Identifying synergies for passive treatment : integrating solar photocatalysis and biological systems

Conventionally, biological treatment processes are considered the best available technologies (BAT) for mine water remediation but suffer from numerous shortcomings, including toxic organometallic treatment by-products, large treatment footprint, and varying treatment consistencies. Biological systems can benefit from upstream or downstream synergistic processes that can improve treatment performance while addressing negative treatment by-products. To this end H2nanO has developed a passive advanced oxidation (P-AOP) treatment technology consisting of a system of buoyant photocatalyst composites that provides off-grid, high strength oxidative treatment without the need for chemical or electrical inputs. Upon exposure to naturally occurring solar or artificial ultraviolet (UV) light, the photocatalyst technology generates free radicals, including hydroxyl and superoxide. As the photocatalyst media is not consumed, it may be collected for reuse once treatment is complete (batch process) using low-energy flotation and skimming or used continuously in a flow-through system. This work presents results from bench-scale studies investigating the feasibility of solar photocatalysis for the passive co-treatment of dissolved manganese and molybdenum and for the oxidative treatment of trace reduced selenium and organoselenium compounds; and provides insights into the enhancement of biological remediation processes through synergies with solar photocatalysis. As a standalone process or as part of a larger water management program, photocatalysis is a promising passive treatment technology for mine water remediation.Non UBCUnreviewedFacultyOthe

LRP1 is a master regulator of tau uptake and spread.

The spread of protein aggregates during disease progression is a common theme underlying many neurodegenerative diseases. The microtubule-associated protein tau has a central role in the pathogenesis of several forms of dementia known as tauopathies-including Alzheimer's disease, frontotemporal dementia and chronic traumatic encephalopathy1. Progression of these diseases is characterized by the sequential spread and deposition of protein aggregates in a predictable pattern that correlates with clinical severity2. This observation and complementary experimental studies3,4 have suggested that tau can spread in a prion-like manner, by passing to naive cells in which it templates misfolding and aggregation. However, although the propagation of tau has been extensively studied, the underlying cellular mechanisms remain poorly understood. Here we show that the low-density lipoprotein receptor-related protein 1 (LRP1) controls the endocytosis of tau and its subsequent spread. Knockdown of LRP1 significantly reduced tau uptake in H4 neuroglioma cells and in induced pluripotent stem cell-derived neurons. The interaction between tau and LRP1 is mediated by lysine residues in the microtubule-binding repeat region of tau. Furthermore, downregulation of LRP1 in an in vivo mouse model of tau spread was found to effectively reduce the propagation of tau between neurons. Our results identify LRP1 as a key regulator of tau spread in the brain, and therefore a potential target for the treatment of diseases that involve tau spread and aggregation

LRP1 is a master regulator of tau uptake and spread

The spread of protein aggregates during disease progression is a common theme underlying many neurodegenerative diseases. The microtubule-associated protein tau has a central role in the pathogenesis of several forms of dementia known as tauopathies—including Alzheimer’s disease, frontotemporal dementia and chronic traumatic encephalopathy. Progression of these diseases is characterized by the sequential spread and deposition of protein aggregates in a predictable pattern that correlates with clinical severity. This observation and complementary experimental studies have suggested that tau can spread in a prion-like manner, by passing to naive cells in which it templates misfolding and aggregation. However, although the propagation of tau has been extensively studied, the underlying cellular mechanisms remain poorly understood. Here we show that the low-density lipoprotein receptor-related protein 1 (LRP1) controls the endocytosis of tau and its subsequent spread. Knockdown of LRP1 significantly reduced tau uptake in H4 neuroglioma cells and in induced pluripotent stem cell-derived neurons. The interaction between tau and LRP1 is mediated by lysine residues in the microtubule-binding repeat region of tau. Furthermore, downregulation of LRP1 in an in vivo mouse model of tau spread was found to effectively reduce the propagation of tau between neurons. Our results identify LRP1 as a key regulator of tau spread in the brain, and therefore a potential target for the treatment of diseases that involve tau spread and aggregation