84 research outputs found

    Human Cytomegalovirus IE1 Protein Elicits a Type II Interferon-Like Host Cell Response That Depends on Activated STAT1 but Not Interferon-γ

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    Human cytomegalovirus (hCMV) is a highly prevalent pathogen that, upon primary infection, establishes life-long persistence in all infected individuals. Acute hCMV infections cause a variety of diseases in humans with developmental or acquired immune deficits. In addition, persistent hCMV infection may contribute to various chronic disease conditions even in immunologically normal people. The pathogenesis of hCMV disease has been frequently linked to inflammatory host immune responses triggered by virus-infected cells. Moreover, hCMV infection activates numerous host genes many of which encode pro-inflammatory proteins. However, little is known about the relative contributions of individual viral gene products to these changes in cellular transcription. We systematically analyzed the effects of the hCMV 72-kDa immediate-early 1 (IE1) protein, a major transcriptional activator and antagonist of type I interferon (IFN) signaling, on the human transcriptome. Following expression under conditions closely mimicking the situation during productive infection, IE1 elicits a global type II IFN-like host cell response. This response is dominated by the selective up-regulation of immune stimulatory genes normally controlled by IFN-γ and includes the synthesis and secretion of pro-inflammatory chemokines. IE1-mediated induction of IFN-stimulated genes strictly depends on tyrosine-phosphorylated signal transducer and activator of transcription 1 (STAT1) and correlates with the nuclear accumulation and sequence-specific binding of STAT1 to IFN-γ-responsive promoters. However, neither synthesis nor secretion of IFN-γ or other IFNs seems to be required for the IE1-dependent effects on cellular gene expression. Our results demonstrate that a single hCMV protein can trigger a pro-inflammatory host transcriptional response via an unexpected STAT1-dependent but IFN-independent mechanism and identify IE1 as a candidate determinant of hCMV pathogenicity

    Offshore power generation with carbon capture and storage to decarbonise mainland electricity and offshore oil and gas installations: A techno-economic analysis

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    his study investigates the techno-economic potential of offshore power generation from natural gas with carbon capture and storage to reduce the climate impact of mainland electricity and the offshore oil and gas industry. This potential is assessed through techno-economic assessments over two relevant cases (“floating” and “shallow water” cases) including comparison with relevant reference concepts. In the base case evaluation, the offshore power plant concept toward decarbonising mainland electricity results in high costs (178 and 258 /MWhrespectivelyforthefloatingandshallowwatercases)comparedtoareferenceonshorepowerplantwithcarboncaptureandstorage(around95/MWh respectively for the floating and shallow water cases) compared to a reference onshore power plant with carbon capture and storage (around 95 /MWh). However, a stronger potential is identified for the concept toward decarbonising offshore oil and gas platforms as the concept results in costs more comparable with the reference electrification concept (137 compared to 133 /MWhinthefloatingcaseand207comparedto166/MWh in the floating case and 207 compared to 166 /MWh in the shallow water case). Although the base cases show a limited potential for the offshore concept, the results show that with technological improvements (advanced capture technology, reuse of infrastructure…) and more suited case characteristics (development based on associated gas…), the offshore concept offers a significant potential for cost-efficiently decarbonising the offshore oil and gas industry, while a more moderate potential is foreseen for the decarbonisation of mainland electricity.Offshore power generation with carbon capture and storage to decarbonise mainland electricity and offshore oil and gas installations: A techno-economic analysisacceptedVersio

    From hypotonic maintenance fluid to severe hyponatremia: a case report

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    Abstract Background The principles for maintenance intravenous fluid prescription in children were developed in the 1950s. These guidelines based on the use of hypotonic solutions have been challenged regularly for they seem to be associated with an increased risk of hospital-acquired hyponatremia. Case presentation We report the case of a 4-week-old Caucasian child admitted for acute bronchiolitis who received hypotonic maintenance fluids and developed severe hyponatremia (94 mmol/L) with hyponatremic encephalopathy. Conclusion This clinical situation can serve as a reminder of the latest recommendations from the American Academy of Pediatrics regarding the use of intravenous fluids that promote the use of isotonic fluids in children
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