生物体砷代谢及其相关酶与蛋白的研究概况

砷在自然界分布广泛,主要以砷化物的形式存在,具有较强毒性。可通过多种途径进入人类的生活环境引起健康危害,砷代谢过程涉及到复杂的酶促或非酶促反应过程,近年来以砷代谢为突破口的砷中毒发病机制探索成为新的研究热点,本文就有关砷在生物体内代谢方面的研究做一综述,以期有助于慢性砷中毒作用机制的研究。     

饥荒造成的营养不良对成年后患代谢综合征的影响

研究生命早期因食物短缺造成的营养不良对成年后患代谢综合征（Metabolic syndrome,MS）的影响．探讨成年人慢性病的起因．为制订妇女儿童营养改善政策提供科学依据．对2005—2008年上半年重庆医科大学附属第一医院体检中心体检资料进行整群抽样．选出14917例样本．将三年自然灾害（1959～1961年）出生的研究对象3650例（G2组）作为受灾害影响人群,将灾害之前（1955～1957年）出生的4497例体检人群（G1组）和灾害之后（1963～1965年）6770例体检人群作为未受灾害影响人群（G3组）,比较3组人群体质指数、血糖值、血压值及血脂值4项MS各分项判断指标．运用SAS9．1分析MS发生情况．G1组检出MS463例,占G1组总人数的10．30％：G2组检出MS403例,占G2组总人数的11．04％：G3组检出MS609侧．占G3组总人数的9．00％．组间比较有统计学意义．男性检出MS1326例．患病率为14．06％．女性检出MS149例,患病率为2．72％．饥荒造成的机体早期营养不良与成年后患MS有关,对MS影响严重程度依次为血脂紊乱〉体质指数超标〉血压超标〉血糖超标．且男性比女性受影响显著,差异有统计学意义．故在选择孕妇、乳母以及婴幼儿饮食上,科学的供给和合理的配比显得尤为重要．可以借以提高整体人群的生存质量．     

代谢酶的非经典功能及代谢感知

代谢是基本的生命活动,代谢网络以代谢酶和代谢物为中心,为细胞的生命活动提供物质和能量基础。一方面,代谢酶发挥经典的功能,催化不同代谢通路中的代谢物,并受到严密调控,维持代谢稳态。另一方面,近年来国内外的研究,包括我们研究团队的工作证实了某些代谢酶和代谢物还可发挥非经典的兼有功能(moonlighting functions),参与信号通路调控和/或作为一个信号分子,对代谢进行更精细的调控,在机体的生理和病理过程中发挥关键作用。     

自噬与代谢及代谢性疾病

细胞自噬是真核生物中一种高度保守的代谢过程,可以清除受损的细胞器,降解糖原、脂类、蛋白质等生物大分子物质供细胞重新利用,对维持细胞内代谢平衡有重要意义。自噬障碍常被发现与代谢性疾病相关,如酸性麦芽糖酶缺乏症、肥胖和神经退行性疾病等。该文就近年来关于自噬与代谢及代谢性疾病的研究作一综述。     

生命活动中信息传递的形态

阐述了生命活动过程中信息传递的形态,强调了信息传递与生命活动的关系,说明了生命活动是以一定的信息传递形态方式进行的。     

基于代谢流量分布信息理解大肠杆菌中异柠檬酸裂解酶调节因子的代谢调控作用

基因的表达受不同的转录调节因子调节。大肠杆菌中的异柠檬酸裂解酶调节因子(IclR)能够抑制编码乙醛酸支路酶的aceBAK操纵子的表达。本研究基于代谢物的13C同位体物质分布来定量解析代谢反应,主要研究了iclR基因在大肠杆菌生理和代谢中的作用。大肠杆菌iclR基因缺失突变株的生长速率、糖耗速率和乙酸的产量相对于原始菌株都有所降低,但菌体得率略有增加。通过代谢途径的流量比率分析发现基因缺失株的乙醛酸支路得到了激活,33%的异柠檬酸流经了乙醛酸支路;戊糖磷酸途径的流量变小,使得CO2的生成量减少。同时,乙醛酸支路激活,但草酰乙酸形成磷酸烯醇式丙酮酸的流量基本不变,说明磷酸烯醇式丙酮酸-乙醛酸循环没有激活,没有过多的碳原子在磷酸烯醇式丙酮酸羧化激酶反应中以CO2形式排出,从而确保了菌体得率。葡萄糖利用速率的降低、乙酰辅酶A的代谢效率提高等使得iclR基因敲除菌的乙酸分泌较原始菌株有所降低。     

基于真实情境的"人体代谢废物的排出"的专题复习

以"人体代谢废物的排出"的专题复习为例,创设"肾脏疾病患者的诊断和治疗及肾病预防方法"这一真实情境,培养学生应用知识解决实际问题的能力.同时,借助病理学中肾脏的异常结构,培养学生的生命观念和科学思维.     

一张适用于总结物质代谢途径的代谢联络图

介绍了一张适用于总结物质代谢途径之间相互联系的代谢联络图。通过此图可让学生对营养物质代谢、能量代谢及其彼此之间的联系有一个整体的认识,还可显现出各条代谢途径间的枢纽性物质,以总结归纳这些物质的来源和去路,并在分子水平上阐明与代谢有关的某些疾病的原因。     

代谢调衡饮对代谢综合征胰岛素抵抗的影响

目的:初步探讨代谢调衡饮对代谢综合征胰岛素抵抗的影响。方法:将60例代谢综合征患者随机分为试验组和对照组,对照组口服卡托普利和二甲双胍,试验组在此基础上加服代谢调衡饮,疗程3个月。结果:两组各个时间点的血糖和HbA1c与治疗前相比,均有显著下降(P<0.01);显著降低空腹、糖负荷后0.5h、1h、2h、3h胰岛素水平(P<0.01),与对照组相比,试验组降低糖负荷后0.5h胰岛素水平更具优势(P<0.01);明显降低HOMA-IR,升高ISI。结论:代谢调衡饮对于改善代谢综合征患者的胰岛素抵抗具有一定疗效。     

天蚕的呼吸代谢

天蚕AntheraeayamamaiGuerin是一种天蚕蛾科柞蚕属的大型野生绢丝昆虫。天蚕丝因其独特的色泽和质地,而被誉为“绿色金子”。近年来,有关天蚕的开发利用研究已引起我国蚕业界的重视,在天蚕的生物学、形态学、饲育与制种、茧丝加工等方面已有许多报道[1],而生理学方面的研究尚很薄弱。本文着重报道天蚕五龄幼虫及蛹期的呼吸代谢变化规律。l材料与方法试虫由山东省蚕业研究所沈孝行先生提供。实验室内自然温度下用麻株Q。rcusacvtiss加a鲜叶单头饲养所获之蛹。本试验于1995年6～7月进行。取五龄起蚕雌雄各1头用CYES—11型0。、CO。气…     

On the observable transition to living matter

In recent developments in chemistry and genetic engineering, the humble researcher dealing with the origin of life finds her(him)self in a grey area of tackling something that even does not yet have a clear definition agreed upon. A series of chemical steps is described to be considered as the life-nonlife transition, if one adheres to the minimalistic definition: life is self-reproduction with variations. The fully artificial RNA system chosen for the exploration corresponds sequence-wise to the reconstructed initial triplet repeats, presumably corresponding to the earliest protein-coding molecules. The demonstrated occurrence of the mismatches (variations) in otherwise complementary syntheses ("self-reproduction"), in this RNA system, opens an experimental and conceptual perspective to explore the origin of life (and its definition), on the apparent edge of the origin.     

Applications of a parametric model for informative censoring

In this article, we explore the use of a parametric model (for analyzing survival data) which is defined to allow sensitivity analysis for the presence of informative censoring. The dependence between the failure and the censoring processes is expressed through a parameter delta and a general bias function B(t, theta). We calculate the expectation of the potential bias due to informative censoring, which is an overall measure of how misleading our results might be if censoring is actually nonignorable. Bounds are also calculated for quantities of interest, e.g., parameter of the distribution of the failure process, which do not depend on the choice of the bias function for fixed delta. An application that relates to systematic lupus erythematosus data illustrates how additional information can result in reducing the uncertainty on estimates of the location parameter. Sensitivity analysis on a relative risk parameter is also explored.     

Studying fatty aldehyde metabolism in living cells with pyrene-labeled compounds

The lack of fatty aldehyde dehydrogenase function in Sjögren Larsson Syndrome (SLS) patient cells not only impairs the conversion of fatty aldehydes into their corresponding fatty acid but also has an effect on connected pathways. Alteration of the lipid profile in these cells is thought to be responsible for severe symptoms such as ichtyosis, mental retardation, and spasticity. Here we present a novel approach to examine fatty aldehyde metabolism in a time-dependent manner by measuring pyrene-labeled fatty aldehyde, fatty alcohol, fatty acid, and alkylglycerol in the culture medium of living cells using HPLC separation and fluorescence detection. Our results show that in fibroblasts from SLS patients, fatty aldehyde is not accumulating but is converted readily into fatty alcohol. In control cells, in contrast, exclusively the corresponding fatty acid is formed. SLS patient cells did not display a hypersensitivity toward hexadecanal or hexadecanol, but 3-fold lower concentrations of the fatty alcohol than the corresponding fatty aldehyde were needed to induce toxicity in SLS patient and in control cells.     

Joint modeling and analysis of longitudinal data with informative observation times

Summary .  In analysis of longitudinal data, it is often assumed that observation times are predetermined and are the same across study subjects. Such an assumption, however, is often violated in practice. As a result, the observation times may be highly irregular. It is well known that if the sampling scheme is correlated with the outcome values, the usual statistical analysis may yield bias. In this article, we propose joint modeling and analysis of longitudinal data with possibly informative observation times via latent variables. A two-step estimation procedure is developed for parameter estimation. We show that the resulting estimators are consistent and asymptotically normal, and that the asymptotic variance can be consistently estimated using the bootstrap method. Simulation studies and a real data analysis demonstrate that our method performs well with realistic sample sizes and is appropriate for practical use.     

Use of summary measures to adjust for informative missingness in repeated measures data with random effects

We discuss how to apply the conditional informative missing model of Wu and Bailey (1989, Biometrics 45, 939-955) to the setting where the probability of missing a visit depends on the random effects of the primary response in a time-dependent fashion. This includes the case where the probability of missing a visit depends on the true value of the primary response. Summary measures for missingness that are weighted sums of the indicators of missed visits are derived for these situations. These summary measures are then incorporated as covariates in a random effects model for the primary response. This approach is illustrated by analyzing data collected from a trial of heroin addicts where missed visits are informative about drug test results. Simulations of realistic experiments indicate that these time-dependent summary measures also work well under a variety of informative censoring models. These summary measures can achieve large reductions in estimation bias and mean squared errors relative to those obtained by using other summary measures.     

Factor analytic models of clustered multivariate data with informative censoring

This article describes a general class of factor analytic models for the analysis of clustered multivariate data in the presence of informative missingness. We assume that there are distinct sets of cluster-level latent variables related to the primary outcomes and to the censoring process, and we account for dependency between these latent variables through a hierarchical model. A linear model is used to relate covariates and latent variables to the primary outcomes for each subunit. A generalized linear model accounts for covariate and latent variable effects on the probability of censoring for subunits within each cluster. The model accounts for correlation within clusters and within subunits through a flexible factor analytic framework that allows multiple latent variables and covariate effects on the latent variables. The structure of the model facilitates implementation of Markov chain Monte Carlo methods for posterior estimation. Data from a spermatotoxicity study are analyzed to illustrate the proposed approach.     

Direct measurement of oxidative metabolism in the living brain by microdialysis: a review

This review summarizes microdialysis studies that address the question of which compounds serve as energy sources in the brain. Microdialysis was used to introduce ¹⁴C-labeled glucose, lactate, pyruvate, glutamate, glutamine, and acetate into the interstitial fluid of the brain to observe their metabolism to ¹⁴CO₂. Although glucose uptake from the systemic system supplies the carbon source for these compounds, compounds synthesized from glucose by the brain are subject to recycling including complete metabolism to CO₂. Therefore, the brain utilizes multiple compounds in its domain to provide the energy needed to fulfill its function. The physiological conditions controlling metabolism and the contribution of compartmentation into different brain regions, cell types, and subcellular spaces are still unresolved. The aconitase inhibitor fluorocitrate, with a lower inhibition threshold in glial cells, was used to identify the proportion of lactate and glucose that was oxidized in glial cells versus neurons. The fluorocitrate data suggest that glial and neuronal cells are capable of utilizing both lactate and glucose for energy metabolism.     

From prebiotic chemistry to cellular metabolism--the chemical evolution of metabolism before Darwinian natural selection

It is generally assumed that the complex map of metabolism is a result of natural selection working at the molecular level. However, natural selection can only work on entities that have three basic features: information, metabolism and membrane. Metabolism must include the capability of producing all cellular structures, as well as energy (ATP), from external sources; information must be established on a material that allows its perpetuity, in order to safeguard the goals achieved; and membranes must be able to preserve the internal material, determining a selective exchange with external material in order to ensure that both metabolism and information can be individualized. It is not difficult to understand that protocellular entities that boast these three qualities can evolve through natural selection. The problem is rather to explain the origin of such features under conditions where natural selection could not work. In the present work we propose that these protocells could be built by chemical evolution, starting from the prebiotic primordial soup, by means of chemical selection. This consists of selective increases of the rates of certain specific reactions because of the kinetic or thermodynamic features of the process, such as stoichiometric catalysis or autocatalysis, cooperativity and others, thereby promoting their prevalence among the whole set of chemical possibilities. Our results show that all chemical processes necessary for yielding the basic materials that natural selection needs to work may be achieved through chemical selection, thus suggesting a way for life to begin.