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- Leggat, DJ, et al.
(author)
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Vaccination induces HIV broadly neutralizing antibody precursors in humans
- 2022
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In: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 378:6623, s. 964-
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Journal article (peer-reviewed)abstract
- Broadly neutralizing antibodies (bnAbs) can protect against HIV infection but have not been induced by human vaccination. A key barrier to bnAb induction is vaccine priming of rare bnAb-precursor B cells. In a randomized, double-blind, placebo-controlled phase 1 clinical trial, the HIV vaccine–priming candidate eOD-GT8 60mer adjuvanted with AS01Bhad a favorable safety profile and induced VRC01-class bnAb precursors in 97% of vaccine recipients with median frequencies reaching 0.1% among immunoglobulin G B cells in blood. bnAb precursors shared properties with bnAbs and gained somatic hypermutation and affinity with the boost. The results establish clinical proof of concept for germline-targeting vaccine priming, support development of boosting regimens to induce bnAbs, and encourage application of the germline-targeting strategy to other targets in HIV and other pathogens.
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- Crotty Alexander, Laura E., et al.
(author)
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Myeloid cell HIF-1 alpha regulates asthma airway resistance and eosinophil function
- 2013
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In: Journal of Molecular Medicine. - : Springer Verlag (Germany). - 0946-2716 .- 1432-1440. ; 91:5, s. 637-644
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Journal article (peer-reviewed)abstract
- Hypoxia-inducible factor (HIF)-1 alpha is a master regulator of inflammatory activities of myeloid cells, including neutrophils and macrophages. These studies examine the role of myeloid cell HIF-1 alpha in regulating asthma induction and pathogenesis, and for the first time, evaluate the roles of HIF-1 alpha and HIF-2 alpha in the chemotactic properties of eosinophils, the myeloid cells most associated with asthma. Wild-type (WT) and myeloid cell-specific HIF-1 alpha knockout (KO) C57BL/6 mice were studied in an ovalbumin (OVA) model of asthma. Administration of the pharmacological HIF-1 alpha antagonist YC-1 was used to corroborate findings from the genetic model. WT, HIF-1 alpha, and HIF-2 alpha KO eosinophils underwent in vitro chemotaxis assays. We found that deletion of HIF-1 alpha in myeloid cells and systemic treatment with YC-1 during asthma induction decreased airway hyperresponsiveness (AHR). Deletion of HIF-1 alpha in myeloid cells in OVA-induced asthma also reduced eosinophil infiltration, goblet cell hyperplasia, and levels of cytokines IL-4, IL-5, and IL-13 in the lung. HIF-1 alpha inhibition with YC-1 during asthma induction decreased eosinophilia in bronchoalveolar lavage, lung parenchyma, and blood, as well as decreased total lung inflammation, IL-5, and serum OVA-specific IgE levels. Deletion of HIF-1 alpha in eosinophils decreased their chemotaxis, while deletion of the isoform HIF-2 alpha led to increased chemotaxis. This work demonstrates that HIF-1 alpha in myeloid cells plays a role in asthma pathogenesis, particularly in AHR development. Additionally, treatment with HIF-1 alpha inhibitors during asthma induction decreases AHR and eosinophilia. Finally, we show that HIF-1 alpha and HIF-2 alpha regulate eosinophil migration in opposing ways.
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- Woolf, Anthony D., et al.
(author)
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Clinical advances – from bench to bedside
- 2020
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In: Best Practice and Research: Clinical Rheumatology. - : Elsevier BV. - 1521-6942. ; 34:5
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Research review (peer-reviewed)
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- Phillips, Helen R. P., et al.
(author)
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Global distribution of earthworm diversity
- 2019
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 366:6464, s. 480-
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Journal article (peer-reviewed)abstract
- Soil organisms, including earthworms, are a key component of terrestrial ecosystems. However, little is known about their diversity, their distribution, and the threats affecting them. We compiled a global dataset of sampled earthworm communities from 6928 sites in 57 countries as a basis for predicting patterns in earthworm diversity, abundance, and biomass. We found that local species richness and abundance typically peaked at higher latitudes, displaying patterns opposite to those observed in aboveground organisms. However, high species dissimilarity across tropical locations may cause diversity across the entirety of the tropics to be higher than elsewhere. Climate variables were found to be more important in shaping earthworm communities than soil properties or habitat cover. These findings suggest that climate change may have serious implications for earthworm communities and for the functions they provide.
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- Stephens, A. N., et al.
(author)
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Too close for comfort : A mixed methods study to understand self-reported tailgating using the theory of planned behaviour
- 2023
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In: Transportation Research Part F. - : Elsevier. - 1369-8478 .- 1873-5517. ; 93, s. 11-22
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Journal article (peer-reviewed)abstract
- Background: Tailgating (following a lead vehicle too closely) is a key contributor to crashes and injury. While vehicle technology has the potential to reduce the trauma resulting from tailgating, full market penetration of these technologies is some time away. In the meantime, efforts to improve road safety can focus on supporting safer driver behaviour by targeting motivations for this behaviour.Method: A mixed methods design was used to understand reasons why drivers tailgate and potential countermeasures to reduce this behaviour. Qualitative data from 247 drivers (males = 29 %; mean age = 39.86; SD = 14.39) were sought to understand circumstances when drivers are tailgated and when they report tailgating. In a second study, 736 drivers (males = 41 %; mean age = 37.69; SD = 14.27) responded to questions developed from the qualitative findings to quantify the frequency of tailgating and reasons behind it. The theory of planned behaviour (TPB) was applied to understand whether self-reported intention to tailgate could be predicted by attitudes, perceived social acceptance of the behaviour, perceived behavioural control, and past tailgating behaviour.Results: Tailgating was a common behaviour. All drivers in the first study had experienced being tailgated by other drivers, while 77% had tailgated other vehicles; albeit 55% reported this was rare. Tailgating was unintentional (due to dense traffic; or lack of knowledge of safe following distance recommendations) or intentional (due to pressure from other drivers, anger or to change others’ behaviour). Structural equation modelling showed that TPB constructs of attitude, social norms, perceived behavioural control and past tailgating behaviour predicted intention to tailgate, accounting for 66% of the variance.Conclusion: TPB is a useful framework for explaining tailgating behaviour, or at least the intention to tailgate, and to develop interventions. These could focus on education of the risks of tailgating, the recommended safe following distances as well as strategies to support drivers maintaining safe following distances across different speed zones
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- Sun, Peifang, et al.
(author)
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Asymptomatic or symptomatic SARS-CoV-2 infection plus vaccination confers increased adaptive immunity to variants of concern
- 2022
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In: iScience. - : Elsevier BV. - 2589-0042. ; 25:10
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Journal article (peer-reviewed)abstract
- The ongoing evolution of SARS-CoV-2 requires monitoring the capability of immune responses to cross-recognize Variants of Concern (VOC). In this cross-sectional study, we examined serological and cell-mediated immune memory to SARS-CoV-2 variants, including Omicron, among a cohort of 18-21-year-old Marines with a history of either asymptomatic or mild SARS-CoV-2 infection 6 to 14 months earlier. Among the 210 participants in the study, 169 were unvaccinated while 41 received 2 doses of mRNA-based COVID-19 vaccines. Vaccination of previously infected participants strongly boosted neutralizing and binding activity and memory B and T cell responses including the recognition of Omicron, compared to infected but unvaccinated participants. Additionally, no measurable differences were observed in immune memory in healthy young adults with previous symptomatic or asymptomatic infections, for ancestral or variant strains. These results provide mechanistic immunological insights into population-based differences observed in immunity against Omicron and other variants among individuals with different clinical histories.
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