519 research outputs found

    Viperin interacts with PEX19 to mediate peroxisomal augmentation of the innate antiviral response.

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    Peroxisomes are recognized as significant platforms for the activation of antiviral innate immunity where stimulation of the key adapter molecule mitochondrial antiviral signaling protein (MAVS) within the RIG-I like receptor (RLR) pathway culminates in the up-regulation of hundreds of ISGs, some of which drive augmentation of multiple innate sensing pathways. However, whether ISGs can augment peroxisome-driven RLR signaling is currently unknown. Using a proteomics-based screening approach, we identified Pex19 as a binding partner of the ISG viperin. Viperin colocalized with numerous peroxisomal proteins and its interaction with Pex19 was in close association with lipid droplets, another emerging innate signaling platform. Augmentation of the RLR pathway by viperin was lost when Pex19 expression was reduced. Expression of organelle-specific MAVS demonstrated that viperin requires both mitochondria and peroxisome MAVS for optimal induction of IFN-β. These results suggest that viperin is required to enhance the antiviral cellular response with a possible role to position the peroxisome at the mitochondrial/MAM MAVS signaling synapse, furthering our understanding of the importance of multiple organelles driving the innate immune response against viral infection

    Plasmalemmal Vesicle Associated Protein-1 (PV-1) is a marker of blood-brain barrier disruption in rodent models

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    <p>Abstract</p> <p>Background</p> <p><it>Plasmalemmal vesicle associated protein-1 </it>(<it>PV-1</it>) is selectively expressed in human brain microvascular endothelial cells derived from clinical specimens of primary and secondary malignant brain tumors, cerebral ischemia, and other central nervous system (CNS) diseases associated with blood-brain barrier breakdown. In this study, we characterize the murine CNS expression pattern of <it>PV-1 </it>to determine whether localized <it>PV-1 </it>induction is conserved across species and disease state.</p> <p>Results</p> <p>We demonstrate that <it>PV-1 </it>is selectively upregulated in mouse blood vessels recruited by brain tumor xenografts at the RNA and protein levels, but is not detected in non-neoplastic brain. Additionally, <it>PV-1 </it>is induced in a mouse model of acute ischemia. Expression is confined to the cerebovasculature within the region of infarct and is temporally regulated.</p> <p>Conclusion</p> <p>Our results confirm that <it>PV-1 </it>is preferentially induced in the endothelium of mouse brain tumors and acute ischemic brain tissue and corresponds to blood-brain barrier disruption in a fashion analogous to human patients. Characterization of <it>PV-1 </it>expression in mouse brain is the first step towards development of rodent models for testing anti-edema and anti-angiogenesis therapeutic strategies based on this molecule.</p

    Thermal Imaging of Aerospace Battery Cells

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    Surface Thermal Profiles of Eagle Picher rabbit-ear 50Ah NiH2 and of Saft 40 Ah Li-ion cylindrical cells have been studied using ThermCAM S60 FLIR Systems. Popping Phenomenon in NiH2 cell is demonstrated Temperature gradient in NiH2 is slightly higher than normally considered, for example. Middle of stack to top or bottom is about 12.9 C compared to <7 C (may be due to passive cooling). Less than 1 C thermal gradient on the Li-Ion cell vessel surface. Significantly lower heat generation in Li-Ion cell compared to NiH2 cell. -May be due to a favorable charge method used for Li-Ion cell

    Viperin is an important host restriction factor in control of Zika virus infection

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    Published online 30 June 2017Zika virus (ZIKV) infection has emerged as a global health threat and infection of pregnant women causes intrauterine growth restriction, spontaneous abortion and microcephaly in newborns. Here we show using biologically relevant cells of neural and placental origin that following ZIKV infection, there is attenuation of the cellular innate response characterised by reduced expression of IFN-β and associated interferon stimulated genes (ISGs). One such ISG is viperin that has well documented antiviral activity against a wide range of viruses. Expression of viperin in cultured cells resulted in significant impairment of ZIKV replication, while MEFs derived from CRISPR/Cas9 derived viperin-/- mice replicated ZIKV to higher titers compared to their WT counterparts. These results suggest that ZIKV can attenuate ISG expression to avoid the cellular antiviral innate response, thus allowing the virus to replicate unchecked. Moreover, we have identified that the ISG viperin has significant anti-ZIKV activity. Further understanding of how ZIKV perturbs the ISG response and the molecular mechanisms utilised by viperin to suppress ZIKV replication will aid in our understanding of ZIKV biology, pathogenesis and possible design of novel antiviral strategies.Kylie H. Van der Hoek, Nicholas S. Eyre, Byron Shue, Onruedee Khantisitthiporn, Kittirat Glab-Ampi, Jillian M. Carr, Matthew J. Gartner, Lachlan A. Jolly, Paul Q. Thomas, Fatwa Adikusuma, Tanja Jankovic-Karasoulos, Claire T. Roberts, Karla J. Helbig and Michael R. Bear

    Individual Rights, Economic Transactions, and Recognition: A Legal Approach to Social Economics

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    Modernity brought the idea of individual property rights as a com- plex phenomenon. However, economics adopted a simplistic view of property as a fundamental institution, understating the complex interaction of different rights and obligations that frame the legal environment of economic processes with an insufficiently elaborated tool. Here, a more elaborate view of legal elements will be propose

    Disappearance of plasmaspheric hiss following interplanetary shock

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    Abstract Plasmaspheric hiss is one of the important plasma waves controlling radiation belt dynamics. Its spatiotemporal distribution and generation mechanism are presently the object of active research. We here give the first report on the shock-induced disappearance of plasmaspheric hiss observed by the Van Allen Probes on 8 October 2013. This special event exhibits the dramatic variability of plasmaspheric hiss and provides a good opportunity to test its generation mechanisms. The origination of plasmaspheric hiss from plasmatrough chorus is suggested to be an appropriate prerequisite to explain this event. The shock increased the suprathermal electron fluxes, and then the enhanced Landau damping promptly prevented chorus waves from entering the plasmasphere. Subsequently, the shrinking magnetopause removed the source electrons for chorus, contributing significantly to the several-hours-long disappearance of plasmaspheric hiss

    Non-ideal climate justice

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    Based on three recently published books on climate justice, this article reviews the field of climate ethics in light of developments of international climate politics. The central problem addressed is how idealised normative theories can be relevant to the political process of negotiating a just distribution of the costs and benefits of mitigating climate change. I distinguish three possible responses, that is, three kinds of non-ideal theories of climate justice: focused on (1) the injustice of some agents not doing their part; (2) the policy process and aiming to be realistic; and (3) grievances related to the transition to a clean-energy economy. The methodological discussion underpinning each response is innovative and should be of interest more generally, even though it is still underdeveloped. The practical upshot, however, is unclear: even non-ideal climate justice may be too disconnected from the fast-moving and messy climate circus

    Evolving Small-Cell Communications towards Mobile-over-FTTx Networks

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    International audienceSmall cell techniques are recognized as the best way to deliver high capacity for broadband cellular communications. Femtocell and distributed antenna systems (DAS) are important components in the overall small cell story, but are not the complete solution. They have major disadvantages of very limited cooperation capability and expensive deployment cost, respectively. In this article, we propose a novel mobile-over-FTTx (MoF) network architecture, where a fiber-to-the-x (FTTx) network is enhanced as an integrated rather than a simple backhauling component of a new mobile network delivering low-cost and powerful small cell solutions. In part, the MoF architecture combines the advantages of femtocell and DAS, while overcoming their disadvantages. Implementation challenges and potential solutions are discussed. Simulation results are presented and demonstrate the strong potential of the MoF in boosting the capacity of mobile networks
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