Large-scale protein identification of human urine proteome by multi-dimensional LC and MS/MS

Urine is a human specimen that is easily obtained non-invasively for clinical diagnosis. We attempted to enhance the resolution of current human urine proteomes and construct a comprehensive reference database for advanced studies, such as the discovery of biomarkers for renal diseases. Multi-dimensional LC-MS/MS was coupled with de novo sequencing and database matching. The proposed approach improved the identification of not only the proteins, but also the post-translational sites of urinary proteins. We identified 165, 200 and 259 unique gene products in the urine proteomes from males, females and pregnant women, respectively. When all of the results were combined and the redundancies removed, a total of 1095 distinct peptides were identified. Of these, 1016 peptides were associated with 334 unique gene products. In this study, over 100 gene products, including some disease-related proteins, were detected in urine for the first time by proteomic approaches. Various proteins with novel post-translational hydroxylation were identified using the MASCOT program and de novo sequencing. All proteins with peptide information were summarized into a comprehensive urine protein database. We believe that this comprehensive urine proteome database will assist in the identification of urinary proteins/polypeptides whose spectra are difficult to interpret in the discovery of urinary biomarkers.     

高效液相色谱-串联质谱法测定植物源食品中特丁硫磷、特丁硫磷砜和特丁硫磷亚砜的残留量

目的 建立高效液相色谱-串联质谱法测定植物源食品中特丁硫磷、特丁硫磷砜和特丁硫磷亚砜残留量的分析方法.方法 样品采用乙腈或1％乙酸-乙腈提取,提取液经分散固相萃取净化.以CORTECS C18(100 mm×2.1 mm,2.7?m)色谱柱分离待测物,以0.1％乙酸铵甲醇溶液和0.1％甲酸加乙酸铵水溶液为流动相,梯度洗...     

基于非靶向代谢组学比较不同发酵方式红茶滋味物质差异

目的 基于非靶向代谢组学,明确恒温发酵和变温发酵红茶的滋味物质差异。方法 采用超高效液相色谱-四极杆-静电场轨道阱高分辨质谱法（ultra performance liquid chromatography-quadrupole-electrostatic orbitrap high-resolution mass spectrometer,U PLC-Q-Orbitrap-MS）对华蓥山不同发酵方式红茶的非挥发性化合物进行了非靶向筛查,采用Compound Discoverer 3.1和Chemspider软件对化合物进行鉴定,并结合多元统计学软件筛选特征差异化合物。结果 通过UHPLC-Q-Orbitrap-MS检测到358种非挥发性化合物,通过正交偏最小二乘-重要变量投影（orthogonal partial least square-variable import project,OPLS-VIP）结合非参数检验,获得了具有标志性差异的成分91种（VIP＞1.0,P＜0.05）;变温发酵红茶有66种物质相对含量显著 高于恒温发酵红茶,有25种物质相对含量显著低于恒温发酵红茶。结论 该研究确定了恒温发酵和变温发酵红茶的差异滋味物质,为四川华蓥山红茶滋味品质的调控和加工工艺的改善提供了参考依据。     

Comparative investigation of InP/InGaAs heterostructure-emitter tunneling and superlattice bipolar transistors

In this article, the characteristics of InP/InGaAs heterostructure-emitter bipolar transistors with 30 n-InP layer tunneling layers and a five-period InP/InGaAs superlattice are demonstrated and comparatively investigated by experimentally results and analysis. In the three devices, a 200 Å n-In_0.53Ga_0.47As layer together with an n-InP tunneling emitter layer (or n-InP/n-InGaAs superlattice) forms heterostructure emitter to decrease collector-emitter offset voltage. The results exhibits that the largest collector current and current gain are obtained for the tunneling transistor with a 30 Å n-InP tunneling emitter layer. On the other hand, some of holes injecting from base to emitter will be blocked at n-InP/n-InGaAs heterojunction due to the relatively small hole transmission coefficient in superlattice device, which will result in a considerable base recombination current in the n-InGaAs layer. Therefore, the collector current and current gain of the superlattice device are the smallest values among of the devices.     

A decision theoretic approach to change point estimation for binomial CUSUM control charts

Detecting when the process has changed is a classical problem in sequential analysis and is an important practical issue in statistical process control. This article is concerned about the binomial cumulative sum (CUSUM) control chart, which is extensively applied to industrial process control, health care, public health surveillance, and other fields. For the binomial CUSUM, a maximum likelihood estimator has been proposed to estimate the change point. In our article, following a decision theoretic approach, we develop a new estimator that aims to improve the existing methods. For interval estimation, we propose a parametric bootstrap procedure to construct the confidence set of the change point. We compare our proposed method with the maximum likelihood estimator and Page's last zero estimator in terms of mean squared error by simulations. We find that the proposed method gives more unbiased and robust results than the existing procedures under various parameter designs. We analyze jewelry manufacturing data for illustration.     

Advances in optical engineering for future telescopes

Significant optical engineering advances at the University of Arizona are being made for design,fabrication,and con-struction of next generation astronomical te...     

腐植酸诱导人早幼粒白血病HL-60细胞凋亡

试验采用人早幼粒白血病HL-60细胞,主要通过细胞活性丧失,染色质凝聚、核小体间DNA断裂等凋亡特征,研究了腐植酸诱导细胞凋亡的效应,观察了不同时间不同剂量(50～400 μg/mL)腐植酸对细胞凋亡的影响.腐植酸诱导HL-60细胞凋亡主要与线粒体内细胞色素c的释放有关,并证明伴随着Caspase-3(天冬氨酸特异性半...     

Characteristics of Ventricular Electrophysiological Substrates in Metabolic Mice Treated with Empagliflozin

Empagliflozin (EMPA) is a sodium–glucose transporter 2 (SGLT2) inhibitor that functions as a new-generation glucose-lowering agent and has been proven to be beneficial for patients with cardiovascular diseases. However, the possible benefits and mechanisms of its antiarrhythmic effects in cardiac tissue have not yet been reported. In this study, we elucidated the possible antiarrhythmic effects and mechanisms of EMPA treatment in cardiac tissues of metabolic syndrome (MS) mice. A total of 20 C57BL/6J mice (age: 8 weeks) were divided into four groups: (1) control group, mice fed a standard chow for 16 weeks; (2) MS group, mice fed a high-fat diet for 16 weeks; (3) EMPA group, mice fed a high-fat diet for 12 weeks and administered EMPA at 10 mg/kg daily for the following 4 weeks; and (4) glibenclamide (GLI) group, mice fed a high-fat diet for 12 weeks and administered GLI at 0.6 mg/kg daily for the following 4 weeks. All mice were sacrificed after 16 weeks of feeding. The parameters of electrocardiography (ECG), echocardiography, and the effective refractory period (ERP) of the left ventricle were recorded. The histological characteristics of cardiac tissue, including connexin (Cx) expression and fibrotic areas, were also evaluated. Compared with the MS group, the ECG QT interval in the EMPA group was significantly shorter (57.06 ± 3.43 ms vs. 50.00 ± 2.62 ms, p = 0.011). The ERP of the left ventricle was also significantly shorter in the EMPA group than that in the GLI group (20.00 ± 10.00 ms vs. 60.00 ± 10.00 ms, p = 0.001). The expression of Cx40 and Cx43 in ventricular tissue was significantly lower in the MS group than in the control group. However, the downregulation of Cx40 and Cx43 was significantly attenuated in the EMPA group compared with the MS and GLI groups. The fibrotic areas of ventricular tissue were also fewer in the EMPA group than that in the MS group. In this study, the ECG QT interval in the EMPA group was shorter than that in the MS group. Compared with the MS group, the EMPA group exhibited significant attenuation of downregulated connexin expression and significantly fewer fibrotic areas in ventricles. These results may provide evidence of possible antiarrhythmic effects of EMPA.     

A Small Cyclic β-Hairpin Peptide Mimics the Rbfox2 RNA Recognition Motif and Binds to the Precursor miRNA 20b

The RNA recognition motif (RRM), which is the most abundant RNA-binding motif in eukaryotes, is a well-structured domain of about 90 amino acids, yet the β2β3 hairpin, corresponding to strands 2 and 3 of the β-sheet, and the intervening loop make essential interactions with RNA in many RRM complexes. A series of small cyclic peptide mimics of the β2β3 hairpin of Rbfox2 protein that recognize the terminal loop of precursor miR-20b have been designed to investigate whether the full RNA-binding protein can be mimicked with a minimal structurally preorganized peptide. Within a small library of seven cyclic peptides, a peptide with low-micromolar affinity for the miR-20b precursor was found. NMR spectroscopy titration data suggest that this peptide specifically targets the apical loop of pre-miR-20b. This work shows that it is possible to mimic RNA-binding proteins with designed stable peptides, which provide a starting point for designing or evolving small peptide mimetics of RRM proteins.