The role of an invariant tryptophan residue in alpha-bungarotoxin and cobrotoxin. Investigation of active derivatives with the invariant tryptophan replaced by kynurenine

Ozone oxidation converted the single, invariant, tryptophan residue to N2-formylkynurenine in alpha-bungarotoxin and cobrotoxin. Upon this modification, the lethal toxicity was significantly reduced in cobrotoxin but mostly retained in alpha-bungarotoxin. Each neurotoxin containing kynurenine instead of tryptophan retained the same antigenicity as the native toxin. Fluorescence and CD spectroscopy revealed that, although the environment and state of the kynurenine residue were similar, [Kyn29]cobrotoxin was much more sensitive to pH change than alpha-[Kyn28]bungarotoxin. In terms of lethal toxicity and conformational stability, the invariant tryptophan residue appears to play a more important role in cobrotoxin, imparting a higher lethal toxicity than that in alpha-bungarotoxin, which has a disulfide bond at Cys29-Cys33.     

城市公园春季声景观与植被结构的关系

城市公园是城市生态系统的重要组成部分和城市生物多样性热点地区，具有丰富的声景观资源。由于声景观及声学方法具有信息量大，成本低，低侵入的特点，因此其研究和应用对生态系统健康及监测具有较高价值。声景观研究通过总结生物声的活动或多样性来衡量生物多样性。记录了北京20个城市公园的春季声景观，使用定量方法描述了声景观特征与变化；测试三种了已被证明与生物多样性相关并被广泛使用的声学指数（BIO、ADI、NDSI）与植被群落关系，完成了城市环境中声景观与环境关系的初步探究。研究结果表明：（1）声学指数能够有效表征城市公园声景观信息，具有显著的时间动态特性，能准确反映鸟类黎明合唱等重要生物生态活动；（2）声学强度指数也具有显著的时间动态变化和沿频率梯度的变化，不同的频率区间反映了不同声学群落的活动信息；（3）植被结构尤其是垂直结构对声景观起着重要作用，垂直异质性越大，声学多样性越高。发现支持声景观作为公园植被状况的度量，强调了其作为生物多样性和生态系统健康状况监测方法，用于城市管理和可持续发展的巨大潜力。     

Magnesium Deficiency in Patients on Long-Term Diuretic Therapy for Heart Failure

Magnesium levels in serum, erythrocytes, skeletal muscle, and bone were measured in 10 patients with valvular heart disease who had received diuretic therapy for heart failure for an average of 3·3 years. Five patients were found to have diminished values for skeletal muscle, indicating significant magnesium deficit. Values for erythrocytes were low in only two of the five patients, and none had low values for serum ultrafiltrate and bone: Magnesium replacement therapy restored skeletal muscle values to normal. Clinical features consistent with the presence of magnesium deficiency were found in all five magnesium-deficient patients. These features were, with few exceptions, corrected by magnesium replacement. The latter also corrected low skeletal muscle potassium values present in all five patients with low skeletal muscle magnesium, four of whom showed clinical features of digoxin poisoning before magnesium therapy was given. Concomitant secondary aldosteronism, inadequate dietary intake, and digoxin therapy had probably augmented the magnesium loss due to diuretic therapy.     

Alpha 1-adrenoceptor blocking properties of spiroxatrine in rat aorta.

This preliminary study has analyzed the potential ability of the 5-HT1A ligand spiroxatrine to interact with vascular alpha 1-adrenoceptors. Norepinephrine and the selective alpha 1-adrenoceptor agonist, methoxamine, elicited concentration-dependent contractions of rat aortic rings. In contrast, (+/-)-spiroxatrine (from 10(-8) to 3.1X10(-7) M) was devoid of any effect on vascular tone per se, but shifted the concentration-response curves of norepinephrine and methoxamine to the right in a concentration-dependent manner with pA2 values of 8.48 +/- 0.22 and 8.93 +/- 0.33, respectively. Endothelium removal did not significantly affect the above pA2 values of (+/-)-spiroxatrine. These data, taken in concert, support the contention that (+/-)-spiroxatrine displays alpha 1-adrenoceptor blocking properties in rat aortic rings.     

A Comprehensive Analysis of Symmetric Arginine Dimethylation in Colorectal Cancer Tissues Using Immunoaffinity Enrichment and Mass Spectrometry

Protein arginine methyltransferase 5 (PRMT5) is a major enzyme responsible for generating monomethyl and symmetric dimethyl arginine in proteins. PRMT5 is essential for cell viability and development, and its overexpression is observed in a variety of cancers. In the present study, it is found that levels of PRMT5 protein and symmetric arginine dimethylation in colorectal cancer (CRC) tissues are increased compared to those in adjacent noncancerous tissues. Using immunoaffinity enrichment of methylated peptides combined with high‐resolution mass spectrometry, a total of 147 symmetric dimethyl‐arginine (SDMA) sites in 94 proteins are identified, many of which are RNA binding proteins and enzymes. Quantitative analysis comparing CRC and normal tissues reveals significant increase in the symmetric dimethylation of 70 arginine sites in 46 proteins and a decrease in that of four arginine sites in four proteins. Among the 94 proteins identified in this study, it is confirmed that KH‐type splicing regulatory protein is a target of PRMT5 and highly expressed in CRC tissues compared to noncancerous tissues. This study is the first comprehensive analysis of symmetric arginine dimethylation using clinical samples and extends the number of known in vivo SDMA sites. The data obtained are available via ProteomeXchange with the identifier PXD015653.     

全球微生态药物研发现状及发展趋势 *

微生态药物在许多复杂性和慢性疾病中显示出极大的潜力,逐渐成为国际制药行业的新趋势。基于科睿唯安旗下的Cortellis数据库,采用定量分析和专家智慧相结合的方法,从总体研发现状、主要国家/地区、主要适应症、重点企业研发管线、重点在研药物、商业化交易多个维度展现全球微生态药物的研发和商业化全景。分析结果显示:全球共有142个在研微生态药物,其中49个药物处于临床阶段。美国在微生态药物研发和商业化方面遥遥领先,其数量占在研药物总量的70%。在研药物的适应症主要集中于炎症性肠病、艰难梭菌感染、溃疡性结肠炎等肠道感染性疾病。4D pharma公司的在研药物数量最多,微生态药物重点研发企业均建立起核心技术平台。处于临床3期的微生态药物共有7个,全球微生态药物商业化交易共有303起,最大的交易金额是27.8亿美元。未来,微生态药物有望在更难被人类征服的肿瘤和神经系统疾病方面取得突破性进展。     

Tillering and small grain 1 dominates the tryptophan aminotransferase family required for local auxin biosynthesis in rice

Auxin is a crucial phytohormone, controlling multiple aspects of plant growth and responses to the changing environment. However, the role of local auxin biosynthesis in specific developmental programs remains unknown in crops. This study characterized the rice tillering and small grain 1 (tsg1) mutant, which has more tillers but a smaller panicle and grain size resulting from a reduction in endogenous auxin. TSG1 encodes a tryptophan aminotransferase that is allelic to the FISH BONE (FIB) gene. The tsg1 mutant showed hypersensitivity to indole‐3‐acetic acid and the competitive inhibitor of aminotransferase, L‐kynurenine. TSG1 knockout resulted in an increased tiller number but reduction in grain number and size, and decrease in height. Meanwhile, deletion of the TSG1 homologs OsTAR1, OsTARL1, and OsTARL2 caused no obvious changes, although the phenotype of the TSG1/OsTAR1 double mutant was intensified and infertile, suggesting gene redundancy in the rice tryptophan aminotransferase family. Interestingly, TSG1 and OsTAR1, but not OsTARL1 and OsTARL2, displayed marked aminotransferase activity. Meanwhile, subcellular localization was identified as the endoplasmic reticulum, while phylogenetic analysis revealed functional divergence of TSG1 and OsTAR1 from OsTARL1 and OsTARL2. These findings suggest that TSG1 dominates the tryptophan aminotransferase family, playing a prominent role in local auxin biosynthesis in rice.     

Natural variation in the promoter of OsHMA3 contributes to differential grain cadmium accumulation between Indica and Japonica rice

Rice is a major source of cadmium(Cd) intake for Asian people. Indica rice usually accumulates more Cd in shoots and grains than Japonica rice. However, underlying genetic bases for differential Cd accumulation between Indica and Japonica rice are still unknown. In this study, we cloned a quantitative trait locus(QTL) grain Cd concentration on chromosome 7(GCC7) responsible for differential grain Cd accumulation between two rice varieties by performing QTL analysis and map-based cloning. We found that the two GCC7 alleles, GCC7~(PA64s) and GCC7~(93-11), had different promoter activity of OsHMA3,leading to different OsHMA3 expression and different shoot and grain Cd concentrations. By analyzing the distribution of different haplotypes of GCC7 among diverse rice accessions, we discovered that the high and low Cd accumulation alleles, namely GCC7~(93-11) and GCC7~(PA64s), were preferentially distributed in Indica and Japonica rice,respectively. We further showed that the GCC7~(PA64s)allele can be used to replace the GCC7~(93-11) allele in the super cultivar 93-11 to reduce grain Cd concentration without adverse effect on agronomic traits. Our results thus reveal that the QTL GCC7 with sequence variation in the OsHMA3 promoter is an important determinant controlling differential grain Cd accumulation between Indica and Japonica rice.     

基于文化与政治生态学的社会生态系统演进机制研究 ——以杭州与西湖为例

科学认识社会生态系统演进机制是对其进行有效管理的重要基础。以文化与政治生态学为理论基础,提出适合杭州—西湖社会生态系统的综合研究框架,识别了杭州—西湖社会生态系统的5个演进阶段,并分析出系统演进中的3种潜在状态。自然、政治、经济以及社会驱动力是影响杭州—西湖社会生态系统的主导因素,人类行为影响整个生态系统中扰动的频率、大小和形式并改变西湖生态系统的结构与功能,进而影响西湖为城市提供生态系统服务的潜能。在不同历史时期,基于自然、社会、经济、文化等多层面的需求,西湖在不同系统状态下为城市供给不同类别和质量的生态系统服务,总体而言供给与调节服务比例逐渐下降,文化服务逐渐上升,并且后者逐步成为最主要的生态系统服务类别。杭州与西湖在长期的互馈共生中建立了社会生态系统的自适应性调节机制,其背后的生态智慧可为现代风景园林规划提供重要启示。