976 resultados para BMPR-IA


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Type IA DNA topoisomerases, typically found in bacteria, are essential enzymes that catalyse the DNA relaxation of negative supercoils. DNA gyrase is the only type II topoisomerase that can carry out the opposite reaction (i.e. the introduction of the DNA supercoils). A number of diverse molecules target DNA gyrase. However, inhibitors that arrest the activity of bacterial topoisomerase I at low concentrations remain to be identified. Towards this end, as a proof of principle, monoclonal antibodies that inhibit Mycobacterium smegmatis topoisomerase I have been characterized and the specific inhibition of Mycobacterium smegmatis topoisomerase I by a monoclonal antibody, 2F3G4, at a nanomolar concentration is described. The enzyme-bound monoclonal antibody stimulated the first transesterification reaction leading to enhanced DNA cleavage, without significantly altering the religation activity of the enzyme. The stimulated DNA cleavage resulted in perturbation of the cleavagereligation equilibrium, increasing single-strand nicks and proteinDNA covalent adducts. Monoclonal antibodies with such a mechanism of inhibition can serve as invaluable tools for probing the structure and mechanism of the enzyme, as well as in the design of novel inhibitors that arrest enzyme activity.

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Type Ia supernovae, sparked off by exploding white dwarfs of mass close to the Chandrasekhar limit, play the key role in understanding the expansion rate of the Universe. However, recent observations of several peculiar type Ia supernovae argue for its progenitor mass to be significantly super-Chandrasekhar. We show that strongly magnetized white dwarfs not only can violate the Chandrasekhar mass limit significantly, but exhibit a different mass limit. We establish from a foundational level that the generic mass limit of white dwarfs is 2.58 solar mass. This explains the origin of overluminous peculiar type Ia supernovae. Our finding further argues for a possible second standard candle, which has many far reaching implications, including a possible reconsideration of the expansion history of the Universe. DOI: 10.1103/PhysRevLett.110.071102

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Several recently discovered peculiar Type Ia supernovae seem to demand an altogether new formation theory that might help explain the puzzling dissimilarities between them and the standard Type Ia supernovae. The most striking aspect of the observational analysis is the necessity of invoking super-Chandrasekhar white dwarfs having masses similar to 2.1-2.8 M-circle dot, M-circle dot being the mass of Sun, as their most probable progenitors. Strongly magnetized white dwarfs having super-Chandrasekhar masses have already been established as potential candidates for the progenitors of peculiar Type Ia supernovae. Owing to the Landau quantization of the underlying electron degenerate gas, theoretical results yielded the observationally inferred mass range. Here, we sketch a possible evolutionary scenario by which super-Chandrasekhar white dwarfs could be formed by accretion on to a commonly observed magnetized white dwarf, invoking the phenomenon of flux freezing. This opens multiple possible evolution scenarios ending in supernova explosions of super-Chandrasekhar white dwarfs having masses within the range stated above. We point out that our proposal has observational support, such as the recent discovery of a large number of magnetized white dwarfs by the Sloan Digital Sky Survey.

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Bacterial DNA topoisomerase I (topoI) catalyzes relaxation of negatively supercoiled DNA. The enzyme alters DNA topology through protein-operated DNA gate, switching between open and closed conformations during its reaction. We describe the mechanism of inhibition of Mycobacterium smegmatis and Mycobacterium tuberculosis topoI by monoclonal antibodies (mAbs) that bind with high affinity and inhibit at 10-50 nM concentration. Unlike other inhibitors of topoisomerases, the mAbs inhibited several steps of relaxation reaction, namely DNA binding, cleavage, strand passage, and enzyme-DNA dissociation. The enhanced religation of the cleaved DNA in presence of the mAb indicated closing of the enzyme DNA gate. The formation of enzyme-DNA heterocatenane in the presence of the mAbs as a result of closing the gate could be inferred by the salt resistance of the complex, visualized by atomic force microscopy and confirmed by fluorescence measurements. Locking the enzyme-DNA complex as a closed clamp restricted the movements of the DNA gate, affecting all of the major steps of the relaxation reaction. Enzyme trapped on DNA in closed clamp conformation formed roadblock for the elongating DNA polymerase. The unusual multistep inhibition of mycobacterial topoisomerases may facilitate lead molecule development, and the mAbs would also serve as valuable tools to probe the enzyme mechanism.

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We explore the effect of modification to Einstein's gravity in white dwarfs for the first time in the literature, to the best of our knowledge. This leads to significantly sub- and super-Chandrasekhar limiting masses of white dwarfs, determined by a single model parameter. On the other hand, type Ia supernovae (SNeIa), a key to unravel the evolutionary history of the universe, are believed to be triggered in white dwarfs having mass close to the Chandrasekhar limit. However, observations of several peculiar, under- and over-luminous SNeIa argue for exploding masses widely different from this limit. We argue that explosions of the modified gravity induced sub- and super-Chandrasekhar limiting mass white dwarfs result in under- and over-luminous SNeIa respectively, thus unifying these two apparently disjoint sub-classes and, hence, serving as a missing link. Our discovery raises two fundamental questions. Is the Chandrasekhar limit unique? Is Einstein's gravity the ultimate theory for understanding astronomical phenomena? Both the answers appear to be no!

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We establish the importance of modified Einstein's gravity (MG) in white dwarfs (WDs) for the first time in the literature. We show that MG leads to significantly sub- and super-Chandrasekhar limiting mass WDs, depending on a single model parameter. However, conventional WDs on approaching Chandrasekhar's limit are expected to trigger Type Ia supernovae (SNeIa), a key to unravel the evolutionary history of the universe. Nevertheless, observations of several peculiar, under-and over-luminous SNeIa argue for the limiting mass widely different from Chandrasekhar's limit. Explosions of MG induced sub-and super-Chandrasekhar limiting mass WDs explain under-and over-luminous SNeIa respectively, thus unifying these two apparently disjoint sub-classes. Our discovery questions both the global validity of Einstein's gravity and the uniqueness of Chandrasekhar's limit.

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A sociedade na qual vivemos vem passando por grandes transformações que influenciam os modos de construir conhecimentos e veicular informações, as formas de se relacionar com o outro, a maneira de perceber o mundo e a si mesmo no mundo. Estas mudanças são marcadas pela interatividade, pela conectividade, pela velocidade, pela multilinearidade, pela complexidade e pela fragmentação tão presentes na cultura digital. Os jovens, nascidos em meio a estas transformações, vivenciam essas marcas em suas práticas culturais cotidianas, construindo uma nova lógica que orienta seu modo de perceber e agir na sociedade. No entanto, ao mesmo tempo em que os jovens orientam suas ações a partir dessa lógica que chamo nesse trabalho de cibercultural, vivenciam uma lógica linear na escola, o que acaba por produzir um hiato entre as culturas juvenis e a cultura escolar. Buscando contribuir para a construção de práticas pedagógicas mais concernentes às necessidades dos jovens contemporâneos, este estudo se propôs investigar o papel mediador das tecnologias digitais nos processos de ensino-aprendizagem. O estudo foi desenvolvido em uma escola de Ensino Médio Integrado, na zona norte do Rio de Janeiro, na qual os alunos têm acesso, em período integral, às disciplinas do currículo do MEC integradas às disciplinas de formação técnica voltadas às tecnologias digitais. Este projeto é fruto de uma parceria da Secretaria de Educação do Estado do Rio de Janeiro com um instituto privado, cujo objetivo é construir um espaço de pesquisa e de inovações em educação. A pesquisa se configurou como um estudo de caso, embora algumas reflexões possam contribuir para debates mais amplos em educação. O estudo apoiou-se teórico-metodologicamente nos Estudos Culturais Latino-americanos (Martín-Barbero e Canclini), que trazem contribuições para pensar o papel das mediações nos processos de recepção dos meios comunicacionais. Baseia-se, também, nos estudos sobre juventude (Dayrell e Carrano) que ajudaram a construir um olhar para os jovens pesquisados a partir do lugar ativo e protagonista de suas práticas dentro e fora da escola. Complementando estes aportes teóricos, o trabalho se fundamenta, ainda, nos estudos sobre a relação dos sujeitos com os ambientes virtuais ou ciberculturais (Lévy, Lemos e Santaella). As entrevistas realizadas com jovens e professores da escola e as observações em sala de aula foram exercícios de alteridade e exotopia, inspirados em Mikhail Bakhtin. O trabalho foi tecido numa perspectiva dialógica, buscando trazer para o texto impresso as experiências vividas no campo e os debates desencadeados a partir dessas experiências, propondo alguns caminhos para contribuir com uma escola mais significativa aos novos tempos.