A CEP104-CSPP1 Complex Is Required for Formation of Primary Cilia Competent in Hedgehog Signaling

CEP104 is an evolutionarily conserved centrosomal and ciliary tip protein. CEP104 loss-of-function mutations are reported in patients with Joubert syndrome, but their function in the etiology of ciliopathies is poorly understood. Here, we show that cep104 silencing in zebrafish causes cilia-related manifestations: shortened cilia in Kupffer's vesicle, heart laterality, and cranial nerve development defects. We show that another Joubert syndrome-associated cilia tip protein, CSPP1, interacts with CEP104 at microtubules for the regulation of axoneme length. We demonstrate in human telomerase reverse transcriptase-immortalized retinal pigmented epithelium (hTERT-RPE1) cells that ciliary translocation of Smoothened in response to Hedgehog pathway stimulation is both CEP104 and CSPP1 dependent. However, CEP104 is not required for the ciliary recruitment of CSPP1, indicating that an intra-ciliary CEP104-CSPP1 complex controls axoneme length and Hedgehog signaling competence. Our in vivo and in vitro analyses of CEP104 define its interaction with CSPP1 as a requirement for the formation of Hedgehog signaling-competent cilia, defects that underlie Joubert syndrome

Food as harm reduction during a drinking session: reducing the harm or normalising harmful use of alcohol? A qualitative comparative analysis of alcohol industry and non-alcohol industry-funded guidance.

BACKGROUND: The aim of this study was to critically analyse information concerning the relationship between alcohol and food consumption provided via alcohol industry (AI) funded and non-AI-funded health-oriented websites, to determine the role it plays within the alcohol information space, and how this serves the interests of the disseminating organisations. METHODS: Information on food as a harm reduction measure while drinking alcohol was extracted from 15 AI websites and websites of AI-funded corporate social responsibility (CSR) organisations. As a comparison group, non-AI-funded health websites were also searched (n = 16 websites with food and alcohol-related content). Information was included from webpage content and associated downloadable documents. Critical discourse analysis (CDA) was adopted to allow the texts analysed to be situated within the broader political and social context. Analysis was carried out iteratively, involving continuous comparison within and between websites. Discursive themes were identified by three researchers. Identified discursive elements were discussed to reach a consensus, and a final coding framework was then developed. "Tone" analysis was used to assess whether the overall tone within individual websites was considered to be pro-alcohol consumption, neutral or discouraging of alcohol consumption. RESULTS: There were some commonalities across AI and non-AI-funded websites, whereby both appeared to normalise alcohol consumption and to encourage use of food as a measure to enable sustained drinking, to avoid drinking in a way that results in short-term harms, and to prevent or "cure" a hangover. The fact that both AI-funded and non-AI-funded organisations shared many of these narratives is particularly concerning. However, a discourse of food and alcohol that served to promote "moderate" drinking as beneficial to health was used exclusively by AI-funded organisations, focusing on special occasions and individual-blaming. CONCLUSIONS: Alcohol consumption, including heavy and harmful consumption, is frequently normalised within the online information space. Emphasising food consumption with alcohol may have the effect of supporting consumers to drink for longer periods of time. Health professionals and independent health organisations should review the information they provide in light of our findings and challenge why AI-funded organisations, with a major conflict of interest, and a history of health misinformation, are often given the responsibility for disseminating health information to the public

Food as harm reduction during a drinking session:reducing the harm or normalising harmful use of alcohol? A qualitative comparative analysis of alcohol industry and non-alcohol industry-funded guidance

BACKGROUND: The aim of this study was to critically analyse information concerning the relationship between alcohol and food consumption provided via alcohol industry (AI) funded and non-AI-funded health-oriented websites, to determine the role it plays within the alcohol information space, and how this serves the interests of the disseminating organisations. METHODS: Information on food as a harm reduction measure while drinking alcohol was extracted from 15 AI websites and websites of AI-funded corporate social responsibility (CSR) organisations. As a comparison group, non-AI-funded health websites were also searched (n = 16 websites with food and alcohol-related content). Information was included from webpage content and associated downloadable documents. Critical discourse analysis (CDA) was adopted to allow the texts analysed to be situated within the broader political and social context. Analysis was carried out iteratively, involving continuous comparison within and between websites. Discursive themes were identified by three researchers. Identified discursive elements were discussed to reach a consensus, and a final coding framework was then developed. "Tone" analysis was used to assess whether the overall tone within individual websites was considered to be pro-alcohol consumption, neutral or discouraging of alcohol consumption. RESULTS: There were some commonalities across AI and non-AI-funded websites, whereby both appeared to normalise alcohol consumption and to encourage use of food as a measure to enable sustained drinking, to avoid drinking in a way that results in short-term harms, and to prevent or "cure" a hangover. The fact that both AI-funded and non-AI-funded organisations shared many of these narratives is particularly concerning. However, a discourse of food and alcohol that served to promote "moderate" drinking as beneficial to health was used exclusively by AI-funded organisations, focusing on special occasions and individual-blaming. CONCLUSIONS: Alcohol consumption, including heavy and harmful consumption, is frequently normalised within the online information space. Emphasising food consumption with alcohol may have the effect of supporting consumers to drink for longer periods of time. Health professionals and independent health organisations should review the information they provide in light of our findings and challenge why AI-funded organisations, with a major conflict of interest, and a history of health misinformation, are often given the responsibility for disseminating health information to the public

Bisphenol A Inhibits the Transporter Function of the Blood-Brain Barrier by Directly Interacting with the ABC Transporter Breast Cancer Resistance Protein (BCRP)

The breast cancer resistance protein (BCRP) is an important efflux transporter in the blood-brain barrier (BBB), protecting the brain from a wide range of substances. In this study, we investigated if BCRP function is affected by bisphenol A (BPA), a high production volume chemical used in common consumer products, as well as by bisphenol F (BPF) and bisphenol S (BPS), which are used to substitute BPA. We employed a transwell-based in vitro cell model of iPSC-derived brain microvascular endothelial cells, where BCRP function was assessed by measuring the intracellular accumulation of its substrate Hoechst 33342. Additionally, we used in silico modelling to predict if the bisphenols could directly interact with BCRP. Our results showed that BPA significantly inhibits the transport function of BCRP. Additionally, BPA was predicted to bind to the cavity that is targeted by known BCRP inhibitors. Taken together, our findings demonstrate that BPA inhibits BCRP function in vitro, probably by direct interaction with the transporter. This effect might contribute to BPA's known impact on neurodevelopment