dOCRL maintains immune cell quiescence in Drosophila by regulating endosomal traffic

Lowe Syndrome is a developmental disorder characterized by eye, kidney, and neurological pathologies, and is caused by mutations in the phosphatidylinositol-5-phosphatase OCRL. OCRL plays diverse roles in endocytic and endolysosomal trafficking, cytokinesis, and ciliogenesis, but it is unclear which of these cellular functions underlie specific patient symptoms. Here, we show that mutation of Drosophila OCRL causes cell-autonomous activation of hemocytes, which are macrophage-like cells of the innate immune system. Among many cell biological defects that we identified in docrl mutant hemocytes, we pinpointed the cause of innate immune cell activation to reduced Rab11-dependent recycling traffic and concomitantly increased Rab7-dependent late endosome traffic. Loss of docrl amplifies multiple immune-relevant signals, including Toll, Jun kinase, and STAT, and leads to Rab11-sensitive mis-sorting and excessive secretion of the Toll ligand Spåtzle. Thus, docrl regulation of endosomal traffic maintains hemocytes in a poised, but quiescent state, suggesting mechanisms by which endosomal misregulation of signaling may contribute to symptoms of Lowe syndrome

Particulate air pollution, systemic oxidative stress, inflammation, and atherosclerosis

Air pollution has been associated with significant adverse health effects leading to increased overall morbidity and mortality of worldwide significance. Epidemiological studies have shown that the largest portion of air pollution-related mortality is due to cardiovascular diseases, predominantly those of ischemic nature. Human studies suggest an association with atherosclerosis and increasing experimental animal data support that this association is likely to be causal. While both gasses and particles have been linked to detrimental health effects, more evidence implicates the particulate matter (PM) components as major responsible for a large portion of the proatherogenic effects. Multiple experimental approaches have revealed the ability of PM components to trigger and/or enhance free radical reactions in cells and tissues, both ex vivo as well as in vivo. It appears that exposure to PM leads to the development of systemic prooxidant and proinflammatory effects that may be of great importance in the development of atherosclerotic lesions. This article reviews the epidemiological studies, experimental animal, and cellular data that support the association of air pollutants, especially the particulate components, with systemic oxidative stress, inflammation, and atherosclerosis. It also reviews the use of transcriptomic studies to elucidate molecular pathways of importance in those systemic effects

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Utilizing Inclusion Instructional Methods to Promote Student Motivation and Success in the Movement Environment: "The Pool Model"

When physical educators look at a swimming pool they can see several adaptations and modifications that are provided to facilitate the safety and skill level proficiency of different swimmers. Depth markers are prominently posted on the side walls and the deck, signs warn against diving into shallow areas (Figure 1) and teachers and lifeguards constantly observe swimmers to insure safe conduct and activity in the pool area. Lane and rope markers warn swimmers of water depth and where it is safe to dive. Spring boards and diving platforms are available at varying heights to appropriately challenge the different skill levels of swimmers and divers at the pool (Figure 2). Flotation equipment is used by physical educators to accommodate the safe learning and improvement of skills in beginners and low-skill swimmers and that same equipment is also used by teachers and coaches to improve the skills and performance levels of elite swimmers (Figure 3). Other modifications like ramps and lift chairs (Figure 4) are also used by adapted physical educators to accommodate swimmers with physical limitations and to create a more inclusive learning environment at the pool. Properly trained and certified physical educators and lifeguards as well as life-saving equipment are necessary to protect swimmers and provide a safe and enjoyable learning environment