1,105 research outputs found

    Biotechnological potential of Phospholipase D for Loxosceles antivenom development

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    Loxoscelism is one of the most important forms of araneism in South America. The Health Authorities from countries with the highest incidence and longer history in registering loxoscelism cases indicate that specific antivenom should be administered during the first hours after the accident, especially in the presence or at risk of the most severe clinical outcome. Current antivenoms are based on immunoglobulins or their fragments, obtained from plasma of hyperimmunized horses. Antivenom has been produced using the same traditional techniques for more than 120 years. Although the whole composition of the spider venom remains unknown, the discovery and biotechnological production of the phospholipase D enzymes represented a milestone for the knowledge of the physiopathology of envenomation and for the introduction of new innovative tools in antivenom production. The fact that this protein is a principal toxin of the venom opens the possibility of replacing the use of whole venom as an immunogen, an attractive alternative considering the laborious techniques and low yields associated with venom extraction. This challenge warrants technological innovation to facilitate production and obtain more effective antidotes. In this review, we compile the reported studies, examining the advances in the expression and application of phospholipase D as a new immunogen and how the new biotechnological tools have introduced some degree of innovation in this field.Fil: Fingermann, Matias. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Ministerio de Salud de la Nación. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud "Doctor Carlos G. Malbrán". Instituto Nacional de Producción de Biológicos; ArgentinaFil: de Roodt, Adolfo Rafael. Ministerio de Salud de la Nación. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud "Doctor Carlos G. Malbrán". Instituto Nacional de Producción de Biológicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Cascone, Osvaldo. Ministerio de Salud de la Nación. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud "Doctor Carlos G. Malbrán". Instituto Nacional de Producción de Biológicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología Industrial y Biotecnología; ArgentinaFil: Miranda, Maria Victoria. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología Industrial y Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; Argentin

    Safeguarding in adolescent mental health research:navigating dilemmas and developing procedures

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    Mental disorders are prevalent during adolescence. Self-harm and suicide are more common in adolescents with a probable mental disorder, with one in four reporting to have attempted self-harm. Research involving adolescents is, therefore, likely to include participants experiencing mental ill health, even if mental health is not the primary focus. Researchers should adopt procedures and principles that safeguard adolescent mental health in their research practice. Yet there are gaps between theory and practice of research with adolescents in relation to their mental health, and limited guidance is available. We discuss emerging safeguarding dilemmas and procedures in adolescent mental health research. Our experiences of safeguarding adolescent mental health are grounded in the UK National Institute for Health and Care Research-funded SMART Schools Study. Drawing from this secondary school-based study, we focus on how our research team encountered and addressed a high prevalence of participants (aged 12–13 and 14–15 years) reporting thoughts and behaviours related to self-harm or suicide (24% of participants). This included reviewing our existing risk mitigation processes and consulting with several committees including young people with lived experiences of mental health. We present the SMART Schools study safeguarding approach for adolescent mental health. This encompasses key safeguarding principles, study procedures and relevant justifications. We address school and university roles and responsibilities, pupil understanding, and efficient, effective and secure communication pathways. We embed guidance throughout this article for researchers working with adolescents in the context of mental health. Lastly, we present five key recommendations to safeguard the mental health of adolescents participating in research, including (1) appointing a safeguarding lead within the research team; (2) codesigning a bespoke study safeguarding approach; (3) adopting a responsive approach to mental health safeguarding; (4) being transparent about the study mental health safeguarding approach and (5) report the implementation and outcomes of safeguarding approaches. Trial registration number ISRCTN77948572

    Safeguarding in adolescent mental health research:navigating dilemmas and developing procedures

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    Mental disorders are prevalent during adolescence. Self-harm and suicide are more common in adolescents with a probable mental disorder, with one in four reporting to have attempted self-harm. Research involving adolescents is, therefore, likely to include participants experiencing mental ill health, even if mental health is not the primary focus. Researchers should adopt procedures and principles that safeguard adolescent mental health in their research practice. Yet there are gaps between theory and practice of research with adolescents in relation to their mental health, and limited guidance is available. We discuss emerging safeguarding dilemmas and procedures in adolescent mental health research. Our experiences of safeguarding adolescent mental health are grounded in the UK National Institute for Health and Care Research-funded SMART Schools Study. Drawing from this secondary school-based study, we focus on how our research team encountered and addressed a high prevalence of participants (aged 12–13 and 14–15 years) reporting thoughts and behaviours related to self-harm or suicide (24% of participants). This included reviewing our existing risk mitigation processes and consulting with several committees including young people with lived experiences of mental health. We present the SMART Schools study safeguarding approach for adolescent mental health. This encompasses key safeguarding principles, study procedures and relevant justifications. We address school and university roles and responsibilities, pupil understanding, and efficient, effective and secure communication pathways. We embed guidance throughout this article for researchers working with adolescents in the context of mental health. Lastly, we present five key recommendations to safeguard the mental health of adolescents participating in research, including (1) appointing a safeguarding lead within the research team; (2) codesigning a bespoke study safeguarding approach; (3) adopting a responsive approach to mental health safeguarding; (4) being transparent about the study mental health safeguarding approach and (5) report the implementation and outcomes of safeguarding approaches. Trial registration number ISRCTN77948572

    Sulfanilic acid-modified chitosan mini-spheres and their application for lysozyme purification from egg white

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    A cation exchange matrix with zwitterionic and multimodal properties was synthesized by a simple reaction sequence coupling sulfanilic acid to a chitosan based support. The novel chromatographic matrix was physico-chemically characterized by ss-NMR and ζ potential, and its chromatographic performance was evaluated for lysozyme purification from diluted egg white. The maximum adsorption capacity, calculated according to Langmuir adsorption isotherm, was 50.07 ± 1.47 mg g-1 while the dissociation constant was 0.074 ± 0.012 mg mL-1 . The process for lysozyme purification from egg white was optimized, with 81.9% yield and a purity degree of 86.5%, according to RP-HPLC analysis. This work shows novel possible applications of chitosan based materials. The simple synthesis reactions combined with the simple mode of use of the chitosan matrix represents a novel method to purify proteins from raw starting materials.Fil: Hirsch, Daniela Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; ArgentinaFil: Baieli, María Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; ArgentinaFil: Urtasun, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; ArgentinaFil: Lazaro Martinez, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas ; ArgentinaFil: Glisoni, Romina Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; ArgentinaFil: Miranda, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; ArgentinaFil: Cascone, Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; ArgentinaFil: Wolman, Federico Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; Argentin

    Microdochium bolleyi (Ascomycota: Xylariales): Caracterización fisiológica y caracteres estructurales de su asociación con trigo

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    Las raíces de las plantas hospedan una gran diversidad de hongos, entre ellos, se encuentran los Endofitos Septados Oscuros (ESO). Microdochium bolleyi coloniza las raíces de trigo y otros cereales, aunque algunos autores lo han considerado un patógeno débil, otros han demostrado su acción biocontroladora contra patógenos agresivos del suelo. En el presente trabajo, se aisló una cepa de M. bolleyi (22-1) de raíces de trigo. Esta cepa fue metabólicamente caracterizada y se realizó un ensayo de resíntesis bajo condiciones controladas con el fin de caracterizar la colonización del hongo en la raíz bajo microscopía óptica y de transmisión. Su crecimiento fue escaso en las fuentes de carbono y nitrógeno evaluadas, sintetizó indoles en cultivo in vitro, pero no mostró habilidades para solubilizar el fósforo, por último, solo se detectó actividad amilasa. La cepa 22-1 coloniza la corteza radicular del trigo, formando clamidosporas melanizadas inter e intracelularmente y en el interior de los pelos radiculares. Microdochium bolleyi (cepa 22-1) coloniza la raíz de trigo formando las típicas estructuras de los ESO y comportándose como un “verdadero endófito”, sin embargo, se necesitan más estudios para terminar de dilucidar su papel en la asociación con el trigo.Plant roots can be colonized by asymptomatic fungal strains belonging to several taxa, among them, the group defined as Dark Septate Endophytes (DSE). Microdochium bolleyi commonly colonizes wheat roots and other crops. It is considered a weak pathogen or even a non-pathogenic fungal species, which has also been considered as a potential biocontrol agent against aggressive soil-borne pathogens in cereal crops. We isolated a strain of M. bolleyi from wheat roots sampled in a crop field in Argentina, and characterized its abilities to grow in different carbon and nitrogen sources, to produce indole and to solubilize phosphorus; also several enzymatic activities were evaluated. In addition, resynthesis was performed under controlled conditions in order to characterize root fungal colonization under both, optical and transmission microscopy. The strain 22-1 colonized wheat root parenchymal tissue, forming chlamysdospores inside parenchymal cells and root hairs, and poorly grew in carbon and nitrogen sources. This fungus also synthesized indoles in in vitro culture, but it cannot solubilize phosphorus. Only amylase activity was detected out of seven enzymatic activity measured. Microdochium bolleyi (strain 22-1) colonized the roots, it formed typical DSE fungal structures and behaved like a “true endophyte”; however further studies are necessary to elucidate its role in the association with wheat.Fil: Rothen, Carolina Paola. Centro Regional de Investigaciones Cientificas y Transferencia Tecnológica La Rioja (CRILAR) - Provincia de La Rioja - UNLaR - SEGEMAR - UNCa - CONICET; ArgentinaFil: Miranda, María Victoria. Centro Regional de Investigaciones Cientificas y Transferencia Tecnológica La Rioja (CRILAR) - Provincia de La Rioja - UNLaR - SEGEMAR - UNCa - CONICET; ArgentinaFil: Fracchia, Sebastian. Centro Regional de Investigaciones Cientificas y Transferencia Tecnológica La Rioja (CRILAR) - Provincia de La Rioja - UNLaR - SEGEMAR - UNCa - CONICET; ArgentinaFil: Godeas, Alicia Margarita. Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Instituto de Biodiversidad y Biología Experimental y Aplicada (IBBEA) -CONICET; ArgentinaFil: Rodriguez, Maria Alejandra. Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Instituto de Biodiversidad y Biología Experimental y Aplicada (IBBEA) -CONICET; Argentin

    Carga postural en cuidadoras del hogar geriátrico Madre Marcelina

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    Introducción: El trabajo realizado por el cuidador de un anciano lo expone a posturas y cargas inadecuadas siendo este riesgo uno de los menos estudiados a pesar de sus efectos nocivos en la salud y bienestar del cuidador. Objetivos: Determinar la carga postural y síntomas músculo esqueléticas en las cuidadoras de adultos mayores del Hogar Madre Marcelina. Método: Estudio transversal en 12 cuidadoras de adultos mayores en el Hogar Geriátrico Madre Marcelina de la ciudad de Barranquilla. Previo consentimiento informado, se indagó sobre molestias músculo esqueléticas en 9 regiones corporales, durante los últimos 7 días y 12 meses anteriores al estudio, mediante el Cuestionario Nórdico. Se evaluaron las posturas de riesgo adoptadas y la carga soportada por el cuidador durante la tarea observada, a través del Método OWAS. Resultados: Todas las cuidadoras son mujeres, con una media de edad de 36,5 años y antigüedad menor de 5 años ejerciendo la labor. El 50% presenta molestias en el cuello y zona alta de la espalda en los últimos 7 días; el 33,3% presenta molestias en hombros, caderas/muslos, rodillas y pies/tobillos en los últimos 7 días; igual porcentaje refiere molestias en la zona alta de la espalda en los últimos 12 meses. El 83,3% adopta posturas dañinas para el sistema músculo esquelético. Conclusiones: Teniendo en cuenta la categoría de riesgo más frecuente en las cuidadoras estudiadas, se requieren acciones correctivas lo antes posible, toda vez que pueden desarrollar o agravar las molestias musculo-esqueléticas que comprometan la funcionalidad de las cuidadoras. ABSTRACTIntroduction: The work done by the caretaker of an elderly man exposes you to positions and loads unsuitable to being this risk one of the least studied despite its harmful effects on the health and well-being of the caregiver. Objectives: To determine the postural load and symptoms muscle skeletal in carers of adults home mother Marcelina. Method: Transversal study in 12 caregivers of older adults in the mother Marcelina geriatric home in the city of Barranquilla. Prior informed consent, asked about skeletal muscle discomfort in 9 parts of the body, during the last 7 days and 12 months prior to the study, by the Nordic questionnaire. We evaluated the risk positions taken and load on the caregiver during the observed task, through the OWAS method. Results: All caregivers are women, with an average age of 36.5 years and less than 5 years old practicing the work. 50% presents discomfort in the neck and upper area of his back in the last 7 days; 33.3% presents discomfort in shoulders, hips/thighs, knees and feet/ankles in the last 7 days; equal percentage means discomfort in the upper area of the back in the past 12 months. 83.3% adopts positions to the musculo-skeletal system. Conclusions: Taking into account the most frequent in the studied nurses risk category, corrective actions are required as soon as possible, since that can develop or aggravate musculoskeletal discomfort that would compromise the functionality of carers

    Photophysical properties of 5-substituted 2-thiopyrimidines

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    The aim of the present work is to determine the influence of C5 substitution on the photophysical properties of 2-thiopyrimidines (2-TPyr). For this purpose, 2-thiouracil, 5-t-butyl-2-thiouracil and 2-thiothymine (TU, BTU and TT, respectively) have been selected as target thionucleobases for the experimental studies and, in parallel, for DFT theoretical calculations. The UV spectra displayed by TU, BTU and TT in EtOH were very similar to each other. They showed a maximum around 275 nm and a shoulder at ca. 290 nm. The three 2-TPyr exhibited a strong phosphorescence emission; from the recorded spectra, triplet excited state energies of ca. 307, 304 and 294 kJ mol(-1) were determined for TU, BTU and TT, respectively. Laser excitation at 308 nm gave rise to a broad transient absorption band from 500 nm to 700 nm, which was in principle assigned to triplet-triplet absorption. This assignment was confirmed by energy transfer experiments using biphenyl (E-T = 274 kJ mol(-1)) as an acceptor. The triplet lifetimes were 70 ns, 1.1 mu s and 2.3 mu s, for TU, BTU and TT, respectively. The obtained photophysical data, both in phosphorescence and transient absorption measurements, point to significantly different properties of the TT triplet excited state in spite of the structural similarities. Theoretical calculations at the B3LYP/aug-cc-pVDZ/PCM level agree well with the experimental range of excited state energies and support the pi pi(star) nature of the lowest triplet states.Financial support by the Spanish Government (CTQ2009-13699, CTQ2012-32621, RyC-2007-00476 to V. L.-V., and contracts JAE-Predoc 2011-00740 and JAE-Doc 2010-06204 to V. V.-C. and J. A. S. respectively) and the computing facilities provided by the Theoretical Organic Chemistry group at the Universitat de Valencia (http://utopia.uv.es) are acknowledged.Vendrell Criado, V.; Sáez Cases, JA.; Lhiaubet, VL.; Cuquerella Alabort, MC.; Miranda Alonso, MÁ. (2013). Photophysical properties of 5-substituted 2-thiopyrimidines. Photochemical & Photobiological Sciences Photochemical and Photobiological Sciences. 12(8):1460-1465. doi:10.1039/c3pp50058fS14601465128Kumar, R. (1997). Synthesis and studies on the effect of 2-thiouridine and 4-thiouridine on sugar conformation and RNA duplex stability. Nucleic Acids Research, 25(6), 1272-1280. doi:10.1093/nar/25.6.1272Sintim, H. O., & Kool, E. T. (2006). Enhanced Base Pairing and Replication Efficiency of Thiothymidines, Expanded-size Variants of Thymidine. Journal of the American Chemical Society, 128(2), 396-397. doi:10.1021/ja0562447Favre, A., & Fourrey, J.-L. (1995). Structural Probing of Small Endonucleolytic Ribozymes in Solution Using Thio-Substituted Nucleobases as Intrinsic Photolabels. Accounts of Chemical Research, 28(9), 375-382. doi:10.1021/ar00057a003Cooper, D. S. (2005). Antithyroid Drugs. New England Journal of Medicine, 352(9), 905-917. doi:10.1056/nejmra042972Reader, S. C. J., Carroll, B., Robertson, W. R., & Lambert, A. (1987). Assessment of the biopotency of anti-thyroid drugs using porcine thyroid cells. Biochemical Pharmacology, 36(11), 1825-1828. doi:10.1016/0006-2952(87)90245-0Massey, A., Xu, Y.-Z., & Karran, P. (2001). Photoactivation of DNA thiobases as a potential novel therapeutic option. Current Biology, 11(14), 1142-1146. doi:10.1016/s0960-9822(01)00272-xKuramochi, H., Kobayashi, T., Suzuki, T., & Ichimura, T. (2010). Excited-State Dynamics of 6-Aza-2-thiothymine and 2-Thiothymine: Highly Efficient Intersystem Crossing and Singlet Oxygen Photosensitization. The Journal of Physical Chemistry B, 114(26), 8782-8789. doi:10.1021/jp102067tHarada, Y., Okabe, C., Kobayashi, T., Suzuki, T., Ichimura, T., Nishi, N., & Xu, Y.-Z. (2009). Ultrafast Intersystem Crossing of 4-Thiothymidine in Aqueous Solution. The Journal of Physical Chemistry Letters, 1(2), 480-484. doi:10.1021/jz900276xFavre, A., Saintomé, C., Fourrey, J.-L., Clivio, P., & Laugâa, P. (1998). Thionucleobases as intrinsic photoaffinity probes of nucleic acid structure and nucleic acid-protein interactions. Journal of Photochemistry and Photobiology B: Biology, 42(2), 109-124. doi:10.1016/s1011-1344(97)00116-4Coleman, R. S., & Siedlecki, J. M. (1992). Synthesis of a 4-thio-2’-deoxyuridine containing oligonucleotide. Development of the thiocarbonyl group as a linker element. Journal of the American Chemical Society, 114(23), 9229-9230. doi:10.1021/ja00049a089Hafner, M., Landthaler, M., Burger, L., Khorshid, M., Hausser, J., Berninger, P., … Tuschl, T. (2010). Transcriptome-wide Identification of RNA-Binding Protein and MicroRNA Target Sites by PAR-CLIP. Cell, 141(1), 129-141. doi:10.1016/j.cell.2010.03.009Basnak, I., Balkan, A., Coe, P. L., & Walker, R. T. (1994). The Synthesis of Some 5-Substituted and 5,6-Disubstituted 2′-Deoxyuridines. Nucleosides and Nucleotides, 13(1-3), 177-196. doi:10.1080/15257779408013234Becke, A. D. (1988). Density-functional exchange-energy approximation with correct asymptotic behavior. Physical Review A, 38(6), 3098-3100. doi:10.1103/physreva.38.3098Lee, C., Yang, W., & Parr, R. G. (1988). Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Physical Review B, 37(2), 785-789. doi:10.1103/physrevb.37.785Yanai, T., Tew, D. P., & Handy, N. C. (2004). A new hybrid exchange–correlation functional using the Coulomb-attenuating method (CAM-B3LYP). Chemical Physics Letters, 393(1-3), 51-57. doi:10.1016/j.cplett.2004.06.011Chai, J.-D., & Head-Gordon, M. (2008). 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    Screening assay for inhibitors of a recombinant Streptococcus pneumoniae UDP-glucose pyrophosphorylase

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    The UDP-glucose pyrophosphorylase of Streptococcus pneumoniae (GalUSpn) is absolutely required for the biosynthesis of capsular polysaccharide, the sine qua non virulence factor of pneumococcus. Since the eukaryotic enzymes are completely unrelated to their prokaryotic counterparts, we propose that the GalU enzyme is a critical target to fight the pneumococcal disease. A recombinant GalUSpn was overexpressed and purified. An enzymatic assay that is rapid, sensitive and easy to perform was developed. This assay was appropriate for screening chemical libraries for searching GalU inhibitors. This work represents a fundamental step in the exploration of novel antipneumococcal drugs.Fil: Zavala, Agustín. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; ArgentinaFil: Kovacec, Verónica Ivana. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; ArgentinaFil: Levín, Gustavo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; ArgentinaFil: Moglioni, Albertina Gladys. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Miranda, Maria Victoria. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: García, Ernesto. Consejo Superior de Investigaciones Científicas. Centro de Investigaciones Biológicas; EspañaFil: Bonofiglio, Laura. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mollerach, Marta Eugenia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

    A positive cooperativity binding model between Ly49 natural killer cell receptors and the viral immunoevasin m157: kinetic and thermodynamic studies

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    Natural killer (NK) cells discriminate between healthy and virally infected or transformed cells using diverse surface receptors that are both activating and inhibitory. Among them, the homodimeric Ly49 NK receptors, which can adopt two distinct conformations (backfolded and extended), are of particular importance for detecting cells infected with mouse cytomegalovirus (CMV) via recognition of the viral immunoevasin m157. The interaction of m157 with activating (Ly49H) and inhibitory (Ly49I) receptors governs the spread of mouseCMV.Wecarried out kinetic and thermodynamic experiments to elucidate the Ly49/m157 binding mechanism. Combining surface plasmon resonance, fluorescence anisotropy, and circular dichroism (CD), we determined that the best model to describe both the Ly49H/m157 and Ly49I/m157 interactions is a conformational selection mechanism where only the extended conformation of Ly49 (Ly49*) is able to bind the first m157 ligand followed by binding of the Ly49*/m157 complex to the second m157. The interaction is characterized by strong positive cooperativity such that the second m157 binds the Ly49 homodimer with a 1000-fold higher sequential constant than the first m157 (108 versus 105 M-1). Using far-UV CD, we obtained evidence for a conformational change in Ly49 upon binding m157 that could explain the positive cooperativity. The rate-limiting step of the overall mechanism is a conformational transition in Ly49 from its backfolded to extended form. The global thermodynamic parameters from the initial state (backfolded Ly49 and m157) to the final state (Ly49*/(m157)2) are characterized by an unfavorable enthalpy that is compensated by a favorable entropy, making the interaction spontaneous.Fil: Romasanta, Pablo Nicolas. Consejo Nacional de Investigaciones Cientiâ­ficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; ArgentinaFil: Curto, Lucrecia María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; ArgentinaFil: Urtasun, Nicolás. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Sarratea, Maria Belén. Consejo Nacional de Investigaciones Cientiâ­ficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; ArgentinaFil: Chiappini, Santiago Andrés. Consejo Nacional de Investigaciones Cientiâ­ficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; ArgentinaFil: Miranda, Maria Victoria. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Delfino, Jose Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; ArgentinaFil: Mariuzza, Roy A.. University Of Maryland. Biotechnology Institute; Estados UnidosFil: Fernández, Marisa Mariel. Consejo Nacional de Investigaciones Cientiâ­ficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; ArgentinaFil: Malchiodi, Emilio Luis. Consejo Nacional de Investigaciones Cientiâ­ficas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "profesor R. A. Margni"; Argentin

    Bone reabsorption associated with silicone implants in mentoplasty: a clinical case report

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    For many years, silicone implants were used in reconstructive and esthetic surgeries, especially in cases in which the facial profile of patients presented deficiencies in the inferior third of the face. This material proved to be successful in most aspects. However, several complications were well reported in the literature, as the case of bone reabsorption in the region of the mandibular chin. In this article, the authors present two clinical cases of bone reabsorption from the anterior cortex of the chin associated with silicone implants and discuss the etiology, complications, and treatment plan
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