• 【胆固醇对模仿人红细胞膜外叶和内叶的多组分朗缪尔单层细胞的影响。】 复制标题 收藏 收藏
    DOI:10.1016/j.colsurfb.2012.10.020 复制DOI
    作者列表:Wydro P
    BACKGROUND & AIMS: :In this work the Langmuir monolayers were used to prepare multicomponent systems mimicking outer and inner layer of human erythrocyte membranes. The aim of performed experiments was to compare the influence of cholesterol on complex artificial membranes reflecting compositional diversity of the respective membranes leaflets. The properties of both systems in the presence of cholesterol at various concentrations were analyzed by means of thermodynamic description of the interactions between molecules in the investigated monolayers, complemented by the analysis of their morphology performed with the application of Brewster Angle Microcopy. It was found that cholesterol induces highly favorable stabilizing effect on the studied monolayers, increases their condensation and strengthens intermolecular forces. However, the influence of cholesterol was found to be stronger on the mixed film imitating outer membrane layer. Detailed discussion of the obtained results proved that the behavior of cholesterol in the model outer vs. inner layers is strongly determined by their compositional differences. The most important findings resulting from these experiments concern the problem of transbilayer distribution of cholesterol in membranes, which despite numerous investigations seems to be still unclear. The data obtained in this work allow one to suggest that cholesterol tends to accumulate preferentially in outer membrane leaflet or it is localized symmetrically in both layers rather than in inner leaflet.
    背景与目标: :在这项工作中,Langmuir单层被用于制备模仿人类红细胞膜外层和内层的多组分系统。进行实验的目的是比较胆固醇对反映各个膜小叶组成多样性的复杂人工膜的影响。通过热力学描述所研究的单分子层中分子之间的相互作用,并用Brewster Angle Microcopy对它们的形态进行分析,对两种系统在不同浓度的胆固醇存在下的性能进行了分析。发现胆固醇对所研究的单分子层具有高度有利的稳定作用,增加了它们的缩合并增强了分子间力。然而,发现胆固醇对模拟外膜层的混合膜的影响更大。对所得结果的详细讨论证明,模型外层和内层中胆固醇的行为强烈取决于它们的组成差异。这些实验产生的最重要发现与膜中胆固醇跨双层分布的问题有关,尽管进行了许多研究,但这仍然不清楚。通过这项工作获得的数据可以表明胆固醇倾向于优先在外膜小叶中积累,或者胆固醇对称地分布在两层而不是内部小叶中。
  • 【优化大流行前流感疫苗的剂量以降低感染发作率。】 复制标题 收藏 收藏
    DOI:10.1371/journal.pmed.0040218 复制DOI
    作者列表:Riley S,Wu JT,Leung GM
    BACKGROUND & AIMS: BACKGROUND:The recent spread of avian influenza in wild birds and poultry may be a precursor to the emergence of a 1918-like human pandemic. Therefore, stockpiles of human pre-pandemic vaccine (targeted at avian strains) are being considered. For many countries, the principal constraint for these vaccine stockpiles will be the total mass of antigen maintained. We tested the hypothesis that lower individual doses (i.e., less than the recommended dose for maximum protection) may provide substantial extra community-level benefits because they would permit wider vaccine coverage for a given total size of antigen stockpile. METHODS AND FINDINGS:We used a mathematical model to predict infection attack rates under different policies. The model incorporated both an individual's response to vaccination at different doses and the process of person-to-person transmission of pandemic influenza. We found that substantial reductions in the attack rate are likely if vaccines are given to more people at lower doses. These results are applicable to all three vaccine candidates for which data are available. As a guide to the magnitude of the effect, we simulated epidemics based on historical studies of immunogenicity. For example, for one of the vaccines for which data are available, the attack rate would drop from 67.6% to 58.7% if 160 out of the total US population of 300 million were given an optimal dose rather than 20 out of 300 million given the maximally protective dose (as promulgated in the US National Pandemic Preparedness Plan). Our results are conservative with respect to a number of alternative assumptions about the precise nature of vaccine protection. We also considered a model variant that includes a single high-risk subgroup representing children. For smaller stockpile sizes that allow vaccine to be offered only to the high-risk group at the optimal dose, the predicted benefits of using the homogenous model formed a lower bound in the presence of a risk group, even when the high-risk group was twice as infective and twice as susceptible. CONCLUSIONS:In addition to individual-level protection (i.e., vaccine efficacy), the population-level implications of pre-pandemic vaccine programs should be considered when deciding on stockpile size and dose. Our results suggest that a lower vaccine dose may be justified in order to increase population coverage, thereby reducing the infection attack rate overall.
    背景与目标: 背景:禽流感最近在野生鸟类和家禽中的传播可能是1918年人类大流行病出现的先兆。因此,正在考虑人类大流行前疫苗的库存(针对禽类)。对于许多国家而言,这些疫苗库存的主要限制因素是维持的抗原总量。我们测试了以下假设:较低的单个剂量(即小于建议的最大保护剂量)可能会提供实质性的社区级额外好处,因为对于给定的抗原库总体积,它们将允许更广泛的疫苗覆盖范围。
    方法和发现:我们使用数学模型来预测不同策略下的感染发作率。该模型结合了个体对不同剂量疫苗接种的反应以及大流行性流感的人际传播过程。我们发现,如果以较低的剂量向更多的人注射疫苗,则可能会大大降低发作率。这些结果适用于可获得数据的所有三种候选疫苗。作为影响程度的指导,我们根据免疫原性的历史研究模拟了流行病。例如,对于一种可获得数据的疫苗,如果给美国3亿总人口中的160人提供最佳剂量,而不是给3亿人中的20人给予最佳剂量,那么其发作率将从67.6%降至58.7%。最大保护剂量(如美国国家大流行防备计划所公布)。关于疫苗保护的确切性质的许多替代假设,我们的结果是保守的。我们还考虑了一个模型变体,其中包括代表儿童的单个高风险亚组。对于允许以最佳剂量仅向高危人群提供疫苗的较小库存,即使存在高危人群,使用均质模型的预期收益也会在低危人群中形成较低的界限传染性和易感性的两倍。
    结论:除了个人层面的保护(即疫苗效力)外,在决定储存量和剂量时还应考虑大流行前疫苗计划在人群层面的影响。我们的结果表明,可以采用较低的疫苗剂量以增加人群覆盖率,从而降低总体感染率。
  • 【急性感染后操纵记忆CD8 T细胞生成的速率。】 复制标题 收藏 收藏
    DOI:10.4049/jimmunol.179.1.53 复制DOI
    作者列表:Badovinac VP,Harty JT
    BACKGROUND & AIMS: :Infection with Listeria monocytogenes elicits expansion in numbers of Ag-specific CD8+ T cells, which then undergo programmed contraction. The remaining cells undergo further phenotypic and functional changes with time, eventually attaining the qualities of memory CD8+ T cells. In this study, we show that L. monocytogenes-specific CD8+ T cell populations primed in antibiotic-pretreated mice undergo brief effector phase, but rapidly develop phenotypic (CD127(high), CD43(low)) and functional (granzyme B(low), IL-2-producing) characteristics of memory CD8+ T cells. These early memory CD8+ T cells were capable of substantial secondary expansion in response to booster challenge at day 7 postinfection, resulting in significantly elevated numbers of secondary effector and memory CD8+ T cells and enhanced protective immunity compared with control-infected mice. Although early expansion in numbers is similar after L. monocytogenes infection of antibiotic-pretreated and control mice, the absence of sustained proliferation coupled with decreased killer cell lectin-like receptor G-1 up-regulation on responding CD8+ T cells may explain the rapid effector to memory CD8+ T cell transition. In addition, antibiotic treatment 2 days post-L. monocytogenes challenge accelerated the generation of CD8+ T cells with memory phenotype and function, and this accelerated memory generation was reversed in the presence of CpG-induced inflammation. Together, these data show that the rate at which Ag-specific CD8+ T cell populations acquire memory characteristics after infection is not fixed, but rather can be manipulated by limiting inflammation that will in turn modulate the timing and extent to which CD8+ T cells proliferate and up-regulate killer cell lectin-like receptor G-1 expression.
    背景与目标: 单核细胞增生性李斯特氏菌感染:会引起大量的Ag特异性CD8 T细胞扩增,然后经历程序性收缩。其余的细胞会随着时间的推移发生进一步的表型和功能变化,最终达到记忆CD8 T细胞的质量。在这项研究中,我们表明在抗生素预处理的小鼠中引发的单核细胞增生李斯特氏菌特异的CD8 T细胞群体经历短暂的效应期,但迅速发展出表型(CD127(高),CD43(低))和功能性(粒酶B(低))。 CD8 T细胞的特性)。这些早期记忆的CD8 T细胞能够在感染后第7天响应加强免疫,进行大量的次级扩增,与对照感染的小鼠相比,导致次级效应子和记忆CD8 T细胞的数量显着增加,并且保护性免疫力增强。尽管单核细胞增生李斯特氏菌感染抗生素预处理和对照小鼠后,早期数量增加相似,但缺乏持续的增殖以及对应答性CD8 T细胞的杀伤细胞凝集素样受体G-1上调的减少可能解释了这种快速效应到记忆CD8 T细胞的转变。另外,L治疗后2天进行抗生素治疗。单核细胞增多症的挑战加速了具有记忆表型和功能的CD8 T细胞的生成,并且这种加速的记忆生成在CpG诱导的炎症存在下被逆转。总之,这些数据表明,Ag特异性CD8 T细胞群在感染后获得记忆特征的速率不是固定的,而是可以通过限制炎症来控制的,而炎症反过来会调节CD8 T细胞增殖的时间和程度,并限制炎症的发生。上调杀伤细胞凝集素样受体G-1的表达。
  • 【H离子通过细菌光合作用反应中心的P QA状态结合的动力学:蛋白质内的速率限制。】 复制标题 收藏 收藏
    DOI:10.1016/S0006-3495(97)78077-9 复制DOI
    作者列表:Maróti P,Wraight CA
    BACKGROUND & AIMS: The kinetics of flash-induced H+ ion binding by isolated reaction centers (RCs) of Rhodobacter sphaeroides, strain R-26, were measured, using pH indicators and conductimetry, in the presence of terbutryn to block electron transfer between the primary and secondary quinones (QA and QB), and in the absence of exogenous electron donors to the oxidized primary donor, P+, i.e., the P+QA-state. Under these conditions, proton binding by RCs is to the protein rather than to any of the cofactors. After light activation to form P+QA-, the kinetics of proton binding were monoexponential at all pH values studied. At neutral pH, the apparent bimolecular rate constant was close to the diffusional limit for proton transfer in aqueous solution (approximately 10(11) M-1 s-1), but increased significantly in the alkaline pH range (e.g., 2 x 10(13) M-1 s-1 at pH 10). The average slope of the pH dependence was -0.4 instead of -1.0, as might be expected for a H+ diffusion-controlled process. High activation energy (0.54 eV at pH 8.0) and weak viscosity dependence showed that H+ ion uptake by RCs is not limited by diffusion. The salt dependence of the H+ ion binding rate and the pK values of the protonatable amino acid residues of the reaction center implicated surface charge influences, and Gouy-Chapman theory provided a workable description of the ionic effects as arising from modulation of the pH at the surface of the RC. Incubation in D2O caused small increases in the pKs of the protonatable groups and a small, pH (pD)-dependent slowing of the binding rate. The salt, pH, temperature, viscosity, and D2O dependences of the proton uptake by RCs in the P+QA- state were accounted for by three considerations1) parallel pathways of H+ delivery to the RC, contributing to the observed (net) H+ disappearance; 2) rate limitation of the protonation of target groups within the protein by conformational dynamics; and 3) electrostatic influences of charged groups in the protein, via the surface pH.

    背景与目标: 在特布瑞林存在下,通过阻断pH值和电导测定了球形球形红球菌R-26的分离反应中心(RC)的闪光诱导的H离子结合的动力学,并测定了叔丁烯的存在以阻止电子在伯醌和仲醌之间的转移( QA和QB),并且在没有外源电子给体到氧化的初级给体P的情况下,即P QA状态。在这些条件下,RC的质子结合是蛋白质而不是任何辅因子。光活化形成P QA-后,质子结合的动力学在所有研究的pH值下都是单指数的。在中性pH下,表观双分子速率常数接近质子在水溶液中的扩散极限(大约10(11)M-1 s-1),但在碱性pH范围内显着增加(例如2 x 10( 13)pH值为10的M-1 s-1。 pH依赖性的平均斜率是-0.4而不是-1.0,这可能是H扩散控制过程所期望的。高活化能(pH 8.0时为0.54 eV)和较弱的粘度依赖性表明RC吸收H离子不受扩散的限制。 H离子结合率与盐的依赖性以及反应中心质子化氨基酸残基的pK值都牵涉表面电荷影响,Gouy-Chapman理论提供了对由于在pH值下pH值的调节而产生的离子效应的可行描述。 RC的表面。在D2O中孵育会导致可质子化基团的pK小幅增加,并导致pH(pD)依赖性的结合速率减慢。 P QA状态下RC吸收质子的盐,pH,温度,粘度和D2O依赖性是由以下三个因素引起的: 2)通过构象动力学限制蛋白质内目标基的质子化速率;和3)通过表面pH值对蛋白质中带电基团的静电影响。

  • 【月经周期的黄体期增加运动中的出汗率。】 复制标题 收藏 收藏
    DOI:10.1590/s0100-879x2006005000007 复制DOI
    作者列表:Garcia AM,Lacerda MG,Fonseca IA,Reis FM,Rodrigues LO,Silami-Garcia E
    BACKGROUND & AIMS: :The present study evaluated whether the luteal phase elevation of body temperature would be offset during exercise by increased sweating, when women are normally hydrated. Eleven women performed 60 min of cycling exercise at 60% of their maximal work load at 32 degrees C and 80% relative air humidity. Each subject participated in two identical experimental sessions: one during the follicular phase (between days 5 and 8) and the other during the luteal phase (between days 22 and 25). Women with serum progesterone >3 ng/mL, in the luteal phase were classified as group 1 (N = 4), whereas the others were classified as group 2 (N = 7). Post-exercise urine volume (213 +/- 80 vs 309 +/- 113 mL) and specific urine gravity (1.008 +/- 0.003 vs 1.006 +/- 0.002) changed (P < 0.05) during the luteal phase compared to the follicular phase in group 1. No menstrual cycle dependence was observed for these parameters in group 2. Sweat rate was higher (P < 0.05) in the luteal (3.10 +/- 0.81 g m-2 min-1) than in the follicular phase (2.80 +/- 0.64 g m(-2) min(-1)) only in group 1. During exercise, no differences related to menstrual cycle phases were seen in rectal temperature, heart rate, rate of perceived exertion, mean skin temperature, and pre- and post-exercise body weight. Women exercising in a warm and humid environment with water intake seem to be able to adapt to the luteal phase increase of basal body temperature through reduced urinary volume and increased sweating rate.
    背景与目标: :本研究评估了在正常情况下为女性补充水分时,出汗增加是否可以抵消黄体期体温的升高。十一名女性在32摄氏度和80%的相对湿度下以最大工作负荷的60%进行了60分钟的自行车运动。每个受试者都参加了两个相同的实验会议:一个在卵泡期(第5至8天之间),另一个在黄体期(第22至25天之间)。黄体期血清孕酮> 3 ng / mL的妇女被分类为第1组(N = 4),而其他人被分类为第2组(N = 7)。与第1组的卵泡期相比,黄体期运动后的尿量(213 /-80 vs 309 /-113 mL)和比重(1.008 /-0.003 vs 1.006 /-0.002)发生了变化(P <0.05) 。在第2组中,没有观察到这些参数对月经周期的依赖性。黄体(3.10 /-0.81 g m-2 min-1)的发汗率高于卵泡期(2.80 /-0.64 gm)(P <0.05) (-2)min(-1))仅在第1组中。运动期间,在直肠温度,心率,感知的劳累率,平均皮肤温度以及运动前后,与月经周期相关的差异均未发现体重。在温暖和潮湿的环境中进行饮水运动的妇女似乎能够通过减少尿量和增加出汗率来适应黄体期基础体温的升高。
  • 【一项静息研究表明,静息的心率可以预测缺血性中风后的抑郁和认知能力。】 复制标题 收藏 收藏
    DOI:10.1016/j.jstrokecerebrovasdis.2017.05.040 复制DOI
    作者列表:Tessier A,Sibon I,Poli M,Audiffren M,Allard M,Pfeuty M
    BACKGROUND & AIMS: BACKGROUND:Early detection of poststroke depression (PSD) and cognitive impairment (PSCI) remains challenging. It is well documented that the function of autonomic nervous system is associated with depression and cognition. However, their relationship has never been investigated in the early poststroke phase. This pilot study aimed at determining whether resting heart rate (HR) parameters measured in early poststroke phase (1) are associated with early-phase measures of depression and cognition and (2) could be used as new tools for early objective prediction of PSD or PSCI, which could be applicable to patients unable to answer usual questionnaires. METHODS:Fifty-four patients with first-ever ischemic stroke, without cardiac arrhythmia, were assessed for resting HR and heart rate variability (HRV) within the first week after stroke and for depression and cognition during the first week and at 3 months after stroke. RESULTS:Multiple regression analyses controlled for age, gender, and stroke severity revealed that higher HR, lower HRV, and higher sympathovagal balance (low-frequency/high-frequency ratio of HRV) were associated with higher severity of depressive symptoms within the first week after stroke. Furthermore, higher sympathovagal balance in early phase predicted higher severity of depressive symptoms at the 3-month follow-up, whereas higher HR and lower HRV in early phase predicted lower global cognitive functioning at the 3-month follow-up. CONCLUSIONS:Resting HR measurements obtained in early poststroke phase could serve as an objective tool, applicable to patients unable to complete questionnaires, to help in the early prediction of PSD and PSCI.
    背景与目标: 背景:早期检测中风后抑郁症(PSD)和认知障碍(PSCI)仍然具有挑战性。有充分的文献证明,自主神经系统的功能与抑郁和认知有关。但是,他们的关系在中风后早期还没有被研究过。这项前瞻性研究旨在确定卒中后早期阶段的静息心率(HR)参数是否与抑郁和认知的早期阶段指标相关;(2)可用作早期客观预测PSD的新工具或PSCI,可能适用于无法回答常规问卷的患者。
    方法:对54例首次有缺血性中风的无心律失常的患者进行评估,评估其在卒中后第一周内的心率和心率变异性(HRV),以及在卒中后第一周和3个月内的抑郁和认知能力。
    结果:对年龄,性别和中风严重程度进行的多项回归分析显示,较高的HR,较低的HRV和较高的交感神经平衡(HRV的低频/高频比)与第一周内抑郁症状的严重程度较高相关中风后。此外,较高的早期交感神经平衡表示在3个月的随访中抑郁症状的严重程度较高,而较高的HR和较低的HRV则表明在3个月的随访中总体认知功能较低。
    结论:中风后早期恢复HR测量值可作为客观工具,适用于无法完成问卷调查的患者,有助于PSD和PSCI的早期预测。
  • 【Solea solea唯一proopiomelanocortin(POMC)cDNA的克隆以及放养密度对POMC mRNA和生长速率的影响。】 复制标题 收藏 收藏
    DOI:10.1016/j.ygcen.2007.05.003 复制DOI
    作者列表:Palermo F,Nabissi M,Cardinaletti G,Tibaldi E,Mosconi G,Polzonetti-Magni AM
    BACKGROUND & AIMS: :Proopiomelanocortin (POMC) is an important gene implicated in different functions, such as the stress response of the hypothalamus-pituitary-adrenal axis. The aim of the present study was to determine whether farming conditions, such as stocking density, can be considered a powerful stressor influencing in turn the growth rate in juvenile fish. Thus, POMC cDNA expression was investigated during adaptation to farming conditions in sole (Solea solea), as a model for studying the effects of rearing densities on stress response; different stocking densities (50, 100, and 250 animals/m(2)) were applied and, after 7 and 21 days, the fishes were examined for body weight and plasma cortisol levels as indicators of stress. In addition, proopiomelanocortin was cloned and sequenced from the brain of sole, allowing semi-quantitative RT-PCR to be performed to evaluate POMC mRNA expression in brain tissue. There was a significant increase in cortisol levels in fish reared at high stocking densities of 250/m(2) compared to fish reared at control densities of 100 and 50/m(2), in both experimental times, i.e., 7 and 21 days. The high stocking densities were also found to decrease the specific growth rate of fish. Moreover, it was demonstrated that the highest stocking density induced a significant decrease in sole POMC mRNA expression. It is concluded that POMC and cortisol are both involved in the stress response due to high rearing densities, during which cortisol may serve as a negative regulator of POMC.
    背景与目标: :Proopiomelanocortin(POMC)是一个重要的基因,涉及不同的功能,例如下丘脑-垂体-肾上腺轴的应激反应。本研究的目的是确定养殖条件,例如放养密度,是否可以被认为是反过来影响幼鱼生长速度的强大压力源。因此,在鞋底适应不同耕作条件的过程中,研究了POMC cDNA的表达(Solea solea),作为研究饲养密度对胁迫反应的影响的模型。应用不同的放养密度(50、100和250动物/平方米(2)),并在7天和21天后,检查鱼的体重和血浆皮质醇水平,作为压力指标。此外,从足底的大脑中克隆了proopiomelanocortin,并对其进行了测序,从而可以进行半定量RT-PCR来评估脑组织中POMC mRNA的表达。在两个实验时间内(即7天和21天),与以100和50 / m(2)的对照密度饲养的鱼相比,以250 / m(2)的高饲养密度饲养的鱼的皮质醇水平显着增加。 。还发现高放养密度降低了鱼类的比生长速度。而且,已经证明最高的放养密度引起单独的POMC mRNA表达的显着降低。结论是,由于高饲养密度,POMC和皮质醇都参与了应激反应,在此期间皮质醇可能是POMC的负调节剂。
  • 【单一肌肉纤维中严格状态发展速率对其张力的影响。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Khromov AS,Srebnitskaya LK,Lednev VV
    BACKGROUND & AIMS: :The rigor tension and stiffness of glycerinated fibres from rabbit psoas muscle were found to vary markedly in dependence on the rate of substitution of the solutions in the experimental chamber. The maximum value of rigor tension, which is close to that activated by Ca2+ with pCa4, was obtained at the slow development of rigor in the absence of Ca2+ ions. The observed dependence is assumed to be due to the different degrees of removal of the 'slack' in fibres, which may be contributed by compliant ends of the preparation. A new method allowing to obtain rather reproducible values of rigor tension is proposed.
    背景与目标: :发现来自兔腰大肌的甘油纤维的严格张力和刚度显着变化,这取决于溶液在实验室中的替代率。在没有Ca2离子的情况下,在缓慢的严酷条件下获得了接近于Ca2激活的pCa4的严酷条件张力的最大值。假定观察到的依赖性是由于去除纤维中“松弛”的程度不同,这可能是由制剂的柔顺性端头造成的。提出了一种新的方法,该方法能够获得相当可再现的严格张力值。
  • 【左心室收缩功能不全患者小波变换模量最大值与心率的多重分形趋势波动分析的比较。】 复制标题 收藏 收藏
    DOI:10.1111/j.1542-474X.2008.00215.x 复制DOI
    作者列表:Galaska R,Makowiec D,Dudkowska A,Koprowski A,Chlebus K,Wdowczyk-Szulc J,Rynkiewicz A
    BACKGROUND & AIMS: BACKGROUND:In recent years the WTMM (wavelet transform modulus maxima) and MDFA (multifractal detrended fluctuation analysis) methods have become widely used techniques for the determination of nonlinear, multifractal heart rate (HR) dynamics. The purpose of our study was to compare multifractal parameters of heart rate calculated using both methods in a group of 90 patients with reduced left ventricular systolic function (rlvs group) and in a group of 39 healthy persons (nsr group). METHODS:For each subject from the rlvs group (LVEF < or =40%) and the nsr group, a 24-hour ECG Holter monitoring was performed. The width of the multifractal spectrum and global Hurst exponent were calculated by means of WTMM and MDFA methods for 5-hour daytime and nighttime subsets. RESULTS:The width of the multifractal spectrum was significantly lower and the Hurst exponent was significantly higher in rlvs group in comparison to nsr group both during diurnal activity and nocturnal rest according to MDFA and only during diurnal activity according to WTMM method. In both groups we observed significant differences of the multifractal spectrum width and the global Hurst exponent between the nighttime and daytime recordings. CONCLUSIONS:MDFA seems to be more sensitive as compared with WTMM method in differentiation between multifractal properties of the heart rate in healthy subjects and patients with left ventricular systolic dysfunction.
    背景与目标: 背景:近年来,WTMM(小波变换模极大值)和MDFA(多重分形趋势波动分析)方法已成为广泛用于确定非线性,多重分形心率(HR)动力学的技术。我们研究的目的是比较90例左室收缩功能降低的患者(rlvs组)和39例健康人的组(nsr组)使用两种方法计算的心率的多重分形参数。
    方法:对来自rlvs组(LVEF <或= 40%)和nsr组的每位受试者进行24小时ECG动态心电图监测。利用WTMM和MDFA方法,针对5小时的白天和夜间子集,计算了多重分形谱的宽度和整体赫斯特指数。
    结果:根据MDFA,rlvs组的昼夜活动和夜间休息时,多重分形谱的宽度明显小于nsr组,Hurst指数显着较高;仅根据WTMM方法,在昼间活动时,多重分形谱的宽度较nsr组高。在两组中,我们观察到夜间和白天记录之间的多重分形谱宽度和全局赫斯特指数存在显着差异。
    结论:与WTMM方法相比,MDFA在区分健康受试者和左室收缩功能不全患者的心率的多重分形特性方面似乎更为敏感。
  • 【前列腺的大小和体积对12项核心前列腺活检的癌症检出率的影响。】 复制标题 收藏 收藏
    DOI:10.1007/s11255-006-9078-5 复制DOI
    作者列表:Ozden E,Turgut AT,Talas H,Yaman O,Göğüş O
    BACKGROUND & AIMS: PURPOSE:To evaluate if volume or any of the three dimensions of prostate influences cancer detection rate by 12-core transrectal ultrasound (TRUS) guided prostate biopsy. MATERIALS AND METHODS:We have searched our database for patients who underwent 12 core TRUS guided prostate biopsy with PSA values between 4.0 and 9.9 ng/ml, benign digital exam and no suspicious lesions at TRUS. The measurements of three dimensions and volume of the prostate of 99 patients were correlated with cancer detection rates of biopsy. RESULTS:There were no statistically significant differences between patients with prostate cancer or with benign histopathologic result for mean age, PSA and % PSA. Patients without cancer had a significantly higher mean prostate volume (58.88 cc) than patients with cancer (48.85 cc) (P = 0.038). A volume of 48.5 cc was determined as a cut-off value above which cancer detection rate decreases. Of the three dimensions, only the difference for the craniocaudal dimension between benign and malignant groups was marginally significant (P = 0.052). CONCLUSIONS:With 12 core biopsy, cancer detection rate is lower in patients with prostates larger than 48.5 cc. Further studies comparing biopsy results with prostatectomy specimens can clarify whether these results necessitates higher number of cores for such patients.
    背景与目标: 目的:通过12芯经直肠超声(TRUS)引导的前列腺活检,评估前列腺的体积或三个维度中的任何一个是否会影响癌症的检出率。
    材料和方法:我们已经搜索了数据库,以进行12例TRUS指导的前列腺活检,PSA值在4.0到9.9 ng / ml之间的患者,进行了良性数字化检查,在TRUS时没有可疑的病变。 99例患者的前列腺的三个维度和体积的测量值与活检的癌症检出率相关。
    结果:前列腺癌或组织学检查结果良好的前列腺癌患者的平均年龄,PSA和%PSA无统计学差异。没有癌症的患者的平均前列腺体积(58.88 cc)明显高于患有癌症的患者(48.85 cc)(P = 0.038)。确定48.5cc的体积作为临界值,在该临界值以上,癌症检测率降低。在这三个维度中,仅良性和恶性组之间的颅尾尺寸差异很小(P = 0.052)。
    结论:经12次核心活检,前列腺癌大于48.5 cc的患者的癌症检出率较低。将活检结果与前列腺切除术标本进行比较的进一步研究可以阐明这些结果是否需要为此类患者提供更多的核心。
  • 【选择和近交抑郁:近交率和近亲环境的影响。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Swindell WR,Bouzat JL
    BACKGROUND & AIMS: :The magnitude of inbreeding depression in small populations may depend on the effectiveness with which natural selection purges deleterious recessive alleles from populations during inbreeding. The effectiveness of this purging process, however, may be influenced by the rate of inbreeding and the environment in which inbreeding occurs. Although some experimental studies have examined these factors individually, no study has examined their joint effect or potential interaction. In the present study, therefore, we performed an experiment in which 180 lineages of Drosophila melanogaster were inbred at slow and fast inbreeding rates within each of three inbreeding environments (benign, high temperature, and competitive). The fitness of all lineages was then measured in a common benign environment. Although slow inbreeding reduced inbreeding depression in lineages inbred under high temperature stress, a similar reduction was not observed with respect to the benign or competitive treatments. Overall, therefore, the effect of inbreeding rate was nonsignificant. The inbreeding environment, in contrast, had a larger and more consistent effect on inbreeding depression. Under both slow and fast rates of inbreeding, inbreeding depression was significantly reduced in lineages inbred in the presence of a competitor D. melanogaster strain. A similar reduction of inbreeding depression occurred in lineages inbred under high temperature stress at a slow inbreeding rate. Overall, our findings show that inbreeding depression is reduced when inbreeding takes place in a stressful environment, possibly due to more effective purging under such conditions.
    背景与目标: :小种群中近交抑郁的严重程度可能取决于自然选择在近交过程中清除种群中有害的隐性等位基因的有效性。然而,该吹扫过程的有效性可能受到近交率和近交发生环境的影响。尽管一些实验研究单独检查了这些因素,但没有研究检查它们的联合作用或潜在的相互作用。因此,在本研究中,我们进行了一项实验,其中在三个近交环境(良性,高温和竞争性)中,分别以慢速和快速近交率近交了180个果蝇果蝇。然后在一个普通的良性环境中测量所有血统的适应性。尽管缓慢的近交减少了在高温胁迫下近交的血统的近交衰退,但在良性或竞争性处理方面未观察到类似的减少。因此,总的来说,近交率的影响不显着。相反,近交环境对近交抑郁症具有更大和更一致的影响。在近交速度和近交速度下,在存在竞争性D. melanogaster毒株的情况下,近交沮丧感在自交系谱系中均显着降低。在高温胁迫下以近交速率缓慢繁殖的近亲谱系发生了近交抑制的相似减少。总体而言,我们的研究结果表明,在压力环境中进行近亲繁殖时,近亲凹陷减少了,这可能是由于在这种条件下进行更有效的清除所致。
  • 【选择性iNOS抑制对链脲佐菌素诱发的糖尿病大鼠内毒素休克的全身血流动力学和死亡率的影响。】 复制标题 收藏 收藏
    DOI:10.1097/SHK.0b013e31804d452d 复制DOI
    作者列表:Kadoi Y,Goto F
    BACKGROUND & AIMS: :The purpose of this study was to examine whether selective iNOS inhibition can restore the hemodynamic changes and reduce the nitrotyrosine levels in the cerebral cortex of rats with streptozotocin-induced diabetes during endotoxin-induced shock. The study was designed to include three sets of experiments: (1) measurement of changes in systemic hemodynamics, (2) measurement of biochemical variables, including iNOS activity and nitrotyrosine formation in the brain, and (3) assessment of mortality rate. Rats were randomly divided into four groups: group 1, control; group 2, LPS: Escherichia coli endotoxin, 10.0 mg/kg (i.v.) bolus; group 3 (i.v.) LPS and L-N6-(1-iminoethyl)-lysine (L-NIL), 4mg/kg (i.p.); and group 4, LPS and NG-nitro-L-arginine methyl ester (L-NAME), 5 mg/kg (i.p.). In nondiabetic rats, administration of L-NIL prevented the hemodynamic and biochemical changes, and increases in plasma nitrite and cerebral nitrotyrosine levels induced by LPS. Administration of L-NAME partially prevented these LPS-induced changes. On the other hand, in diabetic rats, administration of L-NIL only partially prevented the hemodynamic and biochemical changes, and increases in plasma nitrite and cerebral nitrotyrosine levels associated with LPS. Administration of L-NAME, however, had no effects on these LPS-induced changes in diabetic rats. There was a significant difference in nitrotyrosine levels between nondiabetic and diabetic rats in groups 2, 3, and 4 at 2 and 3 h after the treatment (at 3 h; nondiabetic--control, 4.6 +/- 0.4; LPS (i.v.), 8.9 +/- 1.0, LPS (i.v.) + L-NIL, 4.7 +/- 0.5; LPS (i.v.) + L-NAME, 7.1 +/- 0.9; diabetic--control, 5.5 +/- 0.4; LPS (i.v.), 13.6 +/- 1.2; LPS (i.v.) + L-NIL, 9.0 +/- 0.9; LPS (i.v.) + L-NAME, 13.0 +/- 1.0; densitometric units). Insulin therapy resulted in a decrease in iNOS activity (at 3 h: 1.0 +/- 0.5 fmol mg min), nitrotyrosine formation (at 3 h; 5.0 +/- 0.5, densitometric units), and mortality rates (30% at 6 h, 50% at 12 h) in the LPS (i.v.) + L-NIL group of diabetic rats. Selective iNOS inhibition in diabetic rats could not improve hemodynamic instability, chemical changes, iNOS activity, and nitrotyrosine formation during septic shock compared with the improvements observed in nondiabetic rats. Tight glucose control along with administration of L-NIL can result in more effective restoration of the biochemical changes of septicemia in diabetic rats. Thus, hyperglycemia may be one of the mechanisms related to the aggravation of endotoxin-induced shock.
    背景与目标: :本研究的目的是研究选择性内源性iNOS抑制能否在内毒素诱导的休克期间恢复链脲佐菌素诱发的糖尿病大鼠的血流动力学变化并降低其大脑皮质的硝基酪氨酸水平。该研究被设计为包括三组实验:(1)测量全身血流动力学的变化,(2)测量生化变量,包括iNOS活性和脑中硝基酪氨酸的形成,以及(3)死亡率评估。将大鼠随机分为四组:第1组,对照组;第2组,第2组。第2组,LPS:大肠埃希菌内毒素,每次推注10.0 mg / kg(i.v.);第3组(静脉)LPS和L-N6-(1-亚氨基乙基)-赖氨酸(L-NIL),4mg / kg(腹膜);第4组,LPS和NG-硝基-L-精氨酸甲酯(L-NAME),5 mg / kg(腹膜内)。在非糖尿病大鼠中,L-NIL的给药阻止了血流动力学和生化变化,并增加了LPS诱导的血浆亚硝酸盐和脑硝基酪氨酸水平。 L-NAME的管理部分阻止了这些LPS引起的变化。另一方面,在糖尿病大鼠中,L-NIL的施用仅部分阻止了血流动力学和生化变化,并增加了与LPS相关的血浆亚硝酸盐和脑硝基酪氨酸水平。但是,在糖尿病大鼠中,L-NAME的给药对这些LPS诱导的变化没有影响。第2、3和4组的非糖尿病和糖尿病大鼠在治疗后2和3 h的硝酸酪氨酸水平存在显着差异(3 h;非糖尿病对照组4.6 /-0.4; LPS(iv)8.9) /-1.0,LPS(iv)L-NIL,4.7 /-0.5; LPS(iv)L-NAME,7.1 /-0.9;糖尿病对照,5.5 /-0.4; LPS(iv),13.6 /-1.2; LPS(iv)L-NIL,9.0 /-0.9; LPS(iv)L-NAME,13.0 /-1.0;光密度单位)。胰岛素治疗导致iNOS活性(3 h:1.0 /-0.5 fmol mg min),硝基酪氨酸形成(3 h; 5.0 /-0.5,光密度单位)和死亡率(6h,50时30%)降低LPS(iv)L-NIL组的糖尿病大鼠在12 h时的%)。与非糖尿病大鼠相比,对糖尿病大鼠的选择性iNOS抑制不能改善败血性休克期间的血流动力学不稳定,化学变化,iNOS活性和硝基酪氨酸形成。严格的葡萄糖控制以及L-NIL的使用可以使糖尿病大鼠败血病的生化变化更有效地恢复。因此,高血糖症可能是与内毒素诱发的休克加重有关的机制之一。
  • 【细菌蛋白合成的速度和准确性。】 复制标题 收藏 收藏
    DOI:10.1016/j.mib.2008.02.015 复制DOI
    作者列表:Johansson M,Lovmar M,Ehrenberg M
    BACKGROUND & AIMS: :Our understanding of the accuracy of tRNA selection on the messenger RNA programmed ribosome has recently increased dramatically because of high-resolution crystal structures of the ribosome, cryo-electron microscopy reconstructions of its functional complexes, and fast kinetics experiments. Application of single-molecule spectroscopy with fluorescence resonance energy transfer to studies of tRNA selection by the ribosome has also provided new, albeit controversial, insights. Interestingly, when the fundamental trade-off between rate and accuracy in substrate-selective biosynthetic reactions is taken into account, some aspects of the current models of ribosome function appear strikingly suboptimal in the context of growing bacterial cells.
    背景与目标: :由于对核糖体的高分辨率晶体结构,其功能复合物的冷冻电子显微镜重建以及快速的动力学实验,我们对信使RNA程序化核糖体上tRNA选择准确性的了解最近得到了极大的提高。具有荧光共振能量转移的单分子光谱技术在核糖体选择tRNA的研究中的应用,尽管有争议,但也提供了新的见解。有趣的是,当考虑到底物选择性生物合成反应的速率和准确度之间的基本权衡时,在细菌细胞生长的背景下,核糖体功能的当前模型的某些方面显得次优。
  • 【增长速度的热反应范式中的种群间和种群内变化:具有遗传约束的等温线中的纬度补偿的演变。】 复制标题 收藏 收藏
    DOI:10.1111/j.1558-5646.2007.00130.x 复制DOI
    作者列表:Yamahira K,Kawajiri M,Takeshi K,Irie T
    BACKGROUND & AIMS: :In ectotherms, lower temperatures in high-latitude environments would theoretically reduce the annual growth rates of individuals. If slower growth and resultant smaller body size reduce fitness, individuals in higher latitudes may evolve compensatory responses. Two alternative models of such latitudinal compensation are possible: Model I: thermal reaction norms for growth rates of high-latitude individuals may be horizontally shifted to a lower range of temperatures, or Model II: reaction norms may be vertically shifted so that high-latitude individuals can grow faster across all temperatures. Model I is expected when annual growth rates in the wild are only a function of environmental temperatures, whereas Model II is expected when individuals in higher latitudes can only grow during a shorter period of a year. A variety of mixed strategies of these two models are also possible, and the magnitude of horizontal versus vertical variation in reaction norms among latitudinal populations will be indicative of the importance of "temperature" versus "seasonality" in the evolution of latitudinal compensation. However, the form of latitudinal compensation may be affected by possible genetic constraints due to the genetic architecture of reaction norms. In this study, we examine the inter- and intrapopulation variations in thermal reaction norms for growth rate of the medaka fish Oryzias latipes. Common-environment experiments revealed that average reaction norms differed primarily in elevation among latitudinal populations in a manner consistent with Model II (adaptation to "seasonality"), suggesting that natural selection in high latitudes prefers individuals that grow faster even within a shorter growing season to individuals that have longer growing seasons by growing at lower temperatures. However, intrapopulation variation in reaction norms was also vertical: some full-sibling families grew faster than others across all temperatures examined. This tendency in intrapopulation genetic variation for thermal reaction norms may have restricted the evolution of latitudinal compensation, irrespective of the underlying selection pressure.
    背景与目标: :在等温线中,高纬度环境中的低温理论上会降低个人的年增长率。如果较慢的生长和由此产生的较小的体型降低了适应性,则高纬度地区的人们可能会出现代偿性反应。这种纬度补偿的两个替代模型是可能的:模型I:高纬度个体生长速率的热反应规范可以水平移动到较低的温度范围,或者模型II:反应规范可以垂直移动以使高纬度个人可以在所有温度下更快地成长。当野外的年增长率仅是环境温度的函数时,可以预期为模型I,而当纬度较高的人只能在较短的一年内增长时,则可以预测为模型II。这两种模型的多种混合策略也是可能的,并且在纬度种群之间反应规范的水平相对于垂直变化的大小将指示“温度”相对于“季节性”在纬度补偿演变中的重要性。但是,由于反应规范的遗传结构,纬度补偿的形式可能会受到可能的遗传约束的影响。在这项研究中,我们研究了aka对印度med鱼Oryzias latipes生长速度的热反应规范中的种群间和种群内变化。共同环境实验表明,平均反应规范主要在纬度种群之间以与II型一致(适应“季节性”)的方式在海拔高度上有所不同,这表明高纬度地区的自然选择更倾向于即使在较短的生长季节中生长速度更快的个体也比生长在较低温度下的生长季节较长的个体。但是,种群内反应规范的变化也是垂直的:在所有考察的温度范围内,一些全兄弟家庭的生长速度快于其他家庭。无论潜在的选择压力如何,热反应范围内种群遗传变异的这种趋势都可能限制了纬度补偿的演变。
  • 【急性缺氧对清醒犬心率和血压变异性的影响。】 复制标题 收藏 收藏
    DOI:10.1152/ajpheart.2000.279.5.H2344 复制DOI
    作者列表:Yasuma F,Hayano JI
    BACKGROUND & AIMS: :To examine whether the impacts of hypoxia on autonomic regulations involve the phasic modulations as well as tonic controls of cardiovascular variables, heart rate, blood pressure, and their variability during isocapnic progressive hypoxia were analyzed in trained conscious dogs prepared with a permanent tracheostomy and an implanted blood pressure telemetry unit. Data were obtained at baseline and when minute ventilation (VI) first reached 10 (VI10), 15 (VI15), and 20 (VI20) l/min during hypoxia. Time-dependent changes in the amplitudes of the high-frequency component of the R-R interval (RRIHF) and the low-frequency component of mean arterial pressure (MAPLF) were analyzed by complex demodulation. In a total of 47 progressive hypoxic runs in three dogs, RRIHF decreased at VI15 and VI20 and MAPLF increased at VI10 and VI15 but not at VI20, whereas heart rate and arterial pressure increased progressively with advancing hypoxia. We conclude that the autonomic responses to isocapnic progressive hypoxia involve tonic controls and phasic modulations of cardiovascular variables; the latter may be characterized by a progressive reduction in respiratory vagal modulation of heart rate and a transient augmentation in low-frequency sympathetic modulation of blood pressure.
    背景与目标: :为了检验缺氧对自主神经调节的影响是否包括调相以及对心血管变量,心率,血压的强直控制以及在等碳酸血症进行性缺氧期间其可变性的影响,方法是在经过训练的清醒犬中进行永久性气管造口术和麻醉。植入式血压遥测单元。在基线时以及缺氧期间分钟通气量(VI)首次达到10(VI10),15(VI15)和20(VI20)l / min时获得数据。通过复杂解调分析了R-R间隔的高频分量(RRIHF)和平均动脉压的低频分量(MAPLF)随时间变化的幅度。在三只狗中,总共进行了47次进行性低氧,在VI15和VI20时RRIHF降低,而在VI10和VI15时MAPLF升高,但在VI20时则没有,而心率和动脉压随着缺氧而逐渐增加。我们得出的结论是,对等容量渐进性缺氧的自主神经反应涉及进补控制和心血管变量的阶段性调节。后者的特点可能是呼吸迷走性心率调节逐渐降低,而低频交感神经调节血压则短暂升高。

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