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Search Results: 1 - 10 of 231112 matches for " Thérèse Couderc equal contributor "
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Induction of GADD34 Is Necessary for dsRNA-Dependent Interferon-β Production and Participates in the Control of Chikungunya Virus Infection
Giovanna Clavarino equal contributor,Nuno Cláudio equal contributor,Thérèse Couderc equal contributor,Alexandre Dalet,Delphine Judith,Voahirana Camosseto,Enrico K. Schmidt,Till Wenger,Marc Lecuit,Evelina Gatti ? ,Philippe Pierre ?
PLOS Pathogens , 2012, DOI: 10.1371/journal.ppat.1002708
Abstract: Nucleic acid sensing by cells is a key feature of antiviral responses, which generally result in type-I Interferon production and tissue protection. However, detection of double-stranded RNAs in virus-infected cells promotes two concomitant and apparently conflicting events. The dsRNA-dependent protein kinase (PKR) phosphorylates translation initiation factor 2-alpha (eIF2α) and inhibits protein synthesis, whereas cytosolic DExD/H box RNA helicases induce expression of type I-IFN and other cytokines. We demonstrate that the phosphatase-1 cofactor, growth arrest and DNA damage-inducible protein 34 (GADD34/Ppp1r15a), an important component of the unfolded protein response (UPR), is absolutely required for type I-IFN and IL-6 production by mouse embryonic fibroblasts (MEFs) in response to dsRNA. GADD34 expression in MEFs is dependent on PKR activation, linking cytosolic microbial sensing with the ATF4 branch of the UPR. The importance of this link for anti-viral immunity is underlined by the extreme susceptibility of GADD34-deficient fibroblasts and neonate mice to Chikungunya virus infection.
Chikungunya Virus-associated Long-term Arthralgia: A 36-month Prospective Longitudinal Study
Clémentine Schilte equal contributor,Frédérik Staikovsky equal contributor,Thérèse Couderc equal contributor,Yoann Madec,Florence Carpentier,Somar Kassab,Matthew L. Albert,Marc Lecuit ? ,Alain Michault ?
PLOS Neglected Tropical Diseases , 2013, DOI: 10.1371/journal.pntd.0002137
Abstract: Background Arthritogenic alphaviruses, including Chikungunya virus (CHIKV), are responsible for acute fever and arthralgia, but can also lead to chronic symptoms. In 2006, a Chikungunya outbreak occurred in La Réunion Island, during which we constituted a prospective cohort of viremic patients (n = 180) and defined the clinical and biological features of acute infection. Individuals were followed as part of a longitudinal study to investigate in details the long-term outcome of Chikungunya. Methodology/Principal Findings Patients were submitted to clinical investigations 4, 6, 14 and 36 months after presentation with acute CHIKV infection. At 36 months, 22 patients with arthralgia and 20 patients without arthralgia were randomly selected from the cohort and consented for blood sampling. During the 3 years following acute infection, 60% of patients had experienced symptoms of arthralgia, with most reporting episodic relapse and recovery periods. Long-term arthralgias were typically polyarthralgia (70%), that were usually symmetrical (90%) and highly incapacitating (77%). They were often associated with local swelling (63%), asthenia (77%) or depression (56%). The age over 35 years and the presence of arthralgia 4 months after the disease onset are risk factors of long-term arthralgia. Patients with long-term arthralgia did not display biological markers typically found in autoimmune or rheumatoid diseases. These data helped define the features of CHIKV-associated chronic arthralgia and permitted an estimation of the economic burden associated with arthralgia. Conclusions/Significance This study demonstrates that chronic arthralgia is a frequent complication of acute Chikungunya disease and suggests that it results from a local rather than systemic inflammation.
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.
Immunohistochemical Monitoring of Wound Healing in Antibiotic Treated Buruli Ulcer Patients
Arianna Andreoli equal contributor,Marie-Thérèse Ruf equal contributor,Ghislain Emmanuel Sopoh,Peter Schmid,Gerd Pluschke
PLOS Neglected Tropical Diseases , 2014, DOI: 10.1371/journal.pntd.0002809
Abstract: Background While traditionally surgery has dominated the clinical management of Buruli ulcer (BU), the introduction of the combination chemotherapy with oral rifampicin and intramuscular streptomycin greatly improved treatment and reduced recurrence rates. However management of the often extensive lesions after successful specific therapy has remained a challenge, in particular in rural areas of the African countries which carry the highest burden of disease. For reasons not fully understood, wound healing is delayed in a proportion of antibiotic treated BU patients. Therefore, we have performed immunohistochemical investigations to identify markers which may be suitable to monitor wound healing progression. Methodology/Principal findings Tissue specimens from eight BU patients with plaque lesions collected before, during and after chemotherapy were analyzed by immunohistochemistry for the presence of a set of markers associated with connective tissue neo-formation, tissue remodeling and epidermal activation. Several target proteins turned out to be suitable to monitor wound healing. While α-smooth muscle actin positive myofibroblasts were not found in untreated lesions, they emerged during the healing process. These cells produced abundant extracellular matrix proteins, such as pro-collagen 1 and tenascin and were found in fibronectin rich areas. After antibiotic treatment many cells, including myofibroblasts, revealed an activated phenotype as they showed ribosomal protein S6 phosphorylation, a marker for translation initiation. In addition, healing wounds revealed dermal tissue remodeling by apoptosis, and showed increased cytokeratin 16 expression in the epidermis. Conclusion/Significance We have identified a set of markers that allow monitoring wound healing in antibiotic treated BU lesions by immunohistochemistry. Studies with this marker panel may help to better understand disturbances responsible for wound healing delays observed in some BU patients.
Histopathological Changes and Clinical Responses of Buruli Ulcer Plaque Lesions during Chemotherapy: A Role for Surgical Removal of Necrotic Tissue?
Marie-Thérèse Ruf equal contributor,Ghislain Emmanuel Sopoh equal contributor,Luc Valère Brun,Ange Dodji Dossou,Yves Thierry Barogui,Roch Christian Johnson,Gerd Pluschke
PLOS Neglected Tropical Diseases , 2011, DOI: 10.1371/journal.pntd.0001334
Abstract: Background Buruli ulcer (BU) caused by Mycobacterium ulcerans is a necrotizing skin disease usually starting with a subcutaneous nodule or plaque, which may ulcerate and progress, if untreated, over months and years. During the currently recommended antibiotic treatment with rifampicin/streptomycin plaque lesions tend to ulcerate, often associated with retarded wound healing and prolonged hospital stays. Methodology/Principal Findings Included in this study were twelve laboratory reconfirmed, HIV negative BU patients presenting with plaque lesions at the CDTUB in Allada, Benin. Punch biopsies for histopathological and immunohistochemical analysis were taken before start of treatment and after four to five weeks of treatment. Where excision or wound debridement was clinically indicated, the removed tissue was also analyzed. Based on clinical judgment, nine of the twelve patients enrolled in this study received limited surgical excision seven to 39 days after completion of chemotherapy, followed by skin grafting. Lesions of three patients healed without further intervention. Before treatment, plaque lesions were characterized by a destroyed subcutis with extensive necrosis without major signs of infiltration. After completion of antibiotic treatment partial infiltration of the affected tissue was observed, but large necrotic areas remained unchanged. Conclusion/Significance Our histopathological analyses show that ulceration of plaque lesions during antibiotic treatment do not represent a failure to respond to antimycobacterial treatment. Based on our results we suggest formal testing in a controlled clinical trial setting whether limited surgical excision of necrotic tissue favours wound healing and can reduce the duration of hospital stays.
Rapid Evolution of Sex Pheromone-Producing Enzyme Expression in Drosophila
Troy R. Shirangi equal contributor,Hélo?se D. Dufour equal contributor,Thomas M. Williams,Sean B. Carroll
PLOS Biology , 2009, DOI: 10.1371/journal.pbio.1000168
Abstract: A wide range of organisms use sex pheromones to communicate with each other and to identify appropriate mating partners. While the evolution of chemical communication has been suggested to cause sexual isolation and speciation, the mechanisms that govern evolutionary transitions in sex pheromone production are poorly understood. Here, we decipher the molecular mechanisms underlying the rapid evolution in the expression of a gene involved in sex pheromone production in Drosophilid flies. Long-chain cuticular hydrocarbons (e.g., dienes) are produced female-specifically, notably via the activity of the desaturase DESAT-F, and are potent pheromones for male courtship behavior in Drosophila melanogaster. We show that across the genus Drosophila, the expression of this enzyme is correlated with long-chain diene production and has undergone an extraordinary number of evolutionary transitions, including six independent gene inactivations, three losses of expression without gene loss, and two transitions in sex-specificity. Furthermore, we show that evolutionary transitions from monomorphism to dimorphism (and its reversion) in desatF expression involved the gain (and the inactivation) of a binding-site for the sex-determination transcription factor, DOUBLESEX. In addition, we documented a surprising example of the gain of particular cis-regulatory motifs of the desatF locus via a set of small deletions. Together, our results suggest that frequent changes in the expression of pheromone-producing enzymes underlie evolutionary transitions in chemical communication, and reflect changing regimes of sexual selection, which may have contributed to speciation among Drosophila.
GroESL protects superoxide dismutase (SOD)— Deficient cells against oxidative stress and is a chaperone for SOD  [PDF]
Gary J. Hunter, Thérèse Hunter
Health (Health) , 2013, DOI: 10.4236/health.2013.510232
Abstract:

Superoxide dismutase (SOD)-deficient Escherichia coli OX326Acells are protected against chemically-induced oxidative stress by expression of the chaperonin GroESL. This protection is equivalent to expression of superoxide dismutase even though GroESL has no inherent SOD activity. Co-overexpression of GroESL and SOD in the same cells results in higher protein yields of SOD and greater metallation of SOD when compared with expression of SOD alone. Greater metallation results in the higher specific activity of SOD that is observed in heat shock, and is not due to increased synthesis of SOD mRNA or protein.

Probability of Seeing Increases Saccadic Readiness
Thérèse Collins
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0049454
Abstract: Associating movement directions or endpoints with monetary rewards or costs influences movement parameters in humans, and associating movement directions or endpoints with food reward influences movement parameters in non-human primates. Rewarded movements are facilitated relative to non-rewarded movements. The present study examined to what extent successful foveation facilitated saccadic eye movement behavior, with the hypothesis that foveation may constitute an informational reward. Human adults performed saccades to peripheral targets that either remained visible after saccade completion or were extinguished, preventing visual feedback. Saccades to targets that were systematically extinguished were slower and easier to inhibit than saccades to targets that afforded successful foveation, and this effect was modulated by the probability of successful foveation. These results suggest that successful foveation facilitates behavior, and that obtaining the expected sensory consequences of a saccadic eye movement may serve as a reward for the oculomotor system.
Les recherches en éducation au Québec: entre histoire et sociologie
Hamel, Thérèse;
Paidéia (Ribeir?o Preto) , 2000, DOI: 10.1590/S0103-863X2000000100008
Abstract: at the moment, when attention is called to the question of interdisciplinary, it can be observed that the relationships between sociology and history have a particular evolution. they are independent disciplines and they are trying to influence one each other, bypassing their limits, although maintaining their specificity, with the objective of a better understanding of social phenomenon. human sciences are redefining their place in social area and it is important to think about the heuristic contribution of these two major sectors : history and sociology.
Rethinking poverty, power and privilege: A feminist post-structuralist research exploration
Thérèse Hulme
HTS Theological Studies/Teologiese Studies , 2012,
Abstract: In this article, I described how the use of feminist methodology and post-structuralist analyses of the experiences of women in a poor ‘Coloured’ community in my research led to new understandings of the experiences of poverty and privilege. I discovered the relevance of Foucault’s historical analysis of the operation of ‘pastoral power’ through the narratives of women from the Scottsville community. Historical and current accounts of so-called ‘Coloured’ women’s subjugation and categorisation are reminders of how it came about that ‘being Coloured’ became associated in South Africa with shame and with ‘knowing one’s place’. Feminist post-structuralist analyses made visible the conditions that created practices of injustice in poor women’s lives whilst, at the same time, creating conditions of privilege for me. Justice-making in Scottsville therefore started with a radical rethinking of the terms by which people’s marginalisation took place and, consequently also of the terms of ‘just’ cross-cultural engagements.
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