4,153 research outputs found

    Mono- and Cocultures of Bronchial and Alveolar Epithelial Cells Respond Differently to Proinflammatory Stimuli and Their Modulation by Salbutamol and Budesonide

    Full text link
    © 2015 American Chemical Society. The aim of this study was to investigate the changes in transport and effectiveness of salbutamol sulfate (SAL) and budesonide (BD) following stimulation with transforming growth factor-β (TGF-β) in mono- and coculture models of bronchial and alveolar epithelium. Primary bronchial and alveolar epithelial cells, grown at air interface on filters, either as monocultures or in coculture with airway smooth muscle cells or alveolar macrophages, respectively, were stimulated with TGF-β. The biological response was modulated by depositing aerosolized SAL and BD on bronchial and alveolar models, respectively. Barrier integrity, permeability to fluorescein-Na, transport of the deposited drug, and the pharmacological response to SAL (cAMP and IL-8 levels) or BD (IL-6 and -8 levels) were measured. While stimulation with TGF-β did not have any significant effect on the transepithelial electrical resistance and permeability to fluorescein-Na in mono- and coculture models, transport of SAL and BD were affected in cultures from some of the patients (6 out of 12 for bronchial and 2 out of 4 for alveolar cells). The bronchial coculture showed a better responsiveness to SAL in terms of cAMP release than the monoculture. In contrast, the difference between alveolar mono- and cocultures to TGF-β mediated interleukin release and its modulation by BD was less pronounced. Our data point to intrinsic differences in the transport of, and responsiveness to, SAL and BD when epithelial cell cultures originate from different patients. Moreover, if the biological responses (e.g., IL-8, cAMP) involve communication between different cell types, coculture models are more relevant to measure such effects than monocultures

    Efficient immortalization of primary nasopharyngeal epithelial cells for EBV infection study.

    Get PDF
    Nasopharyngeal carcinoma (NPC) is common among southern Chinese including the ethnic Cantonese population living in Hong Kong. Epstein-Barr virus (EBV) infection is detected in all undifferentiated type of NPC in this endemic region. Establishment of stable and latent EBV infection in premalignant nasopharyngeal epithelial cells is an early event in NPC development and may contribute to its pathogenesis. Immortalized primary nasopharyngeal epithelial cells represent an important tool for investigation of EBV infection and its tumorigenic potential in this special type of epithelial cells. However, the limited availability and small sizes of nasopharyngeal biopsies have seriously restricted the establishment of primary nasopharyngeal epithelial cells for immortalization. A reliable and effective method to immortalize primary nasopharyngeal epithelial cells will provide unrestricted materials for EBV infection studies. An earlier study has reported that Bmi-1 expression could immortalize primary nasopharyngeal epithelial cells. However, its efficiency and actions in immortalization have not been fully characterized. Our studies showed that Bmi-1 expression alone has limited ability to immortalize primary nasopharyngeal epithelial cells and additional events are often required for its immortalization action. We have identified some of the key events associated with the immortalization of primary nasopharyngeal epithelial cells. Efficient immortalization of nasopharyngeal epithelial cells could be reproducibly and efficiently achieved by the combined actions of Bmi-1 expression, activation of telomerase and silencing of p16 gene. Activation of MAPK signaling and gene expression downstream of Bmi-1 were detected in the immortalized nasopharyngeal epithelial cells and may play a role in immortalization. Furthermore, these newly immortalized nasopharyngeal epithelial cells are susceptible to EBV infection and supported a type II latent EBV infection program characteristic of EBV-infected nasopharyngeal carcinoma. The establishment of an efficient method to immortalize primary nasopharyngeal epithelial cells will facilitate the investigation into the role of EBV infection in pathogenesis of nasopharyngeal carcinoma.published_or_final_versio

    Al8Mn5 particle settling and interactions with oxide films in liquid AZ91 magnesium alloys

    Get PDF
    Al8Mn5 particles form as primary solidification phases in Mg-Al-based alloys and are important for ensuring adequate corrosion resistance. However, excessive Al8Mn5 formation above the α-Mg liquidus temperature can lead to sludge formation, and the clustering of Al8Mn5 particles on oxide films can generate deleterious casting defects. Here, we use analytical SEM and real-time synchrotron x-ray radiography to study Al8Mn5 particle settling, the formation of a sludge layer, and the mechanism of Al8Mn5 clustering on oxides in AZ91 containing two Fe levels. It is shown that settling Al8Mn5 can become trapped in entrained oxide and that new Al8Mn5 particles also seem to nucleate on oxide films. On cooling, these Al8Mn5 particles continue to grow, creating large Al8Mn5 clusters

    Al8Mn5 in High-Pressure Die Cast AZ91: Twinning, Morphology and Size Distributions

    Get PDF
    EPSRC (UK); National Natural Science Foundation of China

    Optical one-way quantum computing with a simulated valence-bond solid

    Full text link
    One-way quantum computation proceeds by sequentially measuring individual spins (qubits) in an entangled many-spin resource state. It remains a challenge, however, to efficiently produce such resource states. Is it possible to reduce the task of generating these states to simply cooling a quantum many-body system to its ground state? Cluster states, the canonical resource for one-way quantum computing, do not naturally occur as ground states of physical systems. This led to a significant effort to identify alternative resource states that appear as ground states in spin lattices. An appealing candidate is a valence-bond-solid state described by Affleck, Kennedy, Lieb, and Tasaki (AKLT). It is the unique, gapped ground state for a two-body Hamiltonian on a spin-1 chain, and can be used as a resource for one-way quantum computing. Here, we experimentally generate a photonic AKLT state and use it to implement single-qubit quantum logic gates.Comment: 11 pages, 4 figures, 8 tables - added one referenc

    Cyclin D1 overexpression supports stable EBV infection in nasopharyngeal epithelial cells

    Get PDF
    Undifferentiated nasopharyngeal carcinomas (NPCs) are commonly present with latent EBV infection. However, events regulating EBV infection at early stages of the disease and the role of EBV in disease pathogenesis are largely undefined. Genetic alterations leading to activation of cyclin D1 signaling in premalignant nasopharyngeal epithelial (NPE) cells have been postulated to predispose cells to EBV infection. We previously reported that loss of p16, a negative regulator of cyclin D1 signaling, is a frequent feature of NPC tumors. Here, we report that early premalignant lesions of nasopharyngeal epithelium overexpress cyclin D1. Furthermore, overexpression of cyclin D1 is closely associated with EBV infection. Therefore we investigated the potential role of cyclin D1 overexpression in dysplastic NPE cells in vitro. In human telomerase reverse transcriptase-immortalized NPE cells, overexpression of cyclin D1 or a p16-resistant form of CDK4 (CDK4(R24C)) suppressed differentiation. This suppression may have implications for the close association of EBV infection with undifferentiated NPC. In these in vitro models, we found that cellular growth arrest and senescence occurred in EBV-infected cell populations immediately after infection. Nevertheless, overexpression of cyclin D1 or a p16-resistant form of CDK4 or knockdown of p16 in the human telomerase reverse transcriptase-immortalized NPE cell lines could counteract the EBV-induced growth arrest and senescence. We conclude that dysregulated expression of cyclin D1 in NPE cells may contribute to NPC pathogenesis by enabling persistent infection of EBV.published_or_final_versio
    corecore