Heparan sulfate proteoglycans regulate autophagy in Drosophila

Heparan sulfate-modified proteoglycans (HSPGs) are important regulators of signaling and molecular recognition at the cell surface and in the extracellular space. Disruption of HSPG core proteins, HS-synthesis, or HS-degradation can have profound effects on growth, patterning, and cell survival. The Drosophila neuromuscular junction provides a tractable model for understanding the activities of HSPGs at a synapse that displays developmental and activity-dependent plasticity. Muscle cell-specific knockdown of HS biosynthesis disrupted the organization of a specialized postsynaptic membrane, the subsynaptic reticulum (SSR), and affected the number and morphology of mitochondria. We provide evidence that these changes result from a dysregulation of macroautophagy (hereafter referred to as autophagy). Cellular and molecular markers of autophagy are all consistent with an increase in the levels of autophagy in the absence of normal HS-chain biosynthesis and modification. HS production is also required for normal levels of autophagy in the fat body, the central energy storage and nutritional sensing organ in Drosophila. Genetic mosaic analysis indicates that HS-dependent regulation of autophagy occurs non-cell autonomously, consistent with HSPGs influencing this cellular process via signaling in the extracellular space. These findings demonstrate that HS biosynthesis has important regulatory effects on autophagy and that autophagy is critical for normal assembly of postsynaptic membrane specializations.     

Modified heparin inhibits P-selectin-mediated cell adhesion of human colon carcinoma cells to immobilized platelets under dynamic flow conditions

Accumulating evidence indicates that the formation of tumor cell platelet emboli complexes in the blood stream is a very important step during metastases and that the anti-metastasis effects of heparin are partially due to a blockade of P-selectin on platelets. In this study, heparin and chemically modified heparins were tested as inhibitors of three human colon carcinoma cell lines (COLO320, LS174T, and CW-2) binding to P-selectin, adhering to CHO cells expressing a transfected human P-selectin cDNA, and adhering to surface-anchored platelets expressing P-selectin under static and flow conditions. The aim was to screen for heparin derivatives with high anti-adhesion activity but negligible anticoagulant activity. In this study, four modified heparins with high anti-adhesion activity were identified including RO-heparin, CR-heparin, 2/3ODS-heparin, and N/2/3DS-heparin. NMR analysis proved the reliability of structure of the four modified heparins. Our findings suggested that the 6-O-sulfate group of glucosamine units in heparin is critical for the inhibition of P-selectin-mediated tumor cell adhesion. Heparan sulfate-like proteoglycans on these tumor cell surfaces are implicated in adhesion of the tumor cells to P-selectin. Some chemically modified heparins with low anticoagulant activities, such as 2/3ODS-heparin, may have potential value as therapeutic agents that block P-selectin-mediated cell adhesion and prevent tumor metastasis.     

植物激素脱落酸受体的研究进展

脱落酸(abscisic acid, ABA)广泛参与植物生长发育的调控和对多种环境胁迫的适应性反应。有关ABA受体的研究已经在检测受体位置、纯化ABA特异性的结合蛋白和克隆ABA受体基因方面做出了许多重要的工作。最近相继发现一种RNA结合蛋白FCA和一种编码Mg离子螯合酶（Mg-chelatase）H亚基的CHLH作为两种不同的ABA受体分别调控植物的开花时间和介导种子萌发、幼苗生长及叶片的气孔运动。本文从实验策略的角度重点分析总结了研究脱落酸受体相对有效的途径与方法, 同时就有关的研究结果给予了评论和展望。     

层迭灵芝子实体的体外抗肿瘤及免疫活性

【背景】层迭灵芝Ganoderma lobatum是灵芝属中的一个种,在民间有药用历史,但缺乏对其化学成分和药理活性的科学研究。【目的】以赤芝Ganoderma lingzhi子实体为参照,研究对比层迭灵芝子实体的抗肿瘤及免疫活性的强弱,探讨层迭灵芝的药用价值。【方法】采用化学分析及仪器分析的方法,比较2种灵芝子实体中三萜及多糖含量差异,并进行体外抗肿瘤及免疫活性研究。【结果】层迭灵芝和赤芝的子实体中三萜含量差异不大,分别为1.14%和1.21%,但2种灵芝中三萜化合物的种类差异较大。层迭灵芝子实体中的多糖含量较赤芝稍高,分别为3.60%和2.67%,2种子实体中多糖的重均分子量分布特征有所差别。2种灵芝醇提物对肿瘤细胞K562及SW620的增殖均具有一定的抑制活性,其中,层迭灵芝对SW620细胞具有较强的抑制活性,其IC50值达到了52.5μg/mL。2种灵芝水提物可以促进RAW 264.7细胞释放NO,说明两者均具有一定的免疫活性。【结论】层迭灵芝具有较好的抗肿瘤及免疫活性,可以作为药用开发的原料来源。     

马铃薯StCRKs基因家族的鉴定分析及响应逆境信号的表达

为鉴定马铃薯（Solanum tuberosum）中富含半胱氨酸的类受体激酶（cysteine-rich receptor-like kinase,CRKs）,利用Pfam等工具对马铃薯蛋白质组和基因组序列进行分析,共鉴定到18个新的马铃薯StCRKs家族基因,这些基因分布在1、2、11和12号染色体上,均具有典型保守的CRK结构域。StCRKs基因的启动子区具有响应5种植物激素、昼夜节律、生物胁迫、非生物胁迫及种子特异性的响应元件。利用qRT-PCR方法对马铃薯盆栽苗开花期的根、茎、叶和花中的18个StCRKs基因进行组织特异性表达分析,结果显示不同基因的表达部位不同。分别用水杨酸类似物BTH和4 ℃低温处理马铃薯,有13个StCRKs基因能够响应低温信号,10个StCRKs基因能够被水杨酸类似物BTH诱导。为进一步深入研究StCRKs在生物胁迫及非生物胁迫中的功能提供了线索。     

莲幼苗的胚根发育及其筛分子研究

报道了莲无初生根型幼苗的胚根发育过程,其胚根由分生组织转化成贮藏组织,致使胚根不突破种皮;莲幼苗初生维管系统中的筛分子为筛管分子。莲的子叶和胚根连为一体的特殊结构与其生活环境和系统演化密切相关。     

长期不同植被覆盖对黑土团聚体内有机碳组分的影响

为探究黑土团聚体内土壤有机碳(SOC)的“分馏”特征, 揭示不同植被覆盖下土壤团聚体的固碳机制, 该文以中国科学院海伦农业生态系统国家野外综合研究站内不同植被覆盖(草地、农田和裸地)长期定位实验的土样为研究对象, 利用团聚体湿筛分组、有机碳物理和化学分组相结合的方法, 研究了黑土团聚体及其内部的碳密度和腐殖质组分的碳分配特征。研究发现, 黑土经过不同植被覆盖31年后, 长期草地覆盖使土壤表层SOC、全氮(TN)含量显著增加, 农田和无植被覆盖的裸地SOC含量减少, 且在裸地显著降低。3种处理中, 2-0.25 mm (含2 mm, 下同)粒级团聚体均为优粒级。土壤团聚体的稳定性顺序为草地>农田>裸地。草地覆盖使土壤大团聚体的比例和有机碳库增加, 微团聚体和粉黏粒所占比例和碳库均减少, 说明草地覆盖促进了土壤大团聚体形成, 土壤固碳能力显著增强。而农田和裸地因外源碳投入少, 有机碳含量均是微团聚体>大团聚体>粉黏粒, SOC主要分布在微团聚体中。不同植被覆盖处理对土壤团聚体内密度组分和腐殖质各组分碳的富集“分馏”作用很明显, 与农田和裸地相比, 长期草地植被覆盖处理>2 mm和2-0.25 mm粒级团聚体中轻组碳含量富集的较多, 2-0.25 mm粒级团聚体中富里酸、胡敏酸和胡敏素的碳富集均最高, 而农田和裸地促进了微团聚体内腐殖质碳的富集。草地覆盖显著增加了大团聚体内活性有机碳组分, 来源于植物的碳首先进入到大粒径的团聚体中, 使土壤团聚结构显著改善, 农田和无植被覆盖的裸地土壤中轻组碳含量显著降低, 团聚体内有机碳以重组碳和胡敏素为主, 稳定化程度更高。     

棉花SMALL AUXIN UP RNAs X (SAURX)克隆及表达模式分析

【目的】生长素是最重要的植物激素之一,调控了植物多种生物学过程。生长素上调的小RNA（SMALL AUXIN UP RNAs,SAURs）是一类生长素原初响应基因,在调控细胞伸长的过程中具有重要作用,但其在棉花纤维发育过程中的作用并不清楚。【方法】研究从陆地棉中克隆到1个编码SAUR蛋白的基因,命名为GhSAURX,通过表达模式分析、亚细胞定位、转基因拟南芥表型分析及生长素相关基因表达分析初步研究其功能。【结果】进化树分析表明,GhSAURX与拟南芥SAUR76、SAUR77和SAUR78关系较近,属于SAUR76亚家族。qPCR结果发现,GhSAURX基因在快速伸长的纤维中表达量较高,即开花后15,18,21 d。同时,GhSAURX在长纤维品种中的表达水平明显高于短纤维。亚细胞定位分析显示,GhSAURX定位在细胞膜和细胞核中。异源表达GhSAURX可以提高YUCCA6、ARF7及PIN4的表达,增加拟南芥的主根长度和黑暗条件下下胚轴的长度。【结论】GhSAURX可能在生长素调控细胞伸长的过程中具有重要作用。     

Anti‐hsa‐miR‐59 alleviates premature senescence associated with Hutchinson‐Gilford progeria syndrome in mice

Hutchinson‐Gilford progeria syndrome (HGPS) is a lethal premature aging disorder without an effective therapeutic regimen. Because of their targetability and influence on gene expression, microRNAs (miRNAs) are attractive therapeutic tools to treat diseases. Here we identified that hsa‐miR‐59 (miR‐59) was markedly upregulated in HGPS patient cells and in multiple tissues of an HGPS mouse model (Lmna ^G609G/G609G ), which disturbed the interaction between RNAPII and TFIIH, resulting in abnormal expression of cell cycle genes by targeting high‐mobility group A family HMGA1 and HMGA2. Functional inhibition of miR‐59 alleviated the cellular senescence phenotype of HGPS cells. Treatment with AAV9‐mediated anti‐miR‐59 reduced fibrosis in the quadriceps muscle, heart, and aorta, suppressed epidermal thinning and dermal fat loss, and yielded a 25.5% increase in longevity of Lmna ^G609G/G609G mice. These results identify a new strategy for the treatment of HGPS and provide insight into the etiology of HGPS disease.