The amyloid precursor protein controls PIKfyve function

While the Amyloid Precursor Protein (APP) plays a central role in Alzheimer's disease, its cellular function still remains largely unclear. It was our goal to establish APP function which will provide insights into APP's implication in Alzheimer's disease. Using our recently developed proteo-liposome assay we established the interactome of APP's intracellular domain (known as AICD), thereby identifying novel APP interactors that provide mechanistic insights into APP function. By combining biochemical, cell biological and genetic approaches we validated the functional significance of one of these novel interactors. Here we show that APP binds the PIKfyve complex, an essential kinase for the synthesis of the endosomal phosphoinositide phosphatidylinositol-3,5-bisphosphate. This signalling lipid plays a crucial role in endosomal homeostasis and receptor sorting. Loss of PIKfyve function by mutation causes profound neurodegeneration in mammals. Using C. elegans genetics we demonstrate that APP functionally cooperates with PIKfyve in vivo. This regulation is required for maintaining endosomal and neuronal function. Our findings establish an unexpected role for APP in the regulation of endosomal phosphoinositide metabolism with dramatic consequences for endosomal biology and important implications for our understanding of Alzheimer's disease

Chapter 7: Phenotyping, Body Composition, and Precision Nutrition

Precision nutrition, by integrating information from studies of anthropometry, genetics, epigenetics, metabolomics, and the microbiome, may lead to improved personalised recommendations for the prevention and management of overweight and obesity. Obesity results from the interaction of heritable physiology and modifiable lifestyle risk factors. The lifestyle factors which have become more common over the last 50 years, leading to an increased prevalence of obesity in both industrialised and developing countries, include rural-to-urban migration, dietary factors, sedentary lifestyles, poor sleep, and socioeconomic and demographic factors [1]. Heritable factors predisposing to obesity may also influence individual behavioural responses to the obesogenic environment by affecting appetite, dietary patterns, individual preferences for macronutrients, and energy balance [2–9] Genome-wide association studies (GWAS) have found numerous associations of obesity with genetic polymorphisms [10–12]. However, interactions between genetic variants and environmental risk factors, which are prominent in obesity, complicate the calculation of risk based on individual genetic variants. Genetic risk scores formulated from combinations of genetic variants have been used in studies of the interaction of dietary factors and genetic background with some success [13]. However, advances in nutrition science, including the discovery of the role of the microbiome in obesity, have led to the realisation that not only genetics, but epigenetics, metabolomics, and the gut microbiome can impact overweight and obesity, resulting in many intermediate phenotypes which can be differentiated with anthropometric and body composition studies

Carrier relaxation dynamics in annealed and hydrogenated (GaIn)(NAs) quantum wells

We measured time-resolved photoluminescence on as-grown, annealed, as well as annealed and hydrogenated (Ga0.7In0.3)(N0.006As0.994)∕GaAs quantum-well structures. The postgrowth treatment changes not only the photoluminescence decay time but also the intensity of photoluminescence directly after excitation. This initial luminescence intensity is determined by a competition between relaxation of electrons into nitrogen related potential fluctuations in the conduction band and their capture by deep traps. In contrast, the decay of the photoluminescence is mainly determined by the competition between radiative and nonradiative recombination, which are both influenced by localization. Annealing decreases localization effects and nonradiative recombination. Hydrogenation also reduces localization effects but increases nonradiative recombination