Genome‐wide distribution and functions of the AAE complex in epigenetic regulation in Arabidopsis

Heterochromatin is widespread in eukaryotic genomes and has diverse impacts depending on its genomic context. Previous studies have shown that a protein complex, the ASI1‐AIPP1‐EDM2 (AAE) complex, participates in polyadenylation regulation of several intronic heterochromatin‐containing genes. However, the genome‐wide functions of AAE are still unknown. Here, we show that the ASI1 and EDM2 mostly target the common genomic regions on a genome‐wide level and preferentially interacts with genetic heterochromatin. Polyadenylation (poly(A) sequencing reveals that AAE complex has a substantial influence on poly(A) site usage of heterochromatin‐containing genes, including not only intronic heterochromatin‐containing genes but also the genes showing overlap with heterochromatin. Intriguingly, AAE is also involved in the alternative splicing regulation of a number of heterochromatin‐overlapping genes, such as the disease resistance gene RPP4. We provided evidence that genic heterochromatin is indispensable for the recruitment of AAE in polyadenylation and splicing regulation. In addition to conferring RNA processing regulation at genic heterochromatin‐containing genes, AAE also targets some transposable elements (TEs) outside of genes (including TEs sandwiched by genes and island TEs) for epigenetic silencing. Our results reveal new functions of AAE in RNA processing and epigenetic silencing, and thus represent important advances in epigenetic regulation.     

皮层神经发生的分子调控机制

在高等动物神经发育过程中,背侧端脑神经上皮细胞在多种调控基因及环境调控因子的作用下经历了错综复杂的发育事件,逐步形成具有精细的分层结构和高级功能的神经皮层。这些发育中的调控具有严格的时间和区域特性。本文主要就皮层形成中神经干细胞增殖、分化方向及皮层神经元亚型的特化等方面的调控机制予以论述。     

Pim-2抑制肿瘤细胞凋亡机制的研究

随着肿瘤发病学研究的深入,丝／苏氨酸激酶Pim-2抑制肿瘤细胞凋亡的机制越来越受到关注。通过比较Pim-2与其他癌基因作用机制的异同发现,Pim-2可与Myc协同作用,在多个位点磷酸化Bad,通过NF-κB发挥抗凋亡活性,是与Akt不同的抗凋亡通路。Pim-2强大而广泛的抗凋亡作用是多种肿瘤发生发展的重要机制之一。对Pim-2作用机制的深入研究将有助于阐明其在肿瘤发病中的作用,并有望将其作为肿瘤基因治疗的新靶点。     

Depression compromises antiviral innate immunity via the AVP-AHI1-Tyk2 axis

Depression is a serious public-health issue. Recent reports have suggested higher susceptibility to viral infections in depressive patients. However, how depression affects antiviral innate immune signaling remains unknown. Here, we revealed a reduction in expression of Abelson helper integration site 1 (AHI1) in the peripheral blood mononuclear cells (PBMCs) and macrophages from the patients with major depressive disorder (MDD), which leads to attenuated antiviral immune response. We found that depression-related arginine vasopressin (AVP) induces reduction of AHI1 in macrophages. Further studies demonstrated that AHI1 is a critical stabilizer of basal type-I-interferon (IFN-I) signaling. Mechanistically, AHI1 recruits OTUD1 to deubiquitinate and stabilize Tyk2, while AHI1 reduction downregulates Tyk2 and IFN-I signaling activity in macrophages from both MDD patients and depression model mice. Interestingly, we identified a clinical analgesic meptazinol that effectively stimulates AHI1 expression, thus enhancing IFN-I antiviral defense in depression model mice. Our study promotes the understanding of the signaling mechanisms of depression-mediated antiviral immune dysfunction, and reveals meptazinol as an enhancer of antiviral innate immunity in depressive patients.Subject terms: Innate immunity, Ubiquitylation, Cell signalling     

广东省大中型供水水库营养现状及浮游生物的响应

于2000年调查了广东省18座大中型供水水库的水质现状并探讨了浮游生物对营养水平的响应。总氮、总磷、透明度和叶绿素a分别为0．15～7.15mg／L、0．003～0．387mg／L、0．4～6．3m和0．6～32．3ug／L。总氮、总磷、透明度均与叶绿素a呈较高的相关性。根据这4个因子的综合加权营养状态指数为23．7～55．1,季节差异不大,大多数水库处于中营养状态。金藻在中-富及富营养型水库中没有分布,而蓝藻、绿藻、硅藻和甲藻在调查水库中均有比较广的营养生态位,但它们的密度及相对优势度在各营养型水库中有一定的差异。高营养水平水库有较高的细胞密度和叶绿素a含量。营养水平较低的水库浮游植物以硅藻-甲藻、硅藻-绿藻或金藻-硅藻为主;营养水平较高的水库以蓝藻-硅藻或蓝藻-绿藻为主,并有较高的裸藻密度。浮游动物基本上以桡足类为优势种群,但在中-富营养和富营养型水库中,哲水蚤种类比低营养型水库中少。枝角类优势种类在各营养型水库差别不大。轮虫对水体营养水平的响应相对比较显著。低营养水平水库的轮虫以广营养型、中营养型或寡中营养型种类为主,种类数目比较少;富营养和中-富营养型水库的轮虫以喜在中营养到富营养条件下生长的种类为主,且轮虫种类数目比较多。     

流溪河水库水动力学对营养盐和浮游植物分布的影响

流溪河水库2001年年降雨量2250mm,其中79％来自4月至9月的丰水期。入库流量变幅4．25～414．00m^3／s,近60％的入库水量流来自吕田河。流域营养盐输送量取决于流域降雨径流强度,吕田河高于玉溪河。由于营养盐被泥沙吸附沉积,丰水期湖泊区营养盐浓度明显低于河流区。浮游植物密度为17～1245cells／ml,以硅藻为主要优势种群。硅藻密度分布与水流流速和透明度的相关程度明显高于与营养盐和温度的相关程度。在丰水期,由于受水流和透明度的强烈控制,尽管营养盐供应比较充足,硅藻密度处于比较低的水平。丰水期硅藻密度稍低于枯水期,河流区明显低于大坝处。浮游植物香农-威纳多样性指数为0．97～2．75。受水库水动力学(水位波动等因素)的影响,最大浮游植物多样性出现于水位波动比较大的8月份,最小值则出现于水位波动最小的6月份。     

Segmental Kinematic Coupling of the Human Spinal Column during Locomotion

As one of the most important daily motor activities, human locomotion has been investigated intensively in recent decades. The locomotor functions and mechanics of human lower limbs have become relatively well understood. However, so far our understanding of the motions and functional contributions of the human spine during locomotion is still very poor and simultaneous in-vivo limb and spinal column motion data are scarce. The objective of this study is to investigate the delicate in-vivo kinematic coupling between different functional regions of the human spinal column during locomotion as a stepping stone to explore the locomotor function of the human spine complex. A novel infrared reflective marker cluster system was constrncted using stereophotogrammetry techniques to record the 3D in-vivo geometric shape of the spinal column and the segmental position and orientation of each functional spinal region simultaneously. Gait measurements of normal walking were conducted. The preliminary results show that the spinal column shape changes periodically in the frontal plane during locomotion. The segmental motions of different spinal functional regions appear to be strongly coupled, indicating some synergistic strategy may be employed by the human spinal column to facilitate locomotion. In contrast to traditional medical imaging-based methods, the proposed technique can be used to investigate the dynamic characteristics of the spinal column, hence providing more insight into the functional biomechanics of the human spine.     

shRNA‑mediated knockdown of KNTC1 inhibits non-small-cell lung cancer through regulating PSMB8

In view of the important roles played by Kinetochore proteins in mitosis, we believed that they may contribute to the development and progression of human cancers, which has been reported recently elsewhere. Kinetochore-associated 1 (KNTC1) participates in the segregation of sister chromatids during mitosis, the effects of which on non-small-cell lung cancer (NSCLC) remain unclear. Here, we sought to identify the biological significance of KNTC1 in NSCLC. KNTC1 protein expression in NSCLC tissues was investigated by immunohistochemistry. Lentivirus delivered short hairpin RNA (shRNA) was utilized to establish KNTC1 silence NSCLC cell lines. The effects of KNTC1 depletion on NSCLC cell proliferation, migration, apoptosis, and tumor formation were analyzed by MTT assay, wound-healing assay, transwell assay, flow cytometry assay, and in nude mouse models in vivo. After KNTC1 reduction, NSCLC cell viability, proliferation, migration, and invasion were restrained. A xenograft tumor model was also provided to demonstrate the inhibited tumorigenesis in NSCLC. In addition, the downstream mechanism analysis indicated that KNTC1 depletion was positively associated with PSMB8. The findings of the present study suggested that KNTC1 may have a pivotal role in mediating NSCLC progression and may act as a novel therapeutic target for NSCLC.Subject terms: Non-small-cell lung cancer, Cell migration