ER-mitochondria contacts and cholesterol metabolism are disrupted by disease-associated tau protein

Abnormal tau protein impairs mitochondrial function, including transport, dynamics, and bioenergetics. Mitochondria interact with the endoplasmic reticulum (ER) via mitochondria-associated ER membranes (MAMs), which coordinate and modulate many cellular functions, including mitochondrial cholesterol metabolism. Here, we show that abnormal tau loosens the association between the ER and mitochondria in vivo and in vitro. Especially, ER-mitochondria interactions via vesicle-associated membrane protein-associated protein (VAPB)-protein tyrosine phosphatase-interacting protein 51 (PTPIP51) are decreased in the presence of abnormal tau. Disruption of MAMs in cells with abnormal tau alters the levels of mitochondrial cholesterol and pregnenolone, indicating that conversion of cholesterol into pregnenolone is impaired. Opposite effects are observed in the absence of tau. Besides, targeted metabolomics reveals overall alterations in cholesterol-related metabolites by tau. The inhibition of GSK3β decreases abnormal tau hyperphosphorylation and increases VAPB-PTPIP51 interactions, restoring mitochondrial cholesterol and pregnenolone levels. This study is the first to highlight a link between tau-induced impairments in the ER-mitochondria interaction and cholesterol metabolism

Weighing of different impact factors on wet web strength by full-factorial design of experiments

The wet web strength is one of the most important parameters for effective paper machine performance. A huge variety of parameters is known from many studies to have an impact on the wet web strength (WWS). In this study, a full factorial design of experiments (DOE) was used to determine the effect of different factors on the WWS. The goal was to use a DOE method within the field of paper strength research to acquire advanced information on the mechanisms of strength development at different dryness levels. The study was carried out with laboratory handsheets made of commercial unbleached softwood pulp, which was refined in a laboratory Hollander beater. The WWS was measured according to the German standard DIN 54514. The analysis of the data showed that weighing of the influencing factors on WWS is possible, which may lead to a better understanding of paper strength development mechanisms at low dryness levels. The applied method was proven to be reliable for the determination of the impact of various factors and will therefore be used in future work

Chemisch-physikalische Wechselwirkungen und deren Einfluss auf die initiale Nassfestigkeit. 3. Darmstädter Papierchemie-Kolloquium 09. Mai 2014; [Vortrag]

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Demonstration of Strength Development in Initial Wet Paper Web using Field Emission-Scanning Electron Microscopy (FE-SEM)

Various models exist that explain strength development in the wet web. Furthermore the scanning electron microscope (SEM) has been used in the paper industry to characterise cellulosic fibres and paper. The documentation of the initial wet web properties needs very specific requirements for sample preparation. An SEM image shows the sample´s surface, so the wet sample’s water film would cover all fine fibre structures. For this reason the samples must be dried prior to analysis. Freeze drying is a common method that is described to prepare samples for characterisation of single fibres before and after mechanical treatment. In this investigation the structure of the initial wet web was physically fixed by rapid freezing, followed by freeze drying. Afterwards, the samples were analyzed by Field Emission SEM (FE-SEM). The generated images support the hypothesis that fibrils partially extend themselves from the fibre and interact with adjacent fibres

Systematic Comparison of Thermochemical Conversion Processes for Bio-oil Production

Poster präsentiert von M.A. Azeez