Proc. Nat. Acad. Sci. USA

Drosophila Polycomb group (PcG) and Trithorax group (TrxG) proteins are responsible for the maintenance of stable transcription patterns of many developmental regulators, such as the homeotic genes. We have used ChIP-on-chip to compare the distribution of several PcG/TrxG proteins, as well as histone modifications in active and repressed genes across the two homeotic complexes ANT-C and BX-C. Our data indicate the colocalization of the Polycomb repressive complex 1 (PRC1) with Trx and the DNA binding protein Pleiohomeotic (Pho) at discrete sequence elements as well as significant chromatin assembly differences in active and inactive regions. Trx binds to the promoters of active genes and noncoding transcripts. Most strikingly, in the active state, Pho covers extended chromatin domains over many kilobases. This feature of Pho, observed on many polytene chromosome puffs, reflects a previously undescribed function. At the hsp70 gene, we demonstrate in mutants that Pho is required for transcriptional recovery after heat shock. Besides its presumptive function in recruiting PcG complexes to their site of action, our results now uncover that Pho plays an additional role in the repression of already induced genes

Dripping Faucet Dynamics Clarified by an Improved Mass-Spring Model

An improved mass-spring model for a dripping faucet is presented. The model is constructed based on the numerical results which we recently obtained from fluid dynamical calculations. Both the fluid dynamical calculations and the present mass-spring model exhibit a variety of complex behavior including transition to chaos in good agreement with experiments. Further, the mass-spring model reveals fundamental dynamics inherent in the dripping faucet system.Comment: 17 pages, 17 figure

Low thermal conductivity of the layered oxide (Na,Ca)Co_2O_4: Another example of a phonon glass and an electron crystal

The thermal conductivity of polycrystalline samples of (Na,Ca)Co_2O_4 is found to be unusually low, 20 mW/cmK at 280 K. On the assumption of the Wiedemann-Franz law, the lattice thermal conductivity is estimated to be 18 mW/cmK at 280 K, and it does not change appreciably with the substitution of Ca for Na. A quantitative analysis has revealed that the phonon mean free path is comparable with the lattice parameters, where the point-defect scattering plays an important role. Electronically the same samples show a metallic conduction down to 4.2 K, which strongly suggests that NaCo_2O_4 exhibits a glass-like poor thermal conduction together with a metal-like good electrical conduction. The present study further suggests that a strongly correlated system with layered structure can act as a material of a phonon glass and an electron crystal.Comment: 5 pages 3 figures, to be published in Phys. Rev.

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

Applications of CRISPR–Cas systems in neuroscience

Genome-editing tools, and in particular those based on CRISPR-Cas (clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR-associated protein) systems, are accelerating the pace of biological research and enabling targeted genetic interrogation in almost any organism and cell type. These tools have opened the door to the development of new model systems for studying the complexity of the nervous system, including animal models and stem cell-derived in vitro models. Precise and efficient gene editing using CRISPR-Cas systems has the potential to advance both basic and translational neuroscience research.National Institute of Mental Health (U.S.) (Grant 5DP1-MH100706)National Institute of Mental Health (U.S.) (Grant 1R01-MH110049)National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (Grant 5R01DK097768-03

Ste20-Related Proline/Alanine-Rich Kinase (SPAK) Regulated Transcriptionally by Hyperosmolarity Is Involved in Intestinal Barrier Function

The Ste20-related protein proline/alanine-rich kinase (SPAK) plays important roles in cellular functions such as cell differentiation and regulation of chloride transport, but its roles in pathogenesis of intestinal inflammation remain largely unknown. Here we report significantly increased SPAK expression levels in hyperosmotic environments, such as mucosal biopsy samples from patients with Crohn's disease, as well as colon tissues of C57BL/6 mice and Caco2-BBE cells treated with hyperosmotic medium. NF-κB and Sp1-binding sites in the SPAK TATA-less promoter are essential for SPAK mRNA transcription. Hyperosmolarity increases the ability of NF-κB and Sp1 to bind to their binding sites. Knock-down of either NF-κB or Sp1 by siRNA reduces the hyperosmolarity-induced SPAK expression levels. Furthermore, expression of NF-κB, but not Sp1, was upregulated by hyperosmolarity in vivo and in vitro. Nuclear run-on assays showed that hyperosmolarity increases SPAK expression levels at the transcriptional level, without affecting SPAK mRNA stability. Knockdown of SPAK expression by siRNA or overexpression of SPAK in cells and transgenic mice shows that SPAK is involved in intestinal permeability in vitro and in vivo. Together, our data suggest that SPAK, the transcription of which is regulated by hyperosmolarity, plays an important role in epithelial barrier function