Understanding cadherin EGF LAG seven‐pass G‐type receptors

The cadherin epidermal growth factor (EGF) laminin G (LAG) seven‐pass G‐type receptors (CELSRs) are a special subgroup of adhesion G protein‐coupled receptors, which are pivotal regulators of many biologic processes such as neuronal/endocrine cell differentiation, vessel valve formation, and the control of planar cell polarity during embryonic development. All three members of the CELSR family (CELSR1‐3) have large ecto‐domains that form homophilic interactions and encompass more than 2000 amino acids. Mutations in the ecto‐domain or other gene locations of CELSRs are associated with neural tube defects and other diseases in humans. Celsr knockout (KO) animals have many developmental defects. Therefore, specific agonists or antagonists of CELSR members may have therapeutic potential. Although significant progress has been made regarding the functions and biochemical properties of CELSRs, our knowledge of these receptors is still lacking, especially considering that they are broadly distributed but have few characterized functions in a limited number of tissues. The dynamic activation and inactivation of CELSRs and the presence of endogenous ligands beyond homophilic interactions remain elusive, as do the regulatory mechanisms and downstream signaling of these receptors. Given this motivation, future studies with more advanced cell biology or biochemical tools, such as conditional KO mice, may provide further insights into the mechanisms underlying CELSR function, laying the foundation for the design of new CELSR‐targeted therapeutic reagents.

     

吉林珲春自然保护区东北虎和东北豹及其有蹄类猎物的多度与分布

珲春国家级自然保护区是东北虎(Panthera tigris altaica)、东北豹(Panthera pardus orientalis)等濒危物种在中国的核心分布区。为了探究该区域野生动物的多度水平和空间分布, 了解人类干扰情况, 我们运用相对多度指数(relative abundance index, RAI)分析了2013年4-6月设置于此的83个红外相机位点的监测数据。红外相机的总捕获天数6,060 d, 共捕获10科18种野生哺乳动物, 其中鼬科4种, 猫科动物3种, 犬科、鹿科和松鼠科各2种, 猪科、熊科、麝科、猬科和兔科各1种。研究期间共拍摄到东北虎11只个体, 东北豹13只个体。从相对多度指数来看, 东北虎的相对多度(0.84)远高于东北豹(0.48), 它们的有蹄类猎物中梅花鹿(Cervus nippon)的相对多度最高(2.18), 其次为狍(Capreolus pygargus)(1.53)和野猪(Sus scrofa)(0.92)。人类活动和放牧的相对多度水平(分别为40.64和2.76)显著高于野生动物。在空间分布上, 东北虎和梅花鹿主要在保护区的核心区分布, 且与保护区社区共管区的多度水平差异显著, 而东北豹在不同功能区之间的分布差异不显著, 狍在保护区北部的多度水平较高, 但各功能区之间差异不显著, 野猪在社区共管区的多度水平显著高于核心区。可见, 核心区频繁的人类活动和放牧活动对野生动物的保护产生了影响, 未来应加强关于人类干扰对虎、豹种群及其有蹄类猎物的影响评估。     

Identification of a novel aFGF-binding peptide with anti-tumor effect on breast cancer from phage display library

It has been reported that acidic fibroblast growth factor (aFGF) is expressed in breast cancer and via interactions with fibroblast growth factor receptors (FGFRs) to promote the stage and grade of the disease. Thus, aFGF/FGFRs have been considered essential targets in breast cancer therapy. We identified a specific aFGF-binding peptide (AGNWTPI, named AP8) from a phage display heptapeptide library with aFGF after four rounds of biopanning. The peptide AP8 contained two (TP) amino acids identical and showed high homology to the peptides of the 182–188 (GTPNPTL) site of high-affinity aFGF receptor FGFR1. Functional analyses indicated that AP8 specifically competed with the corresponding phage clone A8 for binding to aFGF. In addition, AP8 could inhibit aFGF-stimulated cell proliferation, arrested the cell cycle at the G0/G1 phase by increasing PA2G4 and suppressing Cyclin D1 and PCNA, and blocked the aFGF-induced activation of Erk1/2 and Akt kinase in both breast cancer cells and vascular endothelial cells. Therefore, these results indicate that peptide AP8, acting as an aFGF antagonist, is a promising therapeutic agent for the treatment of breast cancer.     

Substantial reorganization of China's tropical and subtropical forests: based on the permanent plots

There is evidence that climate change induced tree mortalities in boreal and temperate forests and increased forest turnover rates (both mortality and recruitment rates) in Amazon forests. However, no study has examined China's tropical and subtropical evergreen broadleaved forests (TEBF) that cover >26% of China's terrestrial land. The sustainability of this biome is vital to the maintenance of local ecosystem services (e.g., carbon sequestration, biodiversity conservation, climatic regulation), many of which may influence patterns of atmospheric circulation and composition at regional to global scales. Here, we analyze time‐series data collected from thirteen permanent plots within China's unmanaged TEBF to study whether and how this biome has changed over recent decades. We find that the numbers of individuals and species for shrub and small tree have increased since 1978, whereas the numbers of individuals and species for tree have decreased over this same time period. The shift in species composition is accompanied by a decrease in the mean diameter at breast height (DBH) for all individuals combined. China's TEBF may thereby be transitioning from cohorts of fewer and larger individuals to ones of more and smaller individuals, which shows a unique change pattern differing from the documented. Regional‐scale drying is likely responsible for the biome's reorganization. This biome‐wide reconstitution would deeply impact the regimes of carbon sequestration and biodiversity conservation and have implications for the sustainability of economic development in the area.     

不同剂量的塞来昔布对C57BL/6小鼠移植瘤微淋巴管密度抑制作用的研究(英文)

目的:观察不同剂量的塞来昔布对C57BL/6小鼠肺癌移植瘤生长、COX-2表达和微淋巴管密度影响,探讨塞来昔布对C57BL/6小鼠肺癌移植瘤淋巴管生成可能作用机制及量效关系。方法:将Lewis肺癌细胞株接种于C57BL/6小鼠左侧腹股沟皮下建立移植瘤模型,随机分为4组:对照组、塞来昔布低剂量、中剂量、高剂量组。观察荷瘤小鼠生存状态,瘤体积变化,种瘤42天后牺牲小鼠,western blot半定量检测COX-2表达及微淋巴管密度。结果:Western blot半定量显示:塞来昔布高、中剂量组COX-2的表达水平及免疫组织化学染色微淋巴管密度计数均明显减低,差异有统计学意义(P0.05),低剂量组略有减低但差异无统计学意义(P0.05)。抑制程度呈明显的剂量依赖性。结论:塞来昔布抑制Lewis肺癌移植瘤的生长及淋巴转移,可能与下调COX-2的表达,阻遏了淋巴管生成的信号通路,抑制微淋巴管生成有关,该抑制作用呈一定的剂量相关性。     

Genome-Wide Association Study Dissects the Genetic Architecture of Seed Weight and Seed Quality in Rapeseed (Brassica napus L.)

Association mapping can quickly and efficiently dissect complex agronomic traits. Rapeseed is one of the most economically important polyploid oil crops, although its genome sequence is not yet published. In this study, a recently developed 60K Brassica Infinium^® SNP array was used to analyse an association panel with 472 accessions. The single-nucleotide polymorphisms (SNPs) of the array were in silico mapped using ‘pseudomolecules’ representative of the genome of rapeseed to establish their hypothetical order and to perform association mapping of seed weight and seed quality. As a result, two significant associations on A8 and C3 of Brassica napus were detected for erucic acid content, and the peak SNPs were found to be only 233 and 128 kb away from the key genes BnaA.FAE1 and BnaC.FAE1. BnaA.FAE1 was also identified to be significantly associated with the oil content. Orthologues of Arabidopsis thaliana HAG1 were identified close to four clusters of SNPs associated with glucosinolate content on A9, C2, C7 and C9. For seed weight, we detected two association signals on A7 and A9, which were consistent with previous studies of quantitative trait loci mapping. The results indicate that our association mapping approach is suitable for fine mapping of the complex traits in rapeseed.     

Akt2 Is Involved in Loss of Epithelial Cells and Renal Fibrosis following Unilateral Ureteral Obstruction

Obstructive nephropathy is an aggressive form of chronic kidney disease (CKD), which is characterized by an epithelial-to-mesenchymal transition (EMT) and interstitial fibrosis. However, the molecular mechanisms of EMT and fibrosis are complex and not fully understood. In this study, we investigated the contribution of Akt2 to experimental renal EMT and fibrosis using the well-established model of unilateral ureteral obstruction (UUO). We found that Akt2 and phosphor (p)-Akt protein levels were increased in the obstructed kidneys. UUO induced activation of transforming growth factor-β1 (TGF-β1) signaling. Importantly, knockout of Akt2 suppressed UUO-induced EMT, kidney fibrosis, increased GSK3β activity, and decreased expression of Snail and β-catenin. Inhibition of GSK3β with LiCl (the inhibitor of GSK3β) increased the expression of Snail and β-catenin in cultured kidney epithelial cells. Our findings suggest that Akt2 partially contributes to interstitial fibrosis following UUO and that inhibition of this signaling pathway may provide a novel approach of prevent progression of renal fibrosis.     

Structural Insights into the Catalytic Mechanism of Synechocystis Magnesium Protoporphyrin IX O-Methyltransferase (ChlM)

Magnesium protoporphyrin IX O-methyltransferase (ChlM) catalyzes transfer of the methyl group from S-adenosylmethionine to the carboxyl group of the C13 propionate side chain of magnesium protoporphyrin IX. This reaction is the second committed step in chlorophyll biosynthesis from protoporphyrin IX. Here we report the crystal structures of ChlM from the cyanobacterium Synechocystis sp. PCC 6803 in complex with S-adenosylmethionine and S-adenosylhomocysteine at resolutions of 1.6 and 1.7 Å, respectively. The structures illustrate the molecular basis for cofactor and substrate binding and suggest that conformational changes of the two “arm” regions may modulate binding and release of substrates/products to and from the active site. Tyr-28 and His-139 were identified to play essential roles for methyl transfer reaction but are not indispensable for cofactor/substrate binding. Based on these structural and functional findings, a catalytic model is proposed.     

Effect of Off-Season Flooding on Growth,Photosynthesis, Carbohydrate Partitioning,and Nutrient Uptake in Distylium chinense

Distylium chinense is an evergreen shrub used for the vegetation recovery of floodplain and riparian areas in Three Gorges Reservoir Region. To clarify the morphological and physiological responses and tolerance of Distylium chinense to off-season flooding, a simulation flooding experiment was conducted during autumn and winter. Results indicated that the survival rate of seedlings was 100%, and that plant height and stem diameter were not significantly affected by flooding. Adventitious roots and hypertrophic lenticels were observed in flooded seedlings after 30 days of flooding. Flooding significantly reduced the plant biomass of roots, net photosynthetic rate (P _n), stomatal conductance (g _s), transpiration rate (T _r), maximum photochemical efficiency (Fv/Fm), photochemical quenching (qP), and electron transport rate (ETR) in leaves, and also affected the allocation and transport of carbohydrate and nutrients. However, D. chinense was able to maintain stable levels of P _n, Fv/Fm, qP, ETR, and nutrient content (N and P) in leaves and to store a certain amount of carbohydrate in roots over prolonged durations of flooding. Based on these results, we conclude that there is a high flooding tolerance in D. chinense, and the high survival rate of D. chinense may be attributable to a combination of morphological and physiological responses to flooding.