Biological activities of chemically synthesized analogues of the nonreducing sugar moiety of lipid A

Adriamycin-Fe3+ complex catalyzes the formation of hydroxyl radical from hydrogen peroxide but the DNA-adriamycin-iron ternary complex is much more effective. 11-Deoxyadriamycin, which shows no spectral evidence of complex formation with iron, was ineffective. The generation of hydroxyl radical by adriamycin-Fe3+ complex in the presence of DNA correlates with its ability to cleave DNA. Hydroxyl radicals are thus implicated as the reactive oxygen species involved in the DNA damage caused by the adriamycin-Fe3+ complex.     

麦长管蚜抗吡虫啉品系和敏感品系的生殖力比较

通过建立抗性品系和敏感品系的种群生命表,比较麦长管蚜Sitobion avenae(Fabricius)抗吡虫啉品系和敏感品系的生殖力差异,结果表明,抗性品系适合度显著下降,世代历期延长,成蚜寿命缩短;在繁殖上表现为产仔量下降,生殖期缩短。以净生殖率(R0)和内禀增长率(rm)来评价抗性品系的相对生物适合度,抗性品系分别是敏感品系的0.5200和0.7481。因此,麦长管蚜对吡虫啉的抗性品系存在显著的生殖劣势。     

Physiological state influences the antennal response of Anastrepha obliqua to male and host volatiles

The sexual and host‐related behaviours of the fruit fly Anastrepha obliqua Macquart (Diptera: Tephritidae) are mediated by volatile compounds. However, whether the physiological state of this species affects its antennal and behavioural responses to semiochemicals is unknown. The effects of age, mating status, diet and the topical application of methoprene, a Juvenile hormone analogue (JHA), on the antennal sensitivity of this tephritid fruit fly species to selected male [(Z)‐3‐nonenol] and host fruit volatiles (ethyl benzoate, ethyl hexanoate, ethyl butyrate and trans‐β‐ocimene) are investigated using electroantennography (EAG). Overall, (Z)‐3‐nonenol and ethyl benzoate elicit the highest EAG responses in both sexes. Flies of both sexes aged 1, 5 and 10 days old show higher EAG responses to the tested compounds compared with flies aged 20 days old. Virgin females and males show higher EAG responses to volatile compounds than mated flies. Females and males fed with sugar plus protein show higher antennal responses to volatiles compared with flies fed sugar or protein alone. Flies of both sexes treated with methoprene show higher antennal responses than flies treated with acetone (control). These results suggest that the peripheral olfactory system in A. obliqua is modulated by the physiological state of the flies.     

Consecutive incorporation of fluorophore-labeled nucleotides by mammalian DNA polymerase β

In the present study, we investigated mammalian polymerases that consecutively incorporate various fluorophore-labeled nucleotides. We found that rat DNA polymerase β (pol β) consecutively incorporated fluorophore-labeled nucleotides to a greater extent than four bacterial polymerases, Sequenase Version 2.0, Vent_R (exo-), DNA polymerase IIIα and the Klenow fragment, and the mammalian polymerases DNA polymerase α and human DNA polymerase δ, under mesophilic conditions. Furthermore, we investigated the kinetics of correct or mismatched incorporation with labeled nucleotides during synthesis by rat pol β. The kinetic parameters K_m and k_cat were measured and used for evaluating: (i) the discrimination against correct pair incorporation of labeled nucleotides relative to unlabeled nucleotides; and (ii) the fidelity for all nucleotide combinations of mismatched pairs in the presence of labeled or unlabeled nucleotides. We also investigated the effect of fluorophore-labeled nucleotides on terminal deoxynucleotidyl transferase activity of rat pol β. We have demonstrated for the first time that mammalian pol β can consecutively incorporate various fluorophore-labeled dNTPs. These findings suggest that pol β is useful for high-density labeling of DNA probes and single-molecule sequencing for high-speed genome analysis.     

2′-OH of mRNA are critical for the binding of its codons at the 40S ribosomal P site but not at the mRNA entry site

The roles of 2′-OH groups in the binding of mRNA to human ribosomes were studied using site-directed cross-linking. We found that both mRNA and mDNA analogues bearing a cross-linker can modify ribosomal proteins (rps) S3e and S2e at the mRNA entry site independently on tRNA presence, but only mRNA analogues were capable of a tRNA^Phe-dependent binding to human ribosomes and cross-linking to rpS26e in the mRNA binding centre. Thus, 2′-OH groups of mRNA are unimportant for binding at the entry site but they are crucial for codon-anticodon interactions at the P site, implying the existence of mRNA-ribosome contacts that do not occur in bacteria.     

5'-(N-Ethylcarboxamido)adenosine Inhibits Ca2+ Influx and Activates a Protein Phosphatase in Bovine Adrenal Chromaffin Cells

Abstract: We investigated the effect of the adenosine receptor agonist 5'-( N -ethylcarboxamido)adenosine (NECA) in catecholamine secretion from adrenal chromaffin cells that exhibit only the A_2b subtype adenosine receptor. NECA reduced catecholamine release evoked by the nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium (DMPP) in a time-dependent manner. Inhibition reached 25% after 30–40-min exposure to NECA. This effect on DMPP-evoked catecholamine secretion was mirrored by a similar (27.7 ± 3.3%), slowly developing inhibition of [Ca²⁺]_i transients induced by DMPP that peaked at 30-min preincubation with NECA. The capacity of the chromaffin cells to buffer Ca²⁺ load was not affected by the treatment with NECA. Short-term treatment with NECA failed both to modify [Ca²⁺]_i levels and to increase endogenous diacylglycerol production, showing that NECA does not activate the intracellular Ca²⁺/protein kinase C signaling pathway. The inhibitory effects of NECA were accompanied by a 30% increase of protein phosphatase activity in chromaffin cell cytosol. We suggest that dephosphorylation of a protein involved in DMPP-evoked Ca²⁺ influx pathway (e.g., L-type Ca²⁺ channels) could be the mechanism of the inhibitory action of adenosine receptor stimulation on catecholamine secretion from adrenal chromaffin cells.     

经皮椎弓根空心螺钉微创椎体间融合治疗腰椎间盘突出的临床效果分析

目的：探究经皮椎弓根空心螺钉微创椎体间融合治疗腰椎间盘突出的临床效果及安全性。方法：病例来源于我院2009 年12 月~2013 年12 月收治的确诊为腰椎间盘突出症的病患174 例,依据随机数字表法将其均分为观察组与对照组,每组87 例。其 中,观察组施行Quadrant微创通道经皮椎弓根空心螺钉椎间融合术,对照组施行经后入路开放性椎间融合术。评估和比较两组病 患术前和随访结束时的视觉模拟评分系统(VAS)疼痛评分与Oswestry 功能障碍指数(ODI)的变化及术后并发症的发生情况。结 果：观察组治疗前、出院时及随访一年时的VAS 评分与ODI指数与对照组比较差异均不显著(P>0.05)。观察组手术切口长度、术 后住院时间及术中出血量均明显优于对照组(P<0.01),而其手术所需时间明显长于对照组(P<0.01)。对照组患者术后出现20 例神 经根损伤(22.99%),3 例椎间隙感染(3.45%),其并发症总发生率为(26.44%),而观察组患者术后仅出现3 例神经根损伤,发生率为 3.45%,显著低于对照组(P<0.01)。结论：经皮椎弓根空心螺钉微创椎体间融合治疗的临床效果肯定,能减少对病患的创伤,控制术 后并发症的发生,具有较高的临床应用价值。     

Molecular designing,virtual screening and docking study of novel curcumin analogue as mutation (S769L and K846R) selective inhibitor for EGFR

The somatic mutations in ATP binding cleft of the tyrosine kinase binding domain of EGFR are known to occur in 15–40% of non-small cell lung cancer (NSCLC) patients. Although first and second generation anti-EGFR inhibitors are widely used to treat these patients, their therapeutic efficacy is modest and often results in adverse effects or drug resistance. Therefore, there is a need to develop novel as well as safe anti-EGFR drugs. The rapid emergence of computational drug designing provided a great opportunity to both discover and predict the efficacy of novel EGFR inhibitors from plant sources. In the present study, we designed several chemical analogues of edible curcumin (CUCM) compound and assessed their drug likeliness, ADME and toxicity properties using a diverse range of advanced computational methods. We also have examined the structural plasticity and binding characteristics of EGFR wild-type and mutant forms (S769L and K846R) against ligand molecules like Gefitinib, native CUCM, and different CUCM analogues. Through multidimensional experimental approaches, we conclude that CUCM-36 ((1E,4Z,6E)-1-(3,4-Diphenoxyphenyl)-5-hydroxy-7-(4-hydroxy-3-phenoxyphenyl)-1,4,6-heptatrien-3-one) is the best anti-EGFR compound with high drug-likeness, ADME properties, and low toxicity properties. CUCM-36 compound has demonstrated better affinity towards both wild-type (ΔG is ?8.5?kcal/Mol) and mutant forms (V769L & K846R; ΔG for both is >?9.20?kcal/Mol) compared to natural CUCM and Gefitinib inhibitor. This study advises the future laboratory assays to develop CUCM-36 as a novel drug compound for treating EGFR positive non-small cell lung cancer patients.