Hepatitis E Virus-like particles self-assemble in to noninfectious nanocapsids that are resistant to proteolytic/acidic mucosal delivery conditions. Previously, the nanocapsid was engineered to specifically bind and enter breast cancer cells, where successful tumor targeting was demonstrated in animal models. In the present study, the nanocapsid surface was modified with a solvent-exposed cysteine to conjugate monolayer protected gold nanoclusters (AuNC). Unlike commercially available gold nanoparticles, AuNCs monodisperse in water and are composed of a discrete number of gold atoms, forming a crystalline gold core. Au102 pMBA44 (Au102) was an ideal conjugate given its small 2.5 nm size and detectability in cryoEM. Au102 was bound directly to nanocapsid surface cysteines via direct ligand exchange. In addition, Au102 was functionalized with a maleimide linker (Au102_C6MI) for maleimide-thiol conjugation to nanocapsid cysteines. The AuNC-bound nanocapsid constructs were conjugated in various conditions. We found Au102_C6MI to bind nanocapsid more efficiently, while Au102 remained more soluble over time. Nanocapsids conjugated to Au102_C6MI were imaged in cryoEM for single particle reconstruction to localize AuNC position on the nanocapsid surface. We resolved five unique high intensity volumes that formed a ring-shaped density at the 5-fold symmetry center. This finding was further supported by independent rigid modeling.

Like many high‐income countries, in Australia there are a range of programmes in place, from social security to food banks, to help address food insecurity. So far, they have been unable to adequately alleviate and prevent this growing nutrition challenge. This paper presents an evaluation of a new type of intervention in the food security landscape, the social enterprise. The Community Grocer is a social enterprise that operates weekly fresh fruit and vegetable markets in Melbourne, Australia. The aim of the study was to examine the market's ability to increase access, use and availability of nutritious food in a socially acceptable way, for low socioeconomic status urban‐dwelling individuals. The mixed‐method evaluation included: comparative price audits (n = 27) at local (<1 km) stores; analysis of operational data from sample markets (n = 3); customer surveys (n = 91) and customer interviews (n = 12), collected in two phases (Autumn 2017, Summer 2018). The results found common (n = 10) fruit and vegetables cost, on average, approximately 40% less at the social enterprise, than local stores. Over twenty per cent of customers were food insecure and 80% of households were low income. Thirty‐four different nationalities shopped at the market, and just over half (54%) shopped there weekly. More than 50 types of vegetables and fruit were available to purchase, varying for cultural preferences and seasonality, which supported variety and choice. Overall, this enterprise promotes food security in a localised area through low‐cost, convenient, dignified and nutritious offerings.

Background Intracranial internal carotid artery (ICA) calcification is a common incidental finding in non-contrast head CT. We evaluated the predictive value of ICAC (ICAC) for future risk of cognitive decline and compared the results with conventional imaging biomarkers of dementia. Methods In a retrospective observational cohort, we included 230 participants with a PET-CT scan within 18 months of a baseline clinical assessment and longitudinal imaging assessments. Intracranial ICAC was quantified on baseline CT scans using the Agatson calcium score, and the association between baseline ICA calcium scores and the risk of conversion from a CDR of zero in baseline to a persistent CDR > 0 at any follow-up visit, as well as longitudinal changes in cognitive scores, were evaluated through linear and mixed regression models. We also evaluated the association of conventional imaging biomarkers of dementia with longitudinal changes in cognitive scores and a potential indirect effect of ICAC on cognition through these biomarkers. Results Baseline ICA calcium score could not distinguish participants who converted to CDR > 0. ICA calcium score was also unable to predict longitudinal changes in cognitive scores, imaging biomarkers of small vessel disease such as white matter hyperintensities (WMH) volume, or AD such as hippocampal volume, AD cortical signature thickness, and amyloid burden. Severity of intracranial ICAC increased with age and in men. Higher WMH volume and amyloid burden as well as lower hippocampal volume and AD cortical signature thickness at baseline predicted lower Mini-Mental State Exam scores at longitudinal follow-up. Baseline ICAC was indirectly associated with longitudinal cognitive decline, fully mediated through WMH volume. Conclusions In elderly and preclinical AD populations, atherosclerosis of large intracranial vessels as demonstrated through ICAC is not directly associated with a future risk of cognitive impairment, or progression of imaging biomarkers of AD or small vessel disease.

Basal bodies (BBs) are microtubule-based organelles that act as a template for and stabilize cilia at the cell surface. Centrins ubiquitously associate with BBs and function in BB assembly, maturation and stability. Human POC5 (hPOC5) is a highly conserved centrin-binding protein that binds centrins through Sfi1p-like repeats and is required for building full-length, mature centrioles. Here, we use the BB-rich cytoskeleton of Tetrahymena thermophila to characterize Poc5 BB functions. Tetrahymena Poc5 (TtPoc5) uniquely incorporates into assembling BBs and is then removed from mature BBs prior to ciliogenesis. Complete genomic knockout of TtPOC5 leads to a significantly increased production of BBs, yet a markedly reduced ciliary density, both of which are rescued by reintroduction of TtPoc5. A second Tetrahymena POC5-like gene, SFR1, is similarly implicated in modulating BB production. When TtPOC5 and SFR1 are co-deleted, cell viability is compromised and BB overproduction is exacerbated. Overproduced BBs display defective transition zone formation and a diminished capacity for ciliogenesis. This study uncovers a requirement for Poc5 in building mature BBs, providing a possible functional link between hPOC5 mutations and impaired cilia. This article has an associated First Person interview with the first author of the paper.

BackgroundIntracranial internal carotid artery (ICA) calcification is a common incidental finding in non-contrast head CT. We evaluated the predictive value of ICA calcification for future risk of dementia and compared the results with conventional imaging biomarkers of dementia.MethodsIn a retrospective observational cohort, we included 230 participants with a PET-CT scan within 18 months of a baseline clinical assessment and longitudinal imaging assessments. Intracranial ICA calcification was quantified on baseline CT scans using the Agatson calcium score. The ability of baseline ICA calcification to discriminate between a control group (participants who maintained a Clinical Dementia Rating (CDR™) score of zero over all follow-up visits) and a converter group (participants who had a baseline CDR of zero but received a persistent CDR>0 at any follow-up visit) was evaluated along with the predictive value of baseline ICA calcification for longitudinal clinical and imaging biomarkers. ResultsBaseline ICA calcium score could not distinguish participants who converted to CDR>0. ICA calcium score was also unable to predict longitudinal changes in cognitive scores, imaging biomarkers of small vessel disease such as white matter hyperintensities (WMH) volume, or AD such as hippocampal volume, AD cortical signature thickness, and amyloid burden. Severity of intracranial ICA calcification increased with age, male sex, and higher WMH volumes at baseline visit. Higher WMH volume and amyloid burden as well as lower hippocampal volume and AD cortical signature thickness at baseline predicted lower Mini-Mental State Exam scores at longitudinal follow-up. Baseline ICA calcification was indirectly associated with longitudinal cognitive decline, fully mediated through WMH volume.ConclusionsIn elderly and preclinical AD populations, atherosclerosis of large intracranial vessels as demonstrated through ICA calcification is not directly associated with a future risk of dementia, cognitive impairment, or progression of imaging biomarkers of AD or small vessel disease.