iPSC-derived neuronal models of PANK2-associated neurodegeneration reveal mitochondrial dysfunction contributing to early disease

Mutations in PANK2 lead to neurodegeneration with brain iron accumulation. PANK2 has a role in the biosynthesis of coenzyme A (CoA) from dietary vitamin B5, but the neuropathological mechanism and reasons for iron accumulation remain unknown. In this study, atypical patient-derived fibroblasts were reprogrammed into induced pluripotent stem cells (iPSCs) and subsequently differentiated into cortical neuronal cells for studying disease mechanisms in human neurons. We observed no changes in PANK2 expression between control and patient cells, but a reduction in protein levels was apparent in patient cells. CoA homeostasis and cellular iron handling were normal, mitochondrial function was affected; displaying activated NADH-related and inhibited FADH-related respiration, resulting in increased mitochondrial membrane potential. This led to increased reactive oxygen species generation and lipid peroxidation in patient-derived neurons. These data suggest that mitochondrial deficiency is an early feature of the disease process and can be explained by altered NADH/FADH substrate supply to oxidative phosphorylation. Intriguingly, iron chelation appeared to exacerbate the mitochondrial phenotype in both control and patient neuronal cells. This raises caution for the use iron chelation therapy in general when iron accumulation is absent

A Critical Review on the Structural Health Monitoring Methods of the Composite Wind Turbine Blades

With increasing turbine size, monitoring of blades becomes increasingly im-portant, in order to prevent catastrophic damages and unnecessary mainte-nance, minimize the downtime and labor cost and improving the safety is-sues and reliability. The present work provides a review and classification of various structural health monitoring (SHM) methods as strain measurement utilizing optical fiber sensors and Fiber Bragg Gratings (FBG’s), active/ pas-sive acoustic emission method, vibration‒based method, thermal imaging method and ultrasonic methods, based on the recent investigations and prom-ising novel techniques. Since accuracy, comprehensiveness and cost-effectiveness are the fundamental parameters in selecting the SHM method, a systematically summarized investigation encompassing methods capabilities/ limitations and sensors types, is needed. Furthermore, the damages which are included in the present work are fiber breakage, matrix cracking, delamina-tion, fiber debonding, crack opening at leading/ trailing edge and ice accre-tion. Taking into account the types of the sensors relevant to different SHM methods, the advantages/ capabilities and disadvantages/ limitations of repre-sented methods are nominated and analyzed

The Canlex Project: summary and conclusions

The Canadian geotechnical engineering community has completed a major collaborative 5 year research project entitled the Canadian Liquefaction Experiment (CANLEX). The main objective of the project was to study the phenomenon of soil liquefaction, which can occur in saturated sandy soils and is characterized by a large loss of strength or stiffness resulting in substantial deformations. The intent of this paper is to compare, interpret, and summarize the large amount of field and laboratory data obtained for six sites in Western Canada as part of the CANLEX project. The sites are compared in terms of both flow-liquefaction and cyclic-softening considerations. The paper presents a number of conclusions drawn from the project as a whole, in terms of both fundamental and practical significance.published_or_final_versio