15 research outputs found

    Regulation of Human γδ T Cells by BTN3A1 Protein Stability and ATP-Binding Cassette Transporters

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    Activation of human Vγ9/Vδ2 T cells by ‘phosphoantigens’ (pAg), the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP) and the endogenous isoprenoid intermediate isopentenyl pyrophosphate (IPP), requires expression of butyrophilin BTN3A molecules by presenting cells. However, the precise mechanism of activation of Vγ9/Vδ2 T cells by BTN3A molecules remains elusive. It is not clear what conformation of the three BTN3A isoforms transmits activation signals nor how externally delivered pAg accesses the cytosolic B30.2 domain of BTN3A1. To approach this problem we studied two HLA haplo-identical HeLa cell lines, termed HeLa-L and HeLa-M, which showed marked differences in pAg-dependent stimulation of Vγ9/Vδ2 T cells. Levels of IFN-γ secretion by Vγ9/Vδ2 T cells were profoundly increased by pAg loading, or by binding of the pan-BTN3A specific agonist antibody CD277 20.1, in HeLa-M compared to HeLa-L cells. IL-2 production from a murine hybridoma T cell line expressing human Vγ9/Vδ2 TCR transgenes confirmed that the differential responsiveness to HeLa-L and HeLa-M was TCR dependent. By tissue typing, both HeLa lines were shown to be genetically identical and full-length transcripts of the three BTN3A isoforms were detected in equal abundance with no sequence variation. Expression of BTN3A and interacting molecules such as periplakin or RhoB did not account for the functional variation between HeLa-L and HeLa-M cells, although evidence implicates a mechanism controlling BTN3A protein stability and trafficking. Plasma membrane profiling was used to identify proteins upregulated in HMB-PP treated HeLa-M. ABCG2, a member of the ABC transporter family was the most significant candidate, which crucially showed reduced expression in HeLa-L. Expression of a subset of ABC transporters, including ABCA1 and ABCG1, correlated with efficiency of T cell activation by cytokine secretion, although direct evidence of a functional role was not obtained by knockdown experiments. Our findings indicate a link between members of the ABC protein superfamily and the BTN3A-dependent activation of γδ T cells by endogenous and exogenous pAg

    SUDS, LID, BMPs, WSUD and more - The evolution and application of terminology surrounding urban drainage

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    Open Access articleThe management of urban stormwater has become increasingly complex over recent decades. Consequently, terminology describing the principles and practices of urban drainage has become increasingly diverse, increasing the potential for confusion and miscommunication. This paper documents the history, scope, application and underlying principles of terms used in urban drainage and provides recommendations for clear communication of these principles. Terminology evolves locally and thus has an important role in establishing awareness and credibility of new approaches and contains nuanced understandings of the principles that are applied locally to address specific problems. Despite the understandable desire to have a ‘uniform set of terminology’, such a concept is flawed, ignoring the fact that terms reflect locally shared understanding. The local development of terminology thus has an important role in advancing the profession, but authors should facilitate communication between disciplines and between regions of the world, by being explicit and accurate in their application

    Exploring indoor and outdoor dust as a potential tool for detection and monitoring of COVID-19 transmission

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    This study investigated the potential of using SARS-CoV-2 viral concentrations in dust as an additional surveillance tool for early detection and monitoring of COVID-19 transmission. Dust samples were collected from 8 public locations in 16 districts of Bangkok, Thailand, from June to August 2021. SARS-CoV-2 RNA concentrations in dust were quantified, and their correlation with community case incidence was assessed. Our findings revealed a positive correlation between viral concentrations detected in dust and the relative risk of COVID-19. The highest risk was observed with no delay (0-day lag), and this risk gradually decreased as the lag time increased. We observed an overall decline in viral concentrations in public places during lockdown, closely associated with reduced human mobility. The effective reproduction number for COVID-19 transmission remained above one throughout the study period, suggesting that transmission may persist in locations beyond public areas even after the lockdown measures were in place

    Comparison of the Transition to More Sustainable Stormwater Management in China and the USA

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    This paper presents a comparative cross-nation study of the transition to more sustainable stormwater management (SSWM) in the United States and China. Multi-level perspective and multiphase models are used to examine the transition dynamics and reflect on how transition theory explains the change within federal and socialist context. Instead of simply differentiating the two countries’ transition patterns by using terms such as bottom-up or top-down, we consider the importance of changes at all three levels of the system. The main difference between the transition process in the United States and China is the extent to which niche level innovations are developed, especially in the type of actors and activities investigated. The analysis suggests that the Chinese transition is less radical, while the U.S. pathway exhibits signs of reconfiguration, dealignment and realignment. Developing learning networks across sectors and actors to spread knowledge and experience appears to be the next major challenge for the Chinese Sponge City initiative. Despite the feasibility of transition theory for transition comparison, the author suggests its usage with caution and critical reflection to avoid the risk of embedding the mindset of ‘catch-up’ and convergence

    Satisfaction with the condition of local waterways in Aotearoa New Zealand

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    In 2018, adult New Zealanders rated their level of satisfaction with the quality and health of waterways in their local region as part of the New Zealand Attitudes and Values Study. The average satisfaction level (4.8 out of 10) indicates New Zealanders are overall dissatisfied with the quality and health of local waterways. Satisfaction levels varied across regions, being lowest in Hawkes Bay and highest in the West Coast. Urban New Zealanders are slightly less satisfied with the quality and health of local waterways than rural New Zealanders. Younger and Māori participants are less satisfied while participants upholding conservative and social dominance orientations are more satisfied with the quality and health of local waterway

    COVID-19 monitoring with sparse sampling of sewered and non-sewered wastewater in urban and rural communities

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    Summary: Equitable SARS-CoV-2 surveillance in low-resource communities lacking centralized sewers is critical as wastewater-based epidemiology (WBE) progresses. However, large-scale studies on SARS-CoV-2 detection in wastewater from low-and middle-income countries is limited because of economic and technical reasons. In this study, wastewater samples were collected twice a month from 186 urban and rural subdistricts in nine provinces of Thailand mostly having decentralized and non-sewered sanitation infrastructure and analyzed for SARS-CoV-2 RNA variants using allele-specific RT-qPCR. Wastewater SARS-CoV-2 RNA concentration was used to estimate the real-time incidence and time-varying effective reproduction number (Re). Results showed an increase in SARS-CoV-2 RNA concentrations in wastewater from urban and rural areas 14–20 days earlier than infected individuals were officially reported. It also showed that community/food markets were “hot spots” for infected people. This approach offers an opportunity for early detection of transmission surges, allowing preparedness and potentially mitigating significant outbreaks at both spatial and temporal scales
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