3,101 research outputs found

    Environmentally-triggered contraction of the norovirus virion determines diarrheagenic potential

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    Noroviruses are the leading cause of severe childhood diarrhea and foodborne disease worldwide. While they are a major cause of disease in all age groups, infections in the very young can be quite severe with annual estimates of 50,000-200,000 fatalities in children under 5 years old. In spite of the remarkable disease burden associated with norovirus infections in people, very little is known about the pathogenic mechanisms underlying norovirus diarrhea, principally because of the lack of tractable small animal models. We recently demonstrated that wild-type neonatal mice are susceptible to murine norovirus (MNV)-induced acute self-resolving diarrhea in a time course mirroring human norovirus disease. Using this robust pathogenesis model system, we demonstrate that virulence is regulated by the responsiveness of the viral capsid to environmental cues that trigger contraction of the VP1 protruding (P) domain onto the particle shell, thus enhancing receptor binding and infectivity. The capacity of a given MNV strain to undergo this contraction positively correlates with infection of cells expressing low abundance of the virus receptor CD300lf, supporting a model whereby virion contraction triggers infection of CD300l

    Public-Public-Private Partnership for Sustainable Solid Waste Management in Eldoret Town, Kenya

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    Solid waste management is one of the most difficult environmental problems in the urban centers of developing countries, where services are often grossly deficient, especially within low-income settlements. The purpose of this study was to investigate if Public-Public-private Partnership contributed to sustainability of solid waste management, in Eldoret town, Kenya. The objective was to investigate the effects of public-private firm’s resource capacity on sustainability of solid waste management in Eldoret town, Kenya. The researcher used stratified simple random sampling to get the respondents. Data was collected using interviews and questionnaires. Interviews were conducted to the management while the questionnaires were distributed to the sampled staff. Study findings revealed that resource centre has a significant effect on sustainable solid waste management; regulatory framework has a positive significant effect on solid waste management. The involvement of private partners in ensuring sustainable solid waste management is a positive contribution. Municipals should build a uniquely capable workforce enabling it to counter the problem of solid waste management. Clear health and sanitation regulations governing waste procedures should be in place. Municipal should relate well with residents, employees, SMEs and industries since good mutual relationship are paramount for sustainable solid waste management. Private partners should be consulted in formulation and development of bylaws and in making environment management systems for the public and private sectors. Keywords:Sustainable, solid waste, Public private partnership, Eldoret, Keny

    Software Citation in HEP: Current State and Recommendations for the Future

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    In November 2022, the HEP Software Foundation (HSF) and the Institute for Research and Innovation for Software in High-Energy Physics (IRIS-HEP) organized a workshop on the topic of Software Citation and Recognition in HEP. The goal of the workshop was to bring together different types of stakeholders whose roles relate to software citation and the associated credit it provides in order to engage the community in a discussion on: the ways HEP experiments handle citation of software, recognition for software efforts that enable physics results disseminated to the public, and how the scholarly publishing ecosystem supports these activities. Reports were given from the publication board leadership of the ATLAS, CMS, and LHCb experiments and HEP open source software community organizations (ROOT, Scikit-HEP, MCnet), and perspectives were given from publishers (Elsevier, JOSS) and related tool providers (INSPIRE, Zenodo). This paper summarizes key findings and recommendations from the workshop as presented at the 26th International Conference on Computing In High Energy and Nuclear Physics (CHEP 2023).Comment: 7 pages, 2 listings. Contribution to the Proceedings of the 26th International Conference on Computing In High Energy and Nuclear Physics (CHEP 2023

    Apoptosis signal-regulating kinase-1 promotes inflammasome priming in macrophages

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    © 2019 the American Physiological Society. previously showed that mice deficient in apo-ptosis signal-regulating kinase-1 (ASK1) were partially protected against ventilator-induced lung injury. Because ASK1 can promote both cell death and inflammation, we hypothesized that ASK1 activation regulates inflammasome-mediated inflammation. Mice deficient in ASK1 expression (ASK1 +/+ ) exhibited significantly less inflammation and lung injury (as measured by neutrophil infiltration, IL-6, and IL-1β) in response to treatment with inhaled lipopolysaccharide (LPS) compared with wild-type (WT) mice. To determine whether this proinflammatory response was mediated by ASK1, we investigated inflammasome-mediated responses to LPS in primary macrophages and bone marrow-derived macrophages (BMDMs) from WT and ASK1 +/+ mice, as well as the mouse alveolar macrophage cell line MH-S. Cells were treated with LPS alone for priming or LPS followed by ATP for activation. When macrophages were stimulated with LPS followed by ATP to activate the inflammasome, we found a significant increase in secreted IL-1β from WT cells compared with ASK1-deficient cells. LPS priming stimulated an increase in NOD-like receptor 3 (NLRP3) and pro-IL-1β in WT BMDMs, but expression of NLRP3 was significantly decreased in ASK1 +/+ BMDMs. Subsequent ATP treatment stimulated an increase in cleaved caspase-1 and IL-1β in WT BMDMs compared with ASK1 +/+ BMDMs. Similarly, treatment of MH-S cells with LPS + ATP caused an increase in both cleaved caspase-1 and IL-1β that was diminished by the ASK-1 inhibitor NQDI1. These results demonstrate, for the first time, that ASK1 promotes inflammasome priming

    Immersive Installation: “A Virtual St Kilda”

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    This paper discusses a Virtual Histories project, which developed a digital reconstruction of St Kilda. St Kilda is the most remote and western part of the United Kingdom. It was evacuated in the 1930s and lay empty for several decades. It is a world heritage site for both built and natural environment . The Virtual St Kilda acted as a focus for the collection and presentation of tangible and intangible cultural heritage. It was on show as an exhibition in the Taigh Chearsabah museum (Figure 5) located in North Uist Scotland. The exhibition is built around the OpenSimulator Open VirtualWorld server using commodity hardware. The simulation covers some 4 square km of virtual space, and models both tangible and intangible culture. It is integrated into an exhibition and articulates an interpretation of the St Kilda legacy through the prism of contemporary North Uist life.Postprin

    Quantitation of CD8+ T Cell Responses to Newly Identified HLA-A*0201–restricted T Cell Epitopes Conserved Among Vaccinia and Variola (Smallpox) Viruses

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    Immunization with vaccinia virus resulted in long-lasting protection against smallpox and was the approach used to eliminate natural smallpox infections worldwide. Due to the concern about the potential use of smallpox virus as a bioweapon, smallpox vaccination is currently being reintroduced. Severe complications from vaccination were associated with congenital or acquired T cell deficiencies, but not with congenital agammaglobulinemia, suggesting the importance of T cell immunity in recovery from infection. In this report, we identified two CD8+ T cell epitopes restricted by the most common human major histocompatibility complex (MHC) class I allele, HLA-A*0201. Both epitopes are highly conserved in vaccinia and variola viruses. The frequency of vaccinia-specific CD8+ T cell responses to these epitopes measured by interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) assay and HLA/peptide tetramer staining peaked 2 wk after primary immunization and then declined, but were still detectable 1 to 3 yr after primary immunization. 2 wk after immunization, IFN-γ–producing cells specific to these two epitopes were 14% of total vaccinia virus-specific IFN-γ–producing cells in one donor, 35% in the second donor, and 6% in the third donor. This information will be useful for studies of human T cell memory and for the design and analyses of the immunogenicity of experimental vaccinia vaccines
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