PML/RARalpha fusion protein mediates the unique sensitivity to arsenic cytotoxicity in acute promyelocytic leukemia cells: Mechanisms involve the impairment of cAMP signaling and the aberrant regulation of NADPH oxidase

Acute promyelocytic leukemia (APL) cells are characterized by PML/RARalpha fusion protein, high responsiveness to arsenic trioxide (ATO)-induced cytotoxicity and an abundant generation of reactive oxygen species (ROS). In this study we investigated the association among these three features in APL-derived NB4 cells. We found that NADPH oxidase-derived ROS generation was more abundant in NB4 cells compared with monocytic leukemia U937 cells. By using PR9, a sub-line of U937 stably transduced with the inducible PML/RARalpha expression vectors, we attributed disparities on ROS generation and ATO sensitivity to the occurrence of PML/RARalpha fusion protein, since PML/RARalpha-expressing cells appeared higher NADPH oxidase activity, higher ROS level and higher sensitivity to ATO. On the other hand, the basal intensity of cAMP signaling pathway was compared between NB4 and U937 as well as between PR9 cells with or without PML/RARalpha, demonstrating that PML/RARalpha-expressing cells had an impaired cAMP signaling pathway which relieved its inhibitory effect on NADPH oxidase derived ROS generation. In summary, the present study demonstrated the correlation of PML/RARalpha with cAMP signaling pathway, NADPH oxidase and ROS generation in APL cells. PML/RARalpha that bestows NB4 cells various pathological features, paradoxically also endows these cells with the basis for susceptibility to ATO-induced cytotoxcity.     

Perforin and Fas cytolytic pathways coordinately shape the selection and diversity of CD8+-T-cell escape variants of influenza virus

Antigenic variation is a viral strategy exploited to promote survival in the face of the host immune response and represents a major challenge for efficient vaccine development. Influenza viruses are pathogens with high transmissibility and mutation rates, enabling viral escape from immunity induced by prior infection or vaccination. Intense selection from neutralizing antibody drives antigenic changes in the surface glycoproteins, resulting in emergence of new strains able to reinfect hosts immune to previously circulating viruses. CD8+ cytotoxic T cells (CTLs) also provide protective immunity from influenza virus infection and may contribute to the antigenic evolution of influenza viruses. Utilizing mice transgenic for an influenza virus NP366-374 peptide-specific T-cell receptor, we demonstrated that the respiratory tract is a suitable site for generation of escape variants of influenza virus selected by CTL in vivo. In this report the contributions of the perforin and Fas pathways utilized by influenza virus-specific CTLs in viral clearance and selection of CTL escape variants have been evaluated. While transgenic CTLs deficient in either perforin- or Fas-mediated pathways are efficient in initial pulmonary viral control, variant virus emergence was observed in all the mice studied, although the spectrum of viral CTL escape variants selected varied profoundly. Thus, a less-restricted repertoire of escape variants was observed in mice with an intact perforin cytotoxic pathway compared with a limited variant diversity in perforin pathway-deficient mice, although maximal variant diversity was observed in mice having both Fas and perforin pathways intact. We conclude that selection of viral CTL escape variants reflects coordinate action between the tightly controlled perforin/granzyme pathway and the more promiscuous Fas/FasL pathway.     

长链非编码RNA在神经系统发育及神经性疾病中的作用

长链非编码RNA(long non-coding RNA,lncRNA)是一类转录本长度在200至数千个核苷酸序列,且不具有蛋白质编码潜能的非编码RNA。相较于研究较多的微小RNA（microRNA,miRNA）和干扰小RNA（small interfering,siRNA）等非编码小RNA,lncRNA的许多功能仍尚不清楚。但越来越多的研究发现,lncRNA可通过多种方式调控中枢神经系统发育,包括表观遗传组蛋白甲基化、转录辅因子调控、可变剪接调控等途经。而以上途经的异常均与多种人类重大疾病的发生密切相关,例如,阿尔兹海默症（Alzheimer’s disease,AD）、自闭症（autism spectrum disorder,ASD）、精神分裂症（schizophrenia,SZ）等。本文就lncRNA在表观遗传水平、转录水平、转录后水平和翻译水平上调控神经系统发育以及其在人类神经性疾病中的作用进行综述。     

巨膜长蝽的形态特征和生物学特性

【目的】近年来巨膜长蝽Jakowleffia setulosa(Jakovlev)由以往稳定种群的荒漠昆虫上升为暴发性发生并迁移至农区危害的农业害虫。由于缺乏对巨膜长蝽基础生物学的相关研究,对其开展监测预警和农业防治存在困难。开展巨膜长蝽个体生物学研究,填补研究空白对于有效监测预报和防控提供可靠的依据,同时能为下一步分析巨膜长蝽成灾规律提供基础数据。【方法】本文通过室内观察和野外调查相结合,系统阐明该种形态特征、生活史、习性和行为等生物学特性。【结果】巨膜长蝽在宁夏中部干旱带一年发生2代,5月中旬和10月中下旬是两个发生高峰期,6月中旬至8月中旬以成虫进入滞育状态,11月下旬以成虫越冬;雌成虫的平均寿命为(32.14±2.34)d,雄成虫的平均寿命为(28.00±3.13)d,雌雄性比为1︰1.9,有多次交尾多次产卵的习性,每头雌虫抱卵量10粒左右,平均产卵量10~15粒左右;食性杂,群居危害,喜食白茎盐生草(Halogeton arachnoideus)等沙生草本植物的种子。【结论】该虫具有以成虫形态越冬和滞育、迁移性强等生物学特性。在生态环境发生较大变动后,能够经历逆境后迅速恢复种群并迁移危害。宁夏中南部地区种植结构调整,极大改变了该地区的荒漠生态环境,促使巨膜长蝽在经过夏季高温滞育恢复种群后无法获得足够野生寄主的情况下,大规模迁入农田系统危害。     

宁夏甜菜丛根病的研究

发生在宁夏甜菜上的一种病毒病的病株叶丛主要表现为黄化、焦桔和叶脉黄化坏死。从其分离的病毒粒子呈杆状,宽约20nm,长度为65—110nm、270—300nm和390—420nm,能侵染甜菜、菠菜、昆诺阿藜、苋色藜、番杏,与甜菜坏死黄脉病毒(BNYVV)抗血清呈阳性反应。综上所述,认为该病害是由BNYVV引起的。     

Novel 2D supramolecular array based on antibacterial drug norfloxacin

Self-assembly reaction of Cd(ClO₄)₂ · 6H₂O with Norfloxacin (H-Norf) affords a novel 2D rectangular grid framework [Cd(Norf)(ClO₄)(H₂O)] (1) with strong blue luminescent emission (λ_em=425 nm), while Norf⁻ acts as a tetradentate bridging linker to connect three Cd centers and ClO₄ ⁻ completes Cd center octahedron coordination geometry. The compound 1 has crystallographic data of triclinic, space group , a=9.4577(1) Å, b=9.5012(2) Å, c=12.2805(1) Å, V=3624.4(3) ų, Z=2.     

Novel Biomarkers for Non-functioning Invasive Pituitary Adenomas were Identified by Using Analysis of microRNAs Expression Profile

The microRNAs (miRNAs) are involved in multiple pathological processes among various types of tumors. However, the functions of miRNAs in benign brain tumors are largely unexplored. In order to explore the pathogenesis of the invasiveness in non-functional pituitary adenoma (NFPA), the miRNAs expression profile was analyzed between invasive and non-invasive non-functional pituitary adenoma by miRNAs microarray. Six most significant differentially expressed miRNAs were identified including four upregulated miRNAs hsa-miR-181b-5p, hsa-miR-181d, hsa-miR-191-3p, and hsa-miR-598 and two downregulated miRNAs hsa-miR-3676-5p and hsa-miR-383. The functions and corresponding signaling pathways of differentially expressed miRNAs were investigated by bioinformatics techniques, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The result of GO analysis indicates regulation of voltage-gated potassium channel activity, positive regulation of sodium ion transport, positive regulation of GTPase activity, negative regulation of Notch signaling pathway, etc. KEGG pathway reveals a series of biological processes, including prolactin signaling pathway, endocrine and other factor-regulated calcium reabsorption, fatty acid metabolism, neuroactive ligand-receptor interaction, etc. The miRNAs hsa-miR-181a-5p was verified by quantitative real-time PCR, and the expression level was in accordance with the microarray result. Our result can provide the evidence on featured miRNAs which play a prominent role in pituitary adenoma as effective biomarkers and therapeutic targets in the future.     

基于MuSIASEM理论的大连经济技术开发区可持续发展评价

基于社会生态系统代谢多尺度综合评估（MuSIASEM）理论,对2000-2007年大连经济技术开发区人类活动时间、体外能投入量和增加值进行综合评价.结果表明：2000-2007年,大连开发区居民生活水平逐年提高;农业逐渐萎缩;第二产业仍为区域支柱产业,能耗较大;第三产业发展落后于第二产业;区域整体和各个产业的体外能代谢率明显提高,能源密度不断下降;人类活动时间与体外能投入量不断减少的情况下,经济增加值稳步增长,区域整体发展呈可持续态势.     

The Impact of Iodine Excess on Thyroid Hormone Biosynthesis and Metabolism in Rats

Thyroid function ultimately depends on appropriate iodine supply to the gland. There is a complex series of checks and balances that the thyroid uses to control the orderly utilization of iodine for hormone synthesis. The aim of our study is to evaluate the mechanism underlying the effect of iodine excess on thyroid hormone metabolism. Based on the successful establishment of animal models of normal-iodine (NI) and different degrees of high-iodine (HI) intake in Wistar rats, the content of monoiodotyrosine (MIT), diiodotyrosine (DIT), T₄, and T₃ in thyroid tissues, the activity of thyroidal type 1 deiodinase (D1) and its (Dio1) mRNA expression level were measured. Results showed that, in the case of iodine excess, the biosynthesis of both MIT and DIT, especially DIT, was increased. There was an obvious tendency of decreasing in MIT/DIT ratio with increased doses of iodine intake. In addition, iodine excess greatly inhibited thyroidal D1 activity and mRNA expression. T₃ was greatly lower in the HI group, while there was no significant difference of T₄ compared with NI group. The T₃/T₄ ratio was decreased in HI groups, antiparalleled with increased doses of iodine intakes. In conclusion, the increased biosyntheses of DIT relative to MIT and the inhibition of thyroidal Dio1 mRNA expression and D1 activity may be taken as an effective way to protect an organism from impairment caused by too much T₃. These observations provide new insights into the cellular regulation mechanism of thyroid hormones under physiological and pathological conditions.