CLUE-S模型在南京市土地利用变化研究中的应用

土地利用/覆盖变化模型是研究区域景观动态并解释其驱动机制的重要技术手段.应用CLUE-S模型,在Landsat TM影像等相关数据支持下,对南京地区1998-2006年土地利用的时空动态变化进行了研究.结果表明:各土地利用类型变化受地形因素影响最大,人均GDP与城镇用地和农业用地的分布呈显著相关,城乡主干道对土地利用变化的贡献显著大于省级及以上道路;海拔较高区域林地的发生比率较高,而地形低平区域农田、城建用地的发生比率较高.经检验,在300 m空间分辨率水平,对南京地区2003年、2006年土地利用状况模拟的精度分别达到了85.7%和84.1%;而通过将研究区分成若干子区,分别修正模型参数并重新模拟,准确率提高到89.7%和88.3%,分区赋值法有效地提高了模拟精度.研究表明,CLUE-S模型对城市发展的空间结构也有较强的预测能力,对指导城市规划、分析景观动态的驱动机制有重要参考价值.     

基于细菌群感效应人工构建分子开关

对生物体内已有的或者人工组装的生物合成途径进行优化操作涉及两个重要问题:代谢途径中关键酶的活性及蛋白表达水平。对于酶表达水平的研究,传统的做法是采用强启动子控制下的靶蛋白过量表达策略。靶蛋白的过量表达通常会导致细胞内积累大量的无活性包涵体,从而严重影响细胞的生理状态和相关生物途径的有效运转。针对这一问题,设计一种分子开关来精确调控生物合成过程中关键酶的表达水平,对于研究生物合成途径的代谢节律以及促进生物合成途径高效运转都具有重要的实用价值。基于细菌群落中普遍存在群感效应的基本原理并结合酶促催化的动力学特征,首先在大肠杆菌群落中建立信号分子高丝氨酸内酯(AHL)介导的细胞–细胞交流机制,将靶基因egfp置入到启动子PluxI的控制之下。在细胞生长过程中,产生的AHL累积到一定浓度启动靶基因表达。通过在细胞生长的不同阶段启动AHL降解酶AiiA的表达控制环境中信号分子AHL的浓度水平,从而控制靶基因egfp的转录效率,最终实现对靶蛋白EGFP表达水平的精确控制。通过检测细胞的生长状态、靶基因在mRNA水平、蛋白质水平的表达情况证明人工设计的分子开关可以便捷高效地控制靶基因表达水平,具有时空调节的严谨性。该分子开关有望广泛应用于代谢工程和合成生物学等研究领域中。     

A novel BH3 mimetic efficiently induces apoptosis in melanoma cells through direct binding to anti‐apoptotic Bcl‐2 family proteins,including phosphorylated Mcl‐1

The Bcl‐2 family modulates sensitivity to chemotherapy in many cancers, including melanoma, in which the RAS/BRAF/MEK/ERK pathway is constitutively activated. Mcl‐1, a major anti‐apoptotic protein in the Bcl‐2 family, is extensively expressed in melanoma and contributes to melanoma's well‐documented chemoresistance. Here, we provide the first evidence that Mcl‐1 phosphorylation at T163 by ERK1/2 and JNK is associated with the resistance of melanoma cell lines to the existing BH3 mimetics gossypol, S1 and ABT‐737, and a novel anti‐apoptotic mechanism of phosphorylated Mcl‐1 (pMcl‐1) is revealed. pMcl‐1 antagonized the known BH3 mimetics by sequestering pro‐apoptotic proteins that were released from Bcl‐2/Mcl‐1. Furthermore, an anthraquinone BH3 mimetic, compound 6, was identified to be the first small molecule to that induces endogenous apoptosis in melanoma cells by directly binding Bcl‐2, Mcl‐1, and pMcl‐1 and disrupting the heterodimers of these proteins. Although compound 6 induced upregulation of the pro‐apoptotic protein Noxa, its apoptotic induction was independent of Noxa. These data reveal the promising therapeutic potential of targeting pMcl‐1 to treat melanoma. Compound 6 is therefore a potent drug that targets pMcl‐1 in melanoma.     

云雾龙胆内生菌的分离鉴定及抗菌活性分析

从云雾龙胆(Gentiana nubigena)中分离到一株具有抗菌活性的内生细菌LD5,该菌株的发酵上清液对金黄色葡萄球菌和大肠杆菌的生长有显著的抑制作用。通过形态学、生理生化和16SrDNA系统进化分析,鉴定LD5为解淀粉芽孢杆菌(Bacillus amyloliquefaciens)。菌株LD5能合成黄酮类化合物、龙胆苦苷,以及一种与云雾龙胆醇提取物相似的代谢产物。     

CMTM6, the newly identified PD-L1 regulator,correlates with PD-L1 expression in lung cancers

Modulation of Immune check point regulators, especially the PD-1/PD-L1 axis, plays a critical role in successful management of a small proportion of lung cancer patients, but not so effective in the rest of lung cancer patients. A better understanding of immunotherapy non-responsive or resistant patients therefore warranted for future development of novel therapeutics. The newly identified regulator CMTM6 (CKLF-like MARVEL transmembrane domain containing 6) has been reported to serves as the stabilizer of PD-L1 and enhances the inhibitory effect of PD-L1 on immune system in both cell line and animal models, but its clinical relevance associated with PD-L1 is unknown and the current study is designed to address this question. The study using immunohistochemistry demonstrated that CMTM6 positivity from 15 out of 19 types of cancers with our in-house tissue microarray, and PD-L1 expression is always found only in CMTM6 positive cancers. CMTM6 and PD-L1 expression were analyzed in 81 lung cancer patient sample, and we observed that CMTM6 expression correlated with cancer histotypes and inversely correlated with cancer metastases, but not with patients’ age and gender. No PD-L1 expression was observed in negative CMTM6 samples. Higher expression PD-L1 is also associated with higher CMTM6 expression. In summary, CMTM6 expression is associated with PD-L1 expression, as well as lung cancer histotypes and metastasis. The results thus for the first time confirmed earlier reports on CMTM6/PD-L1 connection, from a clinical aspect of analysis.     

A unique FGF23 with the ability to activate FGFR signaling through both αKlotho and βKlotho

Three fibroblast growth factor (FGF) molecules, FGF19, FGF21, and FGF23, form a unique subfamily that functions as endocrine hormones. FGF19 and FGF21 can regulate glucose, lipid, and energy metabolism, while FGF23 regulates phosphate homeostasis. The FGF receptors and co-receptors for these three FGF molecules have been identified, and domains important for receptor interaction and specificity determination are beginning to be elucidated. However, a number of questions remain unanswered, such as the identification of fibroblast growth factor receptor responsible for glucose regulation. Here, we have generated a variant of FGF23: FGF23-21c, where the C-terminal domain of FGF23 was replaced with the corresponding regions from FGF21. FGF23-21c showed a number of interesting and unexpected properties in vitro. In contrast to wild-type FGF23, FGF23-21c gained the ability to activate FGFR1c and FGFR2c in the presence of βKlotho and was able to stimulate glucose uptake into adipocytes in vitro and lower glucose levels in ob/ob diabetic mice model to similar extent as FGF21 in vivo. These results suggest that βKlotho/FGFR1c or FGFR2c receptor complexes are sufficient for glucose regulation. Interestingly, without the FGF23 C-terminal domain, FGF23-21c was still able to activate fibroblast growth factor receptors in the presence of αKlotho. This suggests not only that sequences outside of the C-terminal region may also contribute to the interaction with co-receptors but also that FGF23-21c may be able to regulate both glucose and phosphate metabolisms. This raises an interesting concept of designing an FGF molecule that may be able to address multiple diseases simultaneously. Further understanding of FGF/receptor interactions may allow the development of exciting opportunities for novel therapeutic discovery.     

TCR介导“inside-out”信号通路调控整合素的活化

整合素（integrin）是一类重要的跨膜黏附分子,在T细胞定向迁移到淋巴器官、感染或炎症部位以及T细胞与抗原呈递细胞（antigen presenting cell,APC）之间相互作用等过程中起重要作用。T细胞受到抗原或趋化因子等的刺激后,启动细胞内大量的信号传导分子,并形成＂inside-out＂信号通路,导致整合素构像的改变（conformation change）或促进整合素在细胞表面的聚集（integrinclustering）,最终增强整合素的affinity或avidity,促进其与配体结合的能力,提高淋巴细胞间的黏附。近年来的研究已经鉴定出调控整合素活化的多个关键的信号分子及其形成的信号转导复合体。该文主要阐述T细胞受到抗原刺激后,由T细胞受体（T cell receptor,TCR）介导的＂inside-out＂信号通路中关键的信号分子如ADAP、SKAP-55、RapL、Rap1、Talin和Kindlins等如何与上下游信号分子协同作用,调控整合素LFA-1活化的分子机制。     

同工酶研究在嗜热脂肪芽孢杆菌分类中的应用

嗜热脂肪芽孢杆菌是一个尚未被严格定义的种,它几乎包括芽孢杆菌属内所有能在65℃以上生长的细菌。用聚丙烯酰胺凝胶电泳的方法对151株嗜热脂肪芽孢杆菌的9种酶(G6PDH、LDH、MDH、IDH、AlaDH、LeuDH、过氧化氢酶、过氧化物酶、酯酶)的酶谱进行测定分析。根据其酶谱的差异,可将151株菌株分成两个类型。两型之间8个酶的13或14个基因产物的相异度约为91.8％,两型间的标准遗传距离是2.55。因此这两种类型的细菌也许可以被看作为两个不同的种。     

人发角蛋白人工腱材料体内降解及生物相容性研究

目的研究人发角蛋白人工腱(humanhairkeratinartificaltendon,HHKAT)材料在体内的可降解性及其生物相容性.方法对12只日本大耳白兔随机分组,在脊旁肌埋藏不同处理时间的人发角蛋白人工腱试件F及Z,用正常人发O做对照,分别在2、6、12、24周取材,观察人发角蛋白的降解吸收过程及其周围的组织反应.结果动物植入实验中发现不同时间处理的材料其降解速度不同,其中降解最快的F组在24周已完全吸收,而Z组在24周只有部分降解,O组未见降解.HHKAT及人发在肌肉组织内无明显的炎症排斥反应,随着HHKAT材料的降解吸收,其周围的组织反应逐渐降低.结论本研究表明人发角蛋白人工腱材料具有良好的生物相容性,在体内能够被降解吸收,可根据不同的需要调节其降解速度,是良好的肌腱替代材料.