Genetic analysis of the HLA region of Japanese patients with type 1 autoimmune hepatitis

ArticleJOURNAL OF HEPATOLOGY. 42(4): 578-584 (2005)journal articl

Lack of association between FCRL3 and Fc gamma RII polymorphisms in Japanese type 1 autoimmune hepatitis

ArticleCLINICAL IMMUNOLOGY. 122(3): 338-342 (2007)journal articl

Inertial- and Dissipation-Range Asymptotics in Fluid Turbulence

We propose and verify a wave-vector-space version of generalized extended self similarity and broaden its applicability to uncover intriguing, universal scaling in the far dissipation range by computing high-order (\leq 20\/) structure functions numerically for: (1) the three-dimensional, incompressible Navier Stokes equation (with and without hyperviscosity); and (2) the GOY shell model for turbulence. Also, in case (2), with Taylor-microscale Reynolds numbers 4 \times 10^{4} \leq Re_{\lambda} \leq 3 \times 10^{6}\/, we find that the inertial-range exponents (\zeta_{p}\/) of the order - p\/ structure functions do not approach their Kolmogorov value p/3\/ as Re_{\lambda}\/ increases.Comment: RevTeX file, with six postscript figures. epsf.tex macro is used for figure insertion. Packaged using the 'uufiles' utilit

Engineered polyketide biosynthesis and biocatalysis in Escherichia coli

Polyketides are important bioactive natural products biosynthesized by bacteria, fungi, and plants. The enzymes that synthesize polyketides are collectively referred to as polyketide synthases (PKSs). Because many of the natural hosts that produce polyketides are difficult to culture or manipulate, establishing a universal heterologous host that is genetically tractable has become an important goal toward the engineered biosynthesis of polyketides and analogues. Here, we summarize the recent progresses in engineering Escherichia coli as a heterologous host for reconstituting PKSs of different types. Our increased understanding of PKS enzymology and structural biology, combined with new tools in protein engineering, metabolic engineering, and synthetic biology, has firmly established E. coli as a powerful host for producing polyketides

Materiais didáticos no ensino e aprendizagem da matemática

O relatório final de estágio apresenta-se no âmbito do Mestrado em Educação Pré-Escolar e Ensino do 1.º Ciclo do Ensino Básico. Este inclui uma reflexão crítica relativamente às unidades curriculares de Prática de Ensino Supervisionada (II e III), em contexto de estágio, no 1.º Ciclo do Ensino Básico e na Educação Pré-Escolar. O relatório contempla ainda uma investigação cuja temática se centra na área da Matemática. Para a realização da primeira parte do relatório, foram utilizados diversos materiais construídos e implementados ao longo das PES II e III, bem como autores de referência, de forma a fundamentar o texto. Relativamente à segunda parte do relatório final de estágio foi realizada uma investigação de caráter qualitativo, que teve como principal objetivo perceber de que forma a utilização de materiais didáticos, em aulas do 1.º Ciclo do Ensino Básico, influencia a aprendizagem da Matemática, num tópico muito particular: números racionais. Desta forma, foi realizado um teste diagnóstico de forma a perceber o conteúdo em que os alunos sentiam mais dificuldades. Posteriormente, foram desenvolvidas três tarefas diferentes, utilizando materiais didáticos distintos e, foi ainda realizada uma entrevista semiestruturada aos três participantes do estudo. A análise dos dados recolhidos permitiu concluir, com alguma segurança, que a utilização de materiais didáticos, em conteúdos matemáticos, é benéfica para os alunos, pois revelam maior envolvimento nas tarefas propostas e uma melhor compreensão dos conteúdos abordados.The final apprenticeship report is related to the scope of the Masters Degree of Pre-schooling and Teaching the 1st Cycle of Basic School. It includes a critical reflection in relation to the curricular units of Supervised Teaching Practice (II and III), in the context of apprenticeship, in the 1st Cycle of Basic School and in Pre-school Education. The report also contemplates research whose theme concentrates on the fields of mathematics. For the first part of the report several different materials were used, which had been built and implemented along STP II and III, as well as authors of reference, so as to support the text. In relation to the second part of the apprenticeship final report, a qualitative research was carried out, which main purpose was to understand to which extent the use of didactic materials in the 1st cycle of Basic School classes influences the learning of mathematics, in a very particular topic: rational numbers. This way, a diagnosis was performed for a better understanding of the contents in which learners feel the most difficulties. Later on three tasks were developed, by using different didactic materials, and a semi-structured interview was held to the three participants in the study. The analysis of the collected data allowed to conclude, with some certainty, that the use of didactic materials in mathematical contents is beneficial for learners, because they reveal a greater involvement in the proposed tasks and a better understanding of the addressed contents

Transcriptomics reveal an integrative role for maternal thyroid hormones during zebrafish embryogenesis

Thyroid hormones (THs) are essential for embryonic brain development but the genetic mechanisms involved in the action of maternal THs (MTHs) are still largely unknown. As the basis for understanding the underlying genetic mechanisms of MTHs regulation we used an established zebrafish monocarboxylic acid transporter 8 (MCT8) knock-down model and characterised the transcriptome in 25hpf zebrafish embryos. Subsequent mapping of differentially expressed genes using Reactome pathway analysis together with in situ expression analysis and immunohistochemistry revealed the genetic networks and cells under MTHs regulation during zebrafish embryogenesis. We found 4,343 differentially expressed genes and the Reactome pathway analysis revealed that TH is involved in 1681 of these pathways. MTHs regulated the expression of core developmental pathways, such as NOTCH and WNT in a cell specific context. The cellular distribution of neural MTH-target genes demonstrated their cell specific action on neural stem cells and differentiated neuron classes. Taken together our data show that MTHs have a role in zebrafish neurogenesis and suggest they may be involved in cross talk between key pathways in neural development. Given that the observed MCT8 zebrafish knockdown phenotype resembles the symptoms in human patients with Allan-Herndon-Dudley syndrome our data open a window into understanding the genetics of this human congenital condition.Portuguese Fundacao para Ciencia e Tecnologia (FCT) [PTDC/EXPL/MARBIO/0430/2013]; CCMAR FCT Plurianual financing [UID/Multi/04326/2013]; FCT [SFRH/BD/111226/2015, SFRH/BD/108842/2015, SFRH/BPD/89889/2012]; FCT-IF Starting Grant [IF/01274/2014]info:eu-repo/semantics/publishedVersio

Altered branching patterns of Purkinje cells in mouse model for cortical development disorder

Disrupted cortical cytoarchitecture in cerebellum is a typical pathology in reeler. Particularly interesting are structural problems at the cellular level: dendritic morphology has important functional implication in signal processing. Here we describe a combinatorial imaging method of synchrotron X-ray microtomography with Golgi staining, which can deliver 3-dimensional(3-D) micro-architectures of Purkinje cell(PC) dendrites, and give access to quantitative information in 3-D geometry. In reeler, we visualized in 3-D geometry the shape alterations of planar PC dendrites (i.e., abnormal 3-D arborization). Despite these alterations, the 3-D quantitative analysis of the branching patterns showed no significant changes of the 77 ± 8° branch angle, whereas the branch segment length strongly increased with large fluctuations, comparing to control. The 3-D fractal dimension of the PCs decreased from 1.723 to 1.254, indicating a significant reduction of dendritic complexity. This study provides insights into etiologies and further potential treatment options for lissencephaly and various neurodevelopmental disorders

Interdigital cell death in the embryonic limb is associated with depletion of Reelin in the extracellular matrix

Interdigital cell death is a physiological regression process responsible for sculpturing the digits in the embryonic vertebrate limb. Changes in the intensity of this degenerative process account for the different patterns of interdigital webbing among vertebrate species. Here, we show that Reelin is present in the extracellular matrix of the interdigital mesoderm of chick and mouse embryos during the developmental stages of digit formation. Reelin is a large extracellular glycoprotein which has important functions in the developing nervous system, including neuronal survival; however, the significance of Reelin in other systems has received very little attention. We show that reelin expression becomes intensely downregulated in both the chick and mouse interdigits preceding the establishment of the areas of interdigital cell death. Furthermore, fibroblast growth factors, which are cell survival signals for the interdigital mesoderm, intensely upregulated reelin expression, while BMPs, which are proapototic signals, downregulate its expression in the interdigit. Gene silencing experiments of reelin gene or its intracellular effector Dab-1 confirmed the implication of Reelin signaling as a survival factor for the limb undifferentiated mesoderm. We found that Reelin activates canonical survival pathways in the limb mesoderm involving protein kinase B and focal adhesion kinase. Our findings support that Reelin plays a role in interdigital cell death, and suggests that anoikis (apoptosis secondary to loss of cell adhesion) may be involved in this process