MicroRNA-124-3p affects proliferation, migration and apoptosis of bladder cancer cells through targeting AURKA.

OBJECTIVE: The aim of this study was to establish the relationship between miR-124-3p and Aurora A kinase (AURKA) in bladder cancer (BC). METHODS: The expressions of miR-124-3p and AURKA in BC tissues and cell lines were detected using RT-PCR and western blot. BC cells were transfected with miR-124-3p mimics and AURKA siRNA. After this cell proliferation, migration, cell cycle and apoptosis were measured using CCK-8, colony formation assay, wound healing assay and cytometry tests. The relationship between miR-124-3p and AURKA was confirmed with luciferase reporter assay. Mice xenograft models were constructed to examine the effects of AURKA on BC in vivo. RESULTS: MiR-124-3p expression was significantly down-regulated in BC tissues and cell lines, while AURKA was significantly up-regulated compared to normal samples. MiR-124-3p targeted AURKA and decreased its expression. Transfection of miR-124-3p mimics and AURKA siRNA was shown to down-regulate BC cell proliferation and migration as well as induce cell apoptosis. As suggested by xenograft models, the inhibition of AURKA can effectively suppress tumor growth. CONCLUSION: MiR-124-3p has significant impact on proliferation, migration and apoptosis of BC cells by targeting AURKA.

The inhibition of protein translation mediated by AtGCN1 is essential for cold tolerance in Arabidopsis thaliana.

In yeast, the interaction of General Control Non-derepressible 1 (GCN1) with GCN2 enables GCN2 to phosphorylate eIF2α (the alpha subunit of eukaryotic translation initiation factor 2) under a variety of stresses. Here, we cloned AtGCN1, an Arabidopsis homologue of GCN1. We show that AtGCN1 directly interacts with GCN2 and is essential for the phosphorylation of eIF2α under salicylic acid (SA), ultraviolet (UV), cold stress and amino acid deprivation conditions. Two mutant alleles, atgcn1-1 and atgcn1-2, which are defective in the phosphorylation of eIF2α, showed increased sensitivity to cold stress, compared with the wild type. Ribosome-bound RNA profiles showed that the translational state of mRNA was higher in atgcn1-1 than in the wild type. Our result also showed that cold treatment reduced the tendency of the tor mutant seedlings to produce purple hypocotyls. In addition, the kinase activity of TOR was transiently inhibited when plants were exposed to cold stress, suggesting that the inhibition of TOR is another pathway important for plants to respond to cold stress. In conclusion, our results indicate that the AtGCN1-mediated phosphorylation of eIF2α, which is required for inhibiting the initiation of protein translation, is essential for cold tolerance in Arabidopsis.

Anatomical Calibration through Post-Processing of Standard Motion Tests Data.

The inertial measurement unit is popularly used as a wearable and flexible tool for human motion tracking. Sensor-to-body alignment, or anatomical calibration (AC), is fundamental to improve accuracy and reliability. Current AC methods either require extra movements or are limited to specific joints. In this research, the authors propose a novel method to achieve AC from standard motion tests (such as walking, or sit-to-stand), and compare the results with the AC obtained from specially designed movements. The proposed method uses the limited acceleration range on medial-lateral direction, and applies principal component analysis to estimate the sagittal plane, while the vertical direction is estimated from acceleration during quiet stance. The results show a good correlation between the two sets of IMUs placed on frontal/back and lateral sides of head, trunk and lower limbs. Moreover, repeatability and convergence were verified. The AC obtained from sit-to-stand and walking achieved similar results as the movements specifically designed for upper and lower body AC, respectively, except for the feet. Therefore, the experiments without AC performed can be recovered through post-processing on the walking and sit-to-stand data. Moreover, extra movements for AC can be avoided during the experiment and instead achieved through the proposed method.

Epigenetic suppression of the antitumor cytotoxicity of NK cells by histone deacetylase inhibitor valproic acid.

Natural killer (NK) cells play an essential role in the fight against tumor development. The therapeutic use of autologous NK cells has been exploited to treat human malignancies, yet only limited antitumor activity is observed in cancer patients. In this study, we sought to augment the antitumor activity of NK cells using epigenetic approaches. Four small molecules that have been known to promote epigenetic reprogramming were tested for their ability to enhance the activity of NK cells. Using a tumor cell lysis assay, we found that the DNA demethylating agent 5-azacytidine and vitamin C did not significantly affect the tumor killing ability of NK cells. The thyroid hormone triiodothyronine (T3) slightly increased the activity of NK cells. The histone deacetylase inhibitor valproic acid (VPA), however, inhibited NK cell lytic activity against leukemic cells in a dose-dependent manner. Pretreatment using VPA reduced IFNγ secretion, impaired CD107a degranulation, and induced apoptosis by activating the PD-1/PD-L1 pathway. VPA downregulated the expression of the activating receptor NKG2D (natural-killer group 2, member D) by inducing histone K9 hypermethylation and DNA methylation in the gene promoter. Histone deacetylase inhibitors have been developed as anticancer agents for use as monotherapies or in combination with other anticancer therapies. Our data suggest that the activity of histone deacetylase inhibitors on NK cell activity should be considered in drug development.

Development of subliminal persuasion system to improve the upper limb posture in laparoscopic training: a preliminary study.

PURPOSE: Current training for laparoscopy focuses only on the enhancement of manual skill and does not give advice on improving trainees' posture. However, a poor posture can result in increased static muscle loading, faster fatigue, and impaired psychomotor task performance. In this paper, the authors propose a method, named subliminal persuasion, which gives the trainee real-time advice for correcting the upper limb posture during laparoscopic training like the expert but leads to a lower increment in the workload. METHODS: A 9-axis inertial measurement unit was used to compute the upper limb posture, and a Detection Reaction Time device was developed and used to measure the workload. A monitor displayed not only images from laparoscope, but also a visual stimulus, a transparent red cross superimposed to the laparoscopic images, when the trainee had incorrect upper limb posture. One group was exposed, when their posture was not correct during training, to a short (about 33 ms) subliminal visual stimulus. The control group instead was exposed to longer (about 660 ms) supraliminal visual stimuli. RESULTS: We found that subliminal visual stimulation is a valid method to improve trainees' upper limb posture during laparoscopic training. Moreover, the additional workload required for subconscious processing of subliminal visual stimuli is less than the one required for supraliminal visual stimuli, which is processed instead at the conscious level. CONCLUSIONS: We propose subliminal persuasion as a method to give subconscious real-time stimuli to improve upper limb posture during laparoscopic training. Its effectiveness and efficiency were confirmed against supraliminal stimuli transmitted at the conscious level: Subliminal persuasion improved upper limb posture of trainees, with a smaller increase on the overall workload.

Objective evaluation of oral presentation skills using Inertial Measurement Units.

Oral presentation is considered as one of the most sought after skills by companies and professional organizations and program accreditation agencies. However, both learning process and evaluation of this skill are time demanding and complex tasks that need dedication and experience. Furthermore, the role of the instructor is fundamental during the presentation assessment. The instructor needs to consider several verbal and nonverbal communications cues sent in parallel and this kind of evaluation is often subjective. Even if there are oral presentation rubrics that try to standardize the evaluation, they are not an optimal solution because they do not provide the presenter a real-time feedback. In this paper, we describe a system for behavioral monitoring during presentations. We propose an ecological measurement system based on Inertial Measurement Units to evaluate objectively the presenter's posture through objective parameters. The system can be used to provide a real-time feedback to the presenters unobtrusively.