The pathophysiology of most neurodegenerative diseases includes aberrant accumulation of protein aggregates. Recent evidence highlights the role of protein degradation pathways in neurodegeneration. Concurrently, genetic tools have been generated to enable zebrafish, Danio rerio, to be used as an animal model to study neurodegenerative processes. In addition to optical clarity and fast ex utero development, the zebrafish brain is relatively small and has conserved structures with its mammalian counterparts. To take advantage of this model organism and to aid further studies on autophagy and neurodegeneration, we created a stable transgenic zebrafish line that expresses eGFP-Map1lc3b specifically in post-mitotic neurons under the elavl3 promoter. This line is useful for indirectly monitoring autophagic activity in neurons in vivo and screening for macroautophagy/autophagy-modulating compounds. We determined the applicability of this transgenic line by modulating and quantifying the number of autophagosomes via treatment with a known autophagy inducer (rapamycin) and inhibitors (3-methyladenine, protease inhibitors). Additionally, we proposed an in vivo method for quantifying rates of autophagosome accumulation, which can be used to infer occurrence of autophagic flux. Last, we tested two FDA-approved drugs currently undergoing clinical studies for Parkinson disease, isradipine and nilotinib, and found that isradipine did not modulate autophagy, whereas nilotinib induced both autophagosome number and autophagic flux. It is hoped that others will find this line useful as an in vivo vertebrate model to find or validate autophagy modulators that might be used to halt the progression of neurodegenerative diseases.
A simple and rapid multiplexed direct competitive chemiluminescent (CL) imaging immunoassay had been developed for the simultaneous detection of kanamycin (KAN) and streptomycin (STR), which were widely used against bacterial infections in animals. To achieve the multiplexed detection of the two targets, a microarray format based on nitrocellulose membranes (NCMs) has been designed. Then, the peroxidase activity of the captured HRP-labelled immunocomplex in each channel was measured by an enhanced luminol-based chemiluminescent solution using a cooled low-light CCD with high resolution. For qualitative analysis, the limit of detection (LOD) was 0.5 ng mL À1 for KAN and 3.13 ng mL À1 for STR by the naked eye. Through the CL data collected, KAN and STR could be detected quantitatively at the LOD of 0.03 and 0.33 ng mL À1 , respectively. This method can be utilised as a screening test to evaluate the presence of antibiotics in milk samples.
In this paper, a novel path-following and obstacle avoidance control method is given for nonholonomic wheeled mobile robots (NWMRs), based on deep reinforcement learning. The model for path-following is investigated first, and then applied to the proposed reinforcement learning control strategy. The proposed control method can achieve path-following control through interacting with the environment of the set path. The path-following control method is mainly based on the design of the state and reward function in the training of the reinforcement learning. For extra obstacle avoidance problems in following, the state and reward function is redesigned by utilizing both distance and directional perspective aspects, and a minimum representative value is proposed to deal with the occurrence of multiple obstacles in the path-following environment. Through the reinforcement learning algorithm deep deterministic policy gradient (DDPG), the NWMR can gradually achieve the path it is required to follow and avoid the obstacles in simulation experiments, and the effectiveness of the proposed algorithm is verified.
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