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Search Results: 1 - 10 of 1205 matches for " Florence Guivel-Benhassine "
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Inhibition of mTORC1 Enhances the Translation of Chikungunya Proteins via the Activation of the MnK/eIF4E Pathway
Pierre-Emmanuel Joubert?,Kenneth Stapleford?,Florence Guivel-Benhassine,Marco Vignuzzi?,Olivier Schwartz?,Matthew L. Albert
PLOS Pathogens , 2015, DOI: 10.1371/journal.ppat.1005091
Abstract: Chikungunya virus (CHIKV), the causative agent of a major epidemic spanning five continents, is a positive stranded mRNA virus that replicates using the cell’s cap-dependent translation machinery. Despite viral infection inhibiting mTOR, a metabolic sensor controls cap-dependent translation, viral proteins are efficiently translated. Rapalog treatment, silencing of mtor or raptor genes, but not rictor, further enhanced CHIKV infection in culture cells. Using biochemical assays and real time imaging, we demonstrate that this effect is independent of autophagy or type I interferon production. Providing in vivo evidence for the relevance of our findings, mice treated with mTORC1 inhibitors exhibited increased lethality and showed a higher sensitivity to CHIKV. A systematic evaluation of the viral life cycle indicated that inhibition of mTORC1 has a specific positive effect on viral proteins, enhancing viral replication by increasing the translation of both structural and nonstructural proteins. Molecular analysis defined a role for phosphatidylinositol-3 kinase (PI3K) and MAP kinase-activated protein kinase (MnKs) activation, leading to the hyper-phosphorylation of eIF4E. Finally, we demonstrated that in the context of CHIKV inhibition of mTORC1, viral replication is prioritized over host translation via a similar mechanism. Our study reveals an unexpected bypass pathway by which CHIKV protein translation overcomes viral induced mTORC1 inhibition.
Tetherin Restricts Productive HIV-1 Cell-to-Cell Transmission
Nicoletta Casartelli equal contributor,Marion Sourisseau equal contributor,Jerome Feldmann,Florence Guivel-Benhassine,Adeline Mallet,Anne-Geneviève Marcelin,John Guatelli,Olivier Schwartz
PLOS Pathogens , 2010, DOI: 10.1371/journal.ppat.1000955
Abstract: The IFN-inducible antiviral protein tetherin (or BST-2/CD317/HM1.24) impairs release of mature HIV-1 particles from infected cells. HIV-1 Vpu antagonizes the effect of tetherin. The fate of virions trapped at the cell surface remains poorly understood. Here, we asked whether tetherin impairs HIV cell-to-cell transmission, a major means of viral spread. Tetherin-positive or -negative cells, infected with wild-type or ΔVpu HIV, were used as donor cells and cocultivated with target lymphocytes. We show that tetherin inhibits productive cell-to-cell transmission of ΔVpu to targets and impairs that of WT HIV. Tetherin accumulates with Gag at the contact zone between infected and target cells, but does not prevent the formation of virological synapses. In the presence of tetherin, viruses are then mostly transferred to targets as abnormally large patches. These viral aggregates do not efficiently promote infection after transfer, because they accumulate at the surface of target cells and are impaired in their fusion capacities. Tetherin, by imprinting virions in donor cells, is the first example of a surface restriction factor limiting viral cell-to-cell spread.
Real-Time Whole-Body Visualization of Chikungunya Virus Infection and Host Interferon Response in Zebrafish
Nuno Palha,Florence Guivel-Benhassine,Valérie Briolat,Georges Lutfalla,Marion Sourisseau,Felix Ellett,Chieh-Huei Wang,Graham J. Lieschke,Philippe Herbomel,Olivier Schwartz,Jean-Pierre Levraud
PLOS Pathogens , 2013, DOI: 10.1371/journal.ppat.1003619
Abstract: Chikungunya Virus (CHIKV), a re-emerging arbovirus that may cause severe disease, constitutes an important public health problem. Herein we describe a novel CHIKV infection model in zebrafish, where viral spread was live-imaged in the whole body up to cellular resolution. Infected cells emerged in various organs in one principal wave with a median appearance time of ~14 hours post infection. Timing of infected cell death was organ dependent, leading to a shift of CHIKV localization towards the brain. As in mammals, CHIKV infection triggered a strong type-I interferon (IFN) response, critical for survival. IFN was mainly expressed by neutrophils and hepatocytes. Cell type specific ablation experiments further demonstrated that neutrophils play a crucial, unexpected role in CHIKV containment. Altogether, our results show that the zebrafish represents a novel valuable model to dynamically visualize replication, pathogenesis and host responses to a human virus.
A Mouse Model for Chikungunya: Young Age and Inefficient Type-I Interferon Signaling Are Risk Factors for Severe Disease
Thérèse Couderc equal contributor,Fabrice Chrétien equal contributor,Clémentine Schilte equal contributor,Olivier Disson,Madly Brigitte,Florence Guivel-Benhassine,Yasmina Touret,Georges Barau,Nadège Cayet,Isabelle Schuffenecker,Philippe Desprès,Fernando Arenzana-Seisdedos,Alain Michault,Matthew L Albert equal contributor,Marc Lecuit equal contributor
PLOS Pathogens , 2008, DOI: 10.1371/journal.ppat.0040029
Abstract: Chikungunya virus (CHIKV) is a re-emerging arbovirus responsible for a massive outbreak currently afflicting the Indian Ocean region and India. Infection from CHIKV typically induces a mild disease in humans, characterized by fever, myalgia, arthralgia, and rash. Cases of severe CHIKV infection involving the central nervous system (CNS) have recently been described in neonates as well as in adults with underlying conditions. The pathophysiology of CHIKV infection and the basis for disease severity are unknown. To address these critical issues, we have developed an animal model of CHIKV infection. We show here that whereas wild type (WT) adult mice are resistant to CHIKV infection, WT mouse neonates are susceptible and neonatal disease severity is age-dependent. Adult mice with a partially (IFN-α/βR+/?) or totally (IFN-α/βR?/?) abrogated type-I IFN pathway develop a mild or severe infection, respectively. In mice with a mild infection, after a burst of viral replication in the liver, CHIKV primarily targets muscle, joint, and skin fibroblasts, a cell and tissue tropism similar to that observed in biopsy samples of CHIKV-infected humans. In case of severe infections, CHIKV also disseminates to other tissues including the CNS, where it specifically targets the choroid plexuses and the leptomeninges. Together, these data indicate that CHIKV-associated symptoms match viral tissue and cell tropisms, and demonstrate that the fibroblast is a predominant target cell of CHIKV. These data also identify the neonatal phase and inefficient type-I IFN signaling as risk factors for severe CHIKV-associated disease. The development of a permissive small animal model will expedite the testing of future vaccines and therapeutic candidates.
Characterization of Reemerging Chikungunya Virus
Marion Sourisseau,Clémentine Schilte,Nicoletta Casartelli,Céline Trouillet,Florence Guivel-Benhassine,Dominika Rudnicka,Nathalie Sol-Foulon,Karin Le Roux,Marie-Christine Prevost,Hafida Fsihi,Marie-Pascale Frenkiel,Fabien Blanchet,Philippe V Afonso,Pierre-Emmanuel Ceccaldi,Simona Ozden,Antoine Gessain,Isabelle Schuffenecker,Bruno Verhasselt,Alessia Zamborlini,Ali Sa?b,Felix A Rey,Fernando Arenzana-Seisdedos,Philippe Desprès,Alain Michault,Matthew L Albert,Olivier Schwartz
PLOS Pathogens , 2007, DOI: 10.1371/journal.ppat.0030089
Abstract: An unprecedented epidemic of chikungunya virus (CHIKV) infection recently started in countries of the Indian Ocean area, causing an acute and painful syndrome with strong fever, asthenia, skin rash, polyarthritis, and lethal cases of encephalitis. The basis for chikungunya disease and the tropism of CHIKV remain unknown. Here, we describe the replication characteristics of recent clinical CHIKV strains. Human epithelial and endothelial cells, primary fibroblasts and, to a lesser extent, monocyte-derived macrophages, were susceptible to infection and allowed viral production. In contrast, CHIKV did not replicate in lymphoid and monocytoid cell lines, primary lymphocytes and monocytes, or monocyte-derived dendritic cells. CHIKV replication was cytopathic and associated with an induction of apoptosis in infected cells. Chloroquine, bafilomycin-A1, and short hairpin RNAs against dynamin-2 inhibited viral production, indicating that viral entry occurs through pH-dependent endocytosis. CHIKV was highly sensitive to the antiviral activity of type I and II interferons. These results provide a general insight into the interaction between CHIKV and its mammalian host.
Interest-Rate Setting at the ECB Following the Financial and Sovereign Debt Crises, in Real-Time  [PDF]
Florence Bouvet, Sharmila King
Modern Economy (ME) , 2011, DOI: 10.4236/me.2011.25083
Abstract: We analyse European Central Bank (ECB) policy by estimating a forward-looking, augmented Taylor rule using expectations data. Specifically, we investigate the impact of the financial and sovereign debt crises on ECB policy. We find the European Overnight Index Average (EONIA) rises when expected economic activity is strong. Regardless of the inflation measure, inflation is not associated with the EONIA. Using a recursive estimation and a Chow test, we identify a policy shift in December 2008. The more generally accepted starting date of the crisis, August 2007, does not correspond to a statistically significant shift in the ECB policy. Using December 2008 for a policy shift, general financial market sentiment, as measured by VSTOXX, is not significant in explaining EONIA movements. The ECB’s response to a shock to economic activity has been more moderate since the crises. However, the EONIA increases as Greek sovereign risk rises, possibly from increasing demand for liquidity by banks.
Attitudes of Nursing Faculty Members and Graduates towards the Objective Structured Clinical Examination (OSCE)  [PDF]
Florence E. Omu
Open Journal of Nursing (OJN) , 2016, DOI: 10.4236/ojn.2016.65037
Abstract: The aim of this study was to evaluate the attitudes of faculty and graduates of college of nursing towards Objective Structured Clinical Examination (OSCE) as a valid and reliable method of clinical competency assessment in nursing ten years after its inception. Core nursing courses are based on instructional teaching methods and “hands-on” approach to impact cognitive, psychomotor skills and clinical judgments. Different clinical competency assessment methods are used globally; however, most of them are subjective. A descriptive survey using 16-item five-point likert scale questionnaire was conducted. The study sample consisted of 140 participants: 20 faculty members, 27 graduates of the Bachelor of Science in Nursing (BSN) Degree and 93 graduates of the Associate Degree of Nursing (ADN) programs with OSCE experience during their training. Data collection was carried out between October and November 2015. Eighty percent of faculty members, 74% of BSN and 62.3% of ADN graduates agreed that OSCE represented an objective evaluation method for psychomotor skills. Majority of the graduates perceived their OSCE experience positively although stressful. However, they have suggested the introduction of trial/mock OSCE prior to each exam to minimize the stress associated with it. In conclusion, there appears to be no single “gold-standard” assessment tool for clinical competency. OSCE assesses student nurses’ psychomotor skills in a non-clinical environment, therefore without risks to real patients. In combination with other assessment methods in the clinical settings, OSCE will provide a more comprehensive student psychomotor skill evaluation. OSCE experiences gave new nursing graduates confidence to work as registered nurses in health care settings.
Life Satisfaction and Quality of Life Enjoyment among Retired People Aged 65 or Older  [PDF]
Florence Mei Fung Wong
Open Journal of Social Sciences (JSS) , 2019, DOI: 10.4236/jss.2019.75009
Ageing is a global concern. Today, we emphasize healthy ageing with life satisfaction and better quality of life. The advanced technology in healthcare services and medical treatment has led to greater longevity. Although older people reach retirement age at 65, they continue to work for their career. Retirement can be a financial impact as the working older people cannot continue to earn money for their living. They need to rely on support from their family and the government. Retirement is also the factor to make dramatically changes in roles and responsibilities, authority, social network, and self-value. This study aimed 1) to examine the level of life satisfaction and quality of life enjoyment and 2) to identify relationships between demo-graphic characteristics and life satisfaction and quality of life enjoyment among older people aged 65 or older. The study results are significant to show the important areas to improve life satisfaction and quality of life enjoyment among older people aged 65 or older. Social relationship, particularly, support from family is the most important element to enhance life sat-isfaction and quality of life enjoyment in retired people.
Influence of Processing on Dietary Fiber, Tannin and in Vitro Protein Digestibility of Pearl Millet  [PDF]
Florence Suma Pushparaj, Asna Urooj
Food and Nutrition Sciences (FNS) , 2011, DOI: 10.4236/fns.2011.28122
Abstract: From the nutritional point of view, data on dietary fiber content, tannin and in vitro protein digestibility of processed millet is of importance, because millets are never eaten raw. Effects of commonly used traditional methods on dietary fiber, tannin content and %IVPD of two locally available pearl millet varieties (Kalukombu and Maharashtra Rabi Bajra) were investigated. The millet was subjected to various processing methods like milling (whole flour, semi refined flour and bran rich fraction) roasting, boiling, pressure cooking & germination respectively. Processing had little effect on the total dietary fiber (TDF) content in both varieties; however the bran rich fraction showed highest TDF content of around 29%. Tannins effectively lowered upon boiling and pressure cooking respectively, but significantly increased (P ≥ 0.05) upon germination. Although the % IVPD of the millet (45.5 – 49.3 g/100g) was low, it significantly increased upon milling (bran rich fraction), roasting and germination respectively.
Pharmacological and therapeutic directions in ADHD: Specificity in the PFC
Florence Levy
Behavioral and Brain Functions , 2008, DOI: 10.1186/1744-9081-4-12
Abstract: The actions of dopaminergic vs noradrenergic agents, currently available for the treatment of ADHD have overlapping, but different actions in the prefrontal cortex (PFC) and subcortical centers. While stimulants act on D1 receptors in the dorsolateral prefrontal cortex, they also have effects on D2 receptors in the corpus striatum and may also have serotonergic effects at orbitofrontal areas. At therapeutic levels, dopamine (DA) stimulation (through DAT transporter inhibition) decreases noise level acting on subcortical D2 receptors, while NE stimulation (through alpha-2A agonists) increases signal by acting preferentially in the PFC possibly on DAD1 receptors. On the other hand, alpha-2A noradrenergic transmission is more limited to the prefrontal cortex (PFC), and thus less likely to have motor or stereotypic side effects, while alpha-2B and alpha-2C agonists may have wider cortical effects. The data suggest a possible hierarchy of specificity in the current medications used in the treatment of ADHD, with guanfacine likely to be most specific for the treatment of prefrontal attentional and working memory deficits. Stimulants may have broader effects on both vigilance and motor impulsivity, depending on dose levels, while atomoxetine may have effects on attention, anxiety, social affect, and sedation via noradrenergic transmission.At a theoretical level, the advent of possible specific alpha-2A noradrenergic therapies has posed the question of the role of working memory in ADHD. Head to head comparisons of stimulant and noradrenergic alpha-2A, alpha-2B and alpha-2C agonists, utilizing vigilance and affective measures should help to clarify pharmacological and therapeutic differences.Recent directions in the treatment of ADHD have involved both a broadening of pharmacological perspectives to include nor-adrenergic as well as dopaminergic agents. This offers an opportunity, in conjunction with animal studies for a better understanding of the differential selectivity
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