178 research outputs found

    263 Cardiac characterization of sgca-null mouse, a model of alpha-sarcoglycanopathy, by using echocardiography

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    Alpha-sarcoglycanopathy (LGMD2D) is an autosomal recessive inherited limb-girdle muscular dystrophy caused by mutations in the alpha-sarcoglycan gene, SGCA. Disruption of SGCA gene in mouse (Sgca-null mouse) shares many of clinical pictures observed in patients. Mice disclose progressive muscular dystrophy. We sought to characterize cardiac function in this disease in order to evaluate target therapy. After shaving, Sgca-null mice were anaesthetized with isoflurane before performing echocardiography. Echocardiography was performed with a Vevo 770 Visuals Sonics (30 MHz cardiac probe). Mice were analysed at 5, 13, and 17 months.Control and Sgca-null mice were similar regarding age and heart rate. At age 5 months, in Sgca-null mice, we found significant anatomical differences regarding the inter-ventricular septal (IVS) wall thickness and the posterior wall (PW) thickness, as compared to their control. The IVS diastolic thickness was significantly increased in Sgca-null mice (0.91mm+/–0.06 vs 0.73 mm+/–0.02; p=0.003). Furthermore, the PW diastolic thickness was also increased in Sgca-null mice compared to WT (0.81mm+/–0.07 vs 0.69 mm+/–0.03; p=0.03). Also, LV mass was significantly increased in Sgca-null mice (147mg+/–15 vs 117.6mg+/–5.3; p=0. 02). At age 13 months, LV mass was significantly higher in Sgca-null mice (LV mass 205.22 mg vs 143 mg; p =0.001).The PW thickness was significantly different in the 2 groups (0.89 mm in Sgca-null vs 0.73 mm; p=0,02). Moreover, Sgca-null mice at 13 months disclosed dilatation of the left ventricle (LVEDD: 4.84mm vs 4.29 mm; p= 0.019). Systolic function was conserved in the 2 groups at 13 months regarding SF and EF.At age 17 months, we noted a decreasing of the posterior wall thickening (17% vs 30%; p= 0.036) and an increasing of the LV mass/weight (5.6 vs 3.9; p=0,016). No significant differences were found regarding the other anatomic echocardiography parameters.This study is unique and provides data that will help researchers to evaluate the efficiency of pharmaceutical or gene cardiac therapies

    Ostreid herpesvirus 1 detection and relationship with Crassostrea gigas spat mortality in France between 1998 and 2006

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    Since its molecular characterisation, Ostreid herpesvirus 1 (OsHV-1) has been regularly detected in Crassostrea gigas in France. Although its pathogenicity was demonstrated on larval stages, its involvement during mortality outbreaks at the juvenile stage was highly suspected but not evidenced. To investigate mortality outbreaks, the French National Network for Surveillance and Monitoring of Mollusc Health (REPAMO) carried out two surveys in juvenile C. gigas. The first survey lasted from 1998 to 2006 and was an epidemiological inquiry occurring when oyster farmers reported mortality outbreaks. The second survey, a longitudinal one, was set up in 1998 to complete the network observations on OsHV-1. Data analysis showed a specific pattern of mortality outbreaks associated with OsHV-1 detection. Ostreid herpesvirus 1 detection mainly appeared during the summer, suggesting the influence of the seawater temperature on its occurrence. It mostly presented a patchy distribution in the field in contrast to the nursery. Significant relationship between OsHV-1 detection and spat mortality was found, preferentially in sheltered and closed environments. The longitudinal survey confirmed most of the network observations. Although subsequent works particularly epidemiological surveys would be useful to confirm the causal link between the detection of OsHV-1 and the mortality outbreaks in juvenile C. gigas, the role of OsHV-1 in oyster mortality is progressing

    Live imaging of targeted cell ablation in Xenopus:a new model to study demyelination and repair

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    Live imaging studies of the processes of demyelination and remyelination have so far been technically limited in mammals. We have thus generated a Xenopus laevis transgenic line allowing live imaging and conditional ablation of myelinating oligodendrocytes throughout the central nervous system (CNS). In these transgenic pMBP-eGFP-NTR tadpoles the myelin basic protein (MBP) regulatory sequences, specific to mature oligodendrocytes, are used to drive expression of an eGFP (enhanced green fluorescent protein) reporter fused to the E. coli nitroreductase (NTR) selection enzyme. This enzyme converts the innocuous pro-drug metronidazole (MTZ) to a cytotoxin. Using two-photon imaging in vivo, we show that pMBP-eGFP-NTR tadpoles display a graded oligodendrocyte ablation in response to MTZ, which depends on the exposure time to MTZ. MTZ-induced cell death was restricted to oligodendrocytes, without detectable axonal damage. After cessation of MTZ treatment, remyelination proceeded spontaneously, but was strongly accelerated by retinoic acid. Altogether, these features establish the Xenopus pMBP-eGFP-NTR line as a novel in vivo model for the study of demyelination/remyelination processes and for large-scale screens of therapeutic agents promoting myelin repair

    Chikungunya Virus Infection

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    Chikungunya virus (CHIKV) is an alphavirus transmitted by mosquitoes, mostly Aedes aegypti and Aedes albopictus. After half a century of focal outbreaks of acute febrile polyarthralgia in Africa and Asia, the disease unexpectedly spread in the past decade with large outbreaks in Africa and around the Indian Ocean and rare autochthonous transmission in temperate areas. This emergence brought new insights on its pathogenesis, notably the role of the A226V mutation that improved CHIKV fitness in Ae. albopictus and the possible CHIKV persistence in deep tissue sanctuaries for months after infection. Massive outbreaks also revealed new aspects of the acute stage: the high number of symptomatic cases, unexpected complications, mother-to-child transmission, and low lethality in debilitated patients. The follow-up of patients in epidemic areas has identified frequent, long-lasting, rheumatic disorders, including rare inflammatory joint destruction, and common chronic mood changes associated with quality-of-life impairment. Thus, the globalization of CHIKV exposes countries with Aedes mosquitoes both to brutal outbreaks of acute incapacitating episodes and endemic long-lasting disorders

    The Third Fermi Large Area Telescope Catalog of Gamma-ray Pulsars

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    We present 294 pulsars found in GeV data from the Large Area Telescope (LAT) on the Fermi Gamma-ray Space Telescope. Another 33 millisecond pulsars (MSPs) discovered in deep radio searches of LAT sources will likely reveal pulsations once phase-connected rotation ephemerides are achieved. A further dozen optical and/or X-ray binary systems co-located with LAT sources also likely harbor gamma-ray MSPs. This catalog thus reports roughly 340 gamma-ray pulsars and candidates, 10% of all known pulsars, compared to ≤11\leq 11 known before Fermi. Half of the gamma-ray pulsars are young. Of these, the half that are undetected in radio have a broader Galactic latitude distribution than the young radio-loud pulsars. The others are MSPs, with 6 undetected in radio. Overall, >235 are bright enough above 50 MeV to fit the pulse profile, the energy spectrum, or both. For the common two-peaked profiles, the gamma-ray peak closest to the magnetic pole crossing generally has a softer spectrum. The spectral energy distributions tend to narrow as the spindown power E˙\dot E decreases to its observed minimum near 103310^{33} erg s−1^{-1}, approaching the shape for synchrotron radiation from monoenergetic electrons. We calculate gamma-ray luminosities when distances are available. Our all-sky gamma-ray sensitivity map is useful for population syntheses. The electronic catalog version provides gamma-ray pulsar ephemerides, properties and fit results to guide and be compared with modeling results.Comment: 142 pages. Accepted by the Astrophysical Journal Supplemen

    Information concerning Marteilia refringens

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    Avis et Informations concernant le parasite Marteilia refringen

    L' hystérosonographie pour l'étude de la cavité utérine (à propos d'une série récente de 283 cas et bilan de 10 ans de pratique)

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    BREST-BU Médecine-Odontologie (290192102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

    Endothelial-to-Mesenchymal Transition in Cancer

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    International audienceCancer is one of the most important causes of morbidity and mortality worldwide. Tumor cells grow in a complex microenvironment constituted of immune, stromal, and vascular cells that supports growth, angiogenesis, and metastasis. Endothelial cells (ECs) are major components of the vascular microenvironment. These cells have been described for their plasticity and potential to transdifferentiate into mesenchymal cells through a process known as endothelial-to-mesenchymal transition (EndMT). This complex process is controlled by various factors, by which ECs convert into a phenotype characterized by mesenchymal protein expression and motile, contractile morphology. Initially described in normal heart development, EndMT is now identified in several pathologies, and especially in cancer. In this review, we highlight the process of EndMT in the context of cancer and we discuss it as an important adaptive process of the tumor microenvironment that favors tumor growth and dissemination but also resistance to treatment. Thus, we underline targeting of EndMT as a potential therapeutic strategy

    Induction of apoptosis by UV in the flat oyster, Ostrea edulis

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    Apoptosis is a fundamental feature in the development of many organisms and tissue systems. It is also a mechanism of host defense against environmental stress factors or pathogens by contributing to the elimination of infected cells. Hemocytes play a key role in defense mechanisms in invertebrates and previous studies have shown that physical or chemical stress can increase apoptosis in hemocytes in mollusks. However this phenomenon has rarely been investigated in bivalves especially in the flat oyster Ostrea edulis. The apoptotic response of hemocytes from flat oysters, O. edulis, was investigated after exposure to UV and dexamethasone, two agents known to induce apoptosis in vertebrates. Flow cytometry and microscopy were combined to demonstrate that apoptosis occurs in flat oyster hemocytes. Investigated parameters like intracytoplasmic calcium activity, mitochondrial membrane potential and phosphatidyl-serine externalization were significantly modulated in cells exposed to UV whereas dexamethasone only induced an increase of DNA fragmentation. Morphological changes were also observed on UV-treated cells using fluorescence microscopy and transmission electron microscopy. Our results confirm the apoptotic effect of UV on hemocytes of O. edulis and suggest that apoptosis is an important mechanism developed by the flat oyster against stress factors
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