Nonplanar DNA Base Pairs

Abstract

Three-dimensional structures of a representative set of more than 30 hydrogen-bonded nucleic acids base pairs have been studied by reliable ab initio quantum mechanical methods. We show that many hydrogen-bonded nucleic acid base pairs are intrinsically nonplanar, mainly due to the partial sp³ hybridization of nitrogen atoms of their amino groups and secondary electrostatic interactions. This finding extends the variability of intermolecular interactions of DNA bases in that i) flexibility of the base pairs is larger than has been assumed before, and ii) attractive proton-proton acceptor interactions oriented out of the base pair plane are allowed. For example, all four G…A mismatch base pairs are propeller twisted, and the energy preferences for the nonplanar structures range from less than 0.1 kcal/mol to 1.8 kcal/mol. We predict that nonplanarity of the amino group of guanine in the G(anti)…A(anti) pair of the ApG step of the d(CCAAGATTGG)₂ crystal structure is an important stabilizing factor that improves the energy of this structure by almost 3 kcal/mol. Currently used empirical potentials are not accurate enough to properly cover the interactions associated with amino-group and base-pair nonplanarity.     

Adventitial fibroblasts are activated in the early stages of atherosclerosis in the apolipoprotein E knockout mouse

The role of the adventitia in vascular function and vascular lesion formation has been largely ignored. This study observed the activation of the adventitia and specifically the fibroblasts in the development of atherosclerosis in the apoE(-/-) mouse. The results showed a gradual increase in expression of collagen types I and III after 2, 4, and 8 weeks of hyperlipidic diet. The earliest expression of monocyte chemoattractant protein-1 (MCP-1) protein and mRNA was detected in the adventitial fibroblast before the formation of intimal lesions. Proliferation, too, was first found in the adventitial fibroblasts. We hypothesize that the adventitial fibroblast is activated in the early stage of atherosclerosis. Adventitial inflammation may be an early event in the development of atherosclerotic lesions.     

Identification of the phosphorylation sites on intact TRPM7 channels from mammalian cells

Transient receptor potential melastatin 7 (TRPM7) channels are divalent cation-selective ion channels that are permeable to Ca(2+) and Mg(2+). TRPM7 is ubiquitously expressed in vertebrate cells and contains both an ion channel and a kinase domain. TRPM7 plays an important role in regulating cellular homeostatic levels of Ca(2+) and Mg(2+) in mammalian cells. Although studies have shown that the kinase domain of TRPM7 is required for channel activation and can phosphorylate other target proteins, a systematic analysis of intact TRPM7 channel phosphorylation sites expressed in mammalian cells is lacking. We applied mass spectrometric proteomic techniques to identify and characterize the key phosphorylation sites in TRPM7 channels. We identified 14 phosphorylation sites in the cytoplasmic domain of TRPM7, eight of which have not been previously reported. The identification of phosphorylation sites using antibody-based immunopurification and mass spectrometry is an effective approach for defining the phosphorylation status of TRPM7 channels. The present results show that TRPM7 channels are phosphorylated at multiple sites, which serves as a mechanism to modulate the dynamic functions of TRPM7 channels in mammalian cells.     

Nucleopolyhedrovirus infection enhances plant defences by increasing plant volatile diversity

Plant–herbivore–entomopathogen tri-trophic interactions and biodiversity are relatively understudied topics in ecology. Particularly, the effects of entomopathogens on herbivore-induced plant volatiles and plant volatile diversity on the defensive function of plants have not been studied in detail. We used soybean (Glycine max), beet armyworm larvae (Spodoptera exigua), and nucleopolyhedrovirus (NPV) as a tri-trophic system to determine whether NPV infection can promote the emission and diversity of volatiles from plants. We also investigated whether NPV infection affects the attraction of Microplitis pallidipes, an important endoparasitoid of larval S. exigua. Uninfested soybean plants released 7 detectable volatile compounds while plants fed upon by healthy and NPV-infected S. exigua larvae released 12 and 15 volatiles, respectively. Female parasitoids were more attracted to the volatiles from plants that were fed upon by NPV-infected larvae than healthy larvae, and more attracted to the volatiles from plants that were fed upon by healthy larvae than no larvae. The selective responses of parasitoids to plant odours increased as plant volatile diversity increased. Our study suggests that the NPV infection facilitates the release of plant volatiles and enhances the defensive function of plants by increasing plant volatile diversity which in turn attracts more parasitoids. Also, this work reveals that plants might accrue two indirect benefits from NPV infection, cessation of herbivore feeding and more parasitisation.     

Triaxial compression test of soil–root composites to evaluate influence of roots on soil shear strength

In order to evaluate influences of roots on soil shear strength, a triaxial compression test was carried out to study the shear strength of plain soil samples and composites comprised of roots of Robinia pseucdoacacia and soil from the Loess Plateau in Northwest China. Roots were distributed in soil in three forms: vertical, horizontal, and vertical–horizontal (cross). All samples were tested under two different soil water contents. Test results showed that roots have more impacts on the soil cohesion than the friction angle. The presence of roots in soil substantially increased the soil shear strength. Among three root distribution forms, the reinforcing effect of vertical–horizontal (cross) root distribution was the most effective. Increase in soil water content directly induced a decline in soil cohesion of all test samples and resulted in a decrease in shear strength for both plain soil samples and soil–root composites. It was concluded that the triaxial compression test can be effectively used to study influences of roots on soil shear strength.     

The mating system of the Sichuan snub‐nosed monkey (Rhinopithecus roxellana)

This article reports the first genetic study of the mating system of the Sichuan snub‐nosed monkey (Rhinopithecus roxellana), an endemic and endangered species in China. The investigation was carried out in a population (WRT) in the Qinling Mountains using data from both field observation and paternity analysis through microsatellite DNA profiling. During a mating season, a male on an average copulated with 5.7 females. Approximately 18% of the females were observed to copulate with more than one male over the study period. The majority of copulations (94.5%) were initiated by females. Twenty‐eight of 430 observed matings were extra‐unit copulations. Eight polymorphic microsatellite loci were used for paternity analysis. The number of alleles at each locus ranged from 3 to 7 (mean=4.3). Observed heterozygosity ranged between 0.32 and 0.79. None of the loci showed significant deviation from Hardy–Weinberg equilibrium. Results from paternity exclusion showed that 12 of 21 (57.1%) immature individuals were sired by extra‐unit males. Although the basic social unit of snub‐nosed monkeys is consistent with a polygynous mating system, both field observation and genetic data suggests that their mating system is polygamous. Infanticide and inbreeding avoidance are the most likely explanations for the promiscuity of female snub‐nosed monkeys. Am. J. Primatol. 72:25–32, 2010. © 2009 Wiley‐Liss, Inc.     

凝血因子及血浆蛋白类制品的研究现状及发展前景

血浆制品主要是以血浆为原料,经特殊的分离提纯而得到的血浆单一组分,也有部分血浆制品可以通过生物工程技术合成。不同的组分具有相应的功能,血浆制品是一种特殊的药品。目前市场上分离且临床上使用的血浆制品主要有凝血因子、白蛋白、免疫球蛋白以及凝血酶、蛋白C、α1-抗胰蛋白酶、α2-巨球蛋白、组织纤溶酶原激活剂、补体脂酶抑制剂、血清胆碱酯酶、铜蓝蛋白、转铁蛋白、纤维结合蛋白\高密度脂蛋白等微量血浆蛋白等。凝血因子根据不同的功能分为FI、FII、FIII、FIV、FV、FVII、FVIII、FIX、FX、FXI、FXII以及因子FXIII。随着技术的发展已经人们对血浆制品的认知度越来越高,血浆制品正已前所未有的速度发展。     

Shank2 associates with and regulates Na+/H+ exchanger 3

Na+/H+ exchanger 3 (NHE3) plays a pivotal role in transepithelial Na+ and HCO3(-) absorption across a wide range of epithelia in the digestive and renal-genitourinary systems. Accumulating evidence suggests that PDZ-based adaptor proteins play an important role in regulating the trafficking and activity of NHE3. A search for NHE3-binding modular proteins using yeast two-hybrid assays led us to the PDZ-based adaptor Shank2. The interaction between Shank2 and NHE3 was further confirmed by immunoprecipitation and surface plasmon resonance studies. When expressed in PS120/NHE3 cells, Shank2 increased the membrane expression and basal activity of NHE3 and attenuated the cAMP-dependent inhibition of NHE3 activity. Furthermore, knock-down of native Shank2 expression in Caco-2 epithelial cells by RNA interference decreased NHE3 protein expression as well as activity but amplified the inhibitory effect of cAMP on NHE3. These results indicate that Shank2 is a novel NHE3 interacting protein that is involved in the fine regulation of transepithelial salt and water transport through affecting NHE3 expression and activity.     

Probiotic genomic DNA reduces the production of pro-inflammatory cytokine tumor necrosis factor-alpha

The effect of Lactobacillus plantarum genomic DNA on lipopolysaccharide (LPS)-induced mitogen-activated protein kinase (MAPK) activation, nuclear factor-kappa B activation, and the expressions of tumor necrosis factor-alpha, interleukin-1 receptor-associated kinase M, and the pattern recognition receptor were examined. Pretreatment of p-gDNA inhibited the phosphorylation of MAPKs and nuclear factor-kappa B, and also inhibited LPS-induced TNF-α production in response to subsequent LPS stimulation. L.?plantarum genomic DNA-mediated inhibition of signaling pathway and tumor necrosis factor-alpha was accompanied by the suppression of toll-like receptor (TLR) 2, TLR4, and TLR9 and the induction of interleukin-1 receptor-associated kinase M, a negative regulator of TLR. This study can extend our understanding of the biological function of probiotic genomic DNA as an anti-inflammatory agent.     

Intercrossed Microstructures of Hydroxyapatite Sheets of Tibia Bone

The observation of Scanning Electron Microscope (SEM) shows that a tibia bone is a kind of bioceramic composite consisting of hydroxyapatite layers and collagen protein matrix. All the hydroxyapatite layers are parallel with the surface of the bone and consist of numerous hydroxyapatite sheets. The observation also shows that there is a kind of intercrossed microstructure of the hydroxyapatite sheets. In this kind of microstructure, the hydroxyapatite sheets in an arbitrary hydroxyapatite layer make a large intercrossed angle with the hydroxyapatite sheets in their adjacent hydroxyapatite layers. The maximum pullout force of the intercrossed microstructure, which is closely related to the fracture toughness of the bone, is investigated and compared with that of the parallel microstructure of the sheets through their representative models. The result of the investigation indicates that the maximum pullout force of the intercrossed microstructure is markedly larger than that of the parallel microstructure, which is experimentally verified.