Efficient synthesis and biological evaluation of epiceanothic acid and related compounds

Epiceanothic acid (1) is a naturally occurring, but very rare pentacyclic triterpene with a unique pentacyclic triterpene (PT) structure. An efficient synthesis of 1 starting from betulin (3) has been accomplished in 12-steps with a total yield of 10% in our study. Compound 1 and selected synthetic intermediates were further evaluated as anti-HIV-1 agents, inhibitors of glycogen phosphorylase (GP), and cytotoxic agents. Compound 1 exhibited moderate HIV-1 inhibition. Most importantly, compound 5, with an opened A-ring, showed significant GP inhibitory activity with an IC₅₀ of 0.21 μM, suggesting a potential for development as an anti-diabetic agent. On the other hand, compound 12, with a closed A-ring, showed potent cytotoxicity against A549 and MCF-7 human tumor cell lines, with IC₅₀ values of 0.89 and 0.33 μM, respectively. These results suggest that the A-ring of PTs is an important pharmacophore that could be modified to involve different biological activities.     

Efficacy switching SAR of mGluR5 allosteric modulators: highly potent positive and negative modulators from one chemotype

A series of metabotropic glutamate 5 receptor (mGluR5) allosteric ligands with positive, negative or no modulatory efficacy is described. The ability of this series to yield both mGluR5 PAMs and NAMs with single-digit nanomolar potency is unusual, and the underlying SAR is detailed.     

覆膜与沟垄种植模式对旱作马铃薯产量形成及水分运移的影响

研究了覆膜及不同沟垄种植模式对黄土高原西部半干旱区旱作马铃薯产量形成和水分运移的影响.结果表明:平畦覆膜(T2)、全膜双垄沟播(T3)、全膜双垄垄播(T4)、半膜膜侧种植(T5)和半膜沟垄垄播(T6)种植方式的产量分别比传统平畦不覆膜(T1)方式高50.1%、75.9%、86.8%、69.6%和60.6%;水分利用效率(WUE)分别提高47.0%、82.7%、84.0%、75.2%和54.3%,其中,T4、T3产量和WUE增加幅度最大.与传统方式相比,各覆膜及沟垄处理普遍优化了马铃薯各产量构成性状,其中T4和T3最有利于大薯率和中薯率的提高、绿薯率和烂薯率的降低,其单株结薯数和单株薯产量也较高.因此,全膜双垄垄播和全膜双垄沟播为半干旱区马铃薯适宜的抗旱节水高产种植模式.     

长期施用含硫和含氯化肥对稻田杂草生长动态的影响

利用湖南祁阳红壤稻田长期定位试验,研究了在等量氮磷钾养分条件下,长期施用含Cl-、SO2-4和Cl-+SO2-4化肥水稻生育期间杂草种类和生物量的变化.结果表明:施肥34年后,施用含Cl-化肥处理水稻生育期间杂草的种类最多、总生物量(浮生杂草和湿生杂草的生物量之和)最大,早稻期间杂草平均总干物质量分别比含SO2-4和Cl-+SO2-4化肥处理增加了51.4%和17.6%,晚稻期间分别增加了144%和242%.含SO2-4和Cl-+SO2-4化肥处理稻田中浮生杂草生物量较大,而含Cl-化肥处理田间几乎没有浮生杂草生长.杂草总干物质量和湿生杂草干物质量均与土壤Cl-含量呈显著正相关(相关系数分别为0.764**和0.948**),与土壤SO2-4-S含量呈显著负相关(相关系数分别为0.849**和0.641*).土壤碱解氮和有效磷受土壤SO2-4-S、Cl-及pH的共同作用对杂草总干物质量产生影响.通过各种施肥措施维持土壤适宜pH及碱解氮、有效磷含量,提高土壤SO2-4-S含量、降低Cl-含量,能有效抑制南方红壤稻田中湿生杂草的生长,降低杂草总生物量.     

Microsatellite analysis revealed genetic diversity and population structure among Chinese cashmere goats

Most cashmere goats are found in northern China and Mongolia. They are regarded as precious resources for their production of high quality natural fibre for the textile industry. It was the first time that the genetic diversity and population structure of nine Chinese cashmere populations has been assessed using 14 ISAG/FAO microsatellite markers. In addition, two Iranian populations and one West African goat population were genotyped for comparison. Results indicated that the genetic diversity of Chinese cashmere goats was rich, but less than those of the Iranian goat populations. All pairwise F_ST values between the Chinese cashmere goat populations reached a highly significant level (P < 0.001), suggesting that they should all be considered as separate breeds. Finally, clustering analysis divided Chinese cashmere goats into at least two clusters, with the Tibetan Hegu goats alone in one cluster. An extensive admixture was detected among the Chinese goat breeds (except the Hegu), which have important implications for breeding management.     

A、O型口蹄疫T/B细胞多抗原表位融合基因植物表达载体的构建

通过对(pMD-xsB/xsT/xsBT/xsBTT)4个克隆载体进行PCR,在(xsB/xsT/xsBT/xsBTT)目的基因前接入引导肽序列(用Y表示),克隆中间载体(pM D-xsY B/xsYT/xsYBT/xsYBTT),再利用同尾酶的酶切及连接得到4个重组植物表达载体(pBI-xsYB/xsYT/xsYBT/xsYBTT).经限制性酶切鉴定和测序分析证实表达载体构建正确,为下一步热研2号柱花草转基因植株的获得奠定了基础.     

黄独(Dioscorea bulbifera L.)不同居群叶表皮微形态特征的比较观察

应用扫描电子显微镜(SEM)对15个黄独(Dioscorea bulbifera L.)居群(11个野生居群及4个栽培居群)植株的叶表皮微形态特征(包括气孔器、表皮毛和气孔周围表皮细胞的特征)进行了观察和测量,并据此编制了15个黄独居群的检索表.观察结果表明:15个黄独居群植株叶片在气孔器外拱盖内缘类型,气孔器旋转方向,气孔长轴长度及密度和深度,叶片表皮毛的有无及类型,叶肉腺毛的长、短轴长度及密度,气孔周围表皮细胞垂周壁和平周壁的形态以及平周壁表面颗粒形状等特征上均有明显差异.气孔器外拱盖内缘有光滑和浅波状2种类型;气孔器的旋转方向分为不定向旋转、左旋和右旋3种方式;气孔长轴长度和密度的变化幅度分别为18.59～31.93 μm和86～356 mm-2.叶片表皮毛均仅存在于下表皮,可分为乳突和多细胞头单细胞柄腺毛2种类型,乳突主要分布于主脉,腺毛主要分布于二级脉和叶肉;叶肉腺毛的长、短轴长度的变化幅度分别为25.00～55.00和24.86～44.29μm,大部分居群腺毛密度的变化幅度为6～29 mm-2.叶片气孔周围表皮细胞垂周壁的形状有平直、平直隆起、平直脊状隆起、弯曲、弯曲脊状隆起和弯曲拱状隆起6种类型;表皮细胞平周壁的表面纹饰有具瘤条纹和光滑条纹2种形态,其扩散方式也有2种形式:一种为不环绕气孔且四方扩散,另一种为环绕气孔2～3周后扩散但扩散方向不定;平周壁上的颗粒形状有簇晶状、屑状、密集粉状、粉状、粒状和片状6种类型.比较分析结果显示:黄独不同居群叶表皮微形态特征的多态性较为丰富,地理分布相近的居群微形态特征的相似性较高,这些特征与黄独的各种下分类群相对应.     

Effective Identification of Gram-Negative Bacterial Type III Secreted Effectors Using Position-Specific Residue Conservation Profiles

Backgroud

Type III secretion systems (T3SSs) are central to the pathogenesis and specifically deliver their secreted substrates (type III secreted proteins, T3SPs) into host cells. Since T3SPs play a crucial role in pathogen-host interactions, identifying them is crucial to our understanding of the pathogenic mechanisms of T3SSs. This study reports a novel and effective method for identifying the distinctive residues which are conserved different from other SPs for T3SPs prediction. Moreover, the importance of several sequence features was evaluated and further, a promising prediction model was constructed.

Results

Based on the conservation profiles constructed by a position-specific scoring matrix (PSSM), 52 distinctive residues were identified. To our knowledge, this is the first attempt to identify the distinct residues of T3SPs. Of the 52 distinct residues, the first 30 amino acid residues are all included, which is consistent with previous studies reporting that the secretion signal generally occurs within the first 30 residue positions. However, the remaining 22 positions span residues 30–100 were also proven by our method to contain important signal information for T3SP secretion because the translocation of many effectors also depends on the chaperone-binding residues that follow the secretion signal. For further feature optimisation and compression, permutation importance analysis was conducted to select 62 optimal sequence features. A prediction model across 16 species was developed using random forest to classify T3SPs and non-T3 SPs, with high receiver operating curve of 0.93 in the 10-fold cross validation and an accuracy of 94.29% for the test set. Moreover, when performing on a common independent dataset, the results demonstrate that our method outperforms all the others published to date. Finally, the novel, experimentally confirmed T3 effectors were used to further demonstrate the model’s correct application. The model and all data used in this paper are freely available at http://cic.scu.edu.cn/bioinformatics/T3SPs.zip.     

A Pan-BCL2 Inhibitor Renders Bone-Marrow-Resident Human Leukemia Stem Cells Sensitive to Tyrosine Kinase Inhibition

1. Download : Download high-res image (154KB)
2. Download : Download full-size image

Highlights? Splice-isoform switching favors prosurvival BCL2 family expression in human BC ? BC LSCs are quiescent and TKI-resistant in the marrow niche ? Sabutoclax, a pan-BCL2 inhibitor, enhances TKI sensitivity of bone marrow BC LSCs