皮层神经发生的分子调控机制

在高等动物神经发育过程中,背侧端脑神经上皮细胞在多种调控基因及环境调控因子的作用下经历了错综复杂的发育事件,逐步形成具有精细的分层结构和高级功能的神经皮层。这些发育中的调控具有严格的时间和区域特性。本文主要就皮层形成中神经干细胞增殖、分化方向及皮层神经元亚型的特化等方面的调控机制予以论述。     

Circular RNA circ‐RCCD promotes cardiomyocyte differentiation in mouse embryo development via recruiting YY1 to the promoter of MyD88

Congenital heart disease (CHD) is the most common birth defect, affecting approximately 1% of live births. Genetic and environmental factors are leading factors to CHD, but the mechanism of CHD pathogenesis remains unclear. Circular RNAs (circRNAs) are kinds of endogenous non‐coding RNAs (ncRNAs) involved in a variety of physiological and pathological processes, especially in heart diseases. In this study, three significant differently expressed circRNA between maternal embryonic day (E) E13 and E17 was found by microarray assay. Among them, the content of circ‐RCCD increases with the development of heart and was enriched in primary cardiomyocytes of different species, which arouses our attention. Functional experiments revealed that inhibition of circ‐RCCD dramatically suppressed the formation of beating cell clusters, the fluorescence intensity of cardiac differentiation marker MF20, and the expression of the myocardial‐specific markers CTnT, Mef2c, and GATA4. Next, we found that circ‐RCCD was involved in cardiomyocyte differentiation through negative regulation of MyD88 expression. Further experiments proved that circ‐RCCD inhibited MyD88 levels by recruiting YY1 to the promoter of MyD88; circ‐RCCD inhibited nuclear translocation of YY1. These results reported that circ‐RCCD promoted cardiomyocyte differentiation by recruiting YY1 to the promoter of MyD88. And, this study provided a potential role and molecular mechanism of circ‐RCCD as a target for the treatment of CHD.     

大兴安岭天然沼泽湿地生态系统碳储量

采用碳/氮分析仪测定法与标准木解析法,研究大兴安岭5种典型天然沼泽湿地(草丛沼泽、灌丛沼泽、毛赤杨沼泽、白桦沼泽和落叶松沼泽)的生态系统碳储量(植被和土壤)、净初级生产力、植被年净固碳量及其沿沼泽至森林方向过渡带水分环境梯度的分布格局,揭示其空间变异规律性,并定量评价寒温带5种典型天然沼泽湿地的碳储量与固碳能力及其长期碳汇作用。结果表明:①5种天然沼泽湿地的植被碳储量分布在(0.48±0.08)—(8.33±0.66)kgC/m2之间,沿过渡带环境梯度呈递增趋势;②土壤碳储量分布在(19.21±6.17)—(38.28±4.86)kgC/m2之间,沿过渡带环境梯度却呈递减趋势;③生态系统碳储量分布在(27.54±7.16)—(38.76±4.58)kgC/m2之间,沿过渡带环境梯度基本呈恒定分布规律性,且以湿地土壤碳储量占优势地位(69.8%—98.8%);④植被净初级生产力分布在(0.68±0.10)—(1.08±0.12)kg.m-.2a-1之间,毛赤杨沼泽最高,草丛沼泽、灌丛沼泽、白桦沼泽居中,落叶松沼泽最低,且总体上低于温带森林湿地而高于寒温带天然落叶松林;⑤植被年净固碳量分布在(0.32±0.09)—(0.51±0.06)kgC.m-.2a-1,毛赤杨沼泽最高(高于全球植被平均年净固碳量)、灌丛沼泽和白桦沼泽居中(达到或接近全球平均值)、草丛沼泽和落叶松沼泽最低(略低于全球平均值),故这5种沼泽湿地均属于碳汇功能相对较强的湿地植被类型。     

亚热带城市河流底栖动物完整性评价——以流溪河为例

根据2016年前、后汛期及枯水期流溪河14个断面底栖动物群落组成数据(4门8纲22目52科94属103种),采用底栖动物完整性指数(B-IBI),首次对亚热带地区河流进行健康评价。经筛选(32个候选指标),流溪河B-IBI体系由5个核心指标(总生物量,敏感类群个体%,EPT、摇蚊和耐污类群单元数)组成,评价标准为:健康3.24,亚健康3.24—2.43,一般2.43—1.62,差1.62—0.81,极差0.81,评价结果为:健康位点数占14.3%、亚健康50.0%、一般21.4%、差14.3%、无极差。总体上,B-IBI值反映流溪河上游健康状况较好,以EPT分类单元数和敏感类群个体%贡献最高,下游健康状况恶化,以耐污类群单元数贡献最高。此外,上游支流健康状况要优于上游干流,而下游则情况相反。相关性分析显示,B-IBI值与溶解氧呈极显著正相关(P0.01),与电导率、氨氮、总氮和总磷呈显著负相关(P0.05),反映流溪河当前健康水平受水体污染影响严重。核心指标与环境因子间CCA分析显示,前2主轴对环境因子解释度达68.1%,且对上、下游及干、支流有明显的梯度划分,说明所建B-IBI在流溪河有较高适用性。对比不同温度带研究结果发现,B-IBI体系受人为干扰和水体污染影响更加明显,体现其评价功能不受地理区域影响。     

富营养化河水灌溉对稻田土壤氮磷养分贡献的影响——以太湖地区黄泥土为例

以太湖地区主要稻田土壤类型黄泥土为对象,利用当地富营养化河水对回填土柱和植稻原状土渗漏池进行模拟稻田灌溉试验,系统研究了灌溉水对稻田土壤氮磷营养的贡献.在回填土柱灌溉试验中,在试验初期,不同形态的氮素均有较高的淋失量,以后逐渐降低,表明初期淋失的氮素主要来自土壤,而不是灌溉河水.在整个水稻生长季,均观测到有可溶性有机氮淋失,表明富营养化河水灌溉条件下可溶性有机氮是稻田土壤主要的氮素淋失形态.在本试验中,磷素的淋失动态与氮素的淋失动态截然相反,淹水后很长一段时间内均没有土壤磷素淋失,但在淹水灌溉后期有大量的土壤磷素淋失损失,这可能是淹水后期土壤对磷的吸持已达到饱和状态,不能继续固持土壤中多余的磷所致.与回填土柱模拟灌溉淋洗试验相比,在当前供肥条件下,原状土渗漏池试验氮磷淋失量远低于回填土柱试验,而灌溉水对土壤氮磷养分的贡献远高于回填土柱.通过富营养化河水灌溉带入当季稻田的N量达到每公顷56.3 kg,其中有55.8 kg N可被土壤吸持和作物吸收,表明太湖地区稻田土壤对氮磷养分来说是一个环境友好的生态系统.在利用当地富营养化河水进行稻田土壤灌溉时可适量减少肥料施用量、优化氮磷肥料管理.     

DLGCN:基于图卷积网络的药物-lncRNA[]关联预测

为实现高通量识别新的药物-长链非编码RNA(Long non-coding RNA, lncRNA)关联,本文提出了一种基于图卷积网络模型来识别潜在药物-lncRNA关联的方法DLGCN(Drug-LncRNA graph convolution network)。首先,基于药物的结构信息和lncRNA的序列信息分别构建了药物-药物和lncRNA-lncRNA相似性网络,并整合实验证实的药物-lncRNA关联构建了药物-lncRNA异质性网络。然后,将注意力机制和图卷积运算应用于该网络中,学习药物和lncRNA的低维特征,基于整合的低维特征预测新的药物-lncRNA关联。通过效能评估,DLGCN的受试者工作特性曲线下面积(Area under receiver operating characteristic, AUROC)达到0.843 1,优于经典的机器学习方法和常见的深度学习方法。此外,DLGCN预测到姜黄素能够调控lncRNA MALAT1的表达,已被最近的研究证实。DLGCN能够有效预测药物-lncRNA关联,为肿瘤治疗新靶点的识别和抗癌药物的筛选提供了重要参考。     

Human C1orf27 protein interacts with α2A-adrenergic receptor and regulates its anterograde transport

The molecular mechanisms underlying the anterograde surface transport of G protein–coupled receptors (GPCRs) after their synthesis in the endoplasmic reticulum (ER) are not well defined. In C. elegans, odorant response abnormal 4 has been implicated in the delivery of olfactory GPCRs to the cilia of chemosensory neurons. However, the function and regulation of its human homolog, C1orf27, in GPCR transport or in general membrane trafficking remain unknown. Here, we demonstrate that siRNA-mediated knockdown of C1orf27 markedly impedes the ER-to-Golgi export kinetics of newly synthesized α_2A-adrenergic receptor (α_2A-AR), a prototypic GPCR, with the half-time being prolonged by more than 65%, in mammalian cells in retention using the selective hooks assays. Using modified bioluminescence resonance energy transfer assays and ELISAs, we also show that C1orf27 knockdown significantly inhibits the surface transport of α_2A-AR. Similarly, C1orf27 knockout by CRISPR-Cas9 markedly suppresses the ER–Golgi-surface transport of α_2A-AR. In addition, we demonstrate that C1orf27 depletion attenuates the export of β₂-AR and dopamine D2 receptor but not of epidermal growth factor receptor. We further show that C1orf27 physically associates with α_2A-AR, specifically via its third intracellular loop and C terminus. Taken together, these data demonstrate an important role of C1orf27 in the trafficking of nascent GPCRs from the ER to the cell surface through the Golgi and provide novel insights into the regulation of the biosynthesis and anterograde transport of the GPCR family members.     

马鞍列岛褐菖鲉Sebasticus marmoratus栖息地适宜性评价

为了评估趋礁鱼类在岛礁海域的生境适宜度,选取马鞍列岛的褐菖鲉(Sebasticus marmoratus)为指示物种,以2009年获取的水深、盐度、叶绿素a、浊度和底质数据作为褐菖鲉春、冬季栖息地指示因子,建立栖息地适宜度曲线,并计算各站点的栖息地适宜性指数(HSI)。结果显示:1)绿华、花鸟、嵊山沿岸站点HSI普遍较低,枸杞岛、三横山、东库山沿岸站点褐菖鲉HSI相对较高,其中最大值1.0出现在枸杞岛沿岸的站点;2)春季褐菖鲉幼鱼的适宜水深在6 m左右,成鱼适宜在8—12 m的水深处生存;冬季褐菖鲉对8—12 m的水深适宜性良好;3)春季所有褐菖鲉的适宜盐度为30PSU,冬季幼鱼的适宜盐度为27—31PSU,成鱼的适宜盐度为27PSU、31PSU;4)随着叶绿素a和浊度值的增大,褐菖鲉适宜性逐渐降低。底质类型为岩时最适合褐菖鲉生存。5)相关分析显示,褐菖鲉丰度与底质类型相关性最大,而与叶绿素a、浊度呈显著负相关。研究结果表明,初级生产力和浑浊程度越高对褐菖鲉丰度抑制越明显。底质类型是褐菖鲉丰度分布的重要影响因子,其中分布有较多大型海藻的岩礁生境是其最适宜的栖息地。利用2010年春、冬季环境调查和渔获数据进行HSI模型验证,资源丰度随HSI值升高而增加,因此构建的模型可用于趋礁鱼类在岛礁海域的栖息地适宜性分析。     

Design,synthesis, and biological evaluation of novel carbazole derivatives as potent DNMT1 inhibitors with reasonable PK properties

The DNA methyltransferases (DNMTs) were found in mammals to maintain DNA methylation. Among them, DNMT1 was the first identified, and it is an attractive target for tumour chemotherapy. DC_05 and DC_517 have been reported in our previous work, which is non-nucleoside DNMT1 inhibitor with low micromolar IC₅₀ values and significant selectivity towards other S-adenosyl-_L-methionine (SAM)-dependent protein methyltransferases. In this study, through a process of similarity-based analog searching, a series of DNMT1 inhibitors were designed, synthesized, and evaluated as anticancer agents. SAR studies were conducted based on enzymatic assays. And most of the compounds showed strong inhibitory activity on human DNMT1, especially WK-23 displayed a good inhibitory effect on human DNMT1 with an IC₅₀ value of 5.0 µM. Importantly, the pharmacokinetic (PK) profile of WK-23 was obtained with quite satisfying oral bioavailability and elimination half-life. Taken together, WK-23 is worth developing as DNMT1-selective therapy for the treatment of malignant tumour.