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.     

人参生理生态的研究

人参是我国极其珍贵的药用植物之一。本文从生理生态的角度对其在生长季的各种环境因子的变化规律及光合生理进程作了较为全面、系统的定位定量研究。根据不同观测点的试验数据,得出了有利于人参生长的最适环境范围,为人参的栽培提供了理论依据及基础资料。     

Requirement for Lamin B Receptor and Its Regulation by Importin β and Phosphorylation in Nuclear Envelope Assembly during Mitotic Exit

Lamin B receptor (LBR), a chromatin and lamin B-binding protein in the inner nuclear membrane, has been proposed to target the membrane precursor vesicles to chromatin mediated by importin β during the nuclear envelope (NE) assembly. However, the mechanisms for the binding of LBR with importin β and the membrane targeting by LBR in NE assembly remain largely unknown. In this report, we show that the amino acids (aa) 69–90 of LBR sequences are required to bind with importin β at aa 45–462, and the binding is essential for the NE membrane precursor vesicle targeting to the chromatin during the NE assembly at the end of mitosis. We also show that this binding is cell cycle-regulated and dependent on the phosphorylation of LBR Ser-71 by p34^cdc2 kinase. RNAi knockdown of LBR causes the NE assembly failure and abnormal chromatin decondensation of the daughter cell nuclei, leading to the daughter cell death at early G₁ phase by apoptosis. Perturbation of the interaction of LBR with importin β by deleting the LBR N-terminal spanning region or aa 69–73 also induces the NE assembly failure, the abnormal chromatin decondensation, and the daughter cell death. The first transmembrane domain of LBR promotes the NE production and expansion, because overexpressing this domain is sufficient to induce membrane overproduction of the NE. Thus, these results demonstrate that LBR targets the membrane precursor vesicles to chromatin by interacting with importin β in a LBR phosphorylation-dependent manner during the NE assembly at the end of mitosis and that the first transmembrane domain of LBR promotes the LBR-bearing membrane production and the NE expansion in interphase.     

Novel A14841G mutation is associated with high penetrance of LHON/C4171A family

We report the clinical and genetic characterization of a Chinese LHON family carrying an ND1/C4171A mutation. This family has high penetrance of visual impairment and extremely low frequency of vision recovery, which is in marked contrast to previously reported results for Korean LHON families with the same mutation. Sequence analysis of the complete mtDNA in the partially defined East Asian haplogroup N9a1 revealed the presence of 29 other variants. A novel heteroplasmic A14841G mutation, one of the variants with a serine substituted for a highly conserved asparagine at amino acid 32 of Cytochrome b (Cytb), may play a synergistic role with the C4171A mutation, leading to significantly different clinical manifestations of LHON among these families. The study further confirmed that C4171A was a rare primary LHON mutation, and the mtDNA background could also contribute to the clinical manifestation of the LHON/C4171A mutation.     

不同氮磷钾施肥方式对水稻碳、氮累积与分配的影响

基于我国南方双季稻区20年长期田间定位施肥试验,研究了不同氮磷钾施肥方式对水稻碳、氮积累与分配的影响.结果表明:偏施氮肥处理水稻籽实的碳、氮含量最高,分别达到433和18.9 g·kg-1.水稻植株的碳、氮储量以氮磷钾平衡施肥(NPK)及氮磷钾基础上有机物料循环施肥处理(NPKC)最高,其中NPKC和NPK处理籽实碳储量分别为2015和1960kg hm-2,茎叶碳储量分别为2048和2002 kg·hm-2;籽实氮储量分别为80.6和80.5kg·hm-2,茎叶氮储量则以NPK处理最高,为59.3 kg·hm-2.有机无机肥的配合施用显著增加了水稻植株体内碳和氮的累积;与偏施氮肥处理相比,氮磷钾的综合施用更利于水稻生长过程中碳、氮的累积与分配.     

肽转运载体的分子特征及其分布

动物体内的肽转运载体目前发现的至少有五种,其中研究最为广泛的是：PepT1和PepT2。PepT1和PepT2都是依质子的寡肽转运载体(POT)家族的成员。PepT1是低亲和力／高容量的肽载体,PepT2高亲和力／低容量的肽载体。PepT1主要在消化道中表达,在肾脏中也有微弱的表达;PepT2主要在肾脏中表达。这些肽载体的分子结构特征主要有：(1)有12个假想的穿膜区,在9区和10区之间有一大的胞外环,且所有穿膜区内的序列都高度保守,胞外环上的序列保守的很少;(2)被编码的蛋白上有多个N-糖基化和蛋白激酶的识别位点,它们可能参与肽转运的调控;(3)PepT1上的His-57和PepT2上的His-87是最关键的组氨酸残基,它们可能是转运蛋白发挥吸收功能时最关键的结合位点;(4)不同动物肽转运蛋白的氨基酸范围在707到729之间,且不同动物相同器官肽转运载体的同源性高(大约80％),同种动物不同器官肽转运载体的同源性低(大约50％)。了解肽载体的分子特征和组织分布,可以更好地理解肽吸收的分子机制并有利于肽类药物的研发。     

The evolution of plant microRNAs: insights from a basal eudicot sacred lotus

microRNAs (miRNAs) are important noncoding small RNAs that regulate mRNAs in eukaryotes. However, under which circumstances different miRNAs/miRNA families exhibit different evolutionary trajectories in plants remains unclear. In this study, we sequenced the small RNAs and degradome from a basal eudicot, sacred lotus (Nelumbo nucifera or lotus), to identify miRNAs and their targets. Combining with public miRNAs, we predicted 57 pre‐eudicot miRNA families from different evolutionary stages. We found that miRNA families featuring older age, higher copy and target number tend to show lower propensity for miRNA family loss (PGL) and stronger signature of purifying selection during divergence of temperate and tropical lotus. Further analyses of lotus genome revealed that there is an association between loss of miRNA families in descendent plants and in duplicated genomes. Gene dosage balance is crucial in maintaining those preferentially retained MIRNA duplicates by imposing stronger purifying selection. However, these factors and selection influencing miRNA family evolution are not applicable to the putative MIRNA‐likes. Additionally, the MIRNAs participating in lotus pollen–pistil interaction, a conserved process in angiosperms, also have a strong signature of purifying selection. Functionally, sequence divergence in MIRNAs escalates expression divergence of their target genes between temperate and tropical lotus during rhizome and leaf growth. Overall, our study unravels several important factors and selection that determine the miRNA family distribution in plants and duplicated genomes, and provides evidence for functional impact of MIRNA sequence evolution.     

髓源性防御素的研究进展

防御素是一组含有6个半胱氨酸的阳离子抗微生物多肽。在中性粒细胞内,防御素含量丰富,具有广谱、高效的抗微生物活性,是机体天然免疫机制的重要组成部分。近年来的临床观察表明,测定血浆及各种体液中髓源性防御素的改变有助于某些炎症性疾患的诊断。此外,提纯或重组防御素作为“超级抗生素”则已成为药学界的研究热点。本文着重对髓源性防御素的生化特性、生物学活性及其与疾病的关系作一概述。     

Rescuing infusion of miRNA-1 prevents cardiac remodeling in a heart-selective miRNA deficient mouse

Objective

The decreased expression of muscle-specific microRNA-1 (miR-1) has been found in many cardiovascular diseases and is considered to contribute to heart failure (HF). Here we investigated the role of miR-1 in myocardium protection by infusion of miR-1 in a cardiac global miRNA-deficient mouse.