Endocytic proteins with prion-like domains form viscoelastic condensates that enable membrane remodeling.

Membrane invagination and vesicle formation are key steps in endocytosis and cellular trafficking. Here, we show that endocytic coat proteins with prion-like domains (PLDs) form hemispherical puncta in the budding yeast, Saccharomyces cerevisiae These puncta have the hallmarks of biomolecular condensates and organize proteins at the membrane for actin-dependent endocytosis. They also enable membrane remodeling to drive actin-independent endocytosis. The puncta, which we refer to as endocytic condensates, form and dissolve reversibly in response to changes in temperature and solution conditions. We find that endocytic condensates are organized around dynamic protein-protein interaction networks, which involve interactions among PLDs with high glutamine contents. The endocytic coat protein Sla1 is at the hub of the protein-protein interaction network. Using active rheology, we inferred the material properties of endocytic condensates. These experiments show that endocytic condensates are akin to viscoelastic materials. We use these characterizations to estimate the interfacial tension between endocytic condensates and their surroundings. We then adapt the physics of contact mechanics, specifically modifications of Hertz theory, to develop a quantitative framework for describing how interfacial tensions among condensates, the membrane, and the cytosol can deform the plasma membrane to enable actin-independent endocytosis.

Simulation in a blended learning curriculum for neonatology.

Blended learning is a learner-centered educational method that combines online and traditional face-to-face educational strategies. Simulation is a commonly utilized platform for experiential learning and an ideal component of a blended learning curriculum. This section describes blended learning, including its strengths and limitations, educational frameworks, uses within health professions education, best practices, and challenges. Also included is a brief introduction to simulation-based education, along with theoretical and real-world examples of how simulation may be integrated into a blended learning curriculum. Examples of blended learning in Neonatal-Perinatal Medicine, specifically within the Neonatal Resuscitation Program, procedural skills training, and the National Neonatology Curriculum, are reviewed.

Cardiac surgery after mediastinal radiation: extent of exposure influences outcome.

OBJECTIVES: Mediastinal radiation for thoracic malignancies uses multiple treatment fields and doses. We investigated whether more extensive radiation exposure is associated with more hospital complications and worse survival after cardiac surgery. METHODS: From January 2000 to January 2005, 230 patients underwent cardiac surgery after 3 levels of mediastinal radiation: extensive (Hodgkin disease, thymoma, and testicular cancer; n = 70), variable (eg, non-Hodgkin lymphoma and lung cancer; n = 35); and tangential (breast cancer; n = 125). Hospital complications were recorded prospectively, and time-related survival was assessed by patient follow-up (mean follow-up, 2.2 +/- 1.4 years). RESULTS: Patients receiving extensive exposure were youngest (51 vs 64 vs 72 years), with the longest radiation-to-operation interval (25 vs 13 vs 14 years), and had the most diastolic dysfunction, left main stenosis of greater than 70% (21% vs 9% vs 8%), and aortic regurgitation (79% vs 54% vs 50%). Patients receiving extensive and variable exposure had the poorest pulmonary function (percent predicted forced expiratory volume in 1 second, 57% vs 54% vs 67%; percent predicted forced vital capacity, 56% vs 63% vs 66%). All groups received a similar mix of cardiac procedures. Hospital deaths (13% vs 8.6% vs 2.4%) and respiratory complications (24% vs 20% vs 9.6%) were higher after more extensive radiation, and survival was poorer (4-year survival, 64% vs 57% vs 80%) than for patients receiving tangential radiation exposure, and it deviated more from expected matched-population life tables. CONCLUSIONS: Among patients undergoing cardiac surgery after thoracic radiation, radiation exposure is heterogeneous, and therefore these patients cannot be managed and assessed as a single uniform cohort. Extensively irradiated patients are more likely to develop radiation heart disease, which increases perioperative morbidity and decreases short- and long-term survival.