246 research outputs found

    CD44 regulates Wnt signaling at the level of LRP6

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    New Insights into the Formulation and Polymerization of Pickering Emulsions Stabilized by Natural Organic Particles

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    Pickering emulsions are known to be an efficient and greener alternative to surfactant-stabilized emulsions. Particles, as key component of these systems, are responsible for their higher kinetic stability, and in recent years, the use of natural organic stabilizers has emerged as a solution to promote sustainability. By conferring them stimuli-responsiveness and/or by polymerizing the Pickering emulsion itself, the design of smart and advanced systems can be achieved. Radical polymerization has been by far the most studied polymerization route, and a wide range of materials were successfully synthesized: foams, composites, capsules, or imprinted microspheres. Not only the sustainability of these materials is improved, but also their performances and features are also generally enhanced thanks to the presence of the natural organic stabilizers. This Perspective is putting into light groundbreaking efforts in the field of the polymerization of Pickering emulsions, suggesting the range of accessible material that can be obtained through this powerful pathway

    Enhanced Chondrogenic Differentiation Activities in Human Bone Marrow Aspirates via sox9 Overexpression Mediated by pNaSS-Grafted PCL Film-Guided rAAV Gene Transfer

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    Background: The delivery of therapeutic genes in sites of articular cartilage lesions using non-invasive, scaffold-guided gene therapy procedures is a promising approach to stimulate cartilage repair while protecting the cargos from detrimental immune responses, particularly when targeting chondroreparative bone marrow-derived mesenchymal stromal cells in a natural microenvironment like marrow aspirates. Methods: Here, we evaluated the benefits of providing a sequence for the cartilage-specific sex-determining region Y-type high-mobility group box 9 (SOX9) transcription factor to human marrow aspirates via recombinant adeno-associated virus (rAAV) vectors delivered by poly(Δ-caprolactone) (PCL) films functionalized via grafting with poly(sodium styrene sulfonate) (pNaSS) to enhance the marrow chondrogenic potential over time. Results: Effective sox9 overexpression was observed in aspirates treated with pNaSS-grafted or ungrafted PCL films coated with the candidate rAAV-FLAG-hsox9 (FLAG-tagged rAAV vector carrying a human sox9 gene sequence) vector for at least 21 days relative to other conditions (pNaSS-grafted and ungrafted PCL films without vector coating). Overexpression of sox9 via rAAV sox9/pNaSS-grafted or ungrafted PCL films led to increased biological and chondrogenic differentiation activities (matrix deposition) in the aspirates while containing premature osteogenesis and hypertrophy without impacting cell proliferation, with more potent effects noted when using pNaSS-grafted films. Conclusions: These findings show the benefits of targeting patients’ bone marrow via PCL film-guided therapeutic rAAV (sox9) delivery as an off-the-shelf system for future strategies to enhance cartilage repair in translational applications

    Une ferme du dĂ©but du IIIe s. av. J.-C. au “ Marais du Colombier ”, Varennes-sur-Seine (Seine-et-Marne) : analyse archĂ©ologique et environnementale

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    La fouille, en contexte d’archĂ©ologie prĂ©ventive, du site du “ Marais du Colombier ” Ă  Varennes-sur-Seine (Seine-et-Marne), a permis d’étudier un Ă©tablissement rural datĂ© de la premiĂšre moitiĂ© du IIIe s. av. J.-C. installĂ© dans une zone basse et humide de la plaine situĂ©e Ă  l’aval du confluent Seine – Yonne. L’établissement, structurĂ© autour d’une zone vide interprĂ©tĂ©e comme une cour ou un espace horticole, rassemble presque toutes les composantes d’un Ă©tablissement rural : habitation, greniers et autres bĂątiments annexes, silos, puis et fosses. Parmi les bĂątiments, l’habitation se distingue par l’adoption d’un plan ovalisĂ© s’accordant probablement avec l’hypothĂšse d’une charpente Ă  ferme, ce qui en fait l’un des plus anciens tĂ©moignages de ce type de charpente pour l’ñge du Fer. De nombreux macrorestes vĂ©gĂ©taux, conservĂ©s dans plusieurs puits, dont le puits principal 5003 situĂ© Ă  proximitĂ© de la maison, permettent une analyse palĂ©obotanique. Le croisement des donnĂ©es archĂ©ologiques, archĂ©obotaniques (carpologie, anthracologie, xylologie) et archĂ©ozoologiques permet de restituer un milieu environnant marquĂ© par une grande biodiversitĂ© et son exploitation (plantes cultivĂ©es, milieux de collecte, Ă©levage, chasse). Tous les Ă©lĂ©ments convergent pour voir dans cet Ă©tablissement agricole une unitĂ© de production dotĂ©e d’un niveau de vie aisĂ©, mais sans marque d’ostentation. L’organisation de l’établissement est assez diffĂ©rente de celle de la plupart des habitats de La TĂšne ancienne et du dĂ©but de La TĂšne moyenne de l’espace sĂ©nonais, et semble prĂ©figurer celle des sites Ă  enclos de la fin de La TĂšne moyenne et de La TĂšne finale. La prĂ©sence de restes humains apporte, quant Ă  elle, des Ă©lĂ©ments sur la gestuelle funĂ©raire liĂ©e aux enfants morts en bas Ăąge et sur les pratiques cultuelles en contexte domestique.The rescue excavation of the Marais du Colombier site, Varennes-sur-Seine (Seine-et-Marne) enabled us to study a rural establishment dating back to the first half of the 3rd century BC set in a damp low-lying area of the plain situated in the lower reaches of the Seine/Yonne confluence. The establishment, structured around an empty area interpreted as a courtyard or horticultural space, has nearly all the components of a rural establishment: dwellings, granaries and other annexed buildings, silos, wells and ditches. Among the buildings, the dwelling was notable for the adoption of an oval plan probably supporting the hypothesis of a roof structure, which makes it one of the most ancient of the Iron age. Of the many macro vegetal remains, preserved in several pits, the main one being 5003 situated near the house, enabled a palaeobotanical analysis. The combination of archaeological, archaeobotanical (carpology, anthracology, xylology) and archaeozoological data enables a reconstruction of a surrounding environment marked by its great diversity and exploitation (plants cultivated, collection environment, livestock farming, hunting). All the elements combine in this agricultural establishment to reveal a production unit providing a comfortable level of life. Its organisation is rather different from that of the most part of the early La TĂšne period and from the beginning of middle La TĂšne of the Senonais area and seems to prefigure that of the enclosure sites of the middle and late La TĂšne. As for the presence of human remains, they bring elements on the funerary practices connected to children dying at a young age and on cultural practices in a domestic context

    Une ferme du dĂ©but du IIIe s. av. J.-C. au “ Marais du Colombier ”, Varennes-sur-Seine (Seine-et-Marne) : analyse archĂ©ologique et environnementale

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    La fouille, en contexte d’archĂ©ologie prĂ©ventive, du site du “ Marais du Colombier ” Ă  Varennes-sur-Seine (Seine-et-Marne), a permis d’étudier un Ă©tablissement rural datĂ© de la premiĂšre moitiĂ© du IIIe s. av. J.-C. installĂ© dans une zone basse et humide de la plaine situĂ©e Ă  l’aval du confluent Seine – Yonne. L’établissement, structurĂ© autour d’une zone vide interprĂ©tĂ©e comme une cour ou un espace horticole, rassemble presque toutes les composantes d’un Ă©tablissement rural : habitation, greniers et autres bĂątiments annexes, silos, puis et fosses. Parmi les bĂątiments, l’habitation se distingue par l’adoption d’un plan ovalisĂ© s’accordant probablement avec l’hypothĂšse d’une charpente Ă  ferme, ce qui en fait l’un des plus anciens tĂ©moignages de ce type de charpente pour l’ñge du Fer. De nombreux macrorestes vĂ©gĂ©taux, conservĂ©s dans plusieurs puits, dont le puits principal 5003 situĂ© Ă  proximitĂ© de la maison, permettent une analyse palĂ©obotanique. Le croisement des donnĂ©es archĂ©ologiques, archĂ©obotaniques (carpologie, anthracologie, xylologie) et archĂ©ozoologiques permet de restituer un milieu environnant marquĂ© par une grande biodiversitĂ© et son exploitation (plantes cultivĂ©es, milieux de collecte, Ă©levage, chasse). Tous les Ă©lĂ©ments convergent pour voir dans cet Ă©tablissement agricole une unitĂ© de production dotĂ©e d’un niveau de vie aisĂ©, mais sans marque d’ostentation. L’organisation de l’établissement est assez diffĂ©rente de celle de la plupart des habitats de La TĂšne ancienne et du dĂ©but de La TĂšne moyenne de l’espace sĂ©nonais, et semble prĂ©figurer celle des sites Ă  enclos de la fin de La TĂšne moyenne et de La TĂšne finale. La prĂ©sence de restes humains apporte, quant Ă  elle, des Ă©lĂ©ments sur la gestuelle funĂ©raire liĂ©e aux enfants morts en bas Ăąge et sur les pratiques cultuelles en contexte domestique.The rescue excavation of the Marais du Colombier site, Varennes-sur-Seine (Seine-et-Marne) enabled us to study a rural establishment dating back to the first half of the 3rd century BC set in a damp low-lying area of the plain situated in the lower reaches of the Seine/Yonne confluence. The establishment, structured around an empty area interpreted as a courtyard or horticultural space, has nearly all the components of a rural establishment: dwellings, granaries and other annexed buildings, silos, wells and ditches. Among the buildings, the dwelling was notable for the adoption of an oval plan probably supporting the hypothesis of a roof structure, which makes it one of the most ancient of the Iron age. Of the many macro vegetal remains, preserved in several pits, the main one being 5003 situated near the house, enabled a palaeobotanical analysis. The combination of archaeological, archaeobotanical (carpology, anthracology, xylology) and archaeozoological data enables a reconstruction of a surrounding environment marked by its great diversity and exploitation (plants cultivated, collection environment, livestock farming, hunting). All the elements combine in this agricultural establishment to reveal a production unit providing a comfortable level of life. Its organisation is rather different from that of the most part of the early La TĂšne period and from the beginning of middle La TĂšne of the Senonais area and seems to prefigure that of the enclosure sites of the middle and late La TĂšne. As for the presence of human remains, they bring elements on the funerary practices connected to children dying at a young age and on cultural practices in a domestic context

    From a movement-deficient grapevine fanleaf virus to the identification of a new viral determinant of nematode transmission

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    Grapevine fanleaf virus (GFLV) and arabis mosaic virus (ArMV) are nepoviruses responsible for grapevine degeneration. They are specifically transmitted from grapevine to grapevine by two distinct ectoparasitic dagger nematodes of the genus Xiphinema. GFLV and ArMV move from cell to cell as virions through tubules formed into plasmodesmata by the self-assembly of the viral movement protein. Five surface-exposed regions in the coat protein called R1 to R5, which differ between the two viruses, were previously defined and exchanged to test their involvement in virus transmission, leading to the identification of region R2 as a transmission determinant. Region R4 (amino acids 258 to 264) could not be tested in transmission due to its requirement for plant systemic infection. Here, we present a fine-tuning mutagenesis of the GFLV coat protein in and around region R4 that restored the virus movement and allowed its evaluation in transmission. We show that residues T258, M260, D261, and R301 play a crucial role in virus transmission, thus representing a new viral determinant of nematode transmission

    Pooled Analysis of Prognostic Impact of Urokinase-Type Plasminogen Activator and Its Inhibitor PAI-1 in 8377 Breast Cancer Patients

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    Background: Urokinase-type plasminogen activator (uPA) and its inhibitor (PAI-1) play essential roles in tumor invasion and metastasis. High levels of both uPA and PAI-1 are associated with poor prognosis in breast cancer patients. To confirm the prognostic value of uPA and PAI-1 in primary breast cancer, we reanalyzed individual patient data provided by members of the European Organization for Research and Treatment of Cancer-Receptor and Biomarker Group (EORTC-RBG). Methods: The study included 18 datasets involving 8377 breast cancer patients. During follow-up (median 79 months), 35% of the patients relapsed and 27% died. Levels of uPA and PAI-1 in tumor tissue extracts were determined by different immunoassays; values were ranked within each dataset and divided by the number of patients in that dataset to produce fractional ranks that could be compared directly across datasets. Associations of ranks of uPA and PAI-1 levels with relapse-free survival (RFS) and overall survival (OS) were analyzed by Cox multivariable regression analysis stratified by dataset, including the following traditional prognostic variables: age, menopausal status, lymph node status, tumor size, histologic grade, and steroid hormone-receptor status. All P values were two-sided. Results: Apart from lymph node status, high levels of uPA and PAI-1 were the strongest predictors of both poor RFS and poor OS in the analyses of all patients. Moreover, in both lymph node-positive and lymph node-negative patients, higher uPA and PAI-1 values were independently associated with poor RFS and poor OS. For (untreated) lymph node-negative patients in particular, uPA and PAI-1 included together showed strong prognostic ability (all P<.001). Conclusions: This pooled analysis of the EORTC-RBG datasets confirmed the strong and independent prognostic value of uPA and PAI-1 in primary breast cancer. For patients with lymph node-negative breast cancer, uPA and PAI-1 measurements in primary tumors may be especially useful for designing individualized treatment strategie

    Antiretroviral-naive and -treated HIV-1 patients can harbour more resistant viruses in CSF than in plasma

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    Objectives The neurological disorders in HIV-1-infected patients remain prevalent. The HIV-1 resistance in plasma and CSF was compared in patients with neurological disorders in a multicentre study. Methods Blood and CSF samples were collected at time of neurological disorders for 244 patients. The viral loads were >50 copies/mL in both compartments and bulk genotypic tests were realized. Results On 244 patients, 89 and 155 were antiretroviral (ARV) naive and ARV treated, respectively. In ARV-naive patients, detection of mutations in CSF and not in plasma were reported for the reverse transcriptase (RT) gene in 2/89 patients (2.2%) and for the protease gene in 1/89 patients (1.1%). In ARV-treated patients, 19/152 (12.5%) patients had HIV-1 mutations only in the CSF for the RT gene and 30/151 (19.8%) for the protease gene. Two mutations appeared statistically more prevalent in the CSF than in plasma: M41L (P = 0.0455) and T215Y (P = 0.0455). Conclusions In most cases, resistance mutations were present and similar in both studied compartments. However, in 3.4% of ARV-naive and 8.8% of ARV-treated patients, the virus was more resistant in CSF than in plasma. These results support the need for genotypic resistance testing when lumbar puncture is performe
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