Overexpression of SPINDLIN1 induces cellular senescence, multinucleation and apoptosis

Human or mouse Spindlin1 is expressed in various tissues and cells, but its biological functions are poorly understood. In this study, we show that human SPINDLIN1 is localized to interphase nucleus and mitotic chromosomes, and its expression in HeLa cells is not regulated in a cell cycle-dependent manner. When SPINDLIN1 is stably overexpressed in HeLa cells, it results in multinucleation of cells, and these multinucleated cells exhibits characteristic features of senescence and apoptosis shown by growth and morphological alterations, beta-galactosidase activity, and Annexin V/7-Aminoactinomycin D staining. Mouse Spindlin1 is highly homologous with human Spindlin1, when overexpressed in NIH3T3 cells, it also induces multinucleation, senescence and apoptosis in murine cells. Our results demonstrate that SPINDLIN1 is an important gene for mammalian mitotic chromosome functions, and disrupted regulation results in abnormal cell division, a mechanism that may be involved in tumorigenesis.     

Reproductive biology and the process of domestication of the columnar cactus Stenocereus Stellatus in Central Mexico

Pollination biology, breeding system, and floral phenology of the columnar cactus Stenocereus stellatus were studied in wild, wild managed in situ and cultivated populations of central Mexico, in order to examine whether these aspects have been modified under domestication and whether they determine reproductive barriers between wild and manipulated individuals. Individuals of both wild and manipulated populations are self-incompatible, indicating that artificial selection has not modified the breeding system. Their pollination biology is also similar. Anthesis is mainly nocturnal, with a peak of nectar production between 0200 and 0400 when the stigma presents maximum turgidity. Nocturnal visitors are the effective pollinators. Nearly 75% of flowers exposed for nocturnal pollination set fruit, while none of the flowers exposed for diurnal pollination produced fruits. The bats Leptonycteris curasoae, L. nivalis, and Choeronycteris mexicana (Glossophaginae) are the most likely pollinators, and their time of foraging is synchronized with the time of nectar production and stigma receptivity in S. stellatus. Bats potentially move pollen over a considerable distance, so there is apparently no spatial isolation to prevent pollen exchange between wild and cultivated populations. Phenological studies showed that there are also no apparent temporal barriers. However, manual cross pollination failed between some domesticated and wild phenotypes, suggesting that gene flow between wild and cultivated populations might be limited by pollen incompatibility.     

Ion–dipole interactions and their functions in proteins

Ion–dipole interactions in biological macromolecules are formed between atomic or molecular ions and neutral protein dipolar groups through either hydrogen bond or coordination. Since their discovery 30 years ago, these interactions have proven to be a frequent occurrence in protein structures, appearing in everything from transporters and ion channels to enzyme active sites to protein–protein interfaces. However, their significance and roles in protein functions are largely underappreciated. We performed PDB data mining to identify a sampling of proteins that possess these interactions. In this review, we will define the ion–dipole interaction and discuss several prominent examples of their functional roles in nature.     

Vascular endothelial cell senescence mediated by integrin beta4 in vitro

To understand whether integrin beta4 is involved in vascular endothelial cell (VEC) senescence, we examined integrin beta4 level changes, as well as P53 and reactive oxygen species (ROS) levels and alterations of phosphatidylcholine-specific phospholipase C (PC-PLC) activity before and after knocking-down integrin beta4 by small interfering RNA. We found integrin beta4, P53 and ROS levels increased significantly, while Ca(2+)-independent PC-PLC activity obviously decreased during VEC senescence. On the other hand, integrin beta4 down-regulation attenuated the senescence phenotype and reversed Ca(2+)-independent PC-PLC activity, and P53 and ROS levels. The data suggested that integrin beta4 might mediate VEC senescence through depressing Ca(2+)-independent PC-PLC and elevating the levels of P53 and ROS.     

A cryptic activity in the Nudix hydrolase superfamily

The Nudix hydrolase superfamily is identified by a conserved cassette of 23 amino acids, and it is characterized by its pyrophosphorylytic activity on a wide variety of nucleoside diphosphate derivatives. Of the 13 members of the family in Escherichia coli, only one, Orf180, has not been identified with a substrate, although a host of nucleoside diphosphate compounds has been tested. Several reports have noted a strong similarity in the three‐dimensional structure of the unrelated enzyme, isopentenyl diphosphate isomerase (IDI) to the Nudix structure, and the report that a Nudix enzyme was involved in the synthesis of geraniol, a product of the two substrates of IDI, prompted an investigation of whether the IDI substrates, isopentenyl diphosphate (IPP), and dimethylallyl diphosphate (DAPP) could be substrates of Orf180. This article demonstrates that Orf180 does have a very low activity on IPP, DAPP, and geranyl pyrophosphate (GPP). However, several of the other Nudix enzymes with established nucleoside diphosphate substrates hydrolyze these compounds at substantial rates. In fact, some Nudix hydrolases have higher activities on IPP, DAPP, and GPP than on their signature nucleoside diphosphate derivatives.     

The Bipartite Rac1 Guanine Nucleotide Exchange Factor Engulfment and Cell Motility 1/Dedicator of Cytokinesis 180 (Elmo1/Dock180) Protects Endothelial Cells from Apoptosis in Blood Vessel Development

Engulfment and cell motility 1/dedicator of cytokinesis 180 (Elmo1/Dock180) is a bipartite guanine nucleotide exchange factor for the monomeric GTPase Ras-related C3 botulinum toxin substrate 1 (Rac1). Elmo1/Dock180 regulates Rac1 activity in a specific spatiotemporal manner in endothelial cells (ECs) during zebrafish development and acts downstream of the Netrin-1/Unc5-homolog B (Unc5B) signaling cascade. However, mechanistic details on the pathways by which Elmo1/Dock180 regulates endothelial function and vascular development remained elusive. In this study, we aimed to analyze the vascular function of Elmo1 and Dock180 in human ECs and during vascular development in zebrafish embryos. In vitro overexpression of Elmo1 and Dock180 in ECs reduced caspase-3/7 activity and annexin V-positive cell number upon induction of apoptosis. This protective effect of Elmo1 and Dock180 is mediated by activation of Rac1, p21-activated kinase (PAK) and AKT/protein kinase B (AKT) signaling. In zebrafish, Elmo1 and Dock180 overexpression reduced the total apoptotic cell and apoptotic EC number and promoted the formation of blood vessels during embryogenesis. In conclusion, Elmo1 and Dock180 protect ECs from apoptosis by the activation of the Rac1/PAK/AKT signaling cascade in vitro and in vivo. Thus, Elmo1 and Dock180 facilitate blood vessel formation by stabilization of the endothelium during angiogenesis.     

纳米中药对S180荷瘤小鼠肠道菌群影响的研究及其防治作用

目的研究纳米中药对S180荷瘤小鼠肠道菌群的影响及其抑制作用。方法将S180荷瘤瘤株以2×105/(0.2 m l.鼠)用注射器接种于小鼠右前肢腋下,建立实体瘤模型,肿瘤发生率为100%。观察小鼠的一般状态,用梯度稀释法和培养法测定小鼠4种肠道正常菌群,即乳酸杆菌、双歧杆菌、肠球菌、肠杆菌。用电子天平称瘤重并计算瘤抑制率。病理行HE(苏木精-伊红)染色,在光学显微镜下观察。结果与模型组比较,纳米中药组双歧杆菌和乳酸杆菌数量明显升高,肠球菌和肠杆菌数量明显减少,肿瘤坏死因子数量增加,抑瘤率达64%,病理显示肿瘤组织间坏死灶明显,有大量的炎性细胞浸润。结论纳米中药提高机体免疫屏障功能,增强药物的靶向性,扶植机体正常菌群的生长,实现抗肿瘤的目的。     

Predispersal predation of an understory rainforest herb Aphelandra aurantiaca (Acanthaceae) in gaps and mature forest

The opening of a canopy gap at Los Tuxtlas rainforest has an impact on populations of the understory herb Aphelandra aurantiaca: the ratio of recruited seedlings per reproductive individual is 1:17 in mature forest vs. gaps. Predation occurring before seed dispersal seems a plausible explanation for this observed difference. In a field experiment, in which insecticide was applied to plants growing in gaps and mature forest, we evaluated the extent to which herbivore damage to flowers, fruits, and seeds reduces the number of seeds available for seedling establishment. Under natural conditions, ∼30% of the flowers and >70% of the capsules of A. aurantiaca showed herbivore damage, but its impact changed depending on the type of forest habitat. Flower and fruit herbivores caused more damage in closed forest than in gaps, and this difference was even bigger under the insecticide treatment. Insecticide effectiveness varied depending on the type of forest patch. The highest herbivore impact on seeds was found in the mature forest without insecticide treatment, where most seeds were destroyed. The percentages of seed damage reported here show that predispersal predation is limiting seedling recruitment, especially in mature forest. Other possible explanations might be differences in insect composition, densities, and behavior between gaps and mature forest.     

眼镜蛇毒细胞毒素的抗肿瘤作用

目的　研究眼镜蛇毒细胞毒素（ Ｃ Ｖ Ｃ Ｔ Ｘ）的体内抗肿瘤作用。方法　小鼠皮下、腹腔接种 Ｓ１８０ 、 Ｅ Ａ Ｃ后, 于接种部位注射不同剂量的 Ｃ Ｖ Ｃ Ｔ Ｘ, 每天 １ 次, 连续１０ 天, 观察瘤重抑制率和生命延长率。结果　适当剂量（０２～０８ｍ ｇ／ｋｇ） 的 Ｃ Ｖ Ｃ Ｔ Ｘ 能明显抑制肿瘤的生长 （ Ｐ＜ ００１）,小鼠的存活时间明显延长（ Ｐ ＜ ００１）。结论　 Ｃ Ｖ Ｃ Ｔ Ｘ 在小鼠体内对 Ｓ１８０ 、 Ｅ Ａ Ｃ有明显地抗肿瘤作用。