AMPK regulates homeostasis of invasion and viability in trophoblasts by redirecting glucose metabolism: Implications for pre‐eclampsia

Pre‐eclampsia (PE) is deemed an ischemia‐induced metabolic disorder of the placenta due to defective invasion of trophoblasts during placentation; thus, the driving role of metabolism in PE pathogenesis is largely ignored. Since trophoblasts undergo substantial glycolysis, this study aimed to investigate its function and regulatory mechanism by AMPK in PE development. Metabolomics analysis of PE placentas was performed by gas chromatography–mass spectrometry (GC–MS). Trophoblast‐specific AMPKα1‐deficient mouse placentas were generated to assess morphology. A mouse PE model was established by Reduced Uterine Perfusion Pressure, and placental AMPK was modulated by nanoparticle‐delivered A769662. Trophoblast glucose uptake was measured by 2‐NBDG and 2‐deoxy‐d‐[³H] glucose uptake assays. Cellular metabolism was investigated by the Seahorse assay and GC–MS.PE complicated trophoblasts are associated with AMPK hyperactivation due not to energy deficiency. Thereafter, AMPK activation during placentation exacerbated PE manifestations but alleviated cell death in the placenta. AMPK activation in trophoblasts contributed to GLUT3 translocation and subsequent glucose metabolism, which were redirected into gluconeogenesis, resulting in deposition of glycogen and accumulation of phosphoenolpyruvate; the latter enhanced viability but compromised trophoblast invasion. However, ablation of AMPK in the mouse placenta resulted in decreased glycogen deposition and structural malformation. These data reveal a novel homeostasis between invasiveness and viability in trophoblasts, which is mechanistically relevant for switching between the ‘go’ and ‘grow’ cellular programs.

Pre‐eclampsia (PE) is associated with trophoblast AMPK hyperactivation, presumably due to LKB1 phosphorylation, and glucose uptake is consequently increased via trafficking of GLUT3 from the cytosol to the plasma membrane. Such translocation enhances glycolytic flux and redirects glucose metabolic intermediates into gluconeogenesis, resulting in PEP accumulation, which not only benefits cell survival but also suppresses invasion by repressing MMPs, and thus in turn modulates switching between the ‘go’ and ‘grow’ cellular programs.     

Cloning and characterization of a novel human RNA binding protein gene PNO1.

Present work reported the cloning and characterization of a human novel RNA binding gene Partner of NOB1 (PNO1), with a length of 1637bp and a putative open reading frame of 759 bp, isolated from human kidney. It is composed of seven exons and is localized on chromosome 2p14. Western blot showed that the molecular weight of PNO1 is about 35kDa. RT-PCR results in 16 human tissues indicated that PNO1 is expressed mainly in liver, lung, spleen and kidney, slightly in thymus, testis, ovary, respectively, but not in heart, brain, skeletal muscle, placenta, pancreas, prostate, small intestine, colon and peripheral blood leukocytes. GFP fusion expression in mammalian cells exhibited its localization in the nucleus, especially in nucleoli. Subcellular localization of thirteen GFP fusion PNO1 deletion proteins showed that the region of 92-230 aa is solely responsible for its nucleolar retention, and KH domain alone is not sufficient for nucleolar retention. The PNO1 family shows significant conservation in both eukaryotes and prokaryotes.     

Biological implications of genetic variations in autism spectrum disorders from genomics studies

Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental condition characterized by atypical social interaction and communication together with repetitive behaviors and restricted interests. The prevalence of ASD has been increased these years. Compelling evidence has shown that genetic factors contribute largely to the development of ASD. However, knowledge about its genetic etiology and pathogenesis is limited. Broad applications of genomics studies have revealed the importance of gene mutations at protein-coding regions as well as the interrupted non-coding regions in the development of ASD. In this review, we summarize the current evidence for the known molecular genetic basis and possible pathological mechanisms as well as the risk genes and loci of ASD. Functional studies for the underlying mechanisms are also implicated. The understanding of the genetics and genomics of ASD is important for the genetic diagnosis and intervention for this condition.     

BDCGrid:基于Globus的生物信息高性能计算网格系统

随着分子生物信息数据量高速增长,生物信息学面临着大规模、高通量、密集型计算的巨大挑战。为有效利用计算机资源,缩短高通量生物信息计算程序执行时间,我们基于Globus Toolkit网格中间件,实现了一个支持高通量生物数据计算的网格系统(Biological Data Computing Grid,简称BDCGrid)。BDCGrid计算网格系统模型可以有效整合中小型生物信息学实验室计算机资源,大大缩短高通量生物信息计算程序执行时间,为相关研究人员利用现有计算机资源处理大规模、高通量生物信息计算任务提供一种新的途径。     

Selection of the Maximum Spatial Cluster Size of the Spatial Scan Statistic by Using the Maximum Clustering Set-Proportion Statistic

Spatial scan statistics are widely used in various fields. The performance of these statistics is influenced by parameters, such as maximum spatial cluster size, and can be improved by parameter selection using performance measures. Current performance measures are based on the presence of clusters and are thus inapplicable to data sets without known clusters. In this work, we propose a novel overall performance measure called maximum clustering set–proportion (MCS-P), which is based on the likelihood of the union of detected clusters and the applied dataset. MCS-P was compared with existing performance measures in a simulation study to select the maximum spatial cluster size. Results of other performance measures, such as sensitivity and misclassification, suggest that the spatial scan statistic achieves accurate results in most scenarios with the maximum spatial cluster sizes selected using MCS-P. Given that previously known clusters are not required in the proposed strategy, selection of the optimal maximum cluster size with MCS-P can improve the performance of the scan statistic in applications without identified clusters.     

蹲跳、反向跳和下落跳的膝关节屈伸肌群肌电信号分析

目的：通过观察肌电图（EMG）的变化,了解运动员与普通中学生在纵跳过程中,膝关节屈伸肌群工作特点,为运动员科学选材提供依据。方法：30名男女青少年运动员和30名男女普通中学生进行各种形式纵跳（蹲跳、反向跳、下落跳）,测试膝关节屈伸肌群的EMG变化情况。结果：主动肌（股外肌）EMG的变化存在性别差异,随着下肢工作强度的增加,男运动员积分肌电图（iEMG)和平均功率频率（Fmean)均没有显著变化,女运动员iEMG增加,Fmean没有显著变化,对抗肌（股二头肌）,随着下肢工作强度的增加。青少年运动员EMG活动变化较小,而普通中学生的EMG活动明显增加。结论：在增加工作负荷的过程中,男运动员膝关节伸肌群以提高效率为主,女运动员以提高肌肉的募集数量为主;运动员的对抗肌协调水平高于普通中学生。     

Sunfleck limits the small-scale distribution of endangered <Emphasis Type="Italic">Kingdonia uniflora</Emphasis> in the natural habitat of subalpine forest proved by its photosynthesis

The physiological effects of sunflecks on understory plants are poorly understood. Kingdonia uniflora is an endemic and endangered species in China, with a patchy distribution over much of its range. Sunflecks are reportedly the likely dominant factor in determining its patchy distribution. We studied the photosynthesis of K. uniflora in the field to test whether understory sunflecks result in photoinhibition and, thereby, potentially influence its patchy distribution. K. uniflora exhibited the low dark respiration rates, low light compensation points, and low light saturation points characteristic of shade-tolerant plants, allowing maintenance during the long periods of low understory light. Moreover, K. uniflora was able to regulate light energy utilization by non-photochemical quenching in low light. Gas exchange parameters were measured in six treatments (sunfleck-enriched, sunfleck-enriched with added saturation light, sunfleck-enriched with filtered ultraviolet-B (UV-B) radiation , sunfleck-limited, sunfleck-limited with added saturation light, and sunfleck-limited with filtered UV-B). The sunfleck-enriched treatment caused photoinhibition in K. uniflora, in part due to a UV-B-induced decrease in Pn. In addition, the application of simulated sunflecks indicated that K. uniflora leaves do not need continuous light. The photosynthetic responses of K. uniflora to sunflecks indicate that the sunflecks are a limiting factor in the small-scale distribution of K. uniflora.     

菝葜属和肖菝葜属的核型变异和系统演化研究

基于体细胞染色体核型及花序特征对菝葜科Smilacaceae菝葜属Smilax和肖菝葜属Heterosmilax进行了系统演化研究,报道了国产菝葜科17个分类群的核型。根据已研究的部分形态学特征和已有的核型和分子序列资料,对它们的系统进化进行了分析。结果显示：（1）整个类群的核型变异表现在二型化、多倍化、染色体的微变异以及染色体基数递减（从16-15-13）,16为菝葜类群的基本染色体基数。（2）草本菝葜的核型对称性在东亚到北美种类中,表现出从对称到不对称的变化,而木本菝葜的各组间并未表现出这种趋势。（3）先出叶（prophy11）是宿存的芽鳞,因此在菝葜组sect．China和土茯苓组sect．Coilanthus中具花序的分枝（该分枝基部具先出叶）与圆锥菝葜组sect．Macranthae和穗菝葜组sect．Smilax中着生叶腋的花序分枝或者具关节的单伞形花序是同源的;结合ITS资料,推测花序原始类型是具伞形花序无总花梗呈穗状排列的种类。从祖先类型,花序的分化朝两个方向：一为菝葜属的菝葜组和土茯苓组以及肖菝葜属的全部种类为代表的生于叶腋的单伞形花序,另一为菝葜属的圆锥菝葜组sect．Macranthae的全部种类构成的圆锥．伞形花序。（4）肖菝葜属的核型和ITS数据都表明其为非单系类群,与草本菝葜和土茯苓组成员为姐妹群,首次发现花被2／3联合的过渡类型——筐条菝葜S.corbularia,建议将肖菝葜属降为亚属,置于菝葜属。（5）核型特点支持草本菝葜是东亚起源,扩展到北美,与土茯苓组种类有共同祖先．来自于x=16的木本菝葜,赞同恢复草本组sect．Nemexia。（6）在广布种菝葜S.china中首次发现二倍体居群,已知其存在3种倍性（2x、4x和6x）,发现不同倍性居群的分布规律,推测在第三纪至更新世中期日本、台湾岛与大陆分离之前,菝葜的叙居群已广泛分布,而目前广泛分布的缸居群是岛屿与大陆分离后形靠的。（7）我国西南是菝葜科现代分布和分化中心。