1,385 research outputs found

    Sum-frequency generation and photon-pair creation in AlGaAs nano-scale resonators

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    ©2017 IEEE We demonstrate experimentally sum-frequency generation in AlGaAs nano-resonators, establishing a quantum-classical correspondence with spontaneous parametric down-conversion. We predict that AlGaAs nano-resonators can be utilized as high-rate sources of photon pairs with non-classical correlations

    Characterisation of feline renal cortical fibroblast cultures and their transcriptional response to transforming growth factor beta 1

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    Chronic kidney disease (CKD) is common in geriatric cats, and the most prevalent pathology is chronic tubulointerstitial inflammation and fibrosis. The cell type predominantly responsible for the production of extra-cellular matrix in renal fibrosis is the myofibroblast, and fibroblast to myofibroblast differentiation is probably a crucial event. The cytokine TGF-β1 is reportedly the most important regulator of myofibroblastic differentiation in other species. The aim of this study was to isolate and characterise renal fibroblasts from cadaverous kidney tissue of cats with and without CKD, and to investigate the transcriptional response to TGF-β1

    Microglia promote glioblastoma via mTOR-mediated immunosuppression of the tumour microenvironment

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    Tumour-associated microglia/macrophages (TAM) are the most numerous non-neoplastic populations in the tumour microenvironment in glioblastoma multiforme (GBM), the most common malignant brain tumour in adulthood. The mTOR pathway, an important regulator of cell survival/proliferation, is upregulated in GBM, but little is known about the potential role of this pathway in TAM. Here, we show that GBM-initiating cells induce mTOR signalling in the microglia but not bone marrow-derived macrophages in both in vitro and in vivo GBM mouse models. mTOR-dependent regulation of STAT3 and NF-jB activity promotes an immunosuppressive microglial phenotype. This hinders effector T-cell infiltration, proliferation and immune reactivity, thereby contributing to tumour immune evasion and promoting tumour growth in mouse models. The translational value of our results is demonstrated in whole transcriptome datasets of human GBM and in a novel in vitro model, whereby expandedpotential stem cells (EPSC)-derived microglia-like cells are conditioned by syngeneic patient-derived GBM-initiating cells. These results raise the possibility that microglia could be the primary target of mTOR inhibition, rather than the intrinsic tumour cells in GB

    The effect of sculpting planets on the steepness of debris-disc inner edges

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    This is the final version. Available from Oxford University Press via the DOI in this record. DATA AVAILABILITY: The data underlying this article will be shared upon reasonable request to the corresponding author.Debris discs are our best means to probe the outer regions of planetary systems. Many studies assume that planets lie at the inner edges of debris discs, akin to Neptune and the Kuiper Belt, and use the disc morphologies to constrain those otherwise-undetectable planets. However, this produces a degeneracy in planet mass and semimajor axis. We investigate the effect of a sculpting planet on the radial surface-density profile at the disc inner edge, and show that this degeneracy can be broken by considering the steepness of the edge profile. Like previous studies, we show that a planet on a circular orbit ejects unstable debris and excites surviving material through mean-motion resonances. For a non-migrating, circular-orbit planet, in the case where collisions are negligible, the steepness of the disc inner edge depends on the planet-to-star mass ratio and the initial-disc excitation level. We provide a simple analytic model to infer planet properties from the steepness of ALMA-resolved disc edges. We also perform a collisional analysis, showing that a purely planet-sculpted disc would be distinguishable from a purely collisional disc and that, whilst collisions flatten planet-sculpted edges, they are unlikely to fully erase a planet’s signature. Finally, we apply our results to ALMA-resolved debris discs and show that, whilst many inner edges are too steep to be explained by collisions alone, they are too flat to arise through completed sculpting by non-migrating, circular-orbit planets. We discuss implications of this for the architectures, histories, and dynamics in the outer regions of planetary systems.Deutsche Forschungsgemeinschaft (DFG)Deutsche Forschungsgemeinschaft (DFG)Deutsche Forschungsgemeinschaft (DFG)Deutsche Forschungsgemeinschaft (DFG)European Union’s Horizon 2020Marie Skłodowska-Curie grantRoyal SocietyAlexander von Humboldt FoundationMinistry of Science, Technological Development, and Innovations of the Republic of SerbiaWarwick Prize Fellowshi

    Nuclear receptors in vascular biology

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    Nuclear receptors sense a wide range of steroids and hormones (estrogens, progesterone, androgens, glucocorticoid, and mineralocorticoid), vitamins (A and D), lipid metabolites, carbohydrates, and xenobiotics. In response to these diverse but critically important mediators, nuclear receptors regulate the homeostatic control of lipids, carbohydrate, cholesterol, and xenobiotic drug metabolism, inflammation, cell differentiation and development, including vascular development. The nuclear receptor family is one of the most important groups of signaling molecules in the body and as such represent some of the most important established and emerging clinical and therapeutic targets. This review will highlight some of the recent trends in nuclear receptor biology related to vascular biology

    G-protein inwardly rectifying potassium channel 1 (GIRK 1) gene expression correlates with tumor progression in non-small cell lung cancer

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    BACKGROUND: G-protein inwardly rectifying potassium channel 1 (GIRK1) is thought to play a role in cell proliferation in cancer, and GIRK1 gene expression level may define a more aggressive phenotype. We detected GIRK1 expression in tissue specimens from patients with non-small cell lung cancers (NSCLCs) and assessed their clinical characteristics. METHODS: Using reverse transcription-polymerase chain reaction (RT-PCR) analyses, we quantified the expression of GIRK1 in 72 patients with NSCLCs to investigate the relationship between GIRK1 expression and clinicopathologic factors and prognosis. RESULTS: In 72 NSCLC patients, 50 (69%) samples were evaluated as having high GIRK1 gene expression, and 22 (31%) were evaluated as having low GIRK1 gene expression. GIRK1 gene expression was significantly associated with lymph node metastasis, stage (p = 0.0194 for lymph node metastasis; p = 0.0207 for stage). The overall and stage I survival rates for patients with high GIRK1 gene expressed tumors was significantly worse than for those individuals whose tumors had low GIRK1 expression (p = 0.0004 for the overall group; p = 0.0376 for stage I). CONCLUSIONS: These data indicate that GIRK1 may contribute to tumor progression and GIRK1 gene expression can serve as a useful prognostic marker in the overall and stage I NSCLCs

    Visual laterality in dolphins: importance of the familiarity of stimuli

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    <p>Abstract</p> <p>Background</p> <p>Many studies of cerebral asymmetries in different species lead, on the one hand, to a better understanding of the functions of each cerebral hemisphere and, on the other hand, to develop an evolutionary history of hemispheric laterality. Our animal model is particularly interesting because of its original evolutionary path, i.e. return to aquatic life after a terrestrial phase. The rare reports concerning visual laterality of marine mammals investigated mainly discrimination processes. As dolphins are migrant species they are confronted to a changing environment. Being able to categorize new versus familiar objects would allow dolphins a rapid adaptation to novel environments. Visual laterality could be a prerequisite to this adaptability. To date, no study, to our knowledge, has analyzed the environmental factors that could influence their visual laterality.</p> <p>Results</p> <p>We investigated visual laterality expressed spontaneously at the water surface by a group of five common bottlenose dolphins (<it>Tursiops truncatus</it>) in response to various stimuli. The stimuli presented ranged from very familiar objects (known and manipulated previously) to familiar objects (known but never manipulated) to unfamiliar objects (unknown, never seen previously). At the group level, dolphins used their left eye to observe very familiar objects and their right eye to observe unfamiliar objects. However, eyes are used indifferently to observe familiar objects with intermediate valence.</p> <p>Conclusion</p> <p>Our results suggest different visual cerebral processes based either on the global shape of well-known objects or on local details of unknown objects. Moreover, the manipulation of an object appears necessary for these dolphins to construct a global representation of an object enabling its immediate categorization for subsequent use. Our experimental results pointed out some cognitive capacities of dolphins which might be crucial for their wild life given their fission-fusion social system and migratory behaviour.</p

    Comparative epigenetic analysis of tumour initiating cells and syngeneic EPSC-derived neural stem cells in glioblastoma

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    Epigenetic mechanisms which play an essential role in normal developmental processes, such as self-renewal and fate specification of neural stem cells (NSC) are also responsible for some of the changes in the glioblastoma (GBM) genome. Here we develop a strategy to compare the epigenetic and transcriptional make-up of primary GBM cells (GIC) with patient-matched expanded potential stem cell (EPSC)-derived NSC (iNSC). Using a comparative analysis of the transcriptome of syngeneic GIC/iNSC pairs, we identify a glycosaminoglycan (GAG)-mediated mechanism of recruitment of regulatory T cells (Tregs) in GBM. Integrated analysis of the transcriptome and DNA methylome of GBM cells identifies druggable target genes and patient-specific prediction of drug response in primary GIC cultures, which is validated in 3D and in vivo models. Taken together, we provide a proof of principle that this experimental pipeline has the potential to identify patient-specific disease mechanisms and druggable targets in GBM
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