177 research outputs found

    Transformando corporalidades: Desbordes a la normalidad pedagĂłgica

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    En este escrito reflexionaremos acerca de interpelaciones que corporalidades dislocadas de la ostensiva heteronormatividad realizan a las instituciones educativas, abriendo posibilidades para estirar y desbordar los lĂ­mites epistemolĂłgicosy habilitar acciones pedagĂłgicas y polĂ­ticas en su interior. Las especulaciones que propondremos estĂĄn situadas en perspectivas polĂ­tico epistemolĂłgicas feministas, queer y decoloniales, engarzadas con y entre nuestras prĂĄcticas en el activismo feminista y en nuestro trabajo en el campo de la formaciĂłn docente en instituciones educativas pĂșblicas. El texto consta de tres partes. En la primera, configurada como una breve genealogĂ­a, nos detendremos en aportes del feminismo radical, en tanto abrevamos de ellos para politizar nuestra mirada del mundo y sus relaciones. Lo hacemos sin rehuir algunas menciones crĂ­ticas que mereciĂł esta perspectiva feminista. En la segunda, traeremos lĂ­neas de pensamiento construidas a partir de un proyecto de extensiĂłn: Por una educaciĂłn pĂșblica antidiscriminatoria, no androcĂ©ntrica, no sexista, no heterosexista; de un trabajo de investigaciĂłn: Aproximaciones al estudio del movimiento sexo-genĂ©rico en Argentina; y de intervenciones institucionales desarrolladas en la Universidad Nacional del Comahue y en el Instituto de FormaciĂłn Docente n.Âș 12 de NeuquĂ©n. En la tercera, proyectamos algunos interrogantes en la bĂșsqueda constante por dinamitar las ficcionales fronteras de la heteronormatividad en las aulas,para una pedagogĂ­a otra, para una pedagogĂ­a transgresora al decir de Deborah Britzman

    A Randomized Placebo-Controlled Phase Ia Malaria Vaccine Trial of Two Virosome-Formulated Synthetic Peptides in Healthy Adult Volunteers

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    BACKGROUND AND OBJECTIVES: Influenza virosomes represent an innovative human-compatible antigen delivery system that has already proven its suitability for subunit vaccine design. The aim of the study was to proof the concept that virosomes can also be used to elicit high titers of antibodies against synthetic peptides. The specific objective was to demonstrate the safety and immunogenicity of two virosome-formulated P. falciparum protein derived synthetic peptide antigens given in two different doses alone or in combination. METHODOLOGY/PRINCIPAL FINDINGS: The design was a single blind, randomized, placebo controlled, dose-escalating study involving 46 healthy Caucasian volunteers aged 18-45 years. Five groups of 8 subjects received virosomal formulations containing 10 microg or 50 microg of AMA 49-CPE, an apical membrane antigen-1 (AMA-1) derived synthetic phospatidylethanolamine (PE)-peptide conjugate or 10 ug or 50 ug of UK39, a circumsporozoite protein (CSP) derived synthetic PE-peptide conjugate or 50 ug of both antigens each. A control group of 6 subjects received unmodified virosomes. Virosomal formulations of the antigens (designated PEV301 and PEV302 for the AMA-1 and the CSP virosomal vaccine, respectively) or unmodified virosomes were injected i. m. on days 0, 60 and 180. In terms of safety, no serious or severe adverse events (AEs) related to the vaccine were observed. 11/46 study participants reported 16 vaccine related local AEs. Of these 16 events, all being pain, 4 occurred after the 1(st), 7 after the 2(nd) and 5 after the 3(rd) vaccination. 6 systemic AEs probably related to the study vaccine were reported after the 1(st) injection, 10 after the 2(nd) and 6 after the 3(rd). Generally, no difference in the distribution of the systemic AEs between either the doses applied (10 respectively 50 microg) or the synthetic antigen vaccines (PEV301 and PEV302) used for immunization was found. In terms of immunogenicity, both PEV301 and PEV302 elicited already after two injections a synthetic peptide-specific antibody response in all volunteers immunized with the appropriate dose. In the case of PEV301 the 50 microg antigen dose was associated with a higher mean antibody titer and seroconversion rate than the 10 microg dose. In contrast, for PEV302 mean titer and seroconversion rate were higher with the lower dose. Combined delivery of PEV301 and PEV302 did not interfere with the development of an antibody response to either of the two antigens. No relevant antibody responses against the two malaria antigens were observed in the control group receiving unmodified virosomes. CONCLUSIONS: The present study demonstrates that three immunizations with the virosomal malaria vaccine components PEV301 or/and PEV302 (containing 10 microg or 50 microg of antigen) are safe and well tolerated. At appropriate antigen doses seroconversion rates of 100% were achieved. Two injections may be sufficient for eliciting an appropriate immune response, at least in individuals with pre-existing anti-malarial immunity. These results justify further development of a final multi-stage virosomal vaccine formulation incorporating additional malaria antigens. TRIAL REGISTRATION: ClinicalTrials.gov NCT00400101

    Phytochrome-Based Extracellular Matrix with Reversibly Tunable mechanical Properties

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    Interrogation and control of cellular fate and function using optogenetics is providing revolutionary insights into biology. Optogenetic control of cells is achieved by coupling genetically encoded photoreceptors to cellular effectors and enables unprecedented spatiotemporal control of signaling processes. Here, a fast and reversibly switchable photoreceptor is used to tune the mechanical properties of polymer materials in a fully reversible, wavelength‐specific, and dose‐ and space‐controlled manner. By integrating engineered cyanobacterial phytochrome 1 into a poly(ethylene glycol) matrix, hydrogel materials responsive to light in the cell‐compatible red/far‐red spectrum are synthesized. These materials are applied to study in human mesenchymal stem cells how different mechanosignaling pathways respond to changing mechanical environments and to control the migration of primary immune cells in 3D. This optogenetics‐inspired matrix allows fundamental questions of how cells react to dynamic mechanical environments to be addressed. Further, remote control of such matrices can create new opportunities for tissue engineering or provide a basis for optically stimulated drug depots

    Canine distemper virus persistence in demyelinating encephalitis by swift intracellular cell-to-cell spread in astrocytes is controlled by the viral attachment protein

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    The mechanism of viral persistence, the driving force behind the chronic progression of inflammatory demyelination in canine distemper virus (CDV) infection, is associated with non-cytolytic viral cell-to-cell spread. Here, we studied the molecular mechanisms of viral spread of a recombinant fluorescent protein-expressing virulent CDV in primary canine astrocyte cultures. Time-lapse video microscopy documented that CDV spread was very efficient using cell processes contacting remote target cells. Strikingly, CDV transmission to remote cells could occur in less than 6 h, suggesting that a complete viral cycle with production of extracellular free particles was not essential in enabling CDV to spread in glial cells. Titration experiments and electron microscopy confirmed a very low CDV particle production despite higher titers of membrane-associated viruses. Interestingly, confocal laser microscopy and lentivirus transduction indicated expression and functionality of the viral fusion machinery, consisting of the viral fusion (F) and attachment (H) glycoproteins, at the cell surface. Importantly, using a single-cycle infectious recombinant H-knockout, H-complemented virus, we demonstrated that H, and thus potentially the viral fusion complex, was necessary to enable CDV spread. Furthermore, since we could not detect CD150/SLAM expression in brain cells, the presence of a yet non-identified glial receptor for CDV was suggested. Altogether, our findings indicate that persistence in CDV infection results from intracellular cell-to-cell transmission requiring the CDV-H protein. Viral transfer, happening selectively at the tip of astrocytic processes, may help the virus to cover long distances in the astroglial network, “outrunning” the host’s immune response in demyelinating plaques, thus continuously eliciting new lesions

    NERNST: a genetically-encoded ratiometric non-destructive sensing tool to estimate NADP(H) redox status in bacterial, plant and animal systems

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    NADP(H) is a central metabolic hub providing reducing equivalents to multiple biosynthetic, regulatory and antioxidative pathways in all living organisms. While biosensors are available to determine NADP+ or NADPH levels in vivo, no probe exists to estimate the NADP(H) redox status, a determinant of the cell energy availability. We describe herein the design and characterization of a genetically-encoded ratiometric biosensor, termed NERNST, able to interact with NADP(H) and estimate ENADP(H). NERNST consists of a redox-sensitive green fluorescent protein (roGFP2) fused to an NADPH-thioredoxin reductase C module which selectively monitors NADP(H) redox states via oxidoreduction of the roGFP2 moiety. NERNST is functional in bacterial, plant and animal cells, and organelles such as chloroplasts and mitochondria. Using NERNST, we monitor NADP(H) dynamics during bacterial growth, environmental stresses in plants, metabolic challenges to mammalian cells, and wounding in zebrafish. NERNST estimates the NADP(H) redox poise in living organisms, with various potential applications in biochemical, biotechnological and biomedical research.Fil: Molinari, Pamela EstefanĂ­a. Universidad Nacional de Rosario. Facultad de Ciencias BioquĂ­micas y FarmacĂ©uticas. Instituto de BiologĂ­a Molecular y Celular de Rosario (IBR-CONICET); Argentina.Fil: Krapp, Adriana. Universidad Nacional de Rosario. Facultad de Ciencias BioquĂ­micas y FarmacĂ©uticas. Instituto de BiologĂ­a Molecular y Celular de Rosario (IBR-CONICET); Argentina.Fil: Weiner, Andrea MarĂ­a Julia. Universidad Nacional de Rosario. Facultad de Ciencias BioquĂ­micas y FarmacĂ©uticas. Instituto de BiologĂ­a Molecular y Celular de Rosario (IBR-CONICET); Argentina.Fil: LĂłpez, Melina. Universidad Nacional de Rosario. Facultad de Ciencias BioquĂ­micas y FarmacĂ©uticas. Instituto de BiologĂ­a Molecular y Celular de Rosario (IBR-CONICET); Argentina.Fil: Bustos Sanmamed, Pilar. Universidad Nacional de Rosario. Facultad de Ciencias BioquĂ­micas y FarmacĂ©uticas. Instituto de BiologĂ­a Molecular y Celular de Rosario (IBR-CONICET); Argentina.Fil: Tevere, Evelyn. Universidad Nacional de Rosario. Facultad de Ciencias BioquĂ­micas y FarmacĂ©uticas. Instituto de BiologĂ­a Molecular y Celular de Rosario (IBR-CONICET); Argentina.Fil: Calcaterra, Nora B. Universidad Nacional de Rosario. Facultad de Ciencias BioquĂ­micas y FarmacĂ©uticas. Instituto de BiologĂ­a Molecular y Celular de Rosario (IBR-CONICET); Argentina.Fil: Carrillo, NĂ©stor. Universidad Nacional de Rosario. Facultad de Ciencias BioquĂ­micas y FarmacĂ©uticas. Instituto de BiologĂ­a Molecular y Celular de Rosario (IBR-CONICET); Argentina.Fil: Beyer, Hannes M. University of DĂŒsseldorf. Institute of Synthetic Biology; Germany.Fil: Blomeier, Tim.University of DĂŒsseldorf. Institute of Synthetic Biology; Germany.Fil: Zurbriggen, Matias D. University of DĂŒsseldorf. Institute of Synthetic Biology; Germany.Fil: Kondadi, Arun Kumar. Heinrich-Heine-University DĂŒsseldor. Medical Faculty and University Hospital DĂŒsseldorf. Institute of Biochemistry and Molecular Biology I; Germany.Fil: Reichert, Andreas S. Heinrich-Heine-University DĂŒsseldor. Medical Faculty and University Hospital DĂŒsseldorf. Institute of Biochemistry and Molecular Biology I; Germany.Fil: Weber, Wilfried. University of Freiburg. Faculty of Biology and Signalling Research Centres BIOSS and CIBSS; Germany.Fil: Beller, Mathias. University of DĂŒsseldorf. Institute of Mathematical Modeling of Biological Systems; Germany.Fil: Zurbriggen, Matias D. Cluster of Excellence on Plant Sciences; Germany.Fil: Weber, Wilfried. Saarland University. Leibniz Institute for New Materials and Department of Materials Sciences and Engineering; Germany

    Virosome-Formulated Plasmodium falciparum AMA-1 & CSP Derived Peptides as Malaria Vaccine: Randomized Phase 1b Trial in Semi-Immune Adults & Children

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    BACKGROUND\ud \ud This trial was conducted to evaluate the safety and immunogenicity of two virosome formulated malaria peptidomimetics derived from Plasmodium falciparum AMA-1 and CSP in malaria semi-immune adults and children.\ud \ud METHODS\ud \ud The design was a prospective randomized, double-blind, controlled, age-deescalating study with two immunizations. 10 adults and 40 children (aged 5-9 years) living in a malaria endemic area were immunized with PEV3B or virosomal influenza vaccine Inflexal¼V on day 0 and 90.\ud \ud RESULTS\ud \ud No serious or severe adverse events (AEs) related to the vaccines were observed. The only local solicited AE reported was pain at injection site, which affected more children in the Inflexal¼V group compared to the PEV3B group (p = 0.014). In the PEV3B group, IgG ELISA endpoint titers specific for the AMA-1 and CSP peptide antigens were significantly higher for most time points compared to the Inflexal¼V control group. Across all time points after first immunization the average ratio of endpoint titers to baseline values in PEV3B subjects ranged from 4 to 15 in adults and from 4 to 66 in children. As an exploratory outcome, we found that the incidence rate of clinical malaria episodes in children vaccinees was half the rate of the control children between study days 30 and 365 (0.0035 episodes per day at risk for PEV3B vs. 0.0069 for Inflexal¼V; RR  = 0.50 [95%-CI: 0.29-0.88], p = 0.02).\ud \ud CONCLUSION\ud \ud These findings provide a strong basis for the further development of multivalent virosomal malaria peptide vaccines.\ud \ud TRIAL REGISTRATION\ud \ud ClinicalTrials.gov NCT00513669

    InfluĂȘncia de diferentes agentes auxiliares do preparo biomecĂąnico na obturação de canais laterais artificiais

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    The purpose of the present study was to evaluate the influence of some auxiliary agents of biomechanical preparation of the root canal on the filling of artificial lateral canals in extracted human teeth. A total of eighty single-rooted teeth were employed, which were submitted to preparation of three artificial lateral canals in one of the proximal aspects at the cervical, middle and apical thirds, besides one in the buccal aspect. The main canals were prepared by Profile 0.4 rotary instruments through the crown-down technique and irrigated with the irrigants investigated, as follows: Group A - 1% sodium hypochlorite and final irrigation with trisodium EDTA for 5 minutes; Group B - Endogel (2% chlorhexidine gel); Group C - Endo PTC and Dakin's solution and final irrigation with Tergentol- Furacin; and Group D - File Eze. The root canals were obturated by the Tagger's hybrid technique and then radiographed for assessment of the penetration rate of the filling materials in the lateral canals. Analysis of the results demonstrated no statistically significant difference (pObjetivou-se avaliar a influĂȘncia de alguns agentes auxiliares do preparo biomecĂąnico do canal radicular, na obturação de canais laterais artificiais em dentes humanos extraĂ­dos. Foram utilizados oitenta dentes unirradiculados nos quais, previamente, foram confeccionados trĂȘs canais laterais artificiais em uma das paredes proximais, nos terços cervical, mĂ©dio e apical e um canal na parede vestibular. Os canais principais foram preparados com instrumentação rotatĂłria, instrumentos Profile 0.4, pela tĂ©cnica rotatĂłria coroa- ĂĄpice e irrigados com a substĂąncia irrigadora estudada, sendo no grupo A - hipoclorito de sĂłdio a 1% e irrigação final com EDTA trissĂłdico por 5 minutos; grupo B - Endogel (gel de clorexidina a 2%); grupo C - Endo PTC e solução de Dakin e irrigação final com tergentol-furacin segundo a tĂ©cnica de Paiva e Antoniazzi e no grupo D - File Eze. Os canais foram obturados pela tĂ©cnica hĂ­brida de Tagger e, entĂŁo, radiografados para a anĂĄlise das extensĂ”es de penetração dos materiais obturadores nos canais laterais. ApĂłs a anĂĄlise dos resultados, conclui-se que nĂŁo houve diferença estatĂ­stica significante (

    In the Margins: The Impact of Sexualised Images on the Mental Health of Ageing Women

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    This paper describes key findings of a study exploring how a cohort of 16 rural Australian women aged over 60 years think, feel and respond to the prevalence of sexualised imagery in the media. The qualitative research framework was informed by Feminist Standpoint Theory. Participants in three focus groups responded to semi-structured questions and prompts, interspersed with viewing examples of sexualised images. Five strong thematic categories emerged: concern for the harmful impacts of sexualised images on the vulnerable, the media’s portrayal of sexual content with a focus on physical appearance and youth, descriptions of the impact of viewing sexualised images, moderators of the impact of sexualised images on well-being, and marginalisation of women in the media. Findings from this research indicate that sexualised images in the media do have an impact on older women’s self image and mental health in numerous ways and in a range of situations. Emotional impacts included sadness, anger, concern, envy, desensitisation, marginalisation, and discomfort that their appearance was being judged by others. A strong sense of self apart from appearance, feeling valued by family and community, ignoring or overlooking media content, and being aware that media images are not real and attainable helped buffer the link between sexualised images and well-being. Another important finding is that the impact is variable: women may experience different responses to similar sexualised content depending on a range of social, health and lifestyle factors affecting them at any given time

    Transient Facial Nerve Paralysis (Bell's Palsy) following Intranasal Delivery of a Genetically Detoxified Mutant of Escherichia coli Heat Labile Toxin

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    BACKGROUND: An association was previously established between facial nerve paralysis (Bell's palsy) and intranasal administration of an inactivated influenza virosome vaccine containing an enzymatically active Escherichia coli Heat Labile Toxin (LT) adjuvant. The individual component(s) responsible for paralysis were not identified, and the vaccine was withdrawn. METHODOLOGY/PRINCIPAL FINDINGS: Subjects participating in two contemporaneous non-randomized Phase 1 clinical trials of nasal subunit vaccines against Human Immunodeficiency Virus and tuberculosis, both of which employed an enzymatically inactive non-toxic mutant LT adjuvant (LTK63), underwent active follow-up for adverse events using diary-cards and clinical examination. Two healthy subjects experienced transient peripheral facial nerve palsies 44 and 60 days after passive nasal instillation of LTK63, possibly a result of retrograde axonal transport after neuronal ganglioside binding or an inflammatory immune response, but without exaggerated immune responses to LTK63. CONCLUSIONS/SIGNIFICANCE: While the unique anatomical predisposition of the facial nerve to compression suggests nasal delivery of neuronal-binding LT-derived adjuvants is inadvisable, their continued investigation as topical or mucosal adjuvants and antigens appears warranted on the basis of longstanding safety via oral, percutaneous, and other mucosal routes
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