24 research outputs found
Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses
Betacoronaviruses (betaCoVs) caused the severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) outbreaks, and the SARS-CoV-2 pandemic1â4. Vaccines that elicit protective immunity against SARS-CoV-2 and betaCoVs circulating in animals have the potential to prevent future betaCoV pandemics. Here, we show that macaque immunization with a multimeric SARS-CoV-2 receptor binding domain (RBD) nanoparticle adjuvanted with 3M-052/Alum elicited cross-neutralizing antibody (cross-nAb) responses against batCoVs, SARS-CoV-1, SARS-CoV-2, and SARS-CoV-2 variants B.1.1.7, P.1, and B.1.351. Nanoparticle vaccination resulted in a SARS-CoV-2 reciprocal geometric mean neutralization ID50 titer of 47,216, and protection against SARS-CoV-2 in macaque upper and lower respiratory tracts. Importantly, nucleoside-modified mRNA encoding a stabilized transmembrane spike or monomeric RBD also induced SARS-CoV-1 and batCoV cross-nAbs, albeit at lower titers. These results demonstrate current mRNA vaccines may provide some protection from future zoonotic betaCoV outbreaks, and provide a platform for further development of pan-betaCoV vaccines
Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume
The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimerâs Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-ÎČ PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimerâs Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippocampal volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippocampal volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippocampal volume and the Zhang and Phenoage epigenetic clocks within Amyloid-ÎČ positive individuals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimerâs disease-related phenotypes, including measures of cognition or brain Amyloid-ÎČ burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippocampal volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes
Conference report: Lake Constance turns green
Adamova, G.; Ferguson, J.; Ng, S.; Puga Vaca, A.; Rodriguez, H.; Rountree, S.; Seddon, K.... (2009). Conference report: Lake Constance turns green. Green Chemistry. 11(5):604-608. doi:10.1039/b822925mS60460811
âCunning Histories: privileging narratives in the presentâ
Examining contemporary British witchcraft necessitates representing its historical context, currently a highly contested arena. Both magical practitioners and scholars have heavily critiqued the âorthodoxâ histories of unbroken lines of tradition reaching back to the distant past that were prevalent in the early to midâtwentieth century. However, continuities of knowledge and skills based on the practices of rural cunning folk and folk magic continue to be mobilized by some practitioners as a way of connecting to ideas about the past, a narrative that is also critiqued by others. What is at stake is not only the conflicting foundational histories for contemporary witchcraft, but the ways in which the same textual and material evidence is deployed to substantiate competing accounts: they hinge on the ways evidence is contextualized. Interrogating âcontextâ is not limited to the histories we aim to represent, but is embedded within anthropological writing and knowledge