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Angiopoietin-like 4 (ANGPTL4) is a secreted signaling protein that is implicated in cardiovascular disease, metabolic disorder, and cancer. Outside of its role in lipid metabolism, ANGPTL4 signaling remains poorly understood. Here, we identify ANGPTL4 as a Wnt signaling antagonist that binds to syndecans and forms a ternary complex with the Wnt co-receptor Lipoprotein receptor-related protein 6 (LRP6). This protein complex is internalized via clathrin-mediated endocytosis and degraded in lysosomes, leading to attenuation of Wnt/β-catenin signaling. Angptl4 is expressed in the Spemann organizer of Xenopus embryos and acts as a Wnt antagonist to promote notochord formation and prevent muscle differentiation. This unexpected function of ANGPTL4 invites re-interpretation of its diverse physiological effects in light of Wnt signaling and may open therapeutic avenues for human disease.

Angiopoietin-like 4 (ANGPTL4) is a secreted signaling protein that is implicated in cardiovascular disease, metabolic disorder, and cancer. Outside of its role in lipid metabolism, ANGPTL4 signaling remains poorly understood. Here, we identify ANGPTL4 as a Wnt signaling antagonist that binds to syndecans and forms a ternary complex with the Wnt co-receptor Lipoprotein receptor-related protein 6 (LRP6). This protein complex is internalized via clathrin-mediated endocytosis and degraded in lysosomes, leading to attenuation of Wnt/β-catenin signaling. Angptl4 is expressed in the Spemann organizer of Xenopus embryos and acts as a Wnt antagonist to promote notochord formation and prevent muscle differentiation. This unexpected function of ANGPTL4 invites re-interpretation of its diverse physiological effects in light of Wnt signaling and may open therapeutic avenues for human disease.

ObjectivesPatients with HIV infection vaccinated early in the flu season are more likely to contract influenza or influenza-like illness (ILI) compared with those receiving late vaccination. It is known that antibody titres wane over time, particularly among individuals with HIV infection. It is unclear if the timing of influenza vaccination within the flu season affects the probability of an influenza infection later during the flu season. The aim of this study is to evaluate if there is a relationship between the timing of influenza vaccination and incidence of influenza or ILI in patients with HIV infection.MethodsA retrospective cohort study of HIV-infected patients in care at the Department of Veterans Affairs San Diego Healthcare System was conducted from 1 September 2005 to 31 May 2013. Among these patients, we evaluated whether there was a relationship between the timing of influenza vaccination and the incidence of laboratory-confirmed influenza, influenza diagnosed by a physician, or ILI.ResultsPatients who received influenza vaccine early in the season were more likely to contract influenza or ILI than patients who were vaccinated late (P < 0.01). Vaccinated patients who developed influenza or ILI were more likely to do so later in the season (P < 0.01).ConclusionsHIV-infected patients vaccinated early in the flu season were more likely to contract influenza or ILI than those vaccinated later in the season.

ObjectivesPatients with HIV infection vaccinated early in the flu season are more likely to contract influenza or influenza-like illness (ILI) compared with those receiving late vaccination. It is known that antibody titres wane over time, particularly among individuals with HIV infection. It is unclear if the timing of influenza vaccination within the flu season affects the probability of an influenza infection later during the flu season. The aim of this study is to evaluate if there is a relationship between the timing of influenza vaccination and incidence of influenza or ILI in patients with HIV infection.MethodsA retrospective cohort study of HIV-infected patients in care at the Department of Veterans Affairs San Diego Healthcare System was conducted from 1 September 2005 to 31 May 2013. Among these patients, we evaluated whether there was a relationship between the timing of influenza vaccination and the incidence of laboratory-confirmed influenza, influenza diagnosed by a physician, or ILI.ResultsPatients who received influenza vaccine early in the season were more likely to contract influenza or ILI than patients who were vaccinated late (P < 0.01). Vaccinated patients who developed influenza or ILI were more likely to do so later in the season (P < 0.01).ConclusionsHIV-infected patients vaccinated early in the flu season were more likely to contract influenza or ILI than those vaccinated later in the season.