Hydrogen sulfide reduces mRNA and protein levels of β-site amyloid precursor protein cleaving enzyme 1 in PC12 cells

Hydrogen sulfide (H(2)S) is now identified as a new neuromodulator. Increasing evidence suggest that H(2)S may play an important role in the progression of Alzheimer's disease (AD). The aim of the present study is to investigate the effects of H(2)S on beta-site amyloid precursor protein cleaving enzyme 1 (BACE-1) expression and amyloid beta (Aβ) secretion in PC12 cells. The levels of BACE-1 mRNA were measured by quantitative polymerase chain reaction analysis. BACE-1 protein levels were assessed by Western blot. Cellular culture medium levels of Aβ1-42 were analyzed by ELISA. We found that sodium hydrosulfide (NaHS), a H(2)S donor, decreased BACE-1 mRNA and protein levels and Aβ1-42 release. Furthermore, NaHS promoted the phosphorylation of Akt and ERK but not JNK or p38 MAPK. However, the effects of NaHS on BACE-1 expression and Aβ1-42 secretion were abolished by inhibitors of phosphatidylinositol 3-kinase (PI3-K), but not of mitogen-activated protein kinase kinases (MEK). Our data indicate that H(2)S reduces BACE-1 expression in PC12 cells via activation of PI3-K/Akt signaling pathways. H(2)S releasing drugs may have therapeutic potential in AD patients.     

5-Azacytidine facilitates osteogenic gene expression and differentiation of mesenchymal stem cells by alteration in DNA methylation

Mesenchymal stem cells (MSCs) are considered to be one of the most promising therapeutic cell sources as they encompass a plasticity of multiple cell lineages. The challenge in using these cells lies in developing well-defined protocols for directing cellular differentiation to generate a desired lineage. In this study, we investigated the effect of 5-azacytidine, a DNA demethylating agent, on osteogenic differentiation of MSCs. The cells were exposed to 5-azacytidine in culture medium for 24 h prior to osteogenic induction. Osteogenic differentiation was determined by several the appearance of a number of osteogenesis characteristics, including gene expression, ALP activity, and calcium mineralization. Pretreatment of MSCs with 5-azacytidine significantly facilitated osteogenic differentiation and was accompanied by hypomethylation of genomic DNA and increased osteogenic gene expression. Taking dlx5 as a representative, methylation alterations of the “CpG island shore” in the promoter caused by 5-azacytidine appeared to contribute to osteogenic differentiation.     

Epidermal Features of Leaves and Their Taxonomic Significance in Subfamily Ophiopogonoideae (Liliaceae)

This paper reports epidermal features of leaves in Ophiopogonoideae. Thirty-nine species and one variety (29 species, 1 variety in Ophiopogon, 6 species in Liriope, 4 species in Peliosanthes)were examined under scanning electron microscope. In addition, transections of stomatal apparatuses of six species (Ophiopogon: 3 species; Liriope: 2 species; Peliosanthes: 1 species) were made and examined under light microscope. The stomatal apparatus in Liriope, Ophiopogon and Peliosanthes is of the anomocytic type. These types of epidermal features of leaves in these genera are recognized: Cuticular processes type, No cuticular processes type and No stomatal band type. The cuticular processes type can be further divided into three patterns: Fibrillose, Massive and Wrinkled-massive. The taxonomic value of the epidermal features of leaves in Ophiopogonoideae is rather evident. (1)These epidermal features can be used to distinguish among those species of Ophiopogon, Liriope and Peliosanthes, even in their vegetative state; (2) The different patterns of cuticular processes are helpful to reasonable classification of some species in Ophiopogon, (3)They are of great value for recognizing some sections, (4) These epidermal features of leaves also provide evidence for further discussion on relationships among Ophiopogon, Liriope, and Peliosanthes. The evolutionary trend of the epidermal features of leaves in Ophiopogonoideae is No stomatal band type→No cuticular process type(stomatal band)→Cuticular process type (stomatal band). According to the epidermal features of leaves, flowers and fruits, Ophiopogon, Liriope and Peliosanthes are closely related, forming a subfamily Ophiopogonoideae. Ophiopogon is more close to Liriope than to Peliosanthes, and they should be grouped into the same tribe-Ophiopogoneae. Liriope seems to be more primitive than Ophiopogon. Peliosanthes, which constitutes another tribe of its ownPeliosantheae, is more advanced than Ophiopogon and Liriope, and it might have beenderived from its ancestor early.     

Identification of novel antipoxviral agents: mitoxantrone inhibits vaccinia virus replication by blocking virion assembly

The bioterror threat of a smallpox outbreak in an unvaccinated population has mobilized efforts to develop new antipoxviral agents. By screening a library of known drugs, we identified 13 compounds that inhibited vaccinia virus replication at noncytotoxic doses. The anticancer drug mitoxantrone is unique among the inhibitors identified in that it has no apparent impact on viral gene expression. Rather, it blocks processing of viral structural proteins and assembly of mature progeny virions. The isolation of mitoxantrone-resistant vaccinia strains underscores that a viral protein is the likely target of the drug. Whole-genome sequencing of mitoxantrone-resistant viruses pinpointed missense mutations in the N-terminal domain of vaccinia DNA ligase. Despite its favorable activity in cell culture, mitoxantrone administered intraperitoneally at the maximum tolerated dose failed to protect mice against a lethal intranasal infection with vaccinia virus.     

Parallel Clustering Algorithm for Large-Scale Biological Data Sets

Backgrounds

Recent explosion of biological data brings a great challenge for the traditional clustering algorithms. With increasing scale of data sets, much larger memory and longer runtime are required for the cluster identification problems. The affinity propagation algorithm outperforms many other classical clustering algorithms and is widely applied into the biological researches. However, the time and space complexity become a great bottleneck when handling the large-scale data sets. Moreover, the similarity matrix, whose constructing procedure takes long runtime, is required before running the affinity propagation algorithm, since the algorithm clusters data sets based on the similarities between data pairs.

Methods

Two types of parallel architectures are proposed in this paper to accelerate the similarity matrix constructing procedure and the affinity propagation algorithm. The memory-shared architecture is used to construct the similarity matrix, and the distributed system is taken for the affinity propagation algorithm, because of its large memory size and great computing capacity. An appropriate way of data partition and reduction is designed in our method, in order to minimize the global communication cost among processes.

Result

A speedup of 100 is gained with 128 cores. The runtime is reduced from serval hours to a few seconds, which indicates that parallel algorithm is capable of handling large-scale data sets effectively. The parallel affinity propagation also achieves a good performance when clustering large-scale gene data (microarray) and detecting families in large protein superfamilies.     

Hypergravity Provokes a Temporary Reduction in CD4+CD8+ Thymocyte Number and a Persistent Decrease in Medullary Thymic Epithelial Cell Frequency in Mice

Gravity change affects many immunological systems. We investigated the effects of hypergravity (2G) on murine thymic cells. Exposure of mice to 2G for three days reduced the frequency of CD4⁺CD8⁺ thymocytes (DP) and mature medullary thymic epithelial cells (mTECs), accompanied by an increment of keratin-5 and keratin-8 double-positive (K5⁺K8⁺) TECs that reportedly contain TEC progenitors. Whereas the reduction of DP was recovered by a 14-day exposure to 2G, the reduction of mature mTECs and the increment of K5⁺K8⁺ TEC persisted. Interestingly, a surgical lesion of the inner ear’s vestibular apparatus inhibited these hypergravity effects. Quantitative PCR analysis revealed that the gene expression of Aire and RANK that are critical for mTEC function and development were up-regulated by the 3-day exposure and subsequently down-regulated by the 14-day exposure to 2G. Unexpectedly, this dynamic change in mTEC gene expression was independent of the vestibular apparatus. Overall, data suggest that 2G causes a temporary reduction of DP and a persistent reduction of mature mTECs in a vestibular system-dependent manner, and also dysregulates mTEC gene expression without involving the vestibular system. These data might provide insight on the impact of gravity change on thymic functions during spaceflight and living.     

Interactions between invasive plants and heavy metal stresses: a review

入侵植物与重金属胁迫的相互作用研究进展 全球变化改变了植物群落的分布格局,包括入侵植物,而人为污染可能降低本地植物对入侵植物的抗性。因此,本文总结了近几十年本地植物、入侵植物和植物-土壤生态系统中重金属生物地球化学行为的研究,以加深我们对入侵植物与环境胁迫因子相互作用的认识。我们的研究结合已有文献报道表明：(i)入侵物种对环境胁迫的影响具有异质性, (ii)影响的大小是多变的, (iii)即使在同一影响类型内,影响类型也具有多向性。然而,入侵植物暴露在重金属环境中表现出更强的自我保护机制,对重金属的生物可利用性和毒性有正向或负向的影响。另一方面,由于入侵植物普遍具有较高的耐受性,加之本地植物暴露于有毒重金属污染时具有“逃逸行为”,重金属胁迫环境更有利于植物的成功入侵。但是,对于入侵植物的重金属等元素组成是否与污染地区的本地植物不同,目前尚无共识。因此,在全球范围内对外来入侵植物与本土植物的植物体内、凋落物和土壤污染物含量进行定量比较是今后研究的一个重要方向。