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  1. Article ; Online: Aspergillosis in Wild Birds

    Pascal Arné / Veronica Risco-Castillo / Grégory Jouvion / Cécile Le Barzic / Jacques Guillot

    Journal of Fungi, Vol 7, Iss 241, p

    2021  Volume 241

    Abstract: The ubiquitous fungi belonging to the genus Aspergillus are able to proliferate in a large number of environments on organic substrates. The spores of these opportunistic pathogens, when inhaled, can cause serious and often fatal infections in a wide ... ...

    Abstract The ubiquitous fungi belonging to the genus Aspergillus are able to proliferate in a large number of environments on organic substrates. The spores of these opportunistic pathogens, when inhaled, can cause serious and often fatal infections in a wide variety of captive and free-roaming wild birds. The relative importance of innate immunity and the level of exposure in the development of the disease can vary considerably between avian species and epidemiological situations. Given the low efficacy of therapeutic treatments, it is essential that breeders or avian practitioners know the conditions that favor the emergence of Aspergillosis in order to put adequate preventive measures in place.
    Keywords aspergillosis ; wildlife ; bird ; Aspergillus ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2021-03-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: In Vivo Efficacy of Voriconazole in a Galleria mellonella Model of Invasive Infection Due to Azole-Susceptible or Resistant Aspergillus fumigatus Isolates

    Sana Jemel / Jacques Guillot / Kalthoum Kallel / Grégory Jouvion / Elise Brisebard / Eliane Billaud / Vincent Jullien / Françoise Botterel / Eric Dannaoui

    Journal of Fungi, Vol 7, Iss 1012, p

    2021  Volume 1012

    Abstract: Aspergillus fumigatus is an environmental filamentous fungus responsible for life-threatening infections in humans and animals. Azoles are the first-line treatment for aspergillosis, but in recent years, the emergence of azole resistance in A. fumigatus ... ...

    Abstract Aspergillus fumigatus is an environmental filamentous fungus responsible for life-threatening infections in humans and animals. Azoles are the first-line treatment for aspergillosis, but in recent years, the emergence of azole resistance in A. fumigatus has changed treatment recommendations. The objective of this study was to evaluate the efficacy of voriconazole (VRZ) in a Galleria mellonella model of invasive infection due to azole-susceptible or azole-resistant A. fumigatus isolates. We also sought to describe the pharmacokinetics of VRZ in the G. mellonella model. G. mellonella larvae were infected with conidial suspensions of azole-susceptible and azole-resistant isolates of A. fumigatus . Mortality curves were used to calculate the lethal dose. Assessment of the efficacy of VRZ or amphotericin B (AMB) treatment was based on mortality in the lethal model and histopathologic lesions. The pharmacokinetics of VRZ were determined in larval hemolymph. Invasive fungal infection was obtained after conidial inoculation. A dose-dependent reduction in mortality was observed after antifungal treatment with AMB and VRZ. VRZ was more effective at treating larvae inoculated with azole-susceptible A. fumigatus isolates than larvae inoculated with azole-resistant isolates. The concentration of VRZ was maximal at the beginning of treatment and gradually decreased in the hemolymph to reach a C min (24 h) between 0.11 and 11.30 mg/L, depending on the dose. In conclusion, G. mellonella is a suitable model for testing the efficacy of antifungal agents against A. fumigatus .
    Keywords Aspergillus ; antifungals ; Galleria mellonella ; voriconazole ; azole resistance ; Biology (General) ; QH301-705.5
    Subject code 630
    Language English
    Publishing date 2021-11-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Lyssavirus matrix protein cooperates with phosphoprotein to modulate the Jak-Stat pathway

    Florian Sonthonnax / Benoit Besson / Emilie Bonnaud / Grégory Jouvion / David Merino / Florence Larrous / Hervé Bourhy

    Scientific Reports, Vol 9, Iss 1, Pp 1-

    2019  Volume 13

    Abstract: Abstract Phosphoprotein (P) and matrix protein (M) cooperate to undermine the immune response to rabies virus (RABV) infections. While P is involved in the modulation of the Jak-Stat pathway through the cytoplasmic retention of interferon (IFN)-activated ...

    Abstract Abstract Phosphoprotein (P) and matrix protein (M) cooperate to undermine the immune response to rabies virus (RABV) infections. While P is involved in the modulation of the Jak-Stat pathway through the cytoplasmic retention of interferon (IFN)-activated STAT1 (pSTAT1), M interacts with the RelAp43-p105-ABIN2-TPL2 complex, to efficiently inhibit the nuclear factor-κB (NF-κB) pathway. Using transfections, protein-complementation assays, reverse genetics and DNA ChIP, we identified a role of M protein in the control of Jak-Stat signaling pathway, in synergy with the P protein. In unstimulated cells, both M and P proteins were found to interact with JAK1. Upon type-I IFN stimulation, the M switches toward pSTAT1 interaction, which results in an enhanced capacity of P protein to interact with pSTAT1 and restrain it in the cytoplasm. Furthermore, the role for M-protein positions 77, 100, 104 and 110 was also demonstrated in interaction with both JAK1 and pY-STAT1, and confirmed in vivo. Together, these data indicate that M protein cooperates with P protein to restrain in parallel, and sequentially, NF-κB and Jak-Stat pathways.
    Keywords Medicine ; R ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2019-08-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Aspergillus felis in Patient with Chronic Granulomatous Disease

    Olivier Paccoud / Romain Guery / Sylvain Poirée / Grégory Jouvion / Marie Elisabeth Bougnoux / Emilie Catherinot / Olivier Hermine / Olivier Lortholary / Fanny Lanternier

    Emerging Infectious Diseases, Vol 25, Iss 12, Pp 2319-

    2019  Volume 2321

    Abstract: We report a case of Aspergillus felis infection in a patient with chronic granulomatous disease who had overlapping features of invasive pulmonary aspergillosis and allergic bronchopulmonary aspergillosis. Identifying the species responsible for ... ...

    Abstract We report a case of Aspergillus felis infection in a patient with chronic granulomatous disease who had overlapping features of invasive pulmonary aspergillosis and allergic bronchopulmonary aspergillosis. Identifying the species responsible for aspergillosis by molecular methods can be crucial for directing patient management and selection of appropriate antifungal agents.
    Keywords Aspergillus felis ; invasive pulmonary aspergillosis ; allergic bronchopulmonary aspergillosis ; chronic granulomatous disease ; fungi ; Medicine ; R ; Infectious and parasitic diseases ; RC109-216
    Language English
    Publishing date 2019-12-01T00:00:00Z
    Publisher Centers for Disease Control and Prevention
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: X-rays minibeam radiation therapy at a conventional irradiator

    Marios Sotiropoulos / Elise Brisebard / Marine Le Dudal / Gregory Jouvion / Marjorie Juchaux / Delphine Crépin / Catherine Sebrie / Laurene Jourdain / Dalila Labiod / Charlotte Lamirault / Frederic Pouzoulet / Yolanda Prezado

    Clinical and Translational Radiation Oncology, Vol 27, Iss , Pp 44-

    Pilot evaluation in F98-glioma bearing rats and dose calculations in a human phantom

    2021  Volume 49

    Abstract: Minibeam radiation therapy (MBRT) is a type of spatial fractionated radiotherapy that uses submillimetric beams. This work reports on a pilot study on normal tissue response and the increase of the lifespan of glioma-bearing rats when irradiated with a ... ...

    Abstract Minibeam radiation therapy (MBRT) is a type of spatial fractionated radiotherapy that uses submillimetric beams. This work reports on a pilot study on normal tissue response and the increase of the lifespan of glioma-bearing rats when irradiated with a tabletop x-ray system. Our results show a significant widening of the therapeutic window for brain tumours treated with MBRT: an important proportion of long-term survivals (60%) coupled with a significant reduction of toxicity when compared with conventional (broad beam) irradiations. In addition, the clinical translation of the minibeam treatment at a conventional irradiator is evaluated through a possible human head treatment plan.
    Keywords Minibeam radiation therapy ; Tabletop systems ; High-grade gliomas ; Medical physics. Medical radiology. Nuclear medicine ; R895-920 ; Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282
    Subject code 616
    Language English
    Publishing date 2021-03-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Genetic dissection of Rift Valley fever pathogenesis

    Leandro Batista / Gregory Jouvion / Dominique Simon-Chazottes / Denis Houzelstein / Odile Burlen-Defranoux / Magali Boissière / Satoko Tokuda / Tania Zaverucha do Valle / Ana Cumano / Marie Flamand / Xavier Montagutelli / Jean-Jacques Panthier

    Scientific Reports, Vol 10, Iss 1, Pp 1-

    Rvfs2 locus on mouse chromosome 11 enables survival to early-onset hepatitis

    2020  Volume 12

    Abstract: Abstract Infection of mice with Rift Valley fever virus (RVFV) reproduces major pathological features of severe human disease, notably the early-onset hepatitis and delayed-onset encephalitis. We previously reported that the Rvfs2 locus from the ... ...

    Abstract Abstract Infection of mice with Rift Valley fever virus (RVFV) reproduces major pathological features of severe human disease, notably the early-onset hepatitis and delayed-onset encephalitis. We previously reported that the Rvfs2 locus from the susceptible MBT/Pas strain reduces survival time after RVFV infection. Here, we used BALB/cByJ (BALB) mice congenic for Rvfs2 (C.MBT-Rvfs2) to investigate the pathophysiological mechanisms impacted by Rvfs2. Clinical, biochemical and histopathological features indicated similar liver damage in BALB and C.MBT-Rvfs2 mice until day 5 after infection. However, while C.MBT-Rvfs2 mice succumbed from acute liver injury, most BALB mice recovered and died later of encephalitis. Hepatocytes of BALB infected liver proliferated actively on day 6, promoting organ regeneration and recovery from liver damage. By comparison with C.MBT-Rvfs2, BALB mice had up to 100-fold lower production of infectious virions in the peripheral blood and liver, strongly decreased RVFV protein in liver and reduced viral replication in primary cultured hepatocytes, suggesting that the BALB Rvfs2 haplotype limits RVFV pathogenicity through decreased virus replication. Moreover, bone marrow chimera experiments showed that both hematopoietic and non-hematopoietic cells are required for the protective effect of the BALB Rvfs2 haplotype. Altogether, these results indicate that Rvfs2 controls critical events which allow survival to RVFV-induced hepatitis.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2020-05-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Short and long-term evaluation of the impact of proton minibeam radiation therapy on motor, emotional and cognitive functions

    Charlotte Lamirault / Valérie Doyère / Marjorie Juchaux / Frederic Pouzoulet / Dalila Labiod / Remi Dendale / Annalisa Patriarca / Catherine Nauraye / Marine Le Dudal / Grégory Jouvion / David Hardy / Nicole El Massioui / Yolanda Prezado

    Scientific Reports, Vol 10, Iss 1, Pp 1-

    2020  Volume 14

    Abstract: Abstract Radiotherapy (RT) is one of the most frequently used methods for cancer treatment. Despite remarkable advancements in RT techniquesthe treatment of radioresistant tumours (i.e. high-grade gliomas) is not yet satisfactory. Finding novel ... ...

    Abstract Abstract Radiotherapy (RT) is one of the most frequently used methods for cancer treatment. Despite remarkable advancements in RT techniquesthe treatment of radioresistant tumours (i.e. high-grade gliomas) is not yet satisfactory. Finding novel approaches less damaging for normal tissues is of utmost importance. This would make it possible to increase the dose applied to tumours, resulting in an improvement in the cure rate. Along this line, proton minibeam radiation therapy (pMBRT) is a novel strategy that allows the spatial modulation of the dose, leading to minimal damage to brain structures compared to a high dose (25 Gy in one fraction) of standard proton therapy (PT). The aim of the present study was to evaluate whether pMBRT also preserves important cerebral functions. Comprehensive longitudinal behavioural studies were performed in irradiated (peak dose of 57 Gy in one fraction) and control rats to evaluate the impact of pMBRT on motor function (motor coordination, muscular tonus, and locomotor activity), emotional function (anxiety, fear, motivation, and impulsivity), and cognitive function (learning, memory, temporal processing, and decision making). The evaluations, which were conducted over a period of 10 months, showed no significant motor or emotional dysfunction in pMBRT-irradiated rats compared with control animals. Concerning cognitive functions, similar performance was observed between the groups, although some slight learning delays might be present in some of the tests in the long term after irradiation. This study shows the minimal impact of pMBRT on the normal brain at the functional level.
    Keywords Medicine ; R ; Science ; Q
    Subject code 616
    Language English
    Publishing date 2020-08-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Innate Immune Basis for Rift Valley Fever Susceptibility in Mouse Models

    Rashida Lathan / Dominique Simon-Chazottes / Grégory Jouvion / Ophélie Godon / Marie Malissen / Marie Flamand / Pierre Bruhns / Jean-Jacques Panthier

    Scientific Reports, Vol 7, Iss 1, Pp 1-

    2017  Volume 11

    Abstract: Abstract Rift Valley fever virus (RVFV) leads to varied clinical manifestations in animals and in humans that range from moderate fever to fatal illness, suggesting that host immune responses are important determinants of the disease severity. We ... ...

    Abstract Abstract Rift Valley fever virus (RVFV) leads to varied clinical manifestations in animals and in humans that range from moderate fever to fatal illness, suggesting that host immune responses are important determinants of the disease severity. We investigated the immune basis for the extreme susceptibility of MBT/Pas mice that die with mild to acute hepatitis by day 3 post-infection compared to more resistant BALB/cByJ mice that survive up to a week longer. Lower levels of neutrophils observed in the bone marrow and blood of infected MBT/Pas mice are unlikely to be causative of increased RVFV susceptibility as constitutive neutropenia in specific mutant mice did not change survival outcome. However, whereas MBT/Pas mice mounted an earlier inflammatory response accompanied by higher amounts of interferon (IFN)-α in the serum compared to BALB/cByJ mice, they failed to prevent high viral antigen load. Several immunological alterations were uncovered in infected MBT/Pas mice compared to BALB/cByJ mice, including low levels of leukocytes that expressed type I IFN receptor subunit 1 (IFNAR1) in the blood, spleen and liver, delayed leukocyte activation and decreased percentage of IFN-γ-producing leukocytes in the blood. These observations are consistent with the complex mode of inheritance of RVFV susceptibility in genetic studies.
    Keywords Medicine ; R ; Science ; Q
    Subject code 570 ; 616
    Language English
    Publishing date 2017-08-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Protective or deleterious role of scavenger receptors SR-A and CD36 on host resistance to Staphylococcus aureus depends on the site of infection.

    Charlène Blanchet / Gregory Jouvion / Catherine Fitting / Jean-Marc Cavaillon / Minou Adib-Conquy

    PLoS ONE, Vol 9, Iss 1, p e

    2014  Volume 87927

    Abstract: Staphylococcus aureus is a major human opportunistic pathogen responsible for a broad spectrum of infections ranging from benign skin infection to more severe life threatening disorders (e.g. pneumonia, sepsis), particularly in intensive care patients. ... ...

    Abstract Staphylococcus aureus is a major human opportunistic pathogen responsible for a broad spectrum of infections ranging from benign skin infection to more severe life threatening disorders (e.g. pneumonia, sepsis), particularly in intensive care patients. Scavenger receptors (SR-A and CD36) are known to be involved in S. aureus recognition by immune cells in addition to MARCO, TLR2, NOD2 and α5β1 integrin. In the present study, we further deciphered the contribution of SR-A and CD36 scavenger receptors in the control of infection of mice by S. aureus. Using double SR-A/CD36 knockout mice (S/C-KO) and S. aureus strain HG001, a clinically relevant non-mutagenized strain, we showed that the absence of these two scavenger receptors was protective in peritoneal infection. In contrast, the deletion of these two receptors was detrimental in pulmonary infection following intranasal instillation. For pulmonary infection, susceptible mice (S/C-KO) had more colony-forming units (CFU) in their broncho-alveolar lavages fluids, associated with increased recruitment of macrophages and neutrophils. For peritoneal infection, susceptible mice (wild-type) had more CFU in their blood, but recruited less macrophages and neutrophils in the peritoneal cavity than resistant mice. Exacerbated cytokine levels were often observed in the susceptible mice in the infected compartment as well as in the plasma. The exception was the enhanced compartmentalized expression of IL-1β for the resistant mice (S/C-KO) after peritoneal infection. A similar mirrored susceptibility to S. aureus infection was also observed for MARCO and TLR2. Marco and tlr2 -/- mice were more resistant to peritoneal infection but more susceptible to pulmonary infection than wild type mice. In conclusion, our results show that innate immune receptors can play distinct and opposite roles depending on the site of infection. Their presence is protective for local pulmonary infection, whereas it becomes detrimental in the peritoneal infection.
    Keywords Medicine ; R ; Science ; Q
    Subject code 572
    Language English
    Publishing date 2014-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: A combination of two human monoclonal antibodies cures symptomatic rabies

    Guilherme Dias de Melo / Florian Sonthonnax / Gabriel Lepousez / Grégory Jouvion / Andrea Minola / Fabrizia Zatta / Florence Larrous / Lauriane Kergoat / Camille Mazo / Carine Moigneu / Roberta Aiello / Angela Salomoni / Elise Brisebard / Paola De Benedictis / Davide Corti / Hervé Bourhy

    EMBO Molecular Medicine, Vol 12, Iss 11, Pp n/a-n/a (2020)

    2020  

    Abstract: Abstract Rabies is a neglected disease caused by a neurotropic Lyssavirus, transmitted to humans predominantly by the bite of infected dogs. Rabies is preventable with vaccines or proper post‐exposure prophylaxis (PEP), but it still causes about 60,000 ... ...

    Abstract Abstract Rabies is a neglected disease caused by a neurotropic Lyssavirus, transmitted to humans predominantly by the bite of infected dogs. Rabies is preventable with vaccines or proper post‐exposure prophylaxis (PEP), but it still causes about 60,000 deaths every year. No cure exists after the onset of clinical signs, and the case‐fatality rate approaches 100% even with advanced supportive care. Here, we report that a combination of two potent neutralizing human monoclonal antibodies directed against the viral envelope glycoprotein cures symptomatic rabid mice. Treatment efficacy requires the concomitant administration of antibodies in the periphery and in the central nervous system through intracerebroventricular infusion. After such treatment, recovered mice presented good clinical condition, viral loads were undetectable, and the brain inflammatory profile was almost normal. Our findings provide the unprecedented proof of concept of an antibody‐based therapeutic approach for symptomatic rabies.
    Keywords immunotherapeutics ; monoclonal antibody therapy ; neglected diseases ; neuroinfectious diseases ; rabies virus ; Medicine (General) ; R5-920 ; Genetics ; QH426-470
    Language English
    Publishing date 2020-11-01T00:00:00Z
    Publisher Wiley
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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