American Thoracic Society 2019 Pediatric Core Curriculum

The American Thoracic Society Pediatric Core Curriculum updates clinicians annually in pediatric pulmonary disease in a 3 to 4 year recurring cycle of topics. The 2019 course was presented in May during the Annual International Conference. An American Board of Pediatrics Maintenance of Certification module and a continuing medical education exercise covering the contents of the Core Curriculum can be accessed online at www.thoracic.org.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152541/1/ppul24482_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152541/2/ppul24482.pd

Increased ADORA2B Expression Correlates with Mean Pulmonary Arterial Pressure in Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is often accompanied by pulmonary hypertension (PH), a mortality predictor leading to increased vascular remodeling, right-heart failure and death. Studies have shown that adenosine A2B receptor (ADORA2B) is elevated after tissue injury and it participates in wound healing and tissue remodeling responses. We aimed to show whether mean pulmonary arterial pressure (mPAP) correlated with pulmonary function tests (PFTs) and increased expression of mediators involved in the disease progression. A retrospective review on 30 patients on post-lung transplantation with IPF where native lung was collected from 02/2011 to 09/2012. Results of PFTs and mPAP were collected. RNA and protein were isolated for qRT-PCR and western blot from frozen lung explant samples. Controls were 18srRNA and β-actin. Linear regression and Pearson’s correlation between transcript levels and mPAP were analyzed. p<0.05 was considered significant. 12/30 presented with PH (IPF+PH group); 63% male; 60% Caucasian. Linear regression analysis demonstrates no association between PFTs or Collagen I (Col1A1 transcript) levels and mPAP values. mPAP compared to FVC%, TLC%, DLCO% and FEV1% showed no statistical significance. When mPAP was compared to ADORA2B expression levels, we found a significant correlation (p=0.0373, r2 0.1685) suggesting a link between heightened ADORA2B expression levels and elevated mPAP. [figure 1] Western blot corroborated by showing heightened ADORA2B protein levels in IPF+PH. Results demonstrate a direct positive correlation between ADORA2B and mPAP in patients with IPF; pointing to a role for ADORA2B in the pathophysiology of PH in IPF that could lead to new therapies

Stimulation of Lung Innate Immunity Protects against Lethal Pneumococcal Pneumonia in Mice

Rationale: The lungs are a common site of serious infection in both healthy and immunocompromised subjects, and the most likely route of delivery of a bioterror agent. Since the airway epithelium shows great structural plasticity in response to inflammatory stimuli, we hypothesized it might also show functional plasticity

Sequestration of phosphoinositides by mutated MARCKS effector domain inhibits stimulated Ca2+ mobilization and degranulation in mast cells

A new strategy for interfering with phosphoinositide-dependent processes at the plasma membrane uses high-avidity association of the polybasic MARCKS effector domain with negatively charged phospholipids to provide new insights into roles for phosphoinositides in IgE receptor signaling leading to exocytosis

Multiple roles for the actin cytoskeleton during regulated exocytosis

Regulated exocytosis is the main mechanism utilized by specialized secretory cells to deliver molecules to the cell surface by virtue of membranous containers (i.e. secretory vesicles). The process involves a series of highly coordinated and sequential steps, which include the biogenesis of the vesicles, their delivery to the cell periphery, their fusion with the plasma membrane and the release of their content into the extracellular space. Each of these steps is regulated by the actin cytoskeleton. In this review, we summarize the current knowledge regarding the involvement of actin and its associated molecules during each of the exocytic steps in vertebrates, and suggest that the overall role of the actin cytoskeleton during regulated exocytosis is linked to the architecture and the physiology of the secretory cells under examination. Specifically, in neurons, neuroendocrine, endocrine, and hematopoietic cells, which contain small secretory vesicles that undergo rapid exocytosis (on the order of milliseconds), the actin cytoskeleton plays a role in pre-fusion events, where it acts primarily as a functional barrier and facilitates docking. In exocrine and other secretory cells, which contain large secretory vesicles that undergo slow exocytosis (seconds to minutes), the actin cytoskeleton plays a role in post-fusion events, where it regulates the dynamics of the fusion pore, facilitates the integration of the vesicles into the plasma membrane, provides structural support, and promotes the expulsion of large cargo molecules