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

Physical Methods for the Preparation of Hybrid Nanocomposite Polymer Latex Particles

In this chapter, we will highlight conceptual physical approaches towards the fabrication of nanocomposite polymer latexes in which each individual latex particle contains one or more "hard" nanoparticles, such as clays, silicates, titanates, or other metal(oxides). By "physical approaches" we mean that the "hard" nanoparticles are added as pre-existing entities, and are not synthesized in situ as part of the nanocomposite polymer latex fabrication process. We will narrow our discussion to focus on physical methods that rely on the assembly of nanoparticles onto the latex particles after the latex particles have been formed, or its reciprocal analogue, the adhesion of polymer onto an inorganic nanoparticle. First, will discuss the phenomenon of heterocoagulation and its various driving forces, such as electrostatic interactions, the hydrophobic effect, and secondary molecular interactions. We will then address methods that involve assembly of nanoparticles onto or around the more liquid precursors (i.e., swollen/growing latex particles or monomer droplets). We will focus on the phenomenon of Pickering stabilization. We will then discuss features of particle interaction with soft interfaces, and see how the adhesion of particles onto emulsion droplets can be applied in suspension, miniemulsion, and emulsion polymerization. Finally, we will very briefly mention some interesting methods that make use of interface-driven templating for making well-defined assembled clusters and supracolloidal structures

Meat and Nicotinamide:A Causal Role in Human Evolution, History, and Demographics

Hunting for meat was a critical step in all animal and human evolution. A key brain-trophic element in meat is vitamin B 3 /nicotinamide. The supply of meat and nicotinamide steadily increased from the Cambrian origin of animal predators ratcheting ever larger brains. This culminated in the 3-million-year evolution of Homo sapiens and our overall demographic success. We view human evolution, recent history, and agricultural and demographic transitions in the light of meat and nicotinamide intake. A biochemical and immunological switch is highlighted that affects fertility in the ‘de novo’ tryptophan-to-kynurenine-nicotinamide ‘immune tolerance’ pathway. Longevity relates to nicotinamide adenine dinucleotide consumer pathways. High meat intake correlates with moderate fertility, high intelligence, good health, and longevity with consequent population stability, whereas low meat/high cereal intake (short of starvation) correlates with high fertility, disease, and population booms and busts. Too high a meat intake and fertility falls below replacement levels. Reducing variances in meat consumption might help stabilise population growth and improve human capital