中立型时滞Volterra系统解的稳定性

本文研究中立型时滞Volterra系统解的渐近稳定性，得到系统的正常数平衡点为渐近稳定的充分条件，发展了文献〔6〕的结果，回答了文献〔7〕所留下的一个未解决问题．     

硬毛夏枯草的新三萜——夏枯草酸

硬毛夏枯草(Prunella hispida Benth.)系唇形科夏枯草属植物。该植物具清肝,散结等功效,在民间广泛作为夏枯草的代用品,其化学成分未见报道。本文报道从大理州采集的硬毛夏枯草的乙醚提取物中分离到的四个化学成分:β-谷甾酸〔Ⅱ〕,白桦酯酸〔Ⅲ〕,熊果酸〔Ⅳ〕和夏枯草酸〔Ⅰ〕。经光谱分析和化学方法证明,〔Ⅰ〕的结构为1,2-2α-dihydroxy ursolic acid,系一新的三萜化合物。     

植物的交配系统及其进化机制与种群适应

高等植物的繁殖方式远比高等动物的要复杂多样〔１,２〕,历来受到众多学者的关注。交配系统和作用于交配系统的选择力量,在达尔文时代的进化理论中就有着重要的地位〔３,４〕,达尔文本人对交配系统的进化结果也有着浓厚的兴趣〔５〕。植物交配系统方面的信息,对遗传育种〔６～１０〕、濒危物种遗传多样性检测的取样策略〔１〕、种质遗传资源的保护和利用〔１１～１５〕有着重要的理论指导意义。然而,交配系统与相关概念之间有一定的交叉重合,易引起术语和概念的混乱,笔者将首先探讨交配系统及有关概念的范畴。当然最引人关注的是交…     

RNA原位杂交技术及其在植物基因表达研究中的应用

原位杂交 ( In situ Hybridization)是一种在细胞水平上研究基因表达调控的最直接有效的分子生物学技术。这一技术最初应用于动物染色体上的基因物理定位 〔1〕和特定 m RNA在组织中的空间定位〔2〕,后来又作为诊断工具检测感染病毒的细胞 〔3〕。到 80年代后期 ,原位杂交技术开始应用于植物基因表达调控的研究 〔4～ 6〕。植物基因的时空表达研究是探讨植物生长发育机制的重要手段。由于 RNA原位杂交技术能够精确确定基因表达的时空分布 ,而得到了越来越广泛的应用 ;从营养器官生长发育〔7～ 9〕、生殖器官生长发育〔10～ 13〕、自交不…     

槲皮素对凝血酶诱导的猪血小板肌动蛋白聚合的抑制作用

槲皮素对凝血酶诱导的猪血小板肌动蛋白聚合的抑制作用宋芝娟刘文梁念慈（广东医学院医用生化研究所,湛江５２４０２３）槲皮素（ｑｕｅｒｃｅｔｉｎ）有广泛的药理作用,如舒张血管〔１〕,抑制癌细胞ＤＮＡ合成〔２〕,诱发ＤＮＡ损伤〔３〕,抗超氧阴离子等〔４〕,...     

傅氏按蚊与朝鲜按蚊的形态对比观察

傅氏按蚊(Anopheles freyi Meng,1957)和朝鲜按蚊(An.koreicus Yamada and Watanabe,1918)形态十分相似,二者是独立的种还是同种异名,迄今仍有争议〔1〕,我们用形态特征结合雄蚊抱握器运动频率进行了比较观察,报告如下。1材料与方法傅氏按蚊捕自雅安地区名山县车岭乡牛舍,雌蚊单个鉴定,产卵,培育后代。对成虫观察形态,并按康万民等〔2〕和潘家复等〔3〕方法观察抱握器运动频率。共观察32只,平均69.44±1.48次。朝鲜按蚊形态以冯兰洲〔4〕、陆宝麟〔5〕和雷心田〔1〕描述的形态特征为依据。2结果傅氏按蚊和朝鲜按蚊的翅上白斑、黑斑、抱握…     

关于持久性的李雅普诺夫方法

本文在〔1〕,〔2〕的基础上,将持久函数的定义作了推广和扩充,并将稳定性理论思想方法系统引入持久性讨论中．得到了强持久的充要条件及永久共存的充分条件,并用上述结论讨论了Volterra模型的持久性．     

抑癌基因nm23—H1在逆转录病毒载体的表达

癌症转移是癌症病人死亡的主要原因之一。抑制肿瘤转移的基因ｎｍ２３－Ｈ１与ｎｍ２３－Ｈ２分别编码二磷酸核苷激酶（ＮＤＰＫ）的Ａ与Ｂ亚基〔１〕,ｎｍ２３－Ｈ１基因能有效地抑制肿瘤转移〔２〕。ｎｍ２３－Ｈ１的表达水平与黑色素瘤〔２,３〕、乳腺癌〔４〕、卵巢...     

非自治时滞Logistic方程的振动性

本文研究了时滞Logistic方程和它的线性化方程的振动性。在一定的条件下,我们证明了这两个方程在振动性上等价．所得结果推广和改进了〔1〕的相应结果,同时也给〔2〕的作者提出的问题一个肯定的回答．     

两类肌型血管模型的浑沌现象

一、引言在探讨心肌梗塞的病理研究中,一些医学家认为动脉粥样硬化和动脉痉挛是导致发病的共同原因。为此目的,文〔1〕等探讨了肌肉力学的一般方程,文〔3〕导出了N型血管和S型血管的含集中参数的力学模型     

Structural analysis of the complex of a distamycin analogue with the Dickerson dodecamer 13C labeled at 5'-carbons using NMR spectroscopy.

Structural analysis of the complex of a distamycin analogue (Tallimustine) with the Dickerson dodecamer d(C*G*C*G*A*A*T*T*C*G*C*G) [N*:[5'-(13)C]nucleotide] was performed by NMR spectroscopy and the results will be described in detail.     

'Smoking genes': a genetic association study

Some controversy exists on the specific genetic variants that are associated with nicotine dependence and smoking-related phenotypes. The purpose of this study was to analyse the association of smoking status and smoking-related phenotypes (included nicotine dependence) with 17 candidate genetic variants: CYP2A6*1×2, CYP2A6*2 (1799T>A) [rs1801272], CYP2A6*9 (-48T>G) [rs28399433], CYP2A6*12, CYP2A13*2 (3375C>T) [rs8192789], CYP2A13*3 (7520C>G), CYP2A13*4 (579G>A), CYP2A13*7 (578C>T) [rs72552266], CYP2B6*4 (785A>G), CYP2B6*9 (516G>T), CHRNA3 546C>T [rs578776], CHRNA5 1192G>A [rs16969968], CNR1 3764C>G [rs6928499], DRD2-ANKK1 2137G>A (Taq1A) [rs1800497], 5HTT LPR, HTR2A -1438A>G [rs6311] and OPRM1 118A>G [rs1799971]. We studied the genotypes of the aforementioned polymorphisms in a cohort of Spanish smokers (cases, N = 126) and ethnically matched never smokers (controls, N = 80). The results showed significant between-group differences for CYP2A6*2 and CYP2A6*12 (both P<0.001). Compared with carriers of variant alleles, the odds ratio (OR) for being a non-smoker in individuals with the wild-type genotype of CYP2A6*12 and DRD2-ANKK1 2137G>A (Taq1A) polymorphisms was 3.60 (95%CI: 1.75, 7.44) and 2.63 (95%CI: 1.41, 4.89) respectively. Compared with the wild-type genotype, the OR for being a non-smoker in carriers of the minor CYP2A6*2 allele was 1.80 (95%CI: 1.24, 2.65). We found a significant genotype effect (all P≤0.017) for the following smoking-related phenotypes: (i) cigarettes smoked per day and CYP2A13*3; (ii) pack years smoked and CYP2A6*2, CYP2A6*1×2, CYP2A13*7, CYP2B6*4 and DRD2-ANKK1 2137G>A (Taq1A); (iii) nicotine dependence (assessed with the Fagestrom test) and CYP2A6*9. Overall, our results suggest that genetic variants potentially involved in nicotine metabolization (mainly, CYP2A6 polymorphisms) are those showing the strongest association with smoking-related phenotypes, as opposed to genetic variants influencing the brain effects of nicotine, e.g., through nicotinic acetylcholine (CHRNA5), serotoninergic (HTR2A), opioid (OPRM1) or cannabinoid receptors (CNR1).     

5-Iodo-A-85380 binds to alpha-conotoxin MII-sensitive nicotinic acetylcholine receptors (nAChRs) as well as alpha4beta2* subtypes

Recent work suggests that 5-iodo-A-85380, a radioiodinated analog of the 3-pyridyl ether A-85380, represents a promising imaging agent for non-invasive, in vivo studies of alphaAbeta2* nicotinic acetylcholine receptors (nAChRs; *denotes receptors containing the indicated subunits), because of its low non-specific binding, low in vivo toxicity and high selectivity for alpha4beta2* nAChRs. As an approach to elucidate nAChR subtypes expressed in striatum, we carried out competitive autoradiography in monkey and rat brain using 5-[125I]iodo-A-85380 ([125I]A-85380) and [125I]alpha-conotoxin MII, a ligand that binds with high affinity to alpha6* and alpha3* nAChRs, but not to alpha4beta2* nAChRs. Although A-85380 is reported to be selective for alpha4beta2* nAChRs, we observed that A-85380 completely inhibited [125I]alpha-conotoxin MII binding in rat striatum and that A-85380 blocked >90% of [125I] alpha-conotoxin MII sites in monkey caudate and putamen. These results suggest that A-85380 binds to non-alpha4beta2* nAChRs, including putative alpha6* nAChRs. Experiments to determine the percentage of [125I]A-85380 sites that contain alpha-conotoxin MII-sensitive (alpha6beta2*) nAChRs indicate that they represent about 10% of [125I]A-85380 sites in rodent striatum and about 30% of sites in monkey caudate and putamen. These data are important for identifying alterations in nicotinic receptor subtypes in Parkinson's disease and other basal ganglia disorders both in in vitro and in in vivo imaging studies.     

Mutagenic and genotoxic effects of DNA adducts formed by the anticancer drug cis-diamminedichloroplatinum(II).

The toxicity and mutagenicity of three DNA adducts formed by the anticancer drug cis-diamminedichloroplatinum(II) (cis-DDP or cisplatin) were investigated in Escherichia coli. The adducts studied were cis-[Pt(NH3)2(d(GpG))] (G*G*), cis-[Pt(NH3)2(d(ApG))] (A*G*) and cis-[Pt(NH3)2(d(GpTpG))] (G*TG*), which collectively represent approximately 95% of the DNA adducts reported to form when the drug damages DNA. Oligonucleotide 24-mers containing each adduct were positioned at a known site within the viral strand of single stranded M13mp7L2 bacteriophage DNA. Following transfection into E. coli DL7 cells, the genomes containing the G*G*, A*G* and G*TG* adducts had survival levels of 5.2 +/- 1.2, 22 +/- 2.6 and 14 +/- 2.5% respectively, compared to unmodified genomes. Upon SOS induction, the survival of genomes containing the G*G* and A*G* adducts increased to 31 +/- 5.4 and 32 +/- 4.9% respectively. Survival of the genome containing the G*TG* adduct did not increase upon SOS induction. In SOS induced cells, the G*G* and A*G* adducts gave rise predominantly to G-->T and A-->T transversions respectively, targeted to the 5' modified base. In addition, A-->G transitions were detected for the A*G* adduct and low levels of tandem mutations at the 5' modified base as well as the adjacent 5' base were also observed for both adducts. The A*G* adduct was more mutagenic than the G*G* adduct, with a mutation frequency of 6% compared to 1.4% for the latter adduct. No cis-[Pt(NH3)2)2+ intrastrand crosslink-specific mutations were observed for the G*TG* adduct.     

Effects of metabolic genotypes on intermediary biomarkers in subjects exposed to PAHS: results from the EXPAH study

Data from the EXPAH project on PAH exposure and intermediary biomarkers were analyzed with respect to individual genotypes at seven metabolic gene loci. The GSTM1 null allele was associated with significantly higher levels of two biomarkers, malondialdehyde-2′-deoxyguanosine and benzo[a]pyrene DNA adducts in the total population from three Central and Eastern European countries. The CYP1B1 Leu/Val variant demonstrated effects on both markers of oxidative DNA damage in opposite directions, producing a higher level of M₁dG with a trend from wild type (Leu/Leu) to heterozygotes to homozygous (Val/Val) variants, whereas the effects of these variants were reversed for 8-oxodG. Cluster Analysis was used to group composite genotypes in order to determine if combined genotypes of multiple loci could explain some of the variation seen with the biomarkers, expressed per unit of exposure, referred to as a sensitivity index. This analysis revealed two closely related genotypes each involving four of the loci (GSTM1*0/*0, CYP1A1*1*1, CYP1B1*1/*2, GSTP1*1/*1 and GSTT1*0/*0, CYP1A1*1*1, CYP1B1*1/*2, GSTP1*1/*1.) that conferred significant resistance to the DNA damaging effects of benzo[a]pyrene, measured as the level of a benzo[a]pyrene-like adduct per unit of benzo[a]pyrene exposed.     

Mass spectral data for 64 eluted peptides and structural modeling define peptide binding preferences for class I alleles in two chicken MHC-<Emphasis Type="Italic">B</Emphasis> haplotypes associated with opposite responses to Marek's disease

In the chicken, resistance to lymphomas that form following infection with oncogenic strains of Marek's herpesvirus is strongly linked to the major histocompatibility complex (MHC)-B complex. MHC-B21 haplotype is associated with lower tumor-related mortality compared to other haplotypes including MHC-B13. The single, dominantly expressed class I gene (BF2) is postulated as responsible for the MHC-B haplotype association. We used mass spectrometry to identify peptides and structural modeling to define the peptide binding preferences of BF2*2101 and BF2*1301 proteins. Endogenous peptides (8-12 residues long) were eluted from affinity-purified BF2*2101 and BF2*1301 proteins obtained from transduced cDNA expressed in RP9 cells, hence expressed in the presence of heterologous TAP. Sequences of individual peptides were identified by mass spectrometry. BF2*2101 peptides appear to be tethered at the binding groove margins with longer peptides arching out but selected by preferred residues at positions P3, P5, and P8: X-X-[AVILFP]-X((1-5))-[AVLFWP]-X((2-3))-[VILFM]. BF2*1301 peptides appear selected for residues at P2, P3, P5, and P8: X-[DE]-[AVILFW]-X((1-2))-[DE]-X-X-[ED]-X((0-4)). Some longer BF2*1301 peptides likely also arch out, but others are apparently accommodated by repositioning of Arg83 so that peptides extend beyond the last preferred residue at P8. Comparisons of these peptides with earlier peptides derived in the presence of homologous TAP transport revealed the same side chain preferences. Scanning of Marek's and other viral proteins with the BF2*2101 motif identified many matches, as did the control human leukocyte antigen A*0201 motif. The BF2*1301 motif is more restricting suggesting that this allele may confer a selective advantage only in infections with a subset of viral pathogens.     

Effects of spectator ligands on the specific recognition of intrastrand platinum-DNA cross-links by high mobility group box and TATA-binding proteins

The results presented describe the effects of various spectator ligands, attached to a platinum 1,2-intrastand d(GpG) cross-link in duplex DNA, on the binding of high mobility group box (HMGB) domains and the TATA-binding protein (TBP). In addition to cisplatin-modified DNA, 15-base pair DNA probes modified by [Pt(1R,2R-diaminocyclohexane)](2+), cis-[Pt(NH(3))(cyclohexylamine)](2+), [Pt(ethylenediamine)](2+), cis-[Pt(NH(3))(cyclobutylamine)](2+), and cis-[Pt(NH(3))(2-picoline)](2+) were examined. Electrophoretic mobility shift assays show that both the A and B domains of HMGB1 as well as TBP discriminate between different platinum-DNA adducts. HMGB1 domain A is the most sensitive to the nature of the spectator ligands on platinum. The effect of the spectator ligands on protein binding also depends highly on the base pairs flanking the platinated d(GpG) site. Double-stranded oligonucleotides containing the AG*G*C sequence, where the asterisks denote the sites of platination, with different spectator ligands are only moderately discriminated by the HMGB proteins and TBP, but the recognition of dsTG*G*A is highly dependent on the ligands. The effects of HMGB1 overexpression in a BG-1 ovarian cancer cell line, induced by steroid hormones, on the sensitivity of cells treated with [Pt(1R,2R-diaminocyclohexane)Cl(2)] and cis-[Pt(NH(3))(cyclohexylamine)Cl(2)] were also examined. The results suggest that HMGB1 protein levels influence the cellular processing of cis-[Pt(NH(3))- (cyclohexylamine)](2+), but not [Pt((1R,2R)-diaminocyclohexane)](2+), DNA lesions. This result is consistent with the observed binding of HMGB1a to platinum-modified dsTG*G*A probes but not with the binding affinity of HMGB1a and HMGB1 to platinum-damaged dsAG*G*C oligonucleotides. These experiments reinforce the importance of sequence context in platinum-DNA lesion recognition by cellular proteins.     

Kinetics of redox interaction between substituted quinones and ascorbate under aerobic conditions.

One-electron reduction of quinones (Q) by ascorbate (AscH ); (1) AscH + Q --> Q*- + Asc*- + H+, followed by the oxidation of semiquinone (Q*-) by molecular oxygen; (2) Q*- + O2 --> Q + O2*-, results in the catalytic oxidation of ascorbate (with Q as a catalyst) and formation of active forms of oxygen. Along with enzymatic redox cycling of Q. this process may be related to Q cytotoxicity and underlie an antitumor activity of some Qs. In this work, the kinetics of oxygen consumption accompanied the interaction of ascorbate with 55 Qs including substituted 1,4- and 1,2-benzoquinones, naphthoquinones and other quinoid compounds were studied in 50 mM sodium phosphate buffer, pH 7.40, at 37 degrees C by using the Clark electrode technique. The capability of Q to catalyze ascorbate oxidation was characterized by the effective value of kEFF calculated from the initial rate of oxygen consumption (R(OX)) by the equation R(OX) = kEFF[Q][AscH-] as well as by a temporary change in R(OX). The correlation of kEFF with one-electron reduction potential, E(Q/Q*-), showed a sigma-like plot, the same for different kinds of Qs. Only the Qs which reduction potential E(Q/Q*-) ranged from nearly -250 to + 50 mV displayed a pronounced catalytic activity, kEFF increased with shifting E(Q/Q*-) to positive values. The following linear correlation between kEFF (in M (-1) s(-1)) and E(Q/Q*-) (in mV) might be suggested for these Qs: lg(kEFF)= 3.91 + 0.0143E(Q/Q*-). In contrast, Qs with E(Q/Q*-) < - 250 mV and E(Q/Q*-) > + 50 mV showed no measurable catalytic activity. The Qs studied displayed a wide variety in the kinetic regularities of oxygen consumption. When E(Q/Q*-) was more negative than - 100 mV, Q displayed a simple ('standard') kinetic behavior--R(OX) was proportional to [AscH-][Q] independently of concentration of individual reagents, [AscH-] and [Q]; R(OX) did not decrease with time if [AscH-] was held constant: Q recycling was almost reversible. Meanwhile, Qs with E(Q/Q*-) > - 100 mV demonstrated a dramatic deviation from the 'standard' behavior that was manifested by the fast decrease in R(OX) with time and non-linear dependence of even starting values of R(OX) on [Q] and [AscH-]. These deviations were caused basically by the participation of Q*- in side reactions different from (2). The above findings were confirmed by kinetic computer simulations. Some biological implications of Q-AscH- interaction were discussed.     

Isolation and structure elucidation of caryophyllane sesquiterpenoids from leaves of Eremophila spathulata

Crude extract of Eremophila spathulata leaves was investigated by semi-preparative scale high-performance liquid chromatography (HPLC), analytical scale HPLC, and hyphenated high-performance liquid chromatography-photodiode array-high-resolution mass spectrometry-nuclear magnetic resonance (HPLC-PDA-HRMS-SPE-NMR), which afforded seven previously unreported caryophyllane sesquiterpenoids. Semi-preparative scale separation of the crude extract afforded (1R*,4R*,9S*,E)-8-formyl-11,11-dimethylbicyclo[7.2.0]undec-7-ene-4-carboxylic acid (5) and analytical-scale HPLC separation afforded (1R*,4S*,7S*,9S*)-7-hydroxy-11,11-dimethyl-8-methylenebicyclo[7.2.0]undecane-4-carboxylic acid (1), (1S*,6R*,9R*,E)-10,10-dimethylbicyclo[7.2.0]undec-2-ene-2,6-dicarboxylic acid (2), (1R*,4S*,9S*)-11,11-dimethyl-8-oxobicyclo[7.2.0]undecane-4-carboxylic acid (3), and (1R*,4R*,9S*)-11,11-dimethyl-8-oxobicyclo[7.2.0]undecane-4-carboxylic acid (4). HPLC-PDA-HRMS-SPE-NMR afforded (1R*,4R*,9S*)-11,11-dimethyl-8-methylenebicyclo[7.2.0]undecane-4-carboxylic acid (6) and (1R*,4S*,9S*)-11,11-dimethyl-8-methylenebicyclo[7.2.0]undecane-4-carboxylic acid (7). The structures of all isolated compounds were established based on HRMS as well as extensive 1D and 2D NMR analysis. Relative configurations were determined by correlations in spectra from rotational Overhauser effect spectroscopy.     

The Value of Blood Oxygenation Level-Dependent (BOLD) MR Imaging in Differentiation of Renal Solid Mass and Grading of Renal Cell Carcinoma (RCC): Analysis Based on the Largest Cross-Sectional Area versus the Entire Whole Tumour

Objectives

To study the value of assessing renal masses using different methods in parameter approaches and to determine whether BOLD MRI is helpful in differentiating RCC from benign renal masses, differentiating clear-cell RCC from renal masses other than clear-cell RCC and determining the tumour grade.

Methods

Ninety-five patients with 139 renal masses (93 malignant and 46 benign) who underwent abdominal BOLD MRI were enrolled. R2* values were derived from the largest cross-section (R2*_largest) and from the whole tumour (R2*_whole). Intra-observer and inter-observer agreements were analysed based on two measurements by the same observer and the first measurement from each observer, respectively, and these agreements are reported with intra-class correlation coefficients and 95% confidence intervals. The diagnostic value of the R2* value in the evaluation was assessed with receiver-operating characteristic analysis.

Results

The intra-observer agreement was very good for R2*_largest and R2*_whole (all > 0.8). The inter-observer agreement of R2*_whole (0.75, 95% confidence interval: 0.69~0.79) was good and was significantly improved compared with the R2*_largest (0.61, 95% confidence interval: 0.52~0.68), as there was no overlap in the 95% confidence interval of the intra-class correlation coefficients. The diagnostic value in differentiating renal cell carcinoma from benign lesions with R2*_whole (AUC=0.79/0.78[observer1/observer2]) and R2*_largest (AUC=0.75[observer1]) was good and significantly higher (p=0.01 for R2*_largest[observer2] vs R2*_whole[observer2], p<0.01 for R2*_whole[observer1] vs R2*_largest[observer2]) than R2*_largest for observer 2 (AUC=0.64). For the grading of clear-cell RCC, both R2*_whole and R2*_largest were good (all > 0.7) and were not significantly different (p=0.89/0.93 for R2*largest vs R2*whole[observer1/observer2], 0.96 for R2*whole[observer1] vs R2*largest[observer2] and 0.96 for R2*whole [observer2] vs R2*largest[observer1]).

Conclusions

BOLD MRI could provide a feasible parameter for differentiating renal cell carcinoma from benign renal masses and for predicting clear-cell renal cell carcinoma grading. Compared with the largest cross-section, assessing the whole tumour provides better inter-observer agreement in parameter measurement for differentiating renal cell carcinoma from benign renal masses.