寡聚脱氧核苷酸d(G-C)_3的激光喇曼谱及其分析

用改进的固相磷酰三酯法合成了oligo-d(G-C)_3。以氩离子激光为激发光源,波长488nm.,在室温条件下,分别测定了纯化后的oligo-d(G-C)_3和其组分单体5’-dGMP和5’-dCMP的激光喇曼谱。观察到被测定的物质在300-2500cm~(-1)频率区间,各自都有其特征的谱形和喇曼峰。5’-dGMP和5’-dCMP谱中大多数特征峰在寡聚体的谱中消失,而在oligo-d(G-C)_3谱中出现了几处新的喇曼峰。经查证,峰832,851和899cm~(-1)系糖-磷酸主链的特征喇曼峰,另外几处峰与DNA的构象有关。实验结果表明oligo-d(G-C)_3在水溶液中(室温)主要以B-构象存在。     

Study on models of single populations: an expansion of the logistic and exponential equations

Using the adsorption theory of chemical kinetics, a new equation concerning the growth of single populations is presented:

$\text{d}\text{X}\text{d}\text{t}\text{=}\text{μ}{}_{\mathrm{c}}\text{X(1 ?)}\text{X}\text{X}{}_{\mathrm{m}}\text{1?}\text{X}\text{X}{}_{\mathrm{m}}{}^{\mathrm{\prime }}$

or in its integral form:

$\text{ln}\text{X}\text{X}{}_{\mathrm{o}}\text{?}\text{ln}\text{X}{}_{\mathrm{m}}\text{?X}\text{X}{}_{\mathrm{m}}\text{?X}{}_{\mathrm{o}}\text{+}\text{X}{}_{\mathrm{m}}\text{X}{}^{\mathrm{\prime }}{}_{\mathrm{m}}\text{X}{}_{\mathrm{m}}\text{?X}\text{X}{}_{\mathrm{m}}\text{?X}{}_{\mathrm{o}}\text{=μ}{}_{\mathrm{c}}\text{(t?t}{}_{\mathrm{o}}\text{)}$

This equation attempts to explain the relationship between population increment and limiting resources. It can be reduced to either the logistic or exponential equation under two extreme conditions. The new equation has three parameters, X_m, X′_m and μ_c, each of which has ecological significance. $\text{X}{}_{\mathrm{m}}\text{X′}{}_{\mathrm{m}}$ concerns the efficiency of nutrient utilization by an organism. Its value is between zero and one. With ratios approaching unity, the efficiency is high; lower ratios indicate that population increment is quickly restricted by limiting resources. μ_c, is a velocity parameter lying between μ_e, (exponential growth) and μ_L (logistic growth), and is dependent on the value of $\text{solX}{}_{\mathrm{m}}\text{X′}{}_{\mathrm{m}}$. From μ_c we can predict the time course of population incremental velocity ($\text{d}\text{X}\text{d}\text{t}$), and can observe that it is not symmetrical, unlike that derived from the logistic equation. At $\text{X}{}_{\mathrm{m}}\text{X′}{}_{\mathrm{m}}\text{= 1}$ the maximum velocity of the population increment predicted from the new equation is twice that of the logistic equation.Population growth in nature seems to support the new equation rather than the logistic equation, and it can be successfully fitted by means of a least square method.     

Biochemical and structural characterization of hepatitis A virus 2C reveals an unusual ribonuclease activity on single-stranded RNA

The HAV nonstructural protein 2C is essential for virus replication; however, its precise function remains elusive. Although HAV 2C shares 24–27% sequence identity with other 2Cs, key motifs are conserved. Here, we demonstrate that HAV 2C is an ATPase but lacking helicase activity. We identified an ATPase-independent nuclease activity of HAV 2C with a preference for polyuridylic single-stranded RNAs. We determined the crystal structure of an HAV 2C fragment to 2.2 Å resolution, containing an ATPase domain, a region equivalent to enterovirus 2C zinc-finger (ZFER) and a C-terminal amphipathic helix (PBD). The PBD of HAV 2C occupies a hydrophobic pocket (Pocket) in the adjacent 2C, and we show the PBD–Pocket interaction is vital for 2C functions. We identified acidic residues that are essential for the ribonuclease activity and demonstrated mutations at these sites abrogate virus replication. We built a hexameric-ring model of HAV 2C, revealing the ribonuclease-essential residues clustering around the central pore of the ring, whereas the ATPase active sites line up at the gaps between adjacent 2Cs. Finally, we show the ribonuclease activity is shared by other picornavirus 2Cs. Our findings identified a previously unfound activity of picornavirus 2C, providing novel insights into the mechanisms of virus replication.     

An insight into planarian regeneration

BackgroundPlanarian has attracted increasing attentions in the regeneration field for its usefulness as an important biological model organism attributing to its strong regeneration ability. Both the complexity of multiple regulatory networks and their coordinate functions contribute to the maintenance of normal cellular homeostasis and the process of regeneration in planarian. The polarity, size, location and number of regeneration tissues are regulated by diverse mechanisms. In this review we summarize the recent advances about the importance genetic and molecular mechanisms for regeneration control on various tissues in planarian.MethodsA comprehensive literature search of original articles published in recent years was performed in regards to the molecular mechanism of each cell types during the planarian regeneration, including neoblast, nerve system, eye spot, excretory system and epidermal.ResultsAvailable molecular mechanisms gave us an overview of regeneration process in every tissue. The sense of injuries and initiation of regeneration is regulated by diverse genes like follistatin and ERK signaling. The Neoblasts differentiate into tissue progenitors under the regulation of genes such as egfr‐3. The regeneration polarity is controlled by Wnt pathway, BMP pathway and bioelectric signals. The neoblast within the blastema differentiate into desired cell types and regenerate the missing tissues. Those tissue specific genes regulate the tissue progenitor cells to differentiate into desired cell types to complete the regeneration process.ConclusionAll tissue types in planarian participate in the regeneration process regulated by distinct molecular factors and cellular signaling pathways. The neoblasts play vital roles in tissue regeneration and morphology maintenance. These studies provide new insights into the molecular mechanisms for regulating planarian regeneration.

Genetic and molecular mechanisms for regeneration control on various tissues in planarian.     

温度诱导Targetron系统用于大肠杆菌高效基因失活

构建基于Te I3c/4c嗜热二型内含子的温度诱导Targetron基因失活系统(Thermotargetron),并应用于中温微生物基因编辑。在大肠杆菌HMS174(DE3)基因组中,选择Subunitofflagellum基因(fliC)和C4dicarboxylate orotate:H+symporter基因(dctA)为靶基因。根据Te I3c/4c DNA识别规则,在fliC和dctA基因中选择fliC489a、fliC828s、fliC1038s和dctA2a位点为基因打靶位点。使用重叠延伸PCR方法,基于pHK-TT1A质粒构建打靶载体。打靶载体转化HMS174菌株,对数期转化子培养液48℃热激1h后涂布于氯霉素抗性LB平板上。使用菌落PCR和DNA测序检测突变株并计算基因失活效率。获得突变株后,通过琼脂穿刺和碳源代谢实验,鉴定ΔfliC、ΔdctA突变株表型变化。菌落PCR测序结果表明,Te I3c/4c插入到fliC和dctA基因设计位点,且打靶效率高达100%。突变株表型验证实验表明,ΔfliC突变株运动能力显著下降,ΔdctA突变株苹果酸代谢能力缺失。综上所述,...     

细胞重编程和移植技术用于帕金森病治疗的研究进展

帕金森病(Parkinson disease,PD)是一种复杂的中枢神经系统退行性疾病,主要病理特征为黑质致密部多巴胺神经元的进行性丧失.目前PD主要治疗手段包括药物和手术.但药物存在神经保护活性不足、缺乏对因治疗、晚期无药可用等问题,手术治疗风险较大.近年来,细胞重编程技术取得突破性进展,由重编程产生的诱导多能干细胞(induced pluripotent stem cells,iPSCs)、诱导多巴胺神经元(induced dopamine neurons,iDNs)和诱导神经干细胞(induced neural stem cells,i NSCs)可用于治疗PD.移植iPSCs分化而来的多巴胺能神经元、iDNs和iNSCs至相应脑区,可起到神经替代与修复作用,有效治疗PD.本文重点介绍细胞重编程的机制,总结iPSCs、iDNs和iNSCs治疗PD的优缺点,并阐述尚存在的挑战,探讨可能的解决方案.     

Ginsenoside Rh2 mitigates doxorubicin‐induced cardiotoxicity by inhibiting apoptotic and inflammatory damage and weakening pathological remodelling in breast cancer‐bearing mice

ObjectivesThere are presently a few viable ways to reduce cardiotoxicity of doxorubicin (Dox). The combination of chemotherapy agents with natural compounds delivers greater efficacy and reduces adverse effects in recent researches for cancer treatment. Here, we examined the potential effect of ginsenoside Rh2 on a Dox‐based regimen in chemotherapy treatment.Materials and MethodsHuman breast tumour (MDA‐MB‐231) xenograft nude mice, human cardiac ventricle fibroblasts, and human umbilical vein endothelial cells (HUVEC) were employed in the present study. Histology, immunohistochemistry, immunofluorescence, western blot, antibody array, and RNA‐sequencing analyses were utilized to assess the protective effect of Rh2 on cardiotoxicity induced by Dox and the underlying mechanisms.ResultsRh2‐reduced cardiotoxicity by inhibiting the cardiac histopathological changes, apoptosis and necrosis, and consequent inflammation. Pathological remodelling was attenuated by reducing fibroblast to myofibroblast transition (FMT) and endothelial–mesenchymal transition (EndMT) in hearts. RNA‐sequencing analysis showed that Dox treatment predominantly targets cell cycle and attachment of microtubules and boosted tumour necrosis, chemokine and interferon‐gamma production, response to cytokine and chemokine, and T cell activation, whereas Rh2 regulated these effects. Intriguingly, Rh2 also attenuated fibrosis via promoting senescence in myofibroblasts and reversing established myofibroblast differentiation in EndMT.ConclusionsRh2 regulates multiple pathways in the Dox‐provoked heart, proposing a potential candidate for cancer supplement and therapy‐associated cardiotoxicity.

Doxorubicin is extensively reported to induce severe cardiotoxicity in clinical applications. Our work proposed a natural herbal compound, ginsenoside Rh2, as a potential candidate for attenuating this side effect. Rh2 significantly inhibited cardiac apoptosis and necrosis, inflammation, and pathological remodelling in Dox‐challenged hearts.     

Reconstruction of Surface Porous PEEK Decorated with Strontium-doped Calcium Phosphate Coatings for Enhancing Osteogenic Activity

The aim of this study was to reconstruct surface porous structure with hundreds of micrometers and then bio-mineralize Sr-doped Calcium Phosphate(Sr-doped CaP)o...