No abstract

A pathological hallmark of Alzheimer disease and other tauopathies is the formation of neurofibrillary tangles mainly composed of bundles of fibrils formed by microtubule-associated protein Tau. Here we study the effects of Zn on abnormal aggregation and cytotoxicity of a pathological mutant ΔK280 of full-length human Tau. As revealed by Congo red binding assays, transmission electron microscopy, immunofluorescence, Western blot, and immunogold electron microscopy, pathological concentration of Zn dramatically accelerates the fibrillization of ΔK280 both in vitro and in SH-SY5Y neuroblastoma cells. As evidenced by annexin V-FITC apoptosis detection assay and MTT reduction assay, pathological concentration of Zn remarkably enhances ΔK280 fibrillization-induced apoptosis and toxicity in SH-SY5Y cells. Substitution of Cys-291 and Cys-322 with Ala, however, essentially eliminates such enhancing effects of Zn on the fibrillization and the consequent cytotoxicity of ΔK280. Furthermore, Zn is co-localized with and highly enriched in amyloid fibrils formed by ΔK280 in SH-SY5Y cells. The results from isothermal titration calorimetry show that Zn binds to full-length human Tau by interacting with Cys-291 and Cys-322, forming a 1:1 Zn-Tau complex. Our data demonstrate that zinc dramatically accelerates abnormal aggregation of human Tau and significantly increases Tau toxicity in neuronal cells mainly via bridging Cys-291 and Cys-322. Our findings could explain how pathological zinc regulates Tau aggregation and toxicity associated with Alzheimer disease.

Continuous crystal based PET detectors have features of simple design, low cost, good energy resolution and high detection efficiency. Through single-end readout of scintillation light, direct three-dimensional (3D) position estimation could be another advantage that the continuous crystal detector would have. In this paper, we propose to use artificial neural networks to simultaneously estimate the plane coordinate and DOI coordinate of incident γ photons with detected scintillation light. Using our experimental setup with an '8 + 8' simplified signal readout scheme, the training data of perpendicular irradiation on the front surface and one side surface are obtained, and the plane (x, y) networks and DOI networks are trained and evaluated. The test results show that the artificial neural network for DOI estimation is as effective as for plane estimation. The performance of both estimators is presented by resolution and bias. Without bias correction, the resolution of the plane estimator is on average better than 2 mm and that of the DOI estimator is about 2 mm over the whole area of the detector. With bias correction, the resolution at the edge area for plane estimation or at the end of the block away from the readout PMT for DOI estimation becomes worse, as we expect. The comprehensive performance of the 3D positioning by a neural network is accessed by the experimental test data of oblique irradiations. To show the combined effect of the 3D positioning over the whole area of the detector, the 2D flood images of oblique irradiation are presented with and without bias correction.

M ethods for promoting individuals' pro-environmental behaviours are becoming very important. Besides traditional factors relevant to pro-environmental actions, few studies have examined the licensing effect within this domain. Across three studies we have explored whether the licensing effect really exists in pro-environmental behaviours, how this effect actually works, and how to inhibit or even avoid this effect. Results have revealed that previous pro-environmental behaviours lead to a decrease in subsequent pro-environmental behaviours, indicating a licensing effect. Also, the licensing effect in pro-environmental behaviours can be explained by having individuals focus on goal progress and reduced by focusing on goal commitment. Furthermore, attributional recall could be an intervention for mitigating the licensing effect.

The attachment of planktonic cells to surfaces is the first and most crucial step in biofilm formation. In this paper, we show that planktonic cells of Pseudomonas aeruginosa differently attach to surfaces. Typically, in the later exponential phase, approximately 80% of the cells can quickly attach to surfaces within 15 min, whereas approximately 20% of the cells slowly attach to surfaces, which greatly affects the initial stage of biofilm formation in the presence of flows. This is because fast-attaching cells are more likely to attach on surfaces to form microcolonies, whereas slow-attaching cells are more likely to remain in the mobile phase. This scenario is different from the previous understanding of biofilm formation in the initial stage, in which planktonic cells were thought to uniformly attach to surfaces. Most notably, the results of this study show that the different attachment manner of planktonic cells to surfaces affects the subsequent stages of biofilm formation. This research highlights that the phenotypic variations in planktonic cells plays significant roles in various stages of biofilm formation.