Cutting off the power: inhibition of leukemia cell growth by pausing basal ATP release and P2X receptor signaling?

T cells respond to antigen stimulation with the rapid release of cellular ATP, which stimulates an autocrine feedback mechanism that regulates calcium influx through P2X receptors. This autocrine purinergic feedback mechanism plays an essential role in the activation of T cells resulting in cell proliferation and clonal expansion. We recently reported that increases in mitochondrial ATP production drive this stimulation-induced purinergic signaling mechanism but that low-level mitochondrial ATP production fuels basal T cell functions required to maintain vigilance of unstimulated T cells. Here we studied whether defects in these purinergic signaling mechanisms are involved in the unwanted proliferation of leukemia T cells. We found that acute leukemia T cells (Jurkat) possess a larger number and more active mitochondria than their healthy counterparts. Jurkat cells have higher intracellular ATP concentrations and generat more extracellular ATP than unstimulated T cells from healthy donors. As a result, increased purinergic signaling through P2X1 and P2X7 receptors elevates baseline levels of cytosolic Ca²⁺ in Jurkat cells. We found that pharmacological inhibition of this basal purinergic signaling mechanism decreases mitochondrial activity, Ca²⁺ signaling, and cell proliferation. Similar results were seen in the leukemic cell lines THP-1, U-937, and HL-60. Combined treatment with inhibitors of P2X1 or P2X7 receptors and the chemotherapeutic agent 6-mercaptopurine completely blocked Jurkat cell proliferation. Our results demonstrate that increased mitochondrial metabolism promotes autocrine purinergic signaling and uncontrolled proliferation of leukemia cells. These findings suggest that deranged purinergic signaling can result in T cell malignancy and that therapeutic targeting aimed at purinergic signaling is a potential strategy to combat T cell leukemia.     

Conformal Pad-Printing Electrically Conductive Composites onto Thermoplastic Hemispheres: Toward Sustainable Fabrication of 3-Cents Volumetric Electrically Small Antennas

Electrically small antennas (ESAs) are becoming one of the key components in the compact wireless devices for telecommunications, defence, and aerospace systems, especially for the spherical one whose geometric layout is more closely approaching Chu’s limit, thus yielding significant bandwidth improvements relative to the linear and planar counterparts. Yet broad applications of the volumetric ESAs are still hindered since the low cost fabrication has remained a tremendous challenge. Here we report a state-of-the-art technology to transfer electrically conductive composites (ECCs) from a planar mould to a volumetric thermoplastic substrate by using pad-printing technology without pattern distortion, benefit from the excellent properties of the ECCs as well as the printing-calibration method that we developed. The antenna samples prepared in this way meet the stringent requirement of an ESA (ka is as low as 0.32 and the antenna efficiency is as high as 57%), suggesting that volumetric electronic components i.e. the antennas can be produced in such a simple, green, and cost-effective way. This work can be of interest for the development of studies on green and high performance wireless communication devices.     

Silencing of RASSF3 by DNA Hypermethylation Is Associated with Tumorigenesis in Somatotroph Adenomas

The pathogenic mechanisms underlying pituitary somatotroph adenoma formation, progression are poorly understood. To identify candidate tumor suppressor genes involved in pituitary somatotroph adenoma tumorigenesis, we used HG18 CpG plus Promoter Microarray in 27 human somatotroph adenomas and 4 normal human adenohypophyses. RASSF3 was found with frequent methylation of CpG island in its promoter region in somatotroph adenomas but rarely in adenohypophyses. This result was confirmed by pyrosequencing analysis. We also found that RASSF3 mRNA level correlated negatively to its gene promoter methylation level. RASSF3 hypermethylation and downregulation was also observed in rat GH3 and mouse GT1.1 somatotroph adenoma cell lines. 5-Aza-2′ deoxycytidine and trichostatin-A treatment induced RASSF3 promoter demethylation, and restored its expression in GH3 and GT1.1 cell lines. RASSF3 overexpression in GH3 and GT1.1 cells inhibited proliferation, induced apoptosis accompanied by increased Bax, p53, and caspase-3 protein and decreased Bcl-2 protein expression. We also found that the antitumor effect of RASSF3 was p53 dependent, and p53 knockdown blocked RASSF3-induced apoptosis and growth inhibition. Taken together, our results suggest that hypermethylation-induced RASSF3 silencing plays an important role in the tumorigenesis of pituitary somatotroph adenomas.     

Intracellular delivery of nucleic acid by cell-permeable hPP10 peptide

Although gene therapy offers hope against incurable diseases, nonreplicating transduction vectors remain lacking. We have previously characterized a cell-penetrating peptide hPP10 for the delivery of various cargoes; however, whether hPP10 can mediate nucleic acid delivery is still unknown. Here, examining via different ways, we demonstrate that hPP10 stably complexes with plasmid DNA (pDNA) and safely mediates nucleic acid transfection. hPP10 can mediate GFP-, dsRed-, and luciferase-expressing plasmids into cells with nearly the same efficiency as commercial transfection reagents Turbofectin or Lipofect. Furthermore, hPP10 can mediate Cre fusion protein delivery and pDNA transfection simultaneously in the Cre/loxp system in vitro. In addition, hPP10 fused with an RNA-binding domain can mediate delivery of small interfering RNA into cells to silence the reporter gene expression. Collectively, our results suggest that hPP10 is an option for nucleic acid delivery with efficiencies similar to that of commercial reagents.     

丛枝菌根真菌在田间的分布特征、代谢活性及其对甘薯生长的影响

研究了大田条件下丛枝菌根(AM)真菌的分布特征、代谢活性及其对甘薯的生长效应.结果表明,接种Glomus intraradices 8周后,甘薯地上部干重,薯块鲜重和薯块个数均明显高于不接种对照;植株地上部和根系的吸磷量显著提高.与不接种对照相比,接种处理的甘薯菌根侵染率、甘薯根外菌丝密度以及甘薯根内菌丝的活性(根内菌丝碱性磷酸酶活性)显著提高.进一步分析甘薯根际不同方位上的菌丝分布,发现接种处理中平行于垄的方向的菌丝密度显著高于苗子下方的菌丝密度,而不接种处理的各个方向总菌丝密度无差异;活菌丝(具琥珀酸脱氢酶活性的菌丝)密度在各个方向的分布规律与总菌丝密度的分布规律一致.接种后根内菌丝活性的增强,根外活性菌丝密度的增加及其分布特征的改变,是甘薯产量增加的主要原因.     

大豆曲茎性状的遗传分析和RAPD标记研究

曲茎遗传材料NG94-156与遗传背景不同的3个正常茎品种杂交,获得1个F2群体和2个重组自交家系(F7:8)。后代分离分析的结果表明,NG94-156的曲茎性状受两对隐性重叠基因控制。利用4个亲本和1个重组自交家系筛选260个RAPD随机引物,其中有1个引物S-506扩增出的多态性条带有较好的重复性。经过连锁分析,RAPD标记S-5061600与控制曲茎的基因的遗传距离为6.94 cM。     

巨大儿与足月适于胎龄儿2岁以内的体格及智能发育的对照研究

目的：了解出生体重对婴儿早期体格及智能发育的影响,为巨大儿的早期保健及健康教育提供理论依据。方法：在我院2007年1月～2009年12月出生的巨大儿及足月适于胎龄儿中,随机选取50例足月巨大儿作为观察组（除外生后低血糖、窒息、高胆红素血症者）,及50例与之匹配的足月适于胎龄儿作为对照组。两组孕周、生后评分、性别比例、父母收入、喂养方式比较差异无统计学意义。定期检查和记录两组的各体格及智能发育评估指标,了解两组婴儿体重指数及智能发育特点,采用Gesell发育诊断量表对两组进行评价。结果：观察组出生后3、6、9、12、18、24个月的超重发生率均显著高于对照组,差异均有统计学意义（P〈0.05）,观察组随年龄增长体重指数有下降趋势,6月龄时体重指数最高,24月时最低;观察组6月时大运动发育商数为（100.86±3.34）,对照组则为（104.58±3.19）,差异有统计学意义（P〈0.05）,12月时,观察组的发育商数已接近正常,两组大运动、精细运动、适应行为、语言和个人-社会性行为5个方面的的差异均无统计学意义（P〉0.05）。结论：巨大儿在2岁以内的体重指数显著高于足月适于胎龄儿;较重的体重负荷可对其生后6月内的大运动造成不良影响。     

冠心病强化标准化药物治疗最新进展

冠状动脉粥样硬化性心脏病的患病人数呈逐年上升趋势,目前治疗冠心病的方法主要包括改善生活方式,药物治疗,经皮冠状动脉介入治疗(PCI)和外科冠状动脉旁路移植手术治疗(CABG)。虽然介入治疗在治疗阻塞性冠心病取得了显著的进展,但因支架再狭窄,晚期血栓形成,及未知的机制,其死亡率未见明显下降。冠状动脉旁路移植手术虽可降低死亡率,但因其为侵入性操作及手术费用的较高成本,不能为大部分患者接受。近几年来进行了一些全球多中心的临床试验研究,以评估不同诊疗方案对冠心病的预后及远期疗效。目前一些研究表明强化标准化药物治疗(optimal medical therapy,OMT)可与再血管化治疗同效。本文将针对冠心病强化标准化药物治疗方面的实验研究进展进行简要综述。     

Crystal structure of UAP56, a DExD/H-box protein involved in pre-mRNA splicing and mRNA export

UAP56 is an essential eukaryotic pre-mRNA splicing factor and mRNA export factor. The mechanisms of its functions are not well understood. We determined the crystal structures of the N- and C-terminal domains of human UAP56 (comprising 90% of the full-length UAP56) at 1.9 A resolution. The two domains each have a RecA-like fold and are connected by a flexible linker. The overall fold of each domain is highly similar to the corresponding domains of eIF4A (a prototypic DExD/H-box protein), with differences at the loops and termini. This structural similarity suggests that UAP56 is likely to possess ATPase and helicase activity similar to eIF4A. The NTP binding pocket of UAP56 is occupied by a citrate ion, mimicking the phosphates of NTP and retaining the P loop in an open conformation. The crystal structure of the N-terminal domain of UAP56 also reveals a dimer interface that is potentially important for UAP56's function.