Decrease of Klotho in the Kidney of Streptozotocin-Induced Diabetic Rats

The klotho gene is expressed in a limited number of tissues, most notably in distal convoluted tubules in the kidney and choroid plexus in the brain. A previous study suggested that Klotho increases resistance to oxidative stress. However, changes of Klotho expression in high glucose-induced oxidative stress remain unclear. In the present study, we used streptozotocin-induced diabetic rats (STZ rats) to examine the effects of insulin, phloridzin or antioxidant, tiron on diabetic nephropathy. Both insulin and phloridzin reversed the lower Klotho expression levels in kidneys of STZ rats by the correction of hyperglycemia. Also, renal functions were improved by these treatments. In addition to the improvement of renal functions, the decrease of Klotho expression in kidney of STZ rats was also reversed by tiron without changing blood glucose levels. The reduction of oxidative stress induced by high glucose can be considered for this action of tiron. This view was further confirmed in vitro using high glucose-exposed Madin-Darby canine kidney (MDCK) epithelial cells. Thus, we suggest that decrease of oxidative stress is not only responsible for the improvement of renal function but also for the recovery of Klotho expression in kidney of STZ rats

Comparison of Radical Scavenging Activity, Cytotoxic Effects and Apoptosis Induction in Human Melanoma Cells by Taiwanese Propolis from Different Sources

Propolis is a sticky substance that is collected from plants by honeybees. We previously demonstrated that propolins A, B, C, D, E and F, isolated from Taiwanese propolis (TP), could effectively induce human melanoma cell apoptosis and were strong antioxidant agents. In this study, we evaluated TP for free radical scavenging activity by DPPH (1,2-diphenyl-2-picrylhydrazyl). The phenolic concentrations were quantified by the Folin–Ciocalteu method. The apoptosis trigger activity in human melanoma cells was evaluated. TP contained a higher level of phenolic compounds and showed strong capability to scavenge free radicals. Additionally, TP1g, TP3, TP4 and TP7 exhibited a cytotoxic effect on human melanoma cells, with an IC(50) of ∼2.3, 2.0, 3.3 and 3.3 μg/ml, respectively. Flow cytometric analysis for DNA fragmentation indicated that TP1g, TP2, TP3 and TP7 could induce apoptosis in human melanoma cells and there is a marked loss of cells from the G2/M phase of the cell cycle. To address the mechanism of the apoptosis effect of TP, we evaluated its effects on induction of apoptosis-related proteins in human melanoma cells. The levels of procaspase-3 and PARP [poly(ADP-ribose) polymerase] were markedly decreased. Furthermore, propolins A, B, C, D, E and F in TP were determined using HPLC. The results indicate that TP is a rich source of these compounds. The findings suggest that TP induces apoptosis in human melanoma cells due to its high level of propolins

The Design and Analysis of Passive Pitch Control for Horizontal Axis Wind Turbine

AbstractThe purpose of this thesis is to design and analysis of passive pitch control. Design a mechanics to control different revolution of blade's pitch angle. The use of small wind turbines gradually popularization, but how to overcome the low wind speed start-up and the operation under high wind speed, that is the difficult problems encountered by designers. In order to extend the use and the safe of wind speed, this design is required. This paper is focus on the mechanism design of the passive pitch control for the small horizontal axis wind turbine (HAWT). When the wind speed is fast, the rotation speed is also faster and faster. The system uses centrifugal force to make Pulley disk driven the pitch angle of the blade. It can achieve the effect of passive pitch control. The mechanism is our laboratory's patent. Through the experiments in wind tunnel, it can be observed the variation of the performance curve when the pitch rotation. This system not only successfully operates under high wind speed but also has better performance at low wind speed

A sequence-based hybrid predictor for identifying conformationally ambivalent regions in proteins

<p>Abstract</p> <p>Background</p> <p>Proteins are dynamic macromolecules which may undergo conformational transitions upon changes in environment. As it has been observed in laboratories that protein flexibility is correlated to essential biological functions, scientists have been designing various types of predictors for identifying structurally flexible regions in proteins. In this respect, there are two major categories of predictors. One category of predictors attempts to identify conformationally flexible regions through analysis of protein tertiary structures. Another category of predictors works completely based on analysis of the polypeptide sequences. As the availability of protein tertiary structures is generally limited, the design of predictors that work completely based on sequence information is crucial for advances of molecular biology research.</p> <p>Results</p> <p>In this article, we propose a novel approach to design a sequence-based predictor for identifying conformationally ambivalent regions in proteins. The novelty in the design stems from incorporating two classifiers based on two distinctive supervised learning algorithms that provide complementary prediction powers. Experimental results show that the overall performance delivered by the hybrid predictor proposed in this article is superior to the performance delivered by the existing predictors. Furthermore, the case study presented in this article demonstrates that the proposed hybrid predictor is capable of providing the biologists with valuable clues about the functional sites in a protein chain. The proposed hybrid predictor provides the users with two optional modes, namely, the <it>high-sensitivity </it>mode and the <it>high-specificity </it>mode. The experimental results with an independent testing data set show that the proposed hybrid predictor is capable of delivering sensitivity of 0.710 and specificity of 0.608 under the <it>high-sensitivity </it>mode, while delivering sensitivity of 0.451 and specificity of 0.787 under the <it>high-specificity </it>mode.</p> <p>Conclusion</p> <p>Though experimental results show that the hybrid approach designed to exploit the complementary prediction powers of distinctive supervised learning algorithms works more effectively than conventional approaches, there exists a large room for further improvement with respect to the achieved performance. In this respect, it is of interest to investigate the effects of exploiting additional physiochemical properties that are related to conformational ambivalence. Furthermore, it is of interest to investigate the effects of incorporating lately-developed machine learning approaches, e.g. the random forest design and the multi-stage design. As conformational transition plays a key role in carrying out several essential types of biological functions, the design of more advanced predictors for identifying conformationally ambivalent regions in proteins deserves our continuous attention.</p

Enterovirus type 71 2A protease functions as a transcriptional activator in yeast

Enterovirus type 71 (EV71) 2A protease exhibited strong transcriptional activity in yeast cells. The transcriptional activity of 2A protease was independent of its protease activity. EV71 2A protease retained its transcriptional activity after truncation of 40 amino acids at the N-terminus but lost this activity after truncation of 60 amino acids at the N-terminus or deletion of 20 amino acids at the C-terminus. Thus, the acidic domain at the C-terminus of this protein is essential for its transcriptional activity. Indeed, deletion of amino acids from 146 to 149 (EAME) in this acidic domain lost the transcriptional activity of EV71 2A protein though still retained its protease activity. EV71 2A protease was detected both in the cytoplasm and nucleus using confocal microscopy analysis. Coxsackie virus B3 2A protease also exhibited transcriptional activity in yeast cells. As expected, an acidic domain in the C-terminus of Coxsackie virus B3 2A protease was also identified. Truncation of this acidic domain resulted in the loss of transcriptional activity. Interestingly, this acidic region of poliovirus 2A protease is critical for viral RNA replication. The transcriptional activity of the EV71 or Coxsackie virus B3 2A protease should play a role in viral replication and/or pathogenesis

Increased functional connectivity of the posterior cingulate cortex with the lateral orbitofrontal cortex in depression

To analyze the functioning of the posterior cingulate cortex (PCC) in depression, we performed the first fully voxel-level resting state functional-connectivity neuroimaging analysis of depression of the PCC, with 336 patients with major depressive disorder and 350 controls. Voxels in the PCC had significantly increased functional connectivity with the lateral orbitofrontal cortex, a region implicated in non-reward and which is thereby implicated in depression. In patients receiving medication, the functional connectivity between the lateral orbitofrontal cortex and PCC was decreased back towards that in the controls. In the 350 controls, it was shown that the PCC has high functional connectivity with the parahippocampal regions which are involved in memory. The findings support the theory that the non-reward system in the lateral orbitofrontal cortex has increased effects on memory systems, which contribute to the rumination about sad memories and events in depression. These new findings provide evidence that a key target to ameliorate depression is the lateral orbitofrontal cortex

Role of the supine lateral radiograph of the spine in vertebroplasty for osteoporotic vertebral compression fracture: a prospective study

<p>Abstract</p> <p>Background</p> <p>Severely collapsed vertebral compression fracture (VCF) is usually considered as a contraindication for vertebroplasty because of critically decreased vertebral height (less than one-third the original height). However, osteoporotic VCF can possess dynamic mobility with intravertebral cleft (IVC), which can be demonstrated on supine lateral radiographs (SuLR) and standing lateral radiographs (StLR). The purposes of this study were to: (1) evaluate the efficacy of SuLR to detect IVCs and assess the intravertebral mobility in VCFs, and (2) evaluate the short-term results of vertebroplasty in severely collapsed VCFs with IVCs.</p> <p>Methods</p> <p>We enrolled 37 patients with 40 symptomatic osteoporotic VCFs for vertebroplasty; 11 had severely collapsed VCFs with concurrent IVCs detected on the SuLR, the others had not-severely collapsed VCFs. A preoperative StLR, SuLR, magnetic resonance imaging (MRI), and postoperative StLR were taken from all patients. Radiographs were digitized to calculate vertebral body morphometrics including vertebral height ratio and Cobb's kyphotic angle. The intensity of the patient's pain was assessed by the visual analogue scale (VAS) on the day before operation and 1 day, 1 month, and 4 months after operation. The patient's VAS scores and image measurement results were assessed with the paired <it>t</it>-test and Pearson correlation tests; Mann-Whitney U test was used for VAS subgroup comparison. Significance was defined as <it>p </it>< 0.05.</p> <p>Results</p> <p>IVCs in patients with not-severely collapsed VCFs were detected in 21 vertebrae (72.4%) by MRI, in 15 vertebrae (51.7%) by preoperative SuLR, and in 7 vertebrae (24.1%) by preoperative StLR. Using the MRI as a gold standard to detect IVCs, SuLR exhibit a sensitivity of 0.71 as compared to StLR that yield a sensitivity of 0.33. In patients with VCFs with IVCs detected on SuLR, the average of the postoperative restoration in vertebral height ratio was significantly higher than that in those without IVCs (17.1% vs. 6.4%). There was no statistical difference in the VAS score between severely collapsed VCFs with IVCs detected on SuLR and not-severely collapsed VCFs at any follow-up time point.</p> <p>Conclusions</p> <p>The SuLR efficiently detects an IVC in VCF, which indicates a better vertebral height correction after vertebroplasty compared to VCF without IVC. Before performing a costly MRI, SuLR can identify more IVCs than StLR in patients with severely collapsed VCFs, whom may become the candidates for vertebroplasty.</p