Recasting nonlinear differential equations as S-systems: a canonical nonlinear form

An enormous variety of nonlinear differential equations and functions have been recast exactly in the canonical form called an S-system. This is a system of nonlinear ordinary differential equations, each with the same structure: the change in a variable is equal to a difference of products of power-law functions. We review the development of S-systems, prove that the minimum for the range of equations that can be recast as S-systems consists of all equations composed of elementary functions and nested elementary functions of elementary functions, give a detailed example of the recasting process, and discuss the theoretical and practical implications. Among the latter is the ability to solve numerically nonlinear ordinary differential equations in their S-system form significantly faster than in their original form through utilization of a specially designed algorithm.     

Application of spheroid culture to human hepatocytes and maintenance of their differentiation

Summary— Human hepatocytes cultured with a hormonally defined medium on non-adherent poly-(2-hydroxyethyl methacrylate) coated surface were able to form spheroids. The maintenance of liver-specific functions was assessed by following secretion of albumin, transferrin and α-antitrypsin that were still detectable after 4 months of spheroidal culture. Moreover, cytochrome P-450 IA was induced by methylcholanthrene for up to 2 weeks. This cell system is very promising for long-term in vitro studies of human hepatocyte functions.     

Molecular cloning of the C6A form cDNA of the mouse sixth complement component: functional integrity despite the absence of factor I modules

The sixth complement component (C6) is an essential component of the biologically active C5b-9 membrane attack complex of the complement system. The multimolecular C5b-9 complex is an important mediator of the biological effects of the activated complement system through its prominent cell signaling and cytolytic functions. To begin to provide essential information and reagents needed to analyze the functions of the complement system in mouse models of human diseases, the cDNA of the A form of mouse C6, which is present in all mouse strains, was cloned and characterized structurally and functionally. Although strikingly homologous in deduced amino acid sequence and modular structure to human C6 (75% identity), mouse C6 is substantially smaller due to the absence of the two carboxyl-terminal factor I modules (FIMs) found in human C6. Various approaches, including studies with antibody generated to recombinant mouse C6, failed to reveal evidence for FIMs in this form of mouse C6. Despite the absence of these modules in C6A, reported to be important for interactions with C5 in the human system, mouse C6A is functionally active and is readily incorporated into the mouse C5b-9 complex.     

Semaphorins guide PerPlexeD endothelial cells

Abrogation of the endothelial cell-specific semaphorin receptor PlexinD1 in zebrafish and mouse reveals semaphorin functions selectively affecting the cardiovascular system. Neuropilins team up with PlexinD1 to form a novel endothelial receptor complex for class 3 semaphorins.     

An analysis of the class of gene regulatory functions implied by a biochemical model

Understanding the integrated behavior of genetic regulatory networks, in which genes regulate one another's activities via RNA and protein products, is emerging as a dominant problem in systems biology. One widely studied class of models of such networks includes genes whose expression values assume Boolean values (i.e., on or off). Design decisions in the development of Boolean network models of gene regulatory systems include the topology of the network (including the distribution of input- and output-connectivity) and the class of Boolean functions used by each gene (e.g., canalizing functions, post functions, etc.). For example, evidence from simulations suggests that biologically realistic dynamics can be produced by scale-free network topologies with canalizing Boolean functions. This work seeks further insights into the design of Boolean network models through the construction and analysis of a class of models that include more concrete biochemical mechanisms than the usual abstract model, including genes and gene products, dimerization, cis-binding sites, promoters and repressors. In this model, it is assumed that the system consists of N genes, with each gene producing one protein product. Proteins may form complexes such as dimers, trimers, etc. The model also includes cis-binding sites to which proteins may bind to form activators or repressors. Binding affinities are based on structural complementarity between proteins and binding sites, with molecular binding sites modeled by bit-strings. Biochemically plausible gene expression rules are used to derive a Boolean regulatory function for each gene in the system. The result is a network model in which both topological features and Boolean functions arise as emergent properties of the interactions of components at the biochemical level. A highly biased set of Boolean functions is observed in simulations of networks of various sizes, suggesting a new characterization of the subset of Boolean functions that are likely to appear in gene regulatory networks.     

An improved Tn7-based system for the single-copy insertion of cloned genes into chromosomes of gram-negative bacteria.

A system is described for the single-copy, stable insertion of cloned DNA sequences into the chromosomes of Gram- bacteria. Two narrow-host-range plasmids form the basis of this system: the 'carrier' plasmid contains the mini Tn7-Km transposon, into which foreign DNA can be cloned; the 'helper' plasmid provides the Tn7 transposition functions in trans. Both plasmids are readily transferred into Gram- bacteria by conjugation. The functionality of this system has been demonstrated in Rhodospirillum rubrum.     

Phenotype of hepatocyte spheroids in Arg-GLY-Asp (RGD) containing a thermo-reversible extracellular matrix

The spheroid of specific cells is often regarded as the better form in artificial organs and mammalian cell bioreactors for improved cell-specific functions. In this study, freshly harvested primary rat hepatocytes, which had been cultivated as spheroids and entrapped in a synthetic thermo-reversible extracellular matrix, were examined for differentiated morphology and enhanced liver-specific functions as compared to a control set (hepatocytes in single-cell form). A copolymer of N-isopropylacrylamide (98 mole % in the feed) and acrylic acid (poly(NiPAAm-co-AAc)), and the adhesion molecule, an Arg-Gly-Asp (RGD)-incorporated thermo-reversible matrix, were used to entrap hepatocytes in the form of either spheroids or single cells. In a 28-day culture period, the spheroids in the RGD-incorporated gel maintained higher viability and produced albumin and urea at constant rates, while there was lower cell viability and less albumin secretion by the spheroids in p(NiPAAm-co-AAc). Hepatocytes cultured as spheroids in the RGD-incorporated gel would constitute a potentially useful three-dimensional cell system for application in a bio-artificial liver device.     

The neuropharmacological restoration of cognitive functions in cats after damage to the forebrain basal nuclei (Meynert's nucleus)]

The cognitive functions were studied on experimental model of Alzheimer's disease (destruction of the basal nuclei of Meynert in cats) using the stimulation and inhibition of Ach, GABA, and DA brain systems. Ach system was found to be essential to form generalization function, DA system to improve simple learning, and GABA system to involve in formation of complex associations.     

Isolation and structural characterization of porcine coupling factor 6 from intestinal tissues

A polypeptide purified from an extract of thermostable, porcine intestinal peptides was found to correspond to coupling factor 6, previously known as a component of the mitochondrial oxidative phosphorylation system. The intestinal presence of this peptide offers a new source for preparation of the component in large quantities, and possibly suggests further functions of the polypeptide. Amino acid sequence analysis of this porcine form reveals it to be identical to the bovine form, except for two replacements, at position 62 (Thr in the porcine, Phe/Thr in the bovine form), and position 70 (Ala/Val). The extensive conservation suggests strict structural constraints on the functional properties of the polypeptide.     

Mechanistically novel iron(III) transport system in Serratia marcescens.

A novel iron(III) transport system of Serratia marcescens, named SFU, was cloned and characterized in Escherichia coli. Iron acquisition by this system differed from that by E. coli and related organisms. No siderophore production and no receptor protein related to the SFU system could be detected. In addition, iron uptake was independent of the TonB and ExbB functions. On the cloned 4.8-kilobase sfu fragment, two loci encoding a 36-kilodalton (kDa) protein and three proteins with molecular masses of 40, 38, and 34 kDa were identified; the 40-kDa protein represents a precursor form. Furthermore, chromosomally encoded functions of E. coli were required for the uptake of iron by this system.     

细菌Ⅵ型分泌系统的研究进展

Ⅵ型分泌系统(Type Ⅵ secretion system,T6SS)是最近发现的一种新的分泌系统,广泛存在于革兰氏阴性菌变形菌门细菌中,主要由构成分泌系统的结构蛋白、形成跨膜管道结构的转位蛋白、分泌蛋白以及一些对分泌系统起辅助功能的蛋白组成。T6SS能够增强细菌对外界环境的适应性,介导细菌对宿主细胞的致病力以及其他功能。     

Management into the Development Strategies of Urbanizing Regions in Asia: Implications of Urban Function, Form, and Role

The way urbanization unfolds over the next few decades in the developing countries of Asia will have profound implications for sustainability. One of the more important opportunities is to guide urbanization along pathways that begin to uncouple these gains in well-being from rising levels of energy use. Increasing energy use for transport, construction, climate control in houses and offices, and industrial processes is often accompanied by increasing levels of atmospheric emissions that impact human health, ecosystem functions, and the climate system. Agriculture, forestry, and animal husbandry alter carbon stocks and fluxes as carbon dioxide, methane, and black carbon. In this article we explore how carbon management could be integrated into the development strategies of cities and urbanizing regions. In particular, we explore how changes in urban form, functions, and roles might alter the timing, aggregation, spatial distribution, and composition of carbon emissions. Our emphasis is on identifying system linkages and points of leverage. The study draws primarily on emission inventories and regional development histories carried out in the regions around the cities of Manila, Jakarta, Ho Chi Minh City, New Delhi, and Chiang Mai. We find that how urban functions, such as mobility, shelter, and food, are provided has major implications for carbon emissions, and that each function is influenced by urban form and role in distinct ways. Our case studies highlight the need for major "U-turns" in urban policy.     

Enthalpy distribution functions for protein-DNA complexes: example of the binding of AT-hooks to target DNA

In this article we use the published heat capacity data of Dragan et al. [A.I. Dragan, et al., The energetics of specific binding of AT-hooks from HMGA1 to target DNA, J. Mol. Biol. 327 (2003) 393-411] on the association of proteins with DNA duplexes to construct enthalpy probability distributions for the protein/DNA complexes formed in these systems. We first analyze the multistep equilibrium that determines the species concentrations in this system to determine whether or not the DNA-peptide complex goes cleanly to DNA single-strands and peptide. Using the heat capacity data for this case we employ the maximum-entropy method to construct enthalpy probability distribution functions for the species involved in this equilibrium. We find that the distribution functions for this system clearly show bimodal behavior indicating a two-state transition from complex to non-complex form.     

Modelling spatiotemporal properties of directionally sensitive multi-input single-output systems

The dynamics of directionally tuned linear multi-input single-output systems varies generally as a function of the spatial orientation of the inputs. A linear system receiving directionally specific inputs is represented by a linear combination of the respective input transfer functions. The input-output behaviour of such systems can be described by a vector transfer function which specifies the polarization directions of the system in real space. These directions, which can be either one (unidirectional vector transfer function) or two (bidirectional vector transfer function) but never three, are obtained by computing the eigenvectors and eigenvalues of the system matrix that is defined by the gain and phase values of the system's response to harmonic stimulation directed along three orthogonal directions in space. The spatial tuning behaviour is determined by the quadratic form associated with the system matrix. Neuronal systems with bidirectional vector transfer functions process input information in a plane-specific way and exhibit novel characteristics, very much different from those of systems with unidirectional vector transfer functions.     

From records to self-description: The role played by RNA in early evolutive systems

We study the appearance of genetic information starting from a system where self-reproductive and enzymatic functions are supported by the same sort of molecules. In a first phase, the information must have arisen in the form of rate independent sequences as records of enzymatic functions. Although this stage must have played an important role in evolution, it will be shown how its evolutive capacities were blocked by the impossibility of appearance of geno/phenotype duality. Finally, a logical scheme is proposed for a transition process toward a system with a code offering a simplification of the conditions required from the assumption of a maximum use of the double RNA capacity, both reproductive and enzymatic.     

Hyphal formation of Candida albicans is controlled by electron transfer system

Most Candida albicans cells cultured in RPMI1640 medium at 37 degrees C grow in hyphal form in aerobic conditions, but they grow in yeast form in anaerobic conditions. The hyphal growth of C. albicans was inhibited in glucose-deficient conditions. Malonic acid, an inhibitor of succinate dehydrogenase, enhanced the yeast proliferation of C. albicans, indicating that the hyphal-formation signal was derived from the glycolysis system and the signal was transmitted to the electron transfer system via the citric acid cycle. Thenoyl trifluoro acetone (TTFA), an inhibitor of the signal transmission between complex II and Co Q, significantly inhibited the hyphal growth of C. albicans. Antimycin, KCN, and oligomycin, inhibitors of complex III, IV, and V, respectively, did not inhibit the hyphal growth of C. albicans. The production of mRNAs for the hyphal formation signal was completely inhibited in anaerobic conditions. These results indicate that the electron transfer system functions upstream of the RAS1 signal pathway and activates the expression of the hyphal formation signal. Since the electron transfer system is inactivated in anaerobic conditions, C. albicans grew in yeast form in this condition.     

The multicomponent analysis of estrogens in urine by ion exchange chromatography and GC-MS--I. Quantitation of estrogens after initial hydrolysis of conjugates

A method for the multicomponent analysis of estrogens in urine after initial hydrolysis of the conjugates is described. Following protection of the carbonyl functions by ethoximation, estrogen conjugates were extracted on Sep-Pak C18 cartridges and purified on the acetate form of DEAE-Sephadex. The samples were subsequently hydrolysed by Helix pomatia juice and the hydrolysate was purified on the acetate form of QAE-Sephadex. Estrogens with vicinal cis-hydroxyls and diphenolic compounds were fractionated on the borate and bicarbonate form of QAE-Sephadex, respectively. Neutral steroids were removed by the free base form of DEAE-Sephadex after which estrogens were separated into two groups using Lipidex 5000 in a straight phase system. Following trimethylsilyl ether derivatization estrogens were analysed by selected ion monitoring (SIM). The method allows the quantitation of all the important estrogen metabolites including catechol estrogens. It is precise, accurate and sensitive permitting the quantitation of estrogens in urine of males and non-pregnant females.     

Imaging system for morphometric assessment of absorption or fluorescence in stained cells

An image acquisition and processing system has been developed for quantitative microscopy of absorption or fluorescence in stained cells. Three different light transducers are used in the system to exploit the best characteristics of these sensors for different biological measurements. A digital scanner, in the form of a linear array charge-coupled device (CCD), acquires data with high spatial and photometric resolution. A color (RGB) camera is employed when spectral information is required for the segmentation of cellular subcomponents. An image-intensified charged-injection device (CID) camera provides for very low light intensity measurements, primarily for fluorescence-labeled cells. Properties of these transducers, such as contrast transfer function, linearity, and photo-response nonuniformity, have been measured. Two dedicated image processing units were incorporated into the system. The front-end processor, based on a digital signal processor, provides functions such as object detection, raw image calibration, compression, artifact removal, and filtering. The second image processor is associated with the frame memory and includes a histogram processor, a dedicated arithmetic logic unit for image processing functions, and a graphics module for one-bit overlay functions. An interactive program was developed to acquire cell images and to experiment with a range of segmentation algorithms, feature extractions, and other image processing functions. The results of any image operation are displayed on the video monitor. Once a desired processing sequence is determined, the sequence may be stored to become part of a command library and can be executed thereafter as a single instruction.