The nonvesicular sterol transporter Aster-C plays a minor role in whole body cholesterol balance.

Introduction: The Aster-C protein (encoded by the Gramd1c gene) is an endoplasmic reticulum (ER) resident protein that has been reported to transport cholesterol from the plasma membrane to the ER. Although there is a clear role for the closely-related Aster-B protein in cholesterol transport and downstream esterification in the adrenal gland, the specific role for Aster-C in cholesterol homeostasis is not well understood. Here, we have examined whole body cholesterol balance in mice globally lacking Aster-C under low or high dietary cholesterol conditions. Method: Age-matched Gramd1c +/+ and Gramd1c -/- mice were fed either low (0.02%, wt/wt) or high (0.2%, wt/wt) dietarycholesterol and levels of sterol-derived metabolites were assessed in the feces, liver, and plasma. Results: Compared to wild type controls (Gramd1c +/+) mice, mice lackingGramd1c (Gramd1c -/-) have no significant alterations in fecal, liver, or plasma cholesterol. Given the potential role for Aster C in modulating cholesterol metabolism in diverse tissues, we quantified levels of cholesterol metabolites such as bile acids, oxysterols, and steroid hormones. Compared to Gramd1c +/+ controls, Gramd1c -/- mice had modestly reduced levels of select bile acid species and elevated cortisol levels, only under low dietary cholesterol conditions. However, the vast majority of bile acids, oxysterols, and steroid hormones were unaltered in Gramd1c -/- mice. Bulk RNA sequencing in the liver showed that Gramd1c -/- mice did not exhibit alterations in sterol-sensitive genes, but instead showed altered expression of genes in major urinary protein and cytochrome P450 (CYP) families only under low dietary cholesterol conditions. Discussion: Collectively, these data indicate nominal effects of Aster-C on whole body cholesterol transport and metabolism under divergent dietary cholesterol conditions. These results strongly suggest that Aster-C alone is not sufficient to control whole body cholesterol balance, but can modestly impact circulating cortisol and bile acid levels when dietary cholesterol is limited.

Protocol for the YORKSURe prospective multistage study testing the feasibility for early detection of bladder cancer in populations with high disease-specific mortality risk.

INTRODUCTION: Around 25% of patients with bladder cancer (BCa) present with invasive disease. Non-randomised studies of population-based screening have suggested reductions in BCa-specific mortality are possible through earlier detection. The low prevalence of lethal disease in the general population means screening is not cost-effective and there is no consensus on the best strategy. Yorkshire has some of the highest mortality rates from BCa in England. We aim to test whether population screening in a region of high mortality risk will lead to a downward stage-migration of aggressive BCa, improved survival and is cost-effective. METHODS AND ANALYSIS: YORKSURe is a tiered, randomised, multicohort study to test the feasibility of a large BCa screening randomised controlled trial. In three parallel cohorts, participants will self-test urine (at home) up to six times. Results are submitted via a mobile app or freephone. Those with a positive result will be invited for further investigation at community-based early detection clinics or within usual National Health Service (NHS) pathways. In Cohort 1, we will post self-testing kits to research engaged participants (n=2000) embedded within the Yorkshire Lung Screening Trial. In Cohort 2, we will post self-testing kits to 3000 invitees. Cohort 2 participants will be randomised between haematuria and glycosuria testing using a reveal/conceal design. In Cohort 3, we will post self-testing kits to 500 patients within the NHS pathway for investigation of haematuria. Our primary outcomes are rates of recruitment and randomisation, rates of positive test and acceptability of the design. The study is currently recruiting and scheduled to finish in June 2023. ETHICS AND DISSEMINATION: The study has received the following approvals: London Riverside Research Ethics Committee (22/LO/0018) and Health Research Authority Confidentiality Advisory Group (20/CAG/0009). Results will be made available to providers and researchers via publicly accessible scientific journals. TRIAL REGISTRATION NUMBER: ISRCTN34273159.

Bending a photonic wire into a ring.

Natural light-harvesting systems absorb sunlight and transfer its energy to the reaction centre, where it is used for photosynthesis. Synthetic chromophore arrays provide useful models for understanding energy migration in these systems. Research has focused on mimicking rings of chlorophyll molecules found in purple bacteria, known as 'light-harvesting system 2'. Linear meso-meso linked porphyrin chains mediate rapid energy migration, but until now it has not been possible to bend them into rings. Here we show that oligo-pyridyl templates can be used to bend these rod-like photonic wires to create covalent nanorings that consist of 24 porphyrin units and a single butadiyne link. Their elliptical conformations have been probed by scanning tunnelling microscopy. This system exhibits two excited state energy transfer processes: one from a bound template to the peripheral porphyrins and one, in the template-free ring, from the exciton-coupled porphyrin array to the π-conjugated butadiyne-linked porphyrin dimer segment.

Self-assembly of a strapped linear porphyrin oligomer on HOPG.

Polymeric structures based on porphyrin units exhibit a range of complex properties, such as nanoscale charge transport and quantum interference effects, and have the potential to act as biomimetic materials for light-harvesting and catalysis. These functionalities are based upon the characteristics of the porphyrin monomers, but are also emergent properties of the extended polymer system. Incorporation of these properties within solid-state devices requires transfer of the polymers to a supporting substrate, and may require a high-degree of lateral order. Here we show that highly ordered self-assembled structures can be formed via a simple solution deposition protocol; for a strapped linear porphyrin oligomer adsorbed on a highly oriented pyrolytic graphite (HOPG) substrate. Two distinct molecule-molecule interactions are observed to drive the formation of two molecular phases ('Interdigitated' and 'Bridge-stabilised') characterised by scanning tunnelling microscopy, providing information on the unit cell dimensions and self-assembled structure. The concentration dependence of these phases is investigated, and we conclude that the bridge-stabilised phase is a thermodynamically stable structure at room temperature.

Using community-led development to build health communication about rheumatic heart disease in Aboriginal children: a developmental evaluation.

OBJECTIVE: A high prevalence of acute rheumatic fever (ARF) and rheumatic heart disease (RHD) among Aboriginal children in northern Australia is coupled with low understanding among families. This has negative impacts on children's health, limits opportunities for prevention and suggests that better health communication is needed. METHODS: During an RHD echocardiography screening project, Aboriginal teachers in a remote community school created lessons to teach children about RHD in their home languages, drawing on principles of community-led development. Access to community-level RHD data, previously unknown to teachers and families, was a catalyst for this innovative work. Careful, iterative discussions among speakers of four Aboriginal languages ensured a culturally coherent narrative and accompanying teaching resources. RESULTS: The evaluation demonstrated the importance of collective work, local Indigenous Knowledge and metaphors. As a result of the lessons, some children showed new responses and attitudes to skin infections and their RHD treatment. Language teachers used natural social networks to disseminate new information. A community interagency collaboration working to prevent RHD commenced. Conclusions and implications for public health: Action to address high rates of RHD must include effective health communication strategies that value Indigenous Knowledge, language and culture, collaborative leadership and respect for Indigenous data sovereignty.