Apical bulkheads accumulate as adaptive response to impaired bile flow in liver disease.

Hepatocytes form bile canaliculi that dynamically respond to the signalling activity of bile acids and bile flow. Little is known about their responses to intraluminal pressure. During embryonic development, hepatocytes assemble apical bulkheads that increase the canalicular resistance to intraluminal pressure. Here, we investigate whether they also protect bile canaliculi against elevated pressure upon impaired bile flow in adult liver. Apical bulkheads accumulate upon bile flow obstruction in mouse models and patients with primary sclerosing cholangitis (PSC). Their loss under these conditions leads to abnormally dilated canaliculi, resembling liver cell rosettes described in other hepatic diseases. 3D reconstruction reveals that these structures are sections of cysts and tubes formed by hepatocytes. Mathematical modelling establishes that they positively correlate with canalicular pressure and occur in early PSC stages. Using primary hepatocytes and 3D organoids, we demonstrate that excessive canalicular pressure causes the loss of apical bulkheads and formation of rosettes. Our results suggest that apical bulkheads are a protective mechanism of hepatocytes against impaired bile flow, highlighting the role of canalicular pressure in liver diseases.

Accepting the Aging Body: Protective Factors of Body Acceptance in Persons of Advanced Age.

Introduction: Physical attractiveness, productivity, religiosity, meaningfulness, and relationships are important characteristics of successful aging. To maintain psychological flexibility, acceptance and values-directed interventions have been effective in managing difficulties with aging. Objectives: The present paper aimed to investigate body acceptance and individual values in healthy individuals over the age of 50 living in Austria. Methods: In addition to sociodemographic variables, subjective age, attractiveness, and desire for body changes were assessed in our survey. The Austrian Value Questionnaire was used to record values, and the German Version of the Quality of Marriage scale assessed partnership quality. Data from 187 older adults were recruited via snowball sampling. Analyses were performed in SPSS and R, using a structural equation modeling approach. Results: The results indicate that as age increases and subjective attractiveness decreases, body acceptance declines. Materialism seems to support the desire for cosmetic surgery (ß = .230, p = .016). A negative association between conservatism and changes in desires for body change (ß = -.221, p = .044) suggests that greater value commitment and conservative attitudes are related to fewer change desires. Conclusion: These findings underpin the necessity for encouraging individuals early on to be in touch with their values to promote psychological flexibility.

Hepatocyte apical bulkheads provide a mechanical means to oppose bile pressure.

Hepatocytes grow their apical surfaces anisotropically to generate a 3D network of bile canaliculi (BC). BC elongation is ensured by apical bulkheads, membrane extensions that traverse the lumen and connect juxtaposed hepatocytes. We hypothesize that apical bulkheads are mechanical elements that shape the BC lumen in liver development but also counteract elevated biliary pressure. Here, by resolving their structure using STED microscopy, we found that they are sealed by tight junction loops, connected by adherens junctions, and contain contractile actomyosin, characteristics of mechanical function. Apical bulkheads persist at high pressure upon microinjection of fluid into the BC lumen, and laser ablation demonstrated that they are under tension. A mechanical model based on ablation results revealed that apical bulkheads double the pressure BC can hold. Apical bulkhead frequency anticorrelates with BC connectivity during mouse liver development, consistent with predicted changes in biliary pressure. Our findings demonstrate that apical bulkheads are load-bearing mechanical elements that could protect the BC network against elevated pressure.