102 research outputs found

    The life of Metis: cunning maternal interventions

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    This paper charts the different and co-existent uses of the Greek myth and concept of Metis for feminist philosophy. I show how the move from using the myth of Metis to an engagement with the marginalised ancient Greek concept of cunning intelligence (metis) is significant in addressing problems of agency and political action in contemporary feminist debates. The paper addresses the concept of metis cunning intelligence in relation to the maternal and argues for a theory of metis charcterised by a double action, and finally links this approach to recent ideas in Deleuzian feminist theory

    Gastrointestinal nematode-derived antigens alter colorectal cancer cell proliferation and migration through regulation of cell cycle and epithelial-mesenchymal transition proteins

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    As the global incidences of colorectal cancer rises, there is a growing importance in understanding the interaction between external factors, such as common infections, on the initiation and progression of this disease. While certain helminth infections have been shown to alter the severity and risk of developing colitis-associated colorectal cancer, whether these parasites can directly affect colorectal cancer progression is unknown. Here, we made use of murine and human colorectal cancer cell lines to demonstrate that exposure to antigens derived from the gastrointestinal nematode Heligmosomoides polygyrus significantly reduced colorectal cancer cell proliferation in vitro. Using a range of approaches, we demonstrate that antigen-dependent reductions in cancer cell proliferation and viability are associated with increased expression of the critical cell cycle regulators p53 and p21. Interestingly, H. polygyrus-derived antigens significantly increased murine colorectal cancer cell migration, which was associated with an increased expression of the adherens junction protein β-catenin, whereas the opposite was true for human colorectal cancer cells. Together, these findings demonstrate that antigens derived from a gastrointestinal nematode can significantly alter colorectal cancer cell behavior. Further in-depth analysis may reveal novel candidates for targeting and treating late-stage cancer

    Confinement and edge effects on atomic collapse in graphene nanoribbons

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    Atomic collapse in graphene nanoribbons behaves in a fundamentally different way as compared to monolayer graphene, due to the presence of multiple energy bands and the effect of edges. For armchair nanoribbons we find that bound states gradually transform into atomic collapse states with increasing impurity charge. This is very different in zig-zag nanoribbons where multiple quasi-one-dimensional \emph{bound states} are found that originates from the zero energy zig-zag edge states. They are a consequence of the flat band and the electron distribution of these bound states exhibits two peaks. The lowest energy edge state transforms from a bound state into an atomic collapse resonance and shows a distinct relocalization from the edge to the impurity position with increasing impurity charge

    Mobike’s Bike-Share Battle in India

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    Mobike’s Bike-Share Battle in India: An International Marketing Case Study Amber Cranston, Savannah Rubio, Sam Kroll, Austin Tudor, Eric Jacobs, Evan Coulter, and Miguel Pereira Abstract Mobike, the world’s first cashless and station-free bicycle service, launched in Shanghai in 2016 and now operates in over 19 countries including India (Khanna, 2017). Growing urbanization has led to increasing traffic congestion and pollution in most large cities around the world. Recently, there have been increasing calls for more sustainable transportation methods and one solution that is becoming popular is bike-sharing. The global bike ride-sharing market is projected to be worth around 8.6billionin2019withacompoundannualgrowthrate(CAGR)ofabout6.58.6 billion in 2019 with a compound annual growth rate (CAGR) of about 6.5% by 2023 (Wagner, 2018). Mobike aims to reduce congestion, create a greener environment, solve short-distance connectivity problems, and improve the quality of life for everyone with efficient and inexpensive alternative transportation methods. Mobike entered India in 2018, a seemingly attractive market given the low ownership of vehicles and the many transportation and traffic problems. With 30% of India’s 1.2 billion population living in dense urban areas, massive traffic congestion was costing cities roughly 22 billion a year (Tandon, 2018). Despite the need for short and mid-distance mobility in urban areas in India, Mobike is facing major challenges to adoption such as competition, sustainability issues due to the littering of broken bike parts, government regulations, etc. Moreover, Indian consumers perceive biking to be for the poor (Chen, 2018). This case study examines the economic and cultural context of the bike share market in India to propose changes in Mobike’s marketing strategy to help it succeed. Keywords: Bike ridesharing, India, Marketing Strategy, Sustainability, Connectivity, Transportation, Quality, Cashless, Station-free, Emerging Markets, International Marketing, Case Study. Note: References available on reques

    Loss of Nmp4 optimizes osteogenic metabolism and secretion to enhance bone quality

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    A goal of osteoporosis therapy is to restore lost bone with structurally sound tissue. Mice lacking the transcription factor Nuclear Matrix Protein 4 (Nmp4, Zfp384, Ciz, ZNF384) respond to several classes of osteoporosis drugs with enhanced bone formation compared to wild type (WT) animals. Nmp4-/- mesenchymal stem/progenitor cells (MSPCs) exhibit an accelerated and enhanced mineralization during osteoblast differentiation. To address the mechanisms underlying this hyper-anabolic phenotype, we carried out RNA-sequencing and molecular and cellular analyses of WT and Nmp4-/- MSPCs during osteogenesis to define pathways and mechanisms associated with elevated matrix production. We determined that Nmp4 has a broad impact on the transcriptome during osteogenic differentiation, contributing to the expression of over 5,000 genes. Phenotypic anchoring of transcriptional data was performed for the hypothesis-testing arm through analysis of cell metabolism, protein synthesis and secretion, and bone material properties. Mechanistic studies confirmed that Nmp4-/- MSPCs exhibited an enhanced capacity for glycolytic conversion- a key step in bone anabolism. Nmp4-/- cells showed elevated collagen translation and secretion. Expression of matrix genes that contribute to bone material-level mechanical properties were elevated in Nmp4-/- cells, an observation that was supported by biomechanical testing of bone samples from Nmp4-/- and WT mice. We conclude that loss of Nmp4 increases the magnitude of glycolysis upon the metabolic switch, which fuels the conversion of the osteoblast into a super-secretor of matrix resulting in more bone with improvements in intrinsic quality

    Site-specific vibrational dynamics of the CD3 zeta membrane peptide using heterodyned two-dimensional infrared photon echo spectroscopy

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    Heterodyned two-dimensional infrared (2D IR) spectroscopy has been used to study the amide I vibrational dynamics of a 27-residue peptide in lipid vesicles that encompasses the transmembrane domain of the T-cell receptor CD3zeta. Using 1-C-13=O-18 isotope labeling, the amide I mode of the 49-Leucine residue was spectroscopically isolated and the homogeneous and inhomogeneous linewidths of this mode were measured by fitting the 2D IR spectrum collected with a photon echo pulse sequence. The pure dephasing and inhomogeneous linewidths are 2 and 32 cm(-1), respectively. The population relaxation time of the amide I band was measured with a transient grating, and it contributes 9 cm-1 to the linewidth. Comparison of the 49-Leucine amide I mode and the amide I band of the entire CD3zeta peptide reveals that the vibrational dynamics are not uniform along the length of the peptide. Possible origins for the large amount of inhomogeneity present at the 49-Leucine site are discussed. (C) 2004 American Institute of Physics

    Taenia larvae possess distinct acetylcholinesterase profiles with implications for host cholinergic signalling

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    Larvae of the cestodes Taenia solium and Taenia crassiceps infect the central nervous system of humans. Taenia solium larvae in the brain cause neurocysticercosis, the leading cause of adult-acquired epilepsy worldwide. Relatively little is understood about how cestode-derived products modulate host neural and immune signalling. Acetylcholinesterases, a class of enzyme that breaks down acetylcholine, are produced by a host of parasitic worms to aid their survival in the host. Acetylcholine is an important signalling molecule in both the human nervous and immune systems, with powerful modulatory effects on the excitability of cortical networks. Therefore, it is important to establish whether cestode derived acetylcholinesterases may alter host neuronal cholinergic signalling. Here we make use of multiple techniques to profile acetylcholinesterase activity in different extracts of both Taenia crassiceps and Taenia solium larvae. We find that the larvae of both species contain substantial acetylcholinesterase activity. However, acetylcholinesterase activity is lower in Taenia solium as compared to Taenia crassiceps larvae. Further, whilst we observed acetylcholinesterase activity in all fractions of Taenia crassiceps larvae, including on the membrane surface and in the excreted/secreted extracts, we could not identify acetylcholinesterases on the membrane surface or in the excreted/secreted extracts of Taenia solium larvae. Bioinformatic analysis revealed conservation of the functional protein domains in the Taenia solium acetylcholinesterases, when compared to the homologous human sequence. Finally, using whole-cell patch clamp recordings in rat hippocampal brain slice cultures, we demonstrate that Taenia larval derived acetylcholinesterases can break down acetylcholine at a concentration which induces changes in neuronal signalling. Together, these findings highlight the possibility that Taenia larval acetylcholinesterases can interfere with cholinergic signalling in the host, potentially contributing to pathogenesis in neurocysticercosis
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