181 research outputs found

    The Head-fixed Behaving Rat—Procedures and Pitfalls

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    This paper describes experimental techniques with head-fixed, operantly conditioned rodents that allow the control of stimulus presentation and tracking of motor output at hitherto unprecedented levels of spatio-temporal precision. Experimental procedures for the surgery and behavioral training are presented. We place particular emphasis on potential pitfalls using these procedures in order to assist investigators who intend to engage in this type of experiment. We argue that head-fixed rodent models, by allowing the combination of methodologies from molecular manipulations, intracellular electrophysiology, and imaging to behavioral measurements, will be instrumental in combining insights into the functional neuronal organization at different levels of observation. Provided viable behavioral methods are implemented, model systems based on rodents will be complementary to current primate models—the latter providing highest comparability with the human brain, while the former offer hugely advanced methodologies on the lower levels of organization, for example, genetic alterations, intracellular electrophysiology, and imaging

    Radius and chirality dependent conformation of polymer molecule at nanotube interface

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    Temperature dependent conformations of linear polymer molecules adsorbed at carbon nanotube (CNT) interfaces are investigated through molecule dynamics simulations. Model polyethylene (PE) molecules are shown to have selective conformations on CNT surface, controlled by atomic structures of CNT lattice and geometric coiling energy. PE molecules form entropy driven assembly domains, and their preferred wrapping angles around large radius CNT (40, 40) reflect the molecule configurations with energy minimums on a graphite plane. While PE molecules prefer wrapping on small radius armchair CNT (5, 5) predominantly at low temperatures, their configurations are shifted to larger wrapping angle ones on a similar radius zigzag CNT (10, 0). A nematic transformation around 280 K is identified through Landau-deGennes theory, with molecule aligning along tube axis in extended conformationsComment: 19 pages, 7 figure2, submitted to journa

    Isotropic-nematic phase transition in suspensions of filamentous virus and the neutral polymer Dextran

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    We present an experimental study of the isotropic-nematic phase transition in an aqueous mixture of charged semi-flexible rods (fd virus) and neutral polymer (Dextran). A complete phase diagram is measured as a function of ionic strength and polymer molecular weight. At high ionic strength we find that adding polymer widens the isotropic-nematic coexistence region with polymers preferentially partitioning into the isotropic phase, while at low ionic strength the added polymer has no effect on the phase transition. The nematic order parameter is determined from birefringence measurements and is found to be independent of polymer concentration (or equivalently the strength of attraction). The experimental results are compared with the existing theoretical predictions for the isotropic-nematic transition in rods with attractive interactions.Comment: 8 Figures. To be published in Phys. Rev. E. For more information see http://www.elsie.brandeis.ed

    A origem das parcerias público-privada na governança global da educação

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    Durante a última década, a globalização da governança educacional por meio de parcerias público-privadas (PPP) tem gerado considerável debate quanto ao seu significado, propósito, status e resultados. Este debate é particularmente aquecido no setor da educação por causa da ampla aceitação da educação como atividade complexa, social e política que deve permanecer, em grande parte, se não totalmente, no setor público, servindo a interesses públicos. O artigo analisa a rápida expansão das parcerias público-privadas em educação (PPPE) articulada à introdução de regras de mercado no setor. Neste estudo nos concentramos sobre o papel de uma rede de desenvolvimento global, fundamental na globalização de um tipo particular de PPPE, indicando que a ideia de PPP encaixa-se em um projeto mais amplo de reconstituição da educação pública no âmbito do setor de serviços, a ser governada como parte da construção de uma sociedade de mercado.Over the past decade, the globalization and governing of education through Public Private Partnerships (PPPs) have generated considerable debate as to their meaning, purpose, status and outcomes. This debate is particularly heated in the education sector because of the widely-held view that education is a complex social and political activity that should remain largely, if not wholly, in the public sector serving public interests. The article analyses the rapid expansion of Education Public Private Partnerships (EPPPs) and the associated introduction of market rules into the education sector. We focus on the role of a key global development network in globalizing a particular kind of ePPPs, and show that the EPPP idea fi ts into a wider project of reconstituting public education as an education services industry to be governed as part of the construction of a market society

    Adsorbate-induced curvature and stiffening of graphene

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    The adsorption of the alkane tetratetracontane (TTC, C44H90) on graphene induces the formation of a curved surface stabilized by a gain in adsorption energy. This effect arises from a curvature-dependent variation of a moiré pattern due to the mismatch of the carbon−carbon separation in the adsorbed molecule and the period of graphene. The effect is observed when graphene is transferred onto a deformable substrate, which in our case is the interface between water layers adsorbed on mica and an organic solvent, but is not observed on more rigid substrates such as boron nitride. Our results show that molecular adsorption can be influenced by substrate curvature, provide an example of two-dimensional molecular self-assembly on a soft, responsive interface, and demonstrate that the mechanical properties of graphene may be modified by molecular adsorption, which is of relevance to nanomechanical systems, electronics, and membrane technology

    Caspase-3 Mediates the Pathogenic Effect of \u3cem\u3e Yersinia pestis \u3c/em\u3e YopM in Liver of C57BL/6 Mice and Contributes to YopM\u27s Function in Spleen

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    The virulence protein YopM of the plague bacterium Yersinia pestis has different dominant effects in liver and spleen. Previous studies focused on spleen, where YopM inhibits accumulation of inflammatory dendritic cells. In the present study we focused on liver, where PMN function may be directly undermined by YopM without changes in inflammatory cell numbers in the initial days of infection, and foci of inflammation are easily identified. Mice were infected with parent and ΔyopM-1 Y. pestis KIM5, and effects of YopM were assessed by immunohistochemistry and determinations of bacterial viable numbers in organs. The bacteria were found associated with myeloid cells in foci of inflammation and in liver sinusoids. A new in-vivo phenotype of YopM was revealed: death of inflammatory cells, evidenced by TUNEL staining beginning at d 1 of infection. Based on distributions of Ly6G+, F4/80+, and iNOS+ cells within foci, the cells that were killed could have included both PMNs and macrophages. By 2 d post-infection, YopM had no effect on distribution of these cells, but by 3 d cellular decomposition had outstripped acute inflammation in foci due to parent Y. pestis, while foci due to the Δ-1yopM strain still contained many inflammatory cells. The destruction depended on the presence of both PMNs in the mice and YopM in the bacteria. In mice that lacked the apoptosis mediator caspase-3 the infection dynamics were novel: the parent Y. pestis was limited in growth comparably to the ΔyopM-1 strain in liver, and in spleen a partial growth limitation for parent Y. pestis was seen. This result identified caspase-3 as a co-factor or effector in YopM\u27s action and supports the hypothesis that in liver YopM\u27s main pathogenic effect is mediated by caspase-3 to cause apoptosis of PMNs

    RNA-Seq of Human Neurons Derived from iPS Cells Reveals Candidate Long Non-Coding RNAs Involved in Neurogenesis and Neuropsychiatric Disorders

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    Genome-wide expression analysis using next generation sequencing (RNA-Seq) provides an opportunity for in-depth molecular profiling of fundamental biological processes, such as cellular differentiation and malignant transformation. Differentiating human neurons derived from induced pluripotent stem cells (iPSCs) provide an ideal system for RNA-Seq since defective neurogenesis caused by abnormalities in transcription factors, DNA methylation, and chromatin modifiers lie at the heart of some neuropsychiatric disorders. As a preliminary step towards applying next generation sequencing using neurons derived from patient-specific iPSCs, we have carried out an RNA-Seq analysis on control human neurons. Dramatic changes in the expression of coding genes, long non-coding RNAs (lncRNAs), pseudogenes, and splice isoforms were seen during the transition from pluripotent stem cells to early differentiating neurons. A number of genes that undergo radical changes in expression during this transition include candidates for schizophrenia (SZ), bipolar disorder (BD) and autism spectrum disorders (ASD) that function as transcription factors and chromatin modifiers, such as POU3F2 and ZNF804A, and genes coding for cell adhesion proteins implicated in these conditions including NRXN1 and NLGN1. In addition, a number of novel lncRNAs were found to undergo dramatic changes in expression, one of which is HOTAIRM1, a regulator of several HOXA genes during myelopoiesis. The increase we observed in differentiating neurons suggests a role in neurogenesis as well. Finally, several lncRNAs that map near SNPs associated with SZ in genome wide association studies also increase during neuronal differentiation, suggesting that these novel transcripts may be abnormally regulated in a subgroup of patients

    Effects of macromolecular crowding on intracellular diffusion from a single particle perspective

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    Compared to biochemical reactions taking place in relatively well-defined aqueous solutions in vitro, the corresponding reactions happening in vivo occur in extremely complex environments containing only 60–70% water by volume, with the remainder consisting of an undefined array of bio-molecules. In a biological setting, such extremely complex and volume-occupied solution environments are termed ‘crowded’. Through a range of intermolecular forces and pseudo-forces, this complex background environment may cause biochemical reactions to behave differently to their in vitro counterparts. In this review, we seek to highlight how the complex background environment of the cell can affect the diffusion of substances within it. Engaging the subject from the perspective of a single particle’s motion, we place the focus of our review on two areas: (1) experimental procedures for conducting single particle tracking experiments within cells along with methods for extracting information from these experiments; (2) theoretical factors affecting the translational diffusion of single molecules within crowded two-dimensional membrane and three-dimensional solution environments. We conclude by discussing a number of recent publications relating to intracellular diffusion in light of the reviewed material
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