Kinetics of non-equilibrium metabolism-coupled passive transport in biosystems

Expressions for time course of solute concentration in an arbitrary compartment of a biosystem were derived using simplifying assumptions of unidirectional transport and first order metabolism kinetics. The coefficients of the resulting exponential-summation function comprise, in addition to the volumes and the connecting areas of individual compartments, the rate parameters of the processes mentioned. The equations presented were verified using results obtained in drug potency testing.     

Constant Pharmacologic Effect and Chronopharmacology: Theoretical Aspects

The theoretical drug infusion rates requisite to obtain a constant pharmacologic effect are determined taking into account chronopharmacologic phenomena. The introduction of chronopharmacology into pharmacokinetic theory leads to a clocktime-dependent infusion rate. The infusion modulation depends both on type of chronophenomenon, chronopharmacokinetics or chronestesy, and plasma clearance rate of the drug. In the presence of chronestesy of a biosystem the pharmacologic effect can be maintained constant only when plasma drug clearance is fast enough to allow an adequate modulation of the plasma drug concentration. Although the established equations proceed from theoretical concept they could be useful for programming drug delivery systems.     

Constant Pharmacologic Effect and Chronopharmacology: Theoretical Aspects

The theoretical drug infusion rates requisite to obtain a constant pharmacologic effect are determined taking into account chronopharmacologic phenomena. The introduction of chronopharmacology into pharmacokinetic theory leads to a clocktime-dependent infusion rate. The infusion modulation depends both on type of chronophenomenon, chronopharmacokinetics or chronestesy, and plasma clearance rate of the drug. In the presence of chronestesy of a biosystem the pharmacologic effect can be maintained constant only when plasma drug clearance is fast enough to allow an adequate modulation of the plasma drug concentration. Although the established equations proceed from theoretical concept they could be useful for programming drug delivery systems.     

Poly(amidoamine) (PAMAM) dendritic nanostructures for controlled sitespecific delivery of acidic anti-inflammatory active ingredient

The purpose of the investigation was to evaluate the potential of polyamidoamine (PAMAM) dendrimer as nanoscale drug delivery units for controlled release of water insoluble and acidic anti-inflammatory drug. Flurbiprofen (FB) was selected as a model acidic anti-inflammatory drug. The aqueous solutions of 4.0 generation (G) PAMAM dendrimer in different concentrations were prepared and used further for solubilizing FB. Formation of dendrimer complex was characterized by Fourier transform infrared spectroscopy. The effect of pH on the solubility of FB in dendrimer was evaluated. Dendrimer formulations were further evaluated for in vitro release study and hemolytic toxicity. Pharmacokinetic and biodistribution were studied in male albino rats. Efficacy of dendrimer formulation was tested by carrageenan induced paw edema model. It was observed that the loaded drug displayed initial rapid release (more than 40% till 3rd hour) followed by rather slow release. Pharmacodynamic study revealed 75% inhibition at 4th hour that was maintained above 50% till 8th hour. The mean residence time (MRT) and terminal half-life (THF) of the dendritic formulation increased by 2-fold and 3-fold, respectively, compared with free drug. Hence, with dendritic system the drug is retained for longer duration in the biosystem with 5-fold greater distribution. It may be concluded that the drug-loaded dendrimers not only enhanced the solubility but also controlled the delivery of the bioactive with localized action at the site of inflammation. Published: October 27, 2005     

分子进化研究中的一些问题

本文在强调生物系统的层次结构和非线性特征的基础上,就分子进化研究中存在的某些认识上的和方法学上的问题,提出了作者的观点和简要分析。     

Structure and function of bacterial super-biosystem responsible for import and depolymerization of macromolecules

Generally, when microbes assimilate macromolecules, they incorporate low-molecular-weight products derived from macromolecules through the actions of extracellular degrading enzymes. However, a Gram-negative bacterium, Sphingomonas sp. A1, has a smart biosystem for the import and depolymerization of macromolecules. The bacterial cells directly incorporate a macromolecule, alginate, into the cytoplasm through a "superchannel", as we named it. The superchannel consists of a pit on the cell surface, alginate-binding proteins in the periplasm, and an ATP-binding cassette transporter in the inner membrane. Cytoplasmic polysaccharide lyases depolymerize alginate into the constituent monosaccharides. Other than the proteins characterized so far, novel proteins (e.g., flagellin homologs) have been found to be crucial for the import and depolymerization of alginate through genomics- and proteomics-based identification, thus indicating that the biosystem is precisely constructed and regulated by diverse proteins. In this review, we focus on the structure and function of the bacterial biosystem together with the evolution of related proteins.     

应激的光生物调节作用

功能内稳态( function-specific homeostasis,FSH)是维持生物功能充分稳定发挥的负反馈机制,FSH的品质由功能复杂性和稳定性构成.应激打破FSH,处于应激内稳态(stress-specific homeostasis,StSH)的应激称为成功应激,后者能够实现FSH的升级或降级.低水平激光...     

一种新型蚯蚓纤溶酶的部分性质研究

为获得一种高效的溶栓药物。从赤子爱胜蚓(Eiseniafoelida)中分离纯化得到了一种纤溶酶组分。用Lowry法测定蛋白质浓度,SDSPAGE鉴定纯度为98%,表观相对分子质量(Mr)为14850,纤维蛋白平板法测定其总纤溶活性为65.51×103mm2/mg,直接纤溶活性为15.61×103mm2/mg,间接纤溶活性为26.34×103mm2/mg。水解BAEE的米氏常数(Km)为1.82×105mol/L。水解ChromozymPL的米氏常数(Km)3.98×105mol/L,水解ChromozymtPA的米氏常数(Km)5.55×105mol/L活性,N端氨基酸序列测定的结果为VIGGTNAIPGEFPYQ。结果表明该纤溶酶分子量较小,间接活性较高,适宜作为一种新型的溶栓药物。     

Dynamics of the biological system in turbellarians inhabiting the littoral water bodies of Lake Baikal (Phagocata sibirica) subjected to stress: Model of coupled bistable oscillators

An experimental investigation into the behavior of turbellarians inhabiting the water bodies of the basin of Lake Baikal (Phagocata sibirica (Zabussov, 1903)) under the influence of light, toxicants, and both these factors allows one to find biosystem features under effects other than homeostasis. It is revealed that, when the system is subjected to increasing light intensity, it demonstrates turbulent oscillation with the effects of synchronization and desynchronization. An analysis of the experimental results within the framework of the theory of nonlinear dynamical systems shows that the behavior of the turbellarian biosystem corresponds to the model of coupled bistable oscillators, the synchronization of which is induced by internal biosystem noise.     

Molecular biology, epidemiology, and the demise of the linear no-threshold (LNT) hypothesis

The prime concern of radiation protection policy since 1959 has been protecting DNA from damage. The 1995 NCRP Report 121 on collective dose states that since no human data provides direct support for the linear no threshold hypothesis (LNT), and some studies provide quantitative data that, with statistical significance, contradict LNT, ultimately, confidence in LNT is based on the biophysical concept that the passage of a single charged particle could cause damage to DNA that would result in cancer. Current understanding of the basic molecular biologic mechanisms involved and recent data are examined before presenting several statistically significant epidemiologic studies that contradict the LNT hypothesis. Over eons of time a complex biosystem evolved to control the DNA alterations (oxidative adducts) produced by about 10(10) free radicals/cell/d derived from 2-3% of all metabolized oxygen. Antioxidant prevention, enzymatic repair of DNA damage, and removal of persistent DNA alterations by apoptosis, differentiation, necrosis, and the immune system, sequentially reduce DNA damage from about 10(6) DNA alterations/cell/d to about 1 mutation/cell/d. These mutations accumulate in stem cells during a lifetime with progressive DNA damage-control impairment associated with aging and malignant growth. A comparatively negligible number of mutations, an average of about 10(-7) mutations/cell/d, is produced by low LET radiation background of 0.1 cGy/y. The remarkable efficiency of this biosystem is increased by the adaptive responses to low-dose ionizing radiation. Each of the sequential functions that prevent, repair, and remove DNA damage are adaptively stimulated by low-dose ionizing radiation in contrast to their impairment by high-dose radiation. The biologic effect of radiation is not determined by the number of mutations it creates, but by its effect on the biosystem that controls the relentless enormous burden of oxidative DNA damage. At low doses, radiation stimulates this biosystem with consequent significant decrease of metabolic mutations. Low-dose stimulation of the immune system may not only prevent cancer by increasing removal of premalignant or malignant cells with persistent DNA damage, but used in human radioimmunotherapy may also completely remove malignant tumors with metastases. The reduction of gene mutations in response to low-dose radiation provides a biological explanation of the statistically significant observations of mortality and cancer mortality risk decrements, and contradicts the biophysical concept of the basic mechanisms upon which, ultimately, the NCRPs confidence in the LNT hypothesis is based.     

Pattern of self-organization in tumour systems: complex growth dynamics in a novel brain tumour spheroid model

We propose that a highly malignant brain tumour is an opportunistic, self-organizing and adaptive complex dynamic biosystem rather than an unorganized cell mass. To test the hypothesis of related key behaviour such as cell proliferation and invasion, we have developed a new in vitro assay capable of displaying several of the dynamic features of this multiparameter system in the same experimental setting. This assay investigates the development of multicellular U87MGmEGFR spheroids in a specific extracellular matrix gel over time. The results show that key features such as volumetric growth and cell invasion can be analysed in the same setting over 144 h without continuously supplementing additional nutrition. Moreover, tumour proliferation and invasion are closely correlated and both key features establish a distinct ratio over time to achieve maximum cell velocity and to maintain the system's temporo-spatial expansion dynamics. Single cell invasion follows a chain-like pattern leading to the new concept of a intrabranch homotype attraction . Since preliminary studies demonstrate that heterotype attraction can specifically direct and accelerate the emerging invasive network, we further introduce the concept of least resistance, most permission and highest attraction as an essential principle for tumour invasion. Together, these results support the hypothesis of a self-organizing adaptive biosystem.     

BIO-RESPONSE TO WHITE NOISE EXCITATION

Pink (1/f-) noise is one of the most common behaviors of biosystems. This paper is devoted to clarifying the stochastic answer given to white-noise excitation of bio-systems.

It is assumed that a living system in general is a bifurcative self-organizing system, and has cyclic symmetry with infinite degrees of freedom, and stationary random stochastic processes characterize their dynamism.

We show that this bifurcation characterizes all levels of bioactivity, and the white-noise excited biosystem has a filter function, and generates a pink-noise spectrum.

Environmental white-noise electromagnetic excitation (like ‘electrosmog’ in general) is filtered by the biosystem, and it gives a characteristic pink-noise answer-signal to this excitation.     

Simple example of structure versus property relationship applied to a reduced-friction biosystem,a quite personal opinion

Structure versus property (small-scale) relationship enters when something interesting is going to happen in a biosystem. This special-type “happening” is actually appearing to be manifested at both micro- and mesoscopic levels of always productive soft-matter organization under dynamic response, especially the one characteristic of the articular cartilage—an efficient, designed-by-nature multi-membrane, and virtually, with-ion-channels equipped, absorber and load relaxor.     

Facile synthesis of (−)-vibo-quercitol from maltodextrin via an in vitro synthetic enzymatic biosystem

(−)-vibo-Quercitol (VQ: 1L-1,2,4/3,5-cyclohexanepentol), a form of deoxyinositol, is an alternative chiral building block in the synthesis of bioactive compounds to control diabetes. In this study, an adenosine triphosphate-free in vitro synthetic enzymatic biosystem composed of five enzymes (including one enzyme for NADH regeneration) was constructed to produce VQ from maltodextrin in one-pot. After optimization of reaction conditions, 7.6 g/L VQ was produced from 10 g/L maltodextrin with a product yield (mol/mol) of 77%, and 25.3 g/L VQ with a purity of 87% was produced from 50 g/L maltodextrin through simple scaling up of this nonfermentative enzymatic biosystem. Therefore, this study provides an economical and environmentally friendly method for the envisioned quercitol biosynthesis.     

Component-based software architecture for biosystem reverse engineering

Reverse engineering is defined as the process where the internal structures and dynamics of a given system are inferred and analyzed from external observations and relevant knowledge. The first part of this paper surveys existing techniques for biosystem reverse engineering. Network structure inference techniques such as Correlation Matrix Construction (CMC), Boolean network and Bayesian network-based methods are explained. After the numeric and logical simulation techniques are briefly described, several representative working software tools were introduced. The second part presents our component-based software architecture for biosystem reverse engineering. After three design principles are established, a loosely coupled federation architecture consisting of 11 autonomous components is proposed along with their respective functions.     

Simple example of structure versus property relationship applied to a reduced-friction biosystem, a quite personal opinion

Structure versus property (small-scale) relationship enters when something interesting is going to happen in a biosystem. This special-type "happening" is actually appearing to be manifested at both micro- and mesoscopic levels of always productive soft-matter organization under dynamic response, especially the one characteristic of the articular cartilage--an efficient, designed-by-nature multi-membrane, and virtually, with-ion-channels equipped, absorber and load relaxor.     

现代系统生物技术与图式遗传学

基因组程序化表达调控与生物体形态结构发生的相互对应是图式遗传学和系统生物技术研究复杂生物系统的核心。基因-蛋白质表达与神经-内分泌信号,构成生物系统发生演变的双向调控过程是生物信息控制系统的结构、功能和演变的基础。细胞信号传导与基因差异表达调控是从基因、细胞到器官的细胞动力学转换系统,是基因、蛋白质、脂类等生物高分子相互作用与细胞再生、分化、迁移、凋亡的程序化调控节律,也就是基因定位图谱-细胞定位图谱的基因组-蛋白质组与生物体的细胞节律-形态的发生转换过程。     

Proof of concept and improvement of a triple chamber biosystem coupling anaerobic digestion,nitrification and mixotrophic endogenous denitrification for organic matter,nitrogen and sulfide removal from domestic sewage

Bioprocess and Biosystems Engineering - In this study, two versions of a triple chamber biosystem, coupling anaerobic digestion, nitrification and mixotrophic endogenous denitrification (ADNMED),...