Structural analysis of intrinsically disordered proteins: computer atomistic simulation

Intrinsically disordered proteins (IDPs) are biomolecules that do not have a definite 3D structure; their role in the biochemical network of a cell relates to their ability to switch rapidly among different secondary and tertiary structures. For this reason, applying a simulation computer program to their structural study turns out to be problematic, as their dynamical simulation cannot start from a known list of atomistic positions, as is the case for globular proteins that do crystallize and that one can analyse by X-ray spectroscopy to determine their structure. We have established a method to perform a computer simulation of these proteins, apt to gather statistically significant data on their transient structures. The only required input to start the procedure is the primary sequence of the disordered domains of the protein, and the 3D structure of the ordered domains, if any. For a fully disordered protein the method is as follows: (a) The first step is the creation of a multi-rod-like configuration of the molecule, derived from its primary sequence. This structure evolves dynamically in vacuo or in an implicit model of solvent, until its gyration radius - or any other measure of the overall configuration of the molecule - reaches the experimental average value; at this point, one may follow two different paths. (b1) If the study focuses on transient secondary structures of the molecule, one puts the structure obtained at the end of the first step in a box containing solvent molecules in explicit implementation, and a standard molecular dynamics simulation follows. (b2) If the study focuses on the tertiary structure of the molecule, a larger sampling of the phase space is required, with the molecule moving in very large and diverse regions of the phase space. To this end, the structure of the IDP is let evolve dynamically in an implicit solvent using metadynamics, an algorithm that keeps track of the regions of the phase space already sampled, and forces the system to wander in further regions of the phase space. (c) One can increase the accuracy of the statistical information gathered in both cases by fitting, where available, experimental data of the protein. In this step one extracts an ensemble of ’best’ conformers from the pool of all configurations produced in the simulated dynamics. One derives this ensemble by means of an ensemble optimization method, implementing a genetic algorithm. We have applied this procedure to the simulation of tau, one of the largest fully disordered proteins, which is involved in the development of Alzheimer’s disease and of other neurodegenerative diseases. We have combined the results of our simulation with small-angle X-ray scattering experimental data to extract from the dynamics an optimized ensemble of most probable conformers of tau. The method can be easily adapted to IDPs entailing ordered domains

Representations of the uninterrupted and grotesque carnival celebration in two Utopias of seventeenth-century Germany

En el año 1640 se publicó Utopía, obra homónima a la de Tomás Moro, escrita por Jakob Bidermann, jesuita alemán e inquisidor de la Iglesia Católica en Roma. El autor, miembro activo de la cultura tridentina, escribió el texto en latín con la finalidad didáctica de enseñar ejemplo y moral para los alumnos del colegio de los jesuitas en la ciudad de Augsburgo. En 1677, Christoph von Andreas Hörl Waltersdorf, de quien poco se sabe, tradujo el texto del latín al alemán y lo publicó bajo el título de Bacchusia oder Fastnachtland. A excepción de algunas diferencias entre la obra original y su traducción, el texto se refiere al viaje de tres amigos a un país imaginario donde los habitantes celebran un carnaval eterno, el caos es institucionalizado y se suspenden las reglas de buena conductaIn 1640, Utopia, the homonymous work of Thomas More, written by Jakob Bidermann, German Jesuit and Inquisitor of the Catholic Church in Rome, was published. The author, an active member of the Tridentine Culture, wrote the text in Latin with the didactic purpose of teaching moral example to his students at the Jesuit College in the city of Augsburg. In 1677, Christoph von Andreas Hörl von Waltersdorf, of whom little is known, translated the text from Latin into German, and published it under the title Bacchusia oder Fastnachtland. Except for some differences between the original work and its translation, the text recounts the journey of three friends to an imaginary land where the inhabitants celebrate an eternal carnival, chaos is institutionalized and the rules of good behavior are suspende

The Microstrain-Doping Phase Diagram of the Iron Pnictides Heterostructures at Atomic Limit

The 3D phase diagram of iron pnictides where the critical temperature depends on charge density and microstrain in the active FeAs layers is proposed. The iron pnictides superconductors are shown to be a practical realization of a heterostructure at the atomic limit made of a superlattice of FeAs layers intercalated by spacer layers. We have focussed our interest on the A 1-x BxFe2As2 (122) families and we show that FeAs layers have a tensile microstrain due to the misfit strain between the active layers and the spacers. We have identified the critical range of doping and microstrain where the critical temperature gets amplified to its maximum value.Comment: 5 pages, 3 figure

Nanoscale correlated disorder in out-of-equilibrium myelin ultrastructure

Ultrastructural fluctuations at nanoscale are fundamental to assess properties and functionalities of advanced out-of-equilibrium materials. We have taken myelin as a model of supramolecular assembly in out-of-equilibrium living matter. Myelin sheath is a simple stable multi-lamellar structure of high relevance and impact in biomedicine. Although it is known that myelin has a quasi-crystalline ultrastructure there is no information on its fluctuations at nanoscale in different states due to limitations of the available standard techniques. To overcome these limitations, we have used Scanning micro X-ray Diffraction, which is a non-invasive probe of both reciprocal and real space to visualize statistical fluctuations of myelin order of the sciatic nerve of Xenopus Laevis. The results show that the ultrastructure period of the myelin is stabilized by large anti-correlated fluctuations at nanoscale, between hydrophobic and hydrophilic layers. The ratio between the total thickness of hydrophilic and hydrophobic layers defines the conformational parameter, which describes the different states of myelin. Our key result is that myelin in its out-of-equilibrium functional state fluctuates point-to-point between different conformations showing a correlated disorder described by a Levy distribution. As the system approaches the thermodynamic equilibrium in an aged state the disorder loses its correlation degree and the structural fluctuation distribution changes to Gaussian. In a denatured state at low pH, it changes to a completely disordered stage. Our results clarify also the degradation mechanism in biological systems by associating these states with variation of the ultrastructural dynamic fluctuations at nanoscale.Comment: 21 pages, 6 fugure

Dichotic listening and spect in dyslexic children

Dichotic listening (DL) was evaluated in 36 children with: verbal dichotic listening test, alternating dissilable dichotic test and non-verbal dichotic listening test. Children were separated into two groups: experimental group with 18 dyslexic children and control group with 18 normal children. Both groups were comparable in gender, laterality and social-economic level. All dyslexic children underwent neuroimaging exam (SPECT). Our data showed that there was a statistical difference between both groups in all DL tests. Abnormal SPECT findings were seen in 50% of the dyslexic children, hypoperfusion of the left temporal lobe being the most frequent abnormality. We conclude that dyslexic children present an impairment of central neurologic processing that may be detected by DL tests, and by functional imaging exam, such as SPECT, as well.Aplicamos em um grupo de 36 crianças os testes dicótico de dígitos, dicótico de dissílabos alternados e dicótico não-verbal, os quais fazem parte do conjunto de avaliação do processamento auditivo. As crianças foram divididas em dois grupos que foram correlacionados: grupo experimental (GE) formado por 18 crianças com diagnóstico de dislexia e 18 crianças normais compondo o grupo comparação (GC), sem queixa de aprendizagem e pareadas em relação a sexo, lateralidade e nível sócio-econômico ao GE. Realizamos o exame de imagem (SPECT) no GE. Encontramos em nosso estudo diferença estatisticamente significante entre os grupos (GE e GC) em todos os testes avaliados. Em relação ao SPECT, apesar de não encontrarmos diferença estatisticamente significante entre os resultados, pudemos observar que 50% dos sujeitos avaliados apresentaram alteração, sendo a maior parte em áreas do lobo temporal esquerdo. Concluímos que crianças com dislexia apresentam alterações do processamento neurológico central que podem ser detectadas tanto em testes específicos de processamento auditivo, quanto em exames funcionais de imagem como SPECT.Universidade Estadual de São Paulo Faculdade de Ciências Médicas Departamento de NeurologiaUniversidade Federal de São Paulo (UNIFESP) Departamento de Distúrbios da ComunicaçãoUNIFESP, Depto. de Distúrbios da ComunicaçãoSciEL

AVALIAÇÃO DE DISCIPLINAS EM FAVOR DA FORMAÇÃO DE PROFESSORES: CONTRIBUIÇÕES DO ENSINO SUPERIOR PARA A GESTÃO EDUCACIONAL

O presente artigo deriva de uma pesquisa de doutoramento concluída em agosto de 2011 que objetivou avaliar os programas de disciplinas da área de estrutura e funcionamento da educação básica, ofertadas para os cursos de licenciatura da Universidade Federal do Ceará, e os impactos produzidos por estas na formação inicial de professores que venham a exercer cargos relacionados à gestão escolar. O estudo contou com a significativa amostra de 167 (cento e sessenta e sete) estudantes de graduação; 05 (cinco) professores e 10 (dez) egressos que, na época da pesquisa, ocupavam a função de gestor educacional em diferentes instituições da esfera pública e privada na cidade de Fortaleza (CE). Constitui-se como um estudo qualiquantitativo, caracterizado como uma pesquisa documental e avaliativa. Elegeu-se como suporte teórico, dentre outros, Ristoff (1995), Vianna (2000), Bachelard (1996). Os resultados apontam que a qualidade do processo educativo não depende exclusivamente do processo desenvolvido em sala de aula, mas também está sujeito às ações daqueles que fazem a condução administrativa e organizacional desse processo; nesse caso, do gestor educacional e de diferentes atores que desempenham funções relacionadas à gestão da educação. Daí a necessidade de avaliar as referidas disciplinas com vistas à influência que estas exercem na formação de futuros gestores educacionais, que, por sua vez, são elementos-chave para o sucesso escolar.Palavras-chave: Avaliação. Formação de professores. Gestão educacional

Perfil neuropsicológico e escolar de crianças com discalculia e dislexia : estudo Comparativo

This paper aims to compare the neuropsychological and educational profies of Brazilian children with dyscalculia (n = 8), dyslexia (n = 13) and without learning disabilities (n = 12). The neuropsychological profie was composed of: (a) intelligence assessed by the Wechsler Intelligence Scale for Children (WISC-III); (b) attention - WISC-III Coding and Symbol Search subtests; (c) executive functions - Digit Span (backward order) and WISC-III Arithmetic subtests, Pseudoword Repetition Test for Brazilian Children, Stroop Test and Wisconsin Card Sorting Test; (d) memory - WISC-III Digit Span subtest (forward order) and Rey Complex Figures. The educational profie was composed of reading, writing and mathematics, assessed by the Academic Performance Test and the Arithmetic Test. It was found that the groups with dyscalculia and dyslexia did not differentiate in any of the neuropsychological abilities, only in the reading and writing abilities. Neuropsychological variables that could explain these results were discussed244645659This paper aims to compare the neuropsychological and educational profies of Brazilian children with dyscalculia (n = 8), dyslexia (n = 13) and without learning disabilities (n = 12). The neuropsychological profie was composed of: (a) intelligence assessed by the Wechsler Intelligence Scale for Children (WISC-III); (b) attention - WISC-III Coding and Symbol Search subtests; (c) executive functions - Digit Span (backward order) and WISC-III Arithmetic subtests, Pseudoword Repetition Test for Brazilian Children, Stroop Test and Wisconsin Card Sorting Test; (d) memory - WISC-III Digit Span subtest (forward order) and Rey Complex Figures. The educational profie was composed of reading, writing and mathematics, assessed by the Academic Performance Test and the Arithmetic Test. It was found that the groups with dyscalculia and dyslexia did not differentiate in any of the neuropsychological abilities, only in the reading and writing abilities. Neuropsychological variables that could explain these results were discusse

A UTOPIA DE JAKOB BIDERMANN

Este artigo busca compreender por que Jakob Bidermann, jesuíta alemão, dramaturgo e futuro inquisidor da Igreja Católica em Roma, escolheu dar à sua obra, publicada em 1640, o mesmo título da obra de Thomas Morus: Utopia. Otexto relata a viagem de três amigos para um país imaginário chamado Utopia, onde os habitantes festejam um eterno Carnaval, o caos é institucionalizado, as regras da cultura estão suspensas, os cidadãos andam mascarados, e bebe-se e come-se em demasia. Os viajantes experimentam as terríveis consequências deste “mundo de cabeça para baixo” e as inseguranças de um lugar que vive imerso em vício, vaidade, violência e excesso; descobrem então que o mundo real, se baseado nas virtudes e  na moral cristã, e principalmente se guiado pela Igreja Católica, torna-se um lugar muito mais verdadeiro, tranquilo e belo de se viver

Avaliação da Interface de Interação para a Aplicação Multimídia do Totem Digital do Museu Histórico de Araranguá

TCC (graduação) - Universidade Federal de Santa Catarina. Campus Araranguá. Tecnologias da Informação e COmunicação.A principal função das Tecnologias da Informação e Comunicação diz respeito a favorecer a disseminação e compartilhamento da informação, através de ferramentas que auxiliem na comunicação de modo geral. Um ambiente que caracteriza e oportuniza este processo de comunicação entre pessoas, épocas e lugares, através da informação que mantem em diversos formatos, é o Museu, ou Arquivo Histórico. No entanto, o que percebemos é que a visita ao museu não é mais a principal fonte de informações lembrada no momento da pesquisa, e é neste contexto que as tecnologias da informação e comunicação, as ditas TICs, podem contribuir. A aplicação de instrumentos e mecanismos computacionais no contexto museólogo, não provoca só a modernização, busca facilitar a investigação e recolhimento de informações, e mais, assumir principalmente uma posição de complemento ao museu, e em nenhum momento competindo com o que nunca deixará de ser o ambiente de salvaguarda da história da história. Neste trabalho buscamos a disponibilização virtual do acervo histórico do município de Araranguá e consequente e concomitantemente sua conservação e difusão. E ainda, a divulgação do Museu Histórico de uma forma mais tecnológica e atrativa em um Quiosque de Informação: neste cenário intitulado Totem Digital, que dispõe de um sistema capaz de suportar a interação entre o público e o patrimônio digitalizado, a fim de despertar o interesse em visitar o museu virtual e influenciar à visita ao museu físico e vice-versa. Dentro deste contexto foi realizada a análise da interface de interação da aplicação multimídia para o totem digital com o objetivo de verificar se a interface de interação atende aos critérios de usabilidade

Biosynthesis and physico-chemical characterization of high performing peptide hydrogels@graphene oxide composites

Hydrogels based on short peptide molecules are interesting biomaterials with wide present and prospective use in biotechnologies. A well-known possible drawback of these materials can be their limited mechanical performance. In order to overcome this problem, we prepared Fmoc-Phe3self-assembling peptides by a biocatalytic approach, and we reinforced the hydrogel with graphene oxide nanosheets. The formulation here proposed confers to the hydrogel additional physicochemical properties without hampering peptide self-assembly. We investigated in depth the effect of nanocarbon morphology on hydrogel properties (i.e. morphology, viscoelastic properties, stiffness, resistance to an applied stress). In view of further developments towards possible clinical applications, we have preliminarily tested the biocompatibility of the composites. Our results showed that the innovative hydrogel composite formulation based on FmocPhe3 and GO is a biomaterial with improved mechanical properties that appears suitable for the development of biotechnological applications