Genetic Control Systems Research Articles

Contrasting methods for symbolic analysis of biological regulatory networks

Symbolic dynamics offers a powerful technique to relate the structure and dynamics of complex networks. We contrast the predictions of two methods of symbolic dynamics for the analysis of monotonic networks suggested by models of genetic control systems.

An adaptive neuro-fuzzy sliding mode based genetic algorithm control system for under water remotely operated vehicle

This study presents an adaptive neuro-fuzzy sliding-mode-based genetic algorithm (ANFSGA) control system for a remotely operated vehicle (ROV) with four degrees of freedom (DOF)s. In many applications, ROVs will need to be capable of maneuvering to any given point, following object, and to be controllable from the surface. Therefore, an ANFSGA control system is introduced for tracking control of the ROV to achieve a high precision position control. Since the dynamic of ROVs are highly nonlinear and time varying, an ANFSGA control system is investigated according to direction-based genetic algorithm (GA) with the spirit of sliding mode control and adaptive neuro-fuzzy sliding mode (ANFS) based evolutionary procedure. In this way, on-line learning ability is employed to deal with the parametric uncertainty and disturbance by adjusting the ANFS inference parameters. In this proposed controller a GA control system is utilized to be the major controller, and stability can be indirectly insured by the concept of sliding mode control system without strict constraints and detailed system knowledge.

Construction of intragenic synthetic riboswitches for detection of a small molecule

Bacterial sensors, based on ligand-mediated genetic control systems, are promising for on-site chemical detection because sensing targets and generating signals do not require costly instrumentation. Here, we have constructed intragenic synthetic riboswitches without relying on high-throughput screening and demonstrated that the riboswitches can be harnessed to develop bacterial sensors displaying readily visible reporter signals in response to theophylline. In vivo imaging using the riboswitch showed target-specific changes in the expression of a green fluorescence protein reporter, which was visible even to the naked eye.

Genetic Relationships Among Panicle Characteristics of Rice (Oryza sativa L.) Using Unconditional and Conditional QTL Analyses

Using mixed-model-based composite interval mapping and conditional statistical methods, we studied quantitative trait loci (QTLs) with epistatic effects and QTLs by environment interaction effects for rice seed set percent (SSP), filled grain number per plant (FGP), and panicle length (PL). A population of 241 recombinant inbred lines was used which was derived from a cross between “Zhenshan 97” and “Minghui 63.” Its linkage map included 221 molecular markers. Our QTL analysis detected 28, 25, and 32 QTLs for SSP, FGP, and PL, respectively. Each QTL explained 1.37%∼13.19% of the mean phenotypic variation. A comparison of conventional and conditional mapping provided information about the genetic control system involved in the synthetic process of SSP, FGP, and PL at the level of individual QTLs. Conditional QTLs with reduced (or increased) effects were identified for SSP, which were significantly influenced by FGP or PL. Some QTLs could express independently for the given traits, thereby providing possibilities for simultaneous improvement of SSR and PL, and SSR and FGP. Epistasis was more sensitive to environmental conditions than were additive effects.

Anti-obesity drugs

Background: Recent discoveries about the metabolic and genetic control systems that govern regulation of body weight and energy expenditure have afforded the opportunity to develop pharmacological agents that can be used as adjunctive treatments for patients with obesity. However, the scarcity of medications available or those that have made it to Phase III trials reflects the difficult challenge of manipulating the biology of appetite regulation. Objective: The aim of this study was to inform health professionals about new anti-obesity medications that target neuronal systems within the central nervous system and peripheral humoral proteins that send signals to the central nervous system. Methods: A critical review was conducted of information available from the medical literature. Results/conclusions: An emerging theme is to use combination therapies that are directed towards several targets or leverage existing gastrointestinal satiety hormonal signals. By using combination therapies, it is anticipated that greater weight loss will be achieved compared to monotherapy.

Genetic Algorithm Optimization and Control System Design of Flexible Structures

This paper presents an investigation into the deployment of genetic algorithm (GA)-based controller design and optimization for vibration suppression in flexible structures. The potential of GA is explored in three case studies. In the first case study, the potential of GA is demonstrated in the development and optimization of a hybrid learning control scheme for vibration control of flexible manipulators. In the second case study, an active control mechanism for vibration suppression of flexible beam structures using GA optimization technique is proposed. The third case study presents the development of an effective adaptive command shaping control scheme for vibration control of a twin rotor system, where GA is employed to optimize the amplitudes and time locations of the impulses in the proposed control algorithm. The effectiveness of the proposed control schemes is verified in both an experimental and a simulation environment, and their performances are assessed in both the time and frequency domains.

Long-day rather than autonomous control of flowering in the diploid everbearing strawberry Fragaria vesca ssp. semperflorens

SummaryThe environmental control of flowering in the perpetual-flowering (everbearing) diploid strawberry Fragaria vesca ssp. semperflorens cultivars ‘Rügen’ and ‘Baron Solemacher’ has been studied in controlled environments. Seedpropagated plants were exposed to 10-h short-day (SD) and 24-h long-day (LD) conditions at temperatures ranging from 9° – 27°C. The results revealed a quantitative LD response of flowering that increased in strength with increasing temperature, to become almost obligatory at 27°C. Occasional runner formation was observed in SD at high temperature, conditions which were inhibitory to flowering, demonstrating that runnering ability is not completely lost in these genotypes. A comparison with the perpetual-flowering octoploid F. ananassa ‘Elan’, in one experiment, demonstrated an identical LD temperature interaction in the two species. The results are discussed in relation to available information on the genetics of flowering habits in the two species. Since seasonal flowering types of F. vesca and F. ananassa have also been shown to share a principally identical flowering response, controlled by SD and low temperature, it is concluded that a remarkably similar flowering control system is present in the diploid F. vesca and the octoploid F. ananassa. Despite the large genetic differences between the two species, and regardless of the origin of the cultivars, the seasonal flowering types are all SD plants, while their perpetual-flowering counterparts all appear to be LD plants. In both cases, there is a pronounced interaction with temperature; the photoperiodic responses increasing with increasing temperature, in both cases. This raises the question whether a common genetic flowering control system is present in both species.

Design of Total Sliding-Mode-Based Genetic Algorithm Control for Hybrid Resonant-Driven Linear Piezoelectric Ceramic Motor

This study presents a total sliding-mode-based genetic algorithm control (TSGAC) system for a linear piezoelectric ceramic motor (LPCM) driven by a newly designed hybrid resonant inverter. First, the motor configuration and driving circuit of an LPCM are introduced, and its hypothetical dynamic model is represented by a nonlinear function with unknown system parameters. In the hybrid resonant drive system, it has the merits of the high voltage gain from a parallel-resonant current source, and the invariant output characteristic from a two-inductance two-capacitance resonant driving circuit. Since the dynamic characteristics and motor parameters of the LPCM are highly nonlinear and time varying, a TSGAC system is therefore investigated based on direction-based genetic algorithm with the spirit of total sliding-mode control (TSC) and fuzzy-based evolutionary procedure to achieve high-precision position control under a wide operation range. In this control scheme, a GAC system is utilized to be the major controller, and the stability can be indirectly ensured by the concept of TSC without strict constraints and detailed system knowledge. In addition, the effectiveness of the proposed drive and control system is verified by numerical simulations and experimental results in the presence of uncertainties

Modeling allosteric regulation of de novo pyrimidine biosynthesis in Escherichia coli

With the emergence of multifaceted bioinformatics-derived data, it is becoming possible to merge biochemical and physiological information to develop a new level of understanding of the metabolic complexity of the cell. The biosynthetic pathway of de novo pyrimidine nucleotide metabolism is an essential capability of all free-living cells, and it occupies a pivotal position relative to metabolic processes that are involved in the macromolecular synthesis of DNA, RNA and proteins, as well as energy production and cell division. This regulatory network in all enteric bacteria involves genetic, allosteric, and physiological control systems that need to be integrated into a coordinated set of metabolic checks and balances. Allosterically regulated pathways constitute an exciting and challenging biosynthetic system to be approached from a mathematical perspective. However, to date, a mathematical model quantifying the contribution of allostery in controlling the dynamics of metabolic pathways has not been proposed. In this study, a direct, rigorous mathematical model of the de novo biosynthesis of pyrimidine nucleotides is presented. We corroborate the simulations with experimental data available in the literature and validate it with derepression experiments done in our laboratory. The model is able to faithfully represent the dynamic changes in the intracellular nucleotide pools that occur during metabolic transitions of the de novo pyrimidine biosynthetic pathway and represents a step forward in understanding the role of allosteric regulation in metabolic control.

AN EMBEDDED GENETIC FUZZY MOTION CONTROLLER FOR A MOBILE ROBOT

In this paper, an embedded genetic fuzzy motion control system is developed for autonomous navigation and obstacle avoidance of a mobile robot built in the ARIS Lab. A combination of four infrared sensors is equipped to measure the distance to obstacles around the mobile robot. The distance information is processed by the proposed genetic fuzzy controller to adjust the velocities of two separately-driven wheels of the robot. Here the fuzzy logic is used to process the sensor information generating the control commends; and the genetic algorithm is exploited to tune the membership functions of the fuzzy rules. Local search techniques are utilised to enhance the tuning process. The proposed motion controller has been applied on the mobile robot. Experiments have demonstrated the effectiveness of the developed genetic fuzzy controller.

Biofilms as a Mode of Existence of Bacteria in External Environment and Host Body: The Phenomenon, Genetic Control, and Regulation Systems of Development

Studies of the last decade have shown that most bacteria exist in natural ecosystems as specifically organized, attached to substrates biofilms rather than as freely floating plankton cells. The formation of these biofilms is a complex and highly regulated process. The development of biofilm communities is a primary strategy of bacterial survival not only in the external environment but also in the bodies of infected macroorganisms. In these organisms, bacteria are joined by complicated cell-cell associations, which makes them functionally similar to multicellular organisms. In the present review, we consider the structural organization of biofilms, factors affecting initiation of the biofilm formation, differential expression of bacterial genes at various stages of the biofilm development and their regulation. The significance of studies in this field for medicine, in particular, for prevention and protection against pathogenic bacteria, is discussed.

Serum copper is decreased in premature newborns and increased in newborns with hemolytic jaundice.

Copper is an active component of several enzyme systems, including cytochrome c oxidase and superoxide dismutase (1), and is essential for the prevention of anemia and leucopenia. It is important for the maturation of collagen and the maintenance of skeletal and vascular integrity because of its involvement in the lysyl oxidase enzyme system (2). Deficiency of copper is associated with an increased incidence of infection, as seen in patients with Menke kinky-hair disease, an inherited disease with low copper concentrations (3). The mechanism by which high copper concentrations interact with genetic control systems, leading to liver damage, is still unknown (4). The normal term infant is born with a generous liver copper store, and copper deficiency in neonates is a rare event (5). Copper deficiency has been associated with anemia, neutropenia, and bone demineralization in both preterm and full-term infants (6)(7)(8). Ceruloplasmin, the major serum copper-transporting protein, is synthesized in the liver, but its precise role in copper metabolism is unclear. Neonatal hepatic ceruloplasmin synthesis occurs after birth and is associated with a gradual increase in plasma concentrations (9). We report the concentrations of copper in healthy and jaundiced full-term and premature infants and their correlations with hemoglobin, bilirubin, and liver enzymes. The study was approved by the Greek Ethical Committee, and parental consent was obtained. The study comprised 303 neonates (full-term and premature). Newborns with obstructive jaundice or with infections or inflammatory process were excluded. All patients underwent routine laboratory tests to determine the etiology of their jaundice (see Table 1 in the Data Supplement that accompanies the online version of this Technical Brief at http://www.clinchem.org/content/vol50/issue7/) (10)(11). Patients were divided into the following groups (Table 1⇓ ). View this table: Table 1. Copper concentrations and hemolysis related biochemical tests in full-term and premature newborns with …

Control of gene expression by a natural metabolite-responsive ribozyme.

Most biological catalysts are made of protein; however, eight classes of natural ribozymes have been discovered that catalyse fundamental biochemical reactions. The central functions of ribozymes in modern organisms support the hypothesis that life passed through an 'RNA world' before the emergence of proteins and DNA. We have identified a new class of ribozymes that cleaves the messenger RNA of the glmS gene in Gram-positive bacteria. The ribozyme is activated by glucosamine-6-phosphate (GlcN6P), which is the metabolic product of the GlmS enzyme. Additional data indicate that the ribozyme serves as a metabolite-responsive genetic switch that represses the glmS gene in response to rising GlcN6P concentrations. These findings demonstrate that ribozyme switches may have functioned as metabolite sensors in primitive organisms, and further suggest that modern cells retain some of these ancient genetic control systems.

Copper deficiency and excess in infancy: developing a research agenda.

Copper deficiency and excess have been recognized as potential health problems for infants and children worldwide. Clinical manifestations of copper deficiency and excess are well characterized but the precise sequence by which high copper intake interacts with genetic control systems, leading to liver damage in infants, is unknown. The possibility that genetic mutations or epigenetic factors related to the functional development of copper homeostasis, could make otherwise normal infants on normal copper intake more susceptible to copper toxicity has been an issue of concern. In January 2001 a group of pediatricians and researchers interested in this area met at Tegernsee, Bavaria, Germany, to reviewing the state of knowledge on the topic. They addressed six main issues: 1) The relevance of copper deficit and excess as health problems. 2) The appropriate biomarkers to identify and characterize copper status 3) The genetic variability in copper metabolism 4) The mechanisms of whole body copper homeostasis in early life and their changes with age 5) The development of experimental and animal models to address research questions on copper homeostasis in infants. 6) The safe upper and lower limits of copper intake/exposure from water and food. We present here the highlights of the discussions and the main conclusions of the meeting.

Copper Deficiency And Excess In Infancy: Developing A Research Agenda

ABSTRACTCopper deficiency and excess have been recognized as potential health problems for infants and children worldwide. Clinical manifestations of copper deficiency and excess are well characterized but the precise sequence by which high copper intake interacts with genetic control systems, leading to liver damage in infants, is unknown. The possibility that genetic mutations or epigenetic factors related to the functional development of copper homeostasis, could make otherwise normal infants on normal copper intake more susceptible to copper toxicity has been an issue of concern. In January 2001 a group of pediatricians and researchers interested in this area met at Tegernsee, Bavaria, Germany, to reviewing the state of knowledge on the topic. They addressed six main issues: 1) The relevance of copper deficit and excess as health problems. 2) The appropriate biomarkers to identify and characterize copper status 3) The genetic variability in copper metabolism 4) The mechanisms of whole body copper homeostasis in early life and their changes with age 5) The development of experimental and animal models to address research questions on copper homeostasis in infants. 6) The safe upper and lower limits of copper intake/exposure from water and food. We present here the highlights of the discussions and the main conclusions of the meeting.

Supervisory genetic evolution control for indirect field-oriented induction motor drive

A supervisory genetic evolution control (SGEC) system for achieving high-precision position tracking performance of an indirect field-oriented induction motor (IM) drive is addressed. Based on fuzzy inference and genetic algorithm (GA) methodologies, a newly designed GA control law is developed first for dominating the main control task. However, the stability of the GA control cannot be ensured when huge unpredictable uncertainties occur in practical applications. Thus, a supervisory control is designed within the GA control so that the states of the control system are stabilised around a predetermined bound region. The salient features of this study are that the spirit of a fuzzy inference mechanism is utilised in the design of GA control with a self-organising property, and that the stability of the SGEC system can be guaranteed with the aid of a supervisory control. In addition, the effectiveness of the proposed control scheme is verified by numerical and experimental results, and its advantages are indicated in comparison with a feedback control system.

Coordination of cell growth in cocultures by a genetic proliferation control system.

Advanced cell culture systems such as organotypic cultures or stem cell expansion often involve cocultivation of two or more different cell types. A typical situation is the use of a feeder cell line that supports survival, growth or controls the differentiation status of primary cells. Unequal proliferation capacities result in unbalanced cell growth, such as the undesired expansion of immortalized cells at the expense of the primary cells. We utilized a genetic regulatory system to coordinate cell growth in cocultures. Proliferation control of a feeder cell line by a recombinant transcription factor was employed to prevent feeder cells from overgrowing cocultured stem cells, thereby avoiding premature media exhaustion. Relevant characteristic cell-surface proteins present on the parental feeder cell line were preserved. No special equipment was required and cell-type specific growth could be adjusted even during coculture. When compared to a conventional gamma-irradiation procedure, genetic proliferation control was superior with respect to ease of use, robustness, cell adherence, morphology and viability. The results demonstrate the applicability of genetic proliferation control to coordinate growth of different cell types in cocultures.

Evolution of biological information.

How do genetic systems gain information by evolutionary processes? Answering this question precisely requires a robust, quantitative measure of information. Fortunately, 50 years ago Claude Shannon defined information as a decrease in the uncertainty of a receiver. For molecular systems, uncertainty is closely related to entropy and hence has clear connections to the Second Law of Thermodynamics. These aspects of information theory have allowed the development of a straightforward and practical method of measuring information in genetic control systems. Here this method is used to observe information gain in the binding sites for an artificial 'protein' in a computer simulation of evolution. The simulation begins with zero information and, as in naturally occurring genetic systems, the information measured in the fully evolved binding sites is close to that needed to locate the sites in the genome. The transition is rapid, demonstrating that information gain can occur by punctuated equilibrium.

Controlling your losses: conditional gene silencing in mammals

Methods are now widely used in mice, and to a lesser extent in mammalian-cell culture, for the constitutive silencing of target genes in order to assess their function. For a variety of reasons, not least because many genes are essential for viability, it is important that these methods can be adapted to allow the controlled silencing of target genes. Reviewed here are the ways in which gene-silencing methods can be combined with a growing number of genetic control systems to generate cell lines or mice that are, in effect, conditional mutants. These approaches are still being developed and promise to open up key areas of cell and animal biology to genetic analysis.

A Dynamic Model of theEscherichia coliPhosphate-Starvation Response

A mathematical model of theEscherichia coliPho regulon was developed to study the induction of thephoAgene by starvation for inorganic phosphate. The model includes phosphate transport, detection of the phosphate concentration at the cell surface, and the signal transduction cascade ultimately leading to the induction of various Pho-controlled genes. Four parameters were manipulated to match the dynamic response of a culture growing with phosphate as the growth-limiting substrate to available experimental data for alkaline phosphatase production and internal phosphate concentration. Steady-state analysis demonstrates that the cascade design of this genetic control system gives rise to a harp transition between the uninduced and induced state for a small change in the external phosphate concentration. Parameter sensitivity indicates that the dissociation constant of the repression complex (which holds PhoR in the inactive form when phosphate is in excess), the rate constants for PhoB and PhoR phosphorylation, and the rate constant for induced transcription of Pho genes have the most influence over the expression of Pho-controlled genes. Changes in the repression complex dissociation constant and the PhoB/PhoR phosphorylation rates alter the sensitivity of the phosphate-starvation response to external phosphate concentration, whereas changes in the transcription rate constant affect the gain of the system. The model also predicts that additional Pho promoter (i.e., for the production of a heterologous protein from thephoApromoter on a plasmid) titrate activator protein PhoBA, such that a lower phosphate concentration is required to initiate expression from a high-copy plasmid than from a single-copy plasmid or the chromosome.