the chronification of the disease is frequent and the occurance of liver cirrhosis and hepatocellular carcinoma can be expected. The aim of this study was to determine the way of infection, pathohistological changes of the liver, virus genotype presence and sustained virological response after pegylated interferon and ribavirin therapy in prison inmates. The study included 52 patients with chronic HCV infection classified in two groups managed during 2008-2010. The first group consisted of prisoners (n = 22) and the second one of "non-prisoners" (n = 30). The patients from both groups underwent diagnostic preparation (biochemical analyses, liver biopsy, hepatitis virus detection and genotypisation using polymerase chain reaction issue). The treatment lasted for 24 weeks for virus genotypes 2 and 3, and 48 weeks for genotypes 1 and 4. All the patients were males, approximately the same age (35 +/- 4.1 and 31 +/- 7.6 years). Virus genotype 1 was significantly more frequent in the prisoners (p < 0.05), that demanded longer treatment (48 weeks). At the same time, statistically significant higher number of patients, "non-prisoners", achieved a sustained virological response (p < 0.01). Intravenous drug abuse and tattoos, separately or together, are the most frequent way of infection in prisoners. The dominant presence of virus genotype 1 resulted in lower number of patients with sustained virological response, probably regardless prison environment and regime.

A sustained hypothalamic-pituitary-adrenal axis response to acute psychosocial stress in irritable bowel syndrome.

Science.gov (United States)

Kennedy, P J; Cryan, J F; Quigley, E M M; Dinan, T G; Clarke, G

2014-10-01

Despite stress being considered a key factor in the pathophysiology of the functional gastrointestinal (GI) disorder irritable bowel syndrome (IBS), there is a paucity of information regarding the ability of IBS patients to respond to acute experimental stress. Insights into the stress response in IBS could open the way to novel therapeutic interventions. To this end, we assessed the response of a range of physiological and psychological parameters to the Trier Social Stress Test (TSST) in IBS. Thirteen female patients with IBS and 15 healthy female age-matched control participants underwent a single exposure to the TSST. Salivary cortisol, salivary C-reactive protein (CRP), skin conductance level (SCL), GI symptoms, mood and self-reported stress were measured pre- and post-exposure to the TSST. The hypothalamic-pituitary-adrenal (HPA) axis response to the TSST was sustained in IBS, as shown by a greater total cortisol output throughout (p = 0.035) and higher cortisol levels measured by an area under the curve with respect to ground (AUCG) analysis (p = 0.044). In IBS patients, GI symptoms increased significantly during the recovery period following exposure to the TSST (p = 0.045). Salivary CRP and SCL activity showed significant changes in relation to stress but with no differential effect between experimental groups. Patients with IBS exhibit sustained HPA axis activity, and an increase in problematic GI symptoms in response to acute experimental psychosocial stress. These data pave the way for future interventional studies aimed at identifying novel therapeutic approaches to modulate the HPA axis and GI symptom response to acute psychosocial stress in IBS.

Syphilis and HIV-1 co-infection: influence on CD4 T cell count, HIV-1 viral load and treatment response

DEFF Research Database (Denmark)

Kofoed, Kristian; Gerstoft, Jan; Mathiesen, Lars Reinhardt

2006-01-01

OBJECTIVES: To assess the effect of human immunodeficiency virus (HIV)-1 and syphilis coinfection on HIV-ribonucleic acid (RNA) viral load, CD4 cell count, and the response in rapid plasmin reagin (RPR) to treatment of the syphilis infection. STUDY DESIGN: Cases of syphilis diagnosed during 1 year...... in HIV-infected patients in Copenhagen were included. HIV-RNA, CD4 cell counts, and RPR-serology were measured before, during, and after syphilis. RESULTS: Forty-one patients were included. CD4 cell count decreased significantly during infection in patients with primary and secondary stages of syphilis...... (mean 106 cells/mm, P = 0.03). Treatment of syphilis was associated with an increase in the CD4 cell count and a decrease in HIV-RNA in the overall group (mean 66 cells/mm and -0.261 RNA log10 copies/ml, P = 0.02 and 0.04). The serological response rates for 15 patients treated with penicillin and 25...

The actin-like MreB cytoskeleton organizes viral DNA replication in bacteria.

Science.gov (United States)

Muñoz-Espín, Daniel; Daniel, Richard; Kawai, Yoshikazu; Carballido-López, Rut; Castilla-Llorente, Virginia; Errington, Jeff; Meijer, Wilfried J J; Salas, Margarita

2009-08-11

Little is known about the organization or proteins involved in membrane-associated replication of prokaryotic genomes. Here we show that the actin-like MreB cytoskeleton of the distantly related bacteria Escherichia coli and Bacillus subtilis is required for efficient viral DNA replication. Detailed analyses of B. subtilis phage ϕ29 showed that the MreB cytoskeleton plays a crucial role in organizing phage DNA replication at the membrane. Thus, phage double-stranded DNA and components of the ϕ29 replication machinery localize in peripheral helix-like structures in a cytoskeleton-dependent way. Importantly, we show that MreB interacts directly with the ϕ29 membrane-protein p16.7, responsible for attaching viral DNA at the cell membrane. Altogether, the results reveal another function for the MreB cytoskeleton and describe a mechanism by which viral DNA replication is organized at the bacterial membrane.

Gefitinib and pyrrolidine dithiocarbamate decrease viral replication and cytokine production in dengue virus infected human monocyte cultures.

Science.gov (United States)

Duran, Anyelo; Valero, Nereida; Mosquera, Jesús; Fuenmayor, Edgard; Alvarez-Mon, Melchor

2017-12-15

The epidermal growth factor receptor (EGFR) and nucleotide-binding and oligomerization-domain containing 2 (NOD2) are important in cancer and in microbial recognition, respectively. These molecules trigger intracellular signaling pathways inducing the expression of inflammatory genes by NF-kB translocation. Gefitinib (GBTC) and pyrrolidine dithiocarbamate (PDTC) are capable of inhibiting EGFR/NOD2 and NF-kB, respectively. In earlier stages of dengue virus (DENV) infection, monocytes are capable of sustaining viral replication and increasing cytokine production, suggesting that monocyte/macrophages play an important role in early DENV replication. GBTC and PDTC have not been used to modify the pathogenesis of DENV in infected cells. This study was aimed to determine the effect of GBTC and PDTC on viral replication and cytokine production in DENV serotype 2 (DENV2)-infected human monocyte cultures. GBTC and PDTC were used to inhibit EGFR/NOD2 and NF-kB, respectively. Cytokine production was measured by ELISA and viral replication by plaque forming unit assay. Increased DENV2 replication and anti-viral cytokine production (IFN-α/β, TNF-α, IL-12 and IL-18) in infected cultures were found. These parameters were decreased after EGFR/NOD2 or NF-kB inhibitions. The inhibitory effects of GBTC and PDTC on viral replication and cytokine production can be beneficial in the treatment of patients infected by dengue and suggest a possible role of EGFR/NOD2 receptors and NF-kB in dengue pathogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

Governance through learning: making corporate social responsibility in dutch industry effective from a sustainable development perspective

NARCIS (Netherlands)

Cramer, J.M.; Loeber, A.

2004-01-01

An increasing number of firms try to implement corporate social responsibility (CSR) from the perspective of sustainable development. This article considers these efforts in the light of the changing relation between the state, society and the corporate sector, as a result of which governance

Mechanical and assembly units of viral capsids identified via quasi-rigid domain decomposition.

Directory of Open Access Journals (Sweden)

Guido Polles

Full Text Available Key steps in a viral life-cycle, such as self-assembly of a protective protein container or in some cases also subsequent maturation events, are governed by the interplay of physico-chemical mechanisms involving various spatial and temporal scales. These salient aspects of a viral life cycle are hence well described and rationalised from a mesoscopic perspective. Accordingly, various experimental and computational efforts have been directed towards identifying the fundamental building blocks that are instrumental for the mechanical response, or constitute the assembly units, of a few specific viral shells. Motivated by these earlier studies we introduce and apply a general and efficient computational scheme for identifying the stable domains of a given viral capsid. The method is based on elastic network models and quasi-rigid domain decomposition. It is first applied to a heterogeneous set of well-characterized viruses (CCMV, MS2, STNV, STMV for which the known mechanical or assembly domains are correctly identified. The validated method is next applied to other viral particles such as L-A, Pariacoto and polyoma viruses, whose fundamental functional domains are still unknown or debated and for which we formulate verifiable predictions. The numerical code implementing the domain decomposition strategy is made freely available.

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.  

Treatment of chronic hepatitis C with direct-acting antivirals: The role of resistance.

Science.gov (United States)

Jiménez-Pérez, Miguel; González-Grande, Rocío; España Contreras, Pilar; Pinazo Martínez, Isabel; de la Cruz Lombardo, Jesús; Olmedo Martín, Raúl

2016-08-07

The use of direct-acting antivirals (DAAs) to treat chronic hepatitis C has resulted in a significant increase in rates of sustained viral response (around 90%-95%) as compared with the standard treatment of peginterferon/ribavirin. Despite this, however, the rates of therapeutic failure in daily clinical practice range from 10%-15%. Most of these cases are due to the presence of resistant viral variants, resulting from mutations produced by substitutions of amino acids in the viral target protein that reduce viral sensitivity to DAAs, thus limiting the efficacy of these drugs. The high genetic diversity of hepatitis C virus has resulted in the existence of resistance-associated variants (RAVs), sometimes even before starting treatment with DAAs, though generally at low levels. These pre-existing RAVs do not appear to impact on the sustained viral response, whereas those that appear after DAA therapy could well be determinant in virological failure with future treatments. As well as the presence of RAVs, virological failure to treatment with DAAs is generally associated with other factors related with a poor response, such as the degree of fibrosis, the response to previous therapy, the viral load or the viral genotype. Nonetheless, viral breakthrough and relapse can still occur in the absence of detectable RAVs and after the use of highly effective DAAs, so that the true clinical impact of the presence of RAVs in therapeutic failure remains to be determined.

p53 Activation following Rift Valley fever virus infection contributes to cell death and viral production.

Directory of Open Access Journals (Sweden)

Dana Austin

Full Text Available Rift Valley fever virus (RVFV is an emerging viral zoonosis that is responsible for devastating outbreaks among livestock and is capable of causing potentially fatal disease in humans. Studies have shown that upon infection, certain viruses have the capability of utilizing particular cellular signaling pathways to propagate viral infection. Activation of p53 is important for the DNA damage signaling cascade, initiation of apoptosis, cell cycle arrest and transcriptional regulation of multiple genes. The current study focuses on the role of p53 signaling in RVFV infection and viral replication. These results show an up-regulation of p53 phosphorylation at several serine sites after RVFV MP-12 infection that is highly dependent on the viral protein NSs. qRT-PCR data showed a transcriptional up-regulation of several p53 targeted genes involved in cell cycle and apoptosis regulation following RVFV infection. Cell viability assays demonstrate that loss of p53 results in less RVFV induced cell death. Furthermore, decreased viral titers in p53 null cells indicate that RVFV utilizes p53 to enhance viral production. Collectively, these experiments indicate that the p53 signaling pathway is utilized during RVFV infection to induce cell death and increase viral production.

Expression kinetics of key genes in the early innate immune response to Great Lakes viral hemorrhagic septicemia virus IVb infection in yellow perch (Perca flavescens)

Science.gov (United States)

Olson, Wendy; Emmenegger, Eveline; Glenn, Jolene; Simchick, Crystal; Winton, Jim; Goetz, Frederick

2013-01-01

The recently discovered strain of viral hemorrhagic septicemia virus, VHSV-IVb, represents an example of the introduction of an extremely pathogenic rhabdovirus capable of infecting a wide variety of new fish species in a new host-environment. The goal of the present study was to delineate the expression kinetics of key genes in the innate immune response relative to the very early stages of VHSV-IVb infection using the yellow perch (Perca flavescens) as a model. Administration of VHSV-IVb by IP-injection into juvenile yellow perch resulted in 84% cumulative mortality, indicating their high susceptibility to this disease. In fish sampled in the very early stages of infection, a significant up-regulation of Mx gene expression in the liver, as well as IL-1β and SAA activation in the head kidney, spleen, and liver was directly correlated to viral load. The potential down-regulation of Mx in the hematopoietic tissues, head kidney and spleen, may represent a strategy utilized by the virus to increase replication.

Sustainability of keratinocyte gene transfer and cell survival in vivo.

Science.gov (United States)

Choate, K A; Khavari, P A

1997-05-20

The epidermis is an attractive site for therapeutic gene delivery because it is accessible and capable of delivering polypeptides to the systemic circulation. A number of difficulties, however, have emerged in attempts at cutaneous gene delivery, and central among these is an inability to sustain therapeutic gene production. We have examined two major potential contributing factors, viral vector stamina and involvement of long-lived epidermal progenitor cells. Human keratinocytes were either untreated or transduced with a retroviral vector for beta-galactosidase (beta-Gal) at > 99% efficiency and then grafted onto immunodeficient mice to regenerate human epidermis. Human epidermis was monitored in vivo after grafting for clinical and histologic appearance as well as for gene expression. Although integrated vector sequences persisted unchanged in engineered epidermis at 10 weeks post-grafting, retroviral long terminal repeat (LTR)-driven beta-Gal expression ceased in vivo after approximately 4 weeks. Endogenous cellular promoters, however, maintained consistently normal gene expression levels without evidence of time-dependent decline, as determined by immunostaining with species-specific antibodies for human involucrin, filaggrin, keratinocyte transglutaminase, keratin 10, type VII collagen, and Laminin 5 proteins out to week 14 post-grafting. Transduced human keratinocytes generated multilayer epidermis sustained through multiple epidermal turnover cycles; this epidermis demonstrated retention of a spatially appropriate pattern of basal and suprabasal epidermal marker gene expression. These results confirm previous findings suggesting that viral promoter-driven gene expression is not durable and demonstrate that keratinocytes passaged in vitro can regenerate and sustain normal epidermis for prolonged periods.

Sustained major molecular response on interferon alpha-2b in two patients with polycythemia vera

DEFF Research Database (Denmark)

Larsen, T.S.; Pallisgaard, N.; Andersen, M.T.

2008-01-01

with a JAK2 V617F allele burden below 1.0% in two patients with polycythemia vera treated with interferon alpha-2b (IFN-2b). Discontinuation of IFN-2b in one of the patients was followed by a sustained long-lasting (12 months of follow-up) major molecular response Udgivelsesdato: 2008/10...

Evolution of the Digital Society Reveals Balance between Viral and Mass Media Influence

Science.gov (United States)

Kleineberg, Kaj-Kolja; Boguñá, Marián

2014-07-01

Online social networks (OSNs) enable researchers to study the social universe at a previously unattainable scale. The worldwide impact and the necessity to sustain the rapid growth of OSNs emphasize the importance of unraveling the laws governing their evolution. Empirical results show that, unlike many real-world growing networked systems, OSNs follow an intricate path that includes a dynamical percolation transition. In light of these results, we present a quantitative two-parameter model that reproduces the entire topological evolution of a quasi-isolated OSN with unprecedented precision from the birth of the network. This allows us to precisely gauge the fundamental macroscopic and microscopic mechanisms involved. Our findings suggest that the coupling between the real preexisting underlying social structure, a viral spreading mechanism, and mass media influence govern the evolution of OSNs. The empirical validation of our model, on a macroscopic scale, reveals that virality is 4-5 times stronger than mass media influence and, on a microscopic scale, individuals have a higher subscription probability if invited by weaker social contacts, in agreement with the "strength of weak ties" paradigm.

Special Issue on "Social Responsibility Accounting and Reporting in Times of ‘Sustainability Downturn/Crisis’

Directory of Open Access Journals (Sweden)

Carmen Correa-Ruiz

2011-12-01

Full Text Available At a time when sustainability performance does not seem to match the expectations raised by the sustainable development concept and, moreover, when the economic downturn and crisis could be further eroding social and environmental concerns and values, the notion of sustainability crisis provides an interesting starting point to reflect on the role of Social and Environmental Accounting Research. Lack of humanity and values, short term economic approach, institutional capture and misunderstanding and misuse of democracy, have all served as catalysts of sustainability downturn and crisis. Thus, this editorial attempts to advance public interest accounting by discussing the controversy around Sustainability and Corporate Social Responsibility, expecting that the constitutive effects of researchers’ words in this special issue and in future research agendas, will result in more transformative power relations able to enhance a healthy democracy inspired by the capacity to do things and to transform individuals’ attitudes and behaviours, as well as the institutional response to the sustainability crisis.En una época en la que el desempeño en materia de sostenibilidad parece no cumplir las expectativas creadas por el concepto de desarrollo sostenible y, en la que además, la recesión y la crisis económica podría estar erosionando aún más los valores y preocupaciones sociales y medioambientales, la noción de crisis de sostenibilidad proporciona un interesante punto de partida para reflexionar sobre el papel de la investigación en Contabilidad Social y Medioambiental. La falta de humanidad y la ausencia de valores, el enfoque económico cortoplacista, la captura institucional y la democracia mal entendida y su uso incorrecto, han servido como catalizadores de la crisis y la recesión de la sostenibilidad. Así, el presente editorial pretende avanzar en la contabilidad como interés general, debatiendo sobre la controversia existente

Market efficiency of traditional stock market indices and social responsible indices: the role of sustainability reporting

OpenAIRE

Henry Mynhardt; Inna Makarenko; Alex Plastun

2017-01-01

Corporate social responsibility, disclosed in sustainability reporting, influences the financial performance of companies. As a result, traditional stock market indices (TI) are expanded with the social responsible stock market indices (SRI). The aim of this study was to establish whether there are any differences in the behavior of the TI and SRI. To do this, the authors analyzed their efficiency. They used R/S analysis to calculate the Hurst exponent as a measure of persistence (long-term m...

Taking Responsibility: The integration of Sustainability and Project Management

NARCIS (Netherlands)

Jasper van den Brink; Gilbert Gilbert Silvius

2011-01-01

Sustainability is one of the most important challenges of our time. How can we develop prosperity, without compromising the life of future generations? Companies are integrating ideas of sustainability in their marketing, corporate communications, annual reports and in their actions. Projects as

Annual Sustainability Report FY 2014. Incorporates NREL Site Sustainability Plan

Energy Technology Data Exchange (ETDEWEB)

Rukavina, Frank [National Renewable Energy Lab. (NREL), Golden, CO (United States)

2015-07-01

NREL's Sustainability Program is responsible for upholding all executive orders, federal regulations, U.S. Department of Energy (DOE) orders, and goals related to sustainable and resilient facility operations. But NREL continues to expand sustainable practices above and beyond the laboratory's regulations and requirements to ensure that the laboratory fulfills its mission into the future, leaves the smallest possible legacy footprint, and models sustainable operations and behaviors on national, regional, and local levels. The report, per the GRI reporting format, elaborates on multi-year goals relative to executive orders, achievements, and challenges; and success stories provide specific examples. A section called 'Sustaining NREL's Future Through Integration' provides insight into how NREL is successfully expanding the adoption of renewable energy technologies through integration.

Sustained response to weekly vinblastine in 2 children with pilomyxoid astrocytoma associated with diencephalic syndrome.

Science.gov (United States)

Singh, Gurpreet; Wei, Xing Chang; Hader, Walter; Chan, Jennifer A; Bouffet, Eric; Lafay-Cousin, Lucie

2013-03-01

Diencephalic syndrome (DS) related to hypothalamic/chiasmatic region tumor has mainly been reported with low-grade glioma. We described 2 young children with DS related to pilomyxoid astrocytoma. Despite the recognized more agressive clinical behavior of this histologic subtype, we report successful resolution of DS and sustained tumor response with prolonged use of single-agent vinblastine.

Sustainability or Bust: Malaysian Home Buyers’ Stated Preferences for Sus-Tainable Housing

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Syahid A.

2016-01-01

Full Text Available The lack of data on sustainable home buying behaviour in developing countries such as Malaysia is due to the absence of sustainable housing itself. However, it is still possible to solicit home buyers for their stated preferences and quantify its effects on housing demand. In this study, a sample of 300 responses to a Discrete Choice Experiment (DCE on sustainable housing features was analysed using the “support.CEs” program. This study found that the addition of sustainable features; renewable energy generation, enhanced soundproofing and ventilation, energy saving features, and higher green area ratios significantly increase home buyer’s willingness to pay (WTP for sustainable housing.

Hepatitis A viral load in relation to severity of the infection.

Science.gov (United States)

Fujiwara, Keiichi; Kojima, Hiroshige; Yasui, Shin; Okitsu, Koichiro; Yonemitsu, Yutaka; Omata, Masao; Yokosuka, Osamu

2011-02-01

A correlation between hepatitis A virus (HAV) genomes and the clinical severity of hepatitis A has not been established. The viral load in sera of hepatitis A patients was examined to determine the possible association between hepatitis A severity and HAV replication. One hundred sixty-four serum samples from 91 Japanese patients with sporadic hepatitis A, comprising 11 patients with fulminant hepatitis, 10 with severe acute hepatitis, and 70 with self-limited acute hepatitis, were tested for HAV RNA. The sera included 83 serial samples from 20 patients. Viral load was measured by real-time RT-PCR. The detection rates of HAV RNA from fulminant, severe acute, and acute hepatitis were 10/11 (91%), 10/10 (100%), and 55/70 (79%), respectively. Mean values of HAV RNA at admission were 3.48 ± 1.30 logcopies/ml in fulminant, 4.19 ± 1.03 in severe acute, and 2.65 ± 1.64 in acute hepatitis. Patients with severe infection such as fulminant hepatitis and severe acute hepatitis had higher initial viral load than patients with less severe infection (P hepatitis after clinical onset (P = 0.19). HAV RNA was detectable quantitatively in the majority of the sera of hepatitis A cases during the early convalescent phase by real-time PCR. Higher initial viral replication was found in severely infected patients. An excessive host immune response might follow, reducing the viral load rapidly as a result of the destruction of large numbers of HAV-infected hepatocytes, and in turn severe disease might be induced. 2010 Wiley-Liss, Inc.

EXPOSURE TO URBAN AIR PARTICULATES ALTERS THE MACROPHAGE- MEDIATED INFLAMMATORY RESPONSE TO RESPIRATORY VIRAL INFECTION

Science.gov (United States)

Epidemiology studies associate increased pulmonary morbidity with episodes of high particulate air pollution (size range 0.1-10 microm diameter, PM10). Pneumonia, often viral in origin, is increased following episodes of high PM10 pollution. Therefore, this study was undertaken t...

Time-of-use based electricity demand response for sustainable manufacturing systems

International Nuclear Information System (INIS)

Wang, Yong; Li, Lin

2013-01-01

As required by the Energy Policy Act of 2005, utility companies across the U.S. are offering TOU (time-of-use) based electricity demand response programs. The TOU rate gives consumers opportunities to manage their electricity bill by shifting use from on-peak periods to mid-peak and off-peak periods. Reducing the amount of electricity needed during the peak load times makes it possible for the power grid to meet consumers' needs without building more costly backup infrastructures and help reduce GHG (greenhouse gas) emissions. Previous research on the applications of TOU and other electricity demand response programs has been mainly focused on residential and commercial buildings while largely neglected industrial manufacturing systems. This paper proposes a systems approach for TOU based electricity demand response for sustainable manufacturing systems under the production target constraint. Key features of this approach include: (i) the electricity related costs including both consumption and demand are integrated into production system modeling; (ii) energy-efficient and demand-responsive production scheduling problems are formulated and the solution technique is provided; and (iii) the effects of various factors on the near-optimal scheduling solutions are examined. The research outcome is expected to enhance the energy efficiency, electricity demand responsiveness, and cost effectiveness of modern manufacturing systems. - Highlights: • We propose a TOU based demand response approach for manufacturing systems. • Both electricity consumption and demand are integrated into the system modeling. • Energy-efficient and demand-responsive production scheduling problems are formulated. • The meta-heuristic solution technique is provided. • The effects of various factors on the scheduling solutions are examined

Eicosanoids and Respiratory Viral Infection: Coordinators of Inflammation and Potential Therapeutic Targets

Directory of Open Access Journals (Sweden)

Mary K. McCarthy

2012-01-01

Full Text Available Viruses are frequent causes of respiratory infection, and viral respiratory infections are significant causes of hospitalization, morbidity, and sometimes mortality in a variety of patient populations. Lung inflammation induced by infection with common respiratory pathogens such as influenza and respiratory syncytial virus is accompanied by increased lung production of prostaglandins and leukotrienes, lipid mediators with a wide range of effects on host immune function. Deficiency or pharmacologic inhibition of prostaglandin and leukotriene production often results in a dampened inflammatory response to acute infection with a respiratory virus. These mediators may, therefore, serve as appealing therapeutic targets for disease caused by respiratory viral infection.

Natural Killer Cells in Viral HepatitisSummary

Directory of Open Access Journals (Sweden)

Barbara Rehermann

2015-11-01

Full Text Available Natural killer (NK cells are traditionally regarded as first-line effectors of the innate immune response, but they also have a distinct role in chronic infection. Here, we review the role of NK cells against hepatitis C virus (HCV and hepatitis B virus (HBV, two agents that cause acute and chronic hepatitis in humans. Interest in NK cells was initially sparked by genetic studies that demonstrated an association between NK cell–related genes and the outcome of HCV infection. Viral hepatitis also provides a model to study the NK cell response to both endogenous and exogenous type I interferon (IFN. Levels of IFN-stimulated genes increase in both acute and chronic HCV infection and pegylated IFNα has been the mainstay of HCV and HBV treatment for decades. In chronic viral hepatitis, NK cells display decreased production of antiviral cytokines. This phenotype is found in both HCV and HBV infection but is induced by different mechanisms. Potent antivirals now provide the opportunity to study the reversibility of the suppressed cytokine production of NK cells in comparison with the antigen-induced defect in IFNγ and tumor necrosis factor-α production of virus-specific T cells. This has implications for immune reconstitution in other conditions of chronic inflammation and immune exhaustion, such as human immunodeficiency virus infection and cancer. Keywords: HBV, HCV, Infection, Interferon, T Cell

Use of medicinal plants as the additional therapy of viral hepatitis

Directory of Open Access Journals (Sweden)

I.B. Ershova

2017-04-01

Full Text Available Dear colleagues, continuing the rubric of the journal about the treatment of infectious diseases by medicinal plants, we want to present the methods of using medicinal plants as an additional therapy for treatment of viral hepatitis in addition to the main treatment according to the generally clinical standards of antiviral therapy. Viral hepatitis compiles a large group of human infectious diseases characterized by a predominant liver damage. “Currently, viral hepatitis is recognized as a major public health problem requiring urgent action”, said Dr Margaret Chan, WHO Director-General (WHO Global hepatitis report, 2017. Treatment of viral hepatitis is a complex task and involves the use of generally clinical recommendations or standards. There are criteria for determining the need for pharmacotherapy and the most rational scheme for antiviral treatment in every case of viral hepatitis. The purpose of antiviral therapy is to achieve a stable virologic response, to prevent the progression of the disease, the development of cirrhosis and hepatocellular carcinoma. However, at the present stage a stable virologic response in the general population of patients can be achieved in approximately 60 % of cases. In addition, standard antiviral drugs have side effects, are of high cost and are contraindicated in a number of clinical situations, for example, with a decrease in the number of blood elements (thrombocytopenia, leukopenia, anemia, at the stage of decompensated liver cirrhosis. Probably, all this induces to use alternative methods of therapy, which remain popular both among general practitioners and patients with this infection. The question of the treatment of viral hepatitis with medicinal herbs has been studied for a long time. According to some authors, there is no scientific evidence that hepatitis C can be cured by herbs. The only scientifically proven method of fighting the virus is antiviral therapy. However, there are other points

Response of marine viral populations to a nutrient induced phytoplankton bloom at different pCO2 levels

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R.-A. Sandaa

2008-04-01

Full Text Available During the PeECE III mesocosm experiment in 2005 we investigated how the virioplankton community responded to increased levels of nutrients (N and P and CO2. We applied a combination of flow cytometry, Pulsed Field Gel Electrophoresis and degenerate PCR primers to categorize and quantify individual viral populations, and to investigate their temporal dynamics. Species specific and degenerate primers enabled us to identify two specific large dsDNA viruses, EhV and CeV, infecting the haptophytes Emiliania huxleyi and Crysochromulina ericina, respectively. Some of the viral populations detected and enumerated by flow cytometry did not respond to altered CO2-levels, but the abundance of EhV and an unidentified dsDNA virus decreased with increasing CO2 levels. Our results thus indicate that CO2 conditions, or the related change in pH, may affect the marine pelagic food web at the viral level. Our results also demonstrate that in order to unravel ecological problems as how CO2 and nutrient levels affect the relationship between marine algal viruses and their hosts, we need to continue the effort to develop molecular markers used to identify both hosts and viruses.

[Sustainability and excellence of the Catalan health system. New paradigms, challenges and responses].

Science.gov (United States)

Fernández i Alegre, Roser; Argenter i Giralt, Miquel; Rodríguez i Guasch, Xavier

2015-11-01

The aim of a health system and the priority of any government is to anticipate problems before they appear, provide an innovative response to these new needs and healthcare models, improve access of the general public and patients to health care, especially care for the most vulnerable groups, improve healthcare results and implement the structural reforms necessary to maintain a viable and sustainable quality public healthcare system for everyone. In the current environment, health systems are facing new economic, demographic, care, social, technological and political paradigms to which health policy must respond. Faced with these challenges, health systems, especially in the case of Catalonia, are challenged to take decisions on how best to approach the implementation of structural reform designed to facilitate the necessary economic and fiscal sustainability in the service of fresh and innovative health policies and patient-centred care within a system marked by excellence and equity. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Predictors of sustained virological response in Greek and Egyptian patients with hepatitis C genotype 4: does ethnicity matter?

Science.gov (United States)

Papastergiou, Vasilios; Dimitroulopoulos, Dimitrios; Skorda, Lamprini; Lisgos, Philippos; Ketikoglou, Ioannis; Kostas, Nikolaos; Karatapanis, Stylianos

2012-08-01

Hepatitis C virus genotype 4 (HCV-4) is spreading beyond Africa and the Middle East but data regarding treatment with pegylated interferon alpha and ribavirin of European populations infected with HCV-4 remains limited. Interestingly, European (vs. Egyptian) origin has been associated with lower sustained virological response rates. Hence the aim of this study was to investigate the treatment outcomes of Greek (vs. Egyptian), treatment-naïve patients infected with HCV-4 (subtype a) and to identify factors influencing response rates. One hundred seventy-seven consecutive patients (mean age: 44.6 ± 10.2, males: 143/177; 80.8%, Egyptians: 76/177; 42.9%) treated over a 7-year period at the Hepatology clinics of three tertiary care hospitals in Greece were retrospectively evaluated. Overall, sustained virological response was achieved in 75/177 (42.4%) of the cohort without a significant difference between the two ethnic groups [Greek: 44/101 (43.6%); Egyptian 31/76 (40.8%), P = 0.7598]. In multivariate analysis, it was found that ethnicity was not associated with an impaired response but age ≥45 years [odds ratio (OR): 0.4225, 95% confidence interval (CI): 0.2135-0.8133; P = 0.0134], diabetes (OR: 0.2346, 95% CI: 0.0816-0.0674; P = 0.0071), advanced liver fibrosis (OR: 0.3964, 95% CI: 0.1933-0.8133; P = 0.0116), and treatment suspension (OR: 0.1738, 95% CI: 0.0482-0.6262; P = 0.0075) showed an independent negative association with response to antiviral treatment. In contrast to previous European data suggesting Egyptian ethnicity to be a positive predictor for a sustained virological response, there was no influence of Greek versus Egyptian ethnicity on treatment outcomes. Higher age, advanced liver fibrosis, and diabetes have been shown to reduce significantly response rates in patients infected with HCV-4. Copyright © 2012 Wiley Periodicals, Inc.

Promising approaches for the treatment and prevention of viral respiratory illnesses.

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Papadopoulos, Nikolaos G; Megremis, Spyridon; Kitsioulis, Nikolaos A; Vangelatou, Olympia; West, Peter; Xepapadaki, Paraskevi

2017-10-01

Viral respiratory tract infections are the most common human ailments, leading to enormous health and economic burden. Hundreds of viral species and subtypes have been associated with these conditions, with influenza viruses, respiratory syncytial virus, and rhinoviruses being the most frequent and with the highest burden. When considering prevention or treatment of viral respiratory tract infections, potential targets include the causative pathogens themselves but also the immune response, disease transmission, or even just the symptoms. Strategies targeting all these aspects are developing concurrently, and several novel and promising approaches are emerging. In this perspective we overview the entire range of options and highlight some of the most promising approaches, including new antiviral agents, symptomatic or immunomodulatory drugs, the re-emergence of natural remedies, and vaccines and public health policies toward prevention. Wide-scale prevention through immunization appears to be within reach for respiratory syncytial virus and promising for influenza virus, whereas additional effort is needed in regard to rhinovirus, as well as other respiratory tract viruses. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Succesful therapy of viral leukemia by transplantation of histocompatibly unmatched marrow

International Nuclear Information System (INIS)

Meredith, R.F.; OKunewick, J.P.; Kuhnert, P.M.; Brozovich, B.J.; Weaver, E.V.

1978-01-01

The therapeutic effectiveness on murine viral-leukemia of allogeneic or hybrid hematopoietic cells transplanted from leukemia-virus resistant donors was evaluated and compared with that of syngeneic cells. Transplantation of syngeneic cells gave no protection to the viral-leukemic mice. Transplantation of spleen cells from allogeneic donors resulted in early deaths of both leukemic and non-leukemic recipients. Transplantation of hybrid spleen cells resulted in no long-term survival of the leukemic mice. However, there were a number of long-term survivors among the leukemic recipients of allogeneic or hybrid marrow cells. Engraftment of allogeneic marrow resulted in a large number of survivors. Hybrid marrow recipients showed an even better survival, but some leukemia relapses. Tests of the longterm survivors revealed that even though they gave no evidence of leukemia they still harbored the active virus. This suggests that the mechanism of protection may be related to some inherent characteristic of the donor cells rendering them refractory to viral transformation. A difference in graft-versus-host (GvH) response between the leukemic and control mice was also found after transplantation of allogeneic cells. While all of the controls died of GvH reaction, none of the leukemic recipients showed severe GvH response, suggesting a possible effect of the leukemia on histocompatibility. No GvH reaction was found with hybrid marrow engraftment, although some of the leukemic recipients reconstituted with F 1 cells did die of leukemic relapse. (author)

Setting Up Shop: The Formation and Function of the Viral Factories of Cauliflower mosaic virus

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James E. Schoelz

2017-10-01

Full Text Available Similar to cells, viruses often compartmentalize specific functions such as genome replication or particle assembly. Viral compartments may contain host organelle membranes or they may be mainly composed of viral proteins. These compartments are often termed: inclusion bodies (IBs, viroplasms or viral factories. The same virus may form more than one type of IB, each with different functions, as illustrated by the plant pararetrovirus, Cauliflower mosaic virus (CaMV. CaMV forms two distinct types of IBs in infected plant cells, those composed mainly of the viral proteins P2 (which are responsible for transmission of CaMV by insect vectors and P6 (required for viral intra-and inter-cellular infection, respectively. P6 IBs are the major focus of this review. Much of our understanding of the formation and function of P6 IBs comes from the analyses of their major protein component, P6. Over time, the interactions and functions of P6 have been gradually elucidated. Coupled with new technologies, such as fluorescence microscopy with fluorophore-tagged viral proteins, these data complement earlier work and provide a clearer picture of P6 IB formation. As the activities and interactions of the viral proteins have gradually been determined, the functions of P6 IBs have become clearer. This review integrates the current state of knowledge on the formation and function of P6 IBs to produce a coherent model for the activities mediated by these sophisticated virus-manufacturing machines.

Orienting-defense responses and psychophysiological reactivity in isolated clinic versus sustained hypertension.

Science.gov (United States)

García-Vera, María Paz; Sanz, Jesús; Labrador, Francisco J

2007-04-01

This study sought to determine whether patients with white-coat or isolated clinic hypertension (ICH) show, in comparison to patients with sustained hypertension (SH), a defense response pattern to novel stimuli and an enhanced psychophysiological reactivity to stress. Forty-three patients with essential hypertension were divided into two groups after 16 days of self-monitoring blood pressure (BP): ICH (24 men; self-measured BP men; self-measured BP >or= 135/85 mmHg). Defense responses were measured as the cardiac changes to phasic non-aversive auditory stimuli. Psychophysiological reactivity (heart and breath rate, blood volume pulse, electromyography, and skin conductance) was measured during mental arithmetic and video game tasks. The standard deviation of self-measured BPs and the difference between mean BPs at work and at home were used as indicators of cardiovascular reactivity to daily stress. No significant differences were seen in defense responses or psychophysiological reactivity to laboratory or naturally occurring stressors. These results do not support the hypothesis that ICH can be explained in terms of a generalized hyperreactivity to novel or stressful stimuli.

Adenovirus-encoding virus-associated RNAs suppress HDGF gene expression to support efficient viral replication.

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Saki Kondo

Full Text Available Non-coding small RNAs are involved in many physiological responses including viral life cycles. Adenovirus-encoding small RNAs, known as virus-associated RNAs (VA RNAs, are transcribed throughout the replication process in the host cells, and their transcript levels depend on the copy numbers of the viral genome. Therefore, VA RNAs are abundant in infected cells after genome replication, i.e. during the late phase of viral infection. Their function during the late phase is the inhibition of interferon-inducible protein kinase R (PKR activity to prevent antiviral responses; recently, mivaRNAs, the microRNAs processed from VA RNAs, have been reported to inhibit cellular gene expression. Although VA RNA transcription starts during the early phase, little is known about its function. The reason may be because much smaller amount of VA RNAs are transcribed during the early phase than the late phase. In this study, we applied replication-deficient adenovirus vectors (AdVs and novel AdVs lacking VA RNA genes to analyze the expression changes in cellular genes mediated by VA RNAs using microarray analysis. AdVs are suitable to examine the function of VA RNAs during the early phase, since they constitutively express VA RNAs but do not replicate except in 293 cells. We found that the expression level of hepatoma-derived growth factor (HDGF significantly decreased in response to the VA RNAs under replication-deficient condition, and this suppression was also observed during the early phase under replication-competent conditions. The suppression was independent of mivaRNA-induced downregulation, suggesting that the function of VA RNAs during the early phase differs from that during the late phase. Notably, overexpression of HDGF inhibited AdV growth. This is the first report to show the function, in part, of VA RNAs during the early phase that may be contribute to efficient viral growth.

Plasma response to sustainment with imposed-dynamo current drive in HIT-SI and HIT-SI3

Science.gov (United States)

Hossack, A. C.; Jarboe, T. R.; Chandra, R. N.; Morgan, K. D.; Sutherland, D. A.; Penna, J. M.; Everson, C. J.; Nelson, B. A.

2017-07-01

The helicity injected torus—steady inductive (HIT-SI) program studies efficient, steady-state current drive for magnetic confinement plasmas using a novel experimental method. Stable, high-beta spheromaks have been sustained using steady, inductive current drive. Externally induced loop voltage and magnetic flux are oscillated together so that helicity and power injection are always positive, sustaining the edge plasma current indefinitely. Imposed-dynamo current drive (IDCD) theory further shows that the entire plasma current is sustained. The method is ideal for low aspect ratio, toroidal geometries with closed flux surfaces. Experimental studies of spheromak plasmas sustained with IDCD have shown stable magnetic profiles with evidence of pressure confinement. New measurements show coherent motion of a stable spheromak in response to the imposed perturbations. On the original device two helicity injectors were mounted on either side of the spheromak and the injected mode spectrum was predominantly n  =  1. Coherent, rigid motion indicates that the spheromak is stable and a lack of plasma-generated n  =  1 energy indicates that the maximum q is maintained below 1 during sustainment. Results from the HIT-SI3 device are also presented. Three inductive helicity injectors are mounted on one side of the spheromak flux conserver. Varying the relative injector phasing changes the injected mode spectrum which includes n  =  2, 3, and higher modes.

The Pacific Ocean virome (POV: a marine viral metagenomic dataset and associated protein clusters for quantitative viral ecology.

Directory of Open Access Journals (Sweden)

Bonnie L Hurwitz

Full Text Available Bacteria and their viruses (phage are fundamental drivers of many ecosystem processes including global biogeochemistry and horizontal gene transfer. While databases and resources for studying function in uncultured bacterial communities are relatively advanced, many fewer exist for their viral counterparts. The issue is largely technical in that the majority (often 90% of viral sequences are functionally 'unknown' making viruses a virtually untapped resource of functional and physiological information. Here, we provide a community resource that organizes this unknown sequence space into 27 K high confidence protein clusters using 32 viral metagenomes from four biogeographic regions in the Pacific Ocean that vary by season, depth, and proximity to land, and include some of the first deep pelagic ocean viral metagenomes. These protein clusters more than double currently available viral protein clusters, including those from environmental datasets. Further, a protein cluster guided analysis of functional diversity revealed that richness decreased (i from deep to surface waters, (ii from winter to summer, (iii and with distance from shore in surface waters only. These data provide a framework from which to draw on for future metadata-enabled functional inquiries of the vast viral unknown.

The Pacific Ocean virome (POV): a marine viral metagenomic dataset and associated protein clusters for quantitative viral ecology.

Science.gov (United States)

Hurwitz, Bonnie L; Sullivan, Matthew B

2013-01-01

Bacteria and their viruses (phage) are fundamental drivers of many ecosystem processes including global biogeochemistry and horizontal gene transfer. While databases and resources for studying function in uncultured bacterial communities are relatively advanced, many fewer exist for their viral counterparts. The issue is largely technical in that the majority (often 90%) of viral sequences are functionally 'unknown' making viruses a virtually untapped resource of functional and physiological information. Here, we provide a community resource that organizes this unknown sequence space into 27 K high confidence protein clusters using 32 viral metagenomes from four biogeographic regions in the Pacific Ocean that vary by season, depth, and proximity to land, and include some of the first deep pelagic ocean viral metagenomes. These protein clusters more than double currently available viral protein clusters, including those from environmental datasets. Further, a protein cluster guided analysis of functional diversity revealed that richness decreased (i) from deep to surface waters, (ii) from winter to summer, (iii) and with distance from shore in surface waters only. These data provide a framework from which to draw on for future metadata-enabled functional inquiries of the vast viral unknown.

Viral-specific T-cell transfer from HSCT donor for the treatment of viral infections or diseases after HSCT.

Science.gov (United States)

Qian, C; Wang, Y; Reppel, L; D'aveni, M; Campidelli, A; Decot, V; Bensoussan, D

2018-02-01

Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative option for treatment of some malignant and non-malignant hematological diseases. However, post-HSCT patients are severely immunocompromised and susceptible to viral infections, which are a major cause of morbidity and mortality. Although antiviral agents are now available for most types of viral infections, they are not devoid of side effects and their efficacy is limited when there is no concomitant antiviral immune reconstitution. In recent decades, adoptive transfer of viral-specific T cells (VSTs) became an alternative treatment for viral infection after HSCT. However, two major issues are concerned in VST transfer: the risk of GVHD and antiviral efficacy. We report an exhaustive review of the published studies that focus on prophylactic and/or curative therapy by donor VST transfer for post-HSCT common viral infections. A low incidence of GVHD and a good antiviral efficacy was observed after adoptive transfer of VSTs from HSCT donor. Viral-specific T-cell transfer is a promising approach for a broad clinical application. Nevertheless, a randomized controlled study in a large cohort of patients comparing antiviral treatment alone to antiviral treatment combined with VSTs is still needed to demonstrate efficacy and safety.

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

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.

Stable cytotoxic T cell escape mutation in hepatitis C virus is linked to maintenance of viral fitness.

Directory of Open Access Journals (Sweden)

Luke Uebelhoer

2008-09-01

Full Text Available Mechanisms by which hepatitis C virus (HCV evades cellular immunity to establish persistence in chronically infected individuals are not clear. Mutations in human leukocyte antigen (HLA class I-restricted epitopes targeted by CD8(+ T cells are associated with persistence, but the extent to which these mutations affect viral fitness is not fully understood. Previous work showed that the HCV quasispecies in a persistently infected chimpanzee accumulated multiple mutations in numerous class I epitopes over a period of 7 years. During the acute phase of infection, one representative epitope in the C-terminal region of the NS3/4A helicase, NS3(1629-1637, displayed multiple serial amino acid substitutions in major histocompatibility complex (MHC anchor and T cell receptor (TCR contact residues. Only one of these amino acid substitutions at position 9 (P9 of the epitope was stable in the quasispecies. We therefore assessed the effect of each mutation observed during in vivo infection on viral fitness and T cell responses using an HCV subgenomic replicon system and a recently developed in vitro infectious virus cell culture model. Mutation of a position 7 (P7 TCR-contact residue, I1635T, expectedly ablated the T cell response without affecting viral RNA replication or virion production. In contrast, two mutations at the P9 MHC-anchor residue abrogated antigen-specific T cell responses, but additionally decreased viral RNA replication and virion production. The first escape mutation, L1637P, detected in vivo only transiently at 3 mo after infection, decreased viral production, and reverted to the parental sequence in vitro. The second P9 variant, L1637S, which was stable in vivo through 7 years of follow-up, evaded the antigen-specific T cell response and did not revert in vitro despite being less optimal in virion production compared to the parental virus. These studies suggest that HCV escape mutants emerging early in infection are not necessarily

Distinct phasic and sustained brain responses and connectivity of amygdala and bed nucleus of the stria terminalis during threat anticipation in panic disorder.

Science.gov (United States)

Brinkmann, L; Buff, C; Feldker, K; Tupak, S V; Becker, M P I; Herrmann, M J; Straube, T

2017-11-01

Panic disorder (PD) patients are constantly concerned about future panic attacks and exhibit general hypersensitivity to unpredictable threat. We aimed to reveal phasic and sustained brain responses and functional connectivity of the amygdala and the bed nucleus of the stria terminalis (BNST) during threat anticipation in PD. Using functional magnetic resonance imaging (fMRI), we investigated 17 PD patients and 19 healthy controls (HC) during anticipation of temporally unpredictable aversive and neutral sounds. We used a phasic and sustained analysis model to disentangle temporally dissociable brain activations. PD patients compared with HC showed phasic amygdala and sustained BNST responses during anticipation of aversive v. neutral stimuli. Furthermore, increased phasic activation was observed in anterior cingulate cortex (ACC), insula and prefrontal cortex (PFC). Insula and PFC also showed sustained activation. Functional connectivity analyses revealed partly distinct phasic and sustained networks. We demonstrate a role for the BNST during unpredictable threat anticipation in PD and provide first evidence for dissociation between phasic amygdala and sustained BNST activation and their functional connectivity. In line with a hypersensitivity to uncertainty in PD, our results suggest time-dependent involvement of brain regions related to fear and anxiety.

CRISPR-Cas systems exploit viral DNA injection to establish and maintain adaptive immunity.

Science.gov (United States)

Modell, Joshua W; Jiang, Wenyan; Marraffini, Luciano A

2017-04-06

Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems provide protection against viral and plasmid infection by capturing short DNA sequences from these invaders and integrating them into the CRISPR locus of the prokaryotic host. These sequences, known as spacers, are transcribed into short CRISPR RNA guides that specify the cleavage site of Cas nucleases in the genome of the invader. It is not known when spacer sequences are acquired during viral infection. Here, to investigate this, we tracked spacer acquisition in Staphylococcus aureus cells harbouring a type II CRISPR-Cas9 system after infection with the staphylococcal bacteriophage ϕ12. We found that new spacers were acquired immediately after infection preferentially from the cos site, the viral free DNA end that is first injected into the cell. Analysis of spacer acquisition after infection with mutant phages demonstrated that most spacers are acquired during DNA injection, but not during other stages of the viral cycle that produce free DNA ends, such as DNA replication or packaging. Finally, we showed that spacers acquired from early-injected genomic regions, which direct Cas9 cleavage of the viral DNA immediately after infection, provide better immunity than spacers acquired from late-injected regions. Our results reveal that CRISPR-Cas systems exploit the phage life cycle to generate a pattern of spacer acquisition that ensures a successful CRISPR immune response.

Viral Advertising on Facebook in Vietnam

OpenAIRE

Tran, Phuong

2014-01-01

The purpose of this thesis is to explore which factors affect the effectiveness of viral advertising on Facebook in Vietnam. The quantitative research method is applied in this research and the sample is Vietnamese Facebook users. After the data analysis stage using SPSS, it became clear that weak ties, perceptual affinity and emotions have an impact on the effectiveness of viral advertising. The results provide a pratical implication of how to make an Ad which can go viral on Facebook. Moreo...

Caspase cleavage of viral proteins, another way for viruses to make the best of apoptosis.

Science.gov (United States)

Richard, A; Tulasne, D

2012-03-08

Viral infection constitutes an unwanted intrusion that needs to be eradicated by host cells. On one hand, one of the first protective barriers set up to prevent viral replication, spread or persistence involves the induction of apoptotic cell death that aims to limit the availability of the cellular components for viral amplification. On the other hand, while they completely depend on the host molecular machinery, viruses also need to evade the cellular responses that are meant to destroy them. The existence of numerous antiapoptotic products within the viral kingdom proves that apoptosis constitutes a major threat that should better be bypassed. Among the different strategies developed to deal with apoptosis, one is based on what viruses do best: backfiring the cell on itself. Several unrelated viruses have been described to take advantage of apoptosis induction by expressing proteins targeted by caspases, the key effectors of apoptotic cell death. Caspase cleavage of these proteins results in various consequences, from logical apoptosis inhibition to more surprising enhancement or attenuation of viral replication. The present review aims at discussing the characterization and relevance of this post-translational modification that adds a new complexity in the already intricate host-apoptosis-virus triangle.

CRISPR-Cas type I-A Cascade complex couples viral infection surveillance to host transcriptional regulation in the dependence of Csa3b

Science.gov (United States)

He, Fei; Vestergaard, Gisle; Peng, Wenfang; She, Qunxin

2017-01-01

Abstract CRISPR-Cas (clustered regularly interspaced short palindromic repeats and the associated genes) constitute adaptive immune systems in bacteria and archaea and they provide sequence specific immunity against foreign nucleic acids. CRISPR-Cas systems are activated by viral infection. However, little is known about how CRISPR-Cas systems are activated in response to viral infection or how their expression is controlled in the absence of viral infection. Here, we demonstrate that both the transcriptional regulator Csa3b, and the type I-A interference complex Cascade, are required to transcriptionally repress the interference gene cassette in the archaeon Sulfolobus. Csa3b binds to two palindromic repeat sites in the promoter region of the cassette and facilitates binding of the Cascade to the promoter region. Upon viral infection, loading of Cascade complexes onto crRNA-matching protospacers leads to relief of the transcriptional repression. Our data demonstrate a mechanism coupling CRISPR-Cas surveillance of protospacers to transcriptional regulation of the interference gene cassette thereby allowing a fast response to viral infection. PMID:27980065

Functional difference between sustained and transient modulations of cognitive control in the simon task: evidence from false alarm responses on no-go trials.

Science.gov (United States)

Hasegawa, Kunihiro; Takahashi, Shin'ya

2013-01-01

Cognitive control in response compatibility tasks is modulated by the task context. Two types of contextual modulations have been demonstrated; sustained (block-wise) and transient (trial-by-trial). Recent research suggests that these modulations have different underlying mechanisms. This study presents new evidence supporting this claim by comparing false alarm (FA) responses on no-go trials of the Simon task between the sustained and transient contexts. In Experiment 1, the sustained context was manipulated so that a block included a larger number of incongruent trials. Results showed that participants made more FA responses by the hand opposite to the stimulus location. This suggests a generation of response bias in which the task-irrelevant location information is utilized in a reversed manner (i.e., to respond with the right hand to a stimulus presented on the left side and vice versa). Next, Experiment 2 examined the effect of the transient context and found that overall FA rate was lower when a no-go trial was preceded by an incongruent trial than by a congruent trial, whereas such response bias as that shown in Experiment 1 was not demonstrated. This suggests that the transient conflict context enhances inhibition of the task-irrelevant process but does not make the task-irrelevant information actively usable. Based on these results, we propound two types of cognitive control modulations as adaptive behaviors: response biasing based on utilization of the task-irrelevant information under the sustained conflict context and transient enhancement of inhibition of the task-irrelevant process based on the online conflict monitoring.

Managing sustainability in management education

OpenAIRE

Lystbæk, Christian Tang

2014-01-01

Environmental issues are increasingly becoming a key business concern at local, national, international and global levels. Consequently, environmental issues and sustainability have found their way into management education in terms of business ethics, corporate social or sustainability responsibilities (CSR), etc.. Dominant conceptions of CSR identify a series of different types of corporate responsibilities, fx. economic, legal, social, environmental, etc. (e.g. Crane & Matten, 2010). A...

HIV Viral Load: MedlinePlus Lab Test Information

Science.gov (United States)

... this page: https://medlineplus.gov/labtests/hivviralload.html HIV Viral Load To use the sharing features on this page, please enable JavaScript. What is an HIV Viral Load? An HIV viral load is a ...

Origins and challenges of viral dark matter.

Science.gov (United States)

Krishnamurthy, Siddharth R; Wang, David

2017-07-15

The accurate classification of viral dark matter - metagenomic sequences that originate from viruses but do not align to any reference virus sequences - is one of the major obstacles in comprehensively defining the virome. Depending on the sample, viral dark matter can make up from anywhere between 40 and 90% of sequences. This review focuses on the specific nature of dark matter as it relates to viral sequences. We identify three factors that contribute to the existence of viral dark matter: the divergence and length of virus sequences, the limitations of alignment based classification, and limited representation of viruses in reference sequence databases. We then discuss current methods that have been developed to at least partially circumvent these limitations and thereby reduce the extent of viral dark matter. Copyright © 2017 Elsevier B.V. All rights reserved.

Strategic Leadership of Corporate Sustainability

DEFF Research Database (Denmark)

Strand, Robert

2014-01-01

Strategic leadership and corporate sustainability have recently come together in conspicuously explicit fashion through the emergence of top management team (TMT) positions with dedicated corporate sustainability responsibilities. These TMT positions, commonly referred to as 'Chief Sustainability......? What effects do corporate sustainability TMT positions have at their organizations? We consider these questions through strategic leadership and neoinstitutional theoretical frameworks. Through the latter, we also engage with Weberian considerations of bureaucracy. We find that the reasons why...

Ethics, Corporate Social Responsibility, and Sustainability Education in AACSB Undergraduate and Graduate Marketing Curricula: A Benchmark Study

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Nicholls, Jeananne; Hair, Joseph F., Jr.; Ragland, Charles B.; Schimmel, Kurt E.

2013-01-01

AACSB International advocates integration of ethics, corporate social responsibility, and sustainability in all business school disciplines. This study provides an overview of the implementation of these three topics in teaching initiatives and assessment in business schools accredited by AACSB International. Since no comprehensive studies have…

Prophylactic Herpes Simplex Virus 2 (HSV-2) Vaccines Adjuvanted with Stable Emulsion and Toll-Like Receptor 9 Agonist Induce a Robust HSV-2-Specific Cell-Mediated Immune Response, Protect against Symptomatic Disease, and Reduce the Latent Viral Reservoir.

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Hensel, Michael T; Marshall, Jason D; Dorwart, Michael R; Heeke, Darren S; Rao, Eileen; Tummala, Padmaja; Yu, Li; Cohen, Gary H; Eisenberg, Roselyn J; Sloan, Derek D

2017-05-01

Several prophylactic vaccines targeting herpes simplex virus 2 (HSV-2) have failed in the clinic to demonstrate sustained depression of viral shedding or protection from recurrences. Although these vaccines have generated high titers of neutralizing antibodies (NAbs), their induction of robust CD8 T cells has largely been unreported, even though evidence for the importance of HSV-2 antigen-specific CD8 T cells is mounting in animal models and in translational studies involving subjects with active HSV-2-specific immune responses. We developed a subunit vaccine composed of the NAb targets gD and gB and the novel T cell antigen and tegument protein UL40, and we compared this vaccine to a whole-inactivated-virus vaccine (formaldehyde-inactivated HSV-2 [FI-HSV-2]). We evaluated different formulations in combination with several Th1-inducing Toll-like receptor (TLR) agonists in vivo In mice, the TLR9 agonist cytosine-phosphate-guanine (CpG) oligodeoxynucleotide formulated in a squalene-based oil-in-water emulsion promoted most robust, functional HSV-2 antigen-specific CD8 T cell responses and high titers of neutralizing antibodies, demonstrating its superiority to vaccines adjuvanted by monophosphoryl lipid A (MPL)-alum. We further established that FI-HSV-2 alone or in combination with adjuvants as well as adjuvanted subunit vaccines were successful in the induction of NAbs and T cell responses in guinea pigs. These immunological responses were coincident with a suppression of vaginal HSV-2 shedding, low lesion scores, and a reduction in latent HSV-2 DNA in dorsal root ganglia to undetectable levels. These data support the further preclinical and clinical development of prophylactic HSV-2 vaccines that contain appropriate antigen and adjuvant components responsible for programming elevated CD8 T cell responses. IMPORTANCE Millions of people worldwide are infected with herpes simplex virus 2 (HSV-2), and to date, an efficacious prophylactic vaccine has not met the rigors

Management of Viral Central Nervous System Infections: A Primer for Clinicians

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P Brandon Bookstaver

2017-04-01

Full Text Available Viruses are a common cause of central nervous system (CNS infections with many host, agent, and environmental factors influencing the expression of viral diseases. Viruses can be responsible for CNS disease through a variety of mechanisms including direct infection and replication within the CNS resulting in encephalitis, infection limited to the meninges, or immune-related processes such as acute disseminated encephalomyelitis. Common pathogens including herpes simplex virus, varicella zoster, and enterovirus are responsible for the greatest number of cases in immunocompetent hosts. Other herpes viruses (eg, cytomegalovirus, John Cunningham virus are more common in immunocompromised hosts. Arboviruses such as Japanese encephalitis virus and Zika virus are important pathogens globally, but the prevalence varies significantly by geographic region and often season. Early diagnosis from radiographic evidence and molecular (eg, rapid diagnostics is important for targeted therapy. Antivirals may be used effectively against some pathogens, although several viruses have no effective treatment. This article provides a review of epidemiology, diagnostics, and management of common viral pathogens in CNS disease.