Determination of the Substrate Specificity of Protein-tyrosine Phosphatase TULA-2 and Identification of Syk as a TULA-2 Substrate

TULA-1 (UBASH3A/STS-2) and TULA-2 (p70/STS-1) represent a novel class of protein-tyrosine phosphatases. Previous studies suggest that TULA-2 is sequence-selective toward phosphotyrosyl (Tyr(P)) peptides. In this work the substrate specificity of TULA-1 and -2 was systematically evaluated by screening a combinatorial Tyr(P) peptide library. Although TULA-1 showed no detectable activity toward any of the Tyr(P) peptides in the library, TULA-2 recognizes two distinct classes of Tyr(P) substrates. On the N-terminal side of Tyr(P), the class I substrates contain a proline at the Tyr(P)−1 position, a hydrophilic residue at the Tyr(P)−2 position, and aromatic hydrophobic residues at positions Tyr(P)−3 and beyond. The class II substrates typically contain two or more acidic residues, especially at Tyr(P)−1 to Tyr(P)−3 positions, and aromatic hydrophobic residues at other positions. At the C-terminal side of Tyr(P), TULA-2 generally prefers acidic and aromatic residues. The library screening results were confirmed by kinetic analysis of representative peptides selected from the library as well as Tyr(P) peptides derived from various Tyr(P) proteins. TULA-2 is highly active toward peptides corresponding to the Tyr(P)-323 and Tyr(P)-352 sites of Syk, and the Tyr(P)-397 site of focal adhesion kinase and has lower activity toward other Tyr(P) sites in these proteins. In glycoprotein VI-stimulated platelets, knock-out of the TULA-2 gene significantly increased the phosphorylation level of Syk at Tyr-323 and Tyr-352 sites and to a lesser degree at the Tyr-525/526 sites. These results suggest that Syk is a bona fide TULA-2 substrate in platelets.     

桃金娘叶的化学成分研究

为了解桃金娘[Rhodomyrtus tomentosa(Ait.) Hassk.]的化学成分,从其叶的醇提物中分离得到10个化合物,经波谱分析分别鉴定为羽扇豆醇(1)、杨梅素-3-O-α-L-鼠李糖苷(2)、rhodomyrtone (3)、4,8,9,10-四羟基-2,3,7-三甲氧基蒽醌-6-O-β-D-葡萄糖苷(4)、豆甾醇(5)、山奈酚-3-O-α-L-呋喃阿拉伯糖苷(6)、杨梅素(7)、23-羟基委陵菜酸(8)、2α,3β,19α,23-四羟基乌苏-12-烯-28-酸28-O-β-D-吡喃葡萄糖苷(9)和laricitrin (10)。其中化合物5~10均为首次从桃金娘中分离得到。化合物3对金黄色葡萄球菌、蜡样芽孢杆菌和枯草芽孢杆菌表现出显著的抗菌活性(MIC=0.78μg mL–1)。     

灰黑拟牛肝菌的化学成分

从担子菌灰黑拟牛肝菌（Boletopsis grisea)新鲜子实体的乙醇提取物中首次分离得到10个化合物,包括8个酚性成分,1个含硫成分和1个脑苷脂,它们的结构经各种波谱数据分别鉴定为3－（4－乙酰氧基苯）－1,2,4,7,8－五乙酰氧基二苯并呋喃（1）,3－（4－乙酰氧基苯）－1,2,4－三乙酰氧基－7,8－二羟基二苯并呋喃（2）,3－（4－羟基苯）－1,2－二乙酰氧基－4,7,8－三羟基二苯并呋喃（3）,2,3－二乙酰氧基－4′,4″,5,6－四羟基对联三苯（4）,对苯二酚（5）,对羟基苯甲酸（6）,茴香酸（7）,对羟基苯甲醛（8）,硫代乙酐（9）和1－O－吡喃葡萄糖基－（2S,3R,4E,8E,2′R）-2-N-(2′-羟基棕榈酰）－9－甲基－4,8－sphin-gadienine(10)。其中化合物1,2,3有报道对5－脂氧化酶具有选择性抑制活性。4,9,10均为首次从该属真菌中分离得到。     

4－硒（代）硫酸酯多糖的抗肿瘤免疫调节作用及其机制研究

本实验系统地研究了４－硒（代）硫酸酯多糖的抗肿瘤免疫调节作用及其机制。发现该药在体内外均有抑制肿瘤生长的作用,并认为其抑瘤机制与促进巨噬细胞活性,间接促进淋巴细胞活性,释放具有杀伤肿瘤细胞的效应分子以及选择性抑制肿瘤细胞大分子合成有关。结果表明,４－硒（代）硫酸酯多糖是一种兼具杀伤肿瘤细胞和增强免疫功能双重作用的新型免疫型抗肿瘤药。     

Microfluidic Pneumatic Cages: A Novel Approach for In-chip Crystal Trapping,Manipulation and Controlled Chemical Treatment

The precise localization and controlled chemical treatment of structures on a surface are significant challenges for common laboratory technologies. Herein, we introduce a microfluidic-based technology, employing a double-layer microfluidic device, which can trap and localize in situ and ex situ synthesized structures on microfluidic channel surfaces. Crucially, we show how such a device can be used to conduct controlled chemical reactions onto on-chip trapped structures and we demonstrate how the synthetic pathway of a crystalline molecular material and its positioning inside a microfluidic channel can be precisely modified with this technology. This approach provides new opportunities for the controlled assembly of structures on surface and for their subsequent treatment.     

Chemical constituents from the leaves of Lyonia ovalifolia var. hebecarpa

A phytochemical investigation of the leaves of Lyonia ovalifolia var. hebecarpa (Franch. ex F.B. Forbes & Hemsl.) Chun (Ericaceae) led to the isolation of 22 compounds, including eight diterpenoids (1–8), two sesquiterpenoids (9 and 10), two monoterpenoids (11 and 12), two iridoids (13 and 14), four phenylpropanoids (15–18), and four lignans (19–22). Their structures were determined by spectroscopic data analysis and comparison with literature data. The absolute configuration of bisdeacetylkalmitoxin VI (1) was determined by single-crystal X-ray diffraction analysis for the first time. Notably, all the isolates 1–22 were reported from the genus of Lyonia for the first time, and compounds 9–12 and 15–22 were obtained from the Ericaceae family for the first time. The chemotaxonomic significance of compounds 1–22 was discussed.     

微生态制剂对肉鸡肌肉品质影响的研究

目的 研究微生态制剂（昌健素）对肉鸡肌肉化学成分的影响。方法 选取1日龄健康AA肉鸡180只,随机分为3个处理,每个处理3个重复,每个重复20只。处理1为空白对照,自由饮用清水;处理2在饮水中按0.1%添加10%氟苯尼考,处理3在饮水中按0.1%添加昌健素。结果 昌健素可增加肉鸡肌肉的滴水损失和熟肉率（P<0.05）;增加肌肉中粗蛋白和粗脂肪的含量、降低水分的含量（P<0.05）;提高41日龄肉鸡肌肉中铁和锌的含量,降低钙和锰的含量（P<0.05）;降低肉鸡胸肌中饱和脂肪酸的含量（P<0.05）;提高肌肉中总氨基酸、必需氨基酸和鲜味氨基酸的含量（P<0.05）;增加肉鸡肌肉中丙二醛（MDA）的含量（P<0.05）。结论 微生态制剂昌健素的添加能改善肉鸡的肌肉品质。     

Toward multiplexing the application of solvent accessibility probes for the investigation of RNA three-dimensional structures by electrospray ionization-Fourier transform mass spectrometry

Multiple solvent accessibility probes can be applied simultaneously to investigate the three-dimensional structure of complex RNA substrates when electrospray ionization-Fourier transform mass spectrometry (ESI-FTMS) is employed in place of polyacrylamide gel electrophoresis (PAGE). We show that classic chemical probes, such as dimethylsulfate, kethoxal, and 1-cyclohexyl-3-(2-morpholinoethyl)carbodiimide metho-p-toluenesulfonate, can be combined in probing mixtures designed to assess the full spectrum of base pairing and steric protection for the most abundant ribonucleotides included in RNA. After probe-independent hydrolysis of the alkylated substrate, the mixture of oligonucleotide products is mass mapped by ESI-FTMS analysis, which enables the unambiguous identification of probed bases from the unique mass signatures provided by the different chemical modifiers. In this bottom-up approach, any theoretical limit to the size of the possible target RNA will be determined by the effectiveness of the hydrolysis procedure rather than by the performance of the detection technique. Control experiments performed on the stem-loop 4 of human immunodeficiency virus type 1 have shown no adverse interactions between the reagents combined in the probing cocktails. No significant discrepancies between the alkylation patterns offered by the cocktails and the individual reagents could be detected, indicating that multiplexing the probe application does not necessarily lead to structural distortion but provides valid data on base accessibility and protection. To demonstrate the ruggedness of this approach, optimized cocktails were finally employed to assess the stability of the folded structure of mouse mammary tumor virus pseudoknot in the presence of different amounts of Mg2+. Multiplexing the probe application constitutes an essential step toward high-throughput applications, which will take advantage of a strategy that maximizes the information attainable from a single experiment, while minimizing time and sample consumption over PAGE-based methods.