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Sample records for viral trans-factor independent

  1. Homologous SV40 RNA trans-splicing: Special case or prime example of viral RNA trans-splicing?

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    Sushmita Poddar

    2014-06-01

    Full Text Available To date the Simian Virus 40 (SV40 is the only proven example of a virus that recruits the mechanism of RNA trans-splicing to diversify its sequences and gene products. Thereby, two identical viral transcripts are efficiently joined by homologous trans-splicing triggering the formation of a highly transforming 100 kDa super T antigen. Sequences of other viruses including HIV-1 and the human adenovirus type 5 were reported to be involved in heterologous trans-splicing towards cellular or viral sequences but the meaning of these events remains unclear. We computationally and experimentally investigated molecular features associated with viral RNA trans-splicing and identified a common pattern: Viral RNA trans-splicing occurs between strong cryptic or regular viral splice sites and strong regular or cryptic splice sites of the trans-splice partner sequences. The majority of these splice sites are supported by exonic splice enhancers. Splice sites that could compete with the trans-splicing sites for cis-splice reactions are weaker or inexistent. Finally, all but one of the trans-splice reactions seem to be facilitated by one or more complementary binding domains of 11 to 16 nucleotides in length which, however occur with a statistical probability close to one for the given length of the involved sequences. The chimeric RNAs generated via heterologous viral RNA trans-splicing either did not lead to fusion proteins or led to proteins of unknown function. Our data suggest that distinct viral RNAs are highly susceptible to trans-splicing and that heterologous viral trans-splicing, unlike homologous SV40 trans-splicing, represents a chance event.

  2. Both cis and trans Activities of Foot-and-Mouth Disease Virus 3D Polymerase Are Essential for Viral RNA Replication.

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    Herod, Morgan R; Ferrer-Orta, Cristina; Loundras, Eleni-Anna; Ward, Joseph C; Verdaguer, Nuria; Rowlands, David J; Stonehouse, Nicola J

    2016-08-01

    The Picornaviridae is a large family of positive-sense RNA viruses that contains numerous human and animal pathogens, including foot-and-mouth disease virus (FMDV). The picornavirus replication complex comprises a coordinated network of protein-protein and protein-RNA interactions involving multiple viral and host-cellular factors. Many of the proteins within the complex possess multiple roles in viral RNA replication, some of which can be provided in trans (i.e., via expression from a separate RNA molecule), while others are required in cis (i.e., expressed from the template RNA molecule). In vitro studies have suggested that multiple copies of the RNA-dependent RNA polymerase (RdRp) 3D are involved in the viral replication complex. However, it is not clear whether all these molecules are catalytically active or what other function(s) they provide. In this study, we aimed to distinguish between catalytically active 3D molecules and those that build a replication complex. We report a novel nonenzymatic cis-acting function of 3D that is essential for viral-genome replication. Using an FMDV replicon in complementation experiments, our data demonstrate that this cis-acting role of 3D is distinct from the catalytic activity, which is predominantly trans acting. Immunofluorescence studies suggest that both cis- and trans-acting 3D molecules localize to the same cellular compartment. However, our genetic and structural data suggest that 3D interacts in cis with RNA stem-loops that are essential for viral RNA replication. This study identifies a previously undescribed aspect of picornavirus replication complex structure-function and an important methodology for probing such interactions further. Foot-and-mouth disease virus (FMDV) is an important animal pathogen responsible for foot-and-mouth disease. The disease is endemic in many parts of the world with outbreaks within livestock resulting in major economic losses. Propagation of the viral genome occurs within

  3. 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.

  4. Deep evolutionary comparison of gene expression identifies parallel recruitment of trans-factors in two independent origins of C4 photosynthesis.

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    Aubry, Sylvain; Kelly, Steven; Kümpers, Britta M C; Smith-Unna, Richard D; Hibberd, Julian M

    2014-06-01

    With at least 60 independent origins spanning monocotyledons and dicotyledons, the C4 photosynthetic pathway represents one of the most remarkable examples of convergent evolution. The recurrent evolution of this highly complex trait involving alterations to leaf anatomy, cell biology and biochemistry allows an increase in productivity by ∼ 50% in tropical and subtropical areas. The extent to which separate lineages of C4 plants use the same genetic networks to maintain C4 photosynthesis is unknown. We developed a new informatics framework to enable deep evolutionary comparison of gene expression in species lacking reference genomes. We exploited this to compare gene expression in species representing two independent C4 lineages (Cleome gynandra and Zea mays) whose last common ancestor diverged ∼ 140 million years ago. We define a cohort of 3,335 genes that represent conserved components of leaf and photosynthetic development in these species. Furthermore, we show that genes encoding proteins of the C4 cycle are recruited into networks defined by photosynthesis-related genes. Despite the wide evolutionary separation and independent origins of the C4 phenotype, we report that these species use homologous transcription factors to both induce C4 photosynthesis and to maintain the cell specific gene expression required for the pathway to operate. We define a core molecular signature associated with leaf and photosynthetic maturation that is likely shared by angiosperm species derived from the last common ancestor of the monocotyledons and dicotyledons. We show that deep evolutionary comparisons of gene expression can reveal novel insight into the molecular convergence of highly complex phenotypes and that parallel evolution of trans-factors underpins the repeated appearance of C4 photosynthesis. Thus, exploitation of extant natural variation associated with complex traits can be used to identify regulators. Moreover, the transcription factors that are shared by

  5. Deep evolutionary comparison of gene expression identifies parallel recruitment of trans-factors in two independent origins of C4 photosynthesis.

    Directory of Open Access Journals (Sweden)

    Sylvain Aubry

    2014-06-01

    Full Text Available With at least 60 independent origins spanning monocotyledons and dicotyledons, the C4 photosynthetic pathway represents one of the most remarkable examples of convergent evolution. The recurrent evolution of this highly complex trait involving alterations to leaf anatomy, cell biology and biochemistry allows an increase in productivity by ∼ 50% in tropical and subtropical areas. The extent to which separate lineages of C4 plants use the same genetic networks to maintain C4 photosynthesis is unknown. We developed a new informatics framework to enable deep evolutionary comparison of gene expression in species lacking reference genomes. We exploited this to compare gene expression in species representing two independent C4 lineages (Cleome gynandra and Zea mays whose last common ancestor diverged ∼ 140 million years ago. We define a cohort of 3,335 genes that represent conserved components of leaf and photosynthetic development in these species. Furthermore, we show that genes encoding proteins of the C4 cycle are recruited into networks defined by photosynthesis-related genes. Despite the wide evolutionary separation and independent origins of the C4 phenotype, we report that these species use homologous transcription factors to both induce C4 photosynthesis and to maintain the cell specific gene expression required for the pathway to operate. We define a core molecular signature associated with leaf and photosynthetic maturation that is likely shared by angiosperm species derived from the last common ancestor of the monocotyledons and dicotyledons. We show that deep evolutionary comparisons of gene expression can reveal novel insight into the molecular convergence of highly complex phenotypes and that parallel evolution of trans-factors underpins the repeated appearance of C4 photosynthesis. Thus, exploitation of extant natural variation associated with complex traits can be used to identify regulators. Moreover, the transcription factors

  6. Transmissible gastroenteritis coronavirus genome packaging signal is located at the 5' end of the genome and promotes viral RNA incorporation into virions in a replication-independent process.

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    Morales, Lucia; Mateos-Gomez, Pedro A; Capiscol, Carmen; del Palacio, Lorena; Enjuanes, Luis; Sola, Isabel

    2013-11-01

    Preferential RNA packaging in coronaviruses involves the recognition of viral genomic RNA, a crucial process for viral particle morphogenesis mediated by RNA-specific sequences, known as packaging signals. An essential packaging signal component of transmissible gastroenteritis coronavirus (TGEV) has been further delimited to the first 598 nucleotides (nt) from the 5' end of its RNA genome, by using recombinant viruses transcribing subgenomic mRNA that included potential packaging signals. The integrity of the entire sequence domain was necessary because deletion of any of the five structural motifs defined within this region abrogated specific packaging of this viral RNA. One of these RNA motifs was the stem-loop SL5, a highly conserved motif in coronaviruses located at nucleotide positions 106 to 136. Partial deletion or point mutations within this motif also abrogated packaging. Using TGEV-derived defective minigenomes replicated in trans by a helper virus, we have shown that TGEV RNA packaging is a replication-independent process. Furthermore, the last 494 nt of the genomic 3' end were not essential for packaging, although this region increased packaging efficiency. TGEV RNA sequences identified as necessary for viral genome packaging were not sufficient to direct packaging of a heterologous sequence derived from the green fluorescent protein gene. These results indicated that TGEV genome packaging is a complex process involving many factors in addition to the identified RNA packaging signal. The identification of well-defined RNA motifs within the TGEV RNA genome that are essential for packaging will be useful for designing packaging-deficient biosafe coronavirus-derived vectors and providing new targets for antiviral therapies.

  7. Opportunities for independent power in Ontario : perspective of TransCanada Power

    International Nuclear Information System (INIS)

    Greflund, F.

    1998-01-01

    The recent white paper of the Government of Ontario and its implications for independent power producers (IPPs), vis-a-vis Ontario Hydro's market power and dominance, was discussed. The conclusion was that opportunities do exist to establish a competitive market for power which is open and transparent, has non-discriminatory transmission access, and in which price is a function of supply and demand. However, IPPs will need strong marketing skills to survive in the new marketplace. In addition to skills in power marketing, there will be strong demand for skills in gas marketing, operations, risk management, and financing. Prospects for interconnected markets and generators, and pipeline capacity considerations for Ontario were explored. The corporate profile of TransCanada Power (an affiliate of TransCanada Pipelines) was also reviewed. . 4 figs

  8. Orchestrating the Selection and Packaging of Genomic RNA by Retroviruses: An Ensemble of Viral and Host Factors

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    Kaddis Maldonado, Rebecca J.; Parent, Leslie J.

    2016-01-01

    Infectious retrovirus particles contain two copies of unspliced viral RNA that serve as the viral genome. Unspliced retroviral RNA is transcribed in the nucleus by the host RNA polymerase II and has three potential fates: (1) it can be spliced into subgenomic messenger RNAs (mRNAs) for the translation of viral proteins; or it can remain unspliced to serve as either (2) the mRNA for the translation of Gag and Gag–Pol; or (3) the genomic RNA (gRNA) that is packaged into virions. The Gag structural protein recognizes and binds the unspliced viral RNA to select it as a genome, which is selected in preference to spliced viral RNAs and cellular RNAs. In this review, we summarize the current state of understanding about how retroviral packaging is orchestrated within the cell and explore potential new mechanisms based on recent discoveries in the field. We discuss the cis-acting elements in the unspliced viral RNA and the properties of the Gag protein that are required for their interaction. In addition, we discuss the role of host factors in influencing the fate of the newly transcribed viral RNA, current models for how retroviruses distinguish unspliced viral mRNA from viral genomic RNA, and the possible subcellular sites of genomic RNA dimerization and selection by Gag. Although this review centers primarily on the wealth of data available for the alpharetrovirus Rous sarcoma virus, in which a discrete RNA packaging sequence has been identified, we have also summarized the cis- and trans-acting factors as well as the mechanisms governing gRNA packaging of other retroviruses for comparison. PMID:27657110

  9. Independent predictive factors for significant liver histological changes in patients with HBeAg-positive high-viral-load chronic HBV infection and a normal alanine aminotransferase level

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    LI Qiang

    2016-07-01

    Full Text Available Objective To investigate the independent predictive factors for significant liver histological changes (SLHCs in patients with HBeAg-positive high-viral-load chronic hepatitis B virus (HBV infection and a normal alanine aminotransferase (ALT level. MethodsA retrospective analysis was performed on the clinical data of 116 previously untreated patients with HBeAg-positive high-viral-load (HBV DNA≥105 copies/ml chronic HBV infection and a normal ALT level (<50 U/L who were hospitalized in Shanghai Public Health Clinical Center Affiliated to Fudan University from June 2013 to August 2015. The definition of SLHCs was inflammation ≥G2 and/or fibrosis≥S2. The t-test or Mann-Whitney U rank sum test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups. Univariate and multivariate regression analyses were used to determine independent predictive factors for SLHCs. ResultsOf all the 116 patients, 47(40.5% had SLHCs. The multivariate analysis showed that age (OR=2.828, P<0.05, ALT (OR=1.011, P<0.05, and gamma-glutamyl transpeptidase (GGT (OR=1.089, P<0.05 were independent predictors for SLHCs in patients with HBeAg-positive high-viral-load chronic HBV infection and a normal ALT level. The patients aged ≤30 years had a significantly lower incidence rate of SLHCs than those aged>30 years (21.6% vs 49.4%, χ2=6.42, P=0.015, the patients with ALT ≤30 U/L had a significantly lower incidence rate of SLHCs than those with 30 U/L<ALT≤50 U/L (17.6% vs 50.0%, χ2=19.86, P<0.001, and the patients with GGT≤40 U/L had a significantly lower incidence rate of SLHCs than those with GGT>40 U/L (28.8% vs 66.7%, χ2=28.63, P<0.001. ConclusionIn patients with HBeAg-positive high-viral-load chronic HBV infection and a normal ALT level, those with an age of>30 years, ALT>30 U/L, and GGT>40 U/L tend to develop SLHCs and need liver biopsy.

  10. CD8 T cell memory to a viral pathogen requires trans cosignaling between HVEM and BTLA.

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    Rachel Flynn

    Full Text Available Defining the molecular interactions required to program activated CD8 T cells to survive and become memory cells may allow us to understand how to augment anti-viral immunity. HVEM (herpes virus entry mediator is a member of the tumor necrosis factor receptor (TNFR family that interacts with ligands in the TNF family, LIGHT and Lymphotoxin-α, and in the Ig family, B and T lymphocyte attenuator (BTLA and CD160. The Ig family members initiate inhibitory signaling when engaged with HVEM, but may also activate survival gene expression. Using a model of vaccinia virus infection, we made the unexpected finding that deficiency in HVEM or BTLA profoundly impaired effector CD8 T cell survival and development of protective immune memory. Mixed adoptive transfer experiments indicated that BTLA expressed in CD8α+ dendritic cells functions as a trans-activating ligand that delivers positive co-signals through HVEM expressed in T cells. Our data demonstrate a critical role of HVEM-BTLA bidirectional cosignaling system in antiviral defenses by driving the differentiation of memory CD8 T cells.

  11. Transmissible Gastroenteritis Coronavirus Genome Packaging Signal Is Located at the 5′ End of the Genome and Promotes Viral RNA Incorporation into Virions in a Replication-Independent Process

    Science.gov (United States)

    Morales, Lucia; Mateos-Gomez, Pedro A.; Capiscol, Carmen; del Palacio, Lorena; Sola, Isabel

    2013-01-01

    Preferential RNA packaging in coronaviruses involves the recognition of viral genomic RNA, a crucial process for viral particle morphogenesis mediated by RNA-specific sequences, known as packaging signals. An essential packaging signal component of transmissible gastroenteritis coronavirus (TGEV) has been further delimited to the first 598 nucleotides (nt) from the 5′ end of its RNA genome, by using recombinant viruses transcribing subgenomic mRNA that included potential packaging signals. The integrity of the entire sequence domain was necessary because deletion of any of the five structural motifs defined within this region abrogated specific packaging of this viral RNA. One of these RNA motifs was the stem-loop SL5, a highly conserved motif in coronaviruses located at nucleotide positions 106 to 136. Partial deletion or point mutations within this motif also abrogated packaging. Using TGEV-derived defective minigenomes replicated in trans by a helper virus, we have shown that TGEV RNA packaging is a replication-independent process. Furthermore, the last 494 nt of the genomic 3′ end were not essential for packaging, although this region increased packaging efficiency. TGEV RNA sequences identified as necessary for viral genome packaging were not sufficient to direct packaging of a heterologous sequence derived from the green fluorescent protein gene. These results indicated that TGEV genome packaging is a complex process involving many factors in addition to the identified RNA packaging signal. The identification of well-defined RNA motifs within the TGEV RNA genome that are essential for packaging will be useful for designing packaging-deficient biosafe coronavirus-derived vectors and providing new targets for antiviral therapies. PMID:23966403

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

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    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...

  13. E1A-dependent trans-activation of the human MYC promoter is mediated by the E2F factor

    International Nuclear Information System (INIS)

    Hiebert, S.W.; Lipp, M.; Nevins, J.R.

    1989-01-01

    E2F is a cellular transcription factor that binds to two sites in the adenovirus E2 promoter. Previous experiments have implicated E2F in the E1A-dependent transactivation of the E2 gene since levels of active E2F increase markedly during adenovirus infection in parallel with the increase in E2 transcription, and an E2F binding site can confer E1A inducibility to a heterologous promoter. Here the authors show that E2F binds to two sequence elements within the P2 promoter of the human MYC gene which are within a region that is critical for promoter activity. The MYC promoter can be trans-activated in an E1A-dependent manner and site-directed mutagenesis demonstrates that these E2F elements are essential for trans-activation. Finally, they also find that adenovirus infection of quiescent cells results in a stimulation of the endogenous MYC gene. They conclude that the activation of the E2F factor, which is likely responsible for the activation of viral E2 transcription, is also responsible for the E1A-dependent induction of MYC transcription

  14. Attitudinal Factors Affecting Viral Advertising Pass-On Behaviour of Online Consumers in Food Industry

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    Mohd Salleh, Nurhidayah; Ariff, Mohd Shoki Md; Zakuan, Norhayati; Sulaiman, Zuraidah; Zameri Mat Saman, Muhamad

    2016-05-01

    The increase number of active users of social media, especially Facebook, stimulates viral advertising behaviour among them, thus attracting e-marketers to focus on viral advertising in promoting their products. In global market, use of Facebook platform indicated that food services/restaurant of food industry is ranked number 11 with 18.8% users’ response rate within the platform. This development calls for e-marketers in Malaysia to use Facebook as their viral advertising channel. Attitudinal factors affecting the viral advertising pass-on behaviour (VAPB) especially among members of social media is of interest to many researchers. The typical attitudinal factors used were attitude toward social media (ATSM), attitude toward advertising in social media (AASM) and attitude toward advertising in general (AAIG). Attitude toward advertised brand (ATAB) is important in fast food industry because users of social media tend to share their experience about tastes and features of the food. However, ATAB is less emphasized in the conceptual model between attitudinal factors and VAPB. These four factors of consumer attitude served as independent variables in the conceptual model of this study and their effect on viral advertising pass-on behaviour among members of Domino's Pizza Malaysia Facebook page was examined. Online survey using a set of questionnaire which was sent to the members of this group via private message was employed. A total of 254 sets of usable questionnaires were collected from the respondents. All the attitudinal factors, except for AASM, were found to have positive and significant effect on VAPB. AAIG exerted the strongest effect on VAPB. Therefore, e-marketers should emphasize on developing a favourable attitude toward advertising in general among members of a social media to get them involve in viral advertising. In addition, instilling a favourable attitude towards advertised brand is also vital as it influences the members to viral the brand

  15. 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

  16. Recycling Endosomes and Viral Infection.

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    Vale-Costa, Sílvia; Amorim, Maria João

    2016-03-08

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

  17. Viral hepatitis and HIV-associated tuberculosis: Risk factors and TB treatment outcomes in Thailand

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    Likanonsakul Sirirat

    2008-07-01

    Full Text Available Abstract Background The occurrence of tuberculosis (TB, human immunodeficiency virus (HIV, and viral hepatitis infections in the same patient poses unique clinical and public health challenges, because medications to treat TB and HIV are hepatotoxic. We conducted an observational study to evaluate risk factors for HBsAg and/or anti-HCV reactivity and to assess differences in adverse events and TB treatment outcomes among HIV-infected TB patients. Methods Patients were evaluated at the beginning, during, and at the end of TB treatment. Blood samples were tested for aspartate aminotransferase (AST, alanine aminotransferase (ALT, total bilirubin (BR, complete blood count, and CD4+ T lymphocyte cell count. TB treatment outcomes were assessed at the end of TB treatment according to international guidelines. Results Of 769 enrolled patients, 752 (98% had serologic testing performed for viral hepatitis: 70 (9% were reactive for HBsAg, 237 (31% for anti-HCV, and 472 (63% non-reactive for both markers. At the beginning of TB treatment, 18 (26% patients with HBsAg reactivity had elevated liver function tests compared with 69 (15% patients non-reactive to any viral marker (p = 0.02. At the end of TB treatment, 493 (64% were successfully treated. Factors independently associated with HBsAg reactivity included being a man who had sex with men (adjusted odds ratio [AOR], 2.1; 95% confidence interval [CI], 1.1–4.3 and having low TB knowledge (AOR, 1.8; CI, 1.0–3.0. Factors most strongly associated with anti-HCV reactivity were having injection drug use history (AOR, 12.8; CI, 7.0–23.2 and living in Bangkok (AOR, 15.8; CI, 9.4–26.5. The rate of clinical hepatitis and death during TB treatment was similar in patients HBsAg reactive, anti-HCV reactive, both HBsAg and anti-HCV reactive, and non-reactive to any viral marker. Conclusion Among HIV-infected TB patients living in Thailand, markers of viral hepatitis infection, particularly hepatitis C virus

  18. Induction of viral, 7-methyl-guanosine cap-independent translation and oncolysis by mitogen-activated protein kinase-interacting kinase-mediated effects on the serine/arginine-rich protein kinase.

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    Brown, Michael C; Bryant, Jeffrey D; Dobrikova, Elena Y; Shveygert, Mayya; Bradrick, Shelton S; Chandramohan, Vidyalakshmi; Bigner, Darell D; Gromeier, Matthias

    2014-11-01

    Protein synthesis, the most energy-consuming process in cells, responds to changing physiologic priorities, e.g., upon mitogen- or stress-induced adaptations signaled through the mitogen-activated protein kinases (MAPKs). The prevailing status of protein synthesis machinery is a viral pathogenesis factor, particularly for plus-strand RNA viruses, where immediate translation of incoming viral RNAs shapes host-virus interactions. In this study, we unraveled signaling pathways centered on the ERK1/2 and p38α MAPK-interacting kinases MNK1/2 and their role in controlling 7-methyl-guanosine (m(7)G) "cap"-independent translation at enterovirus type 1 internal ribosomal entry sites (IRESs). Activation of Raf-MEK-ERK1/2 signals induced viral IRES-mediated translation in a manner dependent on MNK1/2. This effect was not due to MNK's known functions as eukaryotic initiation factor (eIF) 4G binding partner or eIF4E(S209) kinase. Rather, MNK catalytic activity enabled viral IRES-mediated translation/host cell cytotoxicity through negative regulation of the Ser/Arg (SR)-rich protein kinase (SRPK). Our investigations suggest that SRPK activity is a major determinant of type 1 IRES competency, host cell cytotoxicity, and viral proliferation in infected cells. We are targeting unfettered enterovirus IRES activity in cancer with PVSRIPO, the type 1 live-attenuated poliovirus (PV) (Sabin) vaccine containing a human rhinovirus type 2 (HRV2) IRES. A phase I clinical trial of PVSRIPO with intratumoral inoculation in patients with recurrent glioblastoma (GBM) is showing early promise. Viral translation proficiency in infected GBM cells is a core requirement for the antineoplastic efficacy of PVSRIPO. Therefore, it is critically important to understand the mechanisms controlling viral cap-independent translation in infected host cells. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  19. Fab-based inhibitors reveal ubiquitin independent functions for HIV Vif neutralization of APOBEC3 restriction factors.

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    Jennifer M Binning

    2018-01-01

    Full Text Available The lentiviral protein Viral Infectivity Factor (Vif counteracts the antiviral effects of host APOBEC3 (A3 proteins and contributes to persistent HIV infection. Vif targets A3 restriction factors for ubiquitination and proteasomal degradation by recruiting them to a multi-protein ubiquitin E3 ligase complex. Here, we describe a degradation-independent mechanism of Vif-mediated antagonism that was revealed through detailed structure-function studies of antibody antigen-binding fragments (Fabs to the Vif complex. Two Fabs were found to inhibit Vif-mediated A3 neutralization through distinct mechanisms: shielding A3 from ubiquitin transfer and blocking Vif E3 assembly. Combined biochemical, cell biological and structural studies reveal that disruption of Vif E3 assembly inhibited A3 ubiquitination but was not sufficient to restore its packaging into viral particles and antiviral activity. These observations establish that Vif can neutralize A3 family members in a degradation-independent manner. Additionally, this work highlights the potential of Fabs as functional probes, and illuminates how Vif uses a multi-pronged approach involving both degradation dependent and independent mechanisms to suppress A3 innate immunity.

  20. 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...

  1. RNA helicase MOV10 functions as a co-factor of HIV-1 Rev to facilitate Rev/RRE-dependent nuclear export of viral mRNAs

    International Nuclear Information System (INIS)

    Huang, Feng; Zhang, Junsong; Zhang, Yijun; Geng, Guannan; Liang, Juanran; Li, Yingniang; Chen, Jingliang; Liu, Chao; Zhang, Hui

    2015-01-01

    Human immunodeficiency virus type 1 (HIV-1) exploits multiple host factors during its replication. The REV/RRE-dependent nuclear export of unspliced/partially spliced viral transcripts needs the assistance of host proteins. Recent studies have shown that MOV10 overexpression inhibited HIV-1 replication at various steps. However, the endogenous MOV10 was required in certain step(s) of HIV-1 replication. In this report, we found that MOV10 potently enhances the nuclear export of viral mRNAs and subsequently increases the expression of Gag protein and other late products through affecting the Rev/RRE axis. The co-immunoprecipitation analysis indicated that MOV10 interacts with Rev in an RNA-independent manner. The DEAG-box of MOV10 was required for the enhancement of Rev/RRE-dependent nuclear export and the DEAG-box mutant showed a dominant-negative activity. Our data propose that HIV-1 utilizes the anti-viral factor MOV10 to function as a co-factor of Rev and demonstrate the complicated effects of MOV10 on HIV-1 life cycle. - Highlights: • MOV10 can function as a co-factor of HIV-1 Rev. • MOV10 facilitates Rev/RRE-dependent transport of viral mRNAs. • MOV10 interacts with Rev in an RNA-independent manner. • The DEAG-box of MOV10 is required for the enhancement of Rev/RRE-dependent export.

  2. RNA helicase MOV10 functions as a co-factor of HIV-1 Rev to facilitate Rev/RRE-dependent nuclear export of viral mRNAs

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Feng; Zhang, Junsong; Zhang, Yijun; Geng, Guannan; Liang, Juanran; Li, Yingniang; Chen, Jingliang [Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Liu, Chao, E-mail: liuchao9@mail.sysu.edu.cn [Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Zhang, Hui [Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China)

    2015-12-15

    Human immunodeficiency virus type 1 (HIV-1) exploits multiple host factors during its replication. The REV/RRE-dependent nuclear export of unspliced/partially spliced viral transcripts needs the assistance of host proteins. Recent studies have shown that MOV10 overexpression inhibited HIV-1 replication at various steps. However, the endogenous MOV10 was required in certain step(s) of HIV-1 replication. In this report, we found that MOV10 potently enhances the nuclear export of viral mRNAs and subsequently increases the expression of Gag protein and other late products through affecting the Rev/RRE axis. The co-immunoprecipitation analysis indicated that MOV10 interacts with Rev in an RNA-independent manner. The DEAG-box of MOV10 was required for the enhancement of Rev/RRE-dependent nuclear export and the DEAG-box mutant showed a dominant-negative activity. Our data propose that HIV-1 utilizes the anti-viral factor MOV10 to function as a co-factor of Rev and demonstrate the complicated effects of MOV10 on HIV-1 life cycle. - Highlights: • MOV10 can function as a co-factor of HIV-1 Rev. • MOV10 facilitates Rev/RRE-dependent transport of viral mRNAs. • MOV10 interacts with Rev in an RNA-independent manner. • The DEAG-box of MOV10 is required for the enhancement of Rev/RRE-dependent export.

  3. Cap-independent translation of plant viral RNAs.

    Science.gov (United States)

    Kneller, Elizabeth L Pettit; Rakotondrafara, Aurélie M; Miller, W Allen

    2006-07-01

    The RNAs of many plant viruses lack a 5' cap and must be translated by a cap-independent mechanism. Here, we discuss the remarkably diverse cap-independent translation elements that have been identified in members of the Potyviridae, Luteoviridae, and Tombusviridae families, and genus Tobamovirus. Many other plant viruses have uncapped RNAs but their translation control elements are uncharacterized. Cap-independent translation elements of plant viruses differ strikingly from those of animal viruses: they are smaller (translation factors, and speculate on their mechanism of action and their roles in the virus replication cycle. Much remains to be learned about how these elements enable plant viruses to usurp the host translational machinery.

  4. Detection of trans-acting factors for hemoglobin switching by cell fusions

    International Nuclear Information System (INIS)

    Broyles, R.H.; Palmer, J.C.; Smith, D.J.; Ramseyer, T.H.

    1986-01-01

    The authors have devised protocols for chemically fusing erythroid cells from amphibians of different developmental stages, so that we may study the short-term effects of trans-acting factors on globin gene expression. The authors are performing both homospecifc (Rana x Rana) and heterospecific (Rana x Xenopus) fusions; and they are detecting the expression of specific globin genes with selective radioactive labeling ( 35 S-methionine is incorporated only into adult globins), polyacrylamide gel electrophoresis, monospecific antisera, and cDNA probes that are species-and developmental stage-specific. Their results indicate that: (1) there are factors in tadpole erythroblasts that can reactivate adult Hb synthesis in mature, synthetically-inactive adult RBCs; (2) there are factors in tadpole erythroblasts that can reactivate tadpole globin genes in adult RBCs; and (3) there are factors in adult erythroid cells that apparently activate adult globin genes in tadpole RBCs. These results suggests that erythroid cells from animals of different developmental stages possess different sets of globin gene-specific trans-acting factors which can be studied with a system that exhibits normal developmental Hb switching

  5. Tombusvirus-yeast interactions identify conserved cell-intrinsic viral restriction factors

    Directory of Open Access Journals (Sweden)

    Zsuzsanna eSasvari

    2014-08-01

    Full Text Available To combat viral infections, plants possess innate and adaptive immune pathways, such as RNA silencing, R gene and recessive gene-mediated resistance mechanisms. However, it is likely that additional cell-intrinsic restriction factors (CIRF are also involved in limiting plant virus replication. This review discusses novel CIRFs with antiviral functions, many of them RNA-binding proteins or affecting the RNA binding activities of viral replication proteins. The CIRFs against tombusviruses have been identified in yeast (Saccharomyces cerevisiae, which is developed as an advanced model organism. Grouping of the identified CIRFs based on their known cellular functions and subcellular localization in yeast reveals that TBSV replication is limited by a wide variety of host gene functions. Yeast proteins with the highest connectivity in the network map include the well-characterized Xrn1p 5’-3’ exoribonuclease, Act1p actin protein and Cse4p centromere protein. The protein network map also reveals an important interplay between the pro-viral Hsp70 cellular chaperone and the antiviral co-chaperones, and possibly key roles for the ribosomal or ribosome-associated factors. We discuss the antiviral functions of selected CIRFs, such as the RNA binding nucleolin, ribonucleases, WW-domain proteins, single- and multi-domain cyclophilins, TPR-domain co-chaperones and cellular ion pumps. These restriction factors frequently target the RNA-binding region in the viral replication proteins, thus interfering with the recruitment of the viral RNA for replication and the assembly of the membrane-bound viral replicase. Although many of the characterized CIRFs act directly against TBSV, we propose that the TPR-domain co-chaperones function as guardians of the cellular Hsp70 chaperone system, which is subverted efficiently by TBSV for viral replicase assembly in the absence of the TPR-domain co-chaperones.

  6. Risk Factors for Non-Suicidal Self-Injury Among Trans Youth.

    Science.gov (United States)

    Arcelus, Jon; Claes, Laurence; Witcomb, Gemma L; Marshall, Ellen; Bouman, Walter Pierre

    2016-03-01

    Previous research has reported high levels of non-suicidal self-injury (NSSI) in trans populations and younger age has been identified as a risk factor. To explore the prevalence of NSSI in a large group of young trans people and to identify risk factors for this group. Sociodemographic variables and measurements of NSSI (Self-Injury Questionnaire), psychopathology (Symptom Checklist-90-Revised), self-esteem (Rosenberg Self-Esteem Scale), victimization (Experiences of Transphobia Scale), interpersonal functioning (Inventory of Interpersonal Problems), and social support (Multidimensional Scale of Perceived Social Support). Two hundred sixty-eight young people attending a national gender clinic completed questionnaires assessing presence and frequency of NSSI and levels of general psychopathology, depression, anxiety, interpersonal problems, self-esteem, social support, transphobia, and information on hormone treatment. A lifetime presence of NSSI was identified in 46.3% of patients and 28.73% reported currently engaging in NSSI (within at least the past few months). Analyses showed that those with a lifetime presence of NSSI had significantly greater general psychopathology, lower self-esteem, had suffered more transphobia, and experienced greater interpersonal problems than those without NSSI. Findings were similar when comparing current with non-current NSSI. Overall, natal male patients reported less social support than natal female patients, but current NSSI was more common in natal female patients. Regression analyses confirmed that natal female gender and greater general psychopathology predicted current and lifetime NSSI. Further analyses confirmed that general psychopathology itself could be predicted by transphobic experiences, low self-esteem, and interpersonal problems, but not by the use of cross-sex hormones. These findings confirm that NSSI is common in trans youth and emphasize the need for interventions that decrease transphobia, increase social

  7. Anomaly depth detection in trans-admittance mammography: a formula independent of anomaly size or admittivity contrast

    International Nuclear Information System (INIS)

    Zhang, Tingting; Lee, Eunjung; Seo, Jin Keun

    2014-01-01

    Trans-admittance mammography (TAM) is a bioimpedance technique for breast cancer detection. It is based on the comparison of tissue conductivity: cancerous tissue is identified by its higher conductivity in comparison with the surrounding normal tissue. In TAM, the breast is compressed between two electrical plates (in a similar architecture to x-ray mammography). The bottom plate has many sensing point electrodes that provide two-dimensional images (trans-admittance maps) that are induced by voltage differences between the two plates. Multi-frequency admittance data (Neumann data) are measured over the range 50 Hz–500 kHz. TAM aims to determine the location and size of any anomaly from the multi-frequency admittance data. Various anomaly detection algorithms can be used to process TAM data to determine the transverse positions of anomalies. However, existing methods cannot reliably determine the depth or size of an anomaly. Breast cancer detection using TAM would be improved if the depth or size of an anomaly could also be estimated, properties that are independent of the admittivity contrast. A formula is proposed here that can estimate the depth of an anomaly independent of its size and the admittivity contrast. This depth estimation can also be used to derive an estimation of the size of the anomaly. The proposed estimations are verified rigorously under a simplified model. Numerical simulation shows that the proposed method also works well in general settings. (paper)

  8. Host and Viral Factors in HIV-Mediated Bystander Apoptosis

    Science.gov (United States)

    Garg, Himanshu; Joshi, Anjali

    2017-01-01

    Human immunodeficiency virus (HIV) infections lead to a progressive loss of CD4 T cells primarily via the process of apoptosis. With a limited number of infected cells and vastly disproportionate apoptosis in HIV infected patients, it is believed that apoptosis of uninfected bystander cells plays a significant role in this process. Disease progression in HIV infected individuals is highly variable suggesting that both host and viral factors may influence HIV mediated apoptosis. Amongst the viral factors, the role of Envelope (Env) glycoprotein in bystander apoptosis is well documented. Recent evidence on the variability in apoptosis induction by primary patient derived Envs underscores the role of Env glycoprotein in HIV disease. Amongst the host factors, the role of C-C Chemokine Receptor type 5 (CCR5), a coreceptor for HIV Env, is also becoming increasingly evident. Polymorphisms in the CCR5 gene and promoter affect CCR5 cell surface expression and correlate with both apoptosis and CD4 loss. Finally, chronic immune activation in HIV infections induces multiple defects in the immune system and has recently been shown to accelerate HIV Env mediated CD4 apoptosis. Consequently, those factors that affect CCR5 expression and/or immune activation in turn indirectly regulate HIV mediated apoptosis making this phenomenon both complex and multifactorial. This review explores the complex role of various host and viral factors in determining HIV mediated bystander apoptosis. PMID:28829402

  9. Paternally expressed Peg3 controls maternally expressed Zim1 as a trans factor.

    Directory of Open Access Journals (Sweden)

    An Ye

    Full Text Available The expression of two adjacent imprinted genes, Peg3 and Zim1, is inversely correlated: down-regulation of Peg3 coinciding with up-regulation of Zim1. The current study characterized this inverse correlation using a mutant allele targeting Peg3. According to the results, the mutation on the paternal allele of Peg3 resulted in a dramatic increase in the transcription levels of the maternal allele of Zim1, suggesting the involvement of unknown trans factors in this trans-allelic event. Subsequent ChIP experiments revealed that the protein encoded by Peg3 itself binds to the zinc finger exon of Zim1, which is modified with the repression mark H3K9me3. Interestingly, the levels of H3K9me3 on Zim1 are also reduced in the mutant cells lacking the protein PEG3, suggesting potential roles for PEG3 in establishing H3K9me3 on Zim1. Reintroducing PEG3 into the mutant cell restored down-regulation of Zim1, confirming the predicted repressor role for Peg3 on Zim1. Overall, these results demonstrated that paternally expressed Peg3 controls maternally expressed Zim1 as a trans factor. The current study also provides the first case for the trans-allelic interaction of two oppositely imprinted genes through their gene products.

  10. Exploring and Prioritizing Factors Influencing Viral Marketing in the Context of Mobile Application

    Directory of Open Access Journals (Sweden)

    Nastaran Hajiheidari

    2017-06-01

    Full Text Available Viral marketing, relying on word of mouth principle is an advertising or a way to publish it on the Internet or mobile networks. The main objective of this article is to explore and prioritize important factors affecting viral marketing in the context of mobile applications. Meta-synthesis technique was used to explore the important factors affecting viral marketing and then using Fuzzy Delphi to determine the significance of the factors. The population of this study in the quantitative section was experts working in the field of viral marketing in the mobile application industry who have been selected by snowball sampling method. In the meantime, 30 experts were selected. The results of meta-synthesis method showed 26 important factors. By using Fuzzy Delphi, 12 factors including speed of message, attractiveness of message, ability to communicate with the product, morality, reliability of the source or validity, personality of the recipient, motivations of people, emotions of people, culture, brand reputation, brand strength as well as brand image were the most important factors

  11. A Strong Case for Viral Genetic Factors in HIV Virulence

    Directory of Open Access Journals (Sweden)

    Joshua T. Herbeck

    2011-03-01

    Full Text Available HIV infections show great variation in the rate of progression to disease, and the role of viral genetic factors in this variation had remained poorly characterized until recently. Now a series of four studies [1–4] published within a year has filled this important gap and has demonstrated a robust effect of the viral genotype on HIV virulence.

  12. 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.

  13. 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.

  14. Tumultuous relationship between the human immunodeficiency virus type 1 viral infectivity factor (Vif) and the human APOBEC-3G and APOBEC-3F restriction factors.

    Science.gov (United States)

    Henriet, Simon; Mercenne, Gaëlle; Bernacchi, Serena; Paillart, Jean-Christophe; Marquet, Roland

    2009-06-01

    The viral infectivity factor (Vif) is dispensable for human immunodeficiency virus type 1 (HIV-1) replication in so-called permissive cells but is required for replication in nonpermissive cell lines and for pathogenesis. Virions produced in the absence of Vif have an aberrant morphology and an unstable core and are unable to complete reverse transcription. Recent studies demonstrated that human APOBEC-3G (hA3G) and APOBEC-3F (hA3F), which are selectively expressed in nonpermissive cells, possess strong anti-HIV-1 activity and are sufficient to confer a nonpermissive phenotype. Vif induces the degradation of hA3G and hA3F, suggesting that its main function is to counteract these cellular factors. Most studies focused on the hypermutation induced by the cytidine deaminase activity of hA3G and hA3F and on their Vif-induced degradation by the proteasome. However, recent studies suggested that several mechanisms are involved both in the antiviral activity of hA3G and hA3F and in the way Vif counteracts these antiviral factors. Attempts to reconcile the studies involving Vif in virus assembly and stability with these recent findings suggest that hA3G and hA3F partially exert their antiviral activity independently of their catalytic activity by destabilizing the viral core and the reverse transcription complex, possibly by interfering with the assembly and/or maturation of the viral particles. Vif could then counteract hA3G and hA3F by excluding them from the viral assembly intermediates through competition for the viral genomic RNA, by regulating the proteolytic processing of Pr55(Gag), by enhancing the efficiency of the reverse transcription process, and by inhibiting the enzymatic activities of hA3G and hA3F.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. TransPlanckian Particles and the Quantization of Time

    NARCIS (Netherlands)

    Hooft, G. 't

    1999-01-01

    Trans-Planckian particles are elementary particles accelerated such that their energies surpass the Planck value. There are several reasons to believe that trans-Planckian particles do not represent independent degrees of freedom in Hilbert space, but they are controlled by the cis-Planckian

  17. Integrase-independent HIV-1 infection is augmented under conditions of DNA damage and produces a viral reservoir

    International Nuclear Information System (INIS)

    Ebina, Hirotaka; Kanemura, Yuka; Suzuki, Yasutsugu; Urata, Kozue; Misawa, Naoko; Koyanagi, Yoshio

    2012-01-01

    HIV-1 possesses a viral protein, integrase (IN), which is necessary for its efficient integration in target cells. However, it has been reported that an IN-defective HIV strain is still capable of integration. Here, we assessed the ability of wild type (WT) HIV-1 to establish infection in the presence of IN inhibitors. We observed a low, yet clear infection of inhibitor-incubated cells infected with WT HIV which was identical to cells infected with IN-deficient HIV, D64A. Furthermore, the IN-independent integration could be enhanced by the pretreatment of cells with DNA-damaging agents suggesting that integration is mediated by a DNA repair system. Moreover, significantly faster viral replication kinetics with augmented viral DNA integration was observed after infection in irradiated cells treated with IN inhibitor compared to nonirradiated cells. Altogether, our results suggest that HIV DNA has integration potential in the presence of an IN inhibitor and may serve as a virus reservoir.

  18. Integrase-independent HIV-1 infection is augmented under conditions of DNA damage and produces a viral reservoir

    Energy Technology Data Exchange (ETDEWEB)

    Ebina, Hirotaka, E-mail: hebina@virus.kyoto-u.ac.jp; Kanemura, Yuka; Suzuki, Yasutsugu; Urata, Kozue; Misawa, Naoko; Koyanagi, Yoshio

    2012-05-25

    HIV-1 possesses a viral protein, integrase (IN), which is necessary for its efficient integration in target cells. However, it has been reported that an IN-defective HIV strain is still capable of integration. Here, we assessed the ability of wild type (WT) HIV-1 to establish infection in the presence of IN inhibitors. We observed a low, yet clear infection of inhibitor-incubated cells infected with WT HIV which was identical to cells infected with IN-deficient HIV, D64A. Furthermore, the IN-independent integration could be enhanced by the pretreatment of cells with DNA-damaging agents suggesting that integration is mediated by a DNA repair system. Moreover, significantly faster viral replication kinetics with augmented viral DNA integration was observed after infection in irradiated cells treated with IN inhibitor compared to nonirradiated cells. Altogether, our results suggest that HIV DNA has integration potential in the presence of an IN inhibitor and may serve as a virus reservoir.

  19. Crystallinity and the effect of ionizing radiation in polyethylene. V. Distribution of trans-vinylene and trans, trans conjugated double bonds in linear polyethylene

    International Nuclear Information System (INIS)

    Patel, G.N.

    1975-01-01

    Freeze-dried chain folded single crystals and the single crystals without amorphous surface layers (crystalline cores) of different thicknesses of linear polyethylene were irradiated with 60 Co γ-rays up to 600 Mrad. Concentration of trans-vinylene double bonds and conjugated diene produced during irradiation of the crystals was measured by infrared. Concentrations of trans-vinylene and of the conjugated diene were independent of thickness of crystalline core which suggest that the double bonds were randomly distributed in the crystalline parts of the crystals. Concentrations of trans-vinylene and of conjugated double bonds were lower in chain-folded crystals than in the crystalline cores and this suggests that the folds (amorphous surface layers) are less preferential sites for formation of the double bonds. The zero-order growth and first-order decay kinetics of trans-vinylene double bonds was studied by the equation derived by Dole et al. The equation is strictly obeyed up to 300 Mrad and the results then deviate. Since there is the decay of trans-vinylene double bonds and though there are no crosslinks in the crystalline cores, it has been suggested that the decay of the double bond does not result in the crosslinks

  20. Omega-6 and trans fatty acids in blood cell membranes: a risk factor for acute coronary syndromes?

    Science.gov (United States)

    Block, Robert C; Harris, William S; Reid, Kimberly J; Spertus, John A

    2008-12-01

    Although fatty acid intake has been associated with risk of coronary disease events, the association between blood omega-6 and trans fatty acids (FAs) at the time of an acute coronary syndrome (ACS) is unknown. The relationship of blood FA composition to ACS was analyzed in 768 incident cases and 768 controls (matched on age, sex, and race). Compared to controls, ACS cases' blood cell membrane content of linoleic acid was 13% lower (P 3 times the odds for being a case (odds ratio [OR] 3.23, 95% confidence interval [CI] 2.63-4.17). The relationship of arachidonic acid to ACS was U shaped; compared to the first quartile of arachidonic acid, the ORs for case status in the second, third, and fourth quartiles were 0.73 (95% CI 0.47-1.13), 0.65 (95% CI 0.41-1.04), and 2.32 (95% CI 1.39-3.90), respectively. The OR for a 1-SD increase in trans oleic acid was 1.24 (95% CI 1.06-1.45), and for trans-trans linoleic acid, 1.1 (95% CI 0.93-1.30). All associations were independent of membrane omega-3 FA content. High blood levels of linoleic acid but low levels of trans oleic acid are inversely associated with ACS. The relationship of arachidonic acid to ACS appears more complex.

  1. 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.

  2. Identification of trans-acting factors regulating SamDC expression in Oryza sativa

    Energy Technology Data Exchange (ETDEWEB)

    Basu, Supratim, E-mail: supratim_genetics@yahoo.co.in [Department of Crop Soil and Environmental Sciences, University of Arkansas, Fayetteville, AR 72701 (United States); Division of Plant Biology, Bose Institute, Kolkata (India); Roychoudhury, Aryadeep [Post Graduate Department of Biotechnology, St. Xavier' s College (Autonomous), 30, Mother Teresa Sarani, Kolkata - 700016, West Bengal (India); Sengupta, Dibyendu N. [Division of Plant Biology, Bose Institute, Kolkata (India)

    2014-03-07

    Highlights: • Identification of cis elements responsible for SamDC expression by in silico analysis. • qPCR analysis of SamDC expression to abiotic and biotic stress treatments. • Detection of SamDC regulators using identified cis-elements as probe by EMSA. • Southwestern Blot analysis to predict the size of the trans-acting factors. - Abstract: Abiotic stress affects the growth and productivity of crop plants; to cope with the adverse environmental conditions, plants have developed efficient defense machinery comprising of antioxidants like phenolics and flavonoids, and osmolytes like polyamines. SamDC is a key enzyme in the polyamine biosynthesis pathway in plants. In our present communication we have done in silico analysis of the promoter region of SamDC to look for the presence of different cis-regulatory elements contributing to its expression. Based on the presence of different cis-regulatory elements we completed comparative analysis of SamDC gene expression in rice lamina of IR-29 and Nonabokra by qPCR in response to the abiotic stress treatments of salinity, drought, cold and the biotic stress treatments of ABA and light. Additionally, to explore the role of the cis-regulatory elements in regulating the expression of SamDC gene in plants we comparatively analyzed the binding of rice nuclear proteins prepared from IR-29 and Nonabokra undergoing various stress treatments. The intensity of the complex formed was low and inducible in IR-29 in contrast to Nonabokra. Southwestern blot analysis helped in predicting the size of the trans-acting factors binding to these cis-elements. To our knowledge this is the first report on the comprehensive analysis of SamDC gene expression in rice and identification of the trans-acting factors regulating its expression.

  3. Investigating the effective factors on electronic trade by viral marketing

    Directory of Open Access Journals (Sweden)

    Nina Ghane

    2014-04-01

    Full Text Available This paper performs an investigation to explore a number of strategies underpinning virtual marketing. The study also provides several suggestions for marketers seeking to use viral marketing to position brands or to change a brand’s image, to encourage new product trials and to increase product uptake rates. In this article, we investigate the effect of external factors such as capturing the imagination, targeting credible sources, leveraging combinations of technology and easy to use product on virtual marketing. In addition, the study considers internal factors such as inclusion (the need to be part of a group, the need to be different and affection on viral marketing. The survey has been accomplished among 140 Iranian people, who were familiar with virtual marketing and they are selected, randomly. Using Pearson correlation as well as regression analysis, the study provides some evidences that there were some positive and meaningful relationship between some internal/external factors and virtual marketing.

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

    Science.gov (United States)

    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.

  5. 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

    Directory of Open Access Journals (Sweden)

    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.

  6. Factors associated with mother-to-child transmission of HIV-1 despite a maternal viral load EPF-ANRS CO1).

    Science.gov (United States)

    Tubiana, Roland; Le Chenadec, Jerome; Rouzioux, Christine; Mandelbrot, Laurent; Hamrene, Karima; Dollfus, Catherine; Faye, Albert; Delaugerre, Constance; Blanche, Stephane; Warszawski, Josiane

    2010-02-15

    The rate of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) type 1 is as low as 0.5% in non-breast-feeding mothers who delivered at term while receiving antiretroviral therapy with a plasma viral load <500 copies/mL. This situation accounted for 20% of the infected children born during the period 1997-2006 in the French Perinatal Cohort. We aimed to identify factors associated with such residual transmission risk. We performed a case-control study nested in the aforementioned subpopulation of the French Perinatal Cohort. Nineteen case patients (transmitters) and 60 control subjects (nontransmitters) were included. Case patients and control subjects did not differ by geographical origin, gestational age at HIV diagnosis, type of antiretroviral therapy received, or elective Cesarean delivery. Case patients were less often receiving treatment at the time that they conceived pregnancy than control subjects (16% vs 45%; P=.017). A lower proportion of case patients had a viral load <500 copies/mL, compared with control subjects, at 14 weeks (0% vs 38.1%; P=.02), 28 weeks (7.7% vs 62.1%; P=.005), and 32 weeks: (21.4% vs 71.1%; P=.004). The difference remained significant when we restricted analysis to the 10 of 16 intrapartum transmission cases. In a multivariate analysis at 30+/-4 weeks adjusted for viral load, CD4(+) T cell count, and time at antiretroviral therapy initiation, viral load was the only factor independently associated with MTCT of HIV (adjusted odds ratio, 23.2; 95% confidence interval, 3.5-553; P<.001). Early and sustained control of viral load is associated with a decreasing residual risk of MTCT of HIV-1. Guidelines should take into account not only CD4(+) T cell count and risk of preterm delivery, but also baseline HIV-1 load for deciding when to start antiretroviral therapy during pregnancy.

  7. Expression of Herpes Simplex Virus Thymidine Kinase/Ganciclovir by RNA Trans-Splicing Induces Selective Killing of HIV-Producing Cells

    Directory of Open Access Journals (Sweden)

    Carin K. Ingemarsdotter

    2017-06-01

    Full Text Available Antiviral strategies targeting hijacked cellular processes are less easily evaded by the virus than viral targets. If selective for viral functions, they can have a high therapeutic index. We used RNA trans-splicing to deliver the herpes simplex virus thymidine kinase-ganciclovir (HSV-tk/GCV cell suicide system into HIV-producing cells. Using an extensive in silico bioinformatics and RNA structural analysis approach, ten HIV RNA trans-splicing constructs were designed targeting eight different HIV splice donor or acceptor sites and were tested in cells expressing HIV. Trans-spliced mRNAs were identified in HIV-expressing cells using qRT-PCR with successful detection of fusion RNA transcripts between HIV RNA and the HSV-tk RNA transcripts from six of ten candidate RNA trans-splicing constructs. Conventional PCR and Sanger sequencing confirmed RNA trans-splicing junctions. Measuring cell viability in the presence or absence of GCV expression of HSV-tk by RNA trans-splicing led to selective killing of HIV-producing cells using either 3′ exon replacement or 5′ exon replacement in the presence of GCV. Five constructs targeting four HIV splice donor and acceptor sites, D4, A5, A7, and A8, involved in regulating the generation of multiple HIV RNA transcripts proved to be effective for trans-splicing mediated selective killing of HIV-infected cells, within which individual constructs targeting D4 and A8 were the most efficient.

  8. Trans-dissemination of exosomes from HIV-1-infected cells fosters both HIV-1 trans-infection in resting CD4+ T lymphocytes and reactivation of the HIV-1 reservoir.

    Science.gov (United States)

    Chiozzini, Chiara; Arenaccio, Claudia; Olivetta, Eleonora; Anticoli, Simona; Manfredi, Francesco; Ferrantelli, Flavia; d'Ettorre, Gabriella; Schietroma, Ivan; Andreotti, Mauro; Federico, Maurizio

    2017-09-01

    Intact HIV-1 and exosomes can be internalized by dendritic cells (DCs) through a common pathway leading to their transmission to CD4 + T lymphocytes by means of mechanisms defined as trans-infection and trans-dissemination, respectively. We previously reported that exosomes from HIV-1-infected cells activate both uninfected quiescent CD4 + T lymphocytes, which become permissive to HIV-1, and latently infected cells, with release of HIV-1 particles. However, nothing is known about the effects of trans-dissemination of exosomes produced by HIV-1-infected cells on uninfected or latently HIV-1-infected CD4 + T lymphocytes. Here, we report that trans-dissemination of exosomes from HIV-1-infected cells induces cell activation in resting CD4 + T lymphocytes, which appears stronger with mature than immature DCs. Using purified preparations of both HIV-1 and exosomes, we observed that mDC-mediated trans-dissemination of exosomes from HIV-1-infected cells to resting CD4 + T lymphocytes induces efficient trans-infection and HIV-1 expression in target cells. Most relevant, when both mDCs and CD4 + T lymphocytes were isolated from combination anti-retroviral therapy (ART)-treated HIV-1-infected patients, trans-dissemination of exosomes from HIV-1-infected cells led to HIV-1 reactivation from the viral reservoir. In sum, our data suggest a role of exosome trans-dissemination in both HIV-1 spread in the infected host and reactivation of the HIV-1 reservoir.

  9. Nopcsa, Baron Franz. 2014. Traveler, Scholar, Politician, Adventurer – A Transylvanian Baron at the Birth of Albanian Independence (ed. and trans. from German Robert Elsie. Budapest: Central European University Press. 227 pp.

    Directory of Open Access Journals (Sweden)

    David Mandler

    2015-01-01

    Full Text Available Nopcsa, Baron Franz. 2014. Traveler, Scholar, Politician, Adventurer – A Transylvanian Baron at the Birth of Albanian Independence (ed. and trans. from German Robert Elsie. Budapest: Central European University Press. 227 pp.  Reviewed by David Mandler, Independent Scholar

  10. TransForm: TransAlta 2000 annual report

    International Nuclear Information System (INIS)

    2001-01-01

    Financial information from TransAlta Corp. was presented along with a review of their operations throughout 2000 and a summary of the how the electric utility is doing in terms of power generation, independent power producers, transmission and energy marketing. The utility has changed from a regulated vertically integrated utility into one of Canada's largest non-regulated electric power generators. The utility sold its retail businesses in Alberta and New Zealand and now focuses on coal and hydro generation, gas generation, high-voltage transmission and energy marketing. The newly constructed Centralia, Washington generation facility was brought on line with 1,340 MW in May 2000, on time and on budget. This was the platform to diversify their generation into the United States. The utility reported a solid financial year with $177.9 million in earnings from continuing operations, an 83 per cent increase from 1999, driven mostly by the results of Centralia and power marketing and trading businesses. A financial loss was suffered when the Wabamum power plant in Alberta was shut down for several months to repair a boiler. The utility made excellent progress toward their goal of 15,000 megawatts by 2005 by starting with the construction of what will be one of Canada's largest cogeneration facilities at Sarnia, Ontario. TransAlta also commissioned a 360 MW cogeneration facility at Poplar Creek at Suncor's Fort McMurray oil sand facility. TransAlta also has an excellent track record in developing power generation projects internationally. refs., tabs., figs

  11. Potyviral VPg enhances viral RNA Translation and inhibits reporter mRNA translation in planta.

    Science.gov (United States)

    Eskelin, Katri; Hafrén, Anders; Rantalainen, Kimmo I; Mäkinen, Kristiina

    2011-09-01

    Viral protein genome-linked (VPg) plays a central role in several stages of potyvirus infection. This study sought to answer questions about the role of Potato virus A (PVA; genus Potyvirus) VPg in viral and host RNA expression. When expressed in Nicotiana benthamiana leaves in trans, a dual role of VPg in translation is observed. It repressed the expression of monocistronic luciferase (luc) mRNA and simultaneously induced a significant upregulation in the expression of both replicating and nonreplicating PVA RNAs. This enhanced viral gene expression was due at least to the 5' untranslated region (UTR) of PVA RNA, eukaryotic initiation factors 4E and iso 4E [eIF4E/eIF(iso)4E], and the presence of a sufficient amount of VPg. Coexpression of VPg with viral RNA increased the viral RNA amount, which was not the case with the monocistronic mRNA. Both mutations at certain lysine residues in PVA VPg and eIF4E/eIF(iso)4E depletion reduced its ability to upregulate the viral RNA expression. These modifications were also involved in VPg-mediated downregulation of monocistronic luc expression. These results suggest that VPg can titrate eIF4Es from capped monocistronic RNAs. Because VPg-mediated enhancement of viral gene expression required eIF4Es, it is possible that VPg directs eIF4Es to promote viral RNA expression. From this study it is evident that VPg can serve as a specific regulator of PVA expression by boosting the viral RNA amounts as well as the accumulation of viral translation products. Such a mechanism could function to protect viral RNA from being degraded and to secure efficient production of coat protein (CP) for virion formation.

  12. Potyviral VPg Enhances Viral RNA Translation and Inhibits Reporter mRNA Translation In Planta▿

    Science.gov (United States)

    Eskelin, Katri; Hafrén, Anders; Rantalainen, Kimmo I.; Mäkinen, Kristiina

    2011-01-01

    Viral protein genome-linked (VPg) plays a central role in several stages of potyvirus infection. This study sought to answer questions about the role of Potato virus A (PVA; genus Potyvirus) VPg in viral and host RNA expression. When expressed in Nicotiana benthamiana leaves in trans, a dual role of VPg in translation is observed. It repressed the expression of monocistronic luciferase (luc) mRNA and simultaneously induced a significant upregulation in the expression of both replicating and nonreplicating PVA RNAs. This enhanced viral gene expression was due at least to the 5′ untranslated region (UTR) of PVA RNA, eukaryotic initiation factors 4E and iso 4E [eIF4E/eIF(iso)4E], and the presence of a sufficient amount of VPg. Coexpression of VPg with viral RNA increased the viral RNA amount, which was not the case with the monocistronic mRNA. Both mutations at certain lysine residues in PVA VPg and eIF4E/eIF(iso)4E depletion reduced its ability to upregulate the viral RNA expression. These modifications were also involved in VPg-mediated downregulation of monocistronic luc expression. These results suggest that VPg can titrate eIF4Es from capped monocistronic RNAs. Because VPg-mediated enhancement of viral gene expression required eIF4Es, it is possible that VPg directs eIF4Es to promote viral RNA expression. From this study it is evident that VPg can serve as a specific regulator of PVA expression by boosting the viral RNA amounts as well as the accumulation of viral translation products. Such a mechanism could function to protect viral RNA from being degraded and to secure efficient production of coat protein (CP) for virion formation. PMID:21697470

  13. Endoplasmic Reticulum Stress Induced Synthesis of a Novel Viral Factor Mediates Efficient Replication of Genotype-1 Hepatitis E Virus.

    Directory of Open Access Journals (Sweden)

    Vidya P Nair

    2016-04-01

    Full Text Available Hepatitis E virus (HEV causes acute hepatitis in many parts of the world including Asia, Africa and Latin America. Though self-limiting in normal individuals, it results in ~30% mortality in infected pregnant women. It has also been reported to cause acute and chronic hepatitis in organ transplant patients. Of the seven viral genotypes, genotype-1 virus infects humans and is a major public health concern in South Asian countries. Sporadic cases of genotype-3 and 4 infection in human and animals such as pigs, deer, mongeese have been reported primarily from industrialized countries. Genotype-5, 6 and 7 viruses are known to infect animals such as wild boar and camel, respectively. Genotype-3 and 4 viruses have been successfully propagated in the laboratory in mammalian cell culture. However, genotype-1 virus replicates poorly in mammalian cell culture and no other efficient model exists to study its life cycle. Here, we report that endoplasmic reticulum (ER stress promotes genotype-1 HEV replication by inducing cap-independent, internal initiation mediated translation of a novel viral protein (named ORF4. Importantly, ORF4 expression and stimulatory effect of ER stress inducers on viral replication is specific to genotype-1. ORF4 protein sequence is mostly conserved among genotype-1 HEV isolates and ORF4 specific antibodies were detected in genotype-1 HEV patient serum. ORF4 interacted with multiple viral and host proteins and assembled a protein complex consisting of viral helicase, RNA dependent RNA polymerase (RdRp, X, host eEF1α1 (eukaryotic elongation factor 1 isoform-1 and tubulinβ. In association with eEF1α1, ORF4 stimulated viral RdRp activity. Furthermore, human hepatoma cells that stably express ORF4 or engineered proteasome resistant ORF4 mutant genome permitted enhanced viral replication. These findings reveal a positive role of ER stress in promoting genotype-1 HEV replication and pave the way towards development of an efficient

  14. Metabolism of trans, trans-muconaldehyde, a cytotoxic metabolite of benzene, in mouse liver by alcohol dehydrogenase Adh1 and aldehyde reductase AKR1A4

    International Nuclear Information System (INIS)

    Short, Duncan M.; Lyon, Robert; Watson, David G.; Barski, Oleg A.; McGarvie, Gail; Ellis, Elizabeth M.

    2006-01-01

    The reductive metabolism of trans, trans-muconaldehyde, a cytotoxic metabolite of benzene, was studied in mouse liver. Using an HPLC-based stopped assay, the primary reduced metabolite was identified as 6-hydroxy-trans, trans-2,4-hexadienal (OH/CHO) and the secondary metabolite as 1,6-dihydroxy-trans, trans-2,4-hexadiene (OH/OH). The main enzymes responsible for the highest levels of reductase activity towards trans, trans-muconaldehyde were purified from mouse liver soluble fraction first by Q-sepharose chromatography followed by either blue or red dye affinity chromatography. In mouse liver, trans, trans-muconaldehyde is predominantly reduced by an NADH-dependent enzyme, which was identified as alcohol dehydrogenase (Adh1). Kinetic constants obtained for trans, trans-muconaldehyde with the native Adh1 enzyme showed a V max of 2141 ± 500 nmol/min/mg and a K m of 11 ± 4 μM. This enzyme was inhibited by pyrazole with a K I of 3.1 ± 0.57 μM. Other fractions were found to contain muconaldehyde reductase activity independent of Adh1, and one enzyme was identified as the NADPH-dependent aldehyde reductase AKR1A4. This showed a V max of 115 nmol/min/mg and a K m of 15 ± 2 μM and was not inhibited by pyrazole

  15. Full trans-activation mediated by the immediate-early protein of equine herpesvirus 1 requires a consensus TATA box, but not its cognate binding sequence.

    Science.gov (United States)

    Kim, Seong K; Shakya, Akhalesh K; O'Callaghan, Dennis J

    2016-01-04

    The immediate-early protein (IEP) of equine herpesvirus 1 (EHV-1) has extensive homology to the IEP of alphaherpesviruses and possesses domains essential for trans-activation, including an acidic trans-activation domain (TAD) and binding domains for DNA, TFIIB, and TBP. Our data showed that the IEP directly interacted with transcription factor TFIIA, which is known to stabilize the binding of TBP and TFIID to the TATA box of core promoters. When the TATA box of the EICP0 promoter was mutated to a nonfunctional TATA box, IEP-mediated trans-activation was reduced from 22-fold to 7-fold. The IEP trans-activated the viral promoters in a TATA motif-dependent manner. Our previous data showed that the IEP is able to repress its own promoter when the IEP-binding sequence (IEBS) is located within 26-bp from the TATA box. When the IEBS was located at 100 bp upstream of the TATA box, IEP-mediated trans-activation was very similar to that of the minimal IE(nt -89 to +73) promoter lacking the IEBS. As the distance from the IEBS to the TATA box decreased, IEP-mediated trans-activation progressively decreased, indicating that the IEBS located within 100 bp from the TATA box sequence functions as a distance-dependent repressive element. These results indicated that IEP-mediated full trans-activation requires a consensus TATA box of core promoters, but not its binding to the cognate sequence (IEBS). Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Viral and immunological factors associated with breast milk transmission of SIV in rhesus macaques

    Directory of Open Access Journals (Sweden)

    Fresh Lynn

    2004-07-01

    Full Text Available Abstract Background The viral and host factors involved in transmission of HIV through breastfeeding are largely unknown, and intervention strategies are urgently needed to protect at-risk populations. To evaluate the viral and immunological factors directly related to milk transmission of virus, we have evaluated the disease course of Simian Immunodeficiency Virus (SIV in lactating rhesus macaques (Macaca mulatta as a model of natural breast milk transmission of HIV. Results Fourteen lactating macaques were infected intravenously with SIV/DeltaB670, a pathogenic isolate of SIV and were pair-housed with their suckling infants throughout the disease course. Transmission was observed in 10 mother-infant pairs over a one-year period. Two mothers transmitted virus during the period of initial viremia 14–21 days post inoculation (p.i. and were classified as early transmitters. Peak viral loads in milk and plasma of early transmitters were similar to other animals, however the early transmitters subsequently displayed a rapid progressor phenotype and failed to control virus expression as well as other animals at 56 days p.i. Eight mothers were classified as late transmitters, with infant infection detected at time points in the chronic stage of the maternal SIV disease course (81 to 360 days. Plasma viral loads, CD4+ T cell counts and SIV-specific antibody titers were similar in late transmitters and non-transmitters. Late breast milk transmission, however, was correlated with higher average milk viral loads and more persistent viral expression in milk 12 to 46 weeks p.i. as compared to non-transmitters. Four mothers failed to transmit virus, despite disease progression and continuous lactation. Conclusion These studies validate the SIV-infected rhesus macaque as a model for breast milk transmission of HIV. As observed in studies of HIV-infected women, transmission occurred at time points throughout the period of lactation. Transmission during the

  17. Faktor Risiko Non Viral Pada Karsinoma Nasofaring

    Directory of Open Access Journals (Sweden)

    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

  18. Role of viral coinfections in asthma development.

    Directory of Open Access Journals (Sweden)

    Maria Luz Garcia-Garcia

    Full Text Available Viral respiratory infections, especially acute bronchiolitis, play a key role in the development of asthma in childhood. However, most studies have focused on respiratory syncytial virus or rhinovirus infections and none of them have compared the long-term evolution of single versus double or multiple viral infections.Our aim was to compare the frequency of asthma development at 6-8 years in children with previous admission for bronchiolitis associated with single versus double or multiple viral infection.A cross-sectional study was performed in 244 children currently aged 6-8 years, previously admitted due to bronchiolitis between September 2008 and December 2011. A structured clinical interview and the ISAAC questionnaire for asthma symptoms for 6-7-year-old children, were answered by parents by telephone. Specimens of nasopharyngeal aspirate for virological study (polymerase chain reaction and clinical data were prospectively taken during admission for bronchiolitis.Median current age at follow-up was 7.3 years (IQR: 6.7-8.1. The rate of recurrent wheezing was 82.7% in the coinfection group and 69.7% in the single-infection group, p = 0.06. The number of wheezing-related admissions was twice as high in coinfections than in single infections, p = 0.004. Regarding the ISAAC questionnaire, 30.8% of coinfections versus 15% of single infections, p = 0.01, presented "wheezing in the last 12 months", data that strongly correlate with current prevalence of asthma. "Dry cough at night" was also reported more frequently in coinfections than in single infections, p = 0.02. The strongest independent risk factors for asthma at 6-8 years of age were: age > 9 months at admission for bronchiolitis (OR: 3.484; CI95%: 1.459-8.317, p:0.005, allergic rhinitis (OR: 5.910; 95%CI: 2.622-13.318, p<0.001, and viral coinfection-bronchiolitis (OR: 3.374; CI95%: 1.542-7.386, p:0.01.Asthma at 6-8 years is more frequent and severe in those children previously hospitalized

  19. Hepatitis B viral factors and treatment responses in chronic hepatitis B

    Directory of Open Access Journals (Sweden)

    Chih-Lin Lin

    2013-06-01

    Full Text Available Baseline and on-treatment hepatitis B viral factors are reported to affect treatment responses. A lower baseline hepatitis B virus (HBV DNA level is a strong predictor of the response to antiviral therapy. HBV genotype A/B patients have better responses to interferon-based therapy than those with genotypes C/D. Regarding the association of HBV mutants with responses to antiviral therapy, current evidence is limited. On-treatment viral suppression is the most important predictor of response to nucleoside analogs. On-treatment hepatitis B surface antigen decline is significantly associated with response to pegylated interferon. In the future, individualized therapy should be based on treatment efficacy, adverse effects, baseline and on-treatment predictors of antiviral therapy.

  20. Translation of a nonpolyadenylated viral RNA is enhanced by binding of viral coat protein or polyadenylation of the RNA.

    Science.gov (United States)

    Neeleman, L; Olsthoorn, R C; Linthorst, H J; Bol, J F

    2001-12-04

    On entering a host cell, positive-strand RNA virus genomes have to serve as messenger for the translation of viral proteins. Efficient translation of cellular messengers requires interactions between initiation factors bound to the 5'-cap structure and the poly(A) binding protein bound to the 3'-poly(A) tail. Initiation of infection with the tripartite RNA genomes of alfalfa mosaic virus (AMV) and viruses from the genus Ilarvirus requires binding of a few molecules of coat protein (CP) to the 3' end of the nonpolyadenylated viral RNAs. Moreover, infection with the genomic RNAs can be initiated by addition of the subgenomic messenger for CP, RNA 4. We report here that extension of the AMV RNAs with a poly(A) tail of 40 to 80 A-residues permitted initiation of infection independently of CP or RNA 4 in the inoculum. Specifically, polyadenylation of RNA 1 relieved an apparent bottleneck in the translation of the viral RNAs. Translation of RNA 4 in plant protoplasts was autocatalytically stimulated by its encoded CP. Mutations that interfered with CP binding to the 3' end of viral RNAs reduced translation of RNA 4 to undetectable levels. Possibly, CP of AMV and ilarviruses stimulates translation of viral RNAs by acting as a functional analogue of poly(A) binding protein or other cellular proteins.

  1. Functional interchangeability of late domains, late domain cofactors and ubiquitin in viral budding.

    Directory of Open Access Journals (Sweden)

    Maria Zhadina

    2010-10-01

    Full Text Available The membrane scission event that separates nascent enveloped virions from host cell membranes often requires the ESCRT pathway, which can be engaged through the action of peptide motifs, termed late (L- domains, in viral proteins. Viral PTAP and YPDL-like L-domains bind directly to the ESCRT-I and ALIX components of the ESCRT pathway, while PPxY motifs bind Nedd4-like, HECT-domain containing, ubiquitin ligases (e.g. WWP1. It has been unclear precisely how ubiquitin ligase recruitment ultimately leads to particle release. Here, using a lysine-free viral Gag protein derived from the prototypic foamy virus (PFV, where attachment of ubiquitin to Gag can be controlled, we show that several different HECT domains can replace the WWP1 HECT domain in chimeric ubiquitin ligases and drive budding. Moreover, artificial recruitment of isolated HECT domains to Gag is sufficient to stimulate budding. Conversely, the HECT domain becomes dispensable if the other domains of WWP1 are directly fused to an ESCRT-1 protein. In each case where budding is driven by a HECT domain, its catalytic activity is essential, but Gag ubiquitination is dispensable, suggesting that ubiquitin ligation to trans-acting proteins drives budding. Paradoxically, however, we also demonstrate that direct fusion of a ubiquitin moiety to the C-terminus of PFV Gag can also promote budding, suggesting that ubiquitination of Gag can substitute for ubiquitination of trans-acting proteins. Depletion of Tsg101 and ALIX inhibits budding that is dependent on ubiquitin that is fused to Gag, or ligated to trans-acting proteins through the action of a PPxY motif. These studies underscore the flexibility in the ways that the ESCRT pathway can be engaged, and suggest a model in which the identity of the protein to which ubiquitin is attached is not critical for subsequent recruitment of ubiquitin-binding components of the ESCRT pathway and viral budding to proceed.

  2. [Prevalence and risk factors of respiratory viral infection in acute exacerbation of chronic obstructive pulmonary disease].

    Science.gov (United States)

    Du, X B; Ma, X; Gao, Y; Wen, L F; Li, J; Wang, Z Z; Liu, S

    2017-04-12

    Objective: To study the prevalence of respiratory viral infection in chronic obstructive pulmonary disease(COPD) exacerbations and to find the factors associated with susceptibility to viral infections. Methods: Eighty patients with exacerbations of COPD and 50 stable COPD patients were recruited. Nasopharyngeal swabs were tested for a range of 18 different respiratory viruses using PCR. Results: Among the COPD exacerbations, viral infection was detected in 18 episodes (22.5%) . The most common virus was rhinovirus (33.3%), followed by coronavirus(27.8%), parainfluenza(22.2%), metapneumovirus(11.1%) and influenza virus B(5.6%). The prevalence of viral infection was 8% in the stable COPD patients. In multivariate regression analysis fever was found to be significantly associated with viral infections in COPD exacerbations (Odds ratio 4.99, 95% CI 1.51-16.48, P =0.008). Conclusion: Viral respiratory pathogens were more often detected in respiratory specimens from hospitalized patients with AECOPD than those with stable COPD. Rhinovirus was the most common infecting agent identified. The symptom of fever was associated with viral detection.

  3. Herpesvirus papio contains a plasmid origin of replication that acts in cis interspecies with an Epstein-Barr virus trans-acting function.

    Science.gov (United States)

    Pesano, R L; Pagano, J S

    1986-01-01

    Herpesvirus papio (HVP) and Epstein-Barr virus (EBV) are closely related biologically and biochemically; lymphoblastoid cells infected with either virus contain episomal viral DNA. The putative origin of replication for EBV plasmids (oriP) has been assigned to a 1,790-base-pair fragment (cis) in the short unique region of the genome which requires a viral function supplied in trans from elsewhere in the genome (J. Yates, N. Warren, D. Reisman, and B. Sugden, Proc. Natl. Acad. Sci. USA 81:3806-3810, 1984). We report here the identification of the putative origin of replication (cis) in HVP; we assigned it to the HVP EcoRI K fragment. The results indicate that the HVP replication process requires both a cis and a trans-acting function, analogous to that found in EBV. Images PMID:3023667

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

    Science.gov (United States)

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

    2015-03-01

    of the host in virus evolution is still understudied. In this study, we used a plant RNA virus, tombusvirus, to examine the role of a cellular proteasomal protein, called Rpn11, in tombusvirus recombination in a yeast model host, in plants, and in vitro. We found that the cellular Rpn11 is subverted for tombusvirus replication and Rpn11 has a proteasome-independent function in facilitating viral replication. When the Rpn11 level is knocked down or a mutated Rpn11 is expressed, then tombusvirus RNA goes through rapid viral recombination and evolution. Taken together, the results show that the co-opted cellular Rpn11 is a critical host factor for tombusviruses by regulating viral replication and genetic recombination. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  5. Chemometric analysis of mass spectra of cis and trans fatty acid picolinyl esters

    DEFF Research Database (Denmark)

    Leth, Torben

    1997-01-01

    and trans fatty acids of C16:1, C18:1,n-9, C18:1,n-12, C18:2 and C22:1 in two- and three-dimensional score plots. With Soft Independent Modelling of Class Analogy (SIMCA), it is possible to calculate models that can predict from the mass spectra of unknown fatty acids whether they are of the cis or trans...... configuration, which is demonstrated for C18:1 trans from hardened margarine and butter....

  6. Trans-complex formation by proteolipid channels in the terminal phase of membrane fusion

    DEFF Research Database (Denmark)

    Peters, C; Bayer, M J; Bühler, S

    2001-01-01

    -complex formation occurs downstream from trans-SNARE pairing, and depends on both the Rab-GTPase Ypt7 and calmodulin. The maintenance of existing complexes and completion of fusion are independent of trans-SNARE pairs. Reconstituted proteolipids form sealed channels, which can expand to form aqueous pores in a Ca2...

  7. Trans-fatty acid consumption and heart rate variability in two separate cohorts of older and younger adults

    Science.gov (United States)

    Soares-Miranda, Luisa; Stein, Phyllis K; Imamura, Fumiaki; Sattelmair, Jacob; Lemaitre, Rozenn N; Siscovick, David S; Mota, Jorge; Mozaffarian, Dariush

    2014-01-01

    Background Trans-fatty acid (TFA) consumption is associated with risk of coronary heart disease, and trans-18:2, but not trans-18:1, in red blood cells membranes has been associated with sudden cardiac arrest. Abnormal heart rate variability (HRV) reflects autonomic dysfunction and predicts cardiac death. Relationships between TFA consumption and HRV remain under-studied. We determined whether total TFA consumption, as well as trans-18:1 and trans-18:2 TFA consumption, were independently associated with HRV in two independent cohorts in the US and Portugal. Methods and Results In two independent cohorts of older US adults (Cardiovascular Health Study ([CHS], age=72±5yrs, 1989/1995) and young Portuguese adults (Porto, age=19±2yrs, 2008/2010), we assessed habitual TFA intake by food frequency questionnaires in CHS (separately estimating trans-18:1 and trans-18:2) and multiple 24-hour recalls in Porto (estimating total TFA only, which in a subset correlated with circulating trans-18:2, but not trans-18:1, suggesting that we captured the former). HRV was assessed using 24-hour Holters in CHS (N=1,076) and repeated short-term (5-min) ECGs in Porto (N=160). We used multivariate-adjusted linear regression to relate TFA consumption to HRV cross-sectionally (CHS, Porto) and longitudinally (CHS). In CHS, higher trans-18:2 consumption was associated with lower 24-hour standard-deviation-of-all-normal-to-normal-intervals (SDNN) both cross-sectionally (−12%, 95%CI=6–19%, p=0.001) and longitudinally (−15%, 95%CI=4–25 %, p= 0.009), and lower 24-hour SDANN and SDNN-index (pHRV, in particular time-domain indices (SDNN, SDANN, SDNN-index; pHRV in both older and young adults. Trans-18:1 consumption is associated with more favorable HRV indices in older adults. Our results support the need to investigate potential HRV related mechanisms whereby trans-18:2 may increase arrhythmic risk. PMID:22772898

  8. Clinical definition of respiratory viral infections in young children and potential bronchiolitis misclassification.

    Science.gov (United States)

    Megalaa, Rosemary; Perez, Geovanny F; Kilaikode-Cheruveettara, Sasikumar; Kotwal, Nidhi; Rodriguez-Martinez, Carlos E; Nino, Gustavo

    2018-01-01

    Viral respiratory infections are often grouped as a single respiratory syndrome named 'viral bronchiolitis', independently of the viral etiology or individual risk factors. Clinical trials and guidelines have used a more stringent definition of viral bronchiolitis, including only the first episode of wheezing in children less than 12 months of age without concomitant respiratory comorbidities. There is increasing evidence suggesting that this definition is not being followed by pediatric care providers, but it is unclear to what extent viral respiratory infections are currently misclassified as viral bronchiolitis using standard definitions. We conducted a retrospective analysis of hospitalized young children (≤3 years) due to viral respiratory infections. Bronchiolitis was defined as the first wheezing episode less than 12 months of age. Demographic variables and comorbidities were obtained by electronic medical record review. The study comprised a total of 513 hospitalizations (n=453). Viral bronchiolitis was diagnosed in 144 admissions (28.1%). Notably, we identified that the majority of children diagnosed with bronchiolitis (63%) were misclassified as they had prior episodes of wheezing. Many children with bronchiolitis misclassification had significant comorbidities, including prematurity (51%), neuromuscular conditions (9.8%), and congenital heart disease (9.8%). Misclassification of bronchiolitis is a common problem that may lead to inappropriate management of viral respiratory infections in young children. A comprehensive approach that takes into consideration viral etiology and individual risk factors may lead to a more accurate clinical assessment of this condition and would potentially prevent bronchiolitis misclassification. © American Federation for Medical Research (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  9. An acutely and latently expressed herpes simplex virus 2 viral microRNA inhibits expression of ICP34.5, a viral neurovirulence factor.

    Science.gov (United States)

    Tang, Shuang; Bertke, Andrea S; Patel, Amita; Wang, Kening; Cohen, Jeffrey I; Krause, Philip R

    2008-08-05

    Latency-associated transcript (LAT) sequences regulate herpes simplex virus (HSV) latency and reactivation from sensory neurons. We found a HSV-2 LAT-related microRNA (miRNA) designated miR-I in transfected and infected cells in vitro and in acutely and latently infected ganglia of guinea pigs in vivo. miR-I is also expressed in human sacral dorsal root ganglia latently infected with HSV-2. miR-I is expressed under the LAT promoter in vivo in infected sensory ganglia. We also predicted and identified a HSV-1 LAT exon-2 viral miRNA in a location similar to miR-I, implying a conserved mechanism in these closely related viruses. In transfected and infected cells, miR-I reduces expression of ICP34.5, a key viral neurovirulence factor. We hypothesize that miR-I may modulate the outcome of viral infection in the peripheral nervous system by functioning as a molecular switch for ICP34.5 expression.

  10. E1B-attenuated onco lytic adenovirus enhances antitumor effect of radionuclide therapy by P53-independent way: cellular basic for radionuclide-viral therapy

    Energy Technology Data Exchange (ETDEWEB)

    Zhenwei, Zhang [Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Hua, Wu; Xuemei, Zhang [Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Xinyuan, Liu [Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai (China)

    2004-07-01

    Purpose: Chemotherapy or external radiation therapy can potentiate the therapeutic effect of E1 B-attenuated oncolytic adenovirus. In this study, the antitumor efficacy of oncolytic adenovirus combined with internal radionuclide therapy was evaluated. Methods: Firstly, viral replication was examined by plaque assay and Southern blotting, after oncolytic adenovirus, ZD55, was exposed to iodine-131. Cell viability was evaluated qualitatively by crystal violet staining and quantitatively by MTT assay. FACS analysis was performed to determine the synergic proapoptotic effect of iodine-131 combined with ZD55. Results: Irradiation of iodine-131 does not influence ZD55 viral DNA replication. In combination with ZD55, iodine-131 can efficiently kill tumor cells in a p53-independent model. ZD55 augments the proapoptotic effect of iodine-131. Conclusion: Radionuclide-viral therapy might be a novel tool for treatment of hepatocarcinoma. (authors)

  11. Coordinate viral induction of tumor necrosis factor α and interferon β in human B cells and monocytes

    International Nuclear Information System (INIS)

    Goldfeld, A.E.; Maniatis, T.

    1989-01-01

    Human tumor necrosis factor α (TNF-α) gene expression can be induced primarily in cells of the monocyte/macrophage lineage by a variety of inducers, including lipopolysaccharide, phorbol esters such as phorbol 12-myristate 13-acetate, and virus or synthetic double-stranded RNA [poly(I)·poly(C)]. In this paper the authors show that the TNF-α gene also responds to virus and phorbol 12-myristate 13-acetate in B lymphocytes and that virus is the most potent inducer of TNF-α mRNA in both monocyte and B-cell lines. In addition, they show that viral infection coinduces the expression of TNF-α and interferon β mRNA and that viral induction of both genes is blocked by the kinase inhibitor 2-aminopurine. Inhibition of protein synthesis with cycloheximide had no effect on mRNA expression of the genes in one of three cell lines tested (U937) but blocked the viral induction of both genes in another (Namalwa). Thus, the regulatory factors required for mRNA induction of both genes are present prior to the addition of virus in U937 but not in Namalwa cells. However, in a third cell line (JY), cycloheximide blocked viral induction of the interferon β gene but not the TNF-α gene. Taken together, these observations suggest that viral induction of TNF-α and interferon β gene expression may involve overlapping pathways with both common and distinct regulatory factors

  12. Promotion of Viral IRES-Mediated Translation Initiation under Mild Hypothermia.

    Directory of Open Access Journals (Sweden)

    Maria Licursi

    Full Text Available Internal ribosome entry site (IRES-mediated translation is an essential replication step for certain viruses. As IRES-mediated translation is regulated differently from cap-dependent translation under various cellular conditions, we sought to investigate whether temperature influences efficiency of viral IRES-mediated translation initiation by using bicistronic reporter constructs containing an IRES element of encephalomyocarditis virus (EMCV, foot-and-mouth disease virus (FMDV, hepatitis C virus (HCV, human rhinovirus (HRV or poliovirus (PV. Under mild hypothermic conditions (30 and 35°C, we observed increases in the efficiency of translation initiation by HCV and HRV IRES elements compared to translation initiation at 37°C. The promotion of HRV IRES activity was observed as early as 2 hours after exposure to mild hypothermia. We also confirmed the promotion of translation initiation by HRV IRES under mild hypothermia in multiple cell lines. The expression levels and locations of polypyrimidine tract-binding protein (PTB and upstream of N-Ras (unr, the IRES trans-acting factors (ITAFs of HCV and HRV IRES elements, were not modulated by the temperature shift from 37°C to 30°C. Taken together, this study demonstrates that efficiency of translation initiation by some viral IRES elements is temperature dependent.

  13. Bioavailability of trans-resveratrol from red wine in humans.

    Science.gov (United States)

    Vitaglione, Paola; Sforza, Stefano; Galaverna, Gianni; Ghidini, Cristiana; Caporaso, Nicola; Vescovi, Pier Paolo; Fogliano, Vincenzo; Marchelli, Rosangela

    2005-05-01

    Many in vitro studies demonstrated significant biological effects of trans-resveratrol. Thus, understanding the rate of intestinal absorption and metabolization in vivo of trans-resveratrol is the prerequisite to evaluate its potential health impact. Bioavailability studies mainly in animals or in humans using the pure compound at very high doses were performed. In this work, trans-resveratrol bioavailability from a moderate consumption of red wine in 25 healthy humans has been studied by three different experiments. The wine ingestion was associated to three different dietary approaches: fasting, a standard meal, a meal with high and low amount of lipids. Trans-resveratrol 3- and 4'-glucuronides were synthesized, purified, and characterized as pure standards. Bioavailability data were obtained by measuring the concentration of free, 3-glucuronide and 4'-glucuronide trans-resveratrol by high-performance liquid chromatography (HPLC), both with ultraviolet (UV) and mass spectrometry (MS) detection, in serum samples taken at different times after red wine administration. Free trans-resveratrol was found, in trace amounts, only in some serum samples collected 30 min after red wine ingestion while after longer times resveratrol glucuronides predominated. Trans-resveratrol bioavailability was shown to be independent from the meal or its lipid content. The finding in human serum of trans-resveratrol glucuronides, rather than the free form of the compound, with a high interindividual variability, raises some doubts about the health effects of dietary resveratrol consumption and suggests that the benefits associated to red wine consumption could be probably due to the whole antioxidant pool present in red wine.

  14. [ALAT and viral RNA as risk factors in 68 blood donors with anti-hepatitis C antibodies].

    Science.gov (United States)

    Tullen, E; De Saussure, P; Soulier-Lauper, M

    1993-01-23

    Determine the risk factors in blood donors with anti hepatitis C antibodies (anti-HCV ab) possible liver involvement and evaluation of their infectious potential by a search for viral RNA in blood. Between July 1990 and October 1991, 19,632 blood donors were screened for hepatitis C. Antibodies to HCV were detected in 74 donors (2nd generation ELISA, Abbott). We evaluated the risk factors, determined ALAT levels and looked for circulating RNA virus by amplification of the non-coding region of the viral genome (RTPCR) in 68 of these 74 donors screened. A control was chosen arbitrarily from 103 donors with high ALAT levels, but with no antibodies to HCV nor detectable circulating viral DNA. The prevalence of anti-HCV ab in blood donors in 0.37%. No risk factor was found in 29 donors (43%). Parenteral exposure (former i.v. drug addiction and history of transfusions) was found to be the mode of transmission of hepatitis C in 23 donors (34%). History of NANB jaundice (non-post transfusion) was reported in 1 donor (1%). The remaining 15 donors (22%) were found to have minor risk factors - either isolated or in combination (exposure, tatoos, multiple sexual partners). Former i.v. drug addiction (p = 0.0000006) as well as a history of transfusions (p = 0.0071) are significantly more frequent in the group of donors with antibodies to HCV. None of the 35 sexual partners of the tested donors proved to be positive. 21 donors (30%) had high ALAT (+2 SD). Viral RNA was detected in blood of 26 donors (38%). The proportion of cases with positive viral RNA was 61% if only those donors with high ALAT levels were taken into consideration (13 positive of 21). Risk factors were found in 39 donors (57%) with antibodies to HCV. History of parenteral exposure was found to be significantly more frequent than in the control group (p = 0.0000054). Sexual transmission within couples was not demonstrated in the population tested. A positive PCR test is a probable indicator of a continuous

  15. Individual and community factors associated with geographic clusters of poor HIV care retention and poor viral suppression.

    Science.gov (United States)

    Eberhart, Michael G; Yehia, Baligh R; Hillier, Amy; Voytek, Chelsea D; Fiore, Danielle J; Blank, Michael; Frank, Ian; Metzger, David S; Brady, Kathleen A

    2015-05-01

    Previous analyses identified specific geographic areas in Philadelphia (hotspots) associated with negative outcomes along the HIV care continuum. We examined individual and community factors associated with residing in these hotspots. Retrospective cohort of 1404 persons newly diagnosed with HIV in 2008-2009 followed for 24 months after linkage to care. Multivariable regression examined associations between individual (age, sex, race/ethnicity, HIV transmission risk, and insurance status) and community (economic deprivation, distance to care, access to public transit, and access to pharmacy services) factors and the outcomes: residence in a hotspot associated with poor retention-in-care and residence in a hotspot associated with poor viral suppression. In total, 24.4% and 13.7% of persons resided in hotspots associated with poor retention and poor viral suppression, respectively. For persons residing in poor retention hotspots, 28.3% were retained in care compared with 40.4% of those residing outside hotspots (P care, and longer distance to pharmacies. Factors significantly associated with residence in poor viral suppression hotspots included female sex, higher economic deprivation, and shorter distance to pharmacies. Individual and community-level associations with geographic hotspots may inform both content and delivery strategies for interventions designed to improve retention-in-care and viral suppression.

  16. Cellular Protein WDR11 Interacts with Specific Herpes Simplex Virus Proteins at the trans-Golgi Network To Promote Virus Replication

    Science.gov (United States)

    Taylor, Kathryne E.

    2015-01-01

    ABSTRACT It has recently been proposed that the herpes simplex virus (HSV) protein ICP0 has cytoplasmic roles in blocking antiviral signaling and in promoting viral replication in addition to its well-known proteasome-dependent functions in the nucleus. However, the mechanisms through which it produces these effects remain unclear. While investigating this further, we identified a novel cytoplasmic interaction between ICP0 and the poorly characterized cellular protein WDR11. During an HSV infection, WDR11 undergoes a dramatic change in localization at late times in the viral replication cycle, moving from defined perinuclear structures to a dispersed cytoplasmic distribution. While this relocation was not observed during infection with viruses other than HSV-1 and correlated with efficient HSV-1 replication, the redistribution was found to occur independently of ICP0 expression, instead requiring viral late gene expression. We demonstrate for the first time that WDR11 is localized to the trans-Golgi network (TGN), where it interacts specifically with some, but not all, HSV virion components, in addition to ICP0. Knockdown of WDR11 in cultured human cells resulted in a modest but consistent decrease in yields of both wild-type and ICP0-null viruses, in the supernatant and cell-associated fractions, without affecting viral gene expression. Although further study is required, we propose that WDR11 participates in viral assembly and/or secondary envelopment. IMPORTANCE While the TGN has been proposed to be the major site of HSV-1 secondary envelopment, this process is incompletely understood, and in particular, the role of cellular TGN components in this pathway is unknown. Additionally, little is known about the cellular functions of WDR11, although the disruption of this protein has been implicated in multiple human diseases. Therefore, our finding that WDR11 is a TGN-resident protein that interacts with specific viral proteins to enhance viral yields improves both

  17. Trans-synaptic zinc mobilization improves social interaction in two mouse models of autism through NMDAR activation

    Science.gov (United States)

    Lee, Eun-Jae; Lee, Hyejin; Huang, Tzyy-Nan; Chung, Changuk; Shin, Wangyong; Kim, Kyungdeok; Koh, Jae-Young; Hsueh, Yi-Ping; Kim, Eunjoon

    2015-01-01

    Genetic aspects of autism spectrum disorders (ASDs) have recently been extensively explored, but environmental influences that affect ASDs have received considerably less attention. Zinc (Zn) is a nutritional factor implicated in ASDs, but evidence for a strong association and linking mechanism is largely lacking. Here we report that trans-synaptic Zn mobilization rapidly rescues social interaction in two independent mouse models of ASD. In mice lacking Shank2, an excitatory postsynaptic scaffolding protein, postsynaptic Zn elevation induced by clioquinol (a Zn chelator and ionophore) improves social interaction. Postsynaptic Zn is mainly derived from presynaptic pools and activates NMDA receptors (NMDARs) through postsynaptic activation of the tyrosine kinase Src. Clioquinol also improves social interaction in mice haploinsufficient for the transcription factor Tbr1, which accompanies NMDAR activation in the amygdala. These results suggest that trans-synaptic Zn mobilization induced by clioquinol rescues social deficits in mouse models of ASD through postsynaptic Src and NMDAR activation. PMID:25981743

  18. Rhesus macaque and chimpanzee DC-SIGN act as HIV/SIV gp120 trans-receptors, similar to human DC-SIGN

    NARCIS (Netherlands)

    Geijtenbeek, T. B.; Koopman, G.; van Duijnhoven, G. C.; van Vliet, S. J.; van Schijndel, A. C.; Engering, A.; Heeney, J. L.; van Kooyk, Y.

    2001-01-01

    Dendritic cells (DC) have been implicated in the pathogenesis of both human and simian immunodeficiency viruses (HIV and SIV, respectively). The DC-specific HIV-1 trans-receptor DC-SIGN is thought to be essential for viral dissemination by DC. Abundant expression in lymphoid tissues also implies a

  19. 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.

  20. Crosslinking of tRNA containing a long extra arm to elongation factor Tu by trans-diamminedichloroplatinum(II)

    DEFF Research Database (Denmark)

    Rasmussen, Nils-Jørgen; Wikman, Friedrik; Clark, Brian F. C.

    1990-01-01

    A tRNA containing a long extra arm, namely E. coli tRNA1Leu has been crosslinked to elongation factor Tu, with the crosslinking reagent trans-diamminedichloroplatinum(II). The nucleotide involved in the crosslinking was identified to be a guanosine in the variable region at position 47F or 47G....

  1. The herpes viral transcription factor ICP4 forms a novel DNA recognition complex

    Science.gov (United States)

    Tunnicliffe, Richard B.; Lockhart-Cairns, Michael P.; Levy, Colin; Mould, A. Paul; Jowitt, Thomas A.; Sito, Hilary; Baldock, Clair; Sandri-Goldin, Rozanne M.

    2017-01-01

    Abstract The transcription factor ICP4 from herpes simplex virus has a central role in regulating the gene expression cascade which controls viral infection. Here we present the crystal structure of the functionally essential ICP4 DNA binding domain in complex with a segment from its own promoter, revealing a novel homo-dimeric fold. We also studied the complex in solution by small angle X-Ray scattering, nuclear magnetic resonance and surface-plasmon resonance which indicated that, in addition to the globular domain, a flanking intrinsically disordered region also recognizes DNA. Together the data provides a rationale for the bi-partite nature of the ICP4 DNA recognition consensus sequence as the globular and disordered regions bind synergistically to adjacent DNA motifs. Therefore in common with its eukaryotic host, the viral transcription factor ICP4 utilizes disordered regions to enhance the affinity and tune the specificity of DNA interactions in tandem with a globular domain. PMID:28505309

  2. Amplification of the Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 lytic origin of DNA replication is dependent upon a cis-acting AT-rich region and an ORF50 response element and the trans-acting factors ORF50 (K-Rta) and K8 (K-bZIP)

    International Nuclear Information System (INIS)

    AuCoin, David P.; Colletti, Kelly S.; Cei, Sylvia A.; Papouskova, Iva; Tarrant, Margaret; Pari, Gregory S.

    2004-01-01

    Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV8), has significant sequence homology to Epstein-Barr virus (EBV). In cell culture, HHV8 is primarily latent, and viral genes associated with lytic replication are not expressed. Two lytic origins of DNA replication (oriLyt) are present within the HHV8 genome and are composed of an AT-rich region adjacent to GC-rich DNA sequences. We have now identified essential cis- and trans-acting elements required for oriLyt-dependent DNA replication. The transient replication assay was used to show that two AT-rich elements, three consensus AP1 transcription factor-binding sites, an ORF50 response element (RE), and a consensus TATA box motif are essential for efficient origin-dependent DNA replication. Transient transfection of luciferase reporter constructs indicated that the downstream region of the HHV8 oriLyt responds to ORF50 and suggests that part of the oriLyt may be an enhancer/promoter. In addition, a transient cotransfection-replication assay elucidated the set of trans-acting factors required for lytic DNA replication. These factors consist of homologues to the core replication proteins: ORF6 (ssDNA binding protein), ORF9 (DNA polymerase), ORF40-41 (primase-associated factor), ORF44 (helicase), ORF56 (primase), and ORF59 (polymerase processivity factor) common to all herpesviruses along with ORF50 (K-Rta) and K8 (K-bZIP)

  3. High efficiency non-viral transfection of retinal and iris pigment epithelial cells with pigment epithelium-derived factor.

    Science.gov (United States)

    Thumann, G; Stöcker, M; Maltusch, C; Salz, A K; Barth, S; Walter, P; Johnen, S

    2010-02-01

    Transplantation of pigment epithelial cells in patients with age-related macular degeneration and Parkinson's disease has the potential to improve functional rehabilitation. Genetic modification of cells before transplantation may allow the delivery of neuroprotective factors to achieve functional improvement. As transplantation of cells modified using viral vectors is complicated by the possible dissemination of viral particles and severe immune reactions, we have explored non-viral methods to insert genetic material in pigment epithelial cells. Using lipofection or nucleofection ARPE-19 cells, freshly isolated and primary retinal and iris pigment epithelial (IPE) cells were transfected with plasmids encoding green fluorescent protein (GFP) and with three plasmids encoding recombinant pigment epithelium-derived factor (PEDF) and GFP. Transfection efficiency was evaluated by fluorescence microscopy and stability of protein expression by immunoblotting. Pigment epithelial cells were successfully transfected with plasmid encoding GFP. Expression of GFP in ARPE-19 was transient, but was observed for up to 1 year in IPE cells. Analysis of pigment epithelial cells transfected with PEDF plasmids revealed that PEDF fusion proteins were successfully expressed and functionally active. In conclusion, efficient transfer of genetic information in pigment epithelial cells can be achieved using non-viral transfection protocols.

  4. Severe NAFLD with hepatic necroinflammatory changes in mice fed trans fats and a high-fructose corn syrup equivalent.

    Science.gov (United States)

    Tetri, Laura H; Basaranoglu, Metin; Brunt, Elizabeth M; Yerian, Lisa M; Neuschwander-Tetri, Brent A

    2008-11-01

    The aims of this study were to determine whether combining features of a western lifestyle in mice with trans fats in a high-fat diet, high-fructose corn syrup in the water, and interventions designed to promote sedentary behavior would cause the hepatic histopathological and metabolic abnormalities that characterize nonalcoholic steatohepatitis (NASH). Male C57BL/6 mice fed ad libitum high-fat chow containing trans fats (partially hydrogenated vegetable oil) and relevant amounts of a high-fructose corn syrup (HFCS) equivalent for 1-16 wk were compared with mice fed standard chow or mice with trans fats or HFCS omitted. Cage racks were removed from western diet mice to promote sedentary behavior. By 16 wk, trans fat-fed mice became obese and developed severe hepatic steatosis with associated necroinflammatory changes. Plasma alanine aminotransferase levels increased, as did liver TNF-alpha and procollagen mRNA, indicating an inflammatory and profibrogenic response to injury. Glucose intolerance and impaired fasting glucose developed within 2 and 4 wk, respectively. Plasma insulin, resistin, and leptin levels increased in a profile similar to that seen in patients with NASH. The individual components of this diet contributed to the phenotype independently; isocaloric replacement of trans fats with lard established that trans fats played a major role in promoting hepatic steatosis and injury, whereas inclusion of HFCS promoted food consumption, obesity, and impaired insulin sensitivity. Combining risk factors for the metabolic syndrome by feeding mice trans fats and HFCS induced histological features of NASH in the context of a metabolic profile similar to patients with this disease. Because dietary trans fats promoted liver steatosis and injury, their role in the epidemic of NASH needs further evaluation.

  5. Plasma Viral miRNAs Indicate a High Prevalence of Occult Viral Infections

    Directory of Open Access Journals (Sweden)

    Enrique Fuentes-Mattei

    2017-06-01

    Full Text Available Prevalence of Kaposi sarcoma-associated herpesvirus (KSHV/HHV-8 varies greatly in different populations. We hypothesized that the actual prevalence of KSHV/HHV8 infection in humans is underestimated by the currently available serological tests. We analyzed four independent patient cohorts with post-surgical or post-chemotherapy sepsis, chronic lymphocytic leukemia and post-surgical patients with abdominal surgical interventions. Levels of specific KSHV-encoded miRNAs were measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR, and KSHV/HHV-8 IgG were measured by immunoassay. We also measured specific miRNAs from Epstein Barr Virus (EBV, a virus closely related to KSHV/HHV-8, and determined the EBV serological status by ELISA for Epstein-Barr nuclear antigen 1 (EBNA-1 IgG. Finally, we identified the viral miRNAs by in situ hybridization (ISH in bone marrow cells. In training/validation settings using independent multi-institutional cohorts of 300 plasma samples, we identified in 78.50% of the samples detectable expression of at least one of the three tested KSHV-miRNAs by RT-qPCR, while only 27.57% of samples were found to be seropositive for KSHV/HHV-8 IgG (P < 0.001. The prevalence of KSHV infection based on miRNAs qPCR is significantly higher than the prevalence determined by seropositivity, and this is more obvious for immuno-depressed patients. Plasma viral miRNAs quantification proved that EBV infection is ubiquitous. Measurement of viral miRNAs by qPCR has the potential to become the “gold” standard method to detect certain viral infections in clinical practice.

  6. TransAlta Corporation 1996 annual report : new directions, new opportunities

    International Nuclear Information System (INIS)

    Anon.

    1997-01-01

    TransAlta Corp. is an energy management company that operates through two subsidiaries: (1) TransAlta Utilities Corp. which owns and operates electricity generation, transmission and distribution assets in Alberta, and (2) TransAlta Energy Corp. which is in the business of electric and thermal energy supply, gas and electricity distribution, energy services and energy marketing in regions of Canada, New Zealand, Australia, Argentina and the United States. This report presents a summary of operations, and provides consolidated financial statements and common share information for 1996. During the year the corporation advanced three significant initiatives (1) operational effectiveness, as shown by impressive productivity increases, and major investments in three independent power projects, (2) improved strategic direction through a review of plans and options, resulting in a clearer, more focused vision of the future, and (3) realignment of the organizational structure by centralizing marketing and sales functions, and establishing a corporate business development group. Details of operational and financial results were provided for both subsidiaries, i. e. TransAlta Utilities and TransAlta Energy. Sales of electric energy for TransAlta Utilities amounted to 27.8 billion kWh; 4.6 billion kWh for TransAlta Energy. Return on equity was 11.4 per cent, down from 11.8 per cent in 1995. Net earnings per common share were $1.14 per share (including one-time items), the same as in 1995. tabs., figs

  7. Socioeconomic factors explain suboptimal adherence to antiretroviral therapy among HIV-infected Australian adults with viral suppression.

    Directory of Open Access Journals (Sweden)

    Krista J Siefried

    Full Text Available Missing more than one tablet of contemporary antiretroviral therapy (ART per month increases the risk of virological failure. Recent studies evaluating a comprehensive range of potential risk factors for suboptimal adherence are not available for high-income settings.Adults on ART with undetectable viral load (UDVL were recruited into a national, multi-centre cohort, completing a comprehensive survey assessing demographics, socio-economic indicators, physical health, well-being, life stressors, social supports, HIV disclosure, HIV-related stigma and discrimination, healthcare access, ART regimen, adherence, side effects, costs and treatment beliefs. Baseline data were assessed, and suboptimal adherence was defined as self-reported missing ≥1 ART dose/month over the previous 3-months; associated factors were identified using bivariate and multivariate binary logistic regression.We assessed 522 participants (494 [94.5%] men, mean age = 50.8 years, median duration UDVL = 3.3 years [IQR = 1.2-6.8] at 17 sexual health, hospital, and general practice clinics across Australia. Seventy-eight participants (14.9% reported missing ≥1 dose/month over the previous three months, which was independently associated with: being Australian-born (AOR [adjusted odds ratio] = 2.4 [95%CI = 1.2-4.9], p = 0.014, not being in a relationship (AOR = 3.3 [95%CI = 1.5-7.3], p = 0.004, reaching the "Medicare safety net" (capping annual medical/pharmaceutical costs (AOR = 2.2 [95%CI = 1.1-4.5], p = 0.024, living in subsidised housing (AOR = 2.5 [95%CI = 1.0-6.2], p = 0.045, receiving home-care services (AOR = 4.4 [95%CI = 1.0-18.8], p = 0.046, HIV community/outreach services linkage (AOR = 2.4 [95%CI = 1.1-5.4], p = 0.033, and starting ART following self-request (AOR = 3.0 [95%CI = 1.3-7.0], p = 0.012.In this population, 15% reported recent suboptimal ART adherence at levels associated in prospective studies with subsequent virological failure, despite all having an

  8. Cleavage of spike protein of SARS coronavirus by protease factor Xa is associated with viral infectivity

    International Nuclear Information System (INIS)

    Du, Lanying; Kao, Richard Y.; Zhou, Yusen; He, Yuxian; Zhao, Guangyu; Wong, Charlotte; Jiang, Shibo; Yuen, Kwok-Yung; Jin, Dong-Yan; Zheng, Bo-Jian

    2007-01-01

    The spike (S) protein of SARS coronavirus (SARS-CoV) has been known to recognize and bind to host receptors, whose conformational changes then facilitate fusion between the viral envelope and host cell membrane, leading to viral entry into target cells. However, other functions of SARS-CoV S protein such as proteolytic cleavage and its implications to viral infection are incompletely understood. In this study, we demonstrated that the infection of SARS-CoV and a pseudovirus bearing the S protein of SARS-CoV was inhibited by a protease inhibitor Ben-HCl. Also, the protease Factor Xa, a target of Ben-HCl abundantly expressed in infected cells, was able to cleave the recombinant and pseudoviral S protein into S1 and S2 subunits, and the cleavage was inhibited by Ben-HCl. Furthermore, this cleavage correlated with the infectivity of the pseudovirus. Taken together, our study suggests a plausible mechanism by which SARS-CoV cleaves its S protein to facilitate viral infection

  9. Cis elements and trans-acting factors involved in the RNA dimerization of the human immunodeficiency virus HIV-1.

    Science.gov (United States)

    Darlix, J L; Gabus, C; Nugeyre, M T; Clavel, F; Barré-Sinoussi, F

    1990-12-05

    The retroviral genome consists of two identical RNA molecules joined at their 5' ends by the Dimer Linkage Structure (DLS). To study the mechanism of dimerization and the DLS of HIV-1 RNA, large amounts of bona fide HIV-1 RNA and of mutants have been synthesized in vitro. We report that HIV-1 RNA forms dimeric molecules and that viral nucleocapsid (NC) protein NCp15 greatly activates dimerization. Deletion mutagenesis in the RNA 5' 1333 nucleotides indicated that a small domain of 100 nucleotides, located between positions 311 to 415 from the 5' end, is necessary and sufficient to promote HIV-1 RNA dimerization. This dimerization domain encompasses an encapsidation element located between the 5' splice donor site and initiator AUG of gag and shows little sequence variations in different strains of HIV-1. Furthermore, cross-linking analysis of the interactions between NC and HIV-1 RNA (311 to 415) locates a major contact site in the encapsidation element of HIV-1 RNA. The genomic RNA dimer is tightly associated with nucleocapsid protein molecules in avian and murine retroviruses, and this ribonucleoprotein structure is believed to be the template for reverse transcription. Genomic RNA-protein interactions have been analyzed in human immunodeficiency virus (HIV) virions and results showed that NC protein molecules are tightly bound to the genomic RNA dimer. Since retroviral RNA dimerization and packaging appear to be under the control of the same cis element, the encapsidation sequences, and trans-acting factor, the NC protein, they are probably related events in the course of virion assembly.

  10. Resistance to Plum pox virus strain C in Arabidopsis thaliana and Chenopodium foetidum involves genome-linked viral protein and other viral determinants and might depend on compatibility with host translation initiation factors.

    Science.gov (United States)

    Calvo, María; Martínez-Turiño, Sandra; García, Juan Antonio

    2014-11-01

    Research performed on model herbaceous hosts has been useful to unravel the molecular mechanisms that control viral infections. The most common Plum pox virus (PPV) strains are able to infect Nicotiana species as well as Chenopodium and Arabidopsis species. However, isolates belonging to strain C (PPV-C) that have been adapted to Nicotiana spp. are not infectious either in Chenopodium foetidum or in Arabidopsis thaliana. In order to determine the mechanism underlying this interesting host-specific behavior, we have constructed chimerical clones derived from Nicotiana-adapted PPV isolates from the D and C strains, which differ in their capacity to infect A. thaliana and C. foetidum. With this approach, we have identified the nuclear inclusion a protein (VPg+Pro) as the major pathogenicity determinant that conditions resistance in the presence of additional secondary determinants, different for each host. Genome-linked viral protein (VPg) mutations similar to those involved in the breakdown of eIF4E-mediated resistance to other potyviruses allow some PPV chimeras to infect A. thaliana. These results point to defective interactions between a translation initiation factor and the viral VPg as the most probable cause of host-specific incompatibility, in which other viral factors also participate, and suggest that complex interactions between multiple viral proteins and translation initiation factors not only define resistance to potyviruses in particular varieties of susceptible hosts but also contribute to establish nonhost resistance.

  11. Viral Restriction Activity of Feline BST2 Is Independent of Its N-Glycosylation and Induction of NF-κB Activation.

    Directory of Open Access Journals (Sweden)

    Weiran Wang

    Full Text Available BST2 (CD317, tetherin, HM1.24 is an interferon-inducible transmembrane protein which can directly inhibit the release of enveloped virus particles from infected cells, and its anti-viral activity is reported to be related to the specific topological arrangement of its four structural domains. The N-terminal cytoplasmic tail of feline BST2 (fBST2 is characterized by a shorter N-terminal region compared to those of other known homologs. In this study, we investigated the functional impact of modifying the cytoplasmic tail region of fBST2 and its molecular mechanism. The fBST2 protein with the addition of a peptide at the N-terminus retained anti-release activity against human immunodeficiency virus type-1 and pseudovirus based on feline immunodeficiency virus at a weaker level compared with the wild-type fBST2. However, the fBST2 protein with addition of a peptide internally in the ectodomain proximal to the GPI anchor still retained its anti-viral activity well. Notably, the N-glycosylation state and the cell surface level of the N-terminally modified variants were unlike those of the wild-type protein, while no difference was observed in their intracellular localizations. However, in contrast to human BST2, the wild-type fBST2 did not show the ability to activate NF-κB. Consistent with previous reports, our findings showed that adding a peptide in the cytoplasmic tail region of fBST2 may influence its anti-viral activity. The shorter N-terminal cytoplasmic region of fBST2 compared with human BST2 did not apparently affect its anti-viral activity, which is independent of its N-glycosylation and ability to activate NF-κB.

  12. Trans fatty acid isomers and the trans-9/trans-11 index in fat containing foods

    Science.gov (United States)

    Kuhnt, Katrin; Baehr, Melanie; Rohrer, Carsten; Jahreis, Gerhard

    2011-01-01

    To determine trans fatty acid (TFA) distribution of contemporary foods, especially regarding individual trans octadecenoic acids (trans C18:1), 339 German foods of six categories (semi-solid fats, deep-fried potato products, bakery products, confectioneries, instant products and butter) were analysed using two GC methods. Results showed a high variation of TFA content between and within the categories containing between 0 and 40.5% of FAME except in butter, which is a source of natural TFA. The mean TFA values were below 2.0% of FAME, however, bakery products contained 4.5% and butter fat 3.2%, respectively. In addition, the distribution of individual trans C18:1 differed. In samples containing ruminant fat (butter and various confectioneries), vaccenic acid (t11-C18:1, t11) predominated, while in foods containing industrially hydrogenated fats, elaidic acid (trans-9, t9-) and t10-C18:1 were the major trans isomers.. This was reflected by a low t9/t11 index of 0.3 and 0.5 in butter and ruminant fat containing confectioneries, respectively, whilst the highest index was observed in shortenings and deep-fried potato products at 5.2 and 6.8, respectively. In conclusion, the TFA content of foods available on the German market is generally declining, but substantial variations are present. The t9/t11 index could be used as an indicator to determine ruminant fat. Practical applications: A number of studies provide evidence that a high TFA intake, particularly of industrial origin, adversely affects human health. The TFA content of foods could be reduced due to the introduction of several mandatory regulations and modifications regarding the hydrogenation process of oils. The most abundant dietary TFA are the isomers of trans C18:1. Unfortunately, the differentiation of these isomers is not yet very common, though the trans C18:1 profile differs depending on its origin (bacterial hydrogenation in the rumen or industrial hydrogenation). To date, data for TFA content

  13. SERINC as a Restriction Factor to Inhibit Viral Infectivity and the Interaction with HIV

    Directory of Open Access Journals (Sweden)

    Gracia Viviana Gonzalez-Enriquez

    2017-01-01

    Full Text Available The serine incorporator 5 (SERINC5 is a recently discovered restriction factor that inhibits viral infectivity by preventing fusion. Retroviruses have developed strategies to counteract the action of SERINC5, such as the expression of proteins like negative regulatory factor (Nef, S2, and glycosylated Gag (glycoGag. These accessory proteins downregulate SERINC5 from the plasma membrane for subsequent degradation in the lysosomes. The observed variability in the action of SERINC5 suggests the participation of other elements like the envelope glycoprotein (Env that modulates susceptibility of the virus towards SERINC5. The exact mechanism by which SERINC5 inhibits viral fusion has not yet been determined, although it has been proposed that it increases the sensitivity of the Env by exposing regions which are recognized by neutralizing antibodies. More studies are needed to understand the role of SERINC5 and to assess its utility as a therapeutic strategy.

  14. The transcription elongation factor ELL2 is specifically upregulated in HTLV-1-infected T-cells and is dependent on the viral oncoprotein Tax.

    Science.gov (United States)

    Mann, Melanie C; Strobel, Sarah; Fleckenstein, Bernhard; Kress, Andrea K

    2014-09-01

    The oncoprotein Tax of human T-cell leukemia virus type 1 (HTLV-1) is a potent transactivator of viral and cellular transcription. Here, we identified ELL2 as the sole transcription elongation factor to be specifically upregulated in HTLV-1-/Tax-transformed T-cells. Tax contributes to regulation of ELL2, since transient transfection of Tax increases ELL2 mRNA, Tax transactivates the ELL2 promoter, and repression of Tax results in decrease of ELL2 in transformed T-lymphocytes. However, we also measured upregulation of ELL2 in HTLV-1-transformed cells exhibiting undetectable amounts of Tax, suggesting that ELL2 can still be maintained independent of continuous Tax expression. We further show that Tax and ELL2 synergistically activate the HTLV-1 promoter, indicating that ELL2 cooperates with Tax in viral transactivation. This is supported by our findings that Tax and ELL2 accumulate in nuclear fractions and that they co-precipitate upon co-expression in transiently-transfected cells. Thus, upregulation of ELL2 could contribute to HTLV-1 gene regulation. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Alterations in cholesterol metabolism restrict HIV-1 trans infection in nonprogressors.

    Science.gov (United States)

    Rappocciolo, Giovanna; Jais, Mariel; Piazza, Paolo; Reinhart, Todd A; Berendam, Stella J; Garcia-Exposito, Laura; Gupta, Phalguni; Rinaldo, Charles R

    2014-04-29

    ABSTRACT HIV-1-infected nonprogressors (NP) inhibit disease progression for years without antiretroviral therapy. Defining the mechanisms for this resistance to disease progression could be important in determining strategies for controlling HIV-1 infection. Here we show that two types of professional antigen-presenting cells (APC), i.e., dendritic cells (DC) and B lymphocytes, from NP lacked the ability to mediate HIV-1 trans infection of CD4(+) T cells. In contrast, APC from HIV-1-infected progressors (PR) and HIV-1-seronegative donors (SN) were highly effective in mediating HIV-1 trans infection. Direct cis infection of T cells with HIV-1 was comparably efficient among NP, PR, and SN. Lack of HIV-1 trans infection in NP was linked to lower cholesterol levels and an increase in the levels of the reverse cholesterol transporter ABCA1 (ATP-binding cassette transporter A1) in APC but not in T cells. Moreover, trans infection mediated by APC from NP could be restored by reconstitution of cholesterol and by inhibiting ABCA1 by mRNA interference. Importantly, this appears to be an inherited trait, as it was evident in APC obtained from NP prior to their primary HIV-1 infection. The present study demonstrates a new mechanism wherein enhanced lipid metabolism in APC results in remarkable control of HIV-1 trans infection that directly relates to lack of HIV-1 disease progression. IMPORTANCE HIV-1 can be captured by antigen-presenting cells (APC) such as dendritic cells and transferred to CD4 helper T cells, which results in greatly enhanced viral replication by a mechanism termed trans infection. A small percentage of HIV-1-infected persons are able to control disease progression for many years without antiretroviral therapy. In our study, we linked this lack of disease progression to a profound inability of APC from these individuals to trans infect T cells. This effect was due to altered lipid metabolism in their APC, which appears to be an inherited trait. These

  16. Epigenetic control of viral life-cycle by a DNA-methylation dependent transcription factor.

    Directory of Open Access Journals (Sweden)

    Kirsty Flower

    Full Text Available Epstein-Barr virus (EBV encoded transcription factor Zta (BZLF1, ZEBRA, EB1 is the prototype of a class of transcription factor (including C/EBPalpha that interact with CpG-containing DNA response elements in a methylation-dependent manner. The EBV genome undergoes a biphasic methylation cycle; it is extensively methylated during viral latency but is reset to an unmethylated state following viral lytic replication. Zta is expressed transiently following infection and again during the switch between latency and lytic replication. The requirement for CpG-methylation at critical Zta response elements (ZREs has been proposed to regulate EBV replication, specifically it could aid the activation of viral lytic gene expression from silenced promoters on the methylated genome during latency in addition to preventing full lytic reactivation from the non-methylated EBV genome immediately following infection. We developed a computational approach to predict the location of ZREs which we experimentally assessed using in vitro and in vivo DNA association assays. A remarkably different binding motif is apparent for the CpG and non-CpG ZREs. Computational prediction of the location of these binding motifs in EBV revealed that the majority of lytic cycle genes have at least one and many have multiple copies of methylation-dependent CpG ZREs within their promoters. This suggests that the abundance of Zta protein coupled with the methylation status of the EBV genome act together to co-ordinate the expression of lytic cycle genes at the majority of EBV promoters.

  17. Structural plasticity of Barley yellow dwarf virus-like cap-independent translation elements in four genera of plant viral RNAs.

    Science.gov (United States)

    Wang, Zhaohui; Kraft, Jelena J; Hui, Alice Y; Miller, W Allen

    2010-06-20

    The 3' untranslated regions (UTRs) of many plant viral RNAs contain cap-independent translation elements (3' CITEs). Among the 3' CITEs, the Barley yellow dwarf virus (BYDV)-like translation elements (BTEs) form a structurally variable and widely distributed group. Viruses in three genera were known to harbor 3' BTEs, defined by the presence of a 17-nt consensus sequence. To understand BTE function, knowledge of phylogenetically conserved structure is essential, yet the secondary structure has been determined only for the BYDV BTE. Here we show that Rose spring dwarf-associated luteovirus, and two viruses in a fourth genus, Umbravirus, contain functional BTEs, despite deviating in the 17nt consensus sequence. Structure probing by selective 2'-hydroxyl acylation and primer extension (SHAPE) revealed conserved and highly variable structures in BTEs in all four genera. We conclude that BTEs tolerate striking evolutionary plasticity in structure, while retaining the ability to stimulate cap-independent translation. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  18. Oxygen tension level and human viral infections

    Energy Technology Data Exchange (ETDEWEB)

    Morinet, Frédéric, E-mail: frederic.morinet@sls.aphp.fr [Centre des Innovations Thérapeutiques en Oncologie et Hématologie (CITOH), CHU Saint-Louis, Paris (France); Université Denis Diderot, Sorbonne Paris Cité Paris, Paris (France); Casetti, Luana [Institut Cochin INSERM U1016, Paris (France); François, Jean-Hugues; Capron, Claude [Institut Cochin INSERM U1016, Paris (France); Laboratoire d' Hématologie, Hôpital Ambroise Paré, Boulogne (France); Université de Versailles Saint-Quentin en Yvelynes, Versailles (France); Pillet, Sylvie [Laboratoire de Bactériologie-Virologie-Hygiène, CHU de Saint-Etienne, Saint-Etienne (France); Université de Lyon et Université de Saint-Etienne, Jean Monnet, GIMAP EA3064, F-42023 Saint-Etienne, Lyon (France)

    2013-09-15

    The role of oxygen tension level is a well-known phenomenon that has been studied in oncology and radiotherapy since about 60 years. Oxygen tension may inhibit or stimulate propagation of viruses in vitro as well as in vivo. In turn modulating oxygen metabolism may constitute a novel approach to treat viral infections as an adjuvant therapy. The major transcription factor which regulates oxygen tension level is hypoxia-inducible factor-1 alpha (HIF-1α). Down-regulating the expression of HIF-1α is a possible method in the treatment of chronic viral infection such as human immunodeficiency virus infection, chronic hepatitis B and C viral infections and Kaposi sarcoma in addition to classic chemotherapy. The aim of this review is to supply an updating concerning the influence of oxygen tension level in human viral infections and to evoke possible new therapeutic strategies regarding this environmental condition. - Highlights: • Oxygen tension level regulates viral replication in vitro and possibly in vivo. • Hypoxia-inducible factor 1 (HIF-1α) is the principal factor involved in Oxygen tension level. • HIF-1α upregulates gene expression for example of HIV, JC and Kaposi sarcoma viruses. • In addition to classical chemotherapy inhibition of HIF-1α may constitute a new track to treat human viral infections.

  19. Trans-Planckian wimpzillas

    CERN Document Server

    Kolb, E W; Tkachev, I I

    2007-01-01

    Two previously proposed conjectures--gravitational trans-Planckian particle creation in the expanding universe, and the existence of ultra-heavy stable particles with masses up to the Planck scale (wimpzillas)--are combined in a proposal for trans-Planckian particle creation of wimpzillas. It is shown that the trans-Planckian particle creation parameter should be rather small to avoid overproduction of such particles. This ensures that wimpzillas are mainly created at the end of primordial inflation. Conditions under which trans-Planckian wimpzillas can constitute the present dark matter are determined.

  20. Effect of Trans, Trans-Farnesol on Pseudogymnoascus destructans and Several Closely Related Species.

    Science.gov (United States)

    Raudabaugh, Daniel B; Miller, Andrew N

    2015-12-01

    Bat white-nose syndrome, caused by the psychrophilic fungus Pseudogymnoascus destructans, has dramatically reduced the populations of many hibernating North American bat species. The search for effective biological control agents targeting P. destructans is of great importance. We report that the sesquiterpene trans, trans-farnesol, which is also a Candida albicans quorum sensing compound, prevented in vitro conidial germination for at least 14 days and inhibited growth of preexisting hyphae of five P. destructans isolates in filtered potato dextrose broth at 10 °C. Depending on the inoculation concentrations, both spore and hyphal inhibition occurred upon exposure to concentrations as low as 15-20 µM trans, trans-farnesol. In contrast, most North American Pseudogymnoascus isolates were more tolerant to the exposure of trans, trans-farnesol. Our results suggest that some Candida isolates may have the potential to inhibit the growth of P. destructans and that the sesquiterpene trans, trans-farnesol has the potential to be utilized as a biological control agent.

  1. Predictors of viral pneumonia in patients with community-acquired pneumonia.

    Directory of Open Access Journals (Sweden)

    Ji Eun Kim

    Full Text Available BACKGROUND: Viruses are increasingly recognized as major causes of community-acquired pneumonia (CAP. Few studies have investigated the clinical predictors of viral pneumonia, and the results have been inconsistent. In this study, the clinical predictors of viral pneumonia were investigated in terms of their utility as indicators for viral pneumonia in patients with CAP. METHODS: Adult patients (≥ 18 years old with CAP, tested by polymerase chain reaction (PCR for respiratory virus, at two teaching hospitals between October 2010 and May 2013, were identified retrospectively. Demographic and clinical data were collected by reviewing the hospital electronic medical records. RESULTS: During the study period, 456 patients with CAP were identified who met the definition, and 327 (72% patients were tested using the respiratory virus PCR detection test. Viral pneumonia (n = 60 was associated with rhinorrhea, a higher lymphocyte fraction in the white blood cells, lower serum creatinine and ground-glass opacity (GGO in radiology results, compared to non-viral pneumonia (n = 250 (p < 0.05, each. In a multivariate analysis, rhinorrhea (Odd ratio (OR 3.52; 95% Confidence interval (CI, 1.58-7.87 and GGO (OR 4.68; 95% CI, 2.48-8.89 were revealed as independent risk factors for viral pneumonia in patients with CAP. The sensitivity, specificity, positive- and negative-predictive values (PPV and NPV of rhinorrhea were 22, 91, 36 and 83%: the sensitivity, specificity, PPV and NPV of GGO were and 43, 84, 40 and 86%, respectively. CONCLUSION: Symptom of rhinorrhea and GGO predicted viral pneumonia in patients with CAP. The high specificity of rhinorrhea and GGO suggested that these could be useful indicators for empirical antiviral therapy.

  2. Viral infection and oral habits as risk factors for oral squamous cell carcinoma in Yemen: a case-control study.

    Science.gov (United States)

    Nasher, Akram T; Al-Hebshi, Nezar N; Al-Moayad, Ebtisam E; Suleiman, Ahmed M

    2014-11-01

    The role of qat chewing, tobacco (shammah) dipping, smoking, alcohol drinking, and oral viral infection as risk factors for oral squamous cell carcinoma (OSCC) in Yemen was assessed. A total of 60 cases of OSCC and 120 age- and gender-matched controls were analyzed with respect to demographic data, history of oral habits, and the presence of human papillomavirus (HPV)-16, HPV-18, or Epstein-Barr virus (EBV) as determined by Taqman quantitative polymerase chain reaction. Logistic regression analysis was used to identify independent predictors of the disease. Shammah use was the only risk factor for OSCC, with an odds ratio of 12.6 (CI, 3.3-48.2) and 39 (CI, 14-105) for the ex-users and current users, respectively. The association of shammah use alone with OSCC exceeded that of shammah use in combination with qat chewing, smoking, or both. EBV infection, smoking, and qat chewing showed no association with OSCC, while neither HPV-16 nor HPV-18 were detected in any sample. Shammah use is a major risk factor for oral cancer in Yemen. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Neural stem cell-derived exosomes mediate viral entry

    Directory of Open Access Journals (Sweden)

    Sims B

    2014-10-01

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

  4. TransAlta 2003 annual report

    International Nuclear Information System (INIS)

    2004-01-01

    This annual report presents financial information from TransAlta Corp., along with a review of its operations throughout 2003 and a summary of the how the electric utility has performed in terms of power generation, independent power producers, transmission and energy marketing. TransAlta is one of the largest non-regulated power generation and wholesale marketing companies in Canada. It's assets include coal-fired, gas-fired, hydro and renewable generation facilities in Canada, the United States, Mexico and Australia. Reported earnings in 2003 were $1.26 per share compared to $1.17 in 2002. The strong first quarter was followed by harsh market conditions, low water levels which affected hydro production, and pricing restrictions in Ontario that reduced contribution from the Sarnia plant. This report outlines the utility's progress in increasing revenue and producing more power. In 2003, unplanned outages were reduced by 7 per cent and injury frequency rate was reduced by 27 per cent. The installation of 114 wind turbines in Fort Macleod, Alberta, increased TransAlta's renewable energy capacity to 3.7 per cent in 2003. The wind farm produces 75 MW of electricity, enough to power more than 32,500 homes annually. This report summarized the company's energy resource activities and presented an operations review as well as consolidated financial statements and common share information. This included the utility's assets, liabilities, revenues, expenses and cash flows. Revenue and expenditure statements were summarized by source. refs., tabs., figs

  5. Wolbachia wStri Blocks Zika Virus Growth at Two Independent Stages of Viral Replication.

    Science.gov (United States)

    Schultz, M J; Tan, A L; Gray, C N; Isern, S; Michael, S F; Frydman, H M; Connor, J H

    2018-05-22

    Mosquito-transmitted viruses are spread globally and present a great risk to human health. Among the many approaches investigated to limit the diseases caused by these viruses are attempts to make mosquitos resistant to virus infection. Coinfection of mosquitos with the bacterium Wolbachia pipientis from supergroup A is a recent strategy employed to reduce the capacity for major vectors in the Aedes mosquito genus to transmit viruses, including dengue virus (DENV), Chikungunya virus (CHIKV), and Zika virus (ZIKV). Recently, a supergroup B Wolbachia w Stri, isolated from Laodelphax striatellus , was shown to inhibit multiple lineages of ZIKV in Aedes albopictus cells. Here, we show that w Stri blocks the growth of positive-sense RNA viruses DENV, CHIKV, ZIKV, and yellow fever virus by greater than 99.9%. w Stri presence did not affect the growth of the negative-sense RNA viruses LaCrosse virus or vesicular stomatitis virus. Investigation of the stages of the ZIKV life cycle inhibited by w Stri identified two distinct blocks in viral replication. We found a reduction of ZIKV entry into w Stri-infected cells. This was partially rescued by the addition of a cholesterol-lipid supplement. Independent of entry, transfected viral genome was unable to replicate in Wolbachia -infected cells. RNA transfection and metabolic labeling studies suggested that this replication defect is at the level of RNA translation, where we saw a 66% reduction in mosquito protein synthesis in w Stri-infected cells. This study's findings increase the potential for application of w Stri to block additional arboviruses and also identify specific blocks in viral infection caused by Wolbachia coinfection. IMPORTANCE Dengue, Zika, and yellow fever viruses are mosquito-transmitted diseases that have spread throughout the world, causing millions of infections and thousands of deaths each year. Existing programs that seek to contain these diseases through elimination of the mosquito population have so

  6. Environmental drivers of viral community composition in Antarctic soils identified by viromics.

    Science.gov (United States)

    Adriaenssens, Evelien M; Kramer, Rolf; Van Goethem, Marc W; Makhalanyane, Thulani P; Hogg, Ian; Cowan, Don A

    2017-07-19

    The Antarctic continent is considered the coldest and driest place on earth with simple ecosystems, devoid of higher plants. Soils in the ice-free regions of Antarctica are known to harbor a wide range of microorganisms from primary producers to grazers, yet their ecology and particularly the role of viruses is poorly understood. In this study, we examined the virus community structures of 14 soil samples from the Mackay Glacier region. Viral communities were extracted from soil and the dsDNA was extracted, amplified using single-primer amplification, and sequenced using the Ion Torrent Proton platform. Metadata on soil physico-chemistry was collected from all sites. Both read and contig datasets were analyzed with reference-independent and reference-dependent methods to assess viral community structures and the influence of environmental parameters on their distribution. We observed a high heterogeneity in virus signatures, independent of geographical proximity. Tailed bacteriophages were dominant in all samples, but the incidences of the affiliated families Siphoviridae and Myoviridae were inversely correlated, suggesting direct competition for hosts. Viruses of the families Phycodnaviridae and Mimiviridae were present at significant levels in high-diversity soil samples and were found to co-occur, implying little competition between them. Combinations of soil factors, including pH, calcium content, and site altitude, were found to be the main drivers of viral community structure. The pattern of viral community structure with higher levels of diversity at lower altitude and pH, and co-occurring viral families, suggests that these cold desert soil viruses interact with each other, the host, and the environment in an intricate manner, playing a potentially crucial role in maintaining host diversity and functioning of the microbial ecosystem in the extreme environments of Antarctic soil.

  7. The transcription elongation factor ELL2 is specifically upregulated in HTLV-1-infected T-cells and is dependent on the viral oncoprotein Tax

    Energy Technology Data Exchange (ETDEWEB)

    Mann, Melanie C., E-mail: melanie.mann@viro.med.uni-erlangen.de; Strobel, Sarah, E-mail: sarah.strobel@viro.med.uni-erlangen.de; Fleckenstein, Bernhard, E-mail: bernhard.fleckenstein@viro.med.uni-erlangen.de; Kress, Andrea K., E-mail: andrea.kress@viro.med.uni-erlangen.de

    2014-09-15

    The oncoprotein Tax of human T-cell leukemia virus type 1 (HTLV-1) is a potent transactivator of viral and cellular transcription. Here, we identified ELL2 as the sole transcription elongation factor to be specifically upregulated in HTLV-1-/Tax-transformed T-cells. Tax contributes to regulation of ELL2, since transient transfection of Tax increases ELL2 mRNA, Tax transactivates the ELL2 promoter, and repression of Tax results in decrease of ELL2 in transformed T-lymphocytes. However, we also measured upregulation of ELL2 in HTLV-1-transformed cells exhibiting undetectable amounts of Tax, suggesting that ELL2 can still be maintained independent of continuous Tax expression. We further show that Tax and ELL2 synergistically activate the HTLV-1 promoter, indicating that ELL2 cooperates with Tax in viral transactivation. This is supported by our findings that Tax and ELL2 accumulate in nuclear fractions and that they co-precipitate upon co-expression in transiently-transfected cells. Thus, upregulation of ELL2 could contribute to HTLV-1 gene regulation. - Highlights: • ELL2, a transcription elongation factor, is upregulated in HTLV-1-positive T-cells. • Tax transactivates the ELL2 promoter. • Tax and ELL2 synergistically activate the HTLV-1 promoter. • Tax and ELL2 interact in vivo.

  8. The transcription elongation factor ELL2 is specifically upregulated in HTLV-1-infected T-cells and is dependent on the viral oncoprotein Tax

    International Nuclear Information System (INIS)

    Mann, Melanie C.; Strobel, Sarah; Fleckenstein, Bernhard; Kress, Andrea K.

    2014-01-01

    The oncoprotein Tax of human T-cell leukemia virus type 1 (HTLV-1) is a potent transactivator of viral and cellular transcription. Here, we identified ELL2 as the sole transcription elongation factor to be specifically upregulated in HTLV-1-/Tax-transformed T-cells. Tax contributes to regulation of ELL2, since transient transfection of Tax increases ELL2 mRNA, Tax transactivates the ELL2 promoter, and repression of Tax results in decrease of ELL2 in transformed T-lymphocytes. However, we also measured upregulation of ELL2 in HTLV-1-transformed cells exhibiting undetectable amounts of Tax, suggesting that ELL2 can still be maintained independent of continuous Tax expression. We further show that Tax and ELL2 synergistically activate the HTLV-1 promoter, indicating that ELL2 cooperates with Tax in viral transactivation. This is supported by our findings that Tax and ELL2 accumulate in nuclear fractions and that they co-precipitate upon co-expression in transiently-transfected cells. Thus, upregulation of ELL2 could contribute to HTLV-1 gene regulation. - Highlights: • ELL2, a transcription elongation factor, is upregulated in HTLV-1-positive T-cells. • Tax transactivates the ELL2 promoter. • Tax and ELL2 synergistically activate the HTLV-1 promoter. • Tax and ELL2 interact in vivo

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

    Directory of Open Access Journals (Sweden)

    Peng-Nien Huang

    2017-05-01

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

  10. Trans-kingdom mimicry underlies ribosome customization by a poxvirus kinase.

    Science.gov (United States)

    Jha, Sujata; Rollins, Madeline G; Fuchs, Gabriele; Procter, Dean J; Hall, Elizabeth A; Cozzolino, Kira; Sarnow, Peter; Savas, Jeffrey N; Walsh, Derek

    2017-06-29

    Ribosomes have the capacity to selectively control translation through changes in their composition that enable recognition of specific RNA elements. However, beyond differential subunit expression during development, evidence for regulated ribosome specification within individual cells has remained elusive. Here we report that a poxvirus kinase phosphorylates serine/threonine residues in the human small ribosomal subunit protein, receptor for activated C kinase (RACK1), that are not phosphorylated in uninfected cells or cells infected by other viruses. These modified residues cluster in an extended loop in RACK1, phosphorylation of which selects for translation of viral or reporter mRNAs with 5' untranslated regions that contain adenosine repeats, so-called polyA-leaders. Structural and phylogenetic analyses revealed that although RACK1 is highly conserved, this loop is variable and contains negatively charged amino acids in plants, in which these leaders act as translational enhancers. Phosphomimetics and inter-species chimaeras have shown that negative charge in the RACK1 loop dictates ribosome selectivity towards viral RNAs. By converting human RACK1 to a charged, plant-like state, poxviruses remodel host ribosomes so that adenosine repeats erroneously generated by slippage of the viral RNA polymerase confer a translational advantage. Our findings provide insight into ribosome customization through trans-kingdom mimicry and the mechanics of species-specific leader activity that underlie poxvirus polyA-leaders.

  11. The HIV-1 Rev/RRE system is required for HIV-1 5' UTR cis elements to augment encapsidation of heterologous RNA into HIV-1 viral particles

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    Ma Hong

    2011-06-01

    Full Text Available Abstract Background The process of HIV-1 genomic RNA (gRNA encapsidation is governed by a number of viral encoded components, most notably the Gag protein and gRNA cis elements in the canonical packaging signal (ψ. Also implicated in encapsidation are cis determinants in the R, U5, and PBS (primer binding site from the 5' untranslated region (UTR. Although conventionally associated with nuclear export of HIV-1 RNA, there is a burgeoning role for the Rev/RRE in the encapsidation process. Pleiotropic effects exhibited by these cis and trans viral components may confound the ability to examine their independent, and combined, impact on encapsidation of RNA into HIV-1 viral particles in their innate viral context. We systematically reconstructed the HIV-1 packaging system in the context of a heterologous murine leukemia virus (MLV vector RNA to elucidate a mechanism in which the Rev/RRE system is central to achieving efficient and specific encapsidation into HIV-1 viral particles. Results We show for the first time that the Rev/RRE system can augment RNA encapsidation independent of all cis elements from the 5' UTR (R, U5, PBS, and ψ. Incorporation of all the 5' UTR cis elements did not enhance RNA encapsidation in the absence of the Rev/RRE system. In fact, we demonstrate that the Rev/RRE system is required for specific and efficient encapsidation commonly associated with the canonical packaging signal. The mechanism of Rev/RRE-mediated encapsidation is not a general phenomenon, since the combination of the Rev/RRE system and 5' UTR cis elements did not enhance encapsidation into MLV-derived viral particles. Lastly, we show that heterologous MLV RNAs conform to transduction properties commonly associated with HIV-1 viral particles, including in vivo transduction of non-dividing cells (i.e. mouse neurons; however, the cDNA forms are episomes predominantly in the 1-LTR circle form. Conclusions Premised on encapsidation of a heterologous RNA into

  12. Trans-Cultural, Trans-Language Practices: Potentialities for Rethinking Doctoral Education Pedagogies

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    Sarojni Choy

    2017-01-01

    Full Text Available Over the last decade, there has been a rapid increase in doctoral enrolments of Asian international students in Australian universities. While policies have been developed to meet the needs of these students, there seems to be some confusion around the terms internationalisation, globalisation, bi-cultural, inter-cultural, multi-cultural, and trans-cultural within these policies. In this paper, we define these terms and advocate for a policy position which orients to a futurist definition of culture. We then review the work of Michael Singh and his research team at Western Sydney University who have responded to this rapid increase in Asian international student doctoral enrolments in Australian universities by developing pedagogic principles around notions of trans-language and trans-cultural practices. In the final section of the paper, we then draw on our own experiences of doctoral supervision in Australian universities to reflect on our positioning within the pedagogic principles around trans-language and trans-cultural practices.

  13. Human cytomegalovirus uracil DNA glycosylase associates with ppUL44 and accelerates the accumulation of viral DNA

    Directory of Open Access Journals (Sweden)

    Dixon Melissa

    2005-07-01

    Full Text Available Abstract Background Human cytomegalovirus UL114 encodes a uracil-DNA glycosylase homolog that is highly conserved in all characterized herpesviruses that infect mammals. Previous studies demonstrated that the deletion of this nonessential gene delays significantly the onset of viral DNA synthesis and results in a prolonged replication cycle. The gene product, pUL114, also appears to be important in late phase DNA synthesis presumably by introducing single stranded breaks. Results A series of experiments was performed to formally assign the observed phenotype to pUL114 and to characterize the function of the protein in viral replication. A cell line expressing pUL114 complemented the observed phenotype of a UL114 deletion virus in trans, confirming that the observed defects were the result of a deficiency in this gene product. Stocks of recombinant viruses without elevated levels of uracil were produced in the complementing cells; however they retained the phenotype of poor growth in normal fibroblasts suggesting that poor replication was unrelated to uracil content of input genomes. Recombinant viruses expressing epitope tagged versions of this gene demonstrated that pUL114 was expressed at early times and that it localized to viral replication compartments. This protein also coprecipitated with the DNA polymerase processivity factor, ppUL44 suggesting that these proteins associate in infected cells. This apparent interaction did not appear to require other viral proteins since ppUL44 could recruit pUL114 to the nucleus in uninfected cells. An analysis of DNA replication kinetics revealed that the initial rate of DNA synthesis and the accumulation of progeny viral genomes were significantly reduced compared to the parent virus. Conclusion These data suggest that pUL114 associates with ppUL44 and that it functions as part of the viral DNA replication complex to increase the efficiency of both early and late phase viral DNA synthesis.

  14. The non conventional gas, a factor of energy independence?

    International Nuclear Information System (INIS)

    Jacques Percebois

    2011-01-01

    As the recent exploitation of non conventional gases (or shale gases) has dramatically changed the energy deal in the USA, and therefore the energy world market, these gases seem to be a factor of energy independence for countries which possess such resources, but also create environmental constrains. The author describes how shale gas produces a technological revolution, and discusses how it can be a factor for the diversification of the energy mix, and above all a way to reconquer some energy independence

  15. Epstein-Barr virus nuclear antigen EBNA-LP is essential for transforming naïve B cells, and facilitates recruitment of transcription factors to the viral genome.

    Science.gov (United States)

    Szymula, Agnieszka; Palermo, Richard D; Bayoumy, Amr; Groves, Ian J; Ba Abdullah, Mohammed; Holder, Beth; White, Robert E

    2018-02-01

    The Epstein-Barr virus (EBV) nuclear antigen leader protein (EBNA-LP) is the first viral latency-associated protein produced after EBV infection of resting B cells. Its role in B cell transformation is poorly defined, but it has been reported to enhance gene activation by the EBV protein EBNA2 in vitro. We generated EBNA-LP knockout (LPKO) EBVs containing a STOP codon within each repeat unit of internal repeat 1 (IR1). EBNA-LP-mutant EBVs established lymphoblastoid cell lines (LCLs) from adult B cells at reduced efficiency, but not from umbilical cord B cells, which died approximately two weeks after infection. Adult B cells only established EBNA-LP-null LCLs with a memory (CD27+) phenotype. Quantitative PCR analysis of virus gene expression after infection identified both an altered ratio of the EBNA genes, and a dramatic reduction in transcript levels of both EBNA2-regulated virus genes (LMP1 and LMP2) and the EBNA2-independent EBER genes in the first 2 weeks. By 30 days post infection, LPKO transcription was the same as wild-type EBV. In contrast, EBNA2-regulated cellular genes were induced efficiently by LPKO viruses. Chromatin immunoprecipitation revealed that EBNA2 and the host transcription factors EBF1 and RBPJ were delayed in their recruitment to all viral latency promoters tested, whereas these same factors were recruited efficiently to several host genes, which exhibited increased EBNA2 recruitment. We conclude that EBNA-LP does not simply co-operate with EBNA2 in activating gene transcription, but rather facilitates the recruitment of several transcription factors to the viral genome, to enable transcription of virus latency genes. Additionally, our findings suggest that EBNA-LP is essential for the survival of EBV-infected naïve B cells.

  16. Epstein-Barr virus nuclear antigen EBNA-LP is essential for transforming naïve B cells, and facilitates recruitment of transcription factors to the viral genome

    Science.gov (United States)

    Szymula, Agnieszka; Palermo, Richard D.; Bayoumy, Amr; Groves, Ian J.

    2018-01-01

    The Epstein-Barr virus (EBV) nuclear antigen leader protein (EBNA-LP) is the first viral latency-associated protein produced after EBV infection of resting B cells. Its role in B cell transformation is poorly defined, but it has been reported to enhance gene activation by the EBV protein EBNA2 in vitro. We generated EBNA-LP knockout (LPKO) EBVs containing a STOP codon within each repeat unit of internal repeat 1 (IR1). EBNA-LP-mutant EBVs established lymphoblastoid cell lines (LCLs) from adult B cells at reduced efficiency, but not from umbilical cord B cells, which died approximately two weeks after infection. Adult B cells only established EBNA-LP-null LCLs with a memory (CD27+) phenotype. Quantitative PCR analysis of virus gene expression after infection identified both an altered ratio of the EBNA genes, and a dramatic reduction in transcript levels of both EBNA2-regulated virus genes (LMP1 and LMP2) and the EBNA2-independent EBER genes in the first 2 weeks. By 30 days post infection, LPKO transcription was the same as wild-type EBV. In contrast, EBNA2-regulated cellular genes were induced efficiently by LPKO viruses. Chromatin immunoprecipitation revealed that EBNA2 and the host transcription factors EBF1 and RBPJ were delayed in their recruitment to all viral latency promoters tested, whereas these same factors were recruited efficiently to several host genes, which exhibited increased EBNA2 recruitment. We conclude that EBNA-LP does not simply co-operate with EBNA2 in activating gene transcription, but rather facilitates the recruitment of several transcription factors to the viral genome, to enable transcription of virus latency genes. Additionally, our findings suggest that EBNA-LP is essential for the survival of EBV-infected naïve B cells. PMID:29462212

  17. The trans-Golgi Network and the Golgi Stacks Behave Independently During Regeneration After Brefeldin A Treatment in Tobacco BY-2 Cells.

    Science.gov (United States)

    Ito, Yoko; Toyooka, Kiminori; Fujimoto, Masaru; Ueda, Takashi; Uemura, Tomohiro; Nakano, Akihiko

    2017-04-01

    The trans-Golgi network (TGN) plays an essential role in intracellular membrane trafficking. In plant cells, recent live-cell imaging studies have revealed the dynamic behavior of the TGN independent from the Golgi apparatus. In order to better understand the relationships between the two organelles, we examined their dynamic responses to the reagent brefeldin A (BFA) and their recovery after BFA removal. Golgi markers responded to BFA similarly over a range of concentrations, whereas the behavior of the TGN was BFA concentration dependent. The TGN formed aggregates at high concentrations of BFA; however, TGN proteins relocalized to numerous small vesicular structures dispersed throughout the cytoplasm at lower BFA concentrations. During recovery from weak BFA treatment, the TGN started to regenerate earlier than the completion of the Golgi. The regeneration of the two organelles proceeded independently of each other for a while, and eventually was completed by their association. Our data suggest that there is some degree of autonomy for the regeneration of the TGN and the Golgi in tobacco BY-2 cells. © The Author 2017. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  18. Trans* Leadership.

    Science.gov (United States)

    Jourian, T J; Simmons, Symone L

    2017-06-01

    Focusing on emerging literature on trans* and gender-nonconforming students and their leadership, this chapter outlines the ways trans* students are engaged in leadership in educational institutions and outside of them and discusses implications for staff and faculty regarding how to support and engage these students and their leadership. © 2017 Wiley Periodicals, Inc., A Wiley Company.

  19. Independent risk factors of morbidity in penetrating colon injuries.

    Science.gov (United States)

    Girgin, Sadullah; Gedik, Ercan; Uysal, Ersin; Taçyildiz, Ibrahim Halil

    2009-05-01

    The present study explored the factors effective on colon-related morbidity in patients with penetrating injury of the colon. The medical records of 196 patients were reviewed for variables including age, gender, factor of trauma, time between injury and operation, shock, duration of operation, Penetrating Abdominal Trauma Index (PATI), Injury Severity Score (ISS), site of colon injury, Colon Injury Score, fecal contamination, number of associated intra- and extraabdominal organ injuries, units of transfused blood within the first 24 hours, and type of surgery. In order to determine the independent risk factors, multivariate logistic regression analysis was performed. Gunshot wounds, interval between injury and operation > or =6 hours, shock, duration of the operation > or =6 hours, PATI > or =25, ISS > or =20, Colon Injury Score > or = grade 3, major fecal contamination, number of associated intraabdominal organ injuries >2, number of associated extraabdominal organ injuries >2, multiple blood transfusions, and diversion were significantly associated with morbidity. Multivariate logistic regression analysis showed diversion and transfusion of > or =4 units in the first 24 hours as independent risk factors affecting colon-related morbidity. Diversion and transfusion of > or =4 units in the first 24 hours were determined to be independent risk factors for colon-related morbidity.

  20. Emerging Viral Diseases of Tomato Crops

    NARCIS (Netherlands)

    Hanssen, I.M.; Lapidot, M.; Thomma, B.P.H.J.

    2010-01-01

    Viral diseases are an important limiting factor in many crop production systems. Because antiviral products are not available, control strategies rely on genetic resistance or hygienic measures to prevent viral diseases, or on eradication of diseased crops to control such diseases. Increasing

  1. Biotransformation of trans-1-chloro-3,3,3-trifluoropropene (trans-HCFO-1233zd)

    International Nuclear Information System (INIS)

    Schmidt, Tobias; Bertermann, Rüdiger; Rusch, George M.; Tveit, Ann; Dekant, Wolfgang

    2013-01-01

    trans-1-Chloro-3,3,3-trifluoropropene (trans-HCFO-1233zd) is a novel foam blowing and precision cleaning agent with a very low impact for global warming and ozone depletion. trans-HCFO-1233zd also has a low potential for toxicity in rodents and is negative in genotoxicity testing. The biotransformation of trans-HCFO-1233zd and kinetics of metabolite excretion with urine were assessed in vitro and in animals after inhalation exposures. For in vitro characterization, liver microsomes from rats, rabbits and humans were incubated with trans-HCFO-1233zd. Male Sprague Dawley rats and female New Zealand White rabbits were exposed to 2,000, 5,000 and 10,000 ppm for 6 h and urine was collected for 48 h after the end of the exposure. Study specimens were analyzed for metabolites using 19 F NMR, LC-MS/MS and GC/MS. S-(3,3,3-trifluoro-trans-propenyl)-glutathione was identified as predominant metabolite of trans-HCFO-1233zd in all microsomal incubation experiments in the presence of glutathione. Products of the oxidative biotransformation of trans-HCFO-1233zd were only minor metabolites when glutathione was present. In rats, both 3,3,3-trifluorolactic acid and N-acetyl-(3,3,3-trifluoro-trans-propenyl)-L-cysteine were observed as major urinary metabolites. 3,3,3-Trifluorolactic acid was not detected in the urine of rabbits. Quantitation showed rapid excretion of both metabolites in both species (t 1/2 1/2 < 6 h). ► Glutathione adduct as predominant in vitro metabolite in all tested species. ► Toxic metabolites could not be detected in any great extent

  2. Endothelium trans differentiated from Wharton's jelly mesenchymal cells promote tissue regeneration: potential role of soluble pro-angiogenic factors.

    Science.gov (United States)

    Aguilera, Valeria; Briceño, Luis; Contreras, Hector; Lamperti, Liliana; Sepúlveda, Esperanza; Díaz-Perez, Francisca; León, Marcelo; Veas, Carlos; Maura, Rafael; Toledo, Jorge Roberto; Fernández, Paulina; Covarrubias, Ambart; Zuñiga, Felipe Andrés; Radojkovic, Claudia; Escudero, Carlos; Aguayo, Claudio

    2014-01-01

    Mesenchymal stem cells have a high capacity for trans-differentiation toward many adult cell types, including endothelial cells. Feto-placental tissue, such as Wharton's jelly is a potential source of mesenchymal stem cells with low immunogenic capacity; make them an excellent source of progenitor cells with a potential use for tissue repair. We evaluated whether administration of endothelial cells derived from mesenchymal stem cells isolated from Wharton's jelly (hWMSCs) can accelerate tissue repair in vivo. Mesenchymal stem cells were isolated from human Wharton's jelly by digestion with collagenase type I. Endothelial trans-differentiation was induced for 14 (hWMSC-End14d) and 30 (hWMSC-End30d) days. Cell phenotyping was performed using mesenchymal (CD90, CD73, CD105) and endothelial (Tie-2, KDR, eNOS, ICAM-1) markers. Endothelial trans-differentiation was demonstrated by the expression of endothelial markers and their ability to synthesize nitric oxide (NO). hWMSCs can be differentiated into adipocytes, osteocytes, chondrocytes and endothelial cells. Moreover, these cells show high expression of CD73, CD90 and CD105 but low expression of endothelial markers prior to differentiation. hWMSCs-End express high levels of endothelial markers at 14 and 30 days of culture, and also they can synthesize NO. Injection of hWMSC-End30d in a mouse model of skin injury significantly accelerated wound healing compared with animals injected with undifferentiated hWMSC or injected with vehicle alone. These effects were also observed in animals that received conditioned media from hWMSC-End30d cultures. These results demonstrate that mesenchymal stem cells isolated from Wharton's jelly can be cultured in vitro and trans-differentiated into endothelial cells. Differentiated hWMSC-End may promote neovascularization and tissue repair in vivo through the secretion of soluble pro-angiogenic factors.

  3. ESCRT-independent budding of HIV-1 gag virus-like particles from Saccharomyces cerevisiae spheroplasts.

    Directory of Open Access Journals (Sweden)

    Andrew P Norgan

    Full Text Available Heterologous expression of HIV-1 Gag in a variety of host cells results in its packaging into virus-like particles (VLPs that are subsequently released into the extracellular milieu. This phenomenon represents a useful tool for probing cellular factors required for viral budding and has contributed to the discovery of roles for ubiquitin ligases and the endosomal sorting complexes required for transport (ESCRTs in viral budding. These factors are highly conserved throughout eukaryotes and have been studied extensively in the yeast Saccharomyces cerevisiae, a model eukaryote previously utilized as a host for the production of VLPs. We used heterologous expression of HIV Gag in yeast spheroplasts to examine the role of ESCRTs and associated factors (Rsp5, a HECT ubiquitin ligase of the Nedd4 family; Bro1, a homolog of Alix; and Vps4, the AAA-ATPase required for ESCRT function in all contexts/organisms investigated in the generation of VLPs. Our data reveal: 1 characterized Gag-ESCRT interaction motifs (late domains are not required for VLP budding, 2 loss of function alleles of the essential HECT ubiquitin ligase Rsp5 do not display defects in VLP formation, and 3 ESCRT function is not required for VLP formation from spheroplasts. These results suggest that the egress of HIV Gag from yeast cells is distinct from the most commonly described mode of exit from mammalian cells, instead mimicking ESCRT-independent VLP formation observed in a subset of mammalian cells. As such, budding of Gag from yeast cells appears to represent ESCRT-independent budding relevant to viral replication in at least some situations. Thus the myriad of genetic and biochemical tools available in the yeast system may be of utility in the study of this aspect of viral budding.

  4. Biotransformation of trans-1-chloro-3,3,3-trifluoropropene (trans-HCFO-1233zd)

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, Tobias [Institut für Toxikologie, Universität Würzburg, Versbacher Str. 9, 97078 Würzburg (Germany); Bertermann, Rüdiger [Institut für Anorganische Chemie, Universität Würzburg, Am Hubland, 97074 Würzburg (Germany); Rusch, George M.; Tveit, Ann [Honeywell, P.O. Box 1057, Morristown, NJ 07962-1057 (United States); Dekant, Wolfgang, E-mail: dekant@toxi.uni-wuerzburg.de [Institut für Toxikologie, Universität Würzburg, Versbacher Str. 9, 97078 Würzburg (Germany)

    2013-05-01

    trans-1-Chloro-3,3,3-trifluoropropene (trans-HCFO-1233zd) is a novel foam blowing and precision cleaning agent with a very low impact for global warming and ozone depletion. trans-HCFO-1233zd also has a low potential for toxicity in rodents and is negative in genotoxicity testing. The biotransformation of trans-HCFO-1233zd and kinetics of metabolite excretion with urine were assessed in vitro and in animals after inhalation exposures. For in vitro characterization, liver microsomes from rats, rabbits and humans were incubated with trans-HCFO-1233zd. Male Sprague Dawley rats and female New Zealand White rabbits were exposed to 2,000, 5,000 and 10,000 ppm for 6 h and urine was collected for 48 h after the end of the exposure. Study specimens were analyzed for metabolites using {sup 19}F NMR, LC-MS/MS and GC/MS. S-(3,3,3-trifluoro-trans-propenyl)-glutathione was identified as predominant metabolite of trans-HCFO-1233zd in all microsomal incubation experiments in the presence of glutathione. Products of the oxidative biotransformation of trans-HCFO-1233zd were only minor metabolites when glutathione was present. In rats, both 3,3,3-trifluorolactic acid and N-acetyl-(3,3,3-trifluoro-trans-propenyl)-L-cysteine were observed as major urinary metabolites. 3,3,3-Trifluorolactic acid was not detected in the urine of rabbits. Quantitation showed rapid excretion of both metabolites in both species (t{sub 1/2} < 6 h) and the extent of biotransformation of trans-HCFO-1233zd was determined as approximately 0.01% of received dose in rabbits and approximately 0.002% in rats. trans-HCFO-1233zd undergoes both oxidative biotransformation and glutathione conjugation at very low rates. The low extent of biotransformation and the rapid excretion of metabolites formed are consistent with the very low potential for toxicity of trans-HCFO-1233zd in mammals. - Highlights: ► No lethality and clinical signs were observed. ► Glutathione S-transferase and cytochrome P-450 dependent

  5. Powdered activated carbon adsorption of two fishy odorants in water: Trans,trans-2,4-heptadienal and trans,trans-2,4-decadienal.

    Science.gov (United States)

    Li, Xin; Wang, Jun; Zhang, Xiaojian; Chen, Chao

    2015-06-01

    Powdered activated carbon (PAC) adsorption of two fishy odorants, trans,trans-2,4-heptadienal (HDE) and trans,trans-2,4-decadienal (DDE), was investigated. Both the pseudo first-order and the pseudo second-order kinetic models well described the kinetics curves, and DDE was more readily removed by PAC. In isotherm tests, both Freundlich and Modified Freundlich isotherms fitted the experimental data well. PAC exhibited a higher adsorption capacity for DDE than for HDE, which could be ascribed to the difference in their hydrophobicity. The calculated thermodynamic parameters (ΔG0, ΔH0, and ΔS0) indicated an exothermic and spontaneous adsorption process. PAC dosage, pH, and natural organic matter (NOM) presence were found to influence the adsorption process. With increasing PAC dosage, the pseudo first-order and pseudo second-order rate constants both increased. The value of pH had little influence on HDE or DDE molecules but altered the surface charge of PAC, and the maximum adsorption capacity occurred at pH9. The presence of NOM, especially the fraction with molecular weight less than 1k Dalton, hindered the adsorption. The study showed that preloaded NOM impaired the adsorption capacity of HDE or DDE more severely than simultaneously fed NOM did. Copyright © 2015. Published by Elsevier B.V.

  6. Carboxy terminal peptide of type I procollagen and epidermal growth factor in patients with different viral hepatitis

    International Nuclear Information System (INIS)

    Han Lihong; Gong Shoujun; Li Guangming; Li Yebing; Xu Bin

    2001-01-01

    The author observed the serum levels of carboxy terminal peptide of type I procollagen (PICP) and epidermal growth factor (EGF) in the patients with viral hepatitis and cirrhosis. The serum PICP and EGF were detected in 164 cases by RIA. The results indicated that two indexes increased significantly in patients with severe chronic hepatitis, chronic persistent hepatitis and post hepatitis cirrhosis compared with normal control (P 0.05). The results showed that detection of serum PICP and EGF may be valuable diagnostic markers to assess the degree of liver inflammation and fibrosis in viral liver diseases

  7. Survey of the trans-resveratrol and trans-piceid content of cocoa-containing and chocolate products.

    Science.gov (United States)

    Hurst, W Jeffrey; Glinski, Jan A; Miller, Kenneth B; Apgar, Joan; Davey, Matthew H; Stuart, David A

    2008-09-24

    Dietary resveratrol (3,4',5-trihydroxystilbene) has been implicated in the health benefits associated with grapes and red wine, more specifically with potential benefits for metabolic syndrome, energy use, and increased endurance. Levels of trans-resveratrol and its glucoside, trans-piceid, were determined in 19 top selling commercially available cocoa-containing and chocolate products from the U.S. market. Amounts of trans-resveratrol and trans-piceid were closely correlated with the amount of nonfat cocoa solids (NFCS) in the cocoa-containing products. Among these products, trans-resveratrol levels were highest in cocoa powders (1.85 +/- 0.43 microg/g), followed by unsweetened baking chocolates (1.24 +/- 0.22), semisweet chocolate baking chips (0.52 +/- 0.14), dark chocolates (0.35 +/- 0.08), milk chocolates (0.10 +/- 0.05), and chocolate syrups (0.09 +/- 0.02). These cocoa-containing and chocolate products have about 3-5 times more trans-piceid than trans-resveratrol. Levels of trans-piceid were highest in the cocoa powders (7.14 +/- 0.80 microg/g), followed by unsweetened baking chocolates (4.04 +/- 0.14), semisweet chocolate baking chips (2.01 +/- 0.18), dark chocolates (1.82 +/- 0.36), milk chocolates (0.44 +/- 0.06), and chocolate syrups (0.35 +/- 0.06). On an equal weight basis, cocoa powder had about half as much trans-resveratrol as the average California red wine. On a per serving basis, cocoa-containing and chocolate products had less trans-resveratrol than red wine and grape juice but more than roasted peanuts. Overall, these cocoa-containing and chocolate products rank second after red wines and grape juice in foods with the highest levels of total trans-resveratrol in the diet.

  8. Sensitive detection of viral transcripts in human tumor transcriptomes.

    Directory of Open Access Journals (Sweden)

    Sven-Eric Schelhorn

    Full Text Available In excess of 12% of human cancer incidents have a viral cofactor. Epidemiological studies of idiopathic human cancers indicate that additional tumor viruses remain to be discovered. Recent advances in sequencing technology have enabled systematic screenings of human tumor transcriptomes for viral transcripts. However, technical problems such as low abundances of viral transcripts in large volumes of sequencing data, viral sequence divergence, and homology between viral and human factors significantly confound identification of tumor viruses. We have developed a novel computational approach for detecting viral transcripts in human cancers that takes the aforementioned confounding factors into account and is applicable to a wide variety of viruses and tumors. We apply the approach to conducting the first systematic search for viruses in neuroblastoma, the most common cancer in infancy. The diverse clinical progression of this disease as well as related epidemiological and virological findings are highly suggestive of a pathogenic cofactor. However, a viral etiology of neuroblastoma is currently contested. We mapped 14 transcriptomes of neuroblastoma as well as positive and negative controls to the human and all known viral genomes in order to detect both known and unknown viruses. Analysis of controls, comparisons with related methods, and statistical estimates demonstrate the high sensitivity of our approach. Detailed investigation of putative viral transcripts within neuroblastoma samples did not provide evidence for the existence of any known human viruses. Likewise, de-novo assembly and analysis of chimeric transcripts did not result in expression signatures associated with novel human pathogens. While confounding factors such as sample dilution or viral clearance in progressed tumors may mask viral cofactors in the data, in principle, this is rendered less likely by the high sensitivity of our approach and the number of biological replicates

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

    Directory of Open Access Journals (Sweden)

    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

  10. Viral factor TAV recruits TOR/S6K1 signalling to activate reinitiation after long ORF translation

    Science.gov (United States)

    Schepetilnikov, Mikhail; Kobayashi, Kappei; Geldreich, Angèle; Caranta, Carole; Robaglia, Christophe; Keller, Mario; Ryabova, Lyubov A

    2011-01-01

    The protein kinase TOR (target-of-rapamycin) upregulates translation initiation in eukaryotes, but initiation restart after long ORF translation is restricted by largely unknown pathways. The plant viral reinitiation factor transactivator–viroplasmin (TAV) exceptionally promotes reinitiation through a mechanism involving retention on 80S and reuse of eIF3 and the host factor reinitiation-supporting protein (RISP) to regenerate reinitiation-competent ribosomal complexes. Here, we show that TAV function in reinitiation depends on physical association with TOR, with TAV–TOR binding being critical for both translation reinitiation and viral fitness. Consistently, TOR-deficient plants are resistant to viral infection. TAV triggers TOR hyperactivation and S6K1 phosphorylation in planta. When activated, TOR binds polyribosomes concomitantly with polysomal accumulation of eIF3 and RISP—a novel and specific target of TOR/S6K1—in a TAV-dependent manner, with RISP being phosphorylated. TAV mutants defective in TOR binding fail to recruit TOR, thereby abolishing RISP phosphorylation in polysomes and reinitiation. Thus, activation of reinitiation after long ORF translation is more complex than previously appreciated, with TOR/S6K1 upregulation being the key event in the formation of reinitiation-competent ribosomal complexes. PMID:21343906

  11. Cis and trans acting factors involved in human cytomegalovirus experimental and natural latent infection of CD14 (+ monocytes and CD34 (+ cells.

    Directory of Open Access Journals (Sweden)

    Cyprian C Rossetto

    Full Text Available The parameters involved in human cytomegalovirus (HCMV latent infection in CD14 (+ and CD34 (+ cells remain poorly identified. Using next generation sequencing we deduced the transcriptome of HCMV latently infected CD14 (+ and CD34 (+ cells in experimental as well as natural latency settings. The gene expression profile from natural infection in HCMV seropositive donors closely matched experimental latency models, and included two long non-coding RNAs (lncRNAs, RNA4.9 and RNA2.7 as well as the mRNAs encoding replication factors UL84 and UL44. Chromatin immunoprecipitation assays on experimentally infected CD14 (+ monocytes followed by next generation sequencing (ChIP-Seq were employed to demonstrate both UL84 and UL44 proteins interacted with the latent viral genome and overlapped at 5 of the 8 loci identified. RNA4.9 interacts with components of the polycomb repression complex (PRC as well as with the MIE promoter region where the enrichment of the repressive H3K27me3 mark suggests that this lncRNA represses transcription. Formaldehyde Assisted Isolation of Regulatory Elements (FAIRE, which identifies nucleosome-depleted viral DNA, was used to confirm that latent mRNAs were associated with actively transcribed, FAIRE analysis also showed that the terminal repeat (TR region of the latent viral genome is depleted of nucleosomes suggesting that this region may contain an element mediating viral genome maintenance. ChIP assays show that the viral TR region interacts with factors associated with the pre replication complex and a plasmid subclone containing the HCMV TR element persisted in latently infected CD14 (+ monocytes, strongly suggesting that the TR region mediates viral chromosome maintenance.

  12. Investigating the role of viral integral membrane proteins in promoting the assembly of nepovirus and comovirus replication factories

    Directory of Open Access Journals (Sweden)

    Helene eSanfacon

    2013-01-01

    Full Text Available Formation of plant virus membrane-associated replication factories requires the association of viral replication proteins and viral RNA with intracellular membranes, the recruitment of host factors and the modification of membranes to form novel structures that house the replication complex. Many viruses encode integral membrane proteins that act as anchors for the replication complex. These hydrophobic proteins contain trans-membrane domains and/or amphipathic helices that associate with the membrane and modify its structure. The comovirus Co-Pro and NTP-binding (NTB, putative helicase proteins and the cognate nepovirus X2 and NTB proteins are among the best characterized plant virus integral membrane replication proteins and are functionally related to the picornavirus 2B, 2C and 3A membrane proteins. The identification of membrane-association domains and analysis of the membrane topology of these proteins is discussed. The evidence suggesting that these proteins have the ability to induce membrane proliferation, alter the structure and integrity of intracellular membranes and modulate the induction of symptoms in infected plants is also reviewed. Finally, areas of research that need further investigation are highlighted.

  13. 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.

  14. Introduction to Trans Australia Airlines CRM training

    Science.gov (United States)

    Davidson, Jim

    1987-01-01

    Trans Australia believes that its excellent accident rate record is due to a number of factors. It has a good group of standard operating procedures, and its crews are pretty well self-disciplined and adhere to those procedures. But the other thing that it believes is a factor in its safety record is that perhaps it is also due to its preparedness to be innovative, to keep up with what is going on in the rest of the world and, if it looks to have value, then to be amongst the first to try it out. Trans Australia commenced a program similar to Line Oriented Flight Training (LOFT) fairly early in 1979--that being its first windshear program-- which leads to why they are doing a course of resource management training, which we have chosen to call Aircrew Team Management (ATM). This course is detailed in another presentation.

  15. 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...

  16. Interactions of trans-acting factor(s) with the estradiol response element and nuclear factor 1 of the vitellogenin II gene of Japanese quail.

    Science.gov (United States)

    Gupta, S; Upadhayay, R; Kanungo, M S

    1996-08-01

    This study was directed at achieving an understanding of the mechanisms by which steroid hormones control the synthesis of vitellogenin (VTG) protein in the liver of the Japanese quail. Northern hybridization shows that administration of estradiol alone or with progesterone stimulates the synthesis of VTG mRNA. Gel mobility shift assay of DNA fragments containing the ERE and NF 1 shows that estradiol alone or with progesterone increases the levels of nuclear proteins that bind to these cis-acting elements of the promoter of the VTG gene. The cooperative effect of the two hormones seen at the level of expression of the VTG gene may be due to protein-protein interactions of trans-acting factors that bind to ERE and NF 1.

  17. 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

  18. Targeted Victimization and Suicidality Among Trans People: A Web-Based Survey.

    Science.gov (United States)

    Zeluf, Galit; Dhejne, Cecilia; Orre, Carolina; Mannheimer, Louise Nilunger; Deogan, Charlotte; Höijer, Jonas; Winzer, Regina; Thorson, Anna Ekéus

    2018-04-01

    The aim of this study was to investigate the associations between a series of empirically known risk and protective factors and suicidality among trans people in Sweden. Participants were self-selected anonymously to a web-based survey conducted in 2014. Univariable and multivariable logistic regression analyses were performed to assess associations between contributing factors and suicide ideation in the past 12 months and lifetime suicide attempts. The analysis included 796 trans individuals, between 15 and 94 years of age, who live in Sweden. A total of 37% of respondents reported that they have seriously considered suicide during the past 12 months and 32% had ever attempted a suicide. Offensive treatment during the past three months and lifetime exposure to trans-related violence were significantly associated with suicidality. Less satisfaction with contacts with friends and acquaintances and with one's own psychological wellbeing were associated with suicide ideation in the past 12 months. Lack of practical support was associated with lifetime suicide attempts. Our findings show that suicidality is directly correlated with trans-related victimization. Preventing targeted victimization is, therefore, a key preventive intervention against this elevated suicidality.

  19. The eukaryotic translation initiation factor 3 subunit E binds to classical swine fever virus NS5A and facilitates viral replication.

    Science.gov (United States)

    Liu, Xiaofeng; Wang, Xiaoyu; Wang, Qian; Luo, Mingyang; Guo, Huancheng; Gong, Wenjie; Tu, Changchun; Sun, Jinfu

    2018-02-01

    Classical swine fever virus (CSFV) NS5A protein is a multifunctional protein, playing critical roles in viral RNA replication, translation and assembly. To further explore its functions in viral replication, interaction of NS5A with host factors was assayed using a his-tag "pull down" assay coupled with shotgun LC-MS/MS. Host protein translation initiation factor 3 subunit E was identified as a binding partner of NS5A, and confirmed by co-immunoprecipitation and co-localization analysis. Overexpression of eIF3E markedly enhanced CSFV genomic replication, viral protein expression and production of progeny virus, and downregulation of eIF3E by siRNA significantly decreased viral proliferation in PK-15 cells. Luciferase reporter assay showed an enhancement of translational activity of the internal ribosome entry site of CSFV by eIF3E and a decrease in cellular translation by NS5A. These data indicate that eIF3E plays an important role in CSFV replication, thereby identifying it as a potential target for inhibition of the virus. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. 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

  1. "There's no chasing involved": cis/trans relationships, "tranny chasers," and the future of a sex-positive trans politics.

    Science.gov (United States)

    Tompkins, Avery Brooks

    2014-01-01

    This article adds to a small, but growing, body of work on trans sexualities and partnerships, and provides a much-needed inquiry into the complex and contested politics of desire when we take trans identities, bodies, and sexualities into account. Using digital ethnographic data from YouTube videos along with in-person observational data from LGBTQ and trans conferences in the U.S., Tompkins argues that a sex-positive trans politics cannot emerge in trans and trans-allied communities if the rhetoric of the "tranny chaser" continues to inform discourses of desire and attraction to trans people.

  2. Plum Pox Virus 6K1 Protein Is Required for Viral Replication and Targets the Viral Replication Complex at the Early Stage of Infection.

    Science.gov (United States)

    Cui, Hongguang; Wang, Aiming

    2016-05-15

    The potyviral RNA genome encodes two polyproteins that are proteolytically processed by three viral protease domains into 11 mature proteins. Extensive molecular studies have identified functions for the majority of the viral proteins. For example, 6K2, one of the two smallest potyviral proteins, is an integral membrane protein and induces the endoplasmic reticulum (ER)-originated replication vesicles that target the chloroplast for robust viral replication. However, the functional role of 6K1, the other smallest protein, remains uncharacterized. In this study, we developed a series of recombinant full-length viral cDNA clones derived from a Canadian Plum pox virus (PPV) isolate. We found that deletion of any of the short motifs of 6K1 (each of which ranged from 5 to 13 amino acids), most of the 6K1 sequence (but with the conserved sequence of the cleavage sites being retained), or all of the 6K1 sequence in the PPV infectious clone abolished viral replication. The trans expression of 6K1 or the cis expression of a dislocated 6K1 failed to rescue the loss-of-replication phenotype, suggesting the temporal and spatial requirement of 6K1 for viral replication. Disruption of the N- or C-terminal cleavage site of 6K1, which prevented the release of 6K1 from the polyprotein, either partially or completely inhibited viral replication, suggesting the functional importance of the mature 6K1. We further found that green fluorescent protein-tagged 6K1 formed punctate inclusions at the viral early infection stage and colocalized with chloroplast-bound viral replicase elements 6K2 and NIb. Taken together, our results suggest that 6K1 is required for viral replication and is an important viral element of the viral replication complex at the early infection stage. Potyviruses account for more than 30% of known plant viruses and consist of many agriculturally important viruses. The genomes of potyviruses encode two polyproteins that are proteolytically processed into 11 mature

  3. Is passive transmission of non-viral vectors through artificial insemination of sperm-DNA mixtures sufficient for chicken transgenesis?

    Science.gov (United States)

    CHAPARIAN, Shahram; ABDULAHNEJAD, Ahad; RASHIDI, Farzad; TOGHYANI, Majid; GHEISARI, Abbasali; EGHBALSAIED, Shahin

    2016-01-01

    DNA uptake in the post-acrosomal region of the spermatozoa takes place exclusively in immotile spermatozoa that are naturally unable to fertilize eggs. The present study aimed to assess whether passive transmission of non-viral vectors to the surrounding areas of chicken embryos could be an alternate mechanism in chicken sperm-mediated gene transfer. First, the presence of nucleases in rooster seminal plasma was evaluated. Semen ejaculates from five roosters were centrifuged and the supernatant was incubated with pBL2 for 1 h. A robust nuclease cocktail was detected in the rooster semen. To overcome these nucleases, plasmid-TransIT combinations were incubated with semen for 1 h. Incubation of exogenous DNA in the lipoplex structure could considerably bypass the semen nuclease effect. Then, intravaginal insemination of 1 × 109 sperm mixed with lipoplexes (40 µg pBL2:40 µl TransIT) was carried out in 15 virgin hens. Neither the epithelial tissue from the inseminated female reproductive tracts nor the produced embryos following artificial insemination showed the transgene. To remove any bias in the transgene transmission possibility, the plasmid-TransIT admixture was directly injected in close vicinity of the embryos in newly laid eggs. Nonetheless, none of the produced fetuses or chicks carried the transgene. In conclusion, the results of the present study revealed a nuclease admixture in rooster seminal plasma, and passive/active transmission of the non-viral vector into close vicinity of the chicken embryo was inefficient for producing transgenic chicks. PMID:26935324

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

    OpenAIRE

    Stålnacke Larsson, Richard; Odén, Niklas

    2011-01-01

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

  5. Regulation of DNA replication in irradiated cells by trans-acting factors

    International Nuclear Information System (INIS)

    Wang, Y.; Huq, M.S.; Cheng, X.; Iliakis, G.

    1995-01-01

    We compared DNA replication activity in cytoplasmic extracts prepared from irradiated and nonirradiated HeLa cells using a simian virus 40 (SV40)-based in vitro replication assay. The assay measures semi-conservative DNA replication in a plasmid carrying the SV40 origin of replication and requires SV40 T antigen as the sole noncellular protein. The plasmid DNA used in the replication reaction is never exposed to radiation. We find that replication of plasmid DNA is significantly reduced when cytoplasmic extracts from irradiated cells are used. Since plasmid replication proceeds to completion in extracts from irradiated cells, the observed reduction in the overall replication activity is probably due to a reduction in the efficiency of initiation events. The degree of inhibition of DNA replication after exposure to 10, 30 and 50 Gy X rays as measured in vitro using this assay is similar to that measured in intact cells immediately before processing for extract preparation. These observations are compatible with the induction or activation by ionizing radiation of a factor(s) that inhibits in trans DNA replication. The results contribute to our understanding of the mechanism(s) developed by the cells to regulate DNA replication when exposed to clastogenic agents. Such processes may be of significance in the restoration of DNA integrity, and may define yet another checkpoint operating during S at the level of clusters of replicons. 26 refs., 4 figs

  6. TransAlta: More than a utility

    International Nuclear Information System (INIS)

    Mikalson, D.A.

    1991-01-01

    TransAlta Utilities Corporation is Canada's largest privately owned utility and is also a major coal mining company. In 1989, TransAlta produced 20.9% of all coal mined in Canada. A brief history of TransAlta is presented along with TransAlta's present coal operations and plans for the next three years. An overview is presented of how TransAlta Fuel Supply is organized to utilize contracted mining operation, engineering and environmental services and in-house capabilities. Recent strategic initiatives to improve organizational efficiency and the mining operations are discussed. These range from developing a common departmental vision to modifying major mining equipment. TransAlta's proactive role in clean coal combustion such as low NOx-SOx burner, integrated combined cycle gasification, and other energy research projects is reviewed. A summary is provided of recent participation of TransAlta in environmental management initiatives. Recent successes of TransAlta's unregulated subsidiary in the development of cogeneration facilities and the future of this area of business are discussed. 8 refs., 4 figs

  7. Evaluating viral marketing: isolating the key criteria in insurance industry

    Directory of Open Access Journals (Sweden)

    Maria Gooyandeh Hagh

    2015-06-01

    Full Text Available This paper presents an empirical investigation to determine the key criteria that viral marketing practitioners believe should be implemented to measure about the success of viral marketing campaigns in insurance industry. The study designs a questionnaire in Likert scale where the effects of four independent variables, personal, message, media and tools characteristics are measured on an Iranian insurance firm’s reputation as well as service expansion. Cronbach alphas were measured for all components of the survey and they were all well above the minimum acceptable level. Using regression analysis, the study has determined positive and meaningful relationships between insurance firm’s reputation as well as service expansion and four independent variables.

  8. Vaginismus as an independent risk factor for cesarean delivery.

    Science.gov (United States)

    Goldsmith, Tomer; Levy, Amalia; Sheiner, Eyal; Goldsmith, Tomer; Levy, Amalia; Sheiner, Eyal

    2009-10-01

    The present study was aimed to investigate pregnancy outcome of patients with vaginismus, and specifically the relationship between vaginismus and cesarean delivery. A population based study comparing all pregnancies in patients with and without vaginismus was conducted. Patients lacking prenatal care were excluded from the analysis. Deliveries occurred during the years 1988-2007. A multivariate logistic regression model, with backward elimination, was constructed to find independent risk factors associated with vaginismus. During the study period there were 192,954 deliveries, of which 118 occurred in patients with vaginismus. Patients with vaginismus tended to be younger (26.04+/-4.89 vs. 28.61+/-5.83; p vaginismus. Patients with vaginismus had higher rates of infertility treatments (5.9%vs. 2.7%, odds ratio [OR] 2.3; 95% confidence interval [CI] 1.1-4.9; p = 0.04) and labor induction (37.3%vs. 27.4%, OR 1.6; 95% CI 1.1-2.3; p = 0.02), vacuum extraction (9.3%vs. 2.8%, OR 3.6, 95% CI 1.9-6.7; p vaginismus remained as an independent risk factor for cesarean delivery (OR 7.1; 95% CI 4.5-11.1; p Vaginismus is an independent risk factor for cesarean delivery.

  9. A Herpesviral Immediate Early Protein Promotes Transcription Elongation of Viral Transcripts.

    Science.gov (United States)

    Fox, Hannah L; Dembowski, Jill A; DeLuca, Neal A

    2017-06-13

    Herpes simplex virus 1 (HSV-1) genes are transcribed by cellular RNA polymerase II (RNA Pol II). While four viral immediate early proteins (ICP4, ICP0, ICP27, and ICP22) function in some capacity in viral transcription, the mechanism by which ICP22 functions remains unclear. We observed that the FACT complex (comprised of SSRP1 and Spt16) was relocalized in infected cells as a function of ICP22. ICP22 was also required for the association of FACT and the transcription elongation factors SPT5 and SPT6 with viral genomes. We further demonstrated that the FACT complex interacts with ICP22 throughout infection. We therefore hypothesized that ICP22 recruits cellular transcription elongation factors to viral genomes for efficient transcription elongation of viral genes. We reevaluated the phenotype of an ICP22 mutant virus by determining the abundance of all viral mRNAs throughout infection by transcriptome sequencing (RNA-seq). The accumulation of almost all viral mRNAs late in infection was reduced compared to the wild type, regardless of kinetic class. Using chromatin immunoprecipitation sequencing (ChIP-seq), we mapped the location of RNA Pol II on viral genes and found that RNA Pol II levels on the bodies of viral genes were reduced in the ICP22 mutant compared to wild-type virus. In contrast, the association of RNA Pol II with transcription start sites in the mutant was not reduced. Taken together, our results indicate that ICP22 plays a role in recruiting elongation factors like the FACT complex to the HSV-1 genome to allow for efficient viral transcription elongation late in viral infection and ultimately infectious virion production. IMPORTANCE HSV-1 interacts with many cellular proteins throughout productive infection. Here, we demonstrate the interaction of a viral protein, ICP22, with a subset of cellular proteins known to be involved in transcription elongation. We determined that ICP22 is required to recruit the FACT complex and other transcription

  10. Fluorescent protein-tagged Vpr dissociates from HIV-1 core after viral fusion and rapidly enters the cell nucleus.

    Science.gov (United States)

    Desai, Tanay M; Marin, Mariana; Sood, Chetan; Shi, Jiong; Nawaz, Fatima; Aiken, Christopher; Melikyan, Gregory B

    2015-10-29

    HIV-1 Vpr is recruited into virions during assembly and appears to remain associated with the viral core after the reverse transcription and uncoating steps of entry. This feature has prompted the use of fluorescently labeled Vpr to visualize viral particles and to follow trafficking of post-fusion HIV-1 cores in the cytoplasm. Here, we tracked single pseudovirus entry and fusion and observed that fluorescently tagged Vpr gradually dissociates from post-fusion viral cores over the course of several minutes and accumulates in the nucleus. Kinetics measurements showed that fluorescent Vpr released from the cores very rapidly entered the cell nucleus. More than 10,000 Vpr molecules can be delivered into the cell nucleus within 45 min of infection by HIV-1 particles pseudotyped with the avian sarcoma and leukosis virus envelope glycoprotein. The fraction of Vpr from cell-bound viruses that accumulated in the nucleus was proportional to the extent of virus-cell fusion and was fully blocked by viral fusion inhibitors. Entry of virus-derived Vpr into the nucleus occurred independently of envelope glycoproteins or target cells. Fluorescence correlation spectroscopy revealed two forms of nuclear Vpr-monomers and very large complexes, likely involving host factors. The kinetics of viral Vpr entering the nucleus after fusion was not affected by point mutations in the capsid protein that alter the stability of the viral core. The independence of Vpr shedding of capsid stability and its relatively rapid dissociation from post-fusion cores suggest that this process may precede capsid uncoating, which appears to occur on a slower time scale. Our results thus demonstrate that a bulk of fluorescently labeled Vpr incorporated into HIV-1 particles is released shortly after fusion. Future studies will address the question whether the quick and efficient nuclear delivery of Vpr derived from incoming viruses can regulate subsequent steps of HIV-1 infection.

  11. Clinical polyomavirus BK variants with agnogene deletion are non-functional but rescued by trans-complementation

    International Nuclear Information System (INIS)

    Myhre, Marit Renee; Olsen, Gunn-Hege; Gosert, Rainer; Hirsch, Hans H.; Rinaldo, Christine Hanssen

    2010-01-01

    High-level replication of polyomavirus BK (BKV) in kidney transplant recipients is associated with the emergence of BKV variants with rearranged (rr) non-coding control region (NCCR) increasing viral early gene expression and cytopathology. Cloning and sequencing revealed the presence of a BKV quasispecies which included non-functional variants when assayed in a recombinant virus assay. Here we report that the rr-NCCR of BKV variants RH-3 and RH-12, both bearing a NCCR deletion including the 5' end of the agnoprotein coding sequence, mediated early and late viral reporter gene expression in kidney cells. However, in a recombinant virus they failed to produce infectious progeny despite large T-antigen and VP1 expression and the formation of nuclear virus-like particles. Infectious progeny was generated when the agnogene was reconstructed in cis or agnoprotein provided in trans from a co-existing BKV rr-NCCR variant. We conclude that complementation can rescue non-functional BKV variants in vitro and possibly in vivo.

  12. Comorbidity is an independent prognostic factor in women with uterine corpus cancer

    DEFF Research Database (Denmark)

    Noer, Mette C; Sperling, Cecilie; Christensen, Ib J

    2014-01-01

    OBJECTIVE: To determine whether comorbidity independently affects overall survival in women with uterine corpus cancer. DESIGN: Cohort study. SETTING: Denmark. STUDY POPULATION: A total of 4244 patients registered in the Danish Gynecologic Cancer database with uterine corpus cancer from 1 January....... RESULTS: Univariate survival analysis showed a significant (p independent prognostic factor with hazard ratios...... ranging from 1.27 to 1.42 in mild, 1.69 to 1.74 in moderate, and 1.72 to 2.48 in severe comorbidity. Performance status was independently associated to overall survival and was found to slightly reduce the prognostic impact of comorbidity. CONCLUSION: Comorbidity is an independent prognostic factor...

  13. Structural and mechanistic analysis of trans-3-chloroacrylic acid dehalogenase activity

    Energy Technology Data Exchange (ETDEWEB)

    Pegan, Scott D., E-mail: pegan@uic.edu [Center of Pharmaceutical Biotechnology and the Department of Medicinal Chemistry and Pharmacognosy, University of Illinois, Chicago (United States); Serrano, Hector; Whitman, Christian P. [Division of Medicinal Chemistry, College of Pharmacy, The University of Texas, Austin (United States); Mesecar, Andrew D., E-mail: pegan@uic.edu [Center of Pharmaceutical Biotechnology and the Department of Medicinal Chemistry and Pharmacognosy, University of Illinois, Chicago (United States)

    2008-12-01

    The X-ray structure of a noncovalently modified trans-3-chloroacrylic acid dehalogenase with a substrate-homolog acetate bound in the active site has been determined to 1.7 Å resolution. Elucidation of catalytically important water is reported and multiple conformations of the catalytic residue αGlu52 are observed. Trans-3-chloroacrylic acid dehalogenase (CaaD) is a critical enzyme in the trans-1, 3-dichloropropene (DCP) degradation pathway in Pseudomonas pavonaceae 170. This enzyme allows bacteria to use trans-DCP, a common component in commercially produced fumigants, as a carbon source. CaaD specifically catalyzes the fourth step of the pathway by cofactor-independent dehalogenation of a vinyl carbon–halogen bond. Previous studies have reported an X-ray structure of CaaD under acidic conditions with a covalent modification of the catalytic βPro1 residue. Here, the 1.7 Å resolution X-ray structure of CaaD under neutral (pH 6.5) conditions is reported without the presence of the covalent adduct. In this new structure, a substrate-like acetate molecule is bound within the active site in a position analogous to the putative substrate-binding site. Additionally, a catalytically important water molecule was identified, consistent with previously proposed reaction schemes. Finally, flexibility of the catalytically relevant side chain αGlu52 is observed in the structure, supporting its role in the catalytic mechanism.

  14. Facts about trans fats

    Science.gov (United States)

    Trans fat is a type of dietary fat . Of all the fats, trans fat is the worst for your health. Too much ... from solid margarine to soft margarine. Ask what type of fats foods are cooked in when you eat out ...

  15. Trigemino-cardiac reflex: occurrence of asystole during trans-sphenoidal adenomectomy: a case report.

    Science.gov (United States)

    Jeon, Dae Geun; Kang, Bong Jin; Hur, Tae Won

    2014-09-01

    The trigemino-cardiac reflex has been reported to occur during various craniofacial surgeries or procedures including manipulation of the trigeminal ganglion, tumor resection in the cerebellopontine angle, various facial reconstructions and trans-sphenoidal adenomectomy. Regarding risk factors during trans-sphenoidal adenomectomy, invasiveness closely related to the size of tumor and the degree of manipulation of cavernous sinus wall have been reported. We report the case of a 40-year-old female patient who had a relatively small-sized (trans-sphenoidal operation of the wall of the cavernous sinus, which strongly suggests the importance of careful manipulation of the cavernous sinus wall. In addition to reporting this rare complication of trans-sphenoidal adenomectomy, we reviewed its clinical management by performing a literature search.

  16. Letter to the editor: healthy alternatives to trans fats

    Directory of Open Access Journals (Sweden)

    Moulin Julie

    2007-04-01

    Full Text Available Abstract Consumption of trans fats is associated with an increase of cardiovascular disease (CVD risk. To comply with regulatory policies and public health authorities recommendations, trans fats should be replaced in food products. The study by Sundram et al. (Nutrition & Metabolism 2007, 4:3 reporting the effect on CVD risk factors of interesterified fat (IE and partially hydrogenated soybean oil (PHSO compared to palm olein (POL has been critically analyzed. The study design and in particular the composition of the tested fats was not suitable to properly answer the question raised regarding the effect of alternative ingredients to trans fats on plasma lipids. The observed effects are divergent with predicted data derived from the literature model consolidated using the individual results of 60 randomized clinical trials. The results of the study published by Sundram and co-workers have to be considered with awareness.

  17. Trans-generational plasticity in response to immune challenge is constrained by heat stress.

    Science.gov (United States)

    Roth, Olivia; Landis, Susanne H

    2017-06-01

    Trans-generational plasticity (TGP) is the adjustment of phenotypes to changing habitat conditions that persist longer than the individual lifetime. Fitness benefits (adaptive TGP) are expected upon matching parent-offspring environments. In a global change scenario, several performance-related environmental factors are changing simultaneously. This lowers the predictability of offspring environmental conditions, potentially hampering the benefits of TGP. For the first time, we here explore how the combination of an abiotic and a biotic environmental factor in the parental generation plays out as trans-generational effect in the offspring. We fully reciprocally exposed the parental generation of the pipefish Syngnathus typhle to an immune challenge and elevated temperatures simulating a naturally occurring heatwave. Upon mating and male pregnancy, offspring were kept in ambient or elevated temperature regimes combined with a heat-killed bacterial epitope treatment. Differential gene expression (immune genes and DNA- and histone-modification genes) suggests that the combined change of an abiotic and a biotic factor in the parental generation had interactive effects on offspring performance, the temperature effect dominated over the immune challenge impact. The benefits of certain parental environmental conditions on offspring performance did not sum up when abiotic and biotic factors were changed simultaneously supporting that available resources that can be allocated to phenotypic trans-generational effects are limited. Temperature is the master regulator of trans-generational phenotypic plasticity, which potentially implies a conflict in the allocation of resources towards several environmental factors. This asks for a reassessment of TGP as a short-term option to buffer environmental variation in the light of climate change.

  18. The influence of demographic, environmental and physical factors on functional independence post stroke

    Directory of Open Access Journals (Sweden)

    M.V. Mamabolo

    2008-01-01

    Full Text Available Purpose: The magnitude of disability observed in strokesurvivors is believed to be dependent in part, on the severity of neurological deficits incurred. A s important but less well understood, is thecontribution of demographic, physical and environmental factors. The objective of this study was to establish what demographic, environmentaland physical factors influence functional independence post stroke. Method: Convenience sampling was used in the selection of subjects from four stroke outpatient public health facilities in the Gauteng Province of South Africa. The data were collected using a structured questionnaire. The analytical tools used included descriptive statistics to measure percentages and cross tabulations to measure the level of associations between functional independence and some of the demographic factors. The Barthel Index was computed to establish the degree of functional independence. Finally the influence of factors on functional independence was investigated using bivariate logistic regressions.Results: The results showed that younger patients (18 - 34 yrs may have a higher likelihood of functional independence compared to older patients at the time of discharge from hospital (18 - 34 years: Odds Ratio = 1. Patients without helpers were more likely to be functionally independent than those with a helper (p = 0.03. Involvement in household activities (p = 0.01, participation in community activities (p = 0.02 and bowel and bladder continence (p = 0.003 and p = 0.04 improved the likelihood of functional independence.Conclusion and im plications: Factors that influence functional independence post stroke are: age, bowel and bladder continence, the presence of a caregiver, participation in household and community activities. It is also of value to encourage patients to participate in household and community activities post stroke as well as being less dependent on helpers in an effort to attain functional independence post

  19. Bim nuclear translocation and inactivation by viral interferon regulatory factor.

    Directory of Open Access Journals (Sweden)

    Young Bong Choi

    2010-08-01

    Full Text Available Viral replication efficiency is in large part governed by the ability of viruses to counteract pro-apoptotic signals induced by infection of the host cell. Human herpesvirus 8 (HHV-8 uses several strategies to block the host's innate antiviral defenses via interference with interferon and apoptotic signaling. Contributors include the four viral interferon regulatory factors (vIRFs 1-4, which function in dominant negative fashion to block cellular IRF activities in addition to targeting IRF signaling-induced proteins such as p53 and inhibiting other inducers of apoptosis such as TGFbeta receptor-activated Smad transcription factors. Here we identify direct targeting by vIRF-1 of BH3-only pro-apoptotic Bcl-2 family member Bim, a key negative regulator of HHV-8 replication, to effect its inactivation via nuclear translocation. vIRF-1-mediated relocalization of Bim was identified in transfected cells, by both immunofluorescence assay and western analysis of fractionated cell extracts. Also, co-localization of vIRF-1 and Bim was detected in nuclei of lytically infected endothelial cells. In vitro co-precipitation assays using purified vIRF-1 and Bim revealed direct interaction between the proteins, and Bim-binding residues of vIRF-1 were mapped by deletion and point mutagenesis. Generation and experimental utilization of Bim-refractory vIRF-1 variants revealed the importance of vIRF-1:Bim interaction, specifically, in pro-replication and anti-apoptotic activity of vIRF-1. Furthermore, blocking of the interaction with cell-permeable peptide corresponding to the Bim-binding region of vIRF-1 confirmed the relevance of vIRF-1:Bim association to vIRF-1 pro-replication activity. To our knowledge, this is the first report of an IRF protein that interacts with a Bcl-2 family member and of nuclear sequestration of Bim or any other member of the family as a means of inactivation. The data presented reveal a novel mechanism utilized by a virus to control

  20. Exploración estocástica de las superficies de energía potencial de dímeros cis-trans y trans-trans del ácido fórmico

    Directory of Open Access Journals (Sweden)

    Said F. Figueredo

    2014-01-01

    Full Text Available Potential energy surface (PES of cis-trans and trans-trans formic acid dimers were sampled using a stochastic method, and the geometries, energies, and vibrational frequencies were computed at B3LYP/6-311++G(3df,2p level of theory. The results show that molar free energy of dimerization deviated up to 108.4% when basis set superposition error (BSSE and zero-point energy (ZPE were not considered. For cis-trans dimers, C=O and O - H bond weakened, whereas C - O bonds strengthened due to dimerization. Also, trans-trans FA dimers did not show a trend regarding strengthening or weakening of the C=O, O - H and C - O bonds.

  1. Mammographic Texture Resemblance generalizes as an independent risk factor of breast cancer

    DEFF Research Database (Denmark)

    Chernoff, Konstantin; Christopher, S G; Karemore, Gopal

    PURPOSE Breast density has been established as a risk factor of breast cancer in numerous studies. Mammographic Texture Resemblance (MTR) has shown to be a density independent risk factor, but only on a single study. We examine if the statistics of the texture recorded in one study generalize...... as an independent risk factor in an unrelated cohort. METHOD AND MATERIALS The statistics of texture were recorded in digitalized film-mammograms of one 4-year prospective study (S1, Dutch screening program) of 245 breast cancers and 250 matched controls. From an independent cohort study (S2, Mayo Mammography...... Health Study cohort) 226 incident breast cancer cases diagnosed through 2008 and 442 matched controls (on age) were used for scoring screening digitized mammograms that were ascertained years prior to diagnosis 1993-2006. Mammographic percent density (PD), using Cumulus, and other major risk factors were...

  2. Contributory factors for the functional independence of oldest old

    Directory of Open Access Journals (Sweden)

    Dâmarys Kohlbeck de Melo Neu Ribeiro

    2015-02-01

    Full Text Available OBJECTIVE To investigate the socioeconomic and clinical factors that contribute to the functional independence of the oldest old of a community. METHOD Cross-sectional quantitative study whose sample consisted of 214 elderly people registered in Basic Health Units. Data were collected through structured interviews and application of the Functional Independence Measure. We used descriptive statistics, and for association of the variables we used the Student t-test, ANOVA and Tukey's test for multiple comparisons. RESULTS The significant variables that contributed to the functional independence were remaining economically active, practicing physical and leisure activities, having a social life, eating fruits, vegetables and meat. The orientation to conduct these practices reduces the demand for care and help needed in everyday activities. CONCLUSION Maintaining independence is primordial to delay disability and presents itself as an excellent field of work for nursing.

  3. Chimeric classical swine fever (CSF)-Japanese encephalitis (JE) viral particles as a non-transmissible bivalent marker vaccine candidate against CSF and JE infections

    Science.gov (United States)

    A trans-complemented CSF- JE chimeric viral replicon was constructed using an infectious cDNA clone of the CSF virus (CSFV) Alfort/187 strain. The E2 gene of CSFV Alfort/187 strain was deleted and the resultant plasmid pA187delE2 was inserted by a fragment containing the region coding for a truncate...

  4. 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.

  5. Trans?generational plasticity in response to immune challenge is constrained by heat stress

    OpenAIRE

    Roth, Olivia; Landis, Susanne H.

    2017-01-01

    Trans-generational plasticity is the adjustment of phenotypes to changing habitat conditions that persist longer than the individual lifetime. Fitness benefits (adaptive TGP) are expected upon matching parent-offspring environments. In a global change scenario, several performance-related environmental factors are changing simultaneously. This lowers the predictability of offspring environmental conditions, potentially hampering the benefits of trans-generational plasticity. For the first tim...

  6. Colorectal mucus binds DC-SIGN and inhibits HIV-1 trans-infection of CD4+ T-lymphocytes.

    Science.gov (United States)

    Stax, Martijn J; Mouser, Emily E I M; van Montfort, Thijs; Sanders, Rogier W; de Vries, Henry J C; Dekker, Henk L; Herrera, Carolina; Speijer, Dave; Pollakis, Georgios; Paxton, William A

    2015-01-01

    Bodily secretions, including breast milk and semen, contain factors that modulate HIV-1 infection. Since anal intercourse caries one of the highest risks for HIV-1 transmission, our aim was to determine whether colorectal mucus (CM) also contains factors interfering with HIV-1 infection and replication. CM from a number of individuals was collected and tested for the capacity to bind DC-SIGN and inhibit HIV-1 cis- or trans-infection of CD4+ T-lymphocytes. To this end, a DC-SIGN binding ELISA, a gp140 trimer competition ELISA and HIV-1 capture/ transfer assays were utilized. Subsequently we aimed to identify the DC-SIGN binding component through biochemical characterization and mass spectrometry analysis. CM was shown to bind DC-SIGN and competes with HIV-1 gp140 trimer for binding. Pre-incubation of Raji-DC-SIGN cells or immature dendritic cells (iDCs) with CM potently inhibits DC-SIGN mediated trans-infection of CD4+ T-lymphocytes with CCR5 and CXCR4 using HIV-1 strains, while no effect on direct infection is observed. Preliminary biochemical characterization demonstrates that the component seems to be large (>100kDa), heat and proteinase K resistant, binds in a α1-3 mannose independent manner and is highly variant between individuals. Immunoprecipitation using DC-SIGN-Fc coated agarose beads followed by mass spectrometry indicated lactoferrin (fragments) and its receptor (intelectin-1) as candidates. Using ELISA we showed that lactoferrin levels within CM correlate with DC-SIGN binding capacity. In conclusion, CM can bind the C-type lectin DC-SIGN and block HIV-1 trans-infection of both CCR5 and CXCR4 using HIV-1 strains. Furthermore, our data indicate that lactoferrin is a DC-SIGN binding component of CM. These results indicate that CM has the potential to interfere with pathogen transmission and modulate immune responses at the colorectal mucosa.

  7. Integrating genome-wide genetic variations and monocyte expression data reveals trans-regulated gene modules in humans.

    Directory of Open Access Journals (Sweden)

    Maxime Rotival

    2011-12-01

    Full Text Available One major expectation from the transcriptome in humans is to characterize the biological basis of associations identified by genome-wide association studies. So far, few cis expression quantitative trait loci (eQTLs have been reliably related to disease susceptibility. Trans-regulating mechanisms may play a more prominent role in disease susceptibility. We analyzed 12,808 genes detected in at least 5% of circulating monocyte samples from a population-based sample of 1,490 European unrelated subjects. We applied a method of extraction of expression patterns-independent component analysis-to identify sets of co-regulated genes. These patterns were then related to 675,350 SNPs to identify major trans-acting regulators. We detected three genomic regions significantly associated with co-regulated gene modules. Association of these loci with multiple expression traits was replicated in Cardiogenics, an independent study in which expression profiles of monocytes were available in 758 subjects. The locus 12q13 (lead SNP rs11171739, previously identified as a type 1 diabetes locus, was associated with a pattern including two cis eQTLs, RPS26 and SUOX, and 5 trans eQTLs, one of which (MADCAM1 is a potential candidate for mediating T1D susceptibility. The locus 12q24 (lead SNP rs653178, which has demonstrated extensive disease pleiotropy, including type 1 diabetes, hypertension, and celiac disease, was associated to a pattern strongly correlating to blood pressure level. The strongest trans eQTL in this pattern was CRIP1, a known marker of cellular proliferation in cancer. The locus 12q15 (lead SNP rs11177644 was associated with a pattern driven by two cis eQTLs, LYZ and YEATS4, and including 34 trans eQTLs, several of them tumor-related genes. This study shows that a method exploiting the structure of co-expressions among genes can help identify genomic regions involved in trans regulation of sets of genes and can provide clues for understanding the

  8. Excited State s-cis Rotamers Produced by Extreme Red Edge Excitation of all-trans-1,4-Diphenyl-1,3-butadiene

    DEFF Research Database (Denmark)

    Wallace-Williams, Stacie E.; Møller, Søren; Goldbeck, Robert A.

    1993-01-01

    with the wavelength independence observed for the excited singlet-state absorption and fluorescence emission spectra of 1,5-diphenyl-2,3,4,6,7,8- hexahydronaphthalene and for the fluorescence emission spectra of 1,4diphenyl-1,3-cyclopentadiene, s-trans and s-cis structural analogs of DPB, respectively. The spectral...... changes in DPB can be explained in terms of an excitation wavelength-dependent production of s-cis and s-trans rotamer populations in the excited state. The DPB fluorescence emission spectrum was resolved into s-cis and s-trans components. The vibronic structure of the s-cis fluorescence spectrum...... is similar to that of s-trans, but the band origin is red-shifted and there is a slightly larger amplitude on the red edge. The excited-state absorption spectrum of s-cis DPB appears to be red-shifted relative to that of s-trans DPB as well....

  9. Psychometric Factors Affecting Female Employees Physical Activity Status: Applying Trans-Theoretical Model and Theory of Planned Behavior

    Directory of Open Access Journals (Sweden)

    M. Shafieinia

    2015-01-01

    Full Text Available Introduction & Objective: Sedentary women are at risk for problems such as obesity, diabetes, depression and cardiovascular disease. Meanwhile, due to long working hours and excessive travel time from home to work and vice versa the employees have minimal physical activity .The purpose of this study was to investigate the effective psychometric factors on physical activity of female employees, according to the Trans-theoretical Model and theory of planned behavior. Materials & Methods: In this cross-sectional study, 95 female staff of Tehran University was selected through a call. In order to collect data, a questionnaire with acceptable, reliability and validity, including demographic data, and constructs of planned behavior theory as well as Trans-theoretical Model was used. The data was analyzed using SPSS version 21 statisti-cal tests; correlation and stepwise regression were also performed. Results: In this study, 72% of the population was in the inactive stages (pre-contemplation, contemplation and preparation and only 28% of patients had regular physical activity. There was a significant positive correlation between the behavioral intention and attitude scores (P = 0.02, perceived behavioral control (P = 0.000, self-efficacy (P = 0.000 and stage of change (P = 0.000, but subjective norms score (P = 0.605 was irrelevant. Conclusion: The results of this study showed that self-efficacy and perceived behavioral con-trol can affect female employees’ intention and physical activity behaviors. So, the authori-ties should seriously consider these factors in educational planning for this stratum of society, remove barriers for the participation of more employees in sporting activities, and offer fa-cilitators at the community level. (Sci J Hamadan Univ Med Sci 2015; 21(4:350-359

  10. Cis By Trans

    OpenAIRE

    Rodovalho,Amara Moira

    2017-01-01

    Cis, trans: above all, metaphors. Cisjordan, region skirting the Jordan River. Cisplatin, Uruguay’s ancient name, region occupying one of the banks of the Prata River. Trans- Amazonian, that which crosses the Amazon; transatlantic, that which crosses the Atlantic. Cisalpine, transalpine. The geometric isomerism of Organic Chemistry, where “cis” are atoms that, when molecules are divided in half, remain on the same side, and “trans” those remaining on opposite sides. Ev...

  11. PUTAS Y TRANS. ¿ESTÁN LAS MUJERES TRANS EN LAS NARRATIVAS SOBRE LA PROSTITUCIÓN?

    Directory of Open Access Journals (Sweden)

    Liza García Reyes

    2015-06-01

    Full Text Available Este artículo evidencia los principales resultados de la investigación cualitativa titulada: Putas y trans. Narrativas sobre mujeres trans en España –desarrollada en 2010–, la cual estudió su presencia en textos académicos sobre prostitución en España, producidos entre los años 2000-2009. El análisis de contenido de 34 narrativas evidenció que las referencias a mujeres trans resulta escasa en ellas, aun siendo ellas quienes tienen mayor presencia en la prostitución, en proporción con las mujeres biológicas. Solo nueve textos mencionan la experiencia trans al interior de la prostitución y, entre estos, el asunto solo aparece asertivamente descrito cuando son las propias mujeres trans quienes escriben. AbstractThis paper shows the results of a qualitative research entitled: Hookers and Trans Women: Narratives about trans women in Spain. This study was developed in 2010 and it is based on presence of trans women in the academic texts of prostitution in Spain produced between 2000 and 2009. The content analysis of thirty four narratives showed that the references to in transsexual women in these texts were few, although they have more presence into prostitution, in relation to the biological women. Only nine texts show an experience of prostitution and among these, transexperience only is described assertively when transsexual women write the texts themselves.

  12. A Herpesviral Immediate Early Protein Promotes Transcription Elongation of Viral Transcripts

    Directory of Open Access Journals (Sweden)

    Hannah L. Fox

    2017-06-01

    Full Text Available Herpes simplex virus 1 (HSV-1 genes are transcribed by cellular RNA polymerase II (RNA Pol II. While four viral immediate early proteins (ICP4, ICP0, ICP27, and ICP22 function in some capacity in viral transcription, the mechanism by which ICP22 functions remains unclear. We observed that the FACT complex (comprised of SSRP1 and Spt16 was relocalized in infected cells as a function of ICP22. ICP22 was also required for the association of FACT and the transcription elongation factors SPT5 and SPT6 with viral genomes. We further demonstrated that the FACT complex interacts with ICP22 throughout infection. We therefore hypothesized that ICP22 recruits cellular transcription elongation factors to viral genomes for efficient transcription elongation of viral genes. We reevaluated the phenotype of an ICP22 mutant virus by determining the abundance of all viral mRNAs throughout infection by transcriptome sequencing (RNA-seq. The accumulation of almost all viral mRNAs late in infection was reduced compared to the wild type, regardless of kinetic class. Using chromatin immunoprecipitation sequencing (ChIP-seq, we mapped the location of RNA Pol II on viral genes and found that RNA Pol II levels on the bodies of viral genes were reduced in the ICP22 mutant compared to wild-type virus. In contrast, the association of RNA Pol II with transcription start sites in the mutant was not reduced. Taken together, our results indicate that ICP22 plays a role in recruiting elongation factors like the FACT complex to the HSV-1 genome to allow for efficient viral transcription elongation late in viral infection and ultimately infectious virion production.

  13. Herd-level risk factors for bovine viral diarrhea infection in cattle of Tamil Nadu.

    Science.gov (United States)

    Kumar, Subbiah Krishna; Palanivel, K M; Sukumar, K; Ronald, B Samuel Masilamoni; Selvaraju, G; Ponnudurai, G

    2018-04-01

    A cross-sectional study was carried out to identify risk factors for bovine viral diarrhea virus (BVDV) infection in 62 randomly selected dairy herds which were tested for BVD serum antibodies by using an indirect ELISA kit (IDEXX). Results from the chi-square test analysis were interpreted by analyzing by chi-square test. A sum of 500 sera samples were screened and 66 animals (13.20%) showed positive for BVDV antibody. Within herd, BVD seroprevalence was 12-65%. This study concluded that epidemiological risk factors like location, herd size, housing patterns like, tail to tail system, roofing pattern, distance between the manure pit and farm, and distance between farms were significantly associated with BVDV serological status (P < 0.05).

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Dynamics of Viremia in Primary HIV-1 infection in Africans: Insights from Analyses of Host and Viral Correlates

    Science.gov (United States)

    Prentice, Heather A.; Price, Matthew A.; Porter, Travis R.; Cormier, Emmanuel; Mugavero, Michael J.; Kamali, Anatoli; Karita, Etienne; Lakhi, Shabir; Sanders, Eduard J.; Anzala, Omu; Amornkul, Pauli N.; Allen, Susan; Hunter, Eric; Kaslow, Richard A.; Gilmour, Jill; Tang, Jianming

    2014-01-01

    In HIV-1 infection, plasma viral load (VL) has dual implications for pathogenesis and public health. Based on well-known patterns of HIV-1 evolution and immune escape, we hypothesized that VL is an evolving quantitative trait that depends heavily on duration of infection (DOI), demographic features, human leukocyte antigen (HLA) genotypes and viral characteristics. Prospective data from 421 African seroconverters with at least four eligible visits did show relatively steady VL beyond 3 months of untreated infection, but host and viral factors independently associated with cross-sectional and longitudinal VL often varied by analytical approaches and sliding time windows. Specifically, the effects of age, HLA-B*53 and infecting HIV-1 subtypes (A1, C and others) on VL were either sporadic or highly sensitive to time windows. These observations were strengthened by the addition of 111 seroconverters with 2–3 eligible VL results, suggesting that DOI should be a critical parameter in epidemiological and clinical studies. PMID:24418560

  16. Radical feminists & trans activists truce

    OpenAIRE

    Mackay, F.

    2014-01-01

    #GenderWeek: Truce! When radical feminists and trans feminists empathise\\ud Feminist Times\\ud By Finn Mackay \\ud read all #GenderWeek articles.\\ud We wanted to explore the ground between the polarised, entrenched positions in the so-called “TERF-war”. Radical feminists on one pole, trans-inclusionary feminists and trans activists on the other. The disputed territory being women-only space, language and the ever changing legal framework surrounding gender.\\ud Entrenchment leads to stalemate. S...

  17. Challenges of implementing collaborative models of decision making with trans-identified patients.

    Science.gov (United States)

    Dewey, Jodie M

    2015-10-01

    Factors health providers face during the doctor-patient encounter both impede and assist the development of collaborative models of treatment. I investigated decision making among medical and therapeutic professionals who work with trans-identified patients to understand factors that might impede or facilitate the adoption of the collaborative decision-making model in their clinical work. Following a grounded theory approach, I collected and analysed data from semi-structured interviews with 10 U.S. physicians and 10 U.S. mental health professionals. Doctors and therapists often desire collaboration with their patients but experience dilemmas in treating the trans-identified patients. Dilemmas include lack of formal education, little to no institutional support and inconsistent understanding and application of the main documents used by professionals treating trans-patients. Providers face considerable risk in providing unconventional treatments due to the lack of institutional and academic support relating to the treatment for trans-people, and the varied interpretation and application of the diagnostic and treatment documents used in treating trans-people. To address this risk, the relationship with the patient becomes crucial. However, trust, a component required for collaboration, is thwarted when the patients feel obliged to present in ways aligned with these documents in order to receive desired treatments. When trust cannot be established, medical and mental health providers can and do delay or deny treatments, resulting in the imbalance of power between patient and provider. The documents created to assist in treatment actually thwart professional desire to work collaboratively with patients. © 2013 John Wiley & Sons Ltd.

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

    Science.gov (United States)

    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

  19. Trans advanced surface laser ablation (TransPRK) outcomes using SmartPulseTechnology.

    Science.gov (United States)

    Aslanides, Ioannis M; Kymionis, George D

    2017-02-01

    To evaluate early visual rehabilitation, post-operative pain, epithelial healing and haze after transepithelial photorefractive keratectomy (TransPRK) using the SmartPulseTechnology (SPT) of Schwind Amaris (Schwind eye-tech-solutions GmbH, Kleinostheim, Germany). This was a retrospective comparative evaluation of a cohort of myopic patients undergoing TransPRK with SPT (group 1), with one matched control group that underwent conventional TransPRK (group 2). All cases had a 6-month post-operative follow-up including visual acuity and slit-lamp examination. Subjective evaluation of pain was recorded post-operatively. 49 eyes of 25 patients in group 1 and 40 eyes of 20 patients in group 2 were enrolled. The patients' visual rehabilitation was significantly faster in group 1, one day and one week post-operatively (P0.05). TransPRK using SPT provides promising results in the early post-operative period. Visual rehabilitation, re-epithelialization and pain were faster in the early post-operative period in group 1 in comparison with group 2. Haze formation was not significantly different between the two groups; however, it was consistently less in group 1. Copyright © 2016 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

  20. Trans as Contested Intelligibility

    DEFF Research Database (Denmark)

    Raun, Tobias

    2014-01-01

    Denne artikel rejser en række epistemologiske og metodologiske spørgsmål vedrørende læsningen af trans som identitetskategori. Disse spørgsmål er stærkt underbelyste i en skandinavisk akademisk kontekst, om end der el- lers i stigende grad produceres analyser af trans identitetsnarrativer. Artikl...

  1. Viral Marketing Determinants of Top Online Shop Brands in Indonesia

    Directory of Open Access Journals (Sweden)

    Aditya Wardhana

    2016-06-01

    Full Text Available The existence of the internet starts to shifting the purchase as a conventional to online. One of marketing strategies used by online store is viral marketing.The purpose of this study is to find determinant that forms viral marketing based on perceived customers in top brand online store such as lazada.com, olx.com, tokopedia.com, zalora.com, blibli.com, and bhinneka.com. The Research methodology used is the quantitative method with descriptive analysis using factor analysis by a population as 3.271.147 people and the number of sample uses Slovin formulas with confidency level at 95 % obtained as 400 respondents. Based on the result of research, there are twelve factors formed a new factor called viral marketing online store. Based on its priority, those dimensions of viral marketing online store can be sorted as follows: customer recommendation, newsletter, linking strategies, communities, free offer, sweepstakes, list of prospective buyers, chatrooms, reference list, product texts, affiliate programs, dan search engine.

  2. HPV-16 viral load in oropharyngeal squamous cell carcinoma using digital PCR.

    Science.gov (United States)

    Antonsson, Annika; Knight, Lani; Panizza, Benedict J; Porceddu, Sandro V; Emmett, Sarah; Whiteman, David C

    2018-05-09

    We did not identify any strong associations between HPV-16 viral load and any of the clinical or lifestyle factors. The epidemiology of oropharyngeal SCC is changing, with an increasing proportion of HPV-positive cases seen in the last decade. It is known that a high viral load is linked to the development of cervical cancer, the relation between viral load and oropharyngeal SCC is less clear. We sought to determine HPV-16 viral load in HPV-positive oropharyngeal SCCs using highly sensitive digital PCR and to identify clinical and lifestyle factors associated with viral load. We analysed 45 HPV-16 positive oropharyngeal SCCs diagnosed between 2013 and 2015. All patients completed a lifestyle questionnaire and clinical data were extracted from medical charts. Viral load was determined using digital PCR assays for HPV-L1 and RNAseP. We found large variations in HPV-16 viral load from 1 to 930 copies per cell (median 34 copies per cell).

  3. Derivation of a JC virus-resistant human glial cell line: implications for the identification of host cell factors that determine viral tropism

    International Nuclear Information System (INIS)

    Gee, Gretchen V.; Manley, Kate; Atwood, Walter J.

    2003-01-01

    JC virus (JCV) is a common human polyomavirus that infects 70-80% of the population worldwide. In immunosuppressed individuals, JCV infects oligodendrocytes and causes a fatal demyelinating disease known as progressive multifocal leukoencephalopathy (PML). The tropism of JCV is restricted to oligodendrocytes, astrocytes, and B lymphocytes. Several mechanisms may contribute to the restricted tropism of JCV, including the presence or absence of cell-type-specific transcription and replication factors and the presence or absence of cell-type-specific receptors. We have established a system to investigate cellular factors that influence viral tropism by selecting JCV-resistant cells from a susceptible glial cell line (SVG-A). SVG-A cells were subjected to several rounds of viral infection using JC virus (M1/SVEΔ). A population of resistant cells emerged (SVGR2) that were refractory to infection with the Mad-4 strain of JCV, the hybrid virus M1/SVEΔ, as well as to the related polyomavirus SV40. SVGR2 cells were as susceptible as the SVG-A cells to infection with an unrelated amphotropic retrovirus. The stage at which these cells are resistant to infection was investigated and the block appears to be at early viral gene transcription. This system should ultimately allow us to identify glial specific factors that influence the tropism of JCV

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

    Science.gov (United States)

    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.

  5. Trigemino-cardiac reflex: occurrence of asystole during trans-sphenoidal adenomectomy: a case report

    OpenAIRE

    Jeon, Dae Geun; Kang, Bong Jin; Hur, Tae Won

    2014-01-01

    The trigemino-cardiac reflex has been reported to occur during various craniofacial surgeries or procedures including manipulation of the trigeminal ganglion, tumor resection in the cerebellopontine angle, various facial reconstructions and trans-sphenoidal adenomectomy. Regarding risk factors during trans-sphenoidal adenomectomy, invasiveness closely related to the size of tumor and the degree of manipulation of cavernous sinus wall have been reported. We report the case of a 40-year-old fem...

  6. The Danish trans-fatty acids ban

    DEFF Research Database (Denmark)

    Vallgårda, Signild

    2017-01-01

    In 2003 an executive order was issued banning industrially produced trans-fatty acids above a low level in food items in Denmark. To date, only a few other countries have followed Denmark’s example. The way health consequences of trans fats were translated by the different actors enabled the crea......In 2003 an executive order was issued banning industrially produced trans-fatty acids above a low level in food items in Denmark. To date, only a few other countries have followed Denmark’s example. The way health consequences of trans fats were translated by the different actors enabled...

  7. Viral Hepatitis

    Science.gov (United States)

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

  8. HIV-1 infection induces changes in expression of cellular splicing factors that regulate alternative viral splicing and virus production in macrophages

    Directory of Open Access Journals (Sweden)

    Purcell Damian FJ

    2008-02-01

    Full Text Available Abstract Background Macrophages are important targets and long-lived reservoirs of HIV-1, which are not cleared of infection by currently available treatments. In the primary monocyte-derived macrophage model of infection, replication is initially productive followed by a decline in virion output over ensuing weeks, coincident with a decrease in the levels of the essential viral transactivator protein Tat. We investigated two possible mechanisms in macrophages for regulation of viral replication, which appears to be primarily regulated at the level of tat mRNA: 1 differential mRNA stability, used by cells and some viruses for the rapid regulation of gene expression and 2 control of HIV-1 alternative splicing, which is essential for optimal viral replication. Results Following termination of transcription at increasing times after infection in macrophages, we found that tat mRNA did indeed decay more rapidly than rev or nef mRNA, but with similar kinetics throughout infection. In addition, tat mRNA decayed at least as rapidly in peripheral blood lymphocytes. Expression of cellular splicing factors in uninfected and infected macrophage cultures from the same donor showed an inverse pattern over time between enhancing factors (members of the SR family of RNA binding proteins and inhibitory factors (members of the hnRNP family. While levels of the SR protein SC35 were greatly up-regulated in the first week or two after infection, hnRNPs of the A/B and H groups were down-regulated. Around the peak of virus production in each culture, SC35 expression declined to levels in uninfected cells or lower, while the hnRNPs increased to control levels or above. We also found evidence for increased cytoplasmic expression of SC35 following long-term infection. Conclusion While no evidence of differential regulation of tat mRNA decay was found in macrophages following HIV-1 infection, changes in the balance of cellular splicing factors which regulate alternative

  9. A trans-activator function is generated by integration of hepatitis B virus preS/S sequences in human hepatocellular carcinoma DNA

    International Nuclear Information System (INIS)

    Caselmann, W.H.; Meyer, M.; Kekule, A.S.; Lauer, U.; Hofschneider, P.H.; Koshy, R.

    1990-01-01

    The X gene of wild-type hepatitis B virus or integrated DNA has recently been shown to stimulate transcription of a variety of enhancers and promoters. To further delineate the viral sequences responsible for trans-activation in hepatomas, the authors cloned the single hepatitis B virus insert from human hepatocellular carcinoma DNA M1. The plasmid pM1 contains 2004 base of hepatitis B virus DNA subtype adr, including truncated preS/S sequences and the enhancer element. The X promoter and 422 nucleotides of the X coding region are present. The entire preC/C gene is deleted. In transient cotransfection assays using Chang liver cells (CCL 13), pM1 DNA exerts a 6- to 10-fold trans-activating effect on the expression of the pSV2CAT reporter plasmid. The transactivation occurs by stimulation of transcription and is dependent on the simian virus 40 enhancer in the reporter plasmid. Deletion analysis of pM1 subclones reveals that the transactivator is encoded by preS/S and not by X sequences. A frameshift mutation within the preS2 open reading frame shows that this portion is indispensable for the trans-activating function. Initiation of transcription has been mapped to the S1 promoter. A comparable trans-activating effect is also observed with cloned wild-type hepatitis B virus sequences similarly truncated. These results show that a transcriptional trans-activator function not present in the intact gene is generated by 3' truncation of integrated hepatitis B virus DNA preS/S sequences

  10. The utrophin A 5'-UTR drives cap-independent translation exclusively in skeletal muscles of transgenic mice and interacts with eEF1A2.

    Science.gov (United States)

    Miura, P; Coriati, A; Bélanger, G; De Repentigny, Y; Lee, J; Kothary, R; Holcik, M; Jasmin, B J

    2010-04-01

    The molecular mechanisms regulating expression of utrophin A are of therapeutic interest since upregulating its expression at the sarcolemma can compensate for the lack of dystrophin in animal models of Duchenne Muscular Dystrophy (DMD). The 5'-UTR of utrophin A has been previously shown to drive cap-independent internal ribosome entry site (IRES)-mediated translation in response to muscle regeneration and glucocorticoid treatment. To determine whether the utrophin A IRES displays tissue specific activity, we generated transgenic mice harboring control (CMV/betaGAL/CAT) or utrophin A 5'-UTR (CMV/betaGAL/UtrA/CAT) bicistronic reporter transgenes. Examination of multiple tissues from two CMV/betaGAL/UtrA/CAT lines revealed that the utrophin A 5'-UTR drives cap-independent translation of the reporter gene exclusively in skeletal muscles and no other examined tissues. This expression pattern suggested that skeletal muscle-specific factors are involved in IRES-mediated translation of utrophin A. We performed RNA-affinity chromatography experiments combined with mass spectrometry to identify trans-factors that bind the utrophin A 5'-UTR and identified eukaryotic elongation factor 1A2 (eEF1A2). UV-crosslinking experiments confirmed the specificity of this interaction. Regions of the utrophin A 5'-UTR that bound eEF1A2 also mediated cap-independent translation in C2C12 muscle cells. Cultured cells lacking eEF1A2 had reduced IRES activity compared with cells overexpressing eEF1A2. Together, these results suggest an important role for eEF1A2 in driving cap-independent translation of utrophin A in skeletal muscle. The trans-factors and signaling pathways driving skeletal-muscle specific IRES-mediated translation of utrophin A could provide unique targets for developing pharmacological-based DMD therapies.

  11. FACTS ABOUT TRANS FATTY ACIDS

    Directory of Open Access Journals (Sweden)

    Sedighe Asgary

    2010-12-01

    be involved in the pathogenesis of atherosclerosis, acute coronary syndromes, sudden death, insulin resistance, dyslipidemia, and heart failure. Fatty acids may also directly or indirectly modulate metabolic and inflammatory responses of the endoplasmic reticulum 31 (Figure 2. Evidence from both observational and experimental studies indicates that TFA are pro-inflammatory. Inflammation is an independent risk factor for cardiovascular diseases (CVD. Epidemiologic studies have suggested that TFA may have an adverse effect on inflammatory markers. In the Nurses’ Health Study, TFA intake, assessed by semi-quantitative food - frequency questionnaires, was  positively associated with tumor necrosis factor receptor (TNFR levels in healthy women (P for trend < 0.001, and was also associated with levels of C-reactive protein (CRP and IL-6 in women with higher BMI (P < 0.05 [32-35]. Limited evidence suggests that pro-inflammatory effects may be stronger for trans isomers of linoleic acid (trans-C18:2 and oleic acid (trans-C18:1, rather than of palmitoleic acid (trans-C16:1, but further study of potential isomer-specific effects is needed. TFA also appear to induce endothelial dysfunction. The mechanisms underlying this effect is not well-established, but may involve TFA incorporation into endothelial cell, monocyte/macrophage, or adipocyte cell membranes (affecting membrane signaling pathway relating to inflammation or ligand-dependent effects on peroxisome proliferator-activated receptor (PPAR or retinoid X receptor (RXR pathways.36,37 Activation of inflammatory responses and endothelial dysfunction may represent important mediating pathways between TFA consumption and risk of coronary heart disease, sudden death, and diabetes.16      The possibility that TFAs decrease the threshold for cardiac arrhythmias has been supported by the results from a more recent case control study of the risk of sudden cardiac death. When levels of TFAs in red blood cells as a marker for

  12. PENYUSUNAN SKENARIO KEBIJAKAN UNTUK PENGEMBANGAN BRT TRANS SEMARANG DENGAN PENDEKATAN SISTEM DINAMIK

    Directory of Open Access Journals (Sweden)

    Aries Susanty

    2014-10-01

    Full Text Available [Preparation for Policy Scenarios for Developing the Bus Rapid Transit (BRT Trans Semarang with Dynamic System Approach] Related to the complexity of the problem faced by Bus Rapid Transit (BRT Trans Semarang, this research attempts to develop a framework for dynamic development of BRT Trans Semarang and provide a platform to support policy making related to performance improvement of BRT Trans Semarang. This research use system dynamics (SD methodology. There are three scenarios constructed in this research and then a system dynamics model built based on them for the next five years. The first scenario is providing some feeder that will take the passenger on the bus, the second scenario is providing some new bus, and the third scenario is a combination of providing a number of feeders and also some new bus. There are three criteria which are used to evaluate the result of each scenario, i. e the achievement of the target of load factor (greater than 70%, the amount of total subsidy for operational of BRT, and percentage of the number of people that change their moda of transportation, from using private vehicles to BRT. The result of simulation with system dynamic indicated that scenario 1 is better than the existing condition; scenario 1 also better than scenario 2 or scenario 3. By providing some feeder, operational BRT can achieve the target of load factor at month 15, the government also does not need to issue subsidies for operational of BRT Trans Semarang, as well as the percentage of the number of people who moved from using private vehicles reached 26%.

  13. Optimizing viral and non-viral gene transfer methods for genetic modification of porcine mesenchymal stem cells

    DEFF Research Database (Denmark)

    Stiehler, Maik; Duch, Mogens; Mygind, Tina

    2006-01-01

    INTRODUCTION: Mesenchymal stem cells (MSCs) provide an excellent source of pluripotent progenitor cells for tissue-engineering applications due to their proliferation capacity and differentiation potential. Genetic modification of MSCs with genes encoding tissue-specific growth factors...... viral and non-viral ex vivo gene delivery systems with respect to gene transfer efficiency, maintenance of transgene expression, and safety issues using primary porcine MSCs as target cells. MATERIALS AND METHODS: MSCs were purified from bone marrow aspirates from the proximal tibiae of four 3-month......-old Danish landrace pigs by Ficoll step gradient separation and polystyrene adherence technique. Vectors expressing enhanced green fluorescent protein (eGFP) and human bone morphogenetic protein-2 (BMP-2) were transferred to the cells by different non-viral methods and by use of recombinant adeno...

  14. Seroprevalence and factors associated with bovine viral diarrhea virus (BVDV) infection in dairy cattle in three milksheds in Ethiopia.

    Science.gov (United States)

    Aragaw, Kassaye; Sibhat, Berhanu; Ayelet, Gelagay; Skjerve, Eystein; Gebremedhin, Endrias Z; Asmare, Kassahun

    2018-05-31

    This work was conducted to estimate the seroprevalence, to identify potential factors that influence seroprevalence of bovine viral diarrhea virus (BVDV), and to investigate the association between BVDV serostatus and occurrence of reproductive disorders in dairy cattle in three milksheds in Ethiopia. A total of 1379 serum samples were obtained from cattle randomly selected from 149 herds from three milksheds representing central, southern, and western Ethiopia. Sera samples were examined for bovine viral diarrhea virus (BVDV) antibodies using commercial competitive enzyme-linked immunosorbent assay (ELISA) kit. Logistic regression analysis was employed to investigate associations between risk factors and the risk of BVDV seroprevalence, and BVDV serostatus and reproductive disorders. Seroreaction to BVDV antigens was detected in 32.6% of the 1379 cattle and 69.8% of the 149 herds sampled. Factors associated with BVDV seroplevalence were age, breed, and herd size (P  0.05). Risk of reproductive disorders was not affected by BVDV serostatus, except for repeat breeding (P > 0.05). The present study demonstrated that BVDV has wide distribution in the country being detected in all the 15 conurbations and 69.8% of herds involved in the study.

  15. Identification of cellular and viral factors related to anti-hepatitis C virus activity of cyclophilin inhibitor.

    Science.gov (United States)

    Goto, Kaku; Watashi, Koichi; Inoue, Daisuke; Hijikata, Makoto; Shimotohno, Kunitada

    2009-10-01

    We have so far reported that an immunosuppressant cyclosporin A (CsA), a well-known cyclophilin (CyP) inhibitor (CPI), strongly suppressed hepatitis C virus (HCV) replication in cell culture, and that CyPB was a cellular cofactor for viral replication. To further investigate antiviral mechanisms of CPI, we here developed cells carrying CsA-resistant HCV replicons, by culturing the HCV subgenomic replicon cells for 4 weeks in the presence of CsA with G418. Transfection of total RNA from the isolated CsA-resistant cells to naïve Huh7 cells conferred CsA resistance, suggesting that the replicon RNA itself was responsible for the resistant phenotype. Of the identified amino acid mutations, D320E in NS5A conferred the CsA resistance. The replicon carrying the D320E mutation was sensitive to interferon-alpha, but was resistant to CsA and other CPIs including NIM811 and sanglifehrin A. Knockdown of individual CyP subtypes revealed CyP40, in addition to CyPA and CyPB, contributed to viral replication, and CsA-resistant replicons acquired independence from CyPA for efficient replication. These data provide important evidence on the mechanisms underlying the regulation of HCV replication by CyP and for designing novel and specific anti-HCV strategies with CPIs.

  16. TransCanada PipeLines Limited 1998 annual report : TransCanada energy solutions

    International Nuclear Information System (INIS)

    1999-01-01

    Financial information from TransCanada PipeLines Limited and a review of the company's 1998 operations was made available for the benefit of shareholders. TransCanada's pipeline system transports natural gas and crude oil from Western Canada Sedimentary Basin to North America's major energy markets. Net earnings from continuing operations for 1998, before unusual charges, were $575 million ($ 355 million after unusual charges) compared to $522 million for 1997. Solid performances from the energy transmission and international business, when compared to 1997, were more than offset by a decreased contribution from energy processing. TransCanada recorded integration costs of $166 million, after tax, related to the merger with NOVA in 1998, which was the major operational accomplishment during the year, creating a seamless economic energy delivery, processing and marketing system from the wellhead to the market. tabs., figs

  17. Comparative evaluation of capillary electrophoresis and high-performance liquid chromatography for the separation of cis-cis, cis-trans, and trans-trans isomers of atracurium besylate.

    Science.gov (United States)

    de Moraes, M de L; Polakiewicz, B; Mattua, M F; Tavares, M F

    1998-01-01

    Atracurium besylate is a highly selective nondepolarizing neuromuscular blocking agent routinely used during anesthetic procedures. The commercial presentation of this drug is a mixture of positional isomers, cis-cis, cis-trans, and trans-trans. Reversed-phase high-performance liquid chromatography has been the technique of choice for the analysis of atracurium besylate formulations at the quality control laboratory of Núcleo de Desenvolvimento Cristália (São Paulo, Brazil), a local pharmaceutical company. HPLC analysis is usually conducted under gradient elution using acetonitrile/0.1 M phosphate buffer eluent mixture as mobile phase and an octadecyl silica (ODS)-packed column. The complete elution of the three isomers takes about 1 hr. In this work, an alternative capillary electrophoresis methodology was developed. The complete resolution of all three isomers was accomplished in about 13 min (+20 kV/72 cm, 211 nm direct detection) using a 60-mM phosphate buffer solution (pH 4) containing 20 mM beta-cyclodextrin and 4 M urea. The isomer ratio was found to be 59.1% cis-cis, 35.9% cis-trans, and 5.02% trans-trans (expected ratio: 59:35:6). Laudanosine, a major metabolite of atracurium besylate, was identified in two commercially available formulations, Tracur (Núcleo de Desenvolvimento Cristália) and Tracrium (Glaxo Wellcome, S.A., Rio de Janeiro, Brazil). Its concentration increases considerably during storage of the product, even if the product is stored at low temperatures.

  18. Host molecular factors and viral genotypes in the mother-to-child HIV-1 transmission in sub-Saharan Africa

    Directory of Open Access Journals (Sweden)

    Linda Chapdeleine M. Mouafo

    2017-07-01

    Full Text Available Maternal viral load and immune status, timing and route of delivery, viral subtype, and host genetics are known to influence the transmission, acquisition and disease progression of human immunodeficiency virus-1 (HIV-1 infection. This review summarizes the findings from published works on host molecular factors and virus genotypes affecting mother to child transmission (MTCT in Africa and identifies the gaps that need to be addressed in future research. Articles in PubMed, Google and AIDSearch and relevant conference abstracts publications were searched. Accessible articles on host factors and viral genetics impacting the MTCT of HIV, done on African populations till 2015 were downloaded. Forty-six articles were found and accessed; 70% described host genes impacting the transmission. The most studied gene was the CCR5 promoter, followed by the CCR2-64I found to reduce MTCT; then SDF1-3’A shown to have no effect on MTCT and others like the DC-SIGNR, CD4, CCL3 and IP- 10. The HLA class I was most studied and was generally linked to the protective effect on MTCT. Breast milk constituents were associated to protection against MTCT. However, existing studies in Sub Saharan Africa were done just in few countries and some done without control groups. Contradictory results obtained may be due to different genetic background, type of controls, different socio-cultural and economic environment and population size. More studies are thus needed to better understand the mechanism of transmission or prevention.

  19. Viral and Host Factors Required for Avian H5N1 Influenza A Virus Replication in Mammalian Cells

    Directory of Open Access Journals (Sweden)

    Hong Zhang

    2013-06-01

    Full Text Available Following the initial and sporadic emergence into humans of highly pathogenic avian H5N1 influenza A viruses in Hong Kong in 1997, we have come to realize the potential for avian influenza A viruses to be transmitted directly from birds to humans. Understanding the basic viral and cellular mechanisms that contribute to infection of mammalian species with avian influenza viruses is essential for developing prevention and control measures against possible future human pandemics. Multiple physical and functional cellular barriers can restrict influenza A virus infection in a new host species, including the cell membrane, the nuclear envelope, the nuclear environment, and innate antiviral responses. In this review, we summarize current knowledge on viral and host factors required for avian H5N1 influenza A viruses to successfully establish infections in mammalian cells. We focus on the molecular mechanisms underpinning mammalian host restrictions, as well as the adaptive mutations that are necessary for an avian influenza virus to overcome them. It is likely that many more viral and host determinants remain to be discovered, and future research in this area should provide novel and translational insights into the biology of influenza virus-host interactions.

  20. Trans Ova Genetics, L.C.

    Science.gov (United States)

    The EPA is providing notice of a proposed Administrative Penalty Assessment against Trans Ova Genetics, L.C., a business located at 2938 380th Street Sioux Center, IA 51250, for alleged violations at the Trans Ova Genetics, L.C.’s facility located in 12425

  1. Nuclear Protein Sam68 Interacts with the Enterovirus 71 Internal Ribosome Entry Site and Positively Regulates Viral Protein Translation.

    Science.gov (United States)

    Zhang, Hua; Song, Lei; Cong, Haolong; Tien, Po

    2015-10-01

    Enterovirus 71 (EV71) recruits various cellular factors to assist in the replication and translation of its genome. Identification of the host factors involved in the EV71 life cycle not only will enable a better understanding of the infection mechanism but also has the potential to be of use in the development of antiviral therapeutics. In this study, we demonstrated that the cellular factor 68-kDa Src-associated protein in mitosis (Sam68) acts as an internal ribosome entry site (IRES) trans-acting factor (ITAF) that binds specifically to the EV71 5' untranslated region (5'UTR). Interaction sites in both the viral IRES (stem-loops IV and V) and the heterogeneous nuclear ribonucleoprotein K homology (KH) domain of Sam68 protein were further mapped using an electrophoretic mobility shift assay (EMSA) and biotin RNA pulldown assay. More importantly, dual-luciferase (firefly) reporter analysis suggested that overexpression of Sam68 positively regulated IRES-dependent translation of virus proteins. In contrast, both IRES activity and viral protein translation significantly decreased in Sam68 knockdown cells compared with the negative-control cells treated with short hairpin RNA (shRNA). However, downregulation of Sam68 did not have a significant inhibitory effect on the accumulation of the EV71 genome. Moreover, Sam68 was redistributed from the nucleus to the cytoplasm and interacts with cellular factors, such as poly(rC)-binding protein 2 (PCBP2) and poly(A)-binding protein (PABP), during EV71 infection. The cytoplasmic relocalization of Sam68 in EV71-infected cells may be involved in the enhancement of EV71 IRES-mediated translation. Since Sam68 is known to be a RNA-binding protein, these results provide direct evidence that Sam68 is a novel ITAF that interacts with EV71 IRES and positively regulates viral protein translation. The nuclear protein Sam68 is found as an additional new host factor that interacts with the EV71 IRES during infection and could potentially

  2. Energetics and Kinetics of trans-SNARE Zippering

    Science.gov (United States)

    Rebane, Aleksander A.; Shu, Tong; Krishnakumar, Shyam; Rothman, James E.; Zhang, Yongli

    Synaptic exocytosis relies on assembly of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins into a four-helix bundle to drive membrane fusion. Complementary SNAREs anchored to the synaptic vesicle (v-SNARE) and the plasma membrane (t-SNARE) associate from their N-termini, transiting a half-assembled intermediate (trans-SNARE), and ending at their C-termini with a rapid power stroke that leads to membrane fusion. Although cytosolic SNARE assembly has been characterized, it remains unknown how membranes modulate the energetics and kinetics of SNARE assembly. Here, we present optical tweezers measurements on folding of single membrane proteins in phospholipid bilayers. To our knowledge, this is the first such report. We measured the energetics, kinetics, and assembly intermediates of trans-SNAREs formed between a t-SNARE inserted into a bead-supported bilayer and a v-SNARE in a nanodisc. We found that the repulsive force of the apposed membranes increases the lifetime of the half-assembled intermediate. Our findings provide a single-molecule platform to study the regulation of trans-SNARE assembly by proteins that act on the half-assembled state, and thus reveal the mechanistic basis of the speed and high fidelity of synaptic transmission. This work was supported by US National Institutes of Health Grants F31 GM119312-01 (to A.A.R) and R01 GM093341 (to Y.Z.).

  3. Spectroscopic and density functional theory studies of trans-3-(trans-4-imidazolyl)acrylic acid.

    Science.gov (United States)

    Arjunan, V; Remya, P; Sathish, U; Rani, T; Mohan, S

    2014-08-14

    The structural parameters, thermodynamic properties and vibrational frequencies of the optimised geometry of trans-3-(trans-4-imidazolyl)acrylic acid have been determined from B3LYP methods with 6-311++G(**) and cc-pVTZ basis sets. The effects of substituents (acrylyl group) on the imidazole vibrational frequencies are analysed. The vibrational frequencies of the fundamental modes of trans-3-(trans-4-imidazolyl)acrylic acid have been precisely assigned and analysed and the theoretical results are compared with the experimental vibrations. (1)H and (13)C NMR isotropic chemical shifts are calculated and the assignments made are compared with the experimental values. The energies of important MO's of the compound are also determined from DFT method. The total electron density and electrostatic potential of the compound are determined by natural bond orbital analysis. Various reactivity and selectivity descriptors such as chemical hardness, chemical potential, softness, electrophilicity, nucleophilicity and the appropriate local quantities employing natural population analysis (NPA) are calculated. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Viral haemorrhagic fever and vascular alterations.

    Science.gov (United States)

    Aleksandrowicz, P; Wolf, K; Falzarano, D; Feldmann, H; Seebach, J; Schnittler, H

    2008-02-01

    Pathogenesis of viral haemorrhagic fever (VHF) is closely associated with alterations of the vascular system. Among the virus families causing VHF, filoviruses (Marburg and Ebola) are the most fatal, and will be focused on here. After entering the body, Ebola primarily targets monocytes/macrophages and dendritic cells. Infected dendritic cells are largely impaired in their activation potency, likely contributing to the immune suppression that occurs during filovirus infection. Monocytes/macrophages, however, immediately activate after viral contact and release reasonable amounts of cytokines that target the vascular system, particularly the endothelial cells. Some underlying molecular mechanisms such as alteration of the vascular endothelial cadherin/catenin complex, tyrosine phosphorylation, expression of cell adhesion molecules, tissue factor and the effect of soluble viral proteins released from infected cells to the blood stream will be discussed.

  5. Building coalitions: The interconnections between feminism and trans* activism in Spain.

    Science.gov (United States)

    Lucas Platero, R; Ortega-Arjonilla, Esther

    2016-01-01

    What made current Spanish feminism shift toward transfeminism? Based on in-depth interviews and literature reviews, we explore what factors facilitated the participation of trans* women in Spanish feminism. Tracing the history through relevant events such as the National Feminist Conferences, it becomes clear that trans* women participated in the 1993, 2000, and 2009 conferences, posing relevant issues regarding prostitution, transgenderism, and the political subject of feminism. Our research allows a break with global oppositional narratives, in which these movements are in conflict, and highlights the importance of understanding the vernacular nuances that take place in a particular geopolitical context.

  6. Prevalence and risk factors for viral exposure in rural dogs around protected areas of the Atlantic forest.

    Science.gov (United States)

    Curi, Nelson Henrique de Almeida; Massara, Rodrigo Lima; de Oliveira Paschoal, Ana Maria; Soriano-Araújo, Amanda; Lobato, Zélia Inês Portela; Demétrio, Guilherme Ramos; Chiarello, Adriano Garcia; Passamani, Marcelo

    2016-01-28

    Despite the crucial role of domestic dogs as reservoirs for zoonosis and some of the most threatening diseases for wild carnivores such as distemper and parvovirosis, little is known about the epidemiological features and the risk factors involved in pathogen exposure of dogs that live in human/wildlife interfaces and actually contacts wildlife. Through a cross-sectional serological approach and questionnaire survey, we assessed the prevalence along with individual and environment-associated risk factors for four important viral diseases of rural dogs living in households around six Atlantic Forest fragments in southeast Brazil. Widespread exposure to canine parvovirus (97%), canine distemper virus (15%) and canine adenovirus (27%) was detected, but none for canine coronavirus. Dogs from small private reserves were more exposed to parvovirus and canine distemper virus than those from larger state parks. Exposure was associated with dog sex and age, lack of health care and the number of people in the households. Remarkably, factors linked to free-ranging behaviour of dogs were associated with the exposure for all pathogens detected. According to identified associations, reducing viral pathogen exposure in dogs will require inhibiting dog's movements and access to nearby forests and villages and improving veterinary assistance. Promoting dog vaccination and population control through sterilization around protected areas is also necessary. The study provides support for preventive management actions aimed to protect the health of rural dogs, and consequently of Atlantic Forest's wild carnivores.

  7. Epoxidation of the methamphetamine pyrolysis product, trans-phenylpropene, to trans-phenylpropylene oxide by CYP enzymes and stereoselective glutathione adduct formation

    International Nuclear Information System (INIS)

    Sanga, Madhu; Younis, Islam R.; Tirumalai, Padma S.; Bland, Tina M.; Banaszewska, Monica; Konat, Gregory W.; Tracy, Timothy S.; Gannett, Peter M.; Callery, Patrick S.

    2006-01-01

    Pyrolytic products of smoked methamphetamine hydrochloride are well established. Among the various degradation products formed, trans-phenylpropene (trans-β-methylstyrene) is structurally similar to styrene analogues known to be bioactivated by CYP enzymes. In human liver microsomes, trans-phenylpropene was converted to the epoxide trans-phenylpropylene oxide (trans-2-methyl-3-phenyloxirane) and cinnamyl alcohol. Incubation of trans-phenylpropene with microsomes in the presence of enzyme-specific P450 enzyme inhibitors indicated the involvement of CYP2E1, CYP1A2, and CYP3A4 enzymes. Both (R,R)-phenylpropylene oxide and (S,S)-phenylpropylene oxide were formed in human liver microsomal preparations. Enantiomers of trans-phenylpropylene oxide were stereoselectively and regioselectively conjugated in a Phase II drug metabolism reaction catalyzed by human liver cytosolic enzymes consisting of conjugation with glutathione. The structure of the phenylpropylene oxide-glutathione adduct is consistent with nucleophilic ring-opening by attack at the benzylic carbon. Exposure of cultured C6 glial cells to (S,S)-phenylpropylene oxide produced a cytotoxic response in a concentration-dependent manner based on cell degeneration and death

  8. PERSONAS TRANS Y SU ADHERENCIA A LA TERAPIA ANTIRRETROVIRAL PARA EL VIH/SIDA

    Directory of Open Access Journals (Sweden)

    Milagros Del Carmen Meléndez Sáez

    2015-01-01

    Full Text Available La población de personas Trans es una poco estudiada. Los escasos estudios publicados sugieren que las personas Trans que viven con Virus de Inmunodeficiencia Humana/Síndrome de Inmunodeficiencia Adquirida (VIH/SIDA se enfrentan a retos únicos en cuanto a la adherencia y los cuidados de tratamiento de esta enfermedad. La complejidad de los factores asociados con la adherencia está implicada en una interacción dinámica entre las variables de comportamiento y el desarrollo cognitivo y emocional. El presente estudio con metodología mixta, tuvo como objetivo analizar y describir la relación entre las variables apoyo social, creencias de salud y depresión con el nivel de adherencia a los tratamientos antirretrovirales (TAR en una muestra de ocho personas Trans (N = 8 que viven con VIH/SIDA en Puerto Rico (PR. Los hallazgos demuestran que el factor principal para la adherencia a TAR es el apoyo social, lo que implica tener significancia clínica.

  9. A comparison of trans-cranial and trans-sphenoidal approaches for vision improvement due to pitutary adenomas

    Directory of Open Access Journals (Sweden)

    Fakhr Tabatabai SA

    1997-07-01

    Full Text Available To improve visual disturbance, optic nerve decompression can be performed via transcranial or tran-sphenoidal approaches. Although the surgical exposure in transcranial approach is favourable, yet the optic nerve's presence in the field may make it vulnerable to damage. Of fighty patients with different types of pituitary adenomas, 35 cases with medium-sized (1-3 cm tumors have been studied in a randomized clinical trial during a three year period, to compare the applicability of these approaches. While short hospital stay with better visual outcome was observed in fifteen trans-sphenoidal cases, in comparison to 20 trans-cranial cases, however the preoperative visual status and underlying disorders were similar in both groups. Decompressing the optic apparatus, trans-sphenoidally, seems beneficial, where there are no contraindications for the procedure in medium-sized pituitary adenomas

  10. Reasons for decision in the matter of Trans Mountain Pipeline Inc. (formerly Terasen Pipelines (Trans Mountain) Inc.) : tariffs

    International Nuclear Information System (INIS)

    2007-01-01

    In 2006 and 2007 Terasen Pipelines (Trans Mountain) Inc. (now Trans Mountain Pipeline Inc.) submitted a series of applications to the National Energy Board for revisions to the Trans Mountain Tariffs. They were filed in response to apportionment concerns on the Trans Mountain pipeline. Four of the applications involved pronounced and contentious changes to the capacity allocation procedures on the pipeline system. For ease of reference, the Board amalgamated its 4 decisions on these applications into a single document. A map of the Trans Mountain pipeline system as a whole was presented along with a detailed map indicating the delivery locations served by the system in the lower mainland of British Columbia and the state of Washington. The issues considered by the Board in each of these decisions included capacity allocation for Westridge Dock; capacity allocations to export destinations; common carriage requirements; and the need for creating a new barge subcategory. Relevant sections of the National Energy Board Act referred to in the decisions were highlighted. This document also listed the Trans Mountain Tariffs that have introduced notable revisions to the capacity allocation procedures on the system since September 2003. 16 refs., 2 figs., 3 appendices

  11. HIV-1 transmitting couples have similar viral load set-points in Rakai, Uganda.

    Directory of Open Access Journals (Sweden)

    T Déirdre Hollingsworth

    2010-05-01

    Full Text Available It has been hypothesized that HIV-1 viral load set-point is a surrogate measure of HIV-1 viral virulence, and that it may be subject to natural selection in the human host population. A key test of this hypothesis is whether viral load set-points are correlated between transmitting individuals and those acquiring infection. We retrospectively identified 112 heterosexual HIV-discordant couples enrolled in a cohort in Rakai, Uganda, in which HIV transmission was suspected and viral load set-point was established. In addition, sequence data was available to establish transmission by genetic linkage for 57 of these couples. Sex, age, viral subtype, index partner, and self-reported genital ulcer disease status (GUD were known. Using ANOVA, we estimated the proportion of variance in viral load set-points which was explained by the similarity within couples (the 'couple effect'. Individuals with suspected intra-couple transmission (97 couples had similar viral load set-points (p = 0.054 single factor model, p = 0.0057 adjusted and the couple effect explained 16% of variance in viral loads (23% adjusted. The analysis was repeated for a subset of 29 couples with strong genetic support for transmission. The couple effect was the major determinant of viral load set-point (p = 0.067 single factor, and p = 0.036 adjusted and the size of the effect was 27% (37% adjusted. Individuals within epidemiologically linked couples with genetic support for transmission had similar viral load set-points. The most parsimonious explanation is that this is due to shared characteristics of the transmitted virus, a finding which sheds light on both the role of viral factors in HIV-1 pathogenesis and on the evolution of the virus.

  12. VIRAL HEPATITIS A TO E IN SOUTH MEDITERRANEAN COUNTRIES

    Directory of Open Access Journals (Sweden)

    Sanaa M. Kamal

    2010-02-01

    Full Text Available Viral hepatitis represents an important health problem in the South Mediterranean countries, Egypt, Libya, Tunisia, Algeria and Morocco.  Emerging natural history and epidemiological information reveal differences in the overall epidemiology, risk factors and modes of transmission of viral hepatitis A, B, C, D, E infections in the South Mediterranean region. The differences in the in incidence and prevalence of viral hepatitis across North African countries is attributed to variations in health care  and sanitation standards, risk factors and immunization strategies. The active continuous population movement through travel, tourism and migration from and to the South Mediterranean countries contribute to the spread of infections due to hepatitis viruses across borders leading to outbreaks and emergence of new patterns of infection or introduction of uncommon genotypes in other countries, particularly in Europe.

  13. Human Adenovirus Core Protein V Is Targeted by the Host SUMOylation Machinery To Limit Essential Viral Functions.

    Science.gov (United States)

    Freudenberger, Nora; Meyer, Tina; Groitl, Peter; Dobner, Thomas; Schreiner, Sabrina

    2018-02-15

    Human adenoviruses (HAdV) are nonenveloped viruses containing a linear, double-stranded DNA genome surrounded by an icosahedral capsid. To allow proper viral replication, the genome is imported through the nuclear pore complex associated with viral core proteins. Until now, the role of these incoming virion proteins during the early phase of infection was poorly understood. The core protein V is speculated to bridge the core and the surrounding capsid. It binds the genome in a sequence-independent manner and localizes in the nucleus of infected cells, accumulating at nucleoli. Here, we show that protein V contains conserved SUMO conjugation motifs (SCMs). Mutation of these consensus motifs resulted in reduced SUMOylation of the protein; thus, protein V represents a novel target of the host SUMOylation machinery. To understand the role of protein V SUMO posttranslational modification during productive HAdV infection, we generated a replication-competent HAdV with SCM mutations within the protein V coding sequence. Phenotypic analyses revealed that these SCM mutations are beneficial for adenoviral replication. Blocking protein V SUMOylation at specific sites shifts the onset of viral DNA replication to earlier time points during infection and promotes viral gene expression. Simultaneously, the altered kinetics within the viral life cycle are accompanied by more efficient proteasomal degradation of host determinants and increased virus progeny production than that observed during wild-type infection. Taken together, our studies show that protein V SUMOylation reduces virus growth; hence, protein V SUMOylation represents an important novel aspect of the host antiviral strategy to limit virus replication and thereby points to potential intervention strategies. IMPORTANCE Many decades of research have revealed that HAdV structural proteins promote viral entry and mainly physical stability of the viral genome in the capsid. Our work over the last years showed that this

  14. A proteomic perspective of inbuilt viral protein regulation: pUL46 tegument protein is targeted for degradation by ICP0 during herpes simplex virus type 1 infection.

    Science.gov (United States)

    Lin, Aaron E; Greco, Todd M; Döhner, Katinka; Sodeik, Beate; Cristea, Ileana M

    2013-11-01

    Much like the host cells they infect, viruses must also regulate their life cycles. Herpes simples virus type 1 (HSV-1), a prominent human pathogen, uses a promoter-rich genome in conjunction with multiple viral trans-activating factors. Following entry into host cells, the virion-associated outer tegument proteins pUL46 and pUL47 act to increase expression of viral immediate-early (α) genes, thereby helping initiate the infection life cycle. Because pUL46 has gone largely unstudied, we employed a hybrid mass spectrometry-based approach to determine how pUL46 exerts its functions during early stages of infection. For a spatio-temporal characterization of pUL46, time-lapse microscopy was performed in live cells to define its dynamic localization from 2 to 24 h postinfection. Next, pUL46-containing protein complexes were immunoaffinity purified during infection of human fibroblasts and analyzed by mass spectrometry to investigate virus-virus and virus-host interactions, as well as post-translational modifications. We demonstrated that pUL46 is heavily phosphorylated in at least 23 sites. One phosphorylation site matched the consensus 14-3-3 phospho-binding motif, consistent with our identification of 14-3-3 proteins and host and viral kinases as specific pUL46 interactions. Moreover, we determined that pUL46 specifically interacts with the viral E3 ubiquitin ligase ICP0. We demonstrated that pUL46 is partially degraded in a proteasome-mediated manner during infection, and that the catalytic activity of ICP0 is responsible for this degradation. This is the first evidence of a viral protein being targeted for degradation by another viral protein during HSV-1 infection. Together, these data indicate that pUL46 levels are tightly controlled and important for the temporal regulation of viral gene expression throughout the virus life cycle. The concept of a structural virion protein, pUL46, performing nonstructural roles is likely to reflect a theme common to many viruses

  15. Positive serology for viral hepatitis and donor self-exclusion in Southern Brazil

    Directory of Open Access Journals (Sweden)

    Julia De Luca Maccarini

    2013-07-01

    Full Text Available Introduction Despite the great advances in serological testing for transfusion-transmitted infections, the selection of blood donors by blood bank operators remains the only way to avoid transmission within the testing window period. Part of this selection is the self-exclusion form, on which the donors can exclude their blood from donation without any explanation. This study assessed the clinical and epidemiological characteristics related to positivity for viral hepatitis and to the use of the confidential self-exclusion (CSE form. Methods This transversal study analyzed the data collected from blood donors' files in a hospital in Southern Brazil. Univariate and multivariate analyses identified the clinical and epidemiological variables related to positive serologies of viral hepatitis and to whether the donor was self-excluded. Results Of the 3,180 donors included in this study, 0.1% tested positive for HBsAg, 2.1% for anti-HBc, and 0.9% for anti-HCV. When the 93 donors with positive serologies for viral hepatitis were compared with those who were negative, a greater proportion of the positive serology group was found to have had a history of blood transfusions (OR=4.908; 95%CI=1.628 - 14.799; p<0.01, had repeatedly donated (OR=2.147; 95%CI=1.236 - 3.729; p<0.01, and used the CSE form for self-exclusion (OR=7.139; 95%CI=2.045 - 24.923; p<0.01. No variables were independently associated with self-exclusion. Conclusions A history of blood transfusion, repeated donations, and self-exclusion are factors that should be considered during viral hepatitis screenings in blood banks.

  16. Colorectal mucus binds DC-SIGN and inhibits HIV-1 trans-infection of CD4+ T-lymphocytes.

    Directory of Open Access Journals (Sweden)

    Martijn J Stax

    Full Text Available Bodily secretions, including breast milk and semen, contain factors that modulate HIV-1 infection. Since anal intercourse caries one of the highest risks for HIV-1 transmission, our aim was to determine whether colorectal mucus (CM also contains factors interfering with HIV-1 infection and replication. CM from a number of individuals was collected and tested for the capacity to bind DC-SIGN and inhibit HIV-1 cis- or trans-infection of CD4+ T-lymphocytes. To this end, a DC-SIGN binding ELISA, a gp140 trimer competition ELISA and HIV-1 capture/ transfer assays were utilized. Subsequently we aimed to identify the DC-SIGN binding component through biochemical characterization and mass spectrometry analysis. CM was shown to bind DC-SIGN and competes with HIV-1 gp140 trimer for binding. Pre-incubation of Raji-DC-SIGN cells or immature dendritic cells (iDCs with CM potently inhibits DC-SIGN mediated trans-infection of CD4+ T-lymphocytes with CCR5 and CXCR4 using HIV-1 strains, while no effect on direct infection is observed. Preliminary biochemical characterization demonstrates that the component seems to be large (>100kDa, heat and proteinase K resistant, binds in a α1-3 mannose independent manner and is highly variant between individuals. Immunoprecipitation using DC-SIGN-Fc coated agarose beads followed by mass spectrometry indicated lactoferrin (fragments and its receptor (intelectin-1 as candidates. Using ELISA we showed that lactoferrin levels within CM correlate with DC-SIGN binding capacity. In conclusion, CM can bind the C-type lectin DC-SIGN and block HIV-1 trans-infection of both CCR5 and CXCR4 using HIV-1 strains. Furthermore, our data indicate that lactoferrin is a DC-SIGN binding component of CM. These results indicate that CM has the potential to interfere with pathogen transmission and modulate immune responses at the colorectal mucosa.

  17. Micro-Sugar-Snap and -Wire-Cut Cookie Baking with Trans- and Zero-Trans-Fat Shortenings

    Science.gov (United States)

    The effect of trans- and zero-trans-fat shortenings on cookie-baking performance was evaluated, using the two AACC micro-cookie-baking methods. Regardless of fat type, sugar-snap cookies made with a given flour were larger in diameter, smaller in height, and greater in weight loss during baking tha...

  18. Assessment of the rabbit as a wildlife reservoir of bovine viral diarrhoea virus: serological analysis and generation of trans-placentally infected offspring

    Directory of Open Access Journals (Sweden)

    Dawn M Grant

    2015-09-01

    Full Text Available Eradication of Bovine viral diarrhoea virus (BVDV is ongoing in many European countries and is based on removal of persistently infected (PI cattle. In this context, low-level risks, including alternative reservoirs of infection, may become more important as the number of BVDV-free herds increases. Alternative reservoirs include livestock, such as sheep and goats, as well as wildlife, including deer and rabbits. Due to the extensive nature of the beef industry in Scotland, where eradication started in 2010, contact between cattle and alternative reservoir hosts is common.Seroprevalence to BVDV in rabbit populations can be high. In addition, rabbits can be infected with BVDV by natural routes, indicating that they could be a wildlife reservoir of infection. We analysed the potential risk to livestock from rabbit populations in the UK by two approaches. First, approximately 260 serum samples from free-ranging wild rabbits in Scotland and northern England were tested for BVDV-specific antibodies by ELISA. Only three samples exhibited low level BVDV-specific reactivity, suggesting that BVDV infection of rabbits was not frequent. Second, rabbits were challenged with BVDV at day 7 or 12 of pregnancy. This did not lead to any clinical signs in the infected animals or obvious increases in abortion or stillbirth in the infected dams. Samples from the dams, placental material and approximately 130 offspring were tested by BVDV-specific RT-PCR and antibody ELISA. Positive PCR results in the placentas and in the tissues and body fluids of rabbits up to 10 days old showed that trans-placental infection of rabbits with BVDV had occurred. Many of the offspring had BVDV-specific antibodies.These data support the view that a wildlife reservoir of BVDV in rabbit poses a small but non-zero risk of re-infection for BVDV-free cattle herds. Rabbits are susceptible to infection with BVDV but a small proportion of free-living rabbits in the UK appear to have been

  19. Viral findings in adult hematological patients with neutropenia.

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    Lars Ohrmalm

    Full Text Available BACKGROUND: Until recently, viral infections in patients with hematological malignancies were concerns primarily in allogeneic hematopoietic stem cell transplant (HSCT recipients. During the last years, changed treatment regimens for non-transplanted patients with hematological malignancies have had potential to increase the incidence of viral infections in this group. In this study, we have prospectively investigated the prevalence of a broad range of respiratory viruses in nasopharyngeal aspirate (NPA as well as viruses that commonly reactivate after allogeneic HSCT. METHODOLOGY/PRINCIPAL FINDINGS: Patients with hematological malignancies and therapy induced neutropenia (n = 159 were screened regarding a broad range of common respiratory viruses in the nasopharynx and for viruses commonly detected in severely immunosuppressed patients in peripheral blood. Quantitative PCR was used for detection of viruses. A viral pathogen was detected in 35% of the patients. The detection rate was rather similar in blood (22% and NPA (18% with polyoma BK virus and rhinovirus as dominating pathogens in blood and NPA, respectively. Patients with chronic lymphocytic leukemia (CLL (p<0.01 and patients with fever (p<0.001 were overrepresented in the virus-positive group. Furthermore, viral findings in NPA were associated with upper respiratory symptoms (URTS (p<0.0001. CONCLUSIONS/SIGNIFICANCE: Both respiratory viral infections and low titers of viruses in blood from patients with neutropenia were common. Patients with CLL and patients with fever were independently associated to these infections, and viral findings in NPA were associated to URTS indicating active infection. These findings motivate further studies on viruses' impact on this patient category and their potential role as causative agents of fever during neutropenia.

  20. The role of psychological factors in the career of the independent dancer

    Directory of Open Access Journals (Sweden)

    Imogen eAujla

    2015-10-01

    Full Text Available Previous research indicates that psychological factors such as motivation and mental skills play an important role in relation to performance and to negotiating talent development stages. However, little is known about these factors in dance, particularly with regard to the independent dancer whose career may involve multiple roles, varied work patterns and periods of instability. The aim of this study was to explore dancers’ motivation to work in an independent capacity, and the extent to which dancers’ psychological characteristics and skills enabled them to navigate a career in this demanding sector. In-depth semi-structured interviews were conducted with 14 dancers at different stages of their careers. Interviews were transcribed verbatim and content analyzed. Analysis revealed that the dancers were intrinsically motivated and highly committed to the profession. Working in the independent sector offered dancers opportunities for growth and fulfillment; they appreciated the autonomy, flexibility and freedom that the independent career afforded, as well as working with new people across roles and disciplines. In order to overcome the various challenges associated with the independent role, optimism, self-belief, social support and career management skills were crucial. The mental skills reported by the participants had developed gradually in response to the demands that they faced. Therefore, mental skills training could be invaluable for dancers to help them successfully negotiate the independent sector.

  1. Understanding the complexity of trans fatty acid reduction in the American diet: American Heart Association Trans Fat Conference 2006: report of the Trans Fat Conference Planning Group.

    Science.gov (United States)

    Eckel, Robert H; Borra, Susan; Lichtenstein, Alice H; Yin-Piazza, Shirley Y

    2007-04-24

    A 2-day forum was convened to discuss the current status and future implications of reducing trans fatty acids without increasing saturated fats in the food supply while maintaining functionality and consumer acceptance of packaged, processed, and prepared foods. Attendees represented the agriculture and oilseed industry and oil processing, food manufacturing, food service, government, food technology, and health and nutrition disciplines. Presentations included food science behind fatty acid technology, the health science of dietary fatty acids, alternatives to trans fatty acids, and the use of alternatives in food manufacturing and food service. The reduction of trans fatty acids in the food supply is a complex issue involving interdependent and interrelated stakeholders. Actions to reduce trans fatty acids need to carefully consider both intended and unintended consequences related to nutrition and public health. The unintended consequence of greatest concern is that fats and oils high in saturated fats, instead of the healthier unsaturated fats, might be used to replace fats and oils with trans fatty acids. Many different options of alternative oils and fats to replace trans fatty acids are available or in development. Decisions on the use of these alternatives need to consider availability, health effects, research and development investments, reformulated food quality and taste, supply-chain management, operational modifications, consumer acceptance, and cost. The conference demonstrated the value of collaboration between the food industry and health and nutrition professionals, and this conference model should be used to address other food development, processing, and/or technology issues.

  2. Becoming lesbian: Monique Wittig's queer-trans-feminism.

    Science.gov (United States)

    Henderson, Kevin

    2018-04-03

    Inspired by Lynne Huffer's queer feminist genealogy, this article explores queer-trans-feminism as a project that would bring together queer, feminist, and transgender theory and politics into a shared critical lineage. I suggest that Monique Wittig is a neglected thinker who could re-enliven connections and debates within queer, feminist, and trans theory and politics. Utilizing recent historiographies of queer and feminist theory, I imagine what it would mean to hold on to the figure of the lesbian as a figure for queer-trans-feminist politics rather than render the lesbian anachronistic. I then explore the implications of Wittig's notion that "lesbians are not women" for a queer-trans-feminism. I argue that Wittig's critique of the language of the social sciences offers queer-trans-feminist scholars a source for contemporary self-critique and coalition.

  3. A first-in-man phase 1 trial for long-acting TransCon Growth Hormone.

    Science.gov (United States)

    Gilfoyle, David; Mortensen, Eva; Christoffersen, Eva Dam; Leff, Jonathan A; Beckert, Michael

    2018-04-01

    TransCon growth hormone (GH) is a sustained-release inactive prodrug consisting of unmodified GH transiently bound to an inert carrier molecule designed to release fully active GH over a one-week period. This was a first-in-man phase 1 randomized trial was to evaluate the safety, tolerability, immunogenicity, pharmacokinetics (PK), and pharmacodynamics (PD) of a single dose of TransCon GH as compared to equivalent doses of daily GH (Omnitrope) or placebo in healthy adults. Forty-four healthy male adults were randomized to 4 cohorts of 11 subjects, distributed in a 7:2:2 ratio (TransCon GH: Omnitrope: placebo). A single injection of 4 possible TransCon GH doses (i.e., 0.04, 0.08, 0.16, or 0.24mg GH/kg/wk) or two different Omnitrope doses (i.e., 0.08 or 0.16mg GH/kg/wk divided into 7 equal daily doses) were administered with subjects evaluated for adverse events, immunogenicity, and GH and insulin-like growth factor-1 (IGF-1) levels. TransCon GH was well tolerated; no serious adverse events occurred, no injection site reaction differences between TransCon GH, Omnitrope, or placebo were identified, no nodules or lipoatrophy were reported, and no anti-GH binding antibodies or ECG changes were detected. Overall, the exposure of GH (C max ) and IGF-1 (AUC 0-168h ) following administration of equivalent doses of TransCon GH and Omnitrope were similar. GH and IGF-1 kinetics showed a dose-proportional increase following a single SC administration of TransCon GH and indicated that the prodrug is suitable for weekly administration. These results support advancement of TransCon GH to pediatric and adult GHD trials. Clinical trial registration numbers: NCT01010425 (clinicaltrials.gov). Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Viral Hepatitis and Thrombosis: A Narrative Review

    NARCIS (Netherlands)

    Squizzato, Alessandro; Gerdes, Victor E. A.

    2012-01-01

    Venous thromboembolism (VTE) is a multicausal disease. Among minor risk factors, acute infections in general are associated with a transient increased risk of VTE. However, acute hepatitis is usually not reported as a potential risk factor for VTE. Recent studies suggest a possible role of viral

  5. Effects of Trans-Resveratrol on hyperglycemia-induced abnormal spermatogenesis, DNA damage and alterations in poly (ADP-ribose) polymerase signaling in rat testis

    Energy Technology Data Exchange (ETDEWEB)

    Abdelali, Ala [Department of Anatomy, Faculty of Medicine, Kuwait University (Kuwait); Al-Bader, Maie [Department of Physiology, Faculty of Medicine, Kuwait University (Kuwait); Kilarkaje, Narayana, E-mail: knarayana@hsc.edu.kw [Department of Anatomy, Faculty of Medicine, Kuwait University (Kuwait)

    2016-11-15

    Diabetes induces oxidative stress, DNA damage and alters several intracellular signaling pathways in organ systems. This study investigated modulatory effects of Trans-Resveratrol on type 1 diabetes mellitus (T1DM)-induced abnormal spermatogenesis, DNA damage and alterations in poly (ADP-ribose) polymerase (PARP) signaling in rat testis. Trans-Resveratrol administration (5mg/kg/day, ip) to Streptozotocin-induced T1DM adult male Wistar rats from day 22–42 resulted in recovery of induced oxidative stress, abnormal spermatogenesis and inhibited DNA synthesis, and led to mitigation of 8-hydroxy-2'-deoxyguanosine formation in the testis and spermatozoa, and DNA double-strand breaks in the testis. Trans-Resveratrol aggravated T1DM-induced up-regulation of aminoacyl tRNA synthetase complex-interacting multifunctional protein 2 expression; however, it did not modify the up-regulated total PARP and down-regulated PARP1 expressions, but recovered the decreased SirT1 (Sirtuin 1) levels in T1DM rat testis. Trans-Resveratrol, when given alone, reduced the poly (ADP-ribosyl)ation (pADPr) process in the testis due to an increase in PAR glycohydrolase activity, but when given to T1DM rats it did not affect the pADPr levels. T1DM with or without Trans-Resveratrol did not induce nuclear translocation of apoptosis-inducing factor and the formation of 50 kb DNA breaks, suggesting to the lack of caspase-3-independent cell death called parthanatos. T1DM with or without Trans-Resveratrol did not increase necrotic cell death in the testis. Primary spermatocytes, Sertoli cells, Leydig cells and intra-testicular vessels showed the expression of PARP pathway related proteins. In conclusion, Trans-Resveratrol mitigates T1DM-induced sperm abnormality and DNA damage, but does not significantly modulate PARP signaling pathway, except the SirT1 expression, in the rat testis. - Highlights: • Resveratrol inhibits diabetes-induced abnormal sperm morphogenesis • Resveratrol recovers

  6. Effects of Trans-Resveratrol on hyperglycemia-induced abnormal spermatogenesis, DNA damage and alterations in poly (ADP-ribose) polymerase signaling in rat testis

    International Nuclear Information System (INIS)

    Abdelali, Ala; Al-Bader, Maie; Kilarkaje, Narayana

    2016-01-01

    Diabetes induces oxidative stress, DNA damage and alters several intracellular signaling pathways in organ systems. This study investigated modulatory effects of Trans-Resveratrol on type 1 diabetes mellitus (T1DM)-induced abnormal spermatogenesis, DNA damage and alterations in poly (ADP-ribose) polymerase (PARP) signaling in rat testis. Trans-Resveratrol administration (5mg/kg/day, ip) to Streptozotocin-induced T1DM adult male Wistar rats from day 22–42 resulted in recovery of induced oxidative stress, abnormal spermatogenesis and inhibited DNA synthesis, and led to mitigation of 8-hydroxy-2'-deoxyguanosine formation in the testis and spermatozoa, and DNA double-strand breaks in the testis. Trans-Resveratrol aggravated T1DM-induced up-regulation of aminoacyl tRNA synthetase complex-interacting multifunctional protein 2 expression; however, it did not modify the up-regulated total PARP and down-regulated PARP1 expressions, but recovered the decreased SirT1 (Sirtuin 1) levels in T1DM rat testis. Trans-Resveratrol, when given alone, reduced the poly (ADP-ribosyl)ation (pADPr) process in the testis due to an increase in PAR glycohydrolase activity, but when given to T1DM rats it did not affect the pADPr levels. T1DM with or without Trans-Resveratrol did not induce nuclear translocation of apoptosis-inducing factor and the formation of 50 kb DNA breaks, suggesting to the lack of caspase-3-independent cell death called parthanatos. T1DM with or without Trans-Resveratrol did not increase necrotic cell death in the testis. Primary spermatocytes, Sertoli cells, Leydig cells and intra-testicular vessels showed the expression of PARP pathway related proteins. In conclusion, Trans-Resveratrol mitigates T1DM-induced sperm abnormality and DNA damage, but does not significantly modulate PARP signaling pathway, except the SirT1 expression, in the rat testis. - Highlights: • Resveratrol inhibits diabetes-induced abnormal sperm morphogenesis • Resveratrol recovers

  7. TransDetect Identifies a New Regulatory Module Controlling Phosphate Accumulation.

    Science.gov (United States)

    Pal, Sikander; Kisko, Mushtak; Dubos, Christian; Lacombe, Benoit; Berthomieu, Pierre; Krouk, Gabriel; Rouached, Hatem

    2017-10-01

    Identifying transcription factor (TFs) cooperation controlling target gene expression is still an arduous challenge. The accuracy of current methods at genome scale significantly drops with the increase in number of genes, which limits their applicability to more complex genomes, like animals and plants. Here, we developed an algorithm, TransDetect, able to predict TF combinations controlling the expression level of a given gene. TransDetect was used to identify novel TF modules regulating the expression of Arabidopsis ( Arabidopsis thaliana ) phosphate transporter PHO1;H3 comprising MYB15, MYB84, bHLH35, and ICE1. These TFs were confirmed to interact between themselves and with the PHO1;H3 promoter. Phenotypic and genetic analyses of TF mutants enable the organization of these four TFs and PHO1;H3 in a new gene regulatory network controlling phosphate accumulation in zinc-dependent manner. This demonstrates the potential of TransDetect to extract directionality in nondynamic transcriptomes and to provide a blueprint to identify gene regulatory network involved in a given biological process. © 2017 American Society of Plant Biologists. All Rights Reserved.

  8. Trans-Kullo jagatakse tükkideks / Kadrin Karner

    Index Scriptorium Estoniae

    Karner, Kadrin

    2008-01-01

    Primos OÜ omanik ja Trans-Kullo osanik Endel Siff ütles, et Trans-Kullo on aktsionäride erinevate ärihuvide tõttu läinud jagunemisele, mis võib lõppeda ettevõtte likvideerimisega. Lisa: Trans-Kullo

  9. Sexual desire in trans persons: associations with sex reassignment treatment.

    Science.gov (United States)

    Wierckx, Katrien; Elaut, Els; Van Hoorde, Birgit; Heylens, Gunter; De Cuypere, Griet; Monstrey, Stan; Weyers, Steven; Hoebeke, Piet; T'Sjoen, Guy

    2014-01-01

    Sex steroids and genital surgery are known to affect sexual desire, but little research has focused on the effects of cross-sex hormone therapy and sex reassignment surgery on sexual desire in trans persons. This study aims to explore associations between sex reassignment therapy (SRT) and sexual desire in a large cohort of trans persons. A cross-sectional single specialized center study including 214 trans women (male-to-female trans persons) and 138 trans men (female-to-male trans persons). Questionnaires assessing demographics, medical history, frequency of sexual desire, hypoactive sexual desire disorder (HSDD), and treatment satisfaction. In retrospect, 62.4% of trans women reported a decrease in sexual desire after SRT. Seventy-three percent of trans women never or rarely experienced spontaneous and responsive sexual desire. A third reported associated personal or relational distress resulting in a prevalence of HSDD of 22%. Respondents who had undergone vaginoplasty experienced more spontaneous sexual desire compared with those who planned this surgery but had not yet undergone it (P = 0.03). In retrospect, the majority of trans men (71.0%) reported an increase in sexual desire after SRT. Thirty percent of trans men never or rarely felt sexual desire; 39.7% from time to time, and 30.6% often or always. Five percent of trans men met the criteria for HSDD. Trans men who were less satisfied with the phalloplasty had a higher prevalence of HSDD (P = 0.02). Trans persons who were more satisfied with the hormonal therapy had a lower prevalence of HSDD (P = 0.02). HSDD was more prevalent in trans women compared with trans men. The majority of trans women reported a decrease in sexual desire after SRT, whereas the opposite was observed in trans men. Our results show a significant sexual impact of surgical interventions and both hormonal and surgical treatment satisfaction on the sexual desire in trans persons. © 2013 International Society for Sexual

  10. Viral Interference and Persistence in Mosquito-Borne Flaviviruses

    Directory of Open Access Journals (Sweden)

    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.

  11. Labor epidural analgesia is independent risk factor for neonatal pyrexia.

    Science.gov (United States)

    Agakidis, Charalampos; Agakidou, Eleni; Philip Thomas, Sumesh; Murthy, Prashanth; John Lloyd, David

    2011-09-01

    To explore whether epidural analgesia (EA) in labor is independent risk factor for neonatal pyrexia after controlling for intrapartum pyrexia. Retrospective observational study of 480 consecutive term singleton infants born to mothers who received EA in labor (EA group) and 480 term infants delivered to mothers who did not receive EA (NEA group). Mothers in the EA group had significantly higher incidence of intrapartum pyrexia [54/480 (11%) vs. 4/480 (0.8%), OR = 15.1, p neonatal pyrexia [68/480 (14.2%) vs. 15/480 (3.1%), OR = 5.1, p Neonates in the EA group had a median duration of pyrexia of 1 h (maximum 5 h) with a peak temperature within 1 h. Stepwise logistic regression analysis showed that maternal EA was independent risk factor for neonatal pyrexia (>37.5°C) after controlling for intrapartum pyrexia (>37.9°C) and other confounders (OR = 3.44, CI = 1.9-6.3, p neonates. It is unnecessary to investigate febrile offspring of mothers who have had epidurals unless pyrexia persists for longer than 5 h or other signs or risk factors for neonatal sepsis are present.

  12. Starch plus sunflower oil addition to the diet of dry dairy cows results in a trans-11 to trans-10 shift of biohydrogenation.

    Science.gov (United States)

    Zened, A; Enjalbert, F; Nicot, M C; Troegeler-Meynadier, A

    2013-01-01

    Trans fatty acids (FA), exhibit different biological properties. Among them, cis-9,trans-11 conjugated linoleic acid has some interesting putative health properties, whereas trans-10,cis-12 conjugated linoleic acid has negative effects on cow milk fat production and would negatively affect human health. In high-yielding dairy cows, a shift from trans-11 to trans-10 pathway of biohydrogenation (BH) can occur in the rumen of cows receiving high-concentrate diets, especially when the diet is supplemented with unsaturated fat sources. To study this shift, 4 rumen-fistulated nonlactating Holstein cows were assigned to a 4×4 Latin square design with 4 different diets during 4 periods. Cows received 12 kg of dry matter per day of 4 diets based on corn silage during 4 successive periods: a control diet (22% starch, diet supplemented with wheat plus barley (35% starch, diet supplemented with 5% of sunflower oil (20% starch, 7.6% crude fat), and a high-starch plus sunflower oil diet (33% starch, 7.3% crude fat). Five hours after feeding, proportions of trans-11 BH isomers greatly increased in the rumen content with the addition of sunflower oil, without change in ruminal pH compared with the control diet. Addition of starch to the control diet had no effect on BH pathways but decreased ruminal pH. The addition of a large amount of starch in association with sunflower oil increased trans-10 FA at the expense of trans-11 FA in the rumen content, revealing a trans-11 to trans-10 shift. Interestingly, with this latter diet, ruminal pH did not change compared with a single addition of starch. This trans-11 to trans-10 shift occurred progressively, after a decrease in the proportion of trans-11 FA in the rumen, suggesting that this shift could result from a dysbiosis in the rumen in favor of trans-10-producing bacteria at the expense of those producing trans-11 or a modification of bacterial activities. Copyright © 2013 American Dairy Science Association. Published by Elsevier

  13. 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

  14. Analysis of Trans Fat in Edible Oils with Cooking Process

    Science.gov (United States)

    Song, Juhee; Park, Joohyeok; Jung, Jinyeong; Lee, Chankyu; Gim, Seo Yeoung; Ka, HyeJung; Yi, BoRa; Kim, Mi-Ja; Kim, Cho-il

    2015-01-01

    Trans fat is a unsaturated fatty acid with trans configuration and separated double bonds. Analytical methods have been introduced to analyze trans fat content in foods including infrared (IR) spectroscopy, gas chromatography (GC), Fourier transform-infrared (FT-IR) spectroscopy, reverses-phase silver ion high performance liquid chromatography, and silver nitrate thin layer chromatography. Currently, FT-IR spectroscopy and GC are mostly used methods. Trans fat content in 6 vegetable oils were analyzed and processing effects including baking, stir-frying, pan-frying, and frying on the formation of trans fat in corn oil was evaluated by GC. Among tested vegetable oils, corn oil has 0.25 g trans fat/100 g, whereas other oils including rapeseed, soybean, olive, perilla, and sesame oils did not have detectable amount of trans fat content. Among cooking methods, stir-frying increased trans fat in corn oil whereas baking, pan-frying, and frying procedures did not make changes in trans fat content compared to untreated corn oils. However, the trans fat content was so low and food label can be declared as ‘0’ trans based on the regulation of Ministry of Food ad Drug Safety (MFDS) (edible oil). PMID:26483890

  15. Sodium 4-phenylbutyrate prevents murine dietary steatohepatitis caused by trans-fatty acid plus fructose.

    Science.gov (United States)

    Morinaga, Maki; Kon, Kazuyoshi; Saito, Hiroaki; Arai, Kumiko; Kusama, Hiromi; Uchiyama, Akira; Yamashina, Shunhei; Ikejima, Kenichi; Watanabe, Sumio

    2015-11-01

    Excess consumption of trans-fatty acid could increase the risk of non-alcoholic steatohepatitis (NASH); however, treatment targeting trans-fatty acid-induced NASH has not been examined. Here we focused on the influence of trans-fatty acid intake on endoplasmic reticulum (ER) stress in hepatocytes, so we investigated the effect of the chemical chaperone 4-phenylbutyric acid (PBA), on trans-fatty acid-caused steatohepatitis using diabetic KK-A(y) mice. Elaidic acid (EA, trans-fatty acid) alone did not cause definitive liver injury. In contrast, EA plus low-dose fructose induced extensive apoptosis in hepatocytes with severe fat accumulation. EA plus fructose significantly increased ER stress markers such as glucose-regulated protein 78 (GRP78), eukaryotic initiation factor 2α (eIF2α) and phosphorylated c-jun N-terminal kinase (JNK), while PBA significantly reduced this response. In vitro, EA promoted expression of GRP78 and phosphorylation of eIF2α in primary-cultured hepatocytes. EA also increased hepatocellular susceptibility to low-dose tert-butyl hydroperoxide. Treatment with PBA significantly reduced these responses. In conclusion, EA potentiates susceptibly to non-hazardous dose of fructose, and increases ER and oxidative stress. PBA improved steatohepatitis induced by EA plus fructose through amelioration of ER stress. Therefore, ER stress-targeted therapy using a chemical chaperone is a promising novel strategy for trans-fatty acid-induced steatohepatitis.

  16. VirSorter: mining viral signal from microbial genomic data

    Directory of Open Access Journals (Sweden)

    Simon Roux

    2015-05-01

    Full Text Available Viruses of microbes impact all ecosystems where microbes drive key energy and substrate transformations including the oceans, humans and industrial fermenters. However, despite this recognized importance, our understanding of viral diversity and impacts remains limited by too few model systems and reference genomes. One way to fill these gaps in our knowledge of viral diversity is through the detection of viral signal in microbial genomic data. While multiple approaches have been developed and applied for the detection of prophages (viral genomes integrated in a microbial genome, new types of microbial genomic data are emerging that are more fragmented and larger scale, such as Single-cell Amplified Genomes (SAGs of uncultivated organisms or genomic fragments assembled from metagenomic sequencing. Here, we present VirSorter, a tool designed to detect viral signal in these different types of microbial sequence data in both a reference-dependent and reference-independent manner, leveraging probabilistic models and extensive virome data to maximize detection of novel viruses. Performance testing shows that VirSorter’s prophage prediction capability compares to that of available prophage predictors for complete genomes, but is superior in predicting viral sequences outside of a host genome (i.e., from extrachromosomal prophages, lytic infections, or partially assembled prophages. Furthermore, VirSorter outperforms existing tools for fragmented genomic and metagenomic datasets, and can identify viral signal in assembled sequence (contigs as short as 3kb, while providing near-perfect identification (>95% Recall and 100% Precision on contigs of at least 10kb. Because VirSorter scales to large datasets, it can also be used in “reverse” to more confidently identify viral sequence in viral metagenomes by sorting away cellular DNA whether derived from gene transfer agents, generalized transduction or contamination. Finally, VirSorter is made

  17. VirSorter: mining viral signal from microbial genomic data

    Science.gov (United States)

    Roux, Simon; Enault, Francois; Hurwitz, Bonnie L.

    2015-01-01

    Viruses of microbes impact all ecosystems where microbes drive key energy and substrate transformations including the oceans, humans and industrial fermenters. However, despite this recognized importance, our understanding of viral diversity and impacts remains limited by too few model systems and reference genomes. One way to fill these gaps in our knowledge of viral diversity is through the detection of viral signal in microbial genomic data. While multiple approaches have been developed and applied for the detection of prophages (viral genomes integrated in a microbial genome), new types of microbial genomic data are emerging that are more fragmented and larger scale, such as Single-cell Amplified Genomes (SAGs) of uncultivated organisms or genomic fragments assembled from metagenomic sequencing. Here, we present VirSorter, a tool designed to detect viral signal in these different types of microbial sequence data in both a reference-dependent and reference-independent manner, leveraging probabilistic models and extensive virome data to maximize detection of novel viruses. Performance testing shows that VirSorter’s prophage prediction capability compares to that of available prophage predictors for complete genomes, but is superior in predicting viral sequences outside of a host genome (i.e., from extrachromosomal prophages, lytic infections, or partially assembled prophages). Furthermore, VirSorter outperforms existing tools for fragmented genomic and metagenomic datasets, and can identify viral signal in assembled sequence (contigs) as short as 3kb, while providing near-perfect identification (>95% Recall and 100% Precision) on contigs of at least 10kb. Because VirSorter scales to large datasets, it can also be used in “reverse” to more confidently identify viral sequence in viral metagenomes by sorting away cellular DNA whether derived from gene transfer agents, generalized transduction or contamination. Finally, VirSorter is made available through the i

  18. Antiretroviral treatment adherence as a mediating factor between psychosocial variables and HIV viral load.

    Science.gov (United States)

    Attonito, Jennifer; Dévieux, Jessy G; Lerner, Brenda D G; Hospital, Michelle M; Rosenberg, Rhonda

    2014-01-01

    Psychosocial factors may directly impact HIV health measures such as viral load (VL) whether or not patients are taking antiretroviral treatment (ART) consistently. Structural equation modeling plus Baron and Kenny's (1986) four-step approach were used to test a mediated model predicting VL among 246 HIV-infected adults who were on ART. Exogenous variables were social support, barriers to adherence, and stress. Moderators were alcohol use, marijuana use, and neurocognitive impairment. A small positive association between marijuana use and ART adherence approached significance. Only barriers to adherence predicted a decrease in adherence rates and an increase in VL. No other factors were significantly associated with either VL or adherence, and no interaction effects between exogenous variables and moderators were identified. The association between barriers to adherence and VL was partially mediated by ART adherence. Findings provide modest support for a direct link between psychosocial variables and a virologic response to ART. Copyright © 2014 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

  19. Ácidos graxos trans: implicações nutricionais e fontes na dieta Trans fatty acids: nutritional implications and sources in the diet

    Directory of Open Access Journals (Sweden)

    Clayton Antunes Martin

    2004-09-01

    Full Text Available Este artigo revisa as principais fontes de ácidos graxos trans na dieta e as implicações nutricionais da ingestão elevada destes isômeros. São apresentados resumidamente os métodos analíticos utilizados na identificação e quantificação dos ácidos graxos trans, sendo abordados as suas vantagens e desvantagens. Os alimentos que empregam gordura parcialmente hidrogenada na sua produção, são fontes importantes de isômeros trans na dieta da maior parte da população em países industrializados. Este estudo compara os níveis de ácidos graxos trans em gorduras hidrogenadas, margarinas e batatas frita, analisados em diversos países, incluindo o Brasil. Esta avaliação indica a presença de níveis elevados de isômeros trans em alimentos produzidos no Brasil.This article review the main sources of trans fatty acids in the diet and nutritional implications of the high intake of these isomers. Analytical methods for the identification and quantification of trans fatty acids are presented briefly with regard to advantages and drawbacks of each method. Foods make with partially hidrogenated fats are important sources of trans isomers in the diets of most people in industrialized countries. It is made a comparison between levels of trans fatty acids in shortenings, margarines and potato chips evaluated in Brazil and in other countries. High levels of trans isomers are noted in Brazilian foods.

  20. Trans-nationalisation Processes in the Ukrainian Economy

    OpenAIRE

    Bolharova Natalya K.; Panevnyk Tetyana M.

    2013-01-01

    The article considers main processes of trans-nationalisation of Ukrainian economy, identifies specific features of trans-national production and explains some theoretical aspects of these issues. It provides main stages of theoretical comprehension of activity of trans-national corporations (TNC), specific features of the theory of competitive advantages of TNC and specifies the basic ones of them. The article conducts analysis of flows of direct foreign investments into the Ukrainian econom...

  1. Finding a Trans-Affirmative Provider: Challenges Faced by Trans and Gender Diverse Psychologists and Psychology Trainees.

    Science.gov (United States)

    Dickey, Lore M; Singh, Anneliese A

    2017-08-01

    This article explores some of the challenges faced by trans and gender diverse (TGD) individuals who not only are attempting to access trans-affirmative care, but who are also members of the very profession from which they are seeking services. The authors explore challenges related to finding supervision, accessing care for assessment services, and finding a provider for personal counseling. With each example, the authors unpack the challenges and also address the implications for training for all involved. Based on these challenges that TGD psychologists and trainees face in attempting to access care, the authors provide recommendations related to trans-affirmative training for psychologists. © 2017 Wiley Periodicals, Inc.

  2. 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.

  3. Anti-inflammatory effects of compounds alpha-humulene and (-)-trans-caryophyllene isolated from the essential oil of Cordia verbenacea.

    Science.gov (United States)

    Fernandes, Elizabeth S; Passos, Giselle F; Medeiros, Rodrigo; da Cunha, Fernanda M; Ferreira, Juliano; Campos, Maria M; Pianowski, Luiz F; Calixto, João B

    2007-08-27

    This study evaluated the anti-inflammatory properties of two sesquiterpenes isolated from Cordia verbenacea's essential oil, alpha-humulene and (-)-trans-caryophyllene. Our results revealed that oral treatment with both compounds displayed marked inhibitory effects in different inflammatory experimental models in mice and rats. alpha-humulene and (-)-trans-caryophyllene were effective in reducing platelet activating factor-, bradykinin- and ovoalbumin-induced mouse paw oedema, while only alpha-humulene was able to diminish the oedema formation caused by histamine injection. Also, both compounds had important inhibitory effects on the mouse and rat carrageenan-induced paw oedema. Systemic treatment with alpha-humulene largely prevented both tumor necrosis factor-alpha (TNFalpha) and interleukin-1beta (IL-1beta) generation in carrageenan-injected rats, whereas (-)-trans-caryophyllene diminished only TNFalpha release. Furthermore, both compounds reduced the production of prostaglandin E(2) (PGE(2)), as well as inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) expression, induced by the intraplantar injection of carrageenan in rats. The anti-inflammatory effects of alpha-humulene and (-)-trans-caryophyllene were comparable to those observed in dexamethasone-treated animals, used as positive control drug. All these findings indicate that alpha-humulene and (-)-trans-caryophyllene, derived from the essential oil of C. verbenacea, might represent important tools for the management and/or treatment of inflammatory diseases.

  4. Trans issues in Liz Lochhead's 'Not Changed'

    OpenAIRE

    Kaličanin Milena M.

    2017-01-01

    The paper is divided into four sections. In the first section entitled 'Introducing and Defining Trans (Issues)', the basic terms of transgender, transvestite, and transsexual are defined by relying on Stryker's Transgender History (2008). The second part of the paper, 'Trans Studies: In-Between Feminist and Queer Theory?', places transgender studies into an academic context by referring to the theoretical framework provided by trans theorists Stryker, Stone, and Ranck who unanimously claim t...

  5. Trans fats in New Zealand: time for labelling regulations?

    Science.gov (United States)

    Gladding, Patrick; Benatar, Jocelyne R

    2007-11-09

    Trans fats (trans fatty acids) are commonly used for deep frying in restaurants and in the fast food, snack food, fried food, and baked goods industries, often to extend the shelf life of foods. However they are widely considered to be harmful to health. Trans fats were banned in New York City restaurants from 1 July 2007, and there is growing vocal opposition to trans fats in the European Union. Denmark became the first country, in March 2003, to introduce laws regulating the content of trans fats in food (maximum of 2% of edible fats and oils). What are trans fats, what harm do they cause, and should New Zealand also consider imposing mandatory regulations on their use in food? This article explores the issues.

  6. Clinical Factors and Viral Load Influencing Severity of Acute Hepatitis A.

    Science.gov (United States)

    Lee, Hyun Woong; Chang, Dong-Yeop; Moon, Hong Ju; Chang, Hye Young; Shin, Eui-Cheol; Lee, June Sung; Kim, Kyung-Ah; Kim, Hyung Joon

    2015-01-01

    Clinical manifestations of hepatitis A virus (HAV) infection vary from mild to fulminant hepatic failure (FHF) in adults. We investigated the relationship between laboratory findings, including viral load, and clinical outcomes in patients with acute hepatitis A (AHA) and evaluated predictive factors for severe acute hepatitis (s-AH). We analyzed the clinical manifestations of AHA in 770 patients. Patients with a prothrombin time (PT) of less than 40% of normal were classified as s-AH and included 4 patients with FHF, 11 patients with acute renal failure, and 3 patients with prolonged jaundice (n = 128). Other patients were defined as mild acute hepatitis (m-AH) (n = 642). Serum samples were obtained from 48 patients with acute hepatitis A. Among them, 20 with s-AH, and 28 with m-AH, were tested for HAV RNA titer. In a multivariate analysis, age (HR = 1.042, P = 0.041), peak creatinine (HR = 4.014, P = 0.001), bilirubin (HR = 1.153, P = 0.003), alanine aminotransferase (ALT) (HR = 1.001, P hepatitis A.

  7. Clinical Factors and Viral Load Influencing Severity of Acute Hepatitis A

    Science.gov (United States)

    Lee, Hyun Woong; Chang, Dong-Yeop; Moon, Hong Ju; Chang, Hye Young; Shin, Eui-Cheol; Lee, June Sung; Kim, Kyung-Ah; Kim, Hyung Joon

    2015-01-01

    Background and Aims Clinical manifestations of hepatitis A virus (HAV) infection vary from mild to fulminant hepatic failure (FHF) in adults. We investigated the relationship between laboratory findings, including viral load, and clinical outcomes in patients with acute hepatitis A (AHA) and evaluated predictive factors for severe acute hepatitis (s-AH). Methods We analyzed the clinical manifestations of AHA in 770 patients. Patients with a prothrombin time (PT) of less than 40% of normal were classified as s-AH and included 4 patients with FHF, 11 patients with acute renal failure, and 3 patients with prolonged jaundice (n = 128). Other patients were defined as mild acute hepatitis (m-AH) (n = 642). Serum samples were obtained from 48 patients with acute hepatitis A. Among them, 20 with s-AH, and 28 with m-AH, were tested for HAV RNA titer. Results In a multivariate analysis, age (HR = 1.042, P = 0.041), peak creatinine (HR = 4.014, P = 0.001), bilirubin (HR = 1.153, P = 0.003), alanine aminotransferase (ALT) (HR = 1.001, Phepatitis A. PMID:26090677

  8. Physics of Trans-Planckian Gravity

    CERN Document Server

    Dvali, Gia; Germani, Cristiano

    2011-01-01

    We study aspects of the phenomenon of gravitational UV-self-completeness and its implications for deformations of Einstein gravity. In a ghost-free theory flowing to Einstein gravity in the IR trans-Planckian propagating quantum degrees of freedom cannot exist. The only physical meaning of a trans-Planckian pole is the one of a classical state (Black Hole) which is fully described by the light IR quantum degrees of freedom and gives exponentially-suppressed contributions to virtual processes. In this sense Einstein gravity is UV self-complete, although not Wilsonian. We show that this UV/IR correspondence puts a severe constraint on any attempt of conventional Wilsonian UV-completion of trans-Planckian gravity. In particular, there is no well-defined energy domain in which gravity could become asymptotically weak or safe.

  9. Is there such a thing as Tech Trans?

    DEFF Research Database (Denmark)

    Helms, Niels Henrik

    2009-01-01

    This short paper is an attempt to start a discussion on some basic issues within the concept of Tech Trans especially the relationship between flow and structure within the concept. The background to this paper is first of all an academic interest in the relationship between flow and structure...... explores the concept of Tech Trans, show rooms and innovation systems, and it suggests that the notion of Tech Trans should be defined in the fix point of vertical and horizontal innovation. Finally this paper suggests a mathematical formula for evaluating Tech Trans....

  10. Acetylcholinesterase Inhibition and Antioxidant Activity of N-trans-Caffeoyldopamine and N-trans-Feruloyldopamine

    Directory of Open Access Journals (Sweden)

    Muamer Dizdar

    2018-04-01

    Full Text Available Phenolic acids and their derivatives found in nature are well-known for their potential biological activity. In this study, two amides derived from trans-caffeic/ferulic acid and dopamine were synthesized and characterized by Fourier-transform infrared spectroscopy (FTIR, mass spectrometry, proton and carbon-13 nuclear magnetic resonance spectroscopy. The compounds were tested for the inhibition of acetylcholinesterase (AChE from Electrophorus electricus and for antioxidant activity by scavenging 2,2-diphenyl-1-pycrylhydrazyl free radical (DPPH• and 2,2′-azinobis(3-ethylbenzothiazoline-6-sulphonic acid radical cation (ABTS•+, reducing ferric ions, and ferrous ions chelation. N-trans-Feruloyldopamine displayed the highest inhibitory effect on AChE with half-maximal inhibitory concentration (IC50 values of 8.52 μM. In addition, an in silico study was done to determine the most favorable AChE cluster with the synthesized compounds. Further, these clusters were investigated for binding positions at the lowest free binding energy. Both synthesized hydroxycinnamates were found to be better antioxidants than the parent acids in in vitro tests applied. N-trans-Caffeoyldopamine showed the best antioxidant activity in the three tested methods—against non-biological stable free radicals IC50 5.95 μM for DPPH•, 0.24 μM for the ABTS•+ method, and for reducing power (ascorbic acid equivalent (AAE 822.45 μmol/mmol—while for chelation activity against Fe2+ ions N-trans-feruloyldopamine had slightly better antioxidant activity (IC50 3.17 mM.

  11. Viral tRNA Mimicry from a Biocommunicative Perspective

    Directory of Open Access Journals (Sweden)

    Ascensión Ariza-Mateos

    2017-12-01

    Full Text Available RNA viruses have very small genomes which limits the functions they can encode. One of the strategies employed by these viruses is to mimic key factors of the host cell so they can take advantage of the interactions and activities these factors typically participate in. The viral RNA genome itself was first observed to mimic cellular tRNA over 40 years ago. Since then researchers have confirmed that distinct families of RNA viruses are accessible to a battery of cellular factors involved in tRNA-related activities. Recently, potential tRNA-like structures have been detected within the sequences of a 100 mRNAs taken from human cells, one of these being the host defense interferon-alpha mRNA; these are then additional to the examples found in bacterial and yeast mRNAs. The mimetic relationship between tRNA, cellular mRNA, and viral RNA is the central focus of two considerations described below. These are subsequently used as a preface for a final hypothesis drawing on concepts relating to mimicry from the social sciences and humanities, such as power relations and creativity. Firstly, the presence of tRNA-like structures in mRNAs indicates that the viral tRNA-like signal could be mimicking tRNA-like elements that are contextualized by the specific carrier mRNAs, rather than, or in addition to, the tRNA itself, which would significantly increase the number of potential semiotic relations mediated by the viral signals. Secondly, and in particular, mimicking a host defense mRNA could be considered a potential new viral strategy for survival. Finally, we propose that mRNA’s mimicry of tRNA could be indicative of an ancestral intracellular conflict in which species of mRNAs invaded the cell, but from within. As the meaning of the mimetic signal depends on the context, in this case, the conflict that arises when the viral signal enters the cell can change the meaning of the mRNAs’ internal tRNA-like signals, from their current significance to that

  12. Illuminating structural proteins in viral "dark matter" with metaproteomics.

    Science.gov (United States)

    Brum, Jennifer R; Ignacio-Espinoza, J Cesar; Kim, Eun-Hae; Trubl, Gareth; Jones, Robert M; Roux, Simon; VerBerkmoes, Nathan C; Rich, Virginia I; Sullivan, Matthew B

    2016-03-01

    Viruses are ecologically important, yet environmental virology is limited by dominance of unannotated genomic sequences representing taxonomic and functional "viral dark matter." Although recent analytical advances are rapidly improving taxonomic annotations, identifying functional dark matter remains problematic. Here, we apply paired metaproteomics and dsDNA-targeted metagenomics to identify 1,875 virion-associated proteins from the ocean. Over one-half of these proteins were newly functionally annotated and represent abundant and widespread viral metagenome-derived protein clusters (PCs). One primarily unannotated PC dominated the dataset, but structural modeling and genomic context identified this PC as a previously unidentified capsid protein from multiple uncultivated tailed virus families. Furthermore, four of the five most abundant PCs in the metaproteome represent capsid proteins containing the HK97-like protein fold previously found in many viruses that infect all three domains of life. The dominance of these proteins within our dataset, as well as their global distribution throughout the world's oceans and seas, supports prior hypotheses that this HK97-like protein fold is the most abundant biological structure on Earth. Together, these culture-independent analyses improve virion-associated protein annotations, facilitate the investigation of proteins within natural viral communities, and offer a high-throughput means of illuminating functional viral dark matter.

  13. Pharyngitis - viral

    Science.gov (United States)

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

  14. Thiazolidinediones inhibit TNFα induction of PAI-1 independent of PPARγ activation

    International Nuclear Information System (INIS)

    Liu, H.B.; Hu, Y.S.; Medcalf, R.L.; Simpson, R.W.; Dear, A.E.

    2005-01-01

    Increased plasminogen activator inhibitor type 1 (PAI-1) levels are observed in endothelial cells stimulated by tumour necrosis factor α (TNFα). Thiazolidinediones (TZDs) may inhibit elevated endothelial cell PAI-1 accounting, in part, for the putative atheroprotective effects of TZDs. In an endothelial cell line, Rosiglitazone (RG) and Pioglitazone (PG) inhibited induction of PAI-1 by TNFα. The specific peroxisome proliferator-activated receptor γ (PPARγ) inhibitor, SR-202, failed to modulate this effect. RG also inhibited the effect of TNFα on a reporter gene construct harbouring the proximal PAI-1 promoter and PAI-1 mRNA in cells co-transfected with a dominant-negative PPARγ construct. RG and PG attenuated TNFα-mediated induction of trans-acting factor(s) Nur77/Nurr1 and binding of nuclear proteins (NP) to the cis-acting element (NBRE). SR-202 failed to modulate these effects. The observations suggest TZDs inhibit TNFα-mediated PAI-1 induction independent of inducible PPARγ activation and this may involve in the modulation of Nur77/Nurr1 expression and NP binding to the PAI-1 NBRE

  15. Trans issues in Liz Lochhead's 'Not Changed'

    Directory of Open Access Journals (Sweden)

    Kaličanin Milena M.

    2017-01-01

    Full Text Available The paper is divided into four sections. In the first section entitled 'Introducing and Defining Trans (Issues', the basic terms of transgender, transvestite, and transsexual are defined by relying on Stryker's Transgender History (2008. The second part of the paper, 'Trans Studies: In-Between Feminist and Queer Theory?', places transgender studies into an academic context by referring to the theoretical framework provided by trans theorists Stryker, Stone, and Ranck who unanimously claim that transgender studies should have a place of its own within the academia and that trans theory should solely be written by transsexuals. These ideas are applied in the interpretation of Lochhead's story 'Not Changed' in the third segment of the paper. The critical insights of Butler (Gender Trouble, 1990; Undoing Gender, 2004 are found to be most helpful in the interpretation of Lochhead's story about Michael who has willingly undergone Hormone Replacement Therapy to become transsexual Michele. Finally, in the concluding remarks, Lochhead's story is viewed as a trans woman manifesto, urging both non-transsexual and transsexual persons to embrace new beginnings in their relationship.

  16. Trans-nationalisation Processes in the Ukrainian Economy

    Directory of Open Access Journals (Sweden)

    Bolharova Natalya K.

    2013-12-01

    Full Text Available The article considers main processes of trans-nationalisation of Ukrainian economy, identifies specific features of trans-national production and explains some theoretical aspects of these issues. It provides main stages of theoretical comprehension of activity of trans-national corporations (TNC, specific features of the theory of competitive advantages of TNC and specifies the basic ones of them. The article conducts analysis of flows of direct foreign investments into the Ukrainian economy. It shows distribution of direct foreign investments into Ukraine by main countries-investors, regions-recipients and types of economic activity. It conducts review and analysis of the modern state of trans-national corporations of foreign origin in the Ukrainian market. It considers functioning of domestic TNC in Ukraine and main tendencies of entering of Ukrainian companies into the world environment and also identifies directions of further development of these phenomena. Prospects of further studies in this direction are identification of the degree of trans-nationalisation processes in the Ukrainian economy and identification of the positive effect, in particular, synergy from integration and globalisation.

  17. Blood omega-3 and trans fatty acids in middle-aged acute coronary syndrome patients.

    Science.gov (United States)

    Harris, William S; Reid, Kimberly J; Sands, Scott A; Spertus, John A

    2007-01-15

    We tested the hypothesis that lower blood omega-3 (omega-3) fatty acids (FAs) and/or higher trans FAs are associated with the risk of an acute coronary syndrome (ACS). Higher levels of omega-3 FA have been associated with decreased risk of sudden cardiac death. However, their association with ACS risk is unclear. Although higher self-reported intakes of trans FAs have been linked to increased coronary risk, the association between blood levels of trans FA and ACS risk is also unknown. We analyzed the FA composition of whole blood from 94 subjects with ACS and 94 age-, gender-, and race-matched controls. Omega-3 and trans FA associations with ACS were assessed using multivariable models after adjusting for smoking status, alcohol use, diabetes, body mass index, serum lipids, and history of myocardial infarction or revascularization. Subjects' mean age was 47 years, 54% were men, and 80% were Caucasian. Whole blood long-chain omega-3 FA (eicosapentaenoic acid [EPA] plus docosahexaenoic acid [DHA]) content was 29% lower in patients than in controls (1.7 +/- 0.9% vs 2.4 +/- 1.4%, p ACS, but higher blood trans FA content is not. Blood EPA + DHA may serve as a new, modifiable risk factor for ACS.

  18. Coevolution within a transcriptional network by compensatory trans and cis mutations

    KAUST Repository

    Kuo, D.

    2010-10-26

    Transcriptional networks have been shown to evolve very rapidly, prompting questions as to how such changes arise and are tolerated. Recent comparisons of transcriptional networks across species have implicated variations in the cis-acting DNA sequences near genes as the main cause of divergence. What is less clear is how these changes interact with trans-acting changes occurring elsewhere in the genetic circuit. Here, we report the discovery of a system of compensatory trans and cis mutations in the yeast AP-1 transcriptional network that allows for conserved transcriptional regulation despite continued genetic change. We pinpoint a single species, the fungal pathogen Candida glabrata, in which a trans mutation has occurred very recently in a single AP-1 family member, distinguishing it from its Saccharomyces ortholog. Comparison of chromatin immunoprecipitation profiles between Candida and Saccharomyces shows that, despite their different DNA-binding domains, the AP-1 orthologs regulate a conserved block of genes. This conservation is enabled by concomitant changes in the cis-regulatory motifs upstream of each gene. Thus, both trans and cis mutations have perturbed the yeast AP-1 regulatory system in such a way as to compensate for one another. This demonstrates an example of “coevolution” between a DNA-binding transcription factor and its cis-regulatory site, reminiscent of the coevolution of protein binding partners.

  19. [Trans fatty acids in the nutrition of children with neurological disorders].

    Science.gov (United States)

    Cortés, E; Aguilar, M J; Rizo, M M; Hidalgo, M J

    2013-01-01

    Trans-fatty acids are present in various foods, being the only source of the same in humans. Its presence in high concentrations is a risk factor for health, being involved in a series of events, cardiovascular, inflammatory, etc. Therefore, steps have been taken for its decrease in the diet. The aim is to determine serum and phospholipids of membranes in healthy children and neurological alterations. It has analyzed the fatty acids trans in 34 healthy children and 374 with various neurological pathologies. Serum and blood cells, making the lipid extraction, samples have been separation of the phospholipids of cells membranes, methylation of fatty acids, separation by gas chromatography and quantification using mass detector. The data have been processed statistically. The distribution of trans fatty acids and their sum is not normally distributed, so its nonparemetric tests were used. The values are higher than in serum phospholipids and membrane with a weak but significant correlation. The tC18: 1 is in a double proportion in children with neurological disorders in healthy children, both in serum and membrane phospholipids, with significant differences. The highest proportion of trans-fatty acids in the group of children with neurological disorders is caused no doubt by an increase in intake, due to less adequate food. Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.

  20. 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 ...

  1. Formation of trans fats during food preparation.

    Science.gov (United States)

    Przybylski, Oman; Aladedunye, Felix A

    2012-01-01

    An investigation was completed to determine how typical cooking procedures used in food preparation, such as baking and stir-frying, affect trans fats formation. Canola oil was used as the main fat ingredient. Zucchini cake and gingersnap cookies were baked at 180o C and 200o C, while stir-fried chicken was prepared at 200o C and 275o C. The lipids from the food were extracted following the Folch procedure, and analyzed for trans fatty acids according to ISO official method 15304. Minimal changes were observed in the amount of trans fats during baking. Application of extreme temperatures during baking, which caused carbonization of the outer layer of products, yielded an insignificant increase in the amount of trans isomers. As with baking, stir-frying did not result in significant isomerization of the fatty acids, even when the oil was heated to 275o C and smoking heavily before the food was placed in it. Irrespective of the cooking procedure, linolenic acid was the most prone to isomerization with the highest amount of trans isomers formation. Baking and stir-frying at normal and/or extreme temperatures do not significantly affect the amounts of trans fats. Likewise, heating oil to the smoking point during stir-frying may decrease the amount of polyunsaturated fatty acids because of oxidative degradation.

  2. Binge-type behavior in rats consuming trans-fat-free shortening.

    Science.gov (United States)

    Wojnicki, F H E; Charny, G; Corwin, R L W

    2008-07-05

    Studies from this and another laboratory involving an animal model of binge-type behavior have used vegetable shortening containing trans-fats. Due to reformulations by vegetable shortening manufacturers to remove trans-fats from their products, only trans-fat-free shortenings are now available. The goal of the present study was to assess binge-type behavior in rats with trans-fat and trans-free vegetable shortening. Trans-fat-free shortening was provided to three different groups of non-food-deprived male Sprague Dawley rats on different schedules of access: continuous access (24 h/day-7 days/week), daily access (1 h every day), and intermittent access (1 h on Mondays, Wednesdays, Fridays). Trans-fat shortening was provided to a fourth group on the intermittent access schedule. A fifth group had no shortening access (chow only). Both intermittent groups (trans-fat-free and trans-fat) consumed significantly more shortening during the 1-h period of availability than did the daily group, and there was no difference in shortening intakes between the intermittent groups. These results are identical to previous reports of binge-type behavior in rats using this model. Thus, binge-type behavior in the present behavioral model depends upon the schedule of access, not the presence of trans-fats in the shortening.

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

    Science.gov (United States)

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

    2018-01-01

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

  4. Influence of Malnutrition on Adverse Outcome in Children with Confirmed or Probable Viral Encephalitis: A Prospective Observational Study

    Directory of Open Access Journals (Sweden)

    Priyanka Singh

    2015-01-01

    Full Text Available A prospective observational study was conducted in a tertiary care teaching hospital from August 2008 to August 2009 to explore the independent predictors of adverse outcome in the patients with confirmed/probable viral encephalitis. The primary outcome variable was the incidence of adverse outcomes defined as death or severe neurological deficit such as loss of speech, motor deficits, behavioural problems, blindness, and cognitive impairment. Patients with confirmed or probable viral encephalitis were classified into two groups based on their Z-score of weight-for-age as per WHO growth charts. Group I. Patients with confirmed or probable viral encephalitis with weight-for-age (W/A Z-scores below −2SD were classified as undernourished. Group II. Patients with confirmed or probable viral encephalitis were classified as having normal nutritional status (weight-for-age Z-score >−2SD. A total of 114 patients were classified as confirmed or probable viral encephalitis based on detailed investigations. On multivariate logistic regression, undernutrition (adjusted OR: 5.05; 95% CI: 1.92 to 13.44 and requirement of ventilation (adjusted OR: 6.75; 95% CI: 3.63 to 77.34 were independent predictors of adverse outcomes in these patients. Thus, the results from our study highlight that the association between undernutrition and adverse outcome could be extended to the patients with confirmed/probable viral encephalitis.

  5. Queratitis infecciosa no viral: factores predisponentes, agentes etiológicos y diagnóstico de laboratorio Non viral infectious keratitis: predisposing factors, etiologic agents and laboratory diagnosis

    Directory of Open Access Journals (Sweden)

    Federico Nicola

    2005-12-01

    Full Text Available Las queratitis infecciosas poseen una elevada morbilidad, poniendo en riesgo la visión en casos graves. Dada la eficaz protección que brinda el epitelio corneal, para que ocurra una infección se requiere la presencia de factores condicionantes. El principal predisponente para las queratitis infecciosas es el uso de lentes de contacto, seguido por traumatismos y cirugías oculares y luego diversas afecciones locales o generales. Los agentes etiológicos abarcan una enorme diversidad de microorganismos, incluyendo bacterias, micobacterias, virus, hongos y parásitos. Para poder instaurar un tratamiento acotado se necesita un diagnóstico etiológico, lo que requiere una correcta toma de muestra y un exhaustivo análisis microbiológico.Infectious keratitis cause significant morbidity and, if it is not promptly and appropriately treated, can lead to severe ocular disability. Almost all cases of keratitis are associated to predisposing conditions. In occident, the main risk factor is contact lens wear, but previous ocular surgery or trauma are also important, as well as various ocular surface diseases. An enormous diversity of etiologic agents for infectious keratitis exist, including virus, bacteria, mycobacteria, fungi and parasites. This review provides literature and personal based information about main predisposing factors, etiologic agents and pathophysiology of infectious keratitis, excluding those of viral origin. Focus is made on microbiologic procedures, describing stains and media that should be used, and highlighting their utility. A special mention on particular situations is made, including laboratory diagnosis of Acanthamoeba keratitis, utility of lens cases analysis, keratitis in patients with previous treatment, as well as molecular biology techniques described in ophthalmology.

  6. Cis-trans photoisomerization of abscisic acid

    International Nuclear Information System (INIS)

    Brabham, D.E.; Biggs, R.H.

    1981-01-01

    An important regulator of numerous physiological processes in higher plants is abscisic acid (ABA), which is photoisomerized from the more biologically active cis isomer to the nearly inactive trans isomer by natural sunlight. It is possible that this photoisomerization is a UV control mechanism in functions regulated by ABA. The quantum yields of both the cis to trans and trans to cis photoisomerizations were measured under various conditions of pH and oxygen concentration at room temperature. The yield for photoisomerization of cis-ABA ranged from 0.25 at pH 3.0 to 0.11 at pH 7.0. Oxygen partially quenched the process. The quantum yield varied only slightly with wavelength. The quantum yield of photolysis of cis-ABA was reported for pH 3.0 as 0.06. This yield also varied slightly with wavelength and was relatively insensitive to oxygen. This relatively high yield explains the loss of potency of ABA during UV irradiation. Phosphorescence of cis- and trans-ABA was observed in methanol at 77 K. Onset of the emission was at 350 nm. The emission spectra were the same for both isomers. From these results a mechanism of UV action on plants based on the photoisomerization of the inactive trans-ABA to the biologically active cis isomer is proposed. (author)

  7. Virology: Independent virus development outside a host

    DEFF Research Database (Denmark)

    Häring, M.; Vestergaard, Gisle Alberg; Rachel, R.

    2005-01-01

    Viruses are thought to be functionally inactive once they are outside and independent of their host cell 1 . Here we describe an exceptional property of a newly discovered virus that infects a hyperthermophilic archaeon growing in acidic hot springs: the lemon-shaped viral particle develops a very...

  8. Temporal trends in fast-food restaurant energy, sodium, saturated fat, and trans fat content, United States, 1996-2013.

    Science.gov (United States)

    Urban, Lorien E; Roberts, Susan B; Fierstein, Jamie L; Gary, Christine E; Lichtenstein, Alice H

    2014-12-31

    Excess intakes of energy, sodium, saturated fat, and trans fat are associated with increased risk for cardiometabolic syndrome. Trends in fast-food restaurant portion sizes can inform policy decisions. We examined the variability of popular food items in 3 fast-food restaurants in the United States by portion size during the past 18 years. Items from 3 national fast-food chains were selected: French fries, cheeseburgers, grilled chicken sandwich, and regular cola. Data on energy, sodium, saturated fat, and trans fat content were collated from 1996 through 2013 using an archival website. Time trends were assessed using simple linear regression models, using energy or a nutrient component as the dependent variable and the year as the independent variable. For most items, energy content per serving differed among chain restaurants for all menu items (P ≤ .04); energy content of 56% of items decreased (β range, -0.1 to -5.8 kcal) and the content of 44% increased (β range, 0.6-10.6 kcal). For sodium, the content of 18% of the items significantly decreased (β range, -4.1 to -24.0 mg) and the content for 33% increased (β range, 1.9-29.6 mg). Absolute differences were modest. The saturated and trans fat content, post-2009, was modest for French fries. In 2013, the energy content of a large-sized bundled meal (cheeseburger, French fries, and regular cola) represented 65% to 80% of a 2,000-calorie-per-day diet, and sodium content represented 63% to 91% of the 2,300-mg-per-day recommendation and 97% to 139% of the 1,500-mg-per-day recommendation. Findings suggest that efforts to promote reductions in energy, sodium, saturated fat, and trans fat intakes need to be shifted from emphasizing portion-size labels to additional factors such as total calories, frequency of eating, number of items ordered, menu choices, and energy-containing beverages.

  9. 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.

  10. Promoter trans-activation of protooncogenes c-fos and c-myc, but not c-Ha-ras, by products of adenovirus early region 1A

    International Nuclear Information System (INIS)

    Sassone-Corsi, P.; Borrelli, E.

    1987-01-01

    The E1A (early region 1A) oncogene products of adenovirus type 2 trans-activate the other early viral transcription units, as well as some cellular promoters. Using a short-term cotransfection assay in murine NIH 3T3 fibroblasts, we show that c-fos and c-myc promoter activities are stimulated by the E1A proteins, whereas c-Ha-ras transcription is not affected. The product of E1A 13S mRNA is responsible for the trans-activation, whereas the 12S mRNA product has no effect. Analysis of the c-fos promoter sequences required for the E1A stimulation shows that responsive sequences are located between positions -402 and -240 upstream of the transcription initiation site. This same region also contains the c-fos serum-responsive element. Furthermore, transcription of the endogenous c-fos gene in HeLa cells is increased after E1A transfection

  11. Host Phylogeny Determines Viral Persistence and Replication in Novel Hosts

    Science.gov (United States)

    Longdon, Ben; Hadfield, Jarrod D.; Webster, Claire L.

    2011-01-01

    Pathogens switching to new hosts can result in the emergence of new infectious diseases, and determining which species are likely to be sources of such host shifts is essential to understanding disease threats to both humans and wildlife. However, the factors that determine whether a pathogen can infect a novel host are poorly understood. We have examined the ability of three host-specific RNA-viruses (Drosophila sigma viruses from the family Rhabdoviridae) to persist and replicate in 51 different species of Drosophilidae. Using a novel analytical approach we found that the host phylogeny could explain most of the variation in viral replication and persistence between different host species. This effect is partly driven by viruses reaching a higher titre in those novel hosts most closely related to the original host. However, there is also a strong effect of host phylogeny that is independent of the distance from the original host, with viral titres being similar in groups of related hosts. Most of this effect could be explained by variation in general susceptibility to all three sigma viruses, as there is a strong phylogenetic correlation in the titres of the three viruses. These results suggest that the source of new emerging diseases may often be predictable from the host phylogeny, but that the effect may be more complex than simply causing most host shifts to occur between closely related hosts. PMID:21966271

  12. [CONTENT OF TRANS FATTY ACIDS IN FOOD PRODUCTS IN SPAIN].

    Science.gov (United States)

    Robledo de Dios, Teresa; Dal Re Saavedra, M Ángeles; Villar Villalba, Carmen; Pérez-Farinós, Napoleón

    2015-09-01

    trans fatty acids are associated to several health disorders, as ischemic heart disease or diabetes mellitus. to assess the content of trans fatty acids in products in Spain, and the percentage of trans fatty acids respecting total fatty acids. 443 food products were acquired in Spain, and they were classified into groups. The content in fatty acids was analyzed using gas chromatography. Estimates of central tendency and variability of the content of trans fatty acids in each food group were computed (in g of trans fatty acids/100 g of product). The percentage of trans fatty acids respecting total fatty acids was calculated in each group. 443 products were grouped into 42 groups. Median of trans fatty acids was less than 0.55 g / 100 g of product in all groups except one. 83 % of groups had less than 2 % of trans fatty acids, and 71 % of groups had less than 1 %. the content of trans fatty acids in Spain is low, and it currently doesn't play a public health problem. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  13. Prevalence and independent risk factors for hearing loss in NICU infants

    NARCIS (Netherlands)

    Hille, E.T.; Straaten, H.L.M. van; Verkerk, P.H.; Straaten, I. van; Verkerk, P.; Hille, E.; Baerts, W.; Bunkers, C.; Smink, E.; Elburg, R. van; Kleine, M. de; Kok, J.H.; Ilsen, A.; Visser, D.; Steiner, K.; Vries, L.S. de; Weisglas-Kuperus, N.; Sprij, A.; Lopriori, E.; Brokx, J.; Gavilanes, D.; Geven, W.; Bos, A.

    2007-01-01

    Aim: To determine the prevalence and independent relationship between hearing loss and risk factors in a representative neonatal intensive care unit (NICU) population. Methods: Automated auditory brainstem response (AABR) hearing screening has been introduced since 1998 in the Dutch NICUs. After a

  14. Trans-nationalizing the African Public Sphere: What Role for Trans ...

    African Journals Online (AJOL)

    seriane.camara

    2011-03-09

    Mar 9, 2011 ... At a time when the notion of 'trans-national public spheres' is gaining .... ple refer specifically to the language and its speakers in Senegal and Mauri- .... of the Pulaar language and the improvement of the social and economic.

  15. Tripartite Evolutionary Game Analysis on Selection Behavior of Trans-Regional Hospitals and Patients in Telemedicine System

    Directory of Open Access Journals (Sweden)

    Yuxuan Gao

    2017-01-01

    Full Text Available This study applies the game theory to the discussion and analysis of trans-regional Telemedicine System, builds the game model of the selection strategies of trans-regional hospitals and patients and analyzes evolving paths, equilibrium states and influencing factors of the three parties. It is derived that medical insurance reimbursement proportion of specialized hospitals, government support for general hospitals and medical expenses in specialized hospitals, operating costs of general hospitals are the influential factors in the Telemedicine System. Finally, a numerical stimulation is conducted with Matlapb based on the data from ligChina Health and Family Planning Statistical Yearbook 2015l/ig.

  16. Reference values of urinary trans,trans-muconic acid: Italian Multicentric Study.

    Science.gov (United States)

    Aprea, C; Sciarra, G; Bozzi, N; Pagliantini, M; Perico, A; Bavazzano, P; Leandri, A; Carrieri, M; Scapellato, M L; Bettinelli, M; Bartolucci, G B

    2008-08-01

    This article reports the results of a study, conducted in the framework of the scientific activities of the Italian Society for Reference Values, aimed at defining reference values of urinary trans,trans-muconic acid (t,t-MA) in the general population not occupationally exposed to benzene. t,t-MA concentrations detected in 376 subjects of the resident population in three areas of Italy, two in central (Florence and southern Tuscany) and one in northern Italy (Padua), by three laboratories, compared by repeated interlaboratory controls, showed an interval of 14.4-225.0 microg/L (5th-95th percentile) and a geometric mean of 52.5 microg/L. The concentrations measured were influenced by tobacco smoking in a statistically significant way: Geometric mean concentrations were 44.8 microg/L and 76.1 microg/Ll in nonsmokers (264 subjects) and smokers (112 subjects), respectively. In the nonsmoking population, a significant influence of gender was found when concentrations were corrected for urinary creatinine, geometric mean concentrations being 36.7 microg/g creatinine in males (128 subjects) and 44.7 microg/g creatinine in females (136 subjects). The place of residence of subjects did not seem to influence urinary excretion of the metabolite, although personal inhalation exposure to benzene over a 24-h period showed slightly higher concentrations in Padua and Florence (geometric means of 6.5 microg/m(3) and 6.6 microg/m(3), respectively) than in southern Tuscany (geometric mean of 3.9 microg/m(3)). Concentration of t,t-MA in urine samples collected at the end of personal air sampling showed little relationship to personal inhalation exposure to benzene, confirming the importance of other factors in determining excretion of t,t-MA when concentrations in personal air samples are very low.

  17. Recent experiences with independent power projects

    International Nuclear Information System (INIS)

    Kline, R.H.; Fitzowitch, J.R.; Dalla-Longa, L.

    1999-01-01

    New opportunities are making it possible to develop independent power projects involving partnerships with the electric power industry, and the petroleum and natural gas industry . This paper described those opportunities, the impediments and the risks involved. Mercury Electric Corp. has been involved in power projects at remote gas field and oil field sites where they use of a turbogenerator which runs on flare gas to generate electricity. TransCanada Power's involvement in independent power projects includes the supply and transport of gas and their ability to provide gas fired combined cycle technology. They are involved in a project at Hermiston, Oregon and also in a cogeneration project in Medicine Hat, Alberta. The CanCarb City of Medicine Hat project makes use of waste heat at an industrial facility. 11 figs

  18. Peel Region TransHelp's experience

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2009-09-15

    TransHelp was founded in the Peel Region of Ontario in 1981 to provide paratransit service to individuals unable to use conventional transit. The TransHelp vehicle fleet consists of 40 buses that make over 220,000 one way trips annually. Each vehicle has a typical life span of between 375,000 and 425,000 km. TransHelp vehicles spend much of their time idling in emissions-sensitive areas, such as outside hospitals. In order to reduce fuel costs, TransHelp adopted the use of propane to fuel its vehicles. However, difficulties were experienced with this technology, particularly on V-10 engines where increased maintenance was a problem. SFI Technologies Inc. provided a solution with their SEQUIN System which allows seamless transitioning between gasoline and propane under all conditions without any operator involvement in fuel selection. The technology favours propane as the fuel of choice and automatically switches between propane and gasoline based on the ideal conditions at the time of operation. The technology has received certification from the Environmental Protection Agency in the United States and the Canadian Standards Association. The use of the SEQUIN System has proven to successful for TransHelp. It has allowed the use of propane to be continued, meaning that vehicle emissions are greatly reduced relative to gasoline or diesel fuelled vehicles. TransHelp has realized a fuel savings of 15-20 per cent over gasoline and receives an additional federal transit rebate of 15 per cent for the conversion cost.

  19. Trans Women Doing Sex in San Francisco.

    Science.gov (United States)

    Williams, Colin J; Weinberg, Martin S; Rosenberger, Joshua G

    2016-10-01

    This research investigates the sexuality of trans women (individuals who were assigned male status at birth who currently identify as women), by focusing on the "bodily techniques" (Crossley, 2006) they use in "doing" sexuality. The "doing sexuality" framework not only is modeled after the "doing gender" approach of West and Zimmerman (1987), but also utilizes the idea of "sexual embodiment" to emphasize the agency of trans women as they conceptualize and organize their sexuality in a socially recognized way. This is often difficult as they confront discrimination from medical and legal professionals as well as intimate partners who may find it difficult to adapt to the trans woman's atypical body and conception of gender. However, with a study group of 25 trans women from San Francisco, we found the study participants to be adept at overcoming such hurdles and developing techniques to "do" their sexuality. At the same time, we found trans women's agency constrained by the erotic habitus (Green, 2008) of the wider society. The interplay between innovation and cultural tradition provides an opportunity to fashion a more general model of "doing" sexuality.

  20. Trans-Z-source Neutral Point Clamped inverter

    DEFF Research Database (Denmark)

    Mo, W.; Loh, P. C.; Li, D.

    2012-01-01

    Transformer based Z-source (trans-Z-source) inverters are recently proposed by extending the traditional Z-source inverter with higher buck-boost capability as well as reducing the passive components at the same time. Multi-Level Z-source inverters are single-stage topological solutions used...... for buck-boost energy conversion with all the favourable advantages of multi-level switching retained. This paper presents three-level trans-Z-source Neutral Point Clamped (NPC) inverter topology, which achieves both the advantages of trans-Z-source and three-level NPC inverter configuration. With proper...... modulation scheme, the three-level trans-Z-source inverter can function with minimum of six device commutations per half carrier cycle (same as the traditional buck NPC inverter), while maintaining to produce the designed volt-sec average and inductive voltage boosting at ac output terminals. The designed...

  1. Repair Activity of trans-Resveratrol toward 2'-Deoxyguanosine Radicals.

    Science.gov (United States)

    Cheng, Xing; An, Ping; Li, Shujin; Zhou, Liping

    2018-04-26

    In the present study, the repair activity of trans-resveratrol toward 2'-deoxyguanosine (dGuo) radicals in polar and nonpolar solvents was studied using density functional theory. The hydrogen transfer/proton coupled electron transfer and single electron transfer (SET) mechanisms between trans-resveratrol and dGuo-radicals were considered. Taking into consideration the molar fraction of neutral trans-resveratrol (ROH) and anionic trans-resveratrol (RO - ), the overall rate constants for repairing dGuo-radicals by trans-resveratrol are 9.94 × 10 8 and 2.01 × 10 9 dm 3 mol -1 s -1 in polar and nonpolar solvents, respectively, and the overall rate constant of repairing cation radical (dGuo •+ ) by trans-resveratrol via an SET mechanism is 7.17 × 10 9 dm 3 mol -1 s -1 . The repair activity of RO - toward dGuo-radicals is better than that of ROH, but the repair activity of ROH toward dGuo •+ is better than that of RO - . Unfortunately, neither ROH nor RO - can repair the 2'-deoxyribose radicals of dGuo. It can therefore be concluded that trans-resveratrol is an effective antioxidant for repairing base radicals of dGuo and dGuo •+ . The study can help us understand the repair activity of trans-resveratrol toward dGuo radicals.

  2. Viral Pneumonia in Patients with Hematologic Malignancy or Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Vakil, Erik; Evans, Scott E

    2017-03-01

    Viral pneumonias in patients with hematologic malignancies and recipients of hematopoietic stem cell transplantation cause significant morbidity and mortality. Advances in diagnostic techniques have enabled rapid identification of respiratory viral pathogens from upper and lower respiratory tract samples. Lymphopenia, myeloablative and T-cell depleting chemotherapy, graft-versus-host disease, and other factors increase the risk of developing life-threatening viral pneumonia. Chest imaging is often nonspecific but may aid in diagnoses. Bronchoscopy with bronchoalveolar lavage is recommended in those at high risk for viral pneumonia who have new infiltrates on chest imaging. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Analysis of cis and trans Requirements for DNA Replication at the Right-End Hairpin of the Human Bocavirus 1 Genome.

    Science.gov (United States)

    Shen, Weiran; Deng, Xuefeng; Zou, Wei; Engelhardt, John F; Yan, Ziying; Qiu, Jianming

    2016-09-01

    capsid has been developed to efficiently deliver the cystic fibrosis transmembrane conductance regulator gene to human airway epithelia. Here, we identified both cis-acting elements and trans-acting proteins that are required for HBoV1 DNA replication at the right-end hairpin in HEK293 cells. We localized the minimal replication origin, which contains both NS1 nicking and binding sites, to a 46-nucleotide sequence in the right-end hairpin. The identification of these essential elements of HBoV1 DNA replication acting both in cis and in trans will provide guidance to develop antiviral strategies targeting viral DNA replication at the right-end hairpin and to design next-generation recombinant HBoV1 vectors, a promising tool for gene therapy of lung diseases. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Lymphocytes Negatively Regulate NK Cell Activity via Qa-1b following Viral Infection

    Directory of Open Access Journals (Sweden)

    Haifeng C. Xu

    2017-11-01

    Full Text Available NK cells can reduce anti-viral T cell immunity during chronic viral infections, including infection with the lymphocytic choriomeningitis virus (LCMV. However, regulating factors that maintain the equilibrium between productive T cell and NK cell immunity are poorly understood. Here, we show that a large viral load resulted in inhibition of NK cell activation, which correlated with increased expression of Qa-1b, a ligand for inhibitory NK cell receptors. Qa-1b was predominantly upregulated on B cells following LCMV infection, and this upregulation was dependent on type I interferons. Absence of Qa-1b resulted in increased NK cell-mediated regulation of anti-viral T cells following viral infection. Consequently, anti-viral T cell immunity was reduced in Qa-1b- and NKG2A-deficient mice, resulting in increased viral replication and immunopathology. NK cell depletion restored anti-viral immunity and virus control in the absence of Qa-1b. Taken together, our findings indicate that lymphocytes limit NK cell activity during viral infection in order to promote anti-viral T cell immunity.

  6. The importance of trans-generational effects in Lepidoptera.

    Science.gov (United States)

    Woestmann, Luisa; Saastamoinen, Marjo

    2016-10-01

    The importance of trans-generational effects in shaping an individuals' phenotype and fitness, and consequently even impacting population dynamics is increasingly apparent. Most of the research on trans-generational effects still focuses on plants, mammals, and birds. In the past few years, however, increasing number of studies, especially on maternal effects, have highlighted their importance also in many insect systems. Lepidoptera, specifically butterflies, have been used as model systems for studying the role of phenotypic plasticity within generations. As ectotherms, they are highly sensitive to environmental variation, and indeed many butterflies show adaptive phenotypic plasticity in response to environmental conditions. Here, we synthesize what is known about trans-generational effects in Lepidoptera, compile evidence for different environmental cues that are important drivers of trans-generational effects, and point out which offspring traits are mainly impacted. Finally, we emphasize directions for future research that are needed for better understanding of the adaptive nature of trans-generational effects in Lepidoptera in particular, but potentially also in other organisms.

  7. Behavior of the viral hepatitis type A according to risk factors in Trinidad municipality.

    Directory of Open Access Journals (Sweden)

    Martha Quesada Concepción

    2010-09-01

    of the viral hepatitis type A on the four health areas in Trinidad municipality in the period betwen january 1 st and 31 st , 2009. The sample was formed by 100 sick persons that keep the inclusion criteria. Some variable were used: incidence, age, sex, healt area and risk factors. It was observed that the highest rates concerning 100 000 inhabitans were found in: the health area of Caracusey (23,1, the masculine sex ( 134,3; Condado gave the lower index under the water potability (94,1%, Policlinic l was the most affected by the presence of uncleaned graves (40% and by garbage deemp (39,0%. There was greater incidence of the desease in the Condado health area, the bad handling of the solid residue and liquids influenced in the morbility of the desease.

  8. Viral and host factors related with histopathologyc activity in patients with chronic hepatitis B and moderate or intermittently elevated alanine aminotransferase levels Influencia de factores virales y del huésped en la actividad histológica en pacientes con hepatitis crónica por virus de la hepatitis B y elevación moderada o intermitente de alanina aminotransferasa

    Directory of Open Access Journals (Sweden)

    E. Molina Pérez

    2010-09-01

    Full Text Available Objective: viral and host factors are related with progression of pathological lesion in chronic hepatitis B. We analyzed these factors in patients with moderate or intermittently elevated ALT levels, and its threshold that determinate significant histological activity. Patients and methods: retrospective analyses of viral and host parameters in 89 consecutive chronic hepatitis B patients biopsied because of moderate or intermittently elevated ALT levels [1-2 x ULN (ULN = 39 IU/mL] and/or DNA-HBV > 2 x 10³ IU/mL in AntiHBe+ patients. It was analyzed age, gender, ALT levels, HBeAg, viral load and genotype. It was considered advanced histological lesion a Knodell Score (KS > 7 and histological lesion indicating treatment, lobular inflammation ≥ 2 or fibrosis ≥ 2 according to Scheuer Classification. Results: KS > 7 and histological lesion indicating treatment was found in 47.8 and 60.7% respectively. It was observed relationship between age, male gender, ALT levels and viral load with histological damage (p ULN (69.1 vs. 47.1%, p = 0.04. There were not significant upper frequencies of advanced lesion when a cut-off of 40 years or DNA-HBV > 2 x 10³ IU/mL viral load or serological status HBeAg was considerate. Histological activity was lesser in genotype D patients than those infected with others genotypes (p Objetivo: analizar factores virales y del huésped relacionados con actividad histológica en un subgrupo de pacientes con hepatitis crónica B y elevación intermitente o moderada de alanina aminotransferasa (ALT, y el umbral que determine daño histológico indicativo de tratamiento. Pacientes y métodos: análisis retrospectivo de parámetros virales y del huésped en 89 pacientes con hepatitis crónica B biopsiados consecutivamente por elevación intermitente o moderada de ALT [1-2 x USN (USN = 39 UI/mL]. Fueron analizados edad, sexo, ALT, HBeAg, carga viral y genotipo. Se consideró como lesion histologica avanzada un Índice de

  9. Research on investment decisions model of trans-regional transmission network based on the theory of NPV

    Science.gov (United States)

    Zai, Wenjiao; Wang, Bo; Liu, Jichun; Shi, Haobo; Zeng, Pingliang

    2018-02-01

    The investment decision model of trans-regional transmission network in the context of Global Energy Internet was studied in this paper. The key factors affecting the trans-regional transmission network investment income: the income tax rate, the loan interest rate, the expected return on investment of the investment subject, the per capita GDP and so on were considered in the transmission network investment income model. First, according to the principle of system dynamics, the causality diagram of key factors was constructed. Then, the dynamic model of transmission investment decision was established. A case study of the power transmission network between China and Mongolia, through the simulation of the system dynamic model, the influence of the above key factors on the investment returns was analyzed, and the feasibility and effectiveness of the model was proved.

  10. Gender identification and sex reassignment surgery in the trans population: a survey study in France.

    Science.gov (United States)

    Giami, Alain; Beaubatie, Emmanuelle

    2014-11-01

    Drawing from controversies between medical, legal, and associative actors about the obligation of sex reassignment surgeries (SRS) for people who intend to change their civil status, this article discusses the role that medical procedures, and particularly SRS, play in contemporary gender identifications and transition pathways in France. In 2010, the French National Institute of Health and Medical Research conducted a national survey in order to study the sociodemographic characteristics, access to medical, and psychological care, and state of health among trans individuals. After a long period of ethnographic work during which a partnership was established with trans actors to map the social, medical, and political landscape of trans communities, a questionnaire was developed and distributed between July and October 2010 in collaboration with most of the trans organizations and public and private health professionals operating in France. Overall, 381 self-identified trans individuals returned the anonymous self-administered questionnaire. The results highlighted the heterogeneity of the trans population, whose definition cannot be reduced to a group of individuals undergoing standardized hormonal treatments and SRS. Two central indicators, sex assigned at birth and gender self-identification, enabled us to describe and analyze different medical and legal pathways with a particular focus on SRS, which is often compulsory for a change of civil status in France. Although SRS remains an important factor in an individual's subjective evaluation of the success of the transition pathway, its practice varies depending on one's sex assigned at birth and gender identification.

  11. Hepatitis viral aguda

    Directory of Open Access Journals (Sweden)

    Héctor Rubén Hernández Garcés

    1998-10-01

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

  12. Sexualidade e experiências trans: do hospital à alcova Sexuality and trans experiences: from the hospital to the bedroom

    Directory of Open Access Journals (Sweden)

    Berenice Bento

    2012-10-01

    Full Text Available Depois dos estudos das masculinidades, não é possível pensar a produção das identidades de gênero sem referenciá-las ao caráter relacional. Esta mudança deveu-se à incorporação da perspectiva relacional nesse campo de estudos e à crítica ao conceito de gênero assentado em uma suposta natureza feminina e masculina para construir as interpretações sobre o lugar dos corpos da ordem de gênero. Os objetivos desse artigo são: 1 apontar como um determinado conceito de gênero pode visibilizar múltiplas expressões de gênero, a exemplo das identidades trans (transexuais, travestis, cross dress, drag queen, drag king, transgêneros ou invisibilizá-las e contribuir para sua patologização. O segundo objetivo será apresentar narrativas de homens trans e de mulheres trans, que nos contarão suas vivências sexuais. Os saberes médicos-psi advogam a inexistência de sexualidade em seus corpos, sendo este um dos indicadores para produção do diagnóstico de transexua­lidade. Tentarei argumentar que a base teórica que sustenta a patologização das identidades trans e a afirmação que as pessoas trans são assexuadas tem como fundamento uma concepção que atrela e condiciona as identidades de gênero às estruturas biológicas.In the aftermath of studies on masculinity, it is impossible to consider the production of gender identities without linking them to the relationship aspect. This change was due to the incorporation of the relationship perspective in this field of study and criticism of the concept of gender founded upon an alleged concept of femininity and masculinity to create interpretations of the place of bodies in the gender order. The objectives of this paper are: 1 to show how a given concept of gender can render multiple expressions of gender visible, like the trans identities (transsexuals, transvestites, cross dressers, drag queens, drag kings, transgenders or sublimate them and contribute to their pathologization

  13. 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,

  14. Irregular menses: an independent risk factor for gestational diabetes mellitus.

    Science.gov (United States)

    Haver, Mary Claire; Locksmith, Gregory J; Emmet, Emily

    2003-05-01

    Our purpose was to determine whether a history of irregular menses predicts gestational diabetes mellitus independently of traditional risk factors. We analyzed demographic characteristics, body mass index, and menstrual history of 85 pregnant women with gestational diabetes mellitus and compared them with 85 systematically selected control subjects who were matched for age, race, and delivery year. Subjects with pregestational diabetes mellitus, previous gestational diabetes mellitus, family history of diabetes mellitus, weight >200 pounds, previous macrosomic infants, or previous stillbirth were excluded. Demographic characteristics between case and control groups were similar. Mean body mass index was higher among cases (26.5 kg/m(2)) versus control subjects (24.5 kg/m(2), P =.004). Irregular cycles were more prevalent in the cases (24% vs 7%, P =.006). With the use of body mass index as a stratification factor, menstrual irregularity maintained a strong association with gestational diabetes mellitus (P =.014). A history of irregular menstrual cycles was a significant independent predictor of gestational diabetes mellitus. If selective screening is implemented for gestational diabetes mellitus, such history should be considered in the decision of whom to test.

  15. Tissue viral load variability in chronic hepatitis C.

    LENUS (Irish Health Repository)

    Fanning, L

    2012-02-03

    OBJECTIVE: Liver biopsy is regarded as the gold standard for assessing disease activity in chronic hepatitis C, but sampling error is a potential limitation. Whether sampling variability applies equally to viral load assessment as it does to histology is uncertain. To examine this, we compared viral load between right- and left-lobe biopsy specimens from patients infected with hepatitis C virus (HCV). METHODS: Bilobe biopsies were taken from 16 patients who were serum positive for HCV RNA by reverse transcription-polymerase chain reaction. Genotype was identified by reverse line probe hybridization. There was an absence of competing risk factors for infectious and other liver diseases in this patient group. Histology and hepatic viral load were assessed blindly. None of the patients had received antiviral therapy at the time of study. RESULTS: Detection of HCV in right and left lobes was concordant with serum positivity in all cases. The viral load between lobes was highly correlated (p = 0.0003, r = 0.79). In contrast, the histological activity indices of inflammation and fibrosis\\/cirrhosis were poorly correlated between lobes (p = 0.038, r = 0.60, and p = 0.098, r = 0.50, respectively). CONCLUSION: Hepatic viral load variability does not suffer from the same degree of heterogeneity of sampling variability as does histology.

  16. TIA-1 and TIAR interact with 5'-UTR of enterovirus 71 genome and facilitate viral replication.

    Science.gov (United States)

    Wang, Xiaohui; Wang, Huanru; Li, Yixuan; Jin, Yu; Chu, Ying; Su, Airong; Wu, Zhiwei

    2015-10-16

    Enterovirus 71 is one of the major causative pathogens of HFMD in children. Upon infection, the viral RNA is translated in an IRES-dependent manner and requires several host factors for effective replication. Here, we found that T-cell-restricted intracellular antigen 1 (TIA-1), and TIA-1 related protein (TIAR) were translocated from nucleus to cytoplasm after EV71 infection and localized to the sites of viral replication. We found that TIA-1 and TIAR can facilitate EV71 replication by enhancing the viral genome synthesis in host cells. We demonstrated that both proteins bound to the stem-loop I of 5'-UTR of viral genome and improved the stability of viral genomic RNA. Our results suggest that TIA-1 and TIAR are two new host factors that interact with 5-UTR of EV71 genome and positively regulate viral replication. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. In trans complementation of lethal factor reveal roles in colonization and dissemination in a murine mouse model.

    Directory of Open Access Journals (Sweden)

    David E Lowe

    Full Text Available Lethal factor (LF is a component of the B. anthracis exotoxin and critical for pathogenesis. The roles of LF in early anthrax pathogenesis, such as colonization and dissemination from the initial site of infection, are poorly understood. In mice models of infection, LF-deficient strains either have altered dissemination patterns or do not colonize, precluding analysis of the role of LF in colonization and dissemination from the portal of entry. Previous reports indicate rabbit and guinea pig models infected with LF-deficient strains have decreased virulence, yet the inability to use bioluminescent imaging techniques to track B. anthracis growth and dissemination in these hosts makes analysis of early pathogenesis challenging. In this study, the roles of LF early in infection were analyzed using bioluminescent signature tagged libraries of B. anthracis with varying ratios of LF-producing and LF-deficient clones. Populations where all clones produced LF and populations where only 40% of clones produce LF were equally virulent. The 40% LF-producing clones trans complimented the LF mutants and permitted them to colonize and disseminate. Decreases of the LF producing strains to 10% or 0.3% of the population led to increased host survival and decreased trans complementation of the LF mutants. A library with 10% LF producing clones could replicate and disseminate, but fewer clones disseminated and the mutant clones were less competitive than wild type. The inoculum with 0.3% LF producing clones could not colonize the host. This strongly suggests that between 10% and 0.3% of the population must produce LF in order to colonize. In total, these findings suggest that a threshold of LF must be produced in order for colonization and dissemination to occur in vivo. These observations suggest that LF has a major role in the early stages of colonization and dissemination.

  18. Does atopy affect the course of viral pneumonia?

    Science.gov (United States)

    Erdem, S B; Can, D; Girit, S; Çatal, F; Şen, V; Pekcan, S; Yüksel, H; Bingöl, A; Bostancı, I; Erge, D; Ersu, R

    The presence of atopy is considered as a risk factor for severe respiratory symptoms in children. The objective of this study was to examine the effect of atopy on the course of disease in children hospitalised with viral pneumonia. Children between the ages of 1 and 6 years hospitalised due to viral pneumonia between the years of 2013 and 2016 were included to this multicentre study. Patients were classified into two groups as mild-moderate and severe according to the course of pneumonia. Presence of atopy was evaluated with skin prick tests. Groups were compared to evaluate the risk factors associated with severe viral pneumonia. A total of 280 patients from nine centres were included in the study. Of these patients, 163 (58.2%) were male. Respiratory syncytial virus (29.7%), Influenza A (20.5%), rhinovirus (18.9%), adenovirus (10%), human metapneumovirus (8%), parainfluenza (5.2%), coronavirus (6%), and bocavirus (1.6%) were isolated from respiratory samples. Eighty-five (30.4%) children had severe pneumonia. Atopic sensitisation was found in 21.4% of the patients. Ever wheezing (RR: 1.6, 95% CI: 1.1-2.4), parental asthma (RR: 1.5, 95% CI: 1.1-2.2), other allergic diseases in the family (RR: 1.8, 95% CI: 1.2-2.9) and environmental tobacco smoke (RR: 1.6, 95% CI: 1.1-3.5) were more common in the severe pneumonia group. When patients with mild-moderate pneumonia were compared to patients with severe pneumonia, frequency of atopy was not different between the two groups. However, parental asthma, ever wheezing and environmental tobacco smoke exposure are risk factors for severe viral pneumonia in children. Copyright © 2017 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.

  19. Viral Organization of Human Proteins

    Science.gov (United States)

    Wuchty, Stefan; Siwo, Geoffrey; Ferdig, Michael T.

    2010-01-01

    Although maps of intracellular interactions are increasingly well characterized, little is known about large-scale maps of host-pathogen protein interactions. The investigation of host-pathogen interactions can reveal features of pathogenesis and provide a foundation for the development of drugs and disease prevention strategies. A compilation of experimentally verified interactions between HIV-1 and human proteins and a set of HIV-dependency factors (HDF) allowed insights into the topology and intricate interplay between viral and host proteins on a large scale. We found that targeted and HDF proteins appear predominantly in rich-clubs, groups of human proteins that are strongly intertwined among each other. These assemblies of proteins may serve as an infection gateway, allowing the virus to take control of the human host by reaching protein pathways and diversified cellular functions in a pronounced and focused way. Particular transcription factors and protein kinases facilitate indirect interactions between HDFs and viral proteins. Discerning the entanglement of directly targeted and indirectly interacting proteins may uncover molecular and functional sites that can provide novel perspectives on the progression of HIV infection and highlight new avenues to fight this virus. PMID:20827298

  20. HIV Cell-to-Cell Spread Results in Earlier Onset of Viral Gene Expression by Multiple Infections per Cell.

    Directory of Open Access Journals (Sweden)

    Mikaël Boullé

    2016-11-01

    Full Text Available Cell-to-cell spread of HIV, a directed mode of viral transmission, has been observed to be more rapid than cell-free infection. However, a mechanism for earlier onset of viral gene expression in cell-to-cell spread was previously uncharacterized. Here we used time-lapse microscopy combined with automated image analysis to quantify the timing of the onset of HIV gene expression in a fluorescent reporter cell line, as well as single cell staining for infection over time in primary cells. We compared cell-to-cell spread of HIV to cell-free infection, and limited both types of transmission to a two-hour window to minimize differences due to virus transit time to the cell. The mean time to detectable onset of viral gene expression in cell-to-cell spread was accelerated by 19% in the reporter cell line and by 35% in peripheral blood mononuclear cells relative to cell-free HIV infection. Neither factors secreted by infected cells, nor contact with infected cells in the absence of transmission, detectably changed onset. We recapitulated the earlier onset by infecting with multiple cell-free viruses per cell. Surprisingly, the acceleration in onset of viral gene expression was not explained by cooperativity between infecting virions. Instead, more rapid onset was consistent with a model where the fastest expressing virus out of the infecting virus pool sets the time for infection independently of the other co-infecting viruses.

  1. 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.

  2. Are Fast Food “Trans-Fat” Claims True? An Infraspec VFA-IR Spectrometer Analysis of Trans-fat content in select food items purchased from Long John Silver’s

    Directory of Open Access Journals (Sweden)

    Sharron Jenkins

    2014-10-01

    Full Text Available Studies linking high trans-fat diets to coronary heart disease (CHD have prompted the need to regulate, limit, or completely ban trans-fat from all commercial food products, including fast foods. Many U.S. fast food chains now claim that their food items, particularly French fries, have "no trans-fat". In a previous study, our lab tested the validity of trans-fat claims made by several popular fast food restaurants by experimentally determining the %trans-fat in oil extracted from fast food French fries. In some cases, the trans-fat content was nearly twice as high as the amount reported by the restaurant in their literature. Long John Silver's, for example, reported a trans-fat content of 25% for their French fries, while our lab actually found over 40% trans-fat. The purpose of this study is to broaden our study of Long John Silver's trans-fat claims by analyzing a variety of their food items and comparing our findings with the %trans-fat reported by the restaurant literature (nutrition fact tables. Variable Filter Array (VFA IR spectroscopy was used to assess the trans-fat content of oil extracted from food samples. Our preliminary findings suggest that nearly every food item under study contained considerably more trans-fat than the amount reported in the restaurant’s literature.

  3. A Sequence-Independent, Unstructured Internal Ribosome Entry Site Is Responsible for Internal Expression of the Coat Protein of Turnip Crinkle Virus.

    Science.gov (United States)

    May, Jared; Johnson, Philip; Saleem, Huma; Simon, Anne E

    2017-04-15

    To maximize the coding potential of viral genomes, internal ribosome entry sites (IRES) can be used to bypass the traditional requirement of a 5' cap and some/all of the associated translation initiation factors. Although viral IRES typically contain higher-order RNA structure, an unstructured sequence of about 84 nucleotides (nt) immediately upstream of the Turnip crinkle virus (TCV) coat protein (CP) open reading frame (ORF) has been found to promote internal expression of the CP from the genomic RNA (gRNA) both in vitro and in vivo An absence of extensive RNA structure was predicted using RNA folding algorithms and confirmed by selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) RNA structure probing. Analysis of the IRES region in vitro by use of both the TCV gRNA and reporter constructs did not reveal any sequence-specific elements but rather suggested that an overall lack of structure was an important feature for IRES activity. The CP IRES is A-rich, independent of orientation, and strongly conserved among viruses in the same genus. The IRES was dependent on eIF4G, but not eIF4E, for activity. Low levels of CP accumulated in vivo in the absence of detectable TCV subgenomic RNAs, strongly suggesting that the IRES was active in the gRNA in vivo Since the TCV CP also serves as the viral silencing suppressor, early translation of the CP from the viral gRNA is likely important for countering host defenses. Cellular mRNA IRES also lack extensive RNA structures or sequence conservation, suggesting that this viral IRES and cellular IRES may have similar strategies for internal translation initiation. IMPORTANCE Cap-independent translation is a common strategy among positive-sense, single-stranded RNA viruses for bypassing the host cell requirement of a 5' cap structure. Viral IRES, in general, contain extensive secondary structure that is critical for activity. In contrast, we demonstrate that a region of viral RNA devoid of extensive secondary

  4. Pur-Alpha Induces JCV Gene Expression and Viral Replication by Suppressing SRSF1 in Glial Cells.

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    Ilker Kudret Sariyer

    Full Text Available PML is a rare and fatal demyelinating disease of the CNS caused by the human polyomavirus, JC virus (JCV, which occurs in AIDS patients and those on immunosuppressive monoclonal antibody therapies (mAbs. We sought to identify mechanisms that could stimulate reactivation of JCV in a cell culture model system and targeted pathways which could affect early gene transcription and JCV T-antigen production, which are key steps of the viral life cycle for blocking reactivation of JCV. Two important regulatory partners we have previously identified for T-antigen include Pur-alpha and SRSF1 (SF2/ASF. SRSF1, an alternative splicing factor, is a potential regulator of JCV whose overexpression in glial cells strongly suppresses viral gene expression and replication. Pur-alpha has been most extensively characterized as a sequence-specific DNA- and RNA-binding protein which directs both viral gene transcription and mRNA translation, and is a potent inducer of the JCV early promoter through binding to T-antigen.Pur-alpha and SRSF1 both act directly as transcriptional regulators of the JCV promoter and here we have observed that Pur-alpha is capable of ameliorating SRSF1-mediated suppression of JCV gene expression and viral replication. Interestingly, Pur-alpha exerted its effect by suppressing SRSF1 at both the protein and mRNA levels in glial cells suggesting this effect can occur independent of T-antigen. Pur-alpha and SRSF1 were both localized to oligodendrocyte inclusion bodies by immunohistochemistry in brain sections from patients with HIV-1 associated PML. Interestingly, inclusion bodies were typically positive for either Pur-alpha or SRSF1, though some cells appeared to be positive for both proteins.Taken together, these results indicate the presence of an antagonistic interaction between these two proteins in regulating of JCV gene expression and viral replication and suggests that they play an important role during viral reactivation leading to

  5. Viral and bacterial contamination in a sedimentary aquifer in Uruguay: evaluation of coliforms as regional indicators of viral contamination.

    Science.gov (United States)

    Gamazo, Pablo; Colina, Rodney; Victoria, Matias; Alvareda, Elena; Burutatran, Luciana; Ramos, Julian; Olivera, María; Soler, Joan

    2015-04-01

    In many areas of Uruguay groundwater is the only source of water for human consumption and for industrial-agricultural economic activities. Traditionally considered as a safe source, groundwater is commonly used without any treatment. The Uruguayan law requires bacteriological (fecal) analysis for most water uses, but virological analyses are not mentioned in the legislation. In the Salto district, where groundwater is used for human consumption and for agricultural activities, bacterial contamination has been detected in several wells but no viruses analysis have been performed. The Republic University (UDELAR), with the support of the National Agency for Research and Innovation (ANII), is studying the incidence of virus and fecal bacteria in groundwater on an intensive agriculture area of the Salto district. An initial screening campaign of 44 wells was performed in which, besides total and fecal coliforms, rotavirus and adenovirus were detected. A subgroup of the screening wells (15) where selected for bimonthly sampling during a year. In accordance with literature results, single well data analysis shows that coliform and viral contamination can be considered as independent variables. However, when spatial data is integrated, coliform and viral contamination show linear correlation. In this work we present the survey results, we analyse the temporal incidence of variables like precipitation, temperature and chemical composition in well contamination and we discuss the value of coliforms as global indicator of viral contamination for the Salto aquifer.

  6. Nonreplicative RNA Recombination of an Animal Plus-Strand RNA Virus in the Absence of Efficient Translation of Viral Proteins

    Science.gov (United States)

    Kleine Büning, Maximiliane; Meyer, Denise; Austermann-Busch, Sophia; Roman-Sosa, Gleyder; Rümenapf, Tillmann

    2017-01-01

    RNA recombination is a major driving force for the evolution of RNA viruses and is significantly implicated in the adaptation of viruses to new hosts, changes of virulence, as well as in the emergence of new viruses including drug-resistant and escape mutants. However, the molecular details of recombination in animal RNA viruses are only poorly understood. In order to determine whether viral RNA recombination depends on translation of viral proteins, a nonreplicative recombination system was established which is based on cotransfection of cells with synthetic bovine viral diarrhea virus (family Flaviviridae) RNA genome fragments either lacking the internal ribosome entry site required for cap-independent translation or lacking almost the complete polyprotein coding region. The emergence of a number of recombinant viruses demonstrated that IRES-mediated translation of viral proteins is dispensable for efficient recombination and suggests that RNA recombination can occur in the absence of viral proteins. Analyses of 58 independently emerged viruses led to the detection of recombinant genomes with duplications, deletions and insertions in the 5′ terminal region of the open reading frame, leading to enlarged core fusion proteins detectable by Western blot analysis. This demonstrates a remarkable flexibility of the pestivirus core protein. Further experiments with capped and uncapped genome fragments containing a luciferase gene for monitoring the level of protein translation revealed that even a ∼1,000-fold enhancement of translation of viral proteins did not increase the frequency of RNA recombination. Taken together, this study highlights that nonreplicative RNA recombination does not require translation of viral proteins. PMID:28338950

  7. Asymmetrically doped one-dimensional trans-polymers

    International Nuclear Information System (INIS)

    Caldas, Heron

    2009-01-01

    More than 30 years ago [H. Shirakawa, E.J. Louis, A.G. MacDiarmid, C.K. Chiang, A.J. Heeger, J. Chem. Soc. Chem. Comm. 578 (1977); S. Etemad, A.J. Heeger, Ann. Rev. Phys. Chem. 33 (1982) 443] it was discovered that doped trans-polyacetylene (CH) x , a one-dimensional (1D) conjugated polymer, exhibits electrical conductivity. In this work we show that an asymmetrically doped 1D trans-polymer has non-conventional properties, as compared to symmetrically doped systems. Depending on the level of asymmetry between the chemical potentials of the two involved fermionic species, the polymer can be in a partially or fully spin polarized state. Some possible experimental consequences of doped 1D trans-polymers used as 1D organic polarized conductors are discussed.

  8. Factors associated with therapeutic success in HIV-positive individuals in southern Brazil.

    Science.gov (United States)

    Silveira, M P T; Maurer, P; Guttier, M C; Moreira, L B

    2015-04-01

    Therapeutic success is characterized by undetectable viral load, immune reconstitution confirmed by CD4+ T-cell count and no clinical manifestations of disease. High treatment adherence is a major determinant of therapeutic success that needs prevention of viral replication, allowing immune reconstitution. Adherence to treatment minimum wage (IQR 1·0-2·3). Therapeutic success was achieved by 90% (122 patients), and it was associated with previously undetectable viral load (PR = 1·30; 95% CI = 1·13-1·49) and treatment adherence prior to study entry (PR = 1·34; 95% CI = 1·07-1·69), independently of sex, age and previous immune status. When undetectable viral load, CD4+ cell count ≥200 cells/mm(3) and treatment adherence above 95% are included in the definition of therapeutic success, the rate was elevated (90%) and the factors associated were previous history of adherence to HAART and previous undetectable viral load. © 2014 John Wiley & Sons Ltd.

  9. The GAAS metagenomic tool and its estimations of viral and microbial average genome size in four major biomes.

    Science.gov (United States)

    Angly, Florent E; Willner, Dana; Prieto-Davó, Alejandra; Edwards, Robert A; Schmieder, Robert; Vega-Thurber, Rebecca; Antonopoulos, Dionysios A; Barott, Katie; Cottrell, Matthew T; Desnues, Christelle; Dinsdale, Elizabeth A; Furlan, Mike; Haynes, Matthew; Henn, Matthew R; Hu, Yongfei; Kirchman, David L; McDole, Tracey; McPherson, John D; Meyer, Folker; Miller, R Michael; Mundt, Egbert; Naviaux, Robert K; Rodriguez-Mueller, Beltran; Stevens, Rick; Wegley, Linda; Zhang, Lixin; Zhu, Baoli; Rohwer, Forest

    2009-12-01

    Metagenomic studies characterize both the composition and diversity of uncultured viral and microbial communities. BLAST-based comparisons have typically been used for such analyses; however, sampling biases, high percentages of unknown sequences, and the use of arbitrary thresholds to find significant similarities can decrease the accuracy and validity of estimates. Here, we present Genome relative Abundance and Average Size (GAAS), a complete software package that provides improved estimates of community composition and average genome length for metagenomes in both textual and graphical formats. GAAS implements a novel methodology to control for sampling bias via length normalization, to adjust for multiple BLAST similarities by similarity weighting, and to select significant similarities using relative alignment lengths. In benchmark tests, the GAAS method was robust to both high percentages of unknown sequences and to variations in metagenomic sequence read lengths. Re-analysis of the Sargasso Sea virome using GAAS indicated that standard methodologies for metagenomic analysis may dramatically underestimate the abundance and importance of organisms with small genomes in environmental systems. Using GAAS, we conducted a meta-analysis of microbial and viral average genome lengths in over 150 metagenomes from four biomes to determine whether genome lengths vary consistently between and within biomes, and between microbial and viral communities from the same environment. Significant differences between biomes and within aquatic sub-biomes (oceans, hypersaline systems, freshwater, and microbialites) suggested that average genome length is a fundamental property of environments driven by factors at the sub-biome level. The behavior of paired viral and microbial metagenomes from the same environment indicated that microbial and viral average genome sizes are independent of each other, but indicative of community responses to stressors and environmental conditions.

  10. 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...

  11. Alpha Power Modulates Perception Independently of Endogenous Factors

    Directory of Open Access Journals (Sweden)

    Sasskia Brüers

    2018-04-01

    Full Text Available Oscillations are ubiquitous in the brain. Alpha oscillations in particular have been proposed to play an important role in sensory perception. Past studies have shown that the power of ongoing EEG oscillations in the alpha band is negatively correlated with visual outcome. Moreover, it also co-varies with other endogenous factors such as attention, vigilance, or alertness. In turn, these endogenous factors influence visual perception. Therefore, it remains unclear how much of the relation between alpha and perception is indirectly mediated by such endogenous factors, and how much reflects a direct causal influence of alpha rhythms on sensory neural processing. We propose to disentangle the direct from the indirect causal routes by introducing modulations of alpha power, independently of any fluctuations in endogenous factors. To this end, we use white-noise sequences to constrain the brain activity of 20 participants. The cross-correlation between the white-noise sequences and the concurrently recorded EEG reveals the impulse response function (IRF, a model of the systematic relationship between stimulation and brain response. These IRFs are then used to reconstruct rather than record the brain activity linked with new random sequences (by convolution. Interestingly, this reconstructed EEG only contains information about oscillations directly linked to the white-noise stimulation; fluctuations in attention and other endogenous factors may still modulate brain alpha rhythms during the task, but our reconstructed EEG is immune to these factors. We found that the detection of near-perceptual threshold targets embedded within these new white-noise sequences depended on the power of the ~10 Hz reconstructed EEG over parieto-occipital channels. Around the time of presentation, higher power led to poorer performance. Thus, fluctuations in alpha power, induced here by random luminance sequences, can directly influence perception: the relation between

  12. Hepatic deficiency of the pioneer transcription factor FoxA restricts hepatitis B virus biosynthesis by the developmental regulation of viral DNA methylation.

    Directory of Open Access Journals (Sweden)

    Vanessa C McFadden

    2017-02-01

    Full Text Available The FoxA family of pioneer transcription factors regulates hepatitis B virus (HBV transcription, and hence viral replication. Hepatocyte-specific FoxA-deficiency in the HBV transgenic mouse model of chronic infection prevents the transcription of the viral DNA genome as a result of the failure of the developmentally controlled conversion of 5-methylcytosine residues to cytosine during postnatal hepatic maturation. These observations suggest that pioneer transcription factors such as FoxA, which mark genes for expression at subsequent developmental steps in the cellular differentiation program, mediate their effects by reversing the DNA methylation status of their target genes to permit their ensuing expression when the appropriate tissue-specific transcription factor combinations arise during development. Furthermore, as the FoxA-deficient HBV transgenic mice are viable, the specific developmental timing, abundance and isoform type of pioneer factor expression must permit all essential liver gene expression to occur at a level sufficient to support adequate liver function. This implies that pioneer transcription factors can recognize and mark their target genes in distinct developmental manners dependent upon, at least in part, the concentration and affinity of FoxA for its binding sites within enhancer and promoter regulatory sequence elements. This selective marking of cellular genes for expression by the FoxA pioneer factor compared to HBV may offer the opportunity for the specific silencing of HBV gene expression and hence the resolution of chronic HBV infections which are responsible for approximately one million deaths worldwide annually due to liver cirrhosis and hepatocellular carcinoma.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Genome-wide analysis of protein-protein interactions and involvement of viral proteins in SARS-CoV replication.

    Directory of Open Access Journals (Sweden)

    Ji'an Pan

    Full Text Available Analyses of viral protein-protein interactions are an important step to understand viral protein functions and their underlying molecular mechanisms. In this study, we adopted a mammalian two-hybrid system to screen the genome-wide intraviral protein-protein interactions of SARS coronavirus (SARS-CoV and therefrom revealed a number of novel interactions which could be partly confirmed by in vitro biochemical assays. Three pairs of the interactions identified were detected in both directions: non-structural protein (nsp 10 and nsp14, nsp10 and nsp16, and nsp7 and nsp8. The interactions between the multifunctional nsp10 and nsp14 or nsp16, which are the unique proteins found in the members of Nidovirales with large RNA genomes including coronaviruses and toroviruses, may have important implication for the mechanisms of replication/transcription complex assembly and functions of these viruses. Using a SARS-CoV replicon expressing a luciferase reporter under the control of a transcription regulating sequence, it has been shown that several viral proteins (N, X and SUD domains of nsp3, and nsp12 provided in trans stimulated the replicon reporter activity, indicating that these proteins may regulate coronavirus replication and transcription. Collectively, our findings provide a basis and platform for further characterization of the functions and mechanisms of coronavirus proteins.

  15. Effective line strengths of trans-nitrous acid near 1275 cm−1 and cis-nitrous acid at 1660 cm−1

    International Nuclear Information System (INIS)

    Lee, B.H.; Wood, E.C.; Wormhoudt, J.; Shorter, J.H.; Herndon, S.C.; Zahniser, M.S.; Munger, J.W.

    2012-01-01

    We determined the effective line strengths of the trans conformer of nitrous acid (HONO) near 1275 cm −1 (R-branch of ν 3 mode, N---O---H bend) and of the cis conformer at 1660 cm −1 (R-branch of ν 2 mode, N=O stretch), both at a spectral resolution of 0.001 cm −1 by tunable infrared laser differential absorption spectroscopy (TILDAS) utilizing continuous-wave quantum cascade (cw-QC) lasers. Absorbance of one conformer was measured while simultaneously quantifying the mixing ratio of total HONO by catalytic conversion to nitric oxide (NO) followed by calibrated absorption spectroscopy. Line strengths obtained here are consistent with previously reported band strengths for the trans conformer but are lower by a factor of approximately 2.4 for the cis conformer. -- Highlights: ► Effective line strengths for the cis-HONO at 1660 cm −1 was quantified. ► Effective line strengths for the trans conformer near 1275 cm −1 was also quantified. ► Results for trans-HONO are in agreement with previously published band strength. ► Previous cis band strength is high by factor of 2.4 due to spectral interference.

  16. Comparison of the patient radiation exposure during coronary angiography and angioplasty procedures using trans-radial and trans-femoral access

    Directory of Open Access Journals (Sweden)

    Ali Tarighatnia

    2016-06-01

    Conclusion: On the basis of the results obtained in this study, no differences were found in patients’ radiation dose in both access groups, therefore with regard to comparatively more clinical advantages associated with the Trans-radial access technique it might be a good substitute for Trans-femoral access.

  17. The inverse-trans-influence in tetravalent lanthanide and actinide bis(carbene) complexes

    Science.gov (United States)

    Gregson, Matthew; Lu, Erli; Mills, David P.; Tuna, Floriana; McInnes, Eric J. L.; Hennig, Christoph; Scheinost, Andreas C.; McMaster, Jonathan; Lewis, William; Blake, Alexander J.; Kerridge, Andrew; Liddle, Stephen T.

    2017-02-01

    Across the periodic table the trans-influence operates, whereby tightly bonded ligands selectively lengthen mutually trans metal-ligand bonds. Conversely, in high oxidation state actinide complexes the inverse-trans-influence operates, where normally cis strongly donating ligands instead reside trans and actually reinforce each other. However, because the inverse-trans-influence is restricted to high-valent actinyls and a few uranium(V/VI) complexes, it has had limited scope in an area with few unifying rules. Here we report tetravalent cerium, uranium and thorium bis(carbene) complexes with trans C=M=C cores where experimental and theoretical data suggest the presence of an inverse-trans-influence. Studies of hypothetical praseodymium(IV) and terbium(IV) analogues suggest the inverse-trans-influence may extend to these ions but it also diminishes significantly as the 4f orbitals are populated. This work suggests that the inverse-trans-influence may occur beyond high oxidation state 5f metals and hence could encompass mid-range oxidation state actinides and lanthanides. Thus, the inverse-trans-influence might be a more general f-block principle.

  18. Mucosal immunization in macaques upregulates the innate APOBEC 3G anti-viral factor in CD4(+) memory T cells.

    Science.gov (United States)

    Wang, Yufei; Bergmeier, Lesley A; Stebbings, Richard; Seidl, Thomas; Whittall, Trevor; Singh, Mahavir; Berry, Neil; Almond, Neil; Lehner, Thomas

    2009-02-05

    APOBEC3G is an innate intracellular anti-viral factor which deaminates retroviral cytidine to uridine. In vivo studies of APOBEC3G (A3G) were carried out in rhesus macaques, following mucosal immunization with SIV antigens and CCR5 peptides, linked to the 70kDa heat shock protein. A progressive increase in A3G mRNA was elicited in PBMC after each immunization (p<0.0002 to p< or =0.02), which was maintained for at least 17 weeks. Analysis of memory T cells showed a significant increase in A3G mRNA and protein in CD4(+)CCR5(+) memory T cells in circulating (p=0.0001), splenic (p=0.0001), iliac lymph nodes (p=0.002) and rectal (p=0.01) cells of the immunized compared with unimmunized macaques. Mucosal challenge with SIVmac 251 showed a significant increase in A3G mRNA in the CD4(+)CCR5(+) circulating cells (p<0.01) and the draining iliac lymph node cells (p<0.05) in the immunized uninfected macaques, consistent with a protective effect exerted by A3G. The results suggest that mucosal immunization in a non-human primate can induce features of a memory response to an innate anti-viral factor in CCR5(+)CD4(+) memory and CD4(+)CD95(+)CCR7(-) effector memory T cells.

  19. Mediation Analysis Demonstrates That Trans-eQTLs Are Often Explained by Cis-Mediation: A Genome-Wide Analysis among 1,800 South Asians

    Science.gov (United States)

    Pierce, Brandon L.; Tong, Lin; Chen, Lin S.; Rahaman, Ronald; Argos, Maria; Jasmine, Farzana; Roy, Shantanu; Paul-Brutus, Rachelle; Westra, Harm-Jan; Franke, Lude; Esko, Tonu; Zaman, Rakibuz; Islam, Tariqul; Rahman, Mahfuzar; Baron, John A.; Kibriya, Muhammad G.; Ahsan, Habibul

    2014-01-01

    A large fraction of human genes are regulated by genetic variation near the transcribed sequence (cis-eQTL, expression quantitative trait locus), and many cis-eQTLs have implications for human disease. Less is known regarding the effects of genetic variation on expression of distant genes (trans-eQTLs) and their biological mechanisms. In this work, we use genome-wide data on SNPs and array-based expression measures from mononuclear cells obtained from a population-based cohort of 1,799 Bangladeshi individuals to characterize cis- and trans-eQTLs and determine if observed trans-eQTL associations are mediated by expression of transcripts in cis with the SNPs showing trans-association, using Sobel tests of mediation. We observed 434 independent trans-eQTL associations at a false-discovery rate of 0.05, and 189 of these trans-eQTLs were also cis-eQTLs (enrichment Pmediator based on Sobel Pmediation signals in two European cohorts, and while only 7 trans-eQTL associations were present in one or both cohorts, 6 showed evidence of cis-mediation. Analyses of simulated data show that complete mediation will be observed as partial mediation in the presence of mediator measurement error or imperfect LD between measured and causal variants. Our data demonstrates that trans-associations can become significantly stronger or switch directions after adjusting for a potential mediator. Using simulated data, we demonstrate that this phenomenon is expected in the presence of strong cis-trans confounding and when the measured cis-transcript is correlated with the true (unmeasured) mediator. In conclusion, by applying mediation analysis to eQTL data, we show that a substantial fraction of observed trans-eQTL associations can be explained by cis-mediation. Future studies should focus on understanding the mechanisms underlying widespread cis-mediation and their relevance to disease biology, as well as using mediation analysis to improve eQTL discovery. PMID:25474530

  20. Marked variability in the extent of protein disorder within and between viral families.

    Directory of Open Access Journals (Sweden)

    Ravindra Pushker

    Full Text Available Intrinsically disordered regions in eukaryotic proteomes contain key signaling and regulatory modules and mediate interactions with many proteins. Many viral proteomes encode disordered proteins and modulate host factors through the use of short linear motifs (SLiMs embedded within disordered regions. However, the degree of viral protein disorder across different viruses is not well understood, so we set out to establish the constraints acting on viruses, in terms of their use of disordered protein regions. We surveyed predicted disorder across 2,278 available viral genomes in 41 families, and correlated the extent of disorder with genome size and other factors. Protein disorder varies strikingly between viral families (from 2.9% to 23.1% of residues, and also within families. However, this substantial variation did not follow the established trend among their hosts, with increasing disorder seen across eubacterial, archaebacterial, protists, and multicellular eukaryotes. For example, among large mammalian viruses, poxviruses and herpesviruses showed markedly differing disorder (5.6% and 17.9%, respectively. Viral families with smaller genome sizes have more disorder within each of five main viral types (ssDNA, dsDNA, ssRNA+, dsRNA, retroviruses, except for negative single-stranded RNA viruses, where disorder increased with genome size. However, surveying over all viruses, which compares tiny and enormous viruses over a much bigger range of genome sizes, there is no strong association of genome size with protein disorder. We conclude that there is extensive variation in the disorder content of viral proteomes. While a proportion of this may relate to base composition, to extent of gene overlap, and to genome size within viral types, there remain important additional family and virus-specific effects. Differing disorder strategies are likely to impact on how different viruses modulate host factors, and on how rapidly viruses can evolve novel

  1. 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

  2. Host phylogeny determines viral persistence and replication in novel hosts.

    Directory of Open Access Journals (Sweden)

    Ben Longdon

    2011-09-01

    Full Text Available Pathogens switching to new hosts can result in the emergence of new infectious diseases, and determining which species are likely to be sources of such host shifts is essential to understanding disease threats to both humans and wildlife. However, the factors that determine whether a pathogen can infect a novel host are poorly understood. We have examined the ability of three host-specific RNA-viruses (Drosophila sigma viruses from the family Rhabdoviridae to persist and replicate in 51 different species of Drosophilidae. Using a novel analytical approach we found that the host phylogeny could explain most of the variation in viral replication and persistence between different host species. This effect is partly driven by viruses reaching a higher titre in those novel hosts most closely related to the original host. However, there is also a strong effect of host phylogeny that is independent of the distance from the original host, with viral titres being similar in groups of related hosts. Most of this effect could be explained by variation in general susceptibility to all three sigma viruses, as there is a strong phylogenetic correlation in the titres of the three viruses. These results suggest that the source of new emerging diseases may often be predictable from the host phylogeny, but that the effect may be more complex than simply causing most host shifts to occur between closely related hosts.

  3. [Basic and clinical studies of pressure-independent damaging factors of open angle glaucoma].

    Science.gov (United States)

    Araie, Makoto

    2011-03-01

    Pathogenesis of open-angle glaucoma involves both pressure-dependent damaging factors and pressure-independent damaging factors. The high prevalence of open-angle glaucoma with normal pressure (normal-tension glaucoma) in Japan implies that treatment of pressure-independent damaging factors in Japanese open-angle glaucoma patients is of importance. In an attempt to investigate the roles of pressure-independent damaging factors in open-angle glaucoma, we carried out basic and clinical studies and obtained the following results. 1. The rate of deterioration of visual field after trabeculectomy in normal tension glaucoma patients with post-operative intraocular pressure (IOP) of 10 mmHg was found to be -0.25 dB/year of mean deviation (MD), suggesting that contribution of pressure-independent damaging factors to the deterioration of MD in open-angle glaucoma is around -0.25 dB/year of mean deviation (MD). 2. Experiments using isolated purified cultured retinal ganglion cells (RGCs) indicated that calcium-channel blockers and some of antiglaucoma drugs showed neuroprotective effects on RGCs at concentrations of 0.01 microM or higher. 3. In mice, damage to RGCs resulted in secondary degeneration of neurons and activation of glial cells in the lateral geniculate nucleous (LGN) and superior colliculus, and these secondary changes in the central nervous system (CNS) due to RGC damage was partly ameliorated by systemic administration of memantine. 4. Mice experimental high IOP glaucoma models could be established using laser irradiation of the limbal area, and the usefulness of Tonolab in IOP measurements of mice eye was confirmed. 5. Monkey experimental high IOP glaucoma models revealed that in the glaucomatous optic nerve head vaso-constrictive reactions to an alpha-1 agonist was abolished, while vasodilative reaction to a prostaglandin FP receptor agonist was retained. 6. In monkeys with experimental high IOP glaucoma, secondary damage to neurons in the LGN and the glial

  4. Physics of trans-Planckian gravity

    International Nuclear Information System (INIS)

    Dvali, Gia; Folkerts, Sarah; Germani, Cristiano

    2011-01-01

    We study the field theoretical description of a generic theory of gravity flowing to Einstein general relativity in IR. We prove that, if ghost-free, in the weakly-coupled regime such a theory can never become weaker than general relativity. Using this fact, as a by-product, we suggest that in a ghost-free theory of gravity trans-Planckian propagating quantum degrees of freedom cannot exist. The only physical meaning of a trans-Planckian pole is the one of a classical state (black hole) which is described by the light IR quantum degrees of freedom and gives exponentially-suppressed contributions to virtual processes. In this picture Einstein gravity is UV self-complete, although not Wilsonian, and sub-Planckian distances are unobservable in any healthy theory of gravity. We then finally show that this UV/IR correspondence puts a severe constraint on any attempt of conventional Wilsonian UV-completion of trans-Planckian gravity. Specifically, there is no well-defined energy domain in which gravity could become asymptotically weak or safe.

  5. Predictive factors for achieving independent walking in children with Guillain-Barre syndrome.

    Science.gov (United States)

    Barzegar, Mohammad; Toopchizadeh, Vahideh; Maher, Mohammad H K; Sadeghi, Paria; Jahanjoo, Fatemeh; Pishgahi, Alireza

    2017-08-01

    BackgroundTo determine the predictors of achieving independent walking at 2 and 6 months after onset of weakness in children with Guillain-Barre syndrome (GBS).MethodsChildren with GBS admitted to the Tabriz Children's Hospital were studied prospectively. All patients had frequent clinical evaluations until achieving independent walking. Unaided walking at 2 and 6 months and factors influencing these outcomes were determined using both univariate and multiple analyses.ResultsBetween 2003 and 2014, 324 children (mean age: 5.3±3.66 years) were admitted. The mean duration to independent walking was 2.97±3.02 months; 90.5% of patients could walk independently at 6 months. In the univariate analysis, disability score of >3 (P=0.03), autonomic nerve involvement (P=0.003), cranial nerve involvement (P=0.008), and absent compound muscle action potential (CMAP; P=0.048) were found to be significantly associated with poor walking outcome at 6 months. In the multivariate analysis, cranial nerve involvement (P=0.008) and absence of CMAP (P=0.022) were independently associated with poor functional outcome.ConclusionDisability score >3, cranial and autonomic nerve involvement, and absence of CMAP were predictors of independent walking in childhood GBS in this study; early rehabilitation program may prevent further impairments secondary to immobility in these patients.

  6. Ruminant and industrial trans-fatty acid uptake in the heart.

    Science.gov (United States)

    Ganguly, Riya; LaVallee, Renee; Maddaford, Thane G; Devaney, Brittany; Bassett, Chantal M C; Edel, Andrea L; Pierce, Grant N

    2016-05-01

    Dietary trans-fats are strongly associated with heart disease. However, the capacity for the tissues of the body, and specifically the heart, to take up trans-fats is unknown. It is also unknown if different trans-fats have different uptake capacities in the heart and other tissues of the body. Diets of low-density lipoprotein receptor-deficient mice were supplemented for 14weeks with foods that contained 1.5% of the trans-fat elaidic acid or vaccenic acid. Tissues were extracted and frozen in liquid nitrogen, and then lipids were analyzed by gas chromatography for fatty acid content. Isolated cardiomyocytes were also exposed to elaidic or vaccenic acid in cell culture media for 24h. Dietary supplementation with vaccenic or elaidic acid resulted in a 20-fold higher accumulation of these TFAs in fat deposits in the body in comparison to liver. Liver tissue accumulated about twice as much per gram tissue as heart. Similar quantities of both elaidic acid and vaccenic acid were taken up by the tissues. Isolated cardiomyocytes exhibited an unusually large uptake of trans-fat, and this was dependent upon both the concentration and duration of exposure to the trans-fats but not upon the type of trans-fat. Expression levels of CD36 and FATP4 were not significantly changed during dietary interventions or exposure of cells to trans-fats. We conclude that fat, liver and heart (including cardiomyocytes) are all capable of accumulating trans-fat in response to dietary supplementation without changes in fatty acid transport protein expression. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Coupled Transcriptome and Proteome Analysis of Human Lymphotropic Tumor Viruses: Insights on the Detection and Discovery of Viral Genes

    Energy Technology Data Exchange (ETDEWEB)

    Dresang, Lindsay R.; Teuton, Jeremy R.; Feng, Huichen; Jacobs, Jon M.; Camp, David G.; Purvine, Samuel O.; Gritsenko, Marina A.; Li, Zhihua; Smith, Richard D.; Sugden, Bill; Moore, Patrick S.; Chang, Yuan

    2011-12-20

    Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) are related human tumor viruses that cause primary effusion lymphomas (PEL) and Burkitt's lymphomas (BL), respectively. Viral genes expressed in naturally-infected cancer cells contribute to disease pathogenesis; knowing which viral genes are expressed is critical in understanding how these viruses cause cancer. To evaluate the expression of viral genes, we used high-resolution separation and mass spectrometry coupled with custom tiling arrays to align the viral proteomes and transcriptomes of three PEL and two BL cell lines under latent and lytic culture conditions. Results The majority of viral genes were efficiently detected at the transcript and/or protein level on manipulating the viral life cycle. Overall the correlation of expressed viral proteins and transcripts was highly complementary in both validating and providing orthogonal data with latent/lytic viral gene expression. Our approach also identified novel viral genes in both KSHV and EBV, and extends viral genome annotation. Several previously uncharacterized genes were validated at both transcript and protein levels. Conclusions This systems biology approach coupling proteome and transcriptome measurements provides a comprehensive view of viral gene expression that could not have been attained using each methodology independently. Detection of viral proteins in combination with viral transcripts is a potentially powerful method for establishing virus-disease relationships.

  8. Trans-Spatial Utopias

    Science.gov (United States)

    Kramsch, Claire

    2018-01-01

    The "trans-" perspectives offered in this special issue are heady stuff. Post-structuralism (philosophy) meets the digital age (electronics), meets globalization (economics), and meets translingual practice (linguistics) to create a perfectly utopian or placeless space for future exploration. I want to first add my voice to the…

  9. TrSDB: a proteome database of transcription factors

    Science.gov (United States)

    Hermoso, Antoni; Aguilar, Daniel; Aviles, Francesc X.; Querol, Enrique

    2004-01-01

    TrSDB—TranScout Database—(http://ibb.uab.es/trsdb) is a proteome database of eukaryotic transcription factors based upon predicted motifs by TranScout and data sources such as InterPro and Gene Ontology Annotation. Nine eukaryotic proteomes are included in the current version. Extensive and diverse information for each database entry, different analyses considering TranScout classification and similarity relationships are offered for research on transcription factors or gene expression. PMID:14681387

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

    Directory of Open Access Journals (Sweden)

    Di Sun

    2016-03-01

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

  11. Viral diseases and human evolution

    Directory of Open Access Journals (Sweden)

    Leal Élcio de Souza

    2000-01-01

    Full Text Available The interaction of man with viral agents was possibly a key factor shaping human evolution, culture and civilization from its outset. Evidence of the effect of disease, since the early stages of human speciation, through pre-historical times to the present suggest that the types of viruses associated with man changed in time. As human populations progressed technologically, they grew in numbers and density. As a consequence different viruses found suitable conditions to thrive and establish long-lasting associations with man. Although not all viral agents cause disease and some may in fact be considered beneficial, the present situation of overpopulation, poverty and ecological inbalance may have devastating effets on human progress. Recently emerged diseases causing massive pandemics (eg., HIV-1 and HCV, dengue, etc. are becoming formidable challenges, which may have a direct impact on the fate of our species.

  12. 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.

  13. Initial 12-h operative fluid volume is an independent risk factor for pleural effusion after hepatectomy.

    Science.gov (United States)

    Cheng, Xiang; Wu, Jia-Wei; Sun, Ping; Song, Zi-Fang; Zheng, Qi-Chang

    2016-12-01

    Pleural effusion after hepatectomy is associated with significant morbidity and prolonged hospital stays. Several studies have addressed the risk factors for postoperative pleural effusion. However, there are no researches concerning the role of the initial 12-h operative fluid volume. The aim of this study was to evaluate whether the initial 12-h operative fluid volume during liver resection is an independent risk factor for pleural effusion after hepatectomy. In this study, we retrospectively analyzed clinical data of 470 patients consecutively undergoing elective hepatectomy between January 2011 and December 2012. We prospectively collected and retrospectively analyzed baseline and clinical data, including preoperative, intraoperative, and postoperative variables. Univariate and multivariate analyses were carried out to identify whether the initial 12-h operative fluid volume was an independent risk factor for pleural effusion after hepatectomy. The multivariate analysis identified 2 independent risk factors for pleural effusion: operative time [odds ratio (OR)=10.2] and initial 12-h operative fluid volume (OR=1.0003). Threshold effect analyses revealed that the initial 12 h operative fluid volume was positively correlated with the incidence of pleural effusion when the initial 12-h operative fluid volume exceeded 4636 mL. We conclude that the initial 12-h operative fluid volume during liver resection and operative time are independent risk factors for pleural effusion after hepatectomy. Perioperative intravenous fluids should be restricted properly.

  14. transPLANT Resources for Triticeae Genomic Data

    Directory of Open Access Journals (Sweden)

    Manuel Spannagl

    2016-03-01

    Full Text Available The genome sequences of many important Triticeae species, including bread wheat ( L. and barley ( L., remained uncharacterized for a long time because their high repeat content, large sizes, and polyploidy. As a result of improvements in sequencing technologies and novel analyses strategies, several of these have recently been deciphered. These efforts have generated new insights into Triticeae biology and genome organization and have important implications for downstream usage by breeders, experimental biologists, and comparative genomicists. transPLANT ( is an EU-funded project aimed at constructing hardware, software, and data infrastructure for genome-scale research in the life sciences. Since the Triticeae data are intrinsically complex, heterogenous, and distributed, the transPLANT consortium has undertaken efforts to develop common data formats and tools that enable the exchange and integration of data from distributed resources. Here we present an overview of the individual Triticeae genome resources hosted by transPLANT partners, introduce the objectives of transPLANT, and outline common developments and interfaces supporting integrated data access.

  15. Dietary trans-fatty acids and metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Zdzisław Kochan

    2010-12-01

    Full Text Available Trans-fatty acids (TFAs, products of partial hydrogenation of vegetable oils, have become more prevalent in our diet since the 1960s, when they replaced animal fats. TFAs also occur naturally in meat and dairy products from ruminants. There is growing evidence that dietary trans-fatty acids may increase the risk of metabolic syndrome. Several studies have demonstrated adverse effects of TFAs on plasma lipids and lipoproteins. In dietary trials, trans-fatty acids have been shown to raise the total cholesterol/HDL cholesterol ratio and Lp(a levels in blood. Moreover, a high intake of TFAs has been associated with an increased risk of coronary heart disease. Prospective cohort studies have shown that dietary trans-fatty acids promote abdominal obesity and weight gain. In addition, it appears that TFA consumption may be associated with the development of insulin resistance and type 2 diabetes. The documented adverse health effects of TFAs emphasise the importance of efforts to reduce the content of partially hydrogenated vegetable oils in foods.

  16. The evolutionary landscape of intergenic trans-splicing events in insects

    Science.gov (United States)

    Kong, Yimeng; Zhou, Hongxia; Yu, Yao; Chen, Longxian; Hao, Pei; Li, Xuan

    2015-01-01

    To explore the landscape of intergenic trans-splicing events and characterize their functions and evolutionary dynamics, we conduct a mega-data study of a phylogeny containing eight species across five orders of class Insecta, a model system spanning 400 million years of evolution. A total of 1,627 trans-splicing events involving 2,199 genes are identified, accounting for 1.58% of the total genes. Homology analysis reveals that mod(mdg4)-like trans-splicing is the only conserved event that is consistently observed in multiple species across two orders, which represents a unique case of functional diversification involving trans-splicing. Thus, evolutionarily its potential for generating proteins with novel function is not broadly utilized by insects. Furthermore, 146 non-mod trans-spliced transcripts are found to resemble canonical genes from different species. Trans-splicing preserving the function of ‘breakup' genes may serve as a general mechanism for relaxing the constraints on gene structure, with profound implications for the evolution of genes and genomes. PMID:26521696

  17. READING COLONIZATION IN CONRAD'S TRANS-RACIAL LOVE PLOTS

    Directory of Open Access Journals (Sweden)

    Sandra Lilyana

    2017-07-01

    Full Text Available The study is about a close look at Conrad's trans-racial romance related to the Victorian period. Trans-racial love between white men and non-white women becomes a popular theme in the early works of Josep Conrad, a famous writer of the late Victorian period. Using a closely technical reading in the three of Conrad's works Lord Jim, Almayer's Folly, and An Outcast of the Island, we can show that such a trans-racial romance is not merely meant for appreciating equivalence. In turn, the trans-racial romance of Conrad's can be understood as the reflection of the Western colonization on the East where the white men take a role as subjects who had dominately explored while the non-white women as objects who are passively being explored. Key words: colonization, race, romance plot, subject, object, and dominance

  18. Technical aspects of trans reduction in margarines

    Directory of Open Access Journals (Sweden)

    Van Duijn Gerrit

    2000-01-01

    Full Text Available The opinion of nutritional science on the effect of trans fatty acids on blood cholesterol has drastically changed during the last decade. As a reaction to these new findings, the European margarine industry decided in the mid nineties to eliminate trans containing components from their margarine fat phase compositions. This excluded practically the use of partially hydrogenated oils and fats. Trans-free margarines have been introduced with optimised fat crystal structures stabilising a maximum of water in oil emulsion with a minimum of solid fat phase. These fat crystal structures are formed by fat phase components obtained from interesterification and/or fractionation of non-hydrogenated and/or fully hydrogenated feedstocks.

  19. Prediction of fibrosis progression in chronic viral hepatitis

    Directory of Open Access Journals (Sweden)

    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.

  20. Nonreplicative RNA Recombination of an Animal Plus-Strand RNA Virus in the Absence of Efficient Translation of Viral Proteins.

    Science.gov (United States)

    Kleine Büning, Maximiliane; Meyer, Denise; Austermann-Busch, Sophia; Roman-Sosa, Gleyder; Rümenapf, Tillmann; Becher, Paul

    2017-04-01

    RNA recombination is a major driving force for the evolution of RNA viruses and is significantly implicated in the adaptation of viruses to new hosts, changes of virulence, as well as in the emergence of new viruses including drug-resistant and escape mutants. However, the molecular details of recombination in animal RNA viruses are only poorly understood. In order to determine whether viral RNA recombination depends on translation of viral proteins, a nonreplicative recombination system was established which is based on cotransfection of cells with synthetic bovine viral diarrhea virus (family Flaviviridae) RNA genome fragments either lacking the internal ribosome entry site required for cap-independent translation or lacking almost the complete polyprotein coding region. The emergence of a number of recombinant viruses demonstrated that IRES-mediated translation of viral proteins is dispensable for efficient recombination and suggests that RNA recombination can occur in the absence of viral proteins. Analyses of 58 independently emerged viruses led to the detection of recombinant genomes with duplications, deletions and insertions in the 5' terminal region of the open reading frame, leading to enlarged core fusion proteins detectable by Western blot analysis. This demonstrates a remarkable flexibility of the pestivirus core protein. Further experiments with capped and uncapped genome fragments containing a luciferase gene for monitoring the level of protein translation revealed that even a ∼1,000-fold enhancement of translation of viral proteins did not increase the frequency of RNA recombination. Taken together, this study highlights that nonreplicative RNA recombination does not require translation of viral proteins. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  1. Unscripting Curriculum: Toward a Critical Trans Pedagogy

    Science.gov (United States)

    Keenan, Harper Benjamin

    2017-01-01

    In this essay, Harper B. Keenan draws on his own experience as a white queer and trans educator to consider the meaning of a critical trans pedagogy. Amid dissonant narratives of equal rights and subjection, he explores how his classroom teaching is shaped by his own experience of gender conditioning as well as by the contemporary political…

  2. Relative Stability of cis- and trans-Hydrindanones

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    Motoo Tori

    2015-01-01

    Full Text Available The relative stabilities of several cis- and trans-hydrindanones were compared using both isomerization experiments and MM2 calculations. The generally believed rule that cis-hydrindanones are more stable than trans-isomers is applicable, but is not always true. This review introduces examples, mainly from studies in our laboratory, to explain these facts.

  3. ASTHMA AND VIRAL INFECTIONS IN CHILDREN

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    D. Sh. Macharadze

    2014-01-01

    Full Text Available Viruses are the most common pathogens of acute respiratory diseases — most often causing mild symptoms of common cold: cough, runny nose, temperature increases. At the same time, 1/3 of children have the following symptoms of lower respiratory tract disorders: shortness of breath, wheezing, coughing, respiratory failure. Virus-induced wheezing are risk factors for development of asthma in childhood. Recent clinical and scientific data suggest: the more difficult are viral respiratory infections in young children, the higher their risk of asthma later on. Another feature is that children with allergic diseases are much more likely to have viral respiratory infections(and with longer clinical course, compared with children without atopy. The use of ibuprofen is safe for children over 3 months, including suffering from bronchial asthma.

  4. Prevalence and risk factors for cervical intraepithelial neoplasia among HIV-infected women

    Directory of Open Access Journals (Sweden)

    Nara Chartuni Pereira Teixeira

    Full Text Available OBJECTIVES: To evaluate the prevalence and the risk factors for cervical intraepithelial neoplasia (CIN among HIV-infected women. METHODS: Cross-sectional study of 494 HIV-infected women in Brazil, between 1998 and 2008. Gynecologic exam was performed, and samples were collected for cervical cytology and for HPV DNA detection. Cervical biopsy was carried out when indicated. HPV infection, CD4 T-lymphocyte count and HIV viral load were compared with cervical histopathology. Univariate and multivariate statistical analyses were performed to evaluate the statistical association of several risk factors. RESULTS: CIN prevalence detected by histopathology was 23.4% (6% of CIN2/3 and 17.4% cases of CIN1. Multivariate analysis confirmed an independent association of CIN with CD4 T-lymphocyte count below 200 cells/mm³ (OR 5.0, 95% CI 2.5-10.1, with a positive detection of HPV DNA (OR 2.0, 95% CI 1.2-3.5, and with age < 34 years old (OR 1.5, 95% CI 1.0-2.4. HIV viral load and antiretroviral use were not independent risk factors for CIN. CONCLUSIONS: Severity of immunosupression, presence of HPV infection and younger age are strong predictors of CIN among HIV-infected women.

  5. Trans and cis influences and effects in cobalamins and in their simple models.

    Science.gov (United States)

    De March, Matteo; Demitri, Nicola; Geremia, Silvano; Hickey, Neal; Randaccio, Lucio

    2012-11-01

    The interligand interactions in coordination compounds have been principally interpreted in terms of cis and trans influences and effects, which can be defined as the ability of a ligand X to affect the bond of another ligand, cis or trans to X, to the metal. This review analyzes these effects/influences in cobalamins (XCbl) and their simple models cobaloximes, LCo(chel)X. Important properties of these complexes, such as geometry, stability, and reactivity, can be rationalized in terms of steric and electronic factors of the ligands. Experimental evidence of normal and inverse trans influence is described in alkylcobaloximes for the first time. The study of simple B(12) models has complemented that on the more complex cobalamins, with particular emphasis on the properties of the axial L-Co-X moiety. Some of the conclusions reached for the axial fragment of simple models have also been qualitatively detected in cobalamins and have furnished new insight into the as yet unestablished mechanism for the homolytic cleavage of the Co - C bond in the AdoCbl-based enzymes. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Experimental Analysis of Mimivirus Translation Initiation Factor 4a Reveals Its Importance in Viral Protein Translation during Infection of Acanthamoeba polyphaga.

    Science.gov (United States)

    Bekliz, Meriem; Azza, Said; Seligmann, Hervé; Decloquement, Philippe; Raoult, Didier; La Scola, Bernard

    2018-05-15

    The Acanthamoeba polyphaga mimivirus is the first giant virus ever described, with a 1.2-Mb genome which encodes 979 proteins, including central components of the translation apparatus. One of these proteins, R458, was predicted to initiate translation, although its specific role remains unknown. We silenced the R458 gene using small interfering RNA (siRNA) and compared levels of viral fitness and protein expression in silenced versus wild-type mimivirus. Silencing decreased the growth rate, but viral particle production at the end of the viral cycle was unaffected. A comparative proteomic approach using two-dimensional difference-in-gel electrophoresis (2D-DIGE) revealed deregulation of the expression of 32 proteins in silenced mimivirus, which were defined as up- or downregulated. Besides revealing proteins with unknown functions, silencing R458 also revealed deregulation in proteins associated with viral particle structures, transcriptional machinery, oxidative pathways, modification of proteins/lipids, and DNA topology/repair. Most of these proteins belong to genes transcribed at the end of the viral cycle. Overall, our data suggest that the R458 protein regulates the expression of mimivirus proteins and, thus, that mimivirus translational proteins may not be strictly redundant in relation to those from the amoeba host. As is the case for eukaryotic initiation factor 4a (eIF4a), the R458 protein is the prototypical member of the ATP-dependent DEAD box RNA helicase mechanism. We suggest that the R458 protein is required to unwind the secondary structures at the 5' ends of mRNAs and to bind the mRNA to the ribosome, making it possible to scan for the start codon. These data are the first experimental evidence of mimivirus translation-related genes, predicted to initiate protein biosynthesis. IMPORTANCE The presence in the genome of a mimivirus of genes coding for many translational processes, with the exception of ribosome constituents, has been the subject of

  7. Structural modification of trans-cinnamic acid using Colletotrichum acutatum

    OpenAIRE

    Velasco B., Rodrigo; Gil G., Jesús H.; García P., Carlos M.; Durango R., Diego L.

    2012-01-01

    The biotransformation of trans-cinnamic acid by whole cells of the Colombian native phytopathogenic fungus Colletotrichum acutatum was studied. Initially, fungitoxicity of this compound against C. acutatum was evaluated; trans-cinnamic acid exhibited a moderate to weak toxicity against the microorganism and apparently a detoxification mechanism was present. Then, in order to study such mechanism and explore the capacity of this fungus to biotransform trans-cinnamic acid into value-added produ...

  8. A method to identify dependencies between organizational factors using statistical independence test

    International Nuclear Information System (INIS)

    Kim, Y.; Chung, C.H.; Kim, C.; Jae, M.; Jung, J.H.

    2004-01-01

    A considerable number of studies on organizational factors in nuclear power plants have been made especially in recent years, most of which have assumed organizational factors to be independent. However, since organizational factors characterize the organization in terms of safety and efficiency etc. and there would be some factors that have close relations between them. Therefore, from whatever point of view, if we want to identify the characteristics of an organization, the dependence relationships should be considered to get an accurate result. In this study the organization of a reference nuclear power plant in Korea was analyzed for the trip cases of that plant using 20 organizational factors that Jacobs and Haber had suggested: 1) coordination of work, 2) formalization, 3) organizational knowledge, 4) roles and responsibilities, 5) external communication, 6) inter-department communications, 7) intra-departmental communications, 8) organizational culture, 9) ownership, 10) safety culture, 11) time urgency, 12) centralization, 13) goal prioritization, 14) organizational learning, 15) problem identification, 16) resource allocation, 17) performance evaluation, 18) personnel selection, 19) technical knowledge, and 20) training. By utilizing the results of the analysis, a method to identify the dependence relationships between organizational factors is presented. The statistical independence test for the analysis result of the trip cases is adopted to reveal dependencies. This method is geared to the needs to utilize many kinds of data that has been obtained as the operating years of nuclear power plants increase, and more reliable dependence relations may be obtained by using these abundant data

  9. 2,3-trans-3,4-trans-3,4-Dihydroxy-L-proline: An amino acid in toxic peptides of Amanita virosa mushrooms

    Science.gov (United States)

    Buku, A.; Faulstich, H.; Wieland, T.; Dabrowski, J.

    1980-01-01

    Among the four possible stereoisomers of 3,4-dihydroxy-L-proline,2,3-trans-3,4-trans-3,4-dihydroxy-L-proline (IV) had not been found in nature previously. It has now been detected as a component of virotoxins, toxic peptides of Amanita virosa mushrooms. Because periodate failed to effect an oxidative glycol splitting reaction, the two hydroxyl groups in positions 3 and 4 were expected to be in a trans configuration. Furthermore, the formation of a 4-lactone on treatment with acids pointed to the carboxyl group and the hydroxyl group at position 4 being in a cis configuration. These results are in agreement with structure IV only. Final proof for structure IV was given by NMR spectroscopy and direct comparison with the 2,3-cis-3,4-trans-3,4-dihydroxy-L-proline isomer. PMID:16592813

  10. Optimization of extraction of high purity all-trans-lycopene from tomato pulp waste.

    Science.gov (United States)

    Poojary, Mahesha M; Passamonti, Paolo

    2015-12-01

    The aim of this work was to optimize the extraction of pure all-trans-lycopene from the pulp fractions of tomato processing waste. A full factorial design (FFD) consisting of four independent variables including extraction temperature (30-50 °C), time (1-60 min), percentage of acetone in n-hexane (25-75%, v/v) and solvent volume (10-30 ml) was used to investigate the effects of process variables on the extraction. The absolute amount of lycopene present in the pulp waste was found to be 0.038 mg/g. The optimal conditions for extraction were as follows: extraction temperature 20 °C, time 40 min, a solvent composition of 25% acetone in n-hexane (v/v) and solvent volume 40 ml. Under these conditions, the maximal recovery of lycopene was 94.7%. The HPLC-DAD analysis demonstrated that, lycopene was obtained in the all-trans-configuration at a very high purity grade of 98.3% while the amount of cis-isomers and other carotenoids were limited. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Tracing the influence of the Trans-European Suture Zone into the mantle transition zone

    Czech Academy of Sciences Publication Activity Database

    Knapmeyer-Endrun, B.; Krüger, F.; Legendre, C. P.; Geissler, W.H.; Plomerová, Jaroslava; Babuška, Vladislav; Gaždová, Renata; Jedlička, Petr; Kolínský, Petr; Málek, Jiří; Novotný, Oldřich; Růžek, Bohuslav

    2013-01-01

    Roč. 363, FEB 1 (2013), s. 73-87 ISSN 0012-821X Institutional support: RVO:67985530 ; RVO:67985891 Keywords : mantle transition zone * Trans-European Suture Zone * East European Craton Subject RIV: DC - Siesmology, Volcanology, Earth Structure Impact factor: 4.724, year: 2013

  12. Pluripotency transcription factors and Tet1/2 maintain Brd4-independent stem cell identity.

    Science.gov (United States)

    Finley, Lydia W S; Vardhana, Santosha A; Carey, Bryce W; Alonso-Curbelo, Direna; Koche, Richard; Chen, Yanyang; Wen, Duancheng; King, Bryan; Radler, Megan R; Rafii, Shahin; Lowe, Scott W; Allis, C David; Thompson, Craig B

    2018-05-01

    A robust network of transcription factors and an open chromatin landscape are hallmarks of the naive pluripotent state. Recently, the acetyllysine reader Brd4 has been implicated in stem cell maintenance, but the relative contribution of Brd4 to pluripotency remains unclear. Here, we show that Brd4 is dispensable for self-renewal and pluripotency of embryonic stem cells (ESCs). When maintained in their ground state, ESCs retain transcription factor binding and chromatin accessibility independent of Brd4 function or expression. In metastable ESCs, Brd4 independence can be achieved by increased expression of pluripotency transcription factors, including STAT3, Nanog or Klf4, so long as the DNA methylcytosine oxidases Tet1 and Tet2 are present. These data reveal that Brd4 is not essential for ESC self-renewal. Rather, the levels of pluripotency transcription factor abundance and Tet1/2 function determine the extent to which bromodomain recognition of protein acetylation contributes to the maintenance of gene expression and cell identity.

  13. 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....

  14. 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

  15. Direct binding of retromer to human papillomavirus type 16 minor capsid protein L2 mediates endosome exit during viral infection.

    Directory of Open Access Journals (Sweden)

    Andreea Popa

    2015-02-01

    Full Text Available Trafficking of human papillomaviruses to the Golgi apparatus during virus entry requires retromer, an endosomal coat protein complex that mediates the vesicular transport of cellular transmembrane proteins from the endosome to the Golgi apparatus or the plasma membrane. Here we show that the HPV16 L2 minor capsid protein is a retromer cargo, even though L2 is not a transmembrane protein. We show that direct binding of retromer to a conserved sequence in the carboxy-terminus of L2 is required for exit of L2 from the early endosome and delivery to the trans-Golgi network during virus entry. This binding site is different from known retromer binding motifs and can be replaced by a sorting signal from a cellular retromer cargo. Thus, HPV16 is an unconventional particulate retromer cargo, and retromer binding initiates retrograde transport of viral components from the endosome to the trans-Golgi network during virus entry. We propose that the carboxy-terminal segment of L2 protein protrudes through the endosomal membrane and is accessed by retromer in the cytoplasm.

  16. Spatio-temporal risk factors for viral haemorrhagic septicaemia (VHS) in Danish aquaculture

    DEFF Research Database (Denmark)

    Jensen, Ann Britt Bang; Ersbøll, Annette Kjær; Korsholm, Henrik

    2014-01-01

    Viral haemorrhagic septicaemia (VHS) is an economically very important fish disease in the northern hemisphere. When the VHS virus was first isolated in Denmark 50 yr ago, more than 80% of the 800 Danish fish farms were considered to be infected, but vigilant surveillance and eradication programmes...

  17. Norovirus translation requires an interaction between the C Terminus of the genome-linked viral protein VPg and eukaryotic translation initiation factor 4G.

    Science.gov (United States)

    Chung, Liliane; Bailey, Dalan; Leen, Eoin N; Emmott, Edward P; Chaudhry, Yasmin; Roberts, Lisa O; Curry, Stephen; Locker, Nicolas; Goodfellow, Ian G

    2014-08-01

    Viruses have evolved a variety of mechanisms to usurp the host cell translation machinery to enable translation of the viral genome in the presence of high levels of cellular mRNAs. Noroviruses, a major cause of gastroenteritis in man, have evolved a mechanism that relies on the interaction of translation initiation factors with the virus-encoded VPg protein covalently linked to the 5' end of the viral RNA. To further characterize this novel mechanism of translation initiation, we have used proteomics to identify the components of the norovirus translation initiation factor complex. This approach revealed that VPg binds directly to the eIF4F complex, with a high affinity interaction occurring between VPg and eIF4G. Mutational analyses indicated that the C-terminal region of VPg is important for the VPg-eIF4G interaction; viruses with mutations that alter or disrupt this interaction are debilitated or non-viable. Our results shed new light on the unusual mechanisms of protein-directed translation initiation. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. 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.

  19. Low Trans Hydrogenation

    Science.gov (United States)

    Although hydrogenation has been the technology of choice for fat formulation for many years recent concerns over the health and nutrition of trans fatty acids have had a profound effect on the edible oil industry. Since Jan. 1, 2006, TFA has been required on nutrition labels along with saturated an...

  20. The GAAS metagenomic tool and its estimations of viral and microbial average genome size in four major biomes.

    Directory of Open Access Journals (Sweden)

    Florent E Angly

    2009-12-01

    Full Text Available Metagenomic studies characterize both the composition and diversity of uncultured viral and microbial communities. BLAST-based comparisons have typically been used for such analyses; however, sampling biases, high percentages of unknown sequences, and the use of arbitrary thresholds to find significant similarities can decrease the accuracy and validity of estimates. Here, we present Genome relative Abundance and Average Size (GAAS, a complete software package that provides improved estimates of community composition and average genome length for metagenomes in both textual and graphical formats. GAAS implements a novel methodology to control for sampling bias via length normalization, to adjust for multiple BLAST similarities by similarity weighting, and to select significant similarities using relative alignment lengths. In benchmark tests, the GAAS method was robust to both high percentages of unknown sequences and to variations in metagenomic sequence read lengths. Re-analysis of the Sargasso Sea virome using GAAS indicated that standard methodologies for metagenomic analysis may dramatically underestimate the abundance and importance of organisms with small genomes in environmental systems. Using GAAS, we conducted a meta-analysis of microbial and viral average genome lengths in over 150 metagenomes from four biomes to determine whether genome lengths vary consistently between and within biomes, and between microbial and viral communities from the same environment. Significant differences between biomes and within aquatic sub-biomes (oceans, hypersaline systems, freshwater, and microbialites suggested that average genome length is a fundamental property of environments driven by factors at the sub-biome level. The behavior of paired viral and microbial metagenomes from the same environment indicated that microbial and viral average genome sizes are independent of each other, but indicative of community responses to stressors and

  1. PASSEQ 2006-2008: Passive Seismic Experiment in Trans-Europe Suture ZoneI

    Czech Academy of Sciences Publication Activity Database

    Wilde-Piórko, M.; Geissler, W.H.; Plomerová, Jaroslava; Grad, M.; Babuška, Vladislav; Brückl, E.; Cyziene, J.; Czuba, W.; England, R.; Gaczyński, E.; Gaždová, Renata; Gregersen, S.; Guterch, A.; Hanka, W.; Hegedüs, E.; Heuer, B.; Jedlička, Petr; Lazauskiene, J.; Keller, G. R.; Kind, R.; Klinge, K.; Kolínský, Petr; Komminaho, K.; Kozlovskaya, E.; Krüger, F.; Larsen, T.; Majdański, M.; Málek, Jiří; Motuza, G.; Novotný, Oldřich; Pietrasiak, R.; Plenefisch, T.; Růžek, Bohuslav; Sliaupa, S.; Środa, P.; Świeczak, M.; Tiira, T.; Voss, P.; Wiejacz, P.

    2008-01-01

    Roč. 52, č. 3 (2008), s. 439-448 ISSN 0039-3169 R&D Projects: GA AV ČR IAA300120709 Institutional research plan: CEZ:AV0Z30120515; CEZ:AV0Z30460519 Keywords : lithosphere-asthenosphere system * Trans-European Suture Zone * Teisseyre- Tor nquist Zone Subject RIV: DC - Siesmology, Volcanology, Earth Structure Impact factor: 0.770, year: 2008

  2. Application of spatial models to the stopover ecology of trans-Gulf migrants

    Science.gov (United States)

    Theodore R. Simons; Scott M. Pearson; Frank R. Moore

    2000-01-01

    Studies at migratory stopover sites along the northern coast of the Gulf of Mexico are providing an understanding of how weather, habitat, and energetic factors combine to shape the stopover ecology of trans-Gulf migrants. We are coupling this understanding with analyses of landscape-level patterns of habitat availability by using spatially explicit models to simulate...

  3. Correlation of Erythrocyte Trans Fatty Acids with Ovulatory Disorder Infertility in Polycystic Ovarian Syndrome

    Directory of Open Access Journals (Sweden)

    Aisa Ghaffarzad

    2014-07-01

    Full Text Available Trans fatty acids are considered to be the important modifiable factor of the ovulatory infertility disorder. The purpose of this study was to test the hypothesis that higher trans fatty acids of erythrocytes (RBC are associated with the risk of ovulatory infertility disorder in polycystic ovarian syndrome (PCOS. Thirty five infertile women with polycystic ovarian syndrome, defined by AES criteria and 29 age-matched healthy women as a control group were recruited for the study. After physical measurements and nutritional assessment, blood samples were collected. Fasting serum glucose and insulin were measured, and then insulin resistance was calculated by homeostasis model assessment (HOMA-IR. Erythrocyte fatty acids were measured by gas chromatography. The patients group had higher waist circumference (WC, insulin levels, HOMA-IR than controls (p< 0.05. Also, case group had lower percentage of normal BMI (BMI<25, physical activity and education levels than healthy women (p< 0.05. Among RBC trans fatty acids only trans linoleate (18:2t were significantly higher in case group than control women (p= 0.019. PCOS group tended to consume more food rich in TFAs than the control group. Logistic regression analysis also showed that only 18:2t is positively associated with risk of ovulatory disorder infertility in PCOS (OR= 1.225, 95% CI. 1.024-1.465; P= 0.026, which was not affected after adjustment for BMI, physical activity and education levels. The results suggested that RBC trans fatty acids might be a predictor of increased risk for ovulatory infertility disorder in women with PCOS.

  4. 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

  5. Perfil nutricional de alimentos com alegação de zero gordura trans Nutritional profile of foods with zero trans fatty acids claim

    Directory of Open Access Journals (Sweden)

    Ana Carolina Moron Gagliardi

    2009-01-01

    Full Text Available OBJETIVO: Avaliar a composição de ácidos graxos de alguns alimentos industrializados disponíveis no mercado brasileiro nos quais houve redução da quantidade de ácidos graxos trans. Verificar também se estes alimentos atendem às quantidades recomendadas de consumo de gordura saturada, após redução de gordura trans. MÉTODOS: Alimentos industrializados (margarina cremosa A e B, margarina com fitosterol, biscoito doce recheado, biscoito salgado sem recheio, batata frita e lanche com hambúrguer de fast food multinacional com alegação de 0% de gordura trans foram adquiridos em pontos comerciais e analisados em cromatógrafo gasoso. RESULTADOS: Apesar da redução nas quantidades de ácidos graxos trans, os alimentos analisados contêm grandes quantidades de gorduras saturadas principalmente o ácido palmítico. Além disso, alguns dos alimentos estudados apresentam uma razão n-3/n-6 fora do recomendado para a prevenção da aterosclerose. CONCLUSÃO: O consumo irrestrito desses alimentos tem forte potencial deletério para a saúde. O rótulo de ausência de ácidos graxos trans deve ser visto com cuidado e não significa uma liberação para o consumo irrestrito desses alimentos.OBJECTIVE: To evaluate the composition of fatty acids in some foods available in the Brazilian market in which there was a claimed reduction in the amount of trans fatty acids. Also evaluate whether these foods meet recommended amounts for saturated fat consumption, after reduction of trans fat amounts. METHODS: Industrialized food (creamy margarine A and B, plant sterol margarine, stuffed sweet biscuit, salty biscuit without stuffing, French fried potatoes and a burger lunch from a multinational chain of "fast food" all with the allegation of 0% trans fat content were purchased in commercial points and analyzed by gas chromatography. RESULTS: Despite the reduction in trans fatty acid amounts, analyzed foods contained large concentrations of saturated fats

  6. Independent Activation of Hepatitis B Virus Biosynthesis by Retinoids, Peroxisome Proliferators, and Bile Acids

    Science.gov (United States)

    Reese, Vanessa C.; Oropeza, Claudia E.

    2013-01-01

    In the human hepatoma cell line HepG2, retinoic acid, clofibric acid, and bile acid treatment can only modestly increase hepatitis B virus (HBV) biosynthesis. Utilizing the human embryonic kidney cell line 293T, it was possible to demonstrate that the retinoid X receptor α (RXRα) plus its ligand can support viral biosynthesis independently of additional nuclear receptors. In addition, RXRα/peroxisome proliferator-activated receptor α (PPARα) and RXRα/farnesoid X receptor α (FXRα) heterodimeric nuclear receptors can also mediate ligand-dependent HBV transcription and replication when activated by clofibric acid and bile acid, respectively, independently of a requirement for the ligand-dependent activation of RXRα. These observations indicate that there are at least three possible modes of ligand-mediated activation of HBV transcription and replication existing within hepatocytes, suggesting that multiple independent mechanisms control viral production in the livers of infected individuals. PMID:23135717

  7. Intake of ruminant trans fatty acids and changes in body weight and waist circumference

    DEFF Research Database (Denmark)

    Hansen, Carsten Palnæs; Berentzen, T L; Halkjær, Jytte

    2012-01-01

    Follow-up studies have suggested that total intake of trans fatty acids (TFA) is a risk factor for gain in body weight and waist circumference (WC). However, in a cross-sectional study individual TFA isomers in adipose tissue had divergent associations with anthropometry. Our objective...

  8. Cis–Trans Configuration of Coumaric Acid Acylation Affects the Spectral and Colorimetric Properties of Anthocyanins

    Directory of Open Access Journals (Sweden)

    Gregory T. Sigurdson

    2018-03-01

    Full Text Available The color expression of anthocyanins can be affected by a variety of environmental factors and structural characteristics. Anthocyanin acylation (type and number of acids is known to be key, but the influence of acyl isomers (with unique stereochemistries remains to be explored. The objective of this study was to investigate the effects of cis–trans configuration of the acylating group on the spectral and colorimetric properties of anthocyanins. Petunidin-3-rutinoside-5-glucoside (Pt-3-rut-5-glu and Delphinidin-3-rutinoside-5-glucoside (Dp-3-rut-5-glu and their cis and trans coumaroylated derivatives were isolated from black goji and eggplant, diluted in pH 1–9 buffers, and analyzed spectrophotometrically (380–700 nm and colorimetrically (CIELAB during 72 h of storage (25 °C, dark. The stereochemistry of the acylating group strongly impacted the spectra, color, and stability of the Dp and Pt anthocyanins. Cis acylated pigments exhibited the greatest λmax in all pH, as much as 66 nm greater than their trans counterparts, showing bluer hues. Cis acylation seemed to reduce hydration across pH, increasing color intensity, while trans acylation generally improved color retention over time. Dp-3-cis-p-cou-rut-5-glu exhibited blue hues even in pH 5 (C*ab = 10, hab = 256° where anthocyanins are typically colorless. Cis or trans double bond configurations of the acylating group affected anthocyanin spectral and stability properties.

  9. Comorbidity is an independent prognostic factor for the survival of ovarian cancer

    DEFF Research Database (Denmark)

    Sperling, Cecilie; Noer, Mette Calundann; Christensen, Ib Jarle

    2013-01-01

    OBJECTIVE: The aim of the study was to examine whether comorbidity is an independent prognostic factor for 3129 women diagnosed with ovarian cancer from 2005 to 2011. As Performance status (PS) might capture the impact of comorbidity we addressed whether comorbidity can be explained by PS or whet...

  10. Fusion of Epstein-Barr virus nuclear antigen-1-derived glycine-alanine repeat to trans-dominant HIV-1 Gag increases inhibitory activities and survival of transduced cells in vivo.

    Science.gov (United States)

    Hammer, Diana; Wild, Jens; Ludwig, Christine; Asbach, Benedikt; Notka, Frank; Wagner, Ralf

    2008-06-01

    Trans-dominant human immunodeficiency virus type 1 (HIV-1) Gag derivatives have been shown to efficiently inhibit late steps of HIV-1 replication in vitro by interfering with Gag precursor assembly, thus ranking among the interesting candidates for gene therapy approaches. However, efficient antiviral activities of corresponding transgenes are likely to be counteracted in particular by cell-mediated host immune responses toward the transgene-expressing cells. To decrease this potential immunogenicity, a 24-amino acid Gly-Ala (GA) stretch derived from Epstein-Barr virus nuclear antigen-1 (EBNA1) and known to overcome proteasomal degradation was fused to a trans-dominant Gag variant (sgD1). To determine the capacity of this fusion polypeptide to repress viral replication, PM-1 cells were transduced with sgD1 and GAsgD1 transgenes, using retroviral gene transfer. Challenge of stably transfected permissive cell lines with various viral strains indicated that N-terminal GA fusion even enhanced the inhibitory properties of sgD1. Further studies revealed that the GA stretch increased protein stability by blocking proteasomal degradation of Gag proteins. Immunization of BALB/c mice with a DNA vaccine vector expressing sgD1 induced substantial Gag-specific immune responses that were, however, clearly diminished in the presence of GA. Furthermore, recognition of cells expressing the GA-fused transgene by CD8(+) T cells was drastically reduced, both in vitro and in vivo, resulting in prolonged survival of the transduced cells in recipient mice.

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

    Directory of Open Access Journals (Sweden)

    Beatriz M. A. Fontoura

    2013-07-01

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

  12. 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

  13. Molecular features contributing to virus-independent intracellular localization and dynamic behavior of the herpesvirus transport protein US9.

    Directory of Open Access Journals (Sweden)

    Manuela Pedrazzi

    Full Text Available Reaching the right destination is of vital importance for molecules, proteins, organelles, and cargoes. Thus, intracellular traffic is continuously controlled and regulated by several proteins taking part in the process. Viruses exploit this machinery, and viral proteins regulating intracellular transport have been identified as they represent valuable tools to understand and possibly direct molecules targeting and delivery. Deciphering the molecular features of viral proteins contributing to (or determining this dynamic phenotype can eventually lead to a virus-independent approach to control cellular transport and delivery. From this virus-independent perspective we looked at US9, a virion component of Herpes Simplex Virus involved in anterograde transport of the virus inside neurons of the infected host. As the natural cargo of US9-related vesicles is the virus (or its parts, defining its autonomous, virus-independent role in vesicles transport represents a prerequisite to make US9 a valuable molecular tool to study and possibly direct cellular transport. To assess the extent of this autonomous role in vesicles transport, we analyzed US9 behavior in the absence of viral infection. Based on our studies, Us9 behavior appears similar in different cell types; however, as expected, the data we obtained in neurons best represent the virus-independent properties of US9. In these primary cells, transfected US9 mostly recapitulates the behavior of US9 expressed from the viral genome. Additionally, ablation of two major phosphorylation sites (i.e. Y32Y33 and S34ES36 have no effect on protein incorporation on vesicles and on its localization on both proximal and distal regions of the cells. These results support the idea that, while US9 post-translational modification may be important to regulate cargo loading and, consequently, virion export and delivery, no additional viral functions are required for US9 role in intracellular transport.

  14. Esophageal Motor Disorders Are a Strong and Independant Associated Factor of Barrett's Esophagus.

    Science.gov (United States)

    Bazin, Camille; Benezech, Alban; Alessandrini, Marine; Grimaud, Jean-Charles; Vitton, Veronique

    2018-04-30

    Esophageal motor disorder (EMD) has been shown to be associated with gastroesophageal reflux disease (GERD). However, the association of EMD with a Barrett's esophagus (BE) is controversial. Our objective was to evaluate whether the presence of EMD was an independent factor associated with BE. A retrospective case-control study was conducted in GERD patients who all had oeso-gastroduodenal endoscopy and high-resolution esophageal manometry. The clinical data collected was known or potential risk factors for BE: male gender, smoking and alcohol consumption, age, body mass index, presence of hiatal hernia, frequency, and age of GERD. EMD were classified according to the Chicago classification into: ineffective motor syndrome, fragmented peristalsis and absence of peristalsis, lower esophageal sphincter hypotonia. Two hundred and one patients (101 in the GERD + BE group and 100 in the GERD without BE) were included. In univariate analysis, male gender, alcohol consumption, presence of hiatal hernia, and EMD appeared to be associated with the presence of BE. In a multivariate analysis, 3 independent factors were identified: the presence of EMD (odds ratio [OR], 3.99; 95% confidence interval [CI], 1.71-9.28; P = 0.001), the presence of hiatal hernia (OR, 5.60; 95% CI, 2.45-12.76; P < 0.001), Helicobacter pylori infection (OR, 0.08; 95% CI, 0.01-0.84; P = 0.035). The presence of EMD (particularly ineffective motor syndrome and lower esophageal sphincter hypotonia) is a strong independent associated factor of BE. Searching systematically for an EMD in patients suffering from GERD could be a new strategy to organize the endoscopic follow-up.

  15. The glycoprotein Ib-IX-V complex contributes to tissue factor-independent thrombin generation by recombinant factor VIIa on the activated platelet surface

    NARCIS (Netherlands)

    Weeterings, Cees; de Groot, Philip G.; Adelmeijer, Jelle; Lisman, Ton

    2008-01-01

    Several lines of evidence suggest that recombinant factor VIIa (rFVIIa) is able to activate factor X on an activated platelet, in a tissue factor-independent manner. We hypothesized that, besides the anionic surface, a receptor on the activated platelet surface is involved in this process. Here, we

  16. Value of Sharing: Viral Advertisement

    OpenAIRE

    Duygu Aydın; Aşina Gülerarslan; Süleyman Karaçor; Tarık Doğan

    2013-01-01

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

  17. Viral Marketing and Academic Institution

    OpenAIRE

    Koktová, Silvie

    2010-01-01

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

  18. cis elements and trans-acting factors involved in dimer formation of murine leukemia virus RNA.

    Science.gov (United States)

    Prats, A C; Roy, C; Wang, P A; Erard, M; Housset, V; Gabus, C; Paoletti, C; Darlix, J L

    1990-02-01

    The genetic material of all retroviruses examined so far consists of two identical RNA molecules joined at their 5' ends by the dimer linkage structure (DLS). Since the precise location of the DLS as well as the mechanism and role(s) of RNA dimerization remain unclear, we analyzed the dimerization process of Moloney murine leukemia virus (MoMuLV) genomic RNA. For this purpose we derived an in vitro model for RNA dimerization. By using this model, murine leukemia virus RNA was shown to form dimeric molecules. Deletion mutagenesis in the 620-nucleotide leader of MoMuLV RNA showed that the dimer promoting sequences are located within the encapsidation element Psi between positions 215 and 420. Furthermore, hybridization assays in which DNA oligomers were used to probe monomer and dimer forms of MoMuLV RNA indicated that the DLS probably maps between positions 280 and 330 from the RNA 5' end. Also, retroviral nucleocapsid protein was shown to catalyze dimerization of MoMuLV RNA and to be tightly bound to genomic dimer RNA in virions. These results suggest that MoMuLV RNA dimerization and encapsidation are probably controlled by the same cis element, Psi, and trans-acting factor, nucleocapsid protein, and thus might be linked during virion formation.

  19. Contribution of the C-terminal tri-lysine regions of human immunodeficiency virus type 1 integrase for efficient reverse transcription and viral DNA nuclear import

    Directory of Open Access Journals (Sweden)

    Fowke Keith R

    2005-10-01

    Full Text Available Abstract Background In addition to mediating the integration process, HIV-1 integrase (IN has also been implicated in different steps during viral life cycle including reverse transcription and viral DNA nuclear import. Although the karyophilic property of HIV-1 IN has been well demonstrated using a variety of experimental approaches, the definition of domain(s and/or motif(s within the protein that mediate viral DNA nuclear import and its mechanism are still disputed and controversial. In this study, we performed mutagenic analyses to investigate the contribution of different regions in the C-terminal domain of HIV-1 IN to protein nuclear localization as well as their effects on virus infection. Results Our analysis showed that replacing lysine residues in two highly conserved tri-lysine regions, which are located within previously described Region C (235WKGPAKLLWKGEGAVV and sequence Q (211KELQKQITK in the C-terminal domain of HIV-1 IN, impaired protein nuclear accumulation, while mutations for RK263,4 had no significant effect. Analysis of their effects on viral infection in a VSV-G pseudotyped RT/IN trans-complemented HIV-1 single cycle replication system revealed that all three C-terminal mutant viruses (KK215,9AA, KK240,4AE and RK263,4AA exhibited more severe defect of induction of β-Gal positive cells and luciferase activity than an IN class 1 mutant D64E in HeLa-CD4-CCR5-β-Gal cells, and in dividing as well as non-dividing C8166 T cells, suggesting that some viral defects are occurring prior to viral integration. Furthermore, by analyzing viral DNA synthesis and the nucleus-associated viral DNA level, the results clearly showed that, although all three C-terminal mutants inhibited viral reverse transcription to different extents, the KK240,4AE mutant exhibited most profound effect on this step, whereas KK215,9AA significantly impaired viral DNA nuclear import. In addition, our analysis could not detect viral DNA integration in each C

  20. Quality control in the development of coagulation factor concentrates.

    Science.gov (United States)

    Snape, T J

    1987-01-01

    Limitation of process change is a major factor contributing to assurance of quality in pharmaceutical manufacturing. This is particularly true in the manufacture of coagulation factor concentrates, for which presumptive testing for poorly defined product characteristics is an integral feature of finished product quality control. The development of new or modified preparations requires that this comfortable position be abandoned, and that the effect on finished product characteristics of changes to individual process steps (and components) be assessed. The degree of confidence in the safety and efficacy of the new product will be determined by, amongst other things, the complexity of the process alteration and the extent to which the results of finished product tests can be considered predictive. The introduction of a heat-treatment step for inactivation of potential viral contaminants in coagulation factor concentrates presents a significant challenge in both respects, quite independent of any consideration of assessment of the effectiveness of the viral inactivation step. These interactions are illustrated by some of the problems encountered with terminal dry heat-treatment (72 h. at 80 degrees C) of factor VIII and prothrombin complex concentrates manufactured by the Blood Products Laboratory.

  1. An Adenovirus DNA Replication Factor, but Not Incoming Genome Complexes, Targets PML Nuclear Bodies.

    Science.gov (United States)

    Komatsu, Tetsuro; Nagata, Kyosuke; Wodrich, Harald

    2016-02-01

    Promyelocytic leukemia protein nuclear bodies (PML-NBs) are subnuclear domains implicated in cellular antiviral responses. Despite the antiviral activity, several nuclear replicating DNA viruses use the domains as deposition sites for the incoming viral genomes and/or as sites for viral DNA replication, suggesting that PML-NBs are functionally relevant during early viral infection to establish productive replication. Although PML-NBs and their components have also been implicated in the adenoviral life cycle, it remains unclear whether incoming adenoviral genome complexes target PML-NBs. Here we show using immunofluorescence and live-cell imaging analyses that incoming adenovirus genome complexes neither localize at nor recruit components of PML-NBs during early phases of infection. We further show that the viral DNA binding protein (DBP), an early expressed viral gene and essential DNA replication factor, independently targets PML-NBs. We show that DBP oligomerization is required to selectively recruit the PML-NB components Sp100 and USP7. Depletion experiments suggest that the absence of one PML-NB component might not affect the recruitment of other components toward DBP oligomers. Thus, our findings suggest a model in which an adenoviral DNA replication factor, but not incoming viral genome complexes, targets and modulates PML-NBs to support a conducive state for viral DNA replication and argue against a generalized concept that PML-NBs target incoming viral genomes. The immediate fate upon nuclear delivery of genomes of incoming DNA viruses is largely unclear. Early reports suggested that incoming genomes of herpesviruses are targeted and repressed by PML-NBs immediately upon nuclear import. Genome localization and/or viral DNA replication has also been observed at PML-NBs for other DNA viruses. Thus, it was suggested that PML-NBs may immediately sense and target nuclear viral genomes and hence serve as sites for deposition of incoming viral genomes and

  2. Non-viral generation of marmoset monkey iPS cells by a six-factor-in-one-vector approach.

    Science.gov (United States)

    Debowski, Katharina; Warthemann, Rita; Lentes, Jana; Salinas-Riester, Gabriela; Dressel, Ralf; Langenstroth, Daniel; Gromoll, Jörg; Sasaki, Erika; Behr, Rüdiger

    2015-01-01

    Groundbreaking studies showed that differentiated somatic cells of mouse and human origin could be reverted to a stable pluripotent state by the ectopic expression of only four proteins. The resulting pluripotent cells, called induced pluripotent stem (iPS) cells, could be an alternative to embryonic stem cells, which are under continuous ethical debate. Hence, iPS cell-derived functional cells such as neurons may become the key for an effective treatment of currently incurable degenerative diseases. However, besides the requirement of efficacy testing of the therapy also its long-term safety needs to be carefully evaluated in settings mirroring the clinical situation in an optimal way. In this context, we chose the long-lived common marmoset monkey (Callithrix jacchus) as a non-human primate species to generate iPS cells. The marmoset monkey is frequently used in biomedical research and is gaining more and more preclinical relevance due to the increasing number of disease models. Here, we describe, to our knowledge, the first-time generation of marmoset monkey iPS cells from postnatal skin fibroblasts by non-viral means. We used the transposon-based, fully reversible piggyback system. We cloned the marmoset monkey reprogramming factors and established robust and reproducible reprogramming protocols with a six-factor-in-one-construct approach. We generated six individual iPS cell lines and characterized them in comparison with marmoset monkey embryonic stem cells. The generated iPS cells are morphologically indistinguishable from marmoset ES cells. The iPS cells are fully reprogrammed as demonstrated by differentiation assays, pluripotency marker expression and transcriptome analysis. They are stable for numerous passages (more than 80) and exhibit euploidy. In summary, we have established efficient non-viral reprogramming protocols for the derivation of stable marmoset monkey iPS cells, which can be used to develop and test cell replacement therapies in

  3. Non-viral generation of marmoset monkey iPS cells by a six-factor-in-one-vector approach.

    Directory of Open Access Journals (Sweden)

    Katharina Debowski

    Full Text Available Groundbreaking studies showed that differentiated somatic cells of mouse and human origin could be reverted to a stable pluripotent state by the ectopic expression of only four proteins. The resulting pluripotent cells, called induced pluripotent stem (iPS cells, could be an alternative to embryonic stem cells, which are under continuous ethical debate. Hence, iPS cell-derived functional cells such as neurons may become the key for an effective treatment of currently incurable degenerative diseases. However, besides the requirement of efficacy testing of the therapy also its long-term safety needs to be carefully evaluated in settings mirroring the clinical situation in an optimal way. In this context, we chose the long-lived common marmoset monkey (Callithrix jacchus as a non-human primate species to generate iPS cells. The marmoset monkey is frequently used in biomedical research and is gaining more and more preclinical relevance due to the increasing number of disease models. Here, we describe, to our knowledge, the first-time generation of marmoset monkey iPS cells from postnatal skin fibroblasts by non-viral means. We used the transposon-based, fully reversible piggyback system. We cloned the marmoset monkey reprogramming factors and established robust and reproducible reprogramming protocols with a six-factor-in-one-construct approach. We generated six individual iPS cell lines and characterized them in comparison with marmoset monkey embryonic stem cells. The generated iPS cells are morphologically indistinguishable from marmoset ES cells. The iPS cells are fully reprogrammed as demonstrated by differentiation assays, pluripotency marker expression and transcriptome analysis. They are stable for numerous passages (more than 80 and exhibit euploidy. In summary, we have established efficient non-viral reprogramming protocols for the derivation of stable marmoset monkey iPS cells, which can be used to develop and test cell replacement

  4. Design of Trypanosoma rangeli sialidase mutants with improved trans-sialidase activity.

    Directory of Open Access Journals (Sweden)

    Christian Nyffenegger

    Full Text Available A sialidase (EC 3.2.1.18 from the non-pathogenic Trypanosoma rangeli, TrSA, has been shown to exert trans-sialidase activity after mutation of five specific amino acids in the active site (M96V, A98P, S120Y, G249Y, Q284P to form the so-called TrSA5mut enzyme. By computational and hypothesis driven approaches additional mutations enhancing the trans-sialidase activity have been suggested. In the present work, we made a systematic combination of these mutations leading to seven new variants of the T. rangeli sialidase, having 6-16 targeted amino acid mutations. The resulting enzyme variants were analyzed via kinetics for their ability to carry out trans-sialidase reaction using CGMP and D-lactose as substrates. The sialidase variants with 15 and 16 mutations, respectively, exhibited significantly improved trans-sialidase activity for D-lactose sialylation. Our results corroborate, that computational studies of trans-glycosylation can be a valuable input in the design of novel trans-glycosidases, but also highlight the importance of experimental validation in order to assess the performance. In conclusion, two of the seven mutants displayed a dramatic switch in specificity from hydrolysis towards trans-sialylation and constitute the most potent trans-sialidase mutants of TrSA described in literature to date.

  5. [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

  6. Depressive symptoms and inflammation are independent risk factors of fatigue in breast cancer survivors.

    Science.gov (United States)

    Xiao, C; Miller, A H; Felger, J; Mister, D; Liu, T; Torres, M A

    2017-07-01

    Psychosocial and inflammatory factors have been associated with fatigue in breast cancer survivors. Nevertheless, the relative contribution and/or interaction of these factors with cancer-related fatigue have not been well documented. This cross-sectional study enrolled 111 stage 0-III breast cancer patients treated with breast surgery followed by whole breast radiotherapy. Fatigue was measured by the total score of the Multidimensional Fatigue Inventory-20. Potential risk factors included inflammatory markers (plasma cytokines and their receptors and C-reactive protein; CRP), depressive symptoms (as assessed by the Inventory of Depressive Symptomatology-Self Reported), sleep (as assessed by the Pittsburgh Sleep Quality Index) and perceived stress (as assessed by the Perceived Stress Scale) as well as age, race, marital status, smoking history, menopause status, endocrine treatment, chemotherapy and cancer stage. Linear regression modeling was employed to examine risk factors of fatigue. Only risk factors with a significance level fatigue. At 1 year post-radiotherapy, depressive symptoms (pfatigue. Mediation analysis showed that depressive symptoms also mediated the associations of fatigue with sleep and stress. Depressive symptoms and inflammation were independent risk factors for cancer-related fatigue at 1 year post-radiotherapy, and thus represent independent treatment targets for this debilitating symptom.

  7. Interesterificação química: alternativa para obtenção de gorduras zero trans Chemical interresterification: alternative to production of zero trans fats

    Directory of Open Access Journals (Sweden)

    Ana Paula Badan Ribeiro

    2007-10-01

    Full Text Available The function of lipids in human nutrition has been intensively debated in the last decade.This context reinforces the concern about controlling the trans fat ingestion, due to its negative implications on health. Interesterification provides an important alternative to modify the consistency of oils and fats without causing formation of trans isomers. This article reports research done towards production of zero trans fats by chemical interesterification, for different industrial purposes. Aspects related to the effect of trans fats on diet, their impact on health and modifications in Brazilian legislation are also covered.

  8. Trans-dinitroglycoluril isomers-A DFT treatment

    Directory of Open Access Journals (Sweden)

    Lemi Türker

    2017-02-01

    Full Text Available Isomers of trans-1,4-Dinitroglycoluril (trans-DINGU and their 1,3-tautomers are considered within the constraints of B3LYP/6-31++G (d,p and B3LYP/CC-PVTZ levels of DFT calculations. Additionally, the interactions of these isomers and proton in vacuum are investigated. The data have revealed that two of the three isomers undergo CH bond cleavage as the result of interaction with proton in vacuum. The total energies, some structural properties, the calculated IR and UV spectra are discussed.

  9. A viral, transporter associated with antigen processing (TAP)-independent, high affinity ligand with alternative interactions endogenously presented by the nonclassical human leukocyte antigen E class I molecule.

    Science.gov (United States)

    Lorente, Elena; Infantes, Susana; Abia, David; Barnea, Eilon; Beer, Ilan; García, Ruth; Lasala, Fátima; Jiménez, Mercedes; Mir, Carmen; Morreale, Antonio; Admon, Arie; López, Daniel

    2012-10-12

    The transporter associated with antigen processing (TAP) enables the flow of viral peptides generated in the cytosol by the proteasome and other proteases to the endoplasmic reticulum, where they complex with nascent human leukocyte antigen (HLA) class I. Later, these peptide-HLA class I complexes can be recognized by CD8(+) lymphocytes. Cancerous cells and infected cells in which TAP is blocked, as well as individuals with unusable TAP complexes, are able to present peptides on HLA class I by generating them through TAP-independent processing pathways. Here, we identify a physiologically processed HLA-E ligand derived from the D8L protein in TAP-deficient vaccinia virus-infected cells. This natural high affinity HLA-E class I ligand uses alternative interactions to the anchor motifs previously described to be presented on nonclassical HLA class I molecules. This octameric peptide was also presented on HLA-Cw1 with similar binding affinity on both classical and nonclassical class I molecules. In addition, this viral peptide inhibits HLA-E-mediated cytolysis by natural killer cells. Comparison between the amino acid sequences of the presenting HLA-E and HLA-Cw1 alleles revealed a shared structural motif in both HLA class molecules, which could be related to their observed similar cross-reactivity affinities. This motif consists of several residues located on the floor of the peptide-binding site. These data expand the role of HLA-E as an antigen-presenting molecule.

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

    Science.gov (United States)

    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

  11. A simplified study of trans-mitral Doppler patterns

    Directory of Open Access Journals (Sweden)

    Thomas George

    2008-11-01

    Full Text Available Abstract Background Trans-mitral Doppler produces complex patterns with a great deal of variability. There are several confusing numerical measures and indices to study these patterns. However trans-mitral Doppler produces readymade data visualization by pattern generation which could be interpreted by pattern analysis. By following a systematic approach we could create an order and use this tool to study cardiac function. Presentation of the hypothesis In this new approach we eliminate the variables and apply pattern recognition as the main criterion of study. Proper terminologies are also devised to avoid confusion. In this way we can get some meaningful information. Testing the hypothesis Trans-mitral Doppler should be seen as patterns rather than the amplitude. The hypothesis can be proven by logical deduction, extrapolation and elimination of variables. Trans-mitral flow is also analyzed vis-à-vis the Starling's Law applied to the left atrium. Implications of the hypothesis Trans-mitral Doppler patterns are not just useful for evaluating diastolic function. They are also useful to evaluate systolic function. By following this schema we could get useful diagnostic information and therapeutic options using simple pattern recognition with minimal measurements. This simplified but practical approach will be useful in day to day clinical practice and help in understanding cardiac function better. This will also standardize research and improve communication.

  12. Technical Note: Assessing predictive capacity and conditional independence of landslide predisposing factors for shallow landslide susceptibility models

    Directory of Open Access Journals (Sweden)

    S. Pereira

    2012-04-01

    Full Text Available The aim of this study is to identify the landslide predisposing factors' combination using a bivariate statistical model that best predicts landslide susceptibility. The best model is one that has simultaneously good performance in terms of suitability and predictive power and has been developed using variables that are conditionally independent. The study area is the Santa Marta de Penaguião council (70 km2 located in the Northern Portugal.

    In order to identify the best combination of landslide predisposing factors, all possible combinations using up to seven predisposing factors were performed, which resulted in 120 predictions that were assessed with a landside inventory containing 767 shallow translational slides. The best landslide susceptibility model was selected according to the model degree of fitness and on the basis of a conditional independence criterion. The best model was developed with only three landslide predisposing factors (slope angle, inverse wetness index, and land use and was compared with a model developed using all seven landslide predisposing factors.

    Results showed that it is possible to produce a reliable landslide susceptibility model using fewer landslide predisposing factors, which contributes towards higher conditional independence.

  13. Trans-sphenoidal excision of craniopharyngiomas.

    Directory of Open Access Journals (Sweden)

    Nagpal R

    1991-04-01

    Full Text Available Craniopharyngiomas have been by and large excised by the transcranial route. Since 1982, 11 patients have been operated by the traus-sphensidal route in the department. The clinical features with which they were presented, diagnostic investigations, details of surgical procedures and follow-up analysis is being presented here. A retrospective study of radiological investigation was done to determine the features that help decide the choice of surgical approach to these lesions. Only lesions that were primarily intrasellar, cystic and those that expanded the sella could be treated by the trans-sphenoidal route. Associated suprasellar extensions could also be removed. Predominantly calcified or firm, fleshy tumours lent themselves poorly to removal by the trans-sphenoidal route.

  14. Acute viral bronchiolitis and risk of asthma in schoolchildren: analysis of a Brazilian newborn cohort.

    Science.gov (United States)

    Brandão, Heli V; Vieira, Graciete O; Vieira, Tatiana O; Cruz, Álvaro A; Guimarães, Armênio C; Teles, Carlos; Camargos, Paulo; Cruz, Constança M S

    To verify whether the occurrence of acute viral bronchiolitis in the first year of life constitutes a risk factor for asthma at age 6 considering a parental history of asthma. Cross-sectional study in a cohort of live births. A standardized questionnaire of the International Study of Asthma and Allergies in Childhood was applied to the mothers to identify asthma in children at the age of 6 years. Acute viral bronchiolitis diagnosis was performed by maternal report of a medical diagnosis and/or presence of symptoms of coryza accompanied by cough, tachypnea, and dyspnea when participants were 3, 6, 9, and 12 months. Socioeconomic, environmental data, parental history of asthma, and data related to pregnancy were collected in the first 72h of life of the newborn and in prospective home visits by trained interviewers. The association between acute viral bronchiolitis and asthma was evaluated by logistic regression analysis and potential modifier effect of parental history was verified by introducing an interaction term into the adjusted logistic regression model. Prevalence of acute viral bronchiolitis in the first year of life was 68.6% (461). The occurrence of acute viral bronchiolitis was a risk factor for asthma at 6 years of age in children with parental history of asthma OR: 2.66, 95% CI (1.10-6.40), modifier effect p=0.002. Parental history of asthma OR: 2.07, 95% CI (1.29-3.30) and male gender OR: 1.69, 95% CI, (1.06-2.69) were other identified risk factors for asthma. Acute viral bronchiolitis in the first year of life is a risk factor for asthma in children with parental history of asthma. Copyright © 2016. Published by Elsevier Editora Ltda.

  15. Acute viral bronchiolitis and risk of asthma in schoolchildren: analysis of a Brazilian newborn cohort,

    Directory of Open Access Journals (Sweden)

    Heli V. Brandão

    Full Text Available Abstract Objective: To verify whether the occurrence of acute viral bronchiolitis in the first year of life constitutes a risk factor for asthma at age 6 considering a parental history of asthma. Methods: Cross-sectional study in a cohort of live births. A standardized questionnaire of the International Study of Asthma and Allergies in Childhood was applied to the mothers to identify asthma in children at the age of 6 years. Acute viral bronchiolitis diagnosis was performed by maternal report of a medical diagnosis and/or presence of symptoms of coryza accompanied by cough, tachypnea, and dyspnea when participants were 3, 6, 9, and 12 months. Socioeconomic, environmental data, parental history of asthma, and data related to pregnancy were collected in the first 72 h of life of the newborn and in prospective home visits by trained interviewers. The association between acute viral bronchiolitis and asthma was evaluated by logistic regression analysis and potential modifier effect of parental history was verified by introducing an interaction term into the adjusted logistic regression model. Results: Prevalence of acute viral bronchiolitis in the first year of life was 68.6% (461. The occurrence of acute viral bronchiolitis was a risk factor for asthma at 6 years of age in children with parental history of asthma OR: 2.66, 95% CI (1.10-6.40, modifier effect p = 0.002. Parental history of asthma OR: 2.07, 95% CI (1.29-3.30 and male gender OR: 1.69, 95% CI, (1.06-2.69 were other identified risk factors for asthma. Conclusion: Acute viral bronchiolitis in the first year of life is a risk factor for asthma in children with parental history of asthma.

  16. Genetic associations with viral respiratory illnesses and asthma control in children

    DEFF Research Database (Denmark)

    Loisel, D A; Du, G; Ahluwalia, T S

    2016-01-01

    of asthma control phenotypes was performed in 2128 children in the Copenhagen Prospective Study on Asthma in Childhood (COPSAC). Significant associations in RhinoGen were further validated using virus-induced wheezing illness and asthma phenotypes in an independent sample of 122 children enrolled...... in the Childhood Origins of Asthma (COAST) birth cohort study. RESULTS: A significant excess of P values smaller than 0.05 was observed in the analysis of the 10 RhinoGen phenotypes. Polymorphisms in 12 genes were significantly associated with variation in the four phenotypes showing a significant enrichment...... differences in childhood viral respiratory illnesses and virus-induced exacerbations of asthma. Defining mechanisms of these associations may provide insight into the pathogenesis of viral respiratory infections and virus-induced exacerbations of asthma....

  17. Factors associated with independent pharmacy owners' satisfaction with Medicare Part D contracts.

    Science.gov (United States)

    Zhang, Su; Doucette, William R; Urmie, Julie M; Xie, Yang; Brooks, John M

    2010-06-01

    As Medicare Part D contracts apply pressure on the profitability of independent pharmacies, there is concern about their owners' willingness to sign such contracts. Identifying factors affecting independent pharmacy owners' satisfaction with Medicare Part D contracts could inform policy makers in managing Medicare Part D. (1) To identify influences on independent pharmacy owners' satisfaction with Medicare Part D contracts and (2) to characterize comments made by independent pharmacy owners about Medicare Part D. This cross-sectional study used a mail survey of independent pharmacy owners in 15 states comprising 6 Medicare regions to collect information on their most- and least-favorable Medicare Part D contracts, including satisfaction, contract management activities, market position, pharmacy operation, and specific payment levels on brand and generic drugs. Of the 1649 surveys mailed, 296 surveys were analyzed. The regression models for satisfaction with both the least and the most-favorable Part D contracts were significant (Pequity. For the least-favorable contract, influences were negotiation, equity, generic rate bonus, and medication therapy management (MTM) payment. About one-third of the survey respondents made at least 1 comment. The most frequent themes in the comments were that Medicare Part D reimbursement rate is too low (28%) and that contracts are offered without negotiation in a "take it or leave it" manner (20%). Equity, contending, negotiation, generic rate bonus, and MTM payments were identified as the influences of independent pharmacy owners' satisfaction toward Medicare Part D contracts. Generic rate bonus and MTM payment provide additional financial incentives to less financially favorable contracts and, in turn, contribute to independent pharmacy owner's satisfaction toward these contracts. Copyright 2010 Elsevier Inc. All rights reserved.

  18. Trans-activation of the 5' to 3' viral DNA strand transfer by nucleocapsid protein during reverse transcription of HIV1 RNA.

    Science.gov (United States)

    Darlix, J L; Vincent, A; Gabus, C; de Rocquigny, H; Roques, B

    1993-08-01

    Two DNA strand transfer reactions take place during reverse transcription of the retroviral genome. The first transfer, that of the minus-strand strong stop DNA from the 5' end of the viral RNA to the 3' end, has been studied in vitro with two RNAs mimicking the 5' and 3' regions of the HIV1 genome and with nucleocapsid protein, NCp7, and reverse transcriptase. The results show that NCp7 strongly activates the 5' to 3' DNA strand transfer during reverse transcription while a basic peptide resembling NCp7 is inactive. Activation of the first transfer by several NCp7 derived peptides and the influence of the terminal redundancies (R) present at the 5' and 3' ends of HIV1 RNA were also examined. The first transfer is optimal in the presence of intact NCp7 and necessitates R on both the 5' and 3' RNAs. Sequencing of full length viral DNA products reveals approximately 40% misincorporations at the first nucleotide beyond the transfer point. If such base misincorporations occur during proviral DNA synthesis with possible homologous recombinations it may well contribute to the high level of genetic variability of HIV.

  19. Mammographic texture resemblance generalizes as an independent risk factor for breast cancer

    DEFF Research Database (Denmark)

    Nielsen, Mads; Vachon, Celine M.; Scott, Christopher G.

    2014-01-01

    INTRODUCTION:Breast density has been established as a major risk factor for breast cancer. We have previously demonstrated that mammographic texture resemblance (MTR), recognizing the local texture patterns of the mammogram, is also a risk factor for breast cancer, independent of percent breast...... density. We examine if these findings generalize to another population.METHODS:Texture patterns were recorded in digitalized pre-diagnosis (3.7years) film mammograms of a nested case-control study within the Dutch screening program (S1) comprising of 245 breast cancers and 250 matched controls...

  20. Biscoitos recheados: quanto mais baratos maior teor de gordura trans? = Filled cookies: the cheaper the higher trans fat content?

    Directory of Open Access Journals (Sweden)

    Galdino, Tatiana Pizzato

    2010-01-01

    Conclusões: quanto maior a quantidade de gorduras trans, menor a quantidade de gordura saturada e menor preço. Sugere-se uma revisão na legislação quanto à inserção da quantidade exata de gorduras trans no rótulo, uma vez que o consumo elevado dessas gorduras está associado a dislipidemias, um fator de risco para doença cardiovascular

  1. Mapping Discrimination Experienced by Indonesian Trans* FtM Persons.

    Science.gov (United States)

    Gordon, Danny; Pratama, Mario Prajna

    2017-01-01

    This work sought to document how Indonesian trans* FtM persons experienced discrimination across the interlinked domains of social networks, religious and educational institutions, employment and the workplace, and health care institutions. Objectives were (1) to map the discrimination experienced by trans* FtM individuals in Indonesia, and (2) to establish the specific priorities of the Indonesian trans* FtM community. In-depth interviews, focus groups, and participant observation was used involving 14 respondents. Findings revealed that respondents experienced othering through rejection, misidentification, harassment, "correction," and bureaucratic discrimination across the five preestablished domains. Health care and a lack of information emerged as areas of particular concern for respondents. This work calls for health care that is sensitive to the needs of trans* FtM people coupled with high-quality information to alleviate the cycles through which discrimination is sustained.

  2. Evolution of cichlid vision via trans-regulatory divergence

    Directory of Open Access Journals (Sweden)

    O’Quin Kelly E

    2012-12-01

    Full Text Available Abstract Background Phenotypic evolution may occur through mutations that affect either the structure or expression of protein-coding genes. Although the evolution of color vision has historically been attributed to structural mutations within the opsin genes, recent research has shown that opsin regulatory mutations can also tune photoreceptor sensitivity and color vision. Visual sensitivity in African cichlid fishes varies as a result of the differential expression of seven opsin genes. We crossed cichlid species that express different opsin gene sets and scanned their genome for expression Quantitative Trait Loci (eQTL responsible for these differences. Our results shed light on the role that different structural, cis-, and trans-regulatory mutations play in the evolution of color vision. Results We identified 11 eQTL that contribute to the divergent expression of five opsin genes. On three linkage groups, several eQTL formed regulatory “hotspots” associated with the expression of multiple opsins. Importantly, however, the majority of the eQTL we identified (8/11 or 73% occur on linkage groups located trans to the opsin genes, suggesting that cichlid color vision has evolved primarily via trans-regulatory divergence. By modeling the impact of just two of these trans-regulatory eQTL, we show that opsin regulatory mutations can alter cichlid photoreceptor sensitivity and color vision at least as much as opsin structural mutations can. Conclusions Combined with previous work, we demonstrate that the evolution of cichlid color vision results from the interplay of structural, cis-, and especially trans-regulatory loci. Although there are numerous examples of structural and cis-regulatory mutations that contribute to phenotypic evolution, our results suggest that trans-regulatory mutations could contribute to phenotypic divergence more commonly than previously expected, especially in systems like color vision, where compensatory changes in the

  3. Effects of cis-9, trans-11 and trans-10, cis-12 conjugated linoleic acid (CLA) isomers on immune function in healthy men

    NARCIS (Netherlands)

    Albers, R.; Wielen, R.P.J. van der; Brink, E.J.; Hendriks, H.F.J.; Dorovska-Taran, V.N.; Mohede, I.C.M.

    2003-01-01

    Objectives: To study the effects of two different mixtures of the main conjugated linoleic acid (CLA) isomers cis-9, trans-11 CLA and trans-10, cis-12 CLA on human immune function. Design: Double-blind, randomized, parallel, reference-controlled intervention study. Subjects and intervention:

  4. Structural modification of trans-cinnamic acid using Colletotrichum acutatum

    OpenAIRE

    Rodrigo Velasco B.; Jesús H. Gil G.; Carlos M. García P.; Diego L. Durango R.

    2012-01-01

    Se estudió la biotransformación de ácido trans-cinámico mediante células completas del hongo fitopatógeno nativo colombiano Colletotrichum acutatum. Inicialmente, se evaluó la fungitoxicidad de este compuesto contraC. acutatum; el ácido trans-cinámico exhibió una toxicidad moderada a débil contra el microorganismo y aparentemente se presentó un mecanismo de detoxificación. Luego, para estudiar tal mecanismo y explorar la capacidad de este hongo para biotransformar el ácido trans-cinámico en ...

  5. She's always a woman: Butch lesbian trans women in the lesbian community.

    Science.gov (United States)

    Rossiter, Hannah

    2016-01-01

    While the visibility and acceptance of trans women have grown globally in recent years, this progress has primarily been within a traditional, heteronormative narrative. But a growing number of trans women identify as butch lesbians and challenge this heteronormative narrative. The existence of butch trans women has created a debate on where they fit within queer and lesbian communities and how their gender performance fits within traditional butch/femme understandings of lesbian or queer relationships. This article seeks to explore the intersections of gender identity and sexual orientation that butch trans women experience when they engage with lesbian and trans communities.

  6. Structural and Molecular Basis for Coordination in a Viral DNA Packaging Motor

    Directory of Open Access Journals (Sweden)

    Huzhang Mao

    2016-03-01

    Full Text Available Ring NTPases are a class of ubiquitous molecular motors involved in basic biological partitioning processes. dsDNA viruses encode ring ATPases that translocate their genomes to near-crystalline densities within pre-assembled viral capsids. Here, X-ray crystallography, cryoEM, and biochemical analyses of the dsDNA packaging motor in bacteriophage phi29 show how individual subunits are arranged in a pentameric ATPase ring and suggest how their activities are coordinated to translocate dsDNA. The resulting pseudo-atomic structure of the motor and accompanying functional analyses show how ATP is bound in the ATPase active site; identify two DNA contacts, including a potential DNA translocating loop; demonstrate that a trans-acting arginine finger is involved in coordinating hydrolysis around the ring; and suggest a functional coupling between the arginine finger and the DNA translocating loop. The ability to visualize the motor in action illuminates how the different motor components interact with each other and with their DNA substrate.

  7. Trans-jugular catheter-directed thrombolysis combined with trans-dorsalis pedis vein thrombolysis for the treatment of deep venous thrombosis of the lower limbs

    International Nuclear Information System (INIS)

    Qian Jiesheng; Li Zhengran; Jiang Zaibo; Zhu Kangshun; Guan Shouhai; Zhou Bing; Xu Changmou; He Keke; Shang Hong

    2009-01-01

    Objective: To investigate the feasibility and efficacy of trans-jugular catheter-directed thrombolysis (CDT) together with trans-dorsalis pedis vein thrombolysis for the treatment of deep venous thrombosis (DVT) of the lower limbs. Methods: Jugular vein puncture, indwelling catheter and placement of IVC filter were performed in 18 patients with DVT (study group) followed by continuous trans-jugular CDT together with trans-dorsalis pedis vein thrombolysis. During the corresponding period, 16 patients with DVT (control group) received trans-dorsalis pedis vein thrombolysis only. Results: The thrombolytic time and total dose of urokinase in study group and control group were (6.6 ± 2.3) days, (5.52 ± 2.24) x 106 units and (8.2 ± 1.4) days, (7.00 ± 1.66) x 106 units respectively. The thrombolytic time and total dose of urokinase in study group were significantly lower than that in control group (P < 0.05). After the treatment the thigh circumference and calf circumference in study group showed a reduction of (4.6 ± 2.1) cm and (4.0 ± 2.1) cm respectively, which were (3.2 ± 1.7) cm and (2.7 ± 1.5) cm respectively in control group, the difference between two groups was statistically significant (P < 0.05). The complete patent of the veins was 66.7% in study group and 31.3% in control group, the difference between two groups was significant (P < 0.05). In four cases of the study group, the filters were withdrawn through the original puncture site after the thrombus was completely dissolved. Conclusion: Trans-jugular CDT combined with trans-dorsalis pedis vein thrombolysis is an effective and safe therapeutic technique for the treatment of deep venous thrombosis of the lower extremities, moreover, the filter can be taken back via the original puncture site when the thrombus is completely dissolved. (authors)

  8. Stereospecific control of peptide gas-phase ion chemistry with cis and trans cyclo ornithine residues

    Czech Academy of Sciences Publication Activity Database

    Marek, Aleš; Nguyen, H. T. H.; Brož, Břetislav; Tureček, F.

    2018-01-01

    Roč. 53, č. 2 (2018), s. 124-137 ISSN 1076-5174 Institutional support: RVO:61388963 Keywords : cis and trans isomers * cyclo ornithine * peptide dissociations * peptide ion structures * stereochemistry Subject RIV: CB - Analytical Chemistry, Separation OBOR OECD: Analytical chemistry Impact factor: 2.422, year: 2016

  9. KSHV Rta promoter specification and viral reactivation

    Directory of Open Access Journals (Sweden)

    Jonathan eGuito

    2012-02-01

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

  10. Design of Trypanosoma rangeli sialidase mutants with improved trans-sialidase activity

    DEFF Research Database (Denmark)

    Nyffenegger, Christian; Nordvang, Rune Thorbjørn; Jers, Carsten

    2017-01-01

    were analyzed via kinetics for their ability to carry out trans-sialidase reaction using CGMP and D-lactose as substrates. The sialidase variants with 15 and 16 mutations, respectively, exhibited significantly improved trans-sialidase activity for D-lactose sialylation. Our results corroborate......, that computational studies of trans-glycosylation can be a valuable input in the design of novel trans-glycosidases, but also highlight the importance of experimental validation in order to assess the performance. In conclusion, two of the seven mutants displayed a dramatic switch in specificity from hydrolysis...

  11. Esophageal Motor Disorders Are a Strong and Independant Associated Factor of Barrett’s Esophagus

    Science.gov (United States)

    Bazin, Camille; Benezech, Alban; Alessandrini, Marine; Grimaud, Jean-Charles; Vitton, Veronique

    2018-01-01

    Background/Aims Esophageal motor disorder (EMD) has been shown to be associated with gastroesophageal reflux disease (GERD). However, the association of EMD with a Barrett’s esophagus (BE) is controversial. Our objective was to evaluate whether the presence of EMD was an independent factor associated with BE. Methods A retrospective case-control study was conducted in GERD patients who all had oeso-gastroduodenal endoscopy and high-resolution esophageal manometry. The clinical data collected was known or potential risk factors for BE: male gender, smoking and alcohol consumption, age, body mass index, presence of hiatal hernia, frequency, and age of GERD. EMD were classified according to the Chicago classification into: ineffective motor syndrome, fragmented peristalsis and absence of peristalsis, lower esophageal sphincter hypotonia. Results Two hundred and one patients (101 in the GERD + BE group and 100 in the GERD without BE) were included. In univariate analysis, male gender, alcohol consumption, presence of hiatal hernia, and EMD appeared to be associated with the presence of BE. In a multivariate analysis, 3 independent factors were identified: the presence of EMD (odds ratio [OR], 3.99; 95% confidence interval [CI], 1.71–9.28; P = 0.001), the presence of hiatal hernia (OR, 5.60; 95% CI, 2.45–12.76; P motor syndrome and lower esophageal sphincter hypotonia) is a strong independent associated factor of BE. Searching systematically for an EMD in patients suffering from GERD could be a new strategy to organize the endoscopic follow-up. PMID:29605977

  12. An oil mixture with trans-10, cis-12 conjugated linoleic acid increases markers of inflammation and in vivo lipid peroxidation compared with cis-9, trans-11 conjugated linoleic acid in postmenopausal women

    DEFF Research Database (Denmark)

    Tholstrup, Tine; Raff, Marianne; Straarup, Ellen Marie

    2008-01-01

    . The plasma cytokines interleukin-6 and tumor necrosis factor-a were not affected by the treatments, nor were any of the other variables measured. In conclusion, oil containing trans-10,cis-12 CLA has several adverse effects on classical and novel markers of coronary vascular disease, whereas the c9, t11 CLA...

  13. Trans-disciplinary community groups: an initiative for improving healthcare.

    Science.gov (United States)

    Sideras, James Demetri

    2016-01-01

    In the context of budget constraints and the current quality crisis facing UK healthcare, the purpose of this paper is to examine the use of trans-disciplinary community groups (TCG)--an innovative and inexpensive initiative for improving patient care. Using an action research study, TCG was implemented within a private healthcare firm for vulnerable adults. Qualitative data were gathered over 12 months from 33 participants using depth interviews and focus groups. TCG led to improved patient activities and increased patient decision-making and confidence in self-advocacy. Key prerequisites were top management commitment, democratic leadership and employee empowerment. However, staff nurses resisted TCG because they were inclined to using managerial control and their own independent clinical judgements. Whilst the findings from this study should not be generalized across all healthcare sectors, its results could be replicated in contexts where there is wide commitment to TCG and where managers adopt a democratic style of leadership. Researchers could take this study further by exploring the applicability of TCG in public healthcare organizations or other multi-disciplinary service contexts. The findings of this research paper provide policy makers and healthcare managers with practical insights on TCG and the factors that are likely to obstruct and facilitate its implementation. Adopting TCG could enable healthcare managers to ameliorate their services with little or no extra cost, which is especially important in a budget constraint context and the current quality crisis facing UK healthcare.

  14. Evidence for RPE65-independent vision in the cone-dominated zebrafish retina.

    Science.gov (United States)

    Schonthaler, Helia B; Lampert, Johanna M; Isken, Andrea; Rinner, Oliver; Mader, Andreas; Gesemann, Matthias; Oberhauser, Vitus; Golczak, Marcin; Biehlmaier, Oliver; Palczewski, Krzysztof; Neuhauss, Stephan C F; von Lintig, Johannes

    2007-10-01

    An enzyme-based cyclic pathway for trans to cis isomerization of the chromophore of visual pigments (11-cis-retinal) is intrinsic to vertebrate cone and rod vision. This process, called the visual cycle, is mostly characterized in rod-dominated retinas and essentially depends on RPE65, an all-trans to 11-cis-retinoid isomerase. Here we analysed the role of RPE65 in zebrafish, a species with a cone-dominated retina. We cloned zebrafish RPE65 and showed that its expression coincided with photoreceptor development. Targeted gene knockdown of RPE65 resulted in morphologically altered rod outer segments and overall reduced 11-cis-retinal levels. Cone vision of RPE65-deficient larvae remained functional as demonstrated by behavioural tests and by metabolite profiling for retinoids. Furthermore, all-trans retinylamine, a potent inhibitor of the rod visual cycle, reduced 11-cis-retinal levels of control larvae to a similar extent but showed no additive effects in RPE65-deficient larvae. Thus, our study of zebrafish provides in vivo evidence for the existence of an RPE65-independent pathway for the regeneration of 11-cis-retinal for cone vision.

  15. Teores de ácidos graxos trans de alguns alimentos consumidos no Rio de Janeiro Trans fatty acids of some foods consumed in Rio de Janeiro, Brazil

    Directory of Open Access Journals (Sweden)

    Vera Lúcia Chiara

    2003-06-01

    Full Text Available Desconhecem-se os teores de ácidos graxos trans em diversos alimentos. Este estudo analisou os teores de ácidos graxos trans, saturados, monoinsaturados e poliinsaturados em batatas fritas, biscoitos e sorvetes. As batatas fritas foram dos tipos chips e de duas redes de fast food, os sorvetes, de duas marcas comerciais e de duas lojas de fast food, e os biscoitos, de marcas diferentes. As amostras de batatas chips e de biscoitos pertenciam a lotes distintos e foram adquiridas em supermercados da região. Analisaram-se seis amostras por produto, através de cromatografia gasosa. O valor médio dos ácidos trans de batatas fritas de redes de fast food foi de 4,74g/100g, enquanto em batatas chips estes ácidos graxos não foram detectados. Nos sorvetes os valores variaram de 0,041g a 1,41g e em biscoitos, de 2,81g a 5,60g. Biscoitos tipo cream cracker apresentaram teores de ácidos graxos trans mais altos e de insaturados mais baixos. Concluiu-se que alguns produtos apresentaram, em 100g, teores de ácidos graxos trans superiores aos recomendados para ingestão total diária em diversos países.The content of trans fatty acids in most consumed foods in Brazil is unknown. This study assessed trans saturated, monounsaturated and polyunsaturated fatty acids in samples of fried potatoes, cookies and ice cream. The analysis included: potato chips and fried potatoes from two popular fast food restaurants, ice cream of two different trademarks and from two fast food restaurants, and cookies of different trademarks. The samples of potato chips and cookies were acquired in different supermarkets in the city of Rio de Janeiro, and distinct manufacture dates were chosen. Six samples of each product were analyzed through gas chromatography. The average trans fatty acids content in fried potatoes from fast food restaurants was 4.74g/100g; in ice cream the values varied from 0.041g to 1.41g; and in cookies the values varied from 2.81g to 5.60g. No trans fatty

  16. Development of a GAL4-VP16/UAS trans-activation system for tissue specific expression in Medicago truncatula.

    Directory of Open Access Journals (Sweden)

    Amélie Sevin-Pujol

    Full Text Available Promoters with tissue-specific activity are very useful to address cell-autonomous and non cell autonomous functions of candidate genes. Although this strategy is widely used in Arabidopsis thaliana, its use to study tissue-specific regulation of root symbiotic interactions in legumes has only started recently. Moreover, using tissue specific promoter activity to drive a GAL4-VP16 chimeric transcription factor that can bind short upstream activation sequences (UAS is an efficient way to target and enhance the expression of any gene of interest. Here, we developed a collection of promoters with different root cell layers specific activities in Medicago truncatula and tested their abilities to drive the expression of a chimeric GAL4-VP16 transcription factor in a trans-activation UAS: β-Glucuronidase (GUS reporter gene system. By developing a binary vector devoted to modular Golden Gate cloning together with a collection of adapted tissue specific promoters and coding sequences we could test the activity of four of these promoters in trans-activation GAL4/UAS systems and compare them to "classical" promoter GUS fusions. Roots showing high levels of tissue specific expression of the GUS activity could be obtained with this trans-activation system. We therefore provide the legume community with new tools for efficient modular Golden Gate cloning, tissue specific expression and a trans-activation system. This study provides the ground work for future development of stable transgenic lines in Medicago truncatula.

  17. Epidermal growth factor receptor: an independent predictor of survival in astrocytic tumors given definitive irradiation

    International Nuclear Information System (INIS)

    An Zhu; Shaeffer, James; Leslie, Susan; Kolm, Paul; El-Mahdi, Anas M.

    1996-01-01

    Purpose: To determine whether the expression of epidermal growth factor receptor (EGFR) protein was predictive of patient survival independently of other prognostic factors in astrocytic tumors. Methods and Materials: Epidermal growth factor receptor protein expression was investigated immunohistochemically in formalin-fixed, paraffin-embedded surgical specimens of 55 glioblastoma multiforme, 14 anaplastic astrocytoma, and 2 astrocytomas given definitive irradiation. We evaluated the relationship of EGFR protein expression and tumor grade, histologic features, age at diagnosis, sex, patient survival, and recurrence-free survival. Results: The percentage of tumor cells which were EGFR positive related to reduced survival by Cox regression analysis in both univariate (p = 0.0424) and multivariate analysis (p = 0.0016). Epidermal growth factor receptor positivity was the only 1 of 11 clinical and histological variables associated with decreased recurrence-free survival by either univariate (p = 0.0353) or multivariate (p = 0.0182) analysis. Epidermal growth factor receptor protein expression was not related to patient age, sex, or histologic features. Conclusion: Epidermal growth factor receptor positivity was a significant and independent prognostic indicator for overall survival and recurrence-free survival for irradiated patients with astrocytic gliomas

  18. Biochemical characterization of trans-sialidase TS1 variants from Trypanosoma congolense

    Directory of Open Access Journals (Sweden)

    Dietz Frank

    2011-07-01

    Full Text Available Abstract Background Animal African trypanosomiasis, sleeping sickness in humans and Nagana in cattle, is a resurgent disease in Africa caused by Trypanosoma parasites. Trans-sialidases expressed by trypanosomes play an important role in the infection cycle of insects and mammals. Whereas trans-sialidases of other trypanosomes like the American T. cruzi are well investigated, relatively little research has been done on these enzymes of T. congolense. Results Based on a partial sequence and an open reading frame in the WTSI database, DNA sequences encoding for eleven T. congolense trans-sialidase 1 variants with 96.3% overall amino acid identity were amplified. Trans-sialidase 1 variants were expressed as recombinant proteins, isolated and assayed for trans-sialylation activity. The purified proteins produced α2,3-sialyllactose from lactose by desialylating fetuin, clearly demonstrating their trans-sialidase activity. Using an HPLC-based assay, substrate specificities and kinetic parameters of two variants were characterized in detail indicating differences in substrate specificities for lactose, fetuin and synthetic substrates. Both enzymes were able to sialylate asialofetuin to an extent, which was sufficient to reconstitute binding sites for Siglec-4. A mass spectrometric analysis of the sialylation pattern of glycopeptides from fetuin revealed clear but generally similar changes in the sialylation pattern of the N-glycans on fetuin catalyzed by the trans-sialidases investigated. Conclusions The identification and characterization of a trans-sialidase gene family of the African parasite T. congolense has opened new perspectives for investigating the biological role of these enzymes in Nagana and sleeping sickness. Based on this study it will be interesting to address the expression pattern of these genes and their activities in the different stages of the parasite in its infection cycle. Furthermore, these trans-sialidases have the

  19. Formation of trans-caffeoyl-CoA from trans-4-coumaroyl-CoA by Zn2+-dependent enzymes in cultured plant cells and its activation by an elicitor-induced pH shift

    NARCIS (Netherlands)

    Kneusel, R.; Matern, U.; Nicolaij, K.

    1989-01-01

    A novel hydroxylase activity catalyzing the formation of trans-caffeoyl-CoA from trans-4-coumaroyl-CoA was identified in crude extracts from cultured parsley cells. The extracts were less active (Vmax/Km) in converting trans-4-coumaric to trans-caffeic acid. Optimal hydroxylase activity was found at

  20. Clinical, morphological, and hemodynamic independent characteristic factors for rupture of posterior communicating artery aneurysms.

    Science.gov (United States)

    Zhang, Ying; Jing, Linkai; Liu, Jian; Li, Chuanhui; Fan, Jixing; Wang, Shengzhang; Li, Haiyun; Yang, Xinjian

    2016-08-01

    To identify clinical, morphological, and hemodynamic independent characteristic factors that discriminate posterior communicating artery (PCoA) aneurysm rupture status. 173 patients with single PCoA aneurysms (108 ruptured, 65 unruptured) between January 2012 and June 2014 were retrospectively collected. Patient-specific models based on their three-dimensional digital subtraction angiography images were constructed and analyzed by a computational fluid dynamic method. All variables were analyzed by univariate analysis and multivariate logistic regression analysis. Two clinical factors (younger age and atherosclerosis), three morphological factors (higher aspect ratio, bifurcation type, and irregular shape), and six hemodynamic factors (lower mean and minimum wall shear stress, higher oscillatory shear index, a greater portion of area under low wall shear stress, unstable and complex flow pattern) were significantly associated with PCoA aneurysm rupture. Independent factors characterizing the rupture status were identified as age (OR 0.956, p=0.015), irregular shape (OR 6.709, pPCoA aneurysm rupture were younger age, irregular shape, and low minimum wall shear stress. This may be useful for guiding risk assessments and subsequent treatment decisions for PCoA aneurysms. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  1. The new on-line marketing medium: viral marketing. Analysis of the field through two case studies

    OpenAIRE

    Sasigain Salvador, Miren

    2014-01-01

    Purpose: This paper synthesizes the emerging literature on viral marketing through the analysis of two case studies and identifies and evaluates important factors that need to be considered when organizing a viral marketing campaign nowadays; the elements used the implemented strategy, the impact and results. The companies to be studied have been successful developing viral marketing strategies even they differ in size, sector and product offered. Literature Review: Definition of tradition...

  2. Multi-faceted proteomic characterization of host protein complement of Rift Valley fever virus virions and identification of specific heat shock proteins, including HSP90, as important viral host factors.

    Science.gov (United States)

    Nuss, Jonathan E; Kehn-Hall, Kylene; Benedict, Ashwini; Costantino, Julie; Ward, Michael; Peyser, Brian D; Retterer, Cary J; Tressler, Lyal E; Wanner, Laura M; McGovern, Hugh F; Zaidi, Anum; Anthony, Scott M; Kota, Krishna P; Bavari, Sina; Hakami, Ramin M

    2014-01-01

    Rift Valley fever is a potentially fatal disease of humans and domestic animals caused by Rift Valley fever virus (RVFV). Infection with RVFV in ruminants can cause near 100% abortion rates and recent outbreaks in naïve human populations have suggested case fatality rates of greater than thirty percent. To elucidate the roles that host proteins play during RVFV infection, proteomic analysis of RVFV virions was conducted using complementary analytical approaches, followed by functional validation studies of select identified host factors. Coupling the more traditional Gel LC/MS/MS approach (SDS PAGE followed by liquid chromatography tandem mass spectrometry) with an alternative technique that preserves protein complexes allowed the protein complement of these viral particles to be thoroughly examined. In addition to viral proteins present within the virions and virion-associated host proteins, multiple macromolecular complexes were identified. Bioinformatic analysis showed that host chaperones were among over-represented protein families associated with virions, and functional experiments using siRNA gene silencing and small molecule inhibitors identified several of these heat shock proteins, including heat shock protein 90 (HSP90), as important viral host factors. Further analysis indicated that HSP inhibition effects occur during the replication/transcription phase of the virus life cycle, leading to significant lowering of viral titers without compromising the functional capacity of released virions. Overall, these studies provide much needed further insight into interactions between RVFV and host cells, increasing our understanding of the infection process and suggesting novel strategies for anti-viral development. In particular, considering that several HSP90 inhibitors have been advancing through clinical trials for cancer treatment, these results also highlight the exciting potential of repurposing HSP90 inhibitors to treat RVF.

  3. Multi-faceted proteomic characterization of host protein complement of Rift Valley fever virus virions and identification of specific heat shock proteins, including HSP90, as important viral host factors.

    Directory of Open Access Journals (Sweden)

    Jonathan E Nuss

    Full Text Available Rift Valley fever is a potentially fatal disease of humans and domestic animals caused by Rift Valley fever virus (RVFV. Infection with RVFV in ruminants can cause near 100% abortion rates and recent outbreaks in naïve human populations have suggested case fatality rates of greater than thirty percent. To elucidate the roles that host proteins play during RVFV infection, proteomic analysis of RVFV virions was conducted using complementary analytical approaches, followed by functional validation studies of select identified host factors. Coupling the more traditional Gel LC/MS/MS approach (SDS PAGE followed by liquid chromatography tandem mass spectrometry with an alternative technique that preserves protein complexes allowed the protein complement of these viral particles to be thoroughly examined. In addition to viral proteins present within the virions and virion-associated host proteins, multiple macromolecular complexes were identified. Bioinformatic analysis showed that host chaperones were among over-represented protein families associated with virions, and functional experiments using siRNA gene silencing and small molecule inhibitors identified several of these heat shock proteins, including heat shock protein 90 (HSP90, as important viral host factors. Further analysis indicated that HSP inhibition effects occur during the replication/transcription phase of the virus life cycle, leading to significant lowering of viral titers without compromising the functional capacity of released virions. Overall, these studies provide much needed further insight into interactions between RVFV and host cells, increasing our understanding of the infection process and suggesting novel strategies for anti-viral development. In particular, considering that several HSP90 inhibitors have been advancing through clinical trials for cancer treatment, these results also highlight the exciting potential of repurposing HSP90 inhibitors to treat RVF.

  4. Trans-kingdom cross-talk

    DEFF Research Database (Denmark)

    Knip, Marijn; Constantin, Maria-Ermioni; Thordal-Christensen, Hans

    2014-01-01

    This review focuses on the mobility of small RNA (sRNA) molecules from the perspective of trans-kingdom gene silencing. Mobility of sRNA molecules within organisms is a well-known phenomenon, facilitating gene silencing between cells and tissues. sRNA signals are also transmitted between organism...

  5. 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.

  6. 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 ...

  7. A trans world journey

    DEFF Research Database (Denmark)

    Stender, Steen; Dyerberg, Jørn; Bysted, Anette

    2006-01-01

    to a maximum of 2% of fat content from 2004. We assessed the potential exposure of consumers to IP-TFA by analysing popular foods in Denmark, and in 25 other countries. Fifty-five servings of French fries and chicken nuggets, 87 packages of microwave popcorn, and 393 samples of biscuits....../cakes/wafers with "partially hydrogenated vegetable fat" listed high on the food label were bought between November 2004, and February 2006. The content of IP-TFA was analysed by standardized methodology. We defined a "high trans menu" as a large size serving of French fries and nuggets, 100 g of microwave popcorn, and 100 g......A high intake of industrially produced trans fatty acids (IP-TFA) is associated with increased risk of coronary heart disease (CHD), and a daily intake as low as possible is required to minimize health risks. To achieve this at the individual level in Denmark, legislation limited IP-TFA in foods...

  8. Postoperative delirium: age and low functional reserve as independent risk factors.

    Science.gov (United States)

    Pinho, Cristiana; Cruz, Sofia; Santos, Alice; Abelha, Fernando J

    2016-09-01

    The aim of this study was to determine the incidence of postoperative delirium (POD) and the presence of previous conditions related to its development. Prospective observational study. The study was performed in adult patients (n=221) scheduled for elective surgery and admitted to the postanesthesia care unit (PACU). The presence of POD was assessed by the Nursing Delirium Screening Scale at discharge from the PACU and 24hours after surgery. Descriptive analyses were carried out, and statistical comparisons were performed with Mann-Whitney U, χ(2), or Fisher exact test. Logistic regression analysis was used for evaluation of independent determinants of POD. POD was found in 25 patients (11%). Patients who developed POD were older (median age, 69 vs 57years; P<.001); had a higher American Society of Anesthesiologists physical status score (≥3) (60% vs 19%, respectively, had American Society of Anesthesiologists physical status III/IV; P<.001); and showed higher incidences of ischemic heart disease (24% vs 6%; P=.001), chronic kidney disease (20% vs 5%; P=.005), hypertension (80% vs 45%; P=.001), chronic obstructive pulmonary disease (20% vs 6%; P=.009), and low functional reserve (LFR) (24% vs 2%; P<.001). Age (odds ratio, 1.06; 95% confidence interval, 1.02-1.10; P=.003) and LFR (odds ratio, 8.04; 95% confidence interval, 3.95-32.27; P=.003) were considered independent risk factors for POD. The incidence of POD in the study population (11%) is consistent with that described in the literature (5%-15%). The comorbidities associated with its development were ischemic heart disease, hypertension, chronic kidney disease, LFR, and chronic obstructive pulmonary disease. Age ≥65years and LFR were independent risk factors for POD development. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Regional Cooperation Towards Trans-country Natural Gas Market

    DEFF Research Database (Denmark)

    Shukla, P.R.; Dhar, Subash

    2009-01-01

    India began gas imports since 2004 through liquified natural gas (LNG) route. Imports through trans-country gas pipelines could help in bringing gas directly into the densely populated Northern part of India, which are far from domestic gas resources as well as coastal LNG terminals. The purpose ...... of this paper is to report scenarios, which quantify the impacts for India of regional cooperation to materialize trans-country pipelines. The analysis covers time period from 2005 to 2030.......India began gas imports since 2004 through liquified natural gas (LNG) route. Imports through trans-country gas pipelines could help in bringing gas directly into the densely populated Northern part of India, which are far from domestic gas resources as well as coastal LNG terminals. The purpose...

  10. A Transplant-Specific Quality Initiative-Introducing TransQIP: A Joint Effort of the ASTS and ACS.

    Science.gov (United States)

    Parekh, J; Ko, C; Lappin, J; Greenstein, S; Hirose, R

    2017-07-01

    In an attempt to improve surgical quality in the field of transplantation, the American College of Surgeons (ACS) and American Society of Transplant Surgeons have initiated a national quality improvement program in transplantation. This transplant-specific quality improvement program, called TransQIP, has been built from the ground up by transplant surgeons and captures detailed information on donor and recipient factors as well as transplant-specific outcomes. It is built upon the existing ACS/National Surgical Quality Improvement Program infrastructure and is designed to capture 100% of liver and kidney transplants performed at participating sites. TransQIP has completed its alpha pilot and will embark upon its beta phase at approximately 30 centers in the spring of 2017. Going forward, we anticipate TransQIP will help satisfy Centers for Medicare and Medicaid Services requirements for a quality improvement program, surgeon requirements for maintenance of certification, and qualify as a clinical practice improvement activity under the Merit-Based Incentive Payment System. Most importantly, we believe TransQIP will provide insight into surgical outcomes in transplantation that will allow the field to provide better care to our patients. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

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

    Science.gov (United States)

    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.

  12. Oleic Acid enhances all-trans retinoic Acid loading in nano-lipid emulsions.

    Science.gov (United States)

    Chinsriwongkul, Akhayachatra; Opanasopit, Praneet; Ngawhirunpat, Tanasait; Rojanarata, Theerasak; Sila-On, Warisada; Ruktanonchai, Uracha

    2010-01-01

    The aim of this study was to investigate the enhancement of all-trans retinoic acid (ATRA) loading in nano-lipid emulsions and stability by using oleic acid. The effect of formulation factors including initial ATRA concentration and the type of oil on the physicochemical properties, that is, percentage yield, percentage drug release, and photostability of formulations, was determined. The solubility of ATRA was increased in the order of oleic acid > MCT > soybean oil > water. The physicochemical properties of ATRA-loaded lipid emulsion, including mean particle diameter and zeta potential, were modulated by changing an initial ATRA concentration as well as the type and mixing ratio of oil and oleic acid as an oil phase. The particles of lipid emulsions had average sizes of less than 250 nm and negative zeta potential. The addition of oleic acid in lipid emulsions resulted in high loading capacity. The photodegradation rate was found to be dependent on the initial drug concentration but independent of the type of oily phase used in this study. The release rates were not affected by initial ATRA concentration but were affected by the type of oil, where oleic acid showed the highest release rate of ATRA from lipid emulsions.

  13. Inhibition of host protein synthesis by Sindbis virus: correlation with viral RNA replication and release of nuclear proteins to the cytoplasm.

    Science.gov (United States)

    Sanz, Miguel A; García-Moreno, Manuel; Carrasco, Luis

    2015-04-01

    Infection of mammalian cells by Sindbis virus (SINV) profoundly blocks cellular mRNA translation. Experimental evidence points to viral non-structural proteins (nsPs), in particular nsP2, as the mediator of this inhibition. However, individual expression of nsP1, nsP2, nsP3 or nsP1-4 does not block cellular protein synthesis in BHK cells. Trans-complementation of a defective SINV replicon lacking most of the coding region for nsPs by the co-expression of nsP1-4 propitiates viral RNA replication at low levels, and inhibition of cellular translation is not observed. Exit of nuclear proteins including T-cell intracellular antigen and polypyrimidine tract-binding protein is clearly detected in SINV-infected cells, but not upon the expression of nsPs, even when the defective replicon was complemented. Analysis of a SINV variant with a point mutation in nsP2, exhibiting defects in the shut-off of host protein synthesis, indicates that both viral RNA replication and the release of nuclear proteins to the cytoplasm are greatly inhibited. Furthermore, nucleoside analogues that inhibit cellular and viral RNA synthesis impede the blockade of host mRNA translation, in addition to the release of nuclear proteins. Prevention of the shut-off of host mRNA translation by nucleoside analogues is not due to the inhibition of eIF2α phosphorylation, as this prevention is also observed in PKR(-/-) mouse embryonic fibroblasts that do not phosphorylate eIF2α after SINV infection. Collectively, our observations are consistent with the concept that for the inhibition of cellular protein synthesis to occur, viral RNA replication must take place at control levels, leading to the release of nuclear proteins to the cytoplasm. © 2014 John Wiley & Sons Ltd.

  14. Multivariate analysis of covariates of adherence among HIV-positive mothers with low viral suppression.

    Science.gov (United States)

    Nsubuga-Nyombi, Tamara; Sensalire, Simon; Karamagi, Esther; Aloyo, Judith; Byabagambi, John; Rahimzai, Mirwais; Nabitaka, Linda Kisaakye; Calnan, Jacqueline

    2018-03-31

    As part of efforts to improve the prevention of mother-to-child transmission in Northern Uganda, we explored reasons for poor viral suppression among 122 pregnant and lactating women who were in care, received viral load tests, but had not achieved viral suppression and had more than 1000 copies/mL. Understanding the patient factors associated with low viral suppression was of interest to the Ministry of Health to guide the development of tools and interventions to achieve viral suppression for pregnant and lactating women newly initiating on ART as well as those on ART with unsuppressed viral load. A facility-based cross-sectional and mixed methods study design was used, with retrospective medical record review. We assessed 122 HIV-positive mothers with known low viral suppression across 31 health facilities in Northern Uganda. Adjusted odds ratios were used to determine the covariates of adherence among HIV positive mothers using logistic regression. A study among health care providers shed further light on predictors of low viral suppression and a history of low early retention. This study was part of a larger national evaluation of the performance of integrated care services for mothers. Adherence defined as taking antiretroviral medications correctly everyday was low at 67.2%. The covariates of low adherence are: taking other medications in addition to ART, missed appointments in the past 6 months, experienced violence in the past 6 months, and faces obstacles to treatment. Mothers who were experiencing each of these covariates were less likely to adhere to treatment. These covariates were triangulated with perspectives of health providers as covariates of low adherence and included: long distances to health facility, missed appointments, running out of pills, sharing antiretroviral drugs, violence, and social lifestyles such as multiple sexual partners coupled with non-disclosure to partners. Inadequate counseling, stigma, and lack of client identity are

  15. TyG index, HOMA score and viral load in patients with chronic hepatitis C due to genotype 1.

    Science.gov (United States)

    Petta, S; Di Marco, V; Di Stefano, R; Cabibi, D; Cammà, C; Marchesini, G; Craxì, A

    2011-07-01

    The triglycerides × glucose (TyG) index is a recently proposed surrogate marker of insulin resistance (IR), calculated from fasting plasma triglyceride and glucose concentrations. We tested the host and viral factors associated with Tyg and homeostasis model assessment (HOMA) scores, comparing their associations with histological features and with sustained virological response (SVR) in patients with genotype 1 chronic hepatitis C(G1CHC). Three hundred and forty consecutive patients with G1CHC were considered. All had a liver biopsy scored by one pathologist for staging and grading (Scheuer), and graded for steatosis, which was considered moderate-severe if ≥30%. Anthropometric and metabolic measurements, including IR measured by both HOMA and TyG, were registered. By linear regression analysis, TyG was independently associated with waist circumference (WC), total cholesterol, presence of arterial hypertension, Log10 HCV-RNA and steatosis. Similarly, WC and steatosis were significantly associated with HOMA. Older age (OR, 1.036; 95%CI, 1.004-1.070, P = 0.02), higher WC (1.031; 1.004-1.060; P = 0.02) and higher TyG (11.496; 3.163-41.784; P HOMA-IR in the model, the latter remained significantly associated with steatosis ≥30% (1.237; 1.058-1.448; P = 0.008). Receiver operating characteristic curves showed a similar performance of TyG (AUC 0.682) and HOMA-IR (AUC 0.699) in predicting moderate-severe steatosis. No independent associations were found between both TyG and HOMA and fibrosis or SVR. In patients with G1CHC , TyG, an easy-to-calculate and low-cost surrogate marker of IR, is linked to liver steatosis and shows an independent association with viral load. © 2011 Blackwell Publishing Ltd.

  16. The analgesic effect of trans-resveratrol is regulated by calcium channels in the hippocampus of mice.

    Science.gov (United States)

    Wang, Weijie; Yu, Yingcong; Li, Jing; Wang, Lin; Li, Zhi; Zhang, Chong; Zhen, Linlin; Ding, Lianshu; Wang, Gang; Sun, Xiaoyang; Xu, Ying

    2017-08-01

    Resveratrol has been widely studied in terms of it's potential to slow the progression of many diseases. But little is known about the mechanism of action in neuropathic pain. Neuropathic pain is the main type of chronic pain associated with tissue injury. Calcium channels and calcium/caffeine-sensitive pools are associated with analgesic pathway involving neuropathic pain. Our previous study suggested that the antinociceptive effect of resveratrol was involved in Ca 2+ /calmodulin-dependent signaling in the spinal cord of mice. The aim of this study was to explore the involvement of Ca 2+ in analgesic effects of trans-resveratrol in neuropathic pain and signal pathway in hippocampus. Hot plate test was used to assess antinociceptive response when mice were treated with trans-resveratrol alone or in combination with Mk 801, nimodipine, CaCl 2 , ryanodine or EGTA. The effects of trans-resveratrol and the combination on Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) and BDNF (brain-derived neurotrophic factor) expression in hippocampus were also investigated. The results showed that trans-resveratrol increased paw withdraw latency in the hot plate test. The effect of resveratrol was enhanced by Mk 801 and nimodipine. Central administration of Ca 2+ , however, abolished the antinociceptive effects of resveratrol. In contrast, centrally administered EGTA or ryanodine improved trans-resveratrol induced antinociception. There was a significant increase in p-CaMKII and BDNF expression in the hippocampus when resveratrol were combined with Mk 801, nimodipine, ryanodine and EGTA. Administration of CaCl 2 blocked changes in p-CaMKII and BDNF levels in the hippocampus. These findings suggest that trans-resveratrol exerts the effects of antinociception through regulation of calcium channels and calcium/caffeine-sensitive pools.

  17. Thiyl radical-induced cis-trans-isomerization of arachidonic acid inhibits prostaglandin metabolism

    International Nuclear Information System (INIS)

    Kratzsch, S.; Droessler, K.; Sprinz, H.; Brede, O.

    2002-01-01

    Complete text of publication follows. Thiyl radicals radiolytically generated from thiophenol in methanolic solution are known to isomerise double bonds of poly-unsaturated fatty acids (PUFA). γ-irradiating of such a system containing all-cis 5,8,11,14 eicosatetraenoic acid (arachidonic acid, AA) with low doses (0.1-0.8 kGy) results in a mixture of 8 to 32% mono-trans-isomers. Here we report about the influence of mono-trans-AA on the primary steps of AA-metabolism and prostaglandin synthesis, catalysed by cyclooxygenase (COX). In the cell-free model system the reaction of COX-1 with AA was analysed by controlling the oxygen level during the enzymatic reaction. As an example, a mixture of a low quantity of mono-trans-isomerized AA (10%) and 90% all-cis-isomer exhibits a marked reduced oxygen consumption by 45%. As further proofs - the yield of reactive oxygen species (ROS) generated by the COX-coupled peroxidase reaction was detected, - and the COX-1 activity in presence of different amounts of trans-AA was characterized using a photometric assay based on the oxidation of TMPD. All these methods indicated semiquantitatively a reduced activity of COX-1, depending on the trans-isomer yield. Therefore, an inhibition of COX-1 activity by only one trans-double-bond in AA could be concluded. Furthermore, in vitro cell-line experiments were performed analysing the influence of mono-trans-isomerized AA on the activity of the cell-own COX-2. Hence, VD 3 -differentiated and LPS-stimulated monocyte-like cells were incubated with mono-trans-AA and ROS-production was detected by the chemiluminescence measurements mentioned above. Compared to the reaction with all-cis-AA we found a considerable lowered formation of ROS. Likewise, we obtained a reduced PGE 2 -expression between 15 and 40% for cells treated with 8 to 29% trans-AA. The model as well as in vivo experiments demonstrate an inhibition effect of mono-trans-AA and give rise for postulating an enzyme blocking mechanism

  18. Disintegration of aerobic granules induced by trans-2-decenoic acid.

    Science.gov (United States)

    Cai, Pei-Jie; Xiao, Xiang; He, Yan-Rong; Li, Wen-Wei; Yu, Lei; Yu, Han-Qing

    2013-01-01

    One current major hurdle to practical implementation of aerobic granule technology is the frequent occurrence of granule disintegration during long-term operation. However, the mechanism behind this is largely unclear today. Here, 2-decenoic acid, which has been previously demonstrated to be released by Pseudomonas aeruginosa and disperse biofilms, was found to also induce the disintegration of aerobic granules. A comparison of the solution compositions from samples of only trans-2-decenoic acid, only aerobic granules, and granules added with trans-2-decenoic acid shows that bacteria and extracellular polymeric substances (EPS) were stripped from granule surface upon trans-2-decenoic acid dosing. Due to the possible toxicity of trans-2-decenoic acid at a saturation concentration, the disintegrated granules and the milky suspension in the disintegration test showed a significantly lower oxygen uptake rate than the un-integrated granules. This work suggests that trans-2-decenoic acid released by microbes might play a critical role in regulating the disintegration of aerobic granules. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Factors influencing secondary care pharmacist and nurse independent prescribers' clinical reasoning: An interprofessional analysis.

    Science.gov (United States)

    Abuzour, Aseel S; Lewis, Penny J; Tully, Mary P

    2018-03-01

    In the United Kingdom, pharmacist and nurse independent prescribers are responsible for both the clinical assessment of and prescribing for patients. Prescribing is a complex skill that entails the application of knowledge, skills, and clinical reasoning to arrive at a clinically appropriate decision. Decision-making is influenced and informed by many factors. This study, the first of its kind, explores what factors influence pharmacist and nurse independent prescribers during the process of clinical reasoning. A think-aloud methodology immediately followed by a semi-structured interview was conducted with 11 active nurse and 10 pharmacist independent prescribers working in secondary care. Each participant was presented with validated clinical vignettes for the think-aloud stage. Participants chose the clinical therapeutic areas for the vignettes, based on their self-perceived competencies. Data were audio-recorded, transcribed verbatim, and a constant-comparative approach was used for analysis. Influences on clinical reasoning were broadly categorised into themes: social interaction, intrinsic, and contextual factors. These themes showed that intrinsic, sociocultural, and contextual aspects heavily influenced the clinical reasoning processes of prescribers. For example, prescribers were aware of treatment pathways, but chose to refer patient cases to avoid making the final prescribing decision. Exploration of this behaviour in the interviews revealed that previous experience and attitudes such as confidence and cautiousness associated with responsibility were strong influencers within the decision-making process. In addition, strengthening the professional identity of prescribers could be achieved through collaborative work with interprofessional healthcare teams to orient their professional practice from within the profession. Findings from this study can be used to inform the education, training, and practice of independent prescribers to improve healthcare

  20. Shifting Paradigms: Moving beyond "Trans 101" in Sexuality Education

    Science.gov (United States)

    Green, Eli R.

    2010-01-01

    Trans-inclusive sexuality education can be complex, confusing, and outright intimidating for even the most seasoned sexuality educator to teach. Historically, standalone "Trans 101" sessions have successfully raised awareness about the highly marginalized transgender community. However, their potential success has been limited by being taught in…

  1. Illela border market: origin and contributions to trans-border ...

    African Journals Online (AJOL)

    Illela border market: origin and contributions to trans-border relations between Nigeria and Niger republic. ... cordial relations between her and her immediate neighbours and thus stem the scourge of smuggling and other trans-border crimes which have negatively affected the Nigerian economy and her international image.

  2. Which adherence measure - self-report, clinician recorded or pharmacy refill - is best able to predict detectable viral load in a public ART programme without routine plasma viral load monitoring?

    Science.gov (United States)

    Mekuria, Legese A; Prins, Jan M; Yalew, Alemayehu W; Sprangers, Mirjam A G; Nieuwkerk, Pythia T

    2016-07-01

    Combination antiretroviral therapy (cART) suppresses viral replication to an undetectable level if a sufficiently high level of adherence is achieved. We investigated which adherence measurement best distinguishes between patients with and without detectable viral load in a public ART programme without routine plasma viral load monitoring. We randomly selected 870 patients who started cART between May 2009 and April 2012 in 10 healthcare facilities in Addis Ababa, Ethiopia. Six hundred and sixty-four (76.3%) patients who were retained in HIV care and were receiving cART for at least 6 months were included and 642 had their plasma HIV-1 RNA concentration measured. Patients' adherence to cART was assessed according to self-report, clinician recorded and pharmacy refill measures. Multivariate logistic regression model was fitted to identify the predictors of detectable viremia. Model accuracy was evaluated by computing the area under the receiver operating characteristic (ROC) curve. A total of 9.2% and 5.5% of the 642 patients had a detectable viral load of ≥40 and ≥400 RNA copies/ml, respectively. In the multivariate analyses, younger age, lower CD4 cell count at cART initiation, being illiterate and widowed, and each of the adherence measures were significantly and independently predictive of having ≥400 RNA copies/ml. The ROC curve showed that these variables altogether had a likelihood of more than 80% to distinguish patients with a plasma viral load of ≥400 RNA copies/ml from those without. Adherence to cART was remarkably high. Self-report, clinician recorded and pharmacy refill non-adherence were all significantly predictive of detectable viremia. The choice for one of these methods to detect non-adherence and predict a detectable viral load can therefore be based on what is most practical in a particular setting. © 2016 John Wiley & Sons Ltd.

  3. Metabolism of all-trans-retinoic acid and all-trans-retinyl acetate. Demonstration of common physiological metabolites in rat small intestinal mucosa and circulation

    International Nuclear Information System (INIS)

    Cullum, M.E.; Zile, M.H.

    1985-01-01

    The kinetics and metabolism of physiological doses of all-trans-retinoic acid were examined in blood and small intestinal mucosa of vitamin A-depleted rats. A major portion of intrajugularly injected retinoic acid is rapidly (within 2 min) sequestered by tissues; subsequently 13-cis-retinoic acid and polar metabolites are released into circulation. All-trans-retinoic acid appears in small intestinal epithelium within 2 min after dosing and is the major radioactive compound there for at least 2 h. Retinoyl glucuronide and 13-cis-retinoic acid are early metabolites of all-trans-retinoic acid in the small intestine of bile duct-cannulated rats. Retinoyl glucuronide, the major metabolite of retinoic acid intestinal epithelium, in contrast to other polar metabolites, was not detected in circulation. An examination of [ 3 H]retinyl acetate metabolites under steady state conditions in vitamin A-repleted rats demonstrates the occurrence of all-trans-retinoic acid and 13-cis-retinoic acid in circulation and in intestinal epithelium, in a pattern similar to that found after injection of retinoic acid into vitamin A-depleted rats. These data establish that all-trans-retinoic acid, 13-cis-retinoic acid, and retinoyl glucuronide are physiological metabolites of vitamin A in target tissues, and therefore are important candidates as mediators of the biological effect of the vitamin

  4. 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

  5. Reprogramming the Dynamin 2 mRNA by Spliceosome-mediated RNA Trans-splicing

    Directory of Open Access Journals (Sweden)

    Delphine Trochet

    2016-01-01

    Full Text Available Dynamin 2 (DNM2 is a large GTPase, ubiquitously expressed, involved in membrane trafficking and regulation of actin and microtubule cytoskeletons. DNM2 mutations cause autosomal dominant centronuclear myopathy which is a rare congenital myopathy characterized by skeletal muscle weakness and histopathological features including nuclear centralization in absence of regeneration. No curative treatment is currently available for the DNM2-related autosomal dominant centronuclear myopathy. In order to develop therapeutic strategy, we evaluated here the potential of Spliceosome-Mediated RNA Trans-splicing technology to reprogram the Dnm2-mRNA in vitro and in vivo in mice. We show that classical 3′-trans-splicing strategy cannot be considered as accurate therapeutic strategy regarding toxicity of the pre-trans-splicing molecules leading to low rate of trans-splicing in vivo. Thus, we tested alternative strategies devoted to prevent this toxicity and enhance frequency of trans-splicing events. We succeeded to overcome the toxicity through a 5′-trans-splicing strategy which also allows detection of trans-splicing events at mRNA and protein levels in vitro and in vivo. These results suggest that the Spliceosome-Mediated RNA Trans-splicing strategy may be used to reprogram mutated Dnm2-mRNA but highlight the potential toxicity linked to the molecular tools which have to be carefully investigated during preclinical development.

  6. Interspecific exchange of avian influenza virus genes in Alaska: The influence of trans-hemispheric migratory tendency and breeding ground sympatry

    Science.gov (United States)

    Pearce, John M.; Reeves, A.B.; Ramey, A.M.; Hupp, J.W.; Ip, Hon S.; Bertram, M.; Petrula, M.J.; Scotton, B.D.; Trust, K.A.; Meixell, B.W.; Runstadler, J.A.

    2011-01-01

    The movement and transmission of avian influenza viral strains via wild migratory birds may vary by host species as a result of migratory tendency and sympatry with other infected individuals. To examine the roles of host migratory tendency and species sympatry on the movement of Eurasian low-pathogenic avian influenza (LPAI) genes into North America, we characterized migratory patterns and LPAI viral genomic variation in mallards (Anas platyrhynchos) of Alaska in comparison with LPAI diversity of northern pintails (Anas acuta). A 50-year band-recovery data set suggests that unlike northern pintails, mallards rarely make trans-hemispheric migrations between Alaska and Eurasia. Concordantly, fewer (14.5%) of 62 LPAI isolates from mallards contained Eurasian gene segments compared to those from 97 northern pintails (35%), a species with greater inter-continental migratory tendency. Aerial survey and banding data suggest that mallards and northern pintails are largely sympatric throughout Alaska during the breeding season, promoting opportunities for interspecific transmission. Comparisons of full-genome isolates confirmed near-complete genetic homology (>99.5%) of seven viruses between mallards and northern pintails. This study found viral segments of Eurasian lineage at a higher frequency in mallards than previous studies, suggesting transmission from other avian species migrating inter-hemispherically or the common occurrence of endemic Alaskan viruses containing segments of Eurasian origin. We conclude that mallards are unlikely to transfer Asian-origin viruses directly to North America via Alaska but that they are likely infected with Asian-origin viruses via interspecific transfer from species with regular migrations to the Eastern Hemisphere.

  7. An indicator for effects of organic toxicants on lotic invertebrate communities: Independence of confounding environmental factors over an extensive river continuum

    International Nuclear Information System (INIS)

    Beketov, Mikhail A.; Liess, Matthias

    2008-01-01

    Distinguishing between effects of natural and anthropogenic environmental factors on ecosystems is a fundamental problem in environmental science. In river systems the longitudinal gradient of environmental factors is one of the most relevant sources of dissimilarity between communities that could be confounded with anthropogenic disturbances. To test the hypothesis that in macroinvertebrate communities the distribution of species' sensitivity to organic toxicants is independent of natural longitudinal factors, but depends on contamination with organic toxicants, we analysed the relationship between community sensitivity SPEAR organic (average community sensitivity to organic toxicants) and natural and anthropogenic environmental factors in a large-scale river system, from alpine streams to a lowland river. The results show that SPEAR organic is largely independent of natural longitudinal factors, but strongly dependent on contamination with organic toxicants (petrochemicals and synthetic surfactants). Usage of SPEAR organic as a stressor-specific longitude-independent measure will facilitate detection of community disturbance by organic toxicants. - Indicator for organic toxicants at community level can be independent of natural environmental factors

  8. Suppression of NYVAC Infection in HeLa Cells Requires RNase L but Is Independent of Protein Kinase R Activity

    Science.gov (United States)

    Fernández-Escobar, Mercedes; Nájera, José Luis; Baldanta, Sara; Rodriguez, Dolores; Way, Michael; Esteban, Mariano

    2015-01-01

    Protein kinase R (PKR) and RNase L are host cell components that function to contain viral spread after infections. In this study, we analyzed the role of both proteins in the abortive infection of human HeLa cells with the poxvirus strain NYVAC, for which an inhibition of viral A27L and B5R gene expression is described. Specifically, the translation of these viral genes is independent of PKR activation, but their expression is dependent on the RNase L activity. PMID:26656695

  9. Metabolism goes viral.

    Science.gov (United States)

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

    2014-04-01

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

  10. Occam factors and model independent Bayesian learning of continuous distributions

    International Nuclear Information System (INIS)

    Nemenman, Ilya; Bialek, William

    2002-01-01

    Learning of a smooth but nonparametric probability density can be regularized using methods of quantum field theory. We implement a field theoretic prior numerically, test its efficacy, and show that the data and the phase space factors arising from the integration over the model space determine the free parameter of the theory ('smoothness scale') self-consistently. This persists even for distributions that are atypical in the prior and is a step towards a model independent theory for learning continuous distributions. Finally, we point out that a wrong parametrization of a model family may sometimes be advantageous for small data sets

  11. TransCanada PipeLines Limited 1996 annual report : profitable today, prepared for tomorrow

    International Nuclear Information System (INIS)

    1997-01-01

    Operations and financial activities of TransCanada PipeLines Limited (TPL) during 1996 were reviewed and made available for the benefit of shareholders. TransCanada PipeLines Limited is a Canadian company with assets in excess of $12 billion. Its pipeline system transports natural gas and crude oil from the Western Canada Sedimentary Basin to North America's major energy markets. By all accounts the company had a successful year in 1996, having delivered a record 2.4 Bcf of gas, up 3.7 per cent from 1995, through the Canadian Mainline, TransCanada's largest asset. Among other notable achievements was the decision to join the Portland Natural Gas Transmission System as a 20 per cent partner in a project to construct a natural gas pipeline between Quebec and Haverhill, Massachusetts. Another accomplishment was the completion of the acquisition of all remaining shares of Alberta Natural Gas company, thereby extending the company's energy transmission, gas processing and specialty chemical operations. Other achievements were the purchase of Enron Louisiana Energy Company, the acquisition of assets that position TPL as one of the largest natural gas liquids processors in North America and the completion and commissioning of two new independent power generation plants in Ontario. Shareholder's return on investment was 34 per cent, more than double the target of between 12 to 15 per cent. Net income to common shares amounted to $1.85 per share, up from $1.75 in 1995. The strong performance was attributed to continued growth in all four segments of TPL's business, i. e. energy transmission, energy marketing, energy processing and international. tabs., figs

  12. Cardiovascular Risk Factors and Ethnicity Are Independent Factors Associated with Lower Urinary Tract Symptoms.

    Directory of Open Access Journals (Sweden)

    Jasmine Lim

    Full Text Available To determine the lower urinary tract symptoms (LUTS profile and factors affecting its degree of severity including cardiovascular risk profile, age, ethnicity, education level and prostate volume in a multiethnic Asian setting.We conducted a cross-sectional study of 1021 men aged 40-79 years with no clinical evidence of prostate cancer, prostate surgery or 5α-reductase inhibitor treatment of known prostate conditions. The severity of LUTS was assessed using the International Prostate Symptom Score (IPSS. Potential factors associated with LUTS including age, ethnicity, education, history of hypertension, diabetes and hypercholesterolemia, height, weight, and prostate volume were evaluated using univariable and multivariable analyses.There were 506 (50% men found to have moderate-to-severe LUTS attaining an IPSS above 7. Overall, nocturia (45.5% was the most frequently reported symptom. Multivariable analysis showed that age, ethnicity, prostate volume and history of hypertension and hypercholesterolemia were independent factors associated with severity of LUTS (p < 0.05. Considering individual lower urinary tract symptoms, we found a strong association of storage symptom with history of hypertension and hypercholesterolemia. Malay men were significantly bothered by post micturition symptom compared to their Chinese and Indian counterparts. Stratified analyses of LUTS demonstrated a mutually exclusive cardiovascular risk factors profile defined by ethnicity.Severity of LUTS varies between different ethnicities across all age groups. In addition to age and prostate volume, ethnicity and cardiovascular risk factors including hypertension and hypercholesterolemia may also need to be taken into account in managing men with LUTS.

  13. Obesity is an independent risk factor for pre-transplant portal vein thrombosis in liver recipients

    Directory of Open Access Journals (Sweden)

    Ayala Rosa

    2012-08-01

    Full Text Available Abstract Background Portal vein thrombosis is a frequent complication in end-stage cirrhosis with a considerable peri-operative risk for liver transplant candidates. We aimed to characterize the pre-transplant portal vein thrombosis in a cohort of liver transplant recipients, and to identify independent risk factors for this complication. Methods 380 consecutive primary orthotopic liver transplants were performed in the Digestive Surgery Department of “12 de Octubre” Hospital (Madrid, Spain, between January 2001 and December 2006. The main risk factors considered were smoking, obesity, metabolic disorders, previous immobility, surgery or trauma, nephrotic syndrome, associated tumor, inflammatory disease, neoplasm myeloprolipherative. Furthermore we have reported genetic thrombophilia results for 271 recipients. Results Sixty-two (16.3% patients developed pre-transplant portal vein thrombosis and its presence had no impact in the overall survival of liver recipients. Obesity was the only independent risk factor for pre-transplant portal vein thrombosis. Conclusion We recommend close control of cardiovascular factors in patients with liver cirrhosis in order to avoid associated thrombosis.

  14. Nonpolar interactions between trans-membrane helical EGF peptide and phosphatidylcholines, sphingomyelins and cholesterol. Molecular dynamics simulation studies

    NARCIS (Netherlands)

    Róg, T.; Murzyn, K.; Karttunen, M.E.J.; Pasenkiewicz-Gierula, M.

    2008-01-01

    A molecular dynamics simulation study of four lipid bilayers with inserted trans-membrane helical fragment of epithelial growth factor (EGF) receptor (EGF peptide) was performed. The lipid bilayers differ in their lipid composition and consist of (i) unsaturated phosphatidylcholine

  15. After runaway: The trans-Hill stage of planetesimal growth

    International Nuclear Information System (INIS)

    Lithwick, Yoram

    2014-01-01

    When planetesimals begin to grow by coagulation, they first enter an epoch of runaway, during which the biggest bodies grow faster than all the others. The questions of how runaway ends and what comes next have not been answered satisfactorily. We show that runaway is followed by a new stage—the 'trans-Hill stage'—that commences when the bodies that dominate viscous stirring ('big bodies') become trans-Hill, i.e., when their Hill velocity matches the random speed of the small bodies they accrete. Subsequently, the small bodies' random speed grows in lockstep with the big bodies' sizes, such that the system remains in the trans-Hill state. Trans-Hill growth is crucial for determining the efficiency of growing big bodies, as well as their growth timescale and size spectrum. Trans-Hill growth has two sub-stages. In the earlier one, which occurs while the stirring bodies remain sufficiently small, the evolution is collisionless, i.e., collisional cooling among all bodies is irrelevant. The efficiency of forming big bodies in this collisionless sub-stage is very low, ∼10α << 1, where α ∼ 0.005(a/AU) –1 is the ratio between the physical size of a body and its Hill radius. Furthermore, the size spectrum is flat (equal mass per size decade, i.e., q = 4). This collisionless trans-Hill solution explains results from previous coagulation simulations for both the Kuiper Belt and the asteroid belt. The second trans-Hill sub-stage commences once the stirring bodies grow big enough (>α –1 × the size of the accreted small bodies). After that time, collisional cooling among small bodies controls the evolution. The efficiency of forming big bodies rises and the size spectrum becomes more top heavy. Trans-Hill growth can terminate in one of two ways, depending on the sizes of the small bodies. First, mutual accretion of big bodies can become significant and conglomeration proceeds until half of the total mass is converted into big bodies

  16. Viral Genotypes and Associated Risk Factors of Hepatocellular Carcinoma in India

    International Nuclear Information System (INIS)

    Sarma, Manash Pratim; Asim, Mohammad; Medhi, Subhash; Bharathi, Thayumanavan; Diwan, Richa; Kar, Premashis

    2012-01-01

    This study aims to investigate the etiological relationship among hepatitis B virus (HBV), hepatitis C virus (HCV), and alcohol as risk factors in a cohort of hepatocellular carcinoma (HCC) patients from India. The clinical and biochemical profiles and tumor characteristics in the HCC cases were also evaluated. A total of 357 consecutive cases of HCC fulfilling the diagnostic criteria from the Barcelona–2000 EASL conference were included in the study. The blood samples were evaluated for serological evidence of HBV and HCV infection, viral load, and genotypes using serological tests, reverse transcription-polymerase chain reaction, and restriction fragment length polymorphism. The male/female ratio for the HCC cases was 5.87:1. Majority of the HCC patients (33.9%) were 50 to 59 years of age, with a mean age of 4±13.23 years. More than half the cases (60.8%) had underlying cirrhosis at presentation. Among the HCC patients, 68.9% were HBV related, 21.3% were HCV related, 18.8% were alcoholic, and 18.2% were of cryptogenic origin. The presence of any marker positive for HBV increased the risk for developing HCC by almost 27 times [OR: 27.33; (12.87–60.0)]. An increased risk of 10.6 times was observed for HCC development for cases positive for any HCV marker [OR: 10.55; (3.13–42.73)]. Heavy alcohol consumption along with HCV RNA positivity in cirrhotic patients was found to be a risk for developing HCC by 3 folds [OR: 3.17; (0.37–70.71)]. Patients of chronic HBV infection followed by chronic HCV infection were at higher risk of developing HCC in India. Chronic alcohol consumption was found to be a risk factor in cirrhotic cases only when it was associated with HCV RNA positivity. Most of the patients had a large tumor size (>5 cm) with multiple liver nodules, indicating an advanced stage of the disease thus making curative therapies difficult

  17. Viral infections as potential triggers of type 1 diabetes

    NARCIS (Netherlands)

    van der Werf, Nienke; Kroese, Frans G. M.; Rozing, Jan; Hillebrands, Jan-Luuk

    During the last decades, the incidence of type 1 diabetes (T1D) has increased significantly, reaching percentages of 3% annually worldwide. This increase suggests that besides genetical factors environmental perturbations (including viral infections) are also involved in the pathogenesis of T1D. T1D

  18. Life cycle synchronization is a viral drug resistance mechanism.

    Directory of Open Access Journals (Sweden)

    Iulia A Neagu

    2018-02-01

    Full Text Available Viral infections are one of the major causes of death worldwide, with HIV infection alone resulting in over 1.2 million casualties per year. Antiviral drugs are now being administered for a variety of viral infections, including HIV, hepatitis B and C, and influenza. These therapies target a specific phase of the virus's life cycle, yet their ultimate success depends on a variety of factors, such as adherence to a prescribed regimen and the emergence of viral drug resistance. The epidemiology and evolution of drug resistance have been extensively characterized, and it is generally assumed that drug resistance arises from mutations that alter the virus's susceptibility to the direct action of the drug. In this paper, we consider the possibility that a virus population can evolve towards synchronizing its life cycle with the pattern of drug therapy. The periodicity of the drug treatment could then allow for a virus strain whose life cycle length is a multiple of the dosing interval to replicate only when the concentration of the drug is lowest. This process, referred to as "drug tolerance by synchronization", could allow the virus population to maximize its overall fitness without having to alter drug binding or complete its life cycle in the drug's presence. We use mathematical models and stochastic simulations to show that life cycle synchronization can indeed be a mechanism of viral drug tolerance. We show that this effect is more likely to occur when the variability in both viral life cycle and drug dose timing are low. More generally, we find that in the presence of periodic drug levels, time-averaged calculations of viral fitness do not accurately predict drug levels needed to eradicate infection, even if there is no synchronization. We derive an analytical expression for viral fitness that is sufficient to explain the drug-pattern-dependent survival of strains with any life cycle length. We discuss the implications of these findings for

  19. In vitro evidence of a tissue factor-independent mode of action of recombinant factor VIIa in hemophilia.

    Science.gov (United States)

    Augustsson, Cecilia; Persson, Egon

    2014-11-13

    Successful competition of activated factor VII (FVIIa) with zymogen factor VII (FVII) for tissue factor (TF) and loading of the platelet surface with FVIIa are plausible driving forces behind the pharmacological effect of recombinant FVIIa (rFVIIa) in hemophilia patients. Thrombin generation measurements in platelet-rich hemophilia A plasma revealed competition for TF, which potentially could reduce the effective (r)FVIIa:TF complex concentration and thereby attenuate factor Xa production. However, (auto)activation of FVII apparently counteracted the negative effect of zymogen binding; a small impact was observed at endogenous concentrations of FVII and FVIIa but was virtually absent at pharmacological amounts of rFVIIa. Moreover, corrections of the propagation phase in hemophilia A required rFVIIa concentrations above the range where a physiological level of FVII was capable to downregulate thrombin generation. These data strongly suggest that rFVIIa acts independently of TF in hemophilia therapy and that FVII displacement by rFVIIa is a negligible mechanistic component. © 2014 by The American Society of Hematology.

  20. Innate immune restriction and antagonism of viral RNA lacking 2'-O methylation

    Energy Technology Data Exchange (ETDEWEB)

    Hyde, Jennifer L. [Departments of Medicine, Washington University School of Medicine, St Louis., MO 63110 (United States); Diamond, Michael S., E-mail: diamond@borcim.wustl.edu [Departments of Medicine, Washington University School of Medicine, St Louis., MO 63110 (United States); Molecular Microbiology, Washington University School of Medicine, St Louis., MO 63110 (United States); Pathology & Immunology, Washington University School of Medicine, St Louis., MO 63110 (United States); The Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St Louis., MO 63110 (United States)

    2015-05-15

    N-7 and 2′-O methylation of host cell mRNA occurs in the nucleus and results in the generation of cap structures (cap 0, m{sup 7}GpppN; cap 1, m{sup 7}GpppNm) that control gene expression by modulating nuclear export, splicing, turnover, and protein synthesis. Remarkably, RNA cap modification also contributes to mammalian cell host defense as viral RNA lacking 2′-O methylation is sensed and inhibited by IFIT1, an interferon (IFN) stimulated gene (ISG). Accordingly, pathogenic viruses that replicate in the cytoplasm have evolved mechanisms to circumvent IFIT1 restriction and facilitate infection of mammalian cells. These include: (a) generating cap 1 structures on their RNA through cap-snatching or virally-encoded 2′-O methyltransferases, (b) using cap-independent means of translation, or (c) using RNA secondary structural motifs to antagonize IFIT1 binding. This review will discuss new insights as to how specific modifications at the 5′-end of viral RNA modulate host pathogen recognition responses to promote infection and disease.

  1. Endometriosis is the independent prognostic factor for survival in Chinese patients with epithelial ovarian carcinoma.

    Science.gov (United States)

    Ren, Tong; Wang, Shu; Sun, Jian; Qu, Ji-Min; Xiang, Yang; Shen, Keng; Lang, Jing He

    2017-10-03

    Clinico-pathological characteristics and possible prognostic factors among women with epithelial ovarian carcinoma (EOC) with or without concurrent endometriosis were explored. We retrospectively identified 304 patients with EOC treated primarily at Peking Union Medical College Hospital with median follow-up time of 60 months. Of 304 patients with EOC, concurrent endometriosis was identified in 69 (22.7%). The patients with concurrent endometriosis were younger and more probably post-menopausal at onset, were less likely to have abdominal distension, with significantly lower level of pre-surgery serum Ca125 and less possibility of having the history of tubal ligation. The women with concurrent endometriosis group were more likely to have early stage tumors (88.41% versus 52.77%), receive optimal cytoreductive surgery (92.75% versus 71.06%), and less likely to have lymph node metastasis or to develop platinum resistance disease (7.25% versus 14.89%, and 7.35% versus 20%), when compared with women without coexisting endometriosis. The univariate analysis showed that concurrent endometriosis was a prognostic factor for overall survival (OS) and disease-free survival (DFS), but this association just remained in the DFS by multivariate analysis. Besides, multivariate analysis also showed that FIGO stage, residual disease, chemotherapy cycles, chemotherapy resistance and concomitant hypertension were the independent impact factors of OS for EOC patients; whereas FIGO stage, lymphadenectomy, residual disease, coexisting endometriosis and chemoresistance were independent impact factors of DFS for those patients. EOC patients with concurrent endometriosis showed distinct characteristics and had longer overall survival and disease-free survival when compared with those without endometriosis. Endometriosis was the independent prognostic factor for DFS for patients in this series.

  2. Monoclonal antibodies to DNA modified with cis- or trans-diamminedichloroplatinum(II)

    International Nuclear Information System (INIS)

    Sundquist, W.I.; Lippard, S.J.; Stollar, B.D.

    1987-01-01

    Murine monoclonal antibodies that bind selectively to adducts formed on DNA by the antitumor drug cis-diamminedichloroplatinum(II), cis-DDP, or to the chemothrapeutically inactive trans isomer trans-DDP were elicited by immunization with calf thymus DNA modified with either cis- or trans-DDP at ratios of bound platinum per nucleotide, (D/N)/sub b/, of 0.06-0.08. The binding of two monoclonal antibodies to cis-DDP-modified DNA was competitively inhibited in an enzyme-linked immunosorbent assay (ELISA) by 4-6 nM concentrations of cis-DDP bound to DNA. Adducts formed by cis-DDP on other synthetic DNA polymers did not inhibit antibody binding to cis-DDP-DNA. The biologically active compounds [Pt(en)Cl 2 ], [Pt(dach)Cl 2 ], and [Pt(NH 3 ) 2 (cbdca)] (carboplatin) all formed antibody-detectable adducts on DNA, whereas the inactive platinum complexes trans-DDP and [Pt(dien)Cl]Cl (dien, diethylenetriamine) did not. The monoclonal antibodies therefore recognize a bifunctional Pt-DNA adduct with cis stereochemistry in which platinum is coordinated by two adjacent guanines or, to a lesser degree, by adjacent adenine and guanine. A monoclonal antibody raised against trans-DDP-DNA was competitively inhibited in an ELISA by 40 nM trans-DDP bound to DNA. This antibody crossreacted with unmodified, denatured DNA. The recognition of cis- or trans-DDP-modified DNAs by monoclonal antibodies thus parallels the known modes of DNA binding of these compounds and may correlate with their biological activities

  3. Reasons for decision in the matter of TransCanada PipeLines Limited and TransCanada Keystone Pipeline GP Ltd. : application dated 5 June 2006 for leave to transfer pipeline facilities and for a determination of the transfer price

    International Nuclear Information System (INIS)

    2007-01-01

    TransCanada Pipelines Limited and its fully owned subsidiary TransCanada Keystone Pipeline GP Ltd. applied to the National Energy Board in June 2006 for leave to transfer certain pipeline facilities comprising part of TransCanada's mainline natural gas transmission system from TransCanada to Keystone for use in Keystone's proposed new oil pipeline. The transfer would involve the conversion of the facilities from gas service to oil service for use in the Keystone Project. The new oil pipeline would extend from Hardisty Alberta to Wood River and Patoka, Illinois. It would initially provide access for western Canada crude oil producers to the southern Petroleum Administration Defence District (PADD) 2 region of the United states. This is a major refining area which presently has minimal access for western Canada crude oil because of the limited pipeline capacity into the region. The Board held a hearing process to seek the views of interested parties regarding the list of issues that should be considered in dealing with the application. The list of issues included arguments of the Communications, Energy and Paperworkers Union of Canada (CEP) regarding the Board's jurisdiction; regulatory standards; energy supply markets and pipelines; potential impacts of the transfer such as potential costs to gas shippers and the impact of the transfer on mainline operations; and, the transfer at net book value (NBV). This document presented the Board's views on the transfer and the public interest. After considering all factors, the Board approved the sale and purchase of the Facilities from TransCanada to Keystone. The Board further ordered that TransCanada may reduce the mainline rate base by the NBV of the facilities upon their transfer to Keystone, and that Keystone may include the NBV in its pipeline oil plant upon the transfer of the facilities. 5 tabs., 14 figs., 6 appendices

  4. Translational research to reduce trans-fat intakes in Northern Québec (Nunavik Inuit communities: a success story?

    Directory of Open Access Journals (Sweden)

    Émilie Counil

    2012-07-01

    Full Text Available Following our results, based on population studies conducted in Greenland and Northern Canada, that Nunavik Inuit were thrice as highly exposed to dietary trans-fat as were Greenlandic Inuit, and that the biological levels found in Nunavik were already associated with deleterious blood lipid profiles, we decided to engage in translational activities. Our goal was to support Inuit communities in the practical implementation of a reduction of the trans-fat content of food sold in Nunavik. We carried out a preliminary feasibility study in Kuujjuaq and participated in several meetings. This translational phase involved an Inuk leader, an Inuk student, a southern student, a southern nutritionist and a southern researcher in the framework of a public health project. In the present article, we recount the different phases of the process, from research implementation to results dissemination and institutional commitment to implement a primary prevention program of reduction in trans-fat exposure in Nunavik. This is the occasion to draw broader conclusions on the factors that could either act in favour of or, on the contrary, would likely compromise the implementation of primary prevention interventions dealing with food and nutrition in the Arctic. Finally, we share some reflections on future translational activities dealing with trans-fat as well as other junk food issues. The analytical framework we propose integrates a range of factors, from geo-climatic to socio-economic, ethno-cultural, and even political, that we think should be examined while identifying and building preventive recommendations and strategies related to the Northern diet.

  5. Trans people's experiences with assisted reproduction services: a qualitative study.

    Science.gov (United States)

    James-Abra, S; Tarasoff, L A; Green, D; Epstein, R; Anderson, S; Marvel, S; Steele, L S; Ross, L E

    2015-06-01

    What are the experiences of trans persons (i.e. those whose gender identity does not match the gender assigned to them at birth) who sought or accessed assisted reproduction (AR) services in Ontario, Canada, between 2007 and 2010? The majority of trans persons report negative experiences with AR service providers. Apart from research examining desire to have children among trans people, most of the literature on this topic has debated the ethics of assisting trans persons to become parents. To-date, all of the published research concerning trans persons' experiences with AR services is solely from the perspective of service providers; no studies have examined the experiences of trans people themselves. Secondary qualitative research study of data from nine trans-identified people and their partners (total n = 11) collected as part of a community-based study of access to AR services for sexual and gender minority people between 2010 and 2012. Trans-identified volunteers (and their partners, when applicable) who had used or attempted to access AR services since 2007 from across Ontario, Canada, participated in a 60-90 minute, semi-structured qualitative interview. Qualitative analysis was performed using a descriptive phenomenological approach. Emerging themes were continually checked against the data as part of an iterative process. The data highlight barriers to accessing AR services for trans people. Participant recommendations for improving AR service provision to better meet the needs of this population are presented. These recommendations address the following areas: (i) AR service provider education and training; (ii) service provider and clinic practices and (iii) clinic environment. The majority of study participants were trans people who identified as men and who resided in major urban areas; those living in smaller communities may have different experiences that were not adequately captured in this analysis. While existing literature debates the ethics of

  6. The importance of trans-generational effects in Lepidoptera

    OpenAIRE

    Woestmann, Luisa; Saastamoinen, Marjo

    2016-01-01

    The importance of trans-generational effects in shaping an individuals' phenotype and fitness, and consequently even impacting population dynamics is increasingly apparent. Most of the research on trans-generational effects still focuses on plants, mammals, and birds. In the past few years, however, increasing number of studies, especially on maternal effects, have highlighted their importance also in many insect systems. Lepidoptera, specifically butterflies, have been used as model systems ...

  7. [Sedentary lifestyle is associated with metabolic and cardiovascular risk factors independent of physical activity].

    Science.gov (United States)

    Leiva, Ana María; Martínez, María Adela; Cristi-Montero, Carlos; Salas, Carlos; Ramírez-Campillo, Rodrigo; Díaz Martínez, Ximena; Aguilar-Farías, Nicolás; Celis-Morales, Carlos

    2017-04-01

    Sedentary behavior is a main risk factor for cardiovascular disease and mortality. To investigate the association between sedentary behavior and metabolic and cardiovascular risk factors. We assessed 322 participants aged between 18 to 65 years. Physical activity and sedentary behavior were measured with accelerometers (Actigraph®). Body mass index (BMI), waist circumference, percentage of body fat, diet and blood markers (glucose, lipid profile, insulin and HOMA-IR) were measured with standardized protocols. Thirty four percent of participants were physically inactive and spent on average 8.7 h/day on sedentary activities. Per one hour increase in sedentary behavior there were significant adverse changes in glucose (4.79 mg/dl), insulin (2.73 pmol/l), HOMA-IR (0.75), BMI (0.69 kg/m²), waist circumference (1.95 cm), fat mass (1.03%), total cholesterol (9.73 mg/dl), HDL-cholesterol (-3.50 mg/dl), LDL-cholesterol (10.7 mg/dl) and triglycerides (12.4 mg/dl). These findings were independent of main confounding factors including total physical activity, dietary factors, BMI and socio-demographics. The detrimental effect of sedentary behaviors on cardiometabolic and obesity-related traits is independent of physical activity levels. Therefore, reducing sedentary time should be targeted in the population apart from increasing their physical activity levels.

  8. Differences in HCV viral decline between low and standard-dose pegylated-interferon-alpha-2a with ribavirin in HIV/HCV genotype 3 patients.

    Directory of Open Access Journals (Sweden)

    Antonio Rivero-Juárez

    Full Text Available BACKGROUND: The aim of the study was to analyze the different impact of standard and low-dose Peg-IFN-α2a/RBV therapies on HCV viral decline in HIV/HCV genotype 3 co-infected patients during the first weeks of treatment. METHODS: Plasma HCV viral decline was analyzed between baseline and weeks 1, 2 and 4 in two groups of treatment-naïve HCV genotype 3 patients with HIV co-infection. The Standard Dose Group (SDG included patients who received Peg-IFN at 180 µg/per week with a weight-adjusted dose of ribavirin; Low-Dose Group (LDG patients received Peg-IFN at 135 µg/per week with 800 mg/day ribavirin. The effect of IL28B genotype on HCV viral decline was evaluated in both groups. HCV viral decline was analyzed using a multivariate linear regression model. RESULTS: One hundred and six patients were included: 48 patients in the SDG and 58 in the LDG. HCV viral decline for patients in the LDG was less than for those in the SDG (week 1:1.72±0.74 log(10 IU/mL versus 1.78±0.67 log(10 IU/mL, p = 0.827; week 2:2.3±0.89 log(10 IU/mL versus 3.01±1.02 log(10 IU/mL, p = 0.013; week 4:3.52±1.2 log(10 IU/mL versus 4.09±1.1 log(10 IU/mL, p = 0.005. The linear regression model identified the Peg-IFN/RBV dose as an independent factor for HCV viral decline at week 4. CONCLUSIONS: Our results showed that HCV viral decline was less for patients in the low-dose group compared to those receiving the standard dose. Until a randomized clinical trial is conducted, clinicians should be cautious about using lower doses of Peg-IFN/RBV in HIV/HCV genotype 3 co-infected patients.

  9. SV40 Utilizes ATM Kinase Activity to Prevent Non-homologous End Joining of Broken Viral DNA Replication Products

    Science.gov (United States)

    Sowd, Gregory A.; Mody, Dviti; Eggold, Joshua; Cortez, David; Friedman, Katherine L.; Fanning, Ellen

    2014-01-01

    Simian virus 40 (SV40) and cellular DNA replication rely on host ATM and ATR DNA damage signaling kinases to facilitate DNA repair and elicit cell cycle arrest following DNA damage. During SV40 DNA replication, ATM kinase activity prevents concatemerization of the viral genome whereas ATR activity prevents accumulation of aberrant genomes resulting from breakage of a moving replication fork as it converges with a stalled fork. However, the repair pathways that ATM and ATR orchestrate to prevent these aberrant SV40 DNA replication products are unclear. Using two-dimensional gel electrophoresis and Southern blotting, we show that ATR kinase activity, but not DNA-PKcs kinase activity, facilitates some aspects of double strand break (DSB) repair when ATM is inhibited during SV40 infection. To clarify which repair factors associate with viral DNA replication centers, we examined the localization of DSB repair proteins in response to SV40 infection. Under normal conditions, viral replication centers exclusively associate with homology-directed repair (HDR) and do not colocalize with non-homologous end joining (NHEJ) factors. Following ATM inhibition, but not ATR inhibition, activated DNA-PKcs and KU70/80 accumulate at the viral replication centers while CtIP and BLM, proteins that initiate 5′ to 3′ end resection during HDR, become undetectable. Similar to what has been observed during cellular DSB repair in S phase, these data suggest that ATM kinase influences DSB repair pathway choice by preventing the recruitment of NHEJ factors to replicating viral DNA. These data may explain how ATM prevents concatemerization of the viral genome and promotes viral propagation. We suggest that inhibitors of DNA damage signaling and DNA repair could be used during infection to disrupt productive viral DNA replication. PMID:25474690

  10. SV40 utilizes ATM kinase activity to prevent non-homologous end joining of broken viral DNA replication products.

    Directory of Open Access Journals (Sweden)

    Gregory A Sowd

    2014-12-01

    Full Text Available Simian virus 40 (SV40 and cellular DNA replication rely on host ATM and ATR DNA damage signaling kinases to facilitate DNA repair and elicit cell cycle arrest following DNA damage. During SV40 DNA replication, ATM kinase activity prevents concatemerization of the viral genome whereas ATR activity prevents accumulation of aberrant genomes resulting from breakage of a moving replication fork as it converges with a stalled fork. However, the repair pathways that ATM and ATR orchestrate to prevent these aberrant SV40 DNA replication products are unclear. Using two-dimensional gel electrophoresis and Southern blotting, we show that ATR kinase activity, but not DNA-PK(cs kinase activity, facilitates some aspects of double strand break (DSB repair when ATM is inhibited during SV40 infection. To clarify which repair factors associate with viral DNA replication centers, we examined the localization of DSB repair proteins in response to SV40 infection. Under normal conditions, viral replication centers exclusively associate with homology-directed repair (HDR and do not colocalize with non-homologous end joining (NHEJ factors. Following ATM inhibition, but not ATR inhibition, activated DNA-PK(cs and KU70/80 accumulate at the viral replication centers while CtIP and BLM, proteins that initiate 5' to 3' end resection during HDR, become undetectable. Similar to what has been observed during cellular DSB repair in S phase, these data suggest that ATM kinase influences DSB repair pathway choice by preventing the recruitment of NHEJ factors to replicating viral DNA. These data may explain how ATM prevents concatemerization of the viral genome and promotes viral propagation. We suggest that inhibitors of DNA damage signaling and DNA repair could be used during infection to disrupt productive viral DNA replication.

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

    Science.gov (United States)

    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

  12. Functional comparison of antisense proteins of HTLV-1 and HTLV-2 in viral pathogenesis

    Directory of Open Access Journals (Sweden)

    Benoit eBarbeau

    2013-08-01

    Full Text Available The production of antisense transcripts from the 3’ long terminal repeat (LTR in human T-lymphotropic retroviruses has now been clearly demonstrated. After the identification of the antisense strand-encoded HTLV-1 bZIP (HBZ factor, we reported that HBZ could interact with CREB transcription factors and consequently turn off the important activating potential of the viral Tax protein on HTLV-1 5’ LTR promoter activity. We have recently accumulated new results demonstrating that antisense transcripts also exist in HTLV-2, -3 and -4. Furthermore, our data have confirmed the existence of encoded proteins from these antisense transcripts (termed antisense proteins of HTLVs or APHs. APHs are also involved in the down-regulation of Tax-dependent viral transcription. In this review, we will focus on the different molecular mechanisms used by HBZ and APH-2 to control viral expression. While HBZ interacts with CREB through its basic zipper domain, APH-2 binds to this cellular factor through a five amino acid motif localized in its carboxyl terminus. Moreover, unlike APH-2, HBZ possesses an N-terminal activation domain that also contributes to the inhibition of the viral transcription by interacting with the KIX domain of p300/CBP. On the other hand, HBZ was found to induce T-cell proliferation while APH-2 was unable to promote such proliferation. Interestingly, HTLV-2 has not been causally linked to human T-cell leukemia, while HTLV-1 is responsible for the development of the Adult T-cell Leukemia/Lymphoma (ATLL. We will further discuss the possible role played by antisense proteins in the establishment of pathologies induced by viral infection.

  13. Science and trans-science in standard setting

    International Nuclear Information System (INIS)

    Majone, G.

    1984-01-01

    Standard-setting is a blending of scientific, trans-scientific, and political elements which result in a number of consequences. Health standards, for example, are influenced by biological and philosophical assumptions and scientific traditions, with the dose-response function treated as a trans-scientific question because of scientific uncertainties. Costs and benefits and other values besides health, safety, or environment also enter into the balancing of regulatory decisions and keep regulations from a purely scientific knowledge is desirable. Recommendations that industry be self-regulatory reflect a shift in emphasis from legal enforcement to information-based compliance

  14. Strange Bedfellows: Anachronisms, Identity Politics, and the Queer Case of Trans.

    Science.gov (United States)

    Gailey, Nerissa

    2017-01-01

    This article explores trans identities, as articulated within a few historical texts. From early literary depictions of gender difference, to medicalized conceptions of transsexualism, to a proliferation of trans and queer identities represented by an ever-expanding "alphabet soup" of identity labels, our understandings of identities, sexualities, and queer community-building continue to change. I use the notion of "kind-making," as elaborated on in the work of Ian Hacking, to illustrate that some queer and trans identifications are affiliative, whereas others are contrastive or oppositional in nature, and these structural differences have important implications with respect to understanding identity and sexuality, and also trans inclusion within LGBT communities and activist efforts.

  15. Characterization of a Proteasome and TAP-independent Presentation of Intracellular Epitopes by HLA-B27 Molecules

    KAUST Repository

    Magnacca, A.

    2012-07-17

    Nascent HLA-class I molecules are stabilized by proteasome-derived peptides in the ER and the new complexes proceed to the cell surface through the post-ER vesicles. It has been shown, however, that less stable complexes can exchange peptides in the Trans Golgi Network (TGN). HLA-B27 are the most studied HLA-class I molecules due to their association with Ankylosing Spondylitis (AS). Chimeric proteins driven by TAT of HIV have been exploited by us to deliver viral epitopes, whose cross-presentation by the HLA-B27 molecules was proteasome and TAP-independent and not restricted to Antigen-Presenting Cells (APC). Here, using these chimeric proteins as epitope suppliers, we compared with each other and with the HLA-A2 molecules, the two HLA-B*2705 and B*2709 alleles differing at residue 116 (D116H) and differentially associated with AS. We found that the antigen presentation by the two HLA-B27 molecules was proteasome-, TAP-, and APC-independent whereas the presentation by the HLA-A2 molecules required proteasome, TAP and professional APC. Assuming that such difference could be due to the unpaired, highly reactive Cys-67 distinguishing the HLA-B27 molecules, C67S mutants in HLA-B*2705 and B*2709 and V67C mutant in HLA-A*0201 were also analyzed. The results showed that this mutation did not influence the HLA-A2-restricted antigen presentation while it drastically affected the HLA-B27-restricted presentation with, however, remarkable differences between B*2705 and B*2709. The data, together with the occurrence on the cell surface of unfolded molecules in the case of C67S-B*2705 mutant but not in that of C67S-B*2709 mutant, indicates that Cys-67 has a more critical role in stabilizing the B*2705 rather than the B*2709 complexes.

  16. 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....

  17. Viral coinfection is shaped by host ecology and virus-virus interactions across diverse microbial taxa and environments.

    Science.gov (United States)

    Díaz-Muñoz, Samuel L

    2017-01-01

    Infection of more than one virus in a host, coinfection, is common across taxa and environments. Viral coinfection can enable genetic exchange, alter the dynamics of infections, and change the course of viral evolution. Yet, a systematic test of the factors explaining variation in viral coinfection across different taxa and environments awaits completion. Here I employ three microbial data sets of virus-host interactions covering cross-infectivity, culture coinfection, and single-cell coinfection (total: 6,564 microbial hosts, 13,103 viruses) to provide a broad, comprehensive picture of the ecological and biological factors shaping viral coinfection. I found evidence that ecology and virus-virus interactions are recurrent factors shaping coinfection patterns. Host ecology was a consistent and strong predictor of coinfection across all three data sets: cross-infectivity, culture coinfection, and single-cell coinfection. Host phylogeny or taxonomy was a less consistent predictor, being weak or absent in the cross-infectivity and single-cell coinfection models, yet it was the strongest predictor in the culture coinfection model. Virus-virus interactions strongly affected coinfection. In the largest test of superinfection exclusion to date, prophage sequences reduced culture coinfection by other prophages, with a weaker effect on extrachromosomal virus coinfection. At the single-cell level, prophage sequences eliminated coinfection. Virus-virus interactions also increased culture coinfection with ssDNA-dsDNA coinfections >2× more likely than ssDNA-only coinfections. The presence of CRISPR spacers was associated with a ∼50% reduction in single-cell coinfection in a marine bacteria, despite the absence of exact spacer matches in any active infection. Collectively, these results suggest the environment bacteria inhabit and the interactions among surrounding viruses are two factors consistently shaping viral coinfection patterns. These findings highlight the role of

  18. On-line pachymetry outcome of ablation in aberration free mode TransPRK.

    Science.gov (United States)

    Adib-Moghaddam, Soheil; Arba-Mosquera, Samuel; Salmanian, Bahram; Omidvari, Amir-Houshang; Noorizadeh, Farsad

    2014-01-01

    There are many independent factors that influence the outcome of refractive surgeries, consisting of patient characteristics and environmental factors. We studied the accuracy of central ablation depth compared to online pachymetry results. A total of 153 eyes that underwent TransPRK at Bina Eye Hospital, Tehran, Iran, were evaluated from November 2010 to January 2012 in a retrospective cross-sectional study. The relevant data were registered and bivariate correlations and linear regression association were investigated statistically. The mean age was 29 ± 5 years. Distribution of refractive errors was as follows: compound myopic astigmatism 123 (80.4%), simple myopia 24 (15.7%), and mixed astigmatism 6 (3.9%). Mean ambient temperature and humidity levels intraoperatively were 23.49 ± 1.16°C and 28.91 ± 6.16%, respectively. There was a significant difference (p<0.001) between the preassumed central ablation depth (131.68 ± 32.72 µm) and the net level of ablation depth (measured by online pachymetry, 168.04 ± 41.47 µm). Temperature and humidity levels were not in any statistically significant correlation with the net amount of difference found. The backward linear regression was done to reveal the association between ablation depth and several variables. This study showed that there is deviation in optical coherence pachymetry online measurements done with SCHWIND AMARIS laser. Ambient temperature and humidity levels intraoperatively do not influence the outcome. However, basic structural characteristics of patients along with change in refractive index and corneal shrinkage because of corneal dehydration are associated with the differences.

  19. 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

  20. 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,

  1. Differential effect of corn oil-based low trans structured fat on the plasma and hepatic lipid profile in an atherogenic mouse model: comparison to hydrogenated trans fat

    Directory of Open Access Journals (Sweden)

    Kim Hye-Jin

    2011-01-01

    Full Text Available Abstract Background Trans fat are not desirable in many aspects on health maintenance. Low trans structured fats have been reported to be relatively more safe than trans fats. Methods We examined the effects of low trans structured fat from corn oil (LC, compared with high trans fat shortening, on cholesterol and fatty acid metabolism in apo E deficient mice which is an atherogenic animal model. The animals were fed a high trans fat (10% fat: commercial shortening (CS or a low trans fat (LC diet for 12 weeks. Results LC decreased apo B and hepatic cholesterol and triglyceride concentration compared to the CS group but significantly increased plasma total cholesterol and triglyceride concentration and fecal lipids with a simultaneous increase in HDL-cholesterol level, apo A-I, and the ratio of HDL-cholesterol to total cholesterol (HTR. Reduction of hepatic lipid levels by inclusion of LC intake was observed alongside modulation of hepatic enzyme activities related to cholesterol esterification, fatty acid metabolism and fecal lipids level compared to the CS group. The differential effects of LC intake on the plasma and hepatic lipid profile seemed to be partly due to the fatty acid composition of LC which contains higher MUFA, PUFA and SFA content as well as lower content of trans fatty acids compared to CS. Conclusions We suggest that LC may exert a dual effect on plasma and hepatic lipid metabolism in an atherogenic animal model. Accordingly, LC, supplemented at 10% in diet, had an anti-atherogenic effect on these apo E-/- mice, and increased fecal lipids, decreased hepatic steatosis, but elevated plasma lipids. Further studies are needed to verify the exact mode of action regarding the complex physiological changes and alteration in lipid metabolism caused by LC.

  2. Differential effect of corn oil-based low trans structured fat on the plasma and hepatic lipid profile in an atherogenic mouse model: comparison to hydrogenated trans fat

    Science.gov (United States)

    2011-01-01

    Background Trans fat are not desirable in many aspects on health maintenance. Low trans structured fats have been reported to be relatively more safe than trans fats. Methods We examined the effects of low trans structured fat from corn oil (LC), compared with high trans fat shortening, on cholesterol and fatty acid metabolism in apo E deficient mice which is an atherogenic animal model. The animals were fed a high trans fat (10% fat: commercial shortening (CS)) or a low trans fat (LC) diet for 12 weeks. Results LC decreased apo B and hepatic cholesterol and triglyceride concentration compared to the CS group but significantly increased plasma total cholesterol and triglyceride concentration and fecal lipids with a simultaneous increase in HDL-cholesterol level, apo A-I, and the ratio of HDL-cholesterol to total cholesterol (HTR). Reduction of hepatic lipid levels by inclusion of LC intake was observed alongside modulation of hepatic enzyme activities related to cholesterol esterification, fatty acid metabolism and fecal lipids level compared to the CS group. The differential effects of LC intake on the plasma and hepatic lipid profile seemed to be partly due to the fatty acid composition of LC which contains higher MUFA, PUFA and SFA content as well as lower content of trans fatty acids compared to CS. Conclusions We suggest that LC may exert a dual effect on plasma and hepatic lipid metabolism in an atherogenic animal model. Accordingly, LC, supplemented at 10% in diet, had an anti-atherogenic effect on these apo E-/- mice, and increased fecal lipids, decreased hepatic steatosis, but elevated plasma lipids. Further studies are needed to verify the exact mode of action regarding the complex physiological changes and alteration in lipid metabolism caused by LC. PMID:21247503

  3. Trans*Forming College Masculinities: Carving out Trans*Masculine Pathways through the Threshold of Dominance

    Science.gov (United States)

    Jourian, T. J.

    2017-01-01

    Men and masculinities studies are gaining prominence in higher education literature, illuminating how cisgender college men understand and grapple with masculinity. Additionally, the increased visibility of trans* students has fueled the expanding scholarship and attention to their experiences, often however centering on white gender-conforming…

  4. Generation of transgene-free induced pluripotent stem cells with non-viral methods.

    Science.gov (United States)

    Wang, Tao; Zhao, Hua-shan; Zhang, Qiu-ling; Xu, Chang-lin; Liu, Chang-bai

    2013-03-01

    Induced pluripotent stem (iPS) cells were originally generated from mouse fibroblasts by enforced expression of Yamanaka factors (Oct3/4, Sox2, Klf4, and c-Myc). The technique was quickly reproduced with human fibroblasts or mesenchymal stem cells. Although having been showed therapeutic potential in animal models of sickle cell anemia and Parkinson's disease, iPS cells generated by viral methods do not suit all the clinical applications. Various non-viral methods have appeared in recent years for application of iPS cells in cell transplantation therapy. These methods mainly include DNA vector-based approaches, transfection of mRNA, and transduction of reprogramming proteins. This review summarized these non-viral methods and compare the advantages, disadvantages, efficiency, and safety of these methods.

  5. Evolution of approaches to viral safety issues for biological products.

    Science.gov (United States)

    Lubiniecki, Anthony S

    2011-01-01

    CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA) Approaches to viral safety issues for biological products have evolved during the past 50+ years. The first cell culture products (viral vaccines) relied largely on the use of in vitro and in vivo virus screening assays that were based upon infectivity of adventitious viral agents. The use of Cohn fractionation and pasteurization by manufacturers of plasma derivatives introduced the concepts that purification and treatment with physical and chemical agents could greatly reduce the risk of viral contamination of human albumin and immunoglobulin products. But the limitations of such approaches became clear for thermolabile products that were removed early in fractionation such as antihemophilic factors, which transmitted hepatitis viruses and HIV-1 to some product recipients. These successes and limitations were taken into account by the early developers of recombinant DNA (rDNA)-derived cell culture products and by regulatory agencies, leading to the utilization of cloning technology to reduce/eliminate contamination due to human viruses and purification technologies to physically remove and inactivate adventitious and endogenous viruses, along with cell banking and cell bank characterization for adventitious and endogenous viruses, viral screening of biological raw materials, and testing of cell culture harvests, to ensure virus safety. Later development and incorporation of nanofiltration technology in the manufacturing process provided additional assurance of viral clearance for safety of biotechnology products. These measures have proven very effective at preventing iatrogenic infection of recipients of biotechnology products; however, viral contamination of production cell cultures has

  6. Phosphorylation of human respiratory syncytial virus P protein at serine 54 regulates viral uncoating

    International Nuclear Information System (INIS)

    Asenjo, Ana; Gonzalez-Armas, Juan C.; Villanueva, Nieves

    2008-01-01

    The human respiratory syncytial virus (HRSV) structural P protein, phosphorylated at serine (S) and threonine (T) residues, is a co-factor of viral RNA polymerase. The phosphorylation of S54 is controlled by the coordinated action of two cellular enzymes: a lithium-sensitive kinase, probably glycogen synthetase kinase (GSK-3) β and protein phosphatase 2A (PP2A). Inhibition of lithium-sensitive kinase, soon after infection, blocks the viral growth cycle by inhibiting synthesis and/or accumulation of viral RNAs, proteins and extracellular particles. P protein phosphorylation at S54 is required to liberate viral ribonucleoproteins (RNPs) from M protein, during the uncoating process. Kinase inhibition, late in infection, produces a decrease in genomic RNA and infectious viral particles. LiCl, intranasally applied to mice infected with HRSV A2 strain, reduces the number of mice with virus in their lungs and the virus titre. Administration of LiCl to humans via aerosol should prevent HRSV infection, without secondary effects

  7. A factor analysis of Functional Independence and Functional Assessment Measure scores among focal and diffuse brain injury patients: The importance of bi-factor models.

    Science.gov (United States)

    Gunn, Sarah; Burgess, Gerald H; Maltby, John

    2018-04-28

    To explore the factor structure of the UK Functional Independence Measure and Functional Assessment Measure (FIM+FAM) among focal and diffuse acquired brain injury patients. Criterion standard. An NHS acute acquired brain injury inpatient rehabilitation hospital. Referred sample of 447 adults (835 cases after exclusions) admitted for inpatient treatment following an acquired brain injury significant enough to justify intensive inpatient neurorehabilitation. Not applicable. Functional Independence Measure and Functional Assessment Measure. Exploratory Factor Analysis suggested a two-factor structure to FIM+FAM scores, among both focal-proximate and diffuse-proximate acquired brain injury aetiologies. Confirmatory Factor Analysis suggested a three-factor bi-factor structure presented the best fit of the FIM+FAM score data across both aetiologies. However, across both analyses, a convergence was found towards a general factor, demonstrated by high correlations between factors in the Exploratory Factor Analysis, and by a general factor explaining the majority of the variance in scores on Confirmatory Factor Analysis. Our findings suggested that although factors describing specific functional domains can be derived from FIM+FAM item scores, there is a convergence towards a single factor describing overall functioning. This single factor informs the specific group factors (e.g. motor, psychosocial and communication function) following brain injury. Further research into the comparative value of the general and group factors as evaluative/prognostic measures is indicated. Copyright © 2018. Published by Elsevier Inc.

  8. Mechanically induced cis to trans reisomerization of azobenzene

    Science.gov (United States)

    Turansky, Robert; Konopka, Martin; Stich, Ivan; Marx, Dominik

    2007-03-01

    Using density functional techniques we study mechanochemistry of the azobenzene molecule. Azobenzene is an optically switchable molecule. Laser light is normally used to achieve molecular switching between the cis and trans isomers. We use mechanochemistry to achieve the switching. Thiolate-gold bond can used to exert mechanical energy on the molecule bonded between two gold electrodes in static AFM apparatus. Our model consists of two realistic gold electrodes bridged by dithioazobenzene. We find that pulling the transisomer leads just to formation of gold nanowires and mechanical breakage of the electrodes. However, mechanochemistry with modest applied forces leads to cis trans reisomerization via rotation mechanism. Contrary, use of simple constraints instead of realistic gold electrodes, leads to cis trans reisomerization, albeit with significantly larger applied forces and via inversion mechanism. Important experimental and theoretical ramifications of these simulations will be discussed.

  9. An in vivo genetic screen for genes involved in spliced leader trans-splicing indicates a crucial role for continuous de novo spliced leader RNP assembly.

    Science.gov (United States)

    Philippe, Lucas; Pandarakalam, George C; Fasimoye, Rotimi; Harrison, Neale; Connolly, Bernadette; Pettitt, Jonathan; Müller, Berndt

    2017-08-21

    Spliced leader (SL) trans-splicing is a critical element of gene expression in a number of eukaryotic groups. This process is arguably best understood in nematodes, where biochemical and molecular studies in Caenorhabditis elegans and Ascaris suum have identified key steps and factors involved. Despite this, the precise details of SL trans-splicing have yet to be elucidated. In part, this is because the systematic identification of the molecules involved has not previously been possible due to the lack of a specific phenotype associated with defects in this process. We present here a novel GFP-based reporter assay that can monitor SL1 trans-splicing in living C. elegans. Using this assay, we have identified mutants in sna-1 that are defective in SL trans-splicing, and demonstrate that reducing function of SNA-1, SNA-2 and SUT-1, proteins that associate with SL1 RNA and related SmY RNAs, impairs SL trans-splicing. We further demonstrate that the Sm proteins and pICln, SMN and Gemin5, which are involved in small nuclear ribonucleoprotein assembly, have an important role in SL trans-splicing. Taken together these results provide the first in vivo evidence for proteins involved in SL trans-splicing, and indicate that continuous replacement of SL ribonucleoproteins consumed during trans-splicing reactions is essential for effective trans-splicing. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  10. Intergenic mRNA molecules resulting from trans-splicing.

    Science.gov (United States)

    Finta, Csaba; Zaphiropoulos, Peter G

    2002-02-22

    Accumulated recent evidence is indicating that alternative splicing represents a generalized process that increases the complexity of human gene expression. Here we show that mRNA production may not necessarily be limited to single genes, as human liver also has the potential to produce a variety of hybrid cytochrome P450 3A mRNA molecules. The four known cytochrome P450 3A genes in humans, CYP3A4, CYP3A5, CYP3A7, and CYP3A43, share a high degree of similarity, consist of 13 exons with conserved exon-intron boundaries, and form a cluster on chromosome 7. The chimeric CYP3A mRNA molecules described herein are characterized by CYP3A43 exon 1 joined at canonical splice sites to distinct sets of CYP3A4 or CYP3A5 exons. Because the CYP3A43 gene is in a head-to-head orientation with the CYP3A4 and CYP3A5 genes, bypassing transcriptional termination can not account for the formation of hybrid CYP3A mRNAs. Thus, the mechanism generating these molecules has to be an RNA processing event that joins exons of independent pre-mRNA molecules, i.e. trans-splicing. Using quantitative real-time polymerase chain reaction, the ratio of one CYP3A43/3A4 intergenic combination was estimated to be approximately 0.15% that of the CYP3A43 mRNAs. Moreover, trans-splicing has been found not to interfere with polyadenylation. Heterologous expression of the chimeric species composed of CYP3A43 exon 1 joined to exons 2-13 of CYP3A4 revealed catalytic activity toward testosterone.

  11. It All Starts with a Sandwich: Identification of Sialidases with Trans-Glycosylation Activity

    DEFF Research Database (Denmark)

    Nordvang, Rune Thorbjørn; Nyffenegger, Christian; Holck, Jesper

    2016-01-01

    structure of two amino acids proximal to the active site of the T. cruzi trans-sialidase infers trans-sialidase activity. On this basis, four enzymes with putative trans-sialidase activity were identified through an iterative alignment from 2909 native sialidases available in GenBank, which were cloned...... and expressed in Escherichia coli. Of these, one enzyme, SialH, derived from Haemophilus parasuis had an aromatic sandwich structure on the protein surface facing the end of the catalytic site (Phe168; Trp366), and was indeed found to exhibit trans-sialidase activity. SialH catalyzed production of the human...... provided data that help understand structure-function relations of trans-sialidases....

  12. Siegel discs via trans-quasiconformal surgery

    DEFF Research Database (Denmark)

    Petersen, Carsten Lunde

    2014-01-01

    kompleksstruktur kan integreres, det vil sige definerer en kompleksstruktur. I denne komplekse struktur er den nye afbildning holomorf og har en Siegel disk. Der findes imidlertid masser af tilfælde hvor dette ikke lader sig gøre, men hvor man istedet kan finde en trans-kvasikonform udvidelse til enheds-disken af...... mængde af rotationstal med fuldt mål på cirklen har konjugationen en trans-kvasi-konform udvidelse til disken. Dette er et skridt i beviset for at for næsten alle (i Lebeguemåls forstand) rotations tal, er randen af Siegel-disken for et kvadratisk polynomium med en Siegel disk med et sådant rotationstal...

  13. Endoscopic treatment of trans-sellar trans-sphenoidal encephalocele associated with morning glory syndrome presenting with non-traumatic cerebrospinal fluid rhinorrhea.

    Science.gov (United States)

    Sasani, M; Ozer, A F; Aydin, A L

    2009-03-01

    Basal encephaloceles are rare, accounting for about 1.5% of all encephaloceles. The trans-sellar trans-sphenoidal encephalocele variety is the rarest. Morning glory syndrome is often associated with basal encephalocele. Spontaneous cerebrospinal fluid (CSF) rhinorrheas are the least common of these, accounting for only 3% to 5% of all CSF rhinorrheas. The authors describe the outcome of a 10-year follow-up study of a 26-year-old male patient with a spontaneous CSF rhinorrhea occurring trans-sphenoidal encephalocele associated with bilateral morning glory syndrome that was treated with an endoscopic endonasal approach. Endoscopic exploration of the sella floor was performed and closed with abdomen fat packing and muscle fascia. The postoperative course was uneventful. A follow-up magnetic resonance (MR) image at 6 months postoperatively showed extension of encephalocele in the sphenoidal sinus, which was repaired. The patient had no further CSF rhinorrhea and showed no ophthalmologic changes over a follow-up period of over 10 years. Ophthalmologic findings such as strabismus, in association with anomalies of the optic nerve, should alert the physician to the possible presence of an unrecognized skull base midline defect and encephalocele before CSF leakage is seen. The authors believe that a surgeon who has equal confidence in performing the endoscopic endonasal and conventional microscopic trans-sphenoidal approaches should choose the less invasive surgery.

  14. 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.

  15. 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

  16. Preoperative carcinoembryonic antigen and prognosis of colorectal cancer. An independent prognostic factor still reliable.

    Science.gov (United States)

    Li Destri, Giovanni; Rubino, Antonio Salvatore; Latino, Rosalia; Giannone, Fabio; Lanteri, Raffaele; Scilletta, Beniamino; Di Cataldo, Antonio

    2015-04-01

    To evaluate whether, in a sample of patients radically treated for colorectal carcinoma, the preoperative determination of the carcinoembryonic antigen (p-CEA) may have a prognostic value and constitute an independent risk factor in relation to disease-free survival. The preoperative CEA seems to be related both to the staging of colorectal neoplasia and to the patient's prognosis, although this-to date-has not been conclusively demonstrated and is still a matter of intense debate in the scientific community. This is a retrospective analysis of prospectively collected data. A total of 395 patients were radically treated for colorectal carcinoma. The preoperative CEA was statistically compared with the 2010 American Joint Committee on Cancer (AJCC) staging, the T and N parameters, and grading. All parameters recorded in our database were tested for an association with disease-free survival (DFS). Only factors significantly associated (P < 0.05) with the DFS were used to build multivariate stepwise forward logistic regression models to establish their independent predictors. A statistically significant relationship was found between p-CEA and tumor staging (P < 0.001), T (P < 0.001) and N parameters (P = 0.006). In a multivariate analysis, the independent prognostic factors found were: p-CEA, stages N1 and N2 according to AJCC, and G3 grading (grade). A statistically significant difference (P < 0.001) was evident between the DFS of patients with normal and high p-CEA levels. Preoperative CEA makes a pre-operative selection possible of those patients for whom it is likely to be able to predict a more advanced staging.

  17. Socioeconomic deprivation is an independent risk factor for behavioral problems in children with epilepsy.

    Science.gov (United States)

    Carson, Joanna; Weir, Andrew; Chin, Richard F; McLellan, Ailsa

    2015-04-01

    The aim of this study was to examine whether socioeconomic deprivation in children with epilepsy (CWE) increases risk for behavioral problems independent of seizure factors. A cross-sectional study was done in which parents of children attending a specialist epilepsy clinic were invited to complete a child behavior checklist (CBCL) questionnaire about their child. Medical and sociodemographic data on CWE were obtained through their pediatric neurologists. Home postal code was used to obtain quintiles of Scottish Index of Multiple Deprivation 2012 (SIMD2012) scores for individuals. Lower (1-3) quintiles correspond to higher socioeconomic deprivation. Regression analysis was used to investigate whether a lower quintile was an independent risk factor for scores >63 (significant behavioral problem). Parents of 87 children (42 male, mean age of 10.5years) were enrolled. Fifty-nine percent had total scores >63. A higher proportion of children from quintiles 1-3 compared to those from quintiles 4-5 had externalizing (49% vs. 25%, p=0.02) and total (54% vs. 30%, p=0.02) scores >63. Adjusted OR of quintiles 1-3 vs. 4-5 for scores >63=14.8, 95% CI=3.0, 68.0. Fewer children with scores >63 and from quintiles 1-3 were known to the child and adolescent mental health service (CAMHS) compared to those in quintiles 4-5 (p=0.01). Socioeconomic deprivation was an independent risk factor for behavioral problems in CWE. Children with epilepsy and behavioral problems who lived in socioeconomically deprived areas received less help. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Viral quasispecies profiles as the result of the interplay of competition and cooperation.

    Science.gov (United States)

    Arbiza, Juan; Mirazo, Santiago; Fort, Hugo

    2010-05-10

    Viral quasispecies can be regarded as a swarm of genetically related mutants. A common approach employed to describe viral quasispecies is by means of the quasispecies equation (QE). However, a main criticism of QE is its lack of frequency-dependent selection. This can be overcome by an alternative formulation for the evolutionary dynamics: the replicator-mutator equation (RME). In turn, a problem with the RME is how to quantify the interaction coefficients between viral variants. Here, this is addressed by adopting an ecological perspective and resorting to the niche theory of competing communities, which assumes that the utilization of resources primarily determines ecological segregation between competing individuals (the different viral variants that constitute the quasispecies). This provides a theoretical framework to estimate quantitatively the fitness landscape. Using this novel combination of RME plus the ecological concept of niche overlapping for describing a quasispecies we explore the population distributions of viral variants that emerge, as well as the corresponding dynamics. We observe that the population distribution requires very long transients both to A) reach equilibrium and B) to show a clear dominating master sequence. Based on different independent and recent experimental evidence, we find that when some cooperation or facilitation between variants is included in appropriate doses we can solve both A) and B). We show that a useful quantity to calibrate the degree of cooperation is the Shannon entropy. In order to get a typical quasispecies profile, at least within the considered mathematical approach, it seems that pure competition is not enough. Some dose of cooperation among viral variants is needed. This has several biological implications that might contribute to shed light on the mechanisms operating in quasispecies dynamics and to understand the quasispecies as a whole entity.

  19. 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...

  20. Reprogramming Acyl Carrier Protein Interactions of an Acyl-CoA Promiscuous trans-Acyltransferase

    DEFF Research Database (Denmark)

    Ye, Zhixia; Musiol-Kroll, Ewa Maria; Weber, Tilmann

    2014-01-01

    Protein interactions between acyl carrier proteins (ACPs) and trans-acting acyltransferase domains (trans-ATs) are critical for regioselective extender unit installation by many polyketide synthases, yet little is known regarding the specificity of these interactions, particularly for trans-ATs w...