Developmental regulation of fear learning and anxiety behavior by endocannabinoids

PubMed Central

Lee, Tiffany T.-Y.; Hill, Matthew N.; Lee, Francis S.

2015-01-01

The developing brain undergoes substantial maturation into adulthood and the development of specific neural structures occurs on differing timelines. Transient imbalances between developmental trajectories of corticolimbic structures, which are known to contribute to regulation over fear learning and anxiety, can leave an individual susceptible to mental illness, particularly anxiety disorders. There is a substantial body of literature indicating that the endocannabinoid system critically regulates stress responsivity and emotional behavior throughout the life span, making this system a novel therapeutic target for stress- and anxiety-related disorders. During early life and adolescence, corticolimbic endocannabinoid signaling changes dynamically and coincides with different sensitive periods of fear learning, suggesting that endocannabinoid signaling underlies age-specific fear learning responses. Moreover, perturbations to these normative fluctuations in corticolimbic endocannabinoid signaling, such as stress or cannabinoid exposure, could serve as a neural substrate contributing to alterations to the normative developmental trajectory of neural structures governing emotional behavior and fear learning. In this review, we first introduce the components of the endocannabinoid system and discuss clinical and rodent models demonstrating endocannabinoid regulation of fear learning and anxiety in adulthood. Next, we highlight distinct fear learning and regulation profiles throughout development and discuss the ontogeny of the endocannabinoid system in the central nervous system, and models of pharmacological augmentation of endocannabinoid signaling during development in the context of fear learning and anxiety. PMID:26419643

Numerical Simulation of Tubular Pumping Systems with Different Regulation Methods

NASA Astrophysics Data System (ADS)

Zhu, Honggeng; Zhang, Rentian; Deng, Dongsheng; Feng, Xusong; Yao, Linbi

2010-06-01

Since the flow in tubular pumping systems is basically along axial direction and passes symmetrically through the impeller, most satisfying the basic hypotheses in the design of impeller and having higher pumping system efficiency in comparison with vertical pumping system, they are being widely applied to low-head pumping engineering. In a pumping station, the fluctuation of water levels in the sump and discharge pool is most common and at most time the pumping system runs under off-design conditions. Hence, the operation of pump has to be flexibly regulated to meet the needs of flow rates, and the selection of regulation method is as important as that of pump to reduce operation cost and achieve economic operation. In this paper, the three dimensional time-averaged Navier-Stokes equations are closed by RNG κ-ɛ turbulent model, and two tubular pumping systems with different regulation methods, equipped with the same pump model but with different designed system structures, are numerically simulated respectively to predict the pumping system performances and analyze the influence of regulation device and help designers make final decision in the selection of design schemes. The computed results indicate that the pumping system with blade-adjusting device needs longer suction box, and the increased hydraulic loss will lower the pumping system efficiency in the order of 1.5%. The pumping system with permanent magnet motor, by means of variable speed regulation, obtains higher system efficiency partly for shorter suction box and partly for different structure design. Nowadays, the varied speed regulation is realized by varied frequency device, the energy consumption of which is about 3˜4% of output power of the motor. Hence, when the efficiency of variable frequency device is considered, the total pumping system efficiency will probably be lower.

Structural Basis for DNA Recognition by the Two-Component Response Regulator RcsB.

PubMed

Filippova, Ekaterina V; Zemaitaitis, Bozena; Aung, Theint; Wolfe, Alan J; Anderson, Wayne F

2018-02-27

RcsB is a highly conserved transcription regulator of the Rcs phosphorelay system, a complex two-component signal transduction system (N. Majdalani and S. Gottesman, Annu Rev Microbiol 59:379-405, 2005; A. J. Wolfe, Curr Opin Microbiol 13:204-209, 2010, https://doi.org/10.1016/j.mib.2010.01.002; D. J. Clarke, Future Microbiol 5:1173-1184, 2010, https://doi.org/10.2217/fmb.10.83). RcsB plays an important role in virulence and pathogenicity in human hosts by regulating biofilm formation. RcsB can regulate transcription alone or together with its auxiliary transcription regulators by forming heterodimers. This complexity allows RcsB to regulate transcription of more than 600 bacterial genes in response to different stresses (D. Wang et al., Mol Plant Microbe Interact 25:6-17, 2012, https://doi.org/10.1094/MPMI-08-11-0207). Despite increasing knowledge of RcsB importance, molecular mechanisms that drive the ability of RcsB to control transcription of a large number of genes remain unclear. Here, we present crystal structures of unphosphorylated RcsB in complex with the consensus DNA-binding sequence of 22-mer (DNA22) and 18-mer (DNA18) of the flhDC operon from Escherichia coli determined at 3.15- and 3.37-Å resolution, respectively. The results of our structural analysis combined with the results of in vitro binding assays provide valuable insights to the protein regulatory mechanism, demonstrate how RcsB recognizes target DNA sequences, and reveal a unique oligomeric state that allows RcsB to form homo- and heterodimers. This information will help us understand the complex mechanisms of transcriptional regulation by RcsB in bacteria. IMPORTANCE RcsB is a well-studied two-component response regulator of the Rcs phosphorelay system, conserved within the family Enterobacteriaceae , which includes many pathogens. It is a global regulator, controlling more than 5% of bacterial genes associated with capsule biosynthesis, flagellar biogenesis, cell wall biosynthesis, antibiotic resistance, biofilm formation, and virulence in pathogens. Knowledge of RcsB structure represents a unique opportunity to explore mechanisms that regulate the Rcs phosphorelay system and its role in the family Enterobacteriaceae . Copyright © 2018 Filippova et al.

Structure of the Francisella response regulator QseB receiver domain, and characterization of QseB inhibition by antibiofilm 2-aminoimidazole-based compounds: Inhibition of response regulator QseB by antibiofilm compounds

DOE Office of Scientific and Technical Information (OSTI.GOV)

Milton, Morgan E.; Allen, C. Leigh; Feldmann, Erik A.

With antibiotic resistance increasing at alarming rates, targets for new antimicrobial therapies must be identified. A particularly promising target is the bacterial two-component system. Two-component systems allow bacteria to detect, evaluate and protect themselves against changes in the environment, such as exposure to antibiotics and also to trigger production of virulence factors. Drugs that target the response regulator portion of two-component systems represent a potent new approach so far unexploited. Here, we focus efforts on the highly virulent bacterium Francisella tularensis tularensis. Francisella contains only three response regulators, making it an ideal system to study. In this study, we initiallymore » present the structure of the N-terminal domain of QseB, the response regulator responsible for biofilm formation. Subsequently, using binding assays, computational docking and cellular studies, we show that QseB interacts with2-aminoimidazole based compounds that impede its function. This information will assist in tailoring compounds to act as adjuvants that will enhance the effect of antibiotics.« less

Sexual dimorphisms in avian and reptilian courtship: two systems that do not play by mammalian rules.

PubMed

Wade, J

1999-01-01

Sexual dimorphisms in the central nervous system exist in numerous vertebrate species, and in many cases these structural differences between males and females parallel differences in the display of reproductive behaviors. Often both the behavioral and anatomical differences are controlled by exposure to gonadal steroid hormones, either during ontogeny or in adulthood. This article reviews some of the evidence supporting the hypothesis that in mammals, testosterone or its metabolites regulate the structure and function of neural and muscle systems involved in the control of masculine sexual behaviors. It then describes data suggesting that the mechanisms regulating sexually dimorphic courtship systems in zebra finches and green anole lizards are not completely parallel to the mammalian systems. Finally, some directions for future study are suggested, with the hope that they will stimulate thought about the nature of comparisons made across vertebrate models when investigators are attempting to determine both which morphological sex differences are important to the control of the reproductive behaviors, and which mechanisms regulating both structure and function are widely employed or are unique.

Self-assembled lipid bilayer materials

DOEpatents

Sasaki, Darryl Y.; Waggoner, Tina A.; Last, Julie A.

2005-11-08

The present invention is a self-assembling material comprised of stacks of lipid bilayers formed in a columnar structure, where the assembly process is mediated and regulated by chemical recognition events. The material, through the chemical recognition interactions, has a self-regulating system that corrects the radial size of the assembly creating a uniform diameter throughout most of the structure. The materials form and are stable in aqueous solution. These materials are useful as structural elements for the architecture of materials and components in nanotechnology, efficient light harvesting systems for optical sensing, chemical processing centers, and drug delivery vehicles.

Developmental regulation of fear learning and anxiety behavior by endocannabinoids.

PubMed

Lee, T T-Y; Hill, M N; Lee, F S

2016-01-01

The developing brain undergoes substantial maturation into adulthood and the development of specific neural structures occurs on differing timelines. Transient imbalances between developmental trajectories of corticolimbic structures, which are known to contribute to regulation over fear learning and anxiety, can leave an individual susceptible to mental illness, particularly anxiety disorders. There is a substantial body of literature indicating that the endocannabinoid (eCB) system critically regulates stress responsivity and emotional behavior throughout the life span, making this system a novel therapeutic target for stress- and anxiety-related disorders. During early life and adolescence, corticolimbic eCB signaling changes dynamically and coincides with different sensitive periods of fear learning, suggesting that eCB signaling underlies age-specific fear learning responses. Moreover, perturbations to these normative fluctuations in corticolimbic eCB signaling, such as stress or cannabinoid exposure, could serve as a neural substrate contributing to alterations to the normative developmental trajectory of neural structures governing emotional behavior and fear learning. In this review, we first introduce the components of the eCB system and discuss clinical and rodent models showing eCB regulation of fear learning and anxiety in adulthood. Next, we highlight distinct fear learning and regulation profiles throughout development and discuss the ontogeny of the eCB system in the central nervous system, and models of pharmacological augmentation of eCB signaling during development in the context of fear learning and anxiety. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

48 CFR 2452.209-70 - Potential organizational conflicts of interest.

Code of Federal Regulations, 2011 CFR

2011-10-01

... conflicts of interest. 2452.209-70 Section 2452.209-70 Federal Acquisition Regulations System DEPARTMENT OF... relevant facts that show how its organizational structure and/or management systems limit its knowledge of... and how that structure or system would avoid or mitigate such organizational conflict. (d) No award...

Adenylyl cyclases in the digestive system.

PubMed

Sabbatini, Maria Eugenia; Gorelick, Fred; Glaser, Shannon

2014-06-01

Adenylyl cyclases (ACs) are a group of widely distributed enzymes whose functions are very diverse. There are nine known transmembrane AC isoforms activated by Gαs. Each has its own pattern of expression in the digestive system and differential regulation of function by Ca(2+) and other intracellular signals. In addition to the transmembrane isoforms, one AC is soluble and exhibits distinct regulation. In this review, the basic structure, regulation and physiological roles of ACs in the digestive system are discussed. Copyright © 2014 Elsevier Inc. All rights reserved.

Adenylyl cyclases in the digestive system

PubMed Central

Sabbatini, Maria Eugenia; Gorelick, Fred; Glaser, Shannon

2015-01-01

Adenylyl cyclases (ACs) are a group of widely distributed enzymes whose functions are very diverse. There are nine known transmembrane AC isoforms activated by Gαs. Each has its own pattern of expression in the digestive system and differential regulation of function by Ca2+ and other intracellular signals. In addition to the transmembrane isoforms, one AC is soluble and exhibits distinct regulation. In this review, the basic structure, regulation and physiological roles of ACs in the digestive system are discussed. PMID:24521753

77 FR 34315 - National Pollutant Discharge Elimination System-Proposed Regulations to Establish Requirements...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-11

...-4] RIN 2040-AE95 National Pollutant Discharge Elimination System--Proposed Regulations to Establish Requirements for Cooling Water Intake Structures at Existing Facilities; Notice of Data Availability Related to... Data Availability. SUMMARY: On April 20, 2011, EPA published proposed standards for cooling water...

[Current aspects of the physiopathology of the infectious process. II. Cybernetic elements in the pathogenetic structure of infectious diseases].

PubMed

Dragomirescu, M; Buzinschi, S

1980-01-01

The authors discuss the applicability of general cybernetic principles (the theory of systems and self-regulated mechanisms based on inversed connections) to the pathophysiologic structure of infections. With reference to concrete examples they outline the following elements: the appartenance of the infectious process to the notion of system (as conceived in the theory of systems), the previsible character of the functional potential of the structured system in the components of infection, and the sequental correspondence between system dynamics and the dynamics of the infectious process. Starting from the mechanism of action of the main microbial toxins, the aptitude of the latter to act upon the functional code of the macroorganism, altering the cellular and supracellular self-regulated biosystems, is demonstrated. Finally, the practical implications of assimilating cybernetic processes in the pathophysiology of infectious diseases are analyzed.

Control design for robust stability in linear regulators: Application to aerospace flight control

NASA Technical Reports Server (NTRS)

Yedavalli, R. K.

1986-01-01

Time domain stability robustness analysis and design for linear multivariable uncertain systems with bounded uncertainties is the central theme of the research. After reviewing the recently developed upper bounds on the linear elemental (structured), time varying perturbation of an asymptotically stable linear time invariant regulator, it is shown that it is possible to further improve these bounds by employing state transformations. Then introducing a quantitative measure called the stability robustness index, a state feedback conrol design algorithm is presented for a general linear regulator problem and then specialized to the case of modal systems as well as matched systems. The extension of the algorithm to stochastic systems with Kalman filter as the state estimator is presented. Finally an algorithm for robust dynamic compensator design is presented using Parameter Optimization (PO) procedure. Applications in a aircraft control and flexible structure control are presented along with a comparison with other existing methods.

Emotion regulation and the dynamics of feelings: a conceptual and methodological framework.

PubMed

Hoeksma, Jan B; Oosterlaan, Jaap; Schipper, Eline M

2004-01-01

The emotional system is defined as a dynamical system that has neurological and biochemical structures that force the system to change in a regular and consistent way. This dynamic view allows for an alternative definition of emotion regulation, which describes when emotion regulation is needed, identifies its goal, and illustrates how regulation is achieved. The thesis developed here is that feelings-the private mental experience of emotion-play a crucial role in emotion regulation. Specifics of regulation are discussed and a parallel with parent-child interaction is drawn. It is shown that emotion regulation can be studied by looking at the variability of feelings. An illustrative application (N=30, age 10-13 years) shows that variability of anger is associated with the core executive function response inhibition.

Codon usage regulates protein structure and function by affecting translation elongation speed in Drosophila cells.

PubMed

Zhao, Fangzhou; Yu, Chien-Hung; Liu, Yi

2017-08-21

Codon usage biases are found in all eukaryotic and prokaryotic genomes and have been proposed to regulate different aspects of translation process. Codon optimality has been shown to regulate translation elongation speed in fungal systems, but its effect on translation elongation speed in animal systems is not clear. In this study, we used a Drosophila cell-free translation system to directly compare the velocity of mRNA translation elongation. Our results demonstrate that optimal synonymous codons speed up translation elongation while non-optimal codons slow down translation. In addition, codon usage regulates ribosome movement and stalling on mRNA during translation. Finally, we show that codon usage affects protein structure and function in vitro and in Drosophila cells. Together, these results suggest that the effect of codon usage on translation elongation speed is a conserved mechanism from fungi to animals that can affect protein folding in eukaryotic organisms. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

The role of symmetry in the regulation of brain dynamics

NASA Astrophysics Data System (ADS)

Tang, Evelyn; Giusti, Chad; Cieslak, Matthew; Grafton, Scott; Bassett, Danielle

Synchronous neural processes regulate a wide range of behaviors from attention to learning. Yet structural constraints on these processes are far from understood. We draw on new theoretical links between structural symmetries and the control of synchronous function, to offer a reconceptualization of the relationships between brain structure and function in human and non-human primates. By classifying 3-node motifs in macaque connectivity data, we find the most prevalent motifs can theoretically ensure a diversity of function including strict synchrony as well as control to arbitrary states. The least prevalent motifs are theoretically controllable to arbitrary states, which may not be desirable in a biological system. In humans, regions with high topological similarity of connections (a continuous notion related to symmetry) are most commonly found in fronto-parietal systems, which may account for their critical role in cognitive control. Collectively, our work underscores the role of symmetry and topological similarity in regulating dynamics of brain function.

State, Federal, and Local Regulation of Cable Television.

ERIC Educational Resources Information Center

Barnett, Stephen R.

1972-01-01

After reviewing the results of local regulation of cable television, the author feels that local governments are not fully capable of properly administering and regulating a cable system. (The Federal Communications Commission (FCC) agrees that this job should be the states' responsibility.) The article then reviews the structure of the current…

Understanding how replication processes can maintain systems away from equilibrium using Algorithmic Information Theory.

PubMed

Devine, Sean D

2016-02-01

Replication can be envisaged as a computational process that is able to generate and maintain order far-from-equilibrium. Replication processes, can self-regulate, as the drive to replicate can counter degradation processes that impact on a system. The capability of replicated structures to access high quality energy and eject disorder allows Landauer's principle, in conjunction with Algorithmic Information Theory, to quantify the entropy requirements to maintain a system far-from-equilibrium. Using Landauer's principle, where destabilising processes, operating under the second law of thermodynamics, change the information content or the algorithmic entropy of a system by ΔH bits, replication processes can access order, eject disorder, and counter the change without outside interventions. Both diversity in replicated structures, and the coupling of different replicated systems, increase the ability of the system (or systems) to self-regulate in a changing environment as adaptation processes select those structures that use resources more efficiently. At the level of the structure, as selection processes minimise the information loss, the irreversibility is minimised. While each structure that emerges can be said to be more entropically efficient, as such replicating structures proliferate, the dissipation of the system as a whole is higher than would be the case for inert or simpler structures. While a detailed application to most real systems would be difficult, the approach may well be useful in understanding incremental changes to real systems and provide broad descriptions of system behaviour. Copyright © 2016 The Author. Published by Elsevier Ireland Ltd.. All rights reserved.

Regulation of chromatin structure in the cardiovascular system.

PubMed

Rosa-Garrido, Manuel; Karbassi, Elaheh; Monte, Emma; Vondriska, Thomas M

2013-01-01

It has been appreciated for some time that cardiovascular disease involves large-scale transcriptional changes in various cell types. What has become increasingly clear only in the past few years, however, is the role of chromatin remodeling in cardiovascular phenotypes in normal physiology, as well as in development and disease. This review summarizes the state of the chromatin field in terms of distinct mechanisms to regulate chromatin structure in vivo, identifying when these modes of regulation have been demonstrated in cardiovascular tissues. We describe areas in which a better understanding of chromatin structure is leading to new insights into the fundamental biology of cardiovascular disease. 

Closed-form solutions for linear regulator design of mechanical systems including optimal weighting matrix selection

NASA Technical Reports Server (NTRS)

Hanks, Brantley R.; Skelton, Robert E.

1991-01-01

Vibration in modern structural and mechanical systems can be reduced in amplitude by increasing stiffness, redistributing stiffness and mass, and/or adding damping if design techniques are available to do so. Linear Quadratic Regulator (LQR) theory in modern multivariable control design, attacks the general dissipative elastic system design problem in a global formulation. The optimal design, however, allows electronic connections and phase relations which are not physically practical or possible in passive structural-mechanical devices. The restriction of LQR solutions (to the Algebraic Riccati Equation) to design spaces which can be implemented as passive structural members and/or dampers is addressed. A general closed-form solution to the optimal free-decay control problem is presented which is tailored for structural-mechanical system. The solution includes, as subsets, special cases such as the Rayleigh Dissipation Function and total energy. Weighting matrix selection is a constrained choice among several parameters to obtain desired physical relationships. The closed-form solution is also applicable to active control design for systems where perfect, collocated actuator-sensor pairs exist.

Effect of simulated microgravitation on phytohormones and cell structure of tropical orchids

NASA Astrophysics Data System (ADS)

Cherevchenko, T.; Zaimenko, N.; Majko, T.; Sytnjanskaja, N.

When studing the effect of two month clinostating on the phytohormonal system of orchids with different types of shoot system branching and different shoot morphology, it was determined that, as a result of simulated microgravitation, endogenous growth regulators changed less in the species with sympodial branching than in species with monopodial branching and without pseudobulbs. Stimulators prevail in the balance of growth regulators in species of the first type and inhibitors in species of the second type. Besides this, comparative analysis of structural organization of juvenile leaf surface tissue of tested orchids was carried out. Variability of size, number and structure of stomatal organization were found according to species belonging to each branching type after clinostating. Electronic microscope studies show some structural peculiarities of epidermal and mesophilous cells.

Structure and mechanisms of Escherichia coli aspartate transcarbamoylase.

PubMed

Lipscomb, William N; Kantrowitz, Evan R

2012-03-20

Enzymes catalyze a particular reaction in cells, but only a few control the rate of this reaction and the metabolic pathway that follows. One specific mechanism for such enzymatic control of a metabolic pathway involves molecular feedback, whereby a metabolite further down the pathway acts at a unique site on the control enzyme to alter its activity allosterically. This regulation may be positive or negative (or both), depending upon the particular system. Another method of enzymatic control involves the cooperative binding of the substrate, which allows a large change in enzyme activity to emanate from only a small change in substrate concentration. Allosteric regulation and homotropic cooperativity are often known to involve significant conformational changes in the structure of the protein. Escherichia coli aspartate transcarbamoylase (ATCase) is the textbook example of an enzyme that regulates a metabolic pathway, namely, pyrimidine nucleotide biosynthesis, by feedback control and by the cooperative binding of the substrate, L-aspartate. The catalytic and regulatory mechanisms of this enzyme have been extensively studied. A series of X-ray crystal structures of the enzyme in the presence and absence of substrates, products, and analogues have provided details, at the molecular level, of the conformational changes that the enzyme undergoes as it shifts between its low-activity, low-affinity form (T state) to its high-activity, high-affinity form (R state). These structural data provide insights into not only how this enzyme catalyzes the reaction between l-aspartate and carbamoyl phosphate to form N-carbamoyl-L-aspartate and inorganic phosphate, but also how the allosteric effectors modulate this activity. In this Account, we summarize studies on the structure of the enzyme and describe how these structural data provide insights into the catalytic and regulatory mechanisms of the enzyme. The ATCase-catalyzed reaction is regulated by nucleotide binding some 60 Å from the active site, inducing structural alterations that modulate catalytic activity. The delineation of the structure and function in this particular model system will help in understanding the molecular basis of cooperativity and allosteric regulation in other systems as well.

Synergetics of hardening construction systems

NASA Astrophysics Data System (ADS)

Tolstoy, A. D.; Lesovik, V. S.; Glagolev, E. S.; Krymova, A. I.

2018-03-01

The study of hardening high-strength systems indicates the relation between the potential of synergetics and issues related to structure formation of aggregates produced on the basis of rationally selected construction mixes. The paper considers challenges of the general principles of synergetics and sustainable development of open dissipative systems and their use in industry, as well as their understanding as complete self-regulating nonequilibrium systems. The main objective of the study was to demonstrate that the principles of self-regulating systems development can be applied in construction technology.

Closed-form solutions for linear regulator-design of mechanical systems including optimal weighting matrix selection

NASA Technical Reports Server (NTRS)

Hanks, Brantley R.; Skelton, Robert E.

1991-01-01

This paper addresses the restriction of Linear Quadratic Regulator (LQR) solutions to the algebraic Riccati Equation to design spaces which can be implemented as passive structural members and/or dampers. A general closed-form solution to the optimal free-decay control problem is presented which is tailored for structural-mechanical systems. The solution includes, as subsets, special cases such as the Rayleigh Dissipation Function and total energy. Weighting matrix selection is a constrained choice among several parameters to obtain desired physical relationships. The closed-form solution is also applicable to active control design for systems where perfect, collocated actuator-sensor pairs exist. Some examples of simple spring mass systems are shown to illustrate key points.

Evolution and Design Governing Signal Precision and Amplification in a Bacterial Chemosensory Pathway

PubMed Central

Espinosa, Leon; Baronian, Grégory; Molle, Virginie; Mauriello, Emilia M. F.; Brochier-Armanet, Céline; Mignot, Tâm

2015-01-01

Understanding the principles underlying the plasticity of signal transduction networks is fundamental to decipher the functioning of living cells. In Myxococcus xanthus, a particular chemosensory system (Frz) coordinates the activity of two separate motility systems (the A- and S-motility systems), promoting multicellular development. This unusual structure asks how signal is transduced in a branched signal transduction pathway. Using combined evolution-guided and single cell approaches, we successfully uncoupled the regulations and showed that the A-motility regulation system branched-off an existing signaling system that initially only controlled S-motility. Pathway branching emerged in part following a gene duplication event and changes in the circuit structure increasing the signaling efficiency. In the evolved pathway, the Frz histidine kinase generates a steep biphasic response to increasing external stimulations, which is essential for signal partitioning to the motility systems. We further show that this behavior results from the action of two accessory response regulator proteins that act independently to filter and amplify signals from the upstream kinase. Thus, signal amplification loops may underlie the emergence of new connectivity in signal transduction pathways. PMID:26291327

The chloroplast ATP synthase features the characteristic redox regulation machinery.

PubMed

Hisabori, Toru; Sunamura, Ei-Ichiro; Kim, Yusung; Konno, Hiroki

2013-11-20

Regulation of the activity of the chloroplast ATP synthase is largely accomplished by the chloroplast thioredoxin system, the main redox regulation system in chloroplasts, which is directly coupled to the photosynthetic reaction. We review the current understanding of the redox regulation system of the chloroplast ATP synthase. The thioredoxin-targeted portion of the ATP synthase consists of two cysteines located on the central axis subunit γ. The redox state of these two cysteines is under the influence of chloroplast thioredoxin, which directly controls rotation during catalysis by inducing a conformational change in this subunit. The molecular mechanism of redox regulation of the chloroplast ATP synthase has recently been determined. Regulation of the activity of the chloroplast ATP synthase is critical in driving efficiency into the ATP synthesis reaction in chloroplasts. The molecular architecture of the chloroplast ATP synthase, which confers redox regulatory properties requires further investigation, in light of the molecular structure of the enzyme complex as well as the physiological significance of the regulation system.

Approaches Mediating Oxytocin Regulation of the Immune System.

PubMed

Li, Tong; Wang, Ping; Wang, Stephani C; Wang, Yu-Feng

2016-01-01

The hypothalamic neuroendocrine system is mainly composed of the neural structures regulating hormone secretion from the pituitary gland and has been considered as the higher regulatory center of the immune system. Recently, the hypothalamo-neurohypophysial system (HNS) emerged as an important component of neuroendocrine-immune network, wherein the oxytocin (OT)-secreting system (OSS) plays an essential role. The OSS, consisting of OT neurons in the supraoptic nucleus, paraventricular nucleus, their several accessory nuclei and associated structures, can integrate neural, endocrine, metabolic, and immune information and plays a pivotal role in the development and functions of the immune system. The OSS can promote the development of thymus and bone marrow, perform immune surveillance, strengthen immune defense, and maintain immune homeostasis. Correspondingly, OT can inhibit inflammation, exert antibiotic-like effect, promote wound healing and regeneration, and suppress stress-associated immune disorders. In this process, the OSS can release OT to act on immune system directly by activating OT receptors or through modulating activities of other hypothalamic-pituitary-immune axes and autonomic nervous system indirectly. However, our understandings of the role of the OSS in neuroendocrine regulation of immune system are largely incomplete, particularly its relationship with other hypothalamic-pituitary-immune axes and the vasopressin-secreting system that coexists with the OSS in the HNS. In addition, it remains unclear about the relationship between the OSS and peripherally produced OT in immune regulation, particularly intrathymic OT that is known to elicit central immunological self-tolerance of T-cells to hypophysial hormones. In this work, we provide a brief review of current knowledge of the features of OSS regulation of the immune system and of potential approaches that mediate OSS coordination of the activities of entire neuroendocrine-immune network.

Resilience as Regulation of Developmental and Family Processes

PubMed Central

MacPhee, David; Lunkenheimer, Erika; Riggs, Nathaniel

2015-01-01

Resilience can be defined as establishing equilibrium subsequent to disturbances to a system caused by significant adversity. When families experience adversity or transitions, multiple regulatory processes may be involved in establishing equilibrium, including adaptability, regulation of negative affect, and effective problem-solving skills. The authors’ resilience-as-regulation perspective integrates insights about the regulation of individual development with processes that regulate family systems. This middle-range theory of family resilience focuses on regulatory processes across levels that are involved in adaptation: whole-family systems such as routines and sense of coherence; coregulation of dyads involving emotion regulation, structuring, and reciprocal influences between social partners; and individual self-regulation. Insights about resilience-as-regulation are then applied to family-strengthening interventions that are designed to promote adaptation to adversity. Unresolved issues are discussed in relation to resilience-as-regulation in families, in particular how risk exposure is assessed, interrelations among family regulatory mechanisms, and how families scaffold the development of children’s resilience. PMID:26568647

Simultaneous structural and control optimization via linear quadratic regulator eigenstructure assignment

NASA Technical Reports Server (NTRS)

Becus, G. A.; Lui, C. Y.; Venkayya, V. B.; Tischler, V. A.

1987-01-01

A method for simultaneous structural and control design of large flexible space structures (LFSS) to reduce vibration generated by disturbances is presented. Desired natural frequencies and damping ratios for the closed loop system are achieved by using a combination of linear quadratic regulator (LQR) synthesis and numerical optimization techniques. The state and control weighing matrices (Q and R) are expressed in terms of structural parameters such as mass and stiffness. The design parameters are selected by numerical optimization so as to minimize the weight of the structure and to achieve the desired closed-loop eigenvalues. An illustrative example of the design of a two bar truss is presented.

Structural Basis for Conserved Regulation and Adaptation of the Signal Recognition Particle Targeting Complex.

PubMed

Wild, Klemens; Bange, Gert; Motiejunas, Domantas; Kribelbauer, Judith; Hendricks, Astrid; Segnitz, Bernd; Wade, Rebecca C; Sinning, Irmgard

2016-07-17

The signal recognition particle (SRP) is a ribonucleoprotein complex with a key role in targeting and insertion of membrane proteins. The two SRP GTPases, SRP54 (Ffh in bacteria) and FtsY (SRα in eukaryotes), form the core of the targeting complex (TC) regulating the SRP cycle. The architecture of the TC and its stimulation by RNA has been described for the bacterial SRP system while this information is lacking for other domains of life. Here, we present the crystal structures of the GTPase heterodimers of archaeal (Sulfolobus solfataricus), eukaryotic (Homo sapiens), and chloroplast (Arabidopsis thaliana) SRP systems. The comprehensive structural comparison combined with Brownian dynamics simulations of TC formation allows for the description of the general blueprint and of specific adaptations of the quasi-symmetric heterodimer. Our work defines conserved external nucleotide-binding sites for SRP GTPase activation by RNA. Structural analyses of the GDP-bound, post-hydrolysis states reveal a conserved, magnesium-sensitive switch within the I-box. Overall, we provide a general model for SRP cycle regulation by RNA. Copyright © 2016 Elsevier Ltd. All rights reserved.

Optimal Regulation of Structural Systems with Uncertain Parameters.

DTIC Science & Technology

1981-02-02

been addressed, in part, by Statistical Energy Analysis . Moti- vated by a concern with high frequency vibration and acoustical- structural...Parameter Systems," AFOSR-TR-79-0753 (May, 1979). 25. R. H. Lyon, Statistical Energy Analysis of Dynamical Systems: Theory and Applications, (M.I.T...Press, Cambridge, Mass., 1975). 26. E. E. Ungar, " Statistical Energy Analysis of Vibrating Systems," Trans. ASME, J. Eng. Ind. 89, 626 (1967). 139 27

18 CFR 1304.209 - Land-based structures/alterations.

Code of Federal Regulations, 2014 CFR

2014-04-01

..., satellite antennas, septic tanks, and septic drainfields shall not be allowed on TVA land. (c) Utility lines... APPROVAL OF CONSTRUCTION IN THE TENNESSEE RIVER SYSTEM AND REGULATION OF STRUCTURES AND OTHER ALTERATIONS...

18 CFR 1304.209 - Land-based structures/alterations.

Code of Federal Regulations, 2013 CFR

2013-04-01

..., satellite antennas, septic tanks, and septic drainfields shall not be allowed on TVA land. (c) Utility lines... APPROVAL OF CONSTRUCTION IN THE TENNESSEE RIVER SYSTEM AND REGULATION OF STRUCTURES AND OTHER ALTERATIONS...

Prokaryotic 2-component systems and the OmpR/PhoB superfamily.

PubMed

Nguyen, Minh-Phuong; Yoon, Joo-Mi; Cho, Man-Ho; Lee, Sang-Won

2015-11-01

In bacteria, 2-component regulatory systems (TCSs) are the critical information-processing pathways that link stimuli to specific adaptive responses. Signals perceived by membrane sensors, which are generally histidine kinases, are transmitted by response regulators (RRs) to allow cells to cope rapidly and effectively with environmental challenges. Over the past few decades, genes encoding components of TCSs and their responsive proteins have been identified, crystal structures have been described, and signaling mechanisms have been elucidated. Here, we review recent findings and interesting breakthroughs in bacterial TCS research. Furthermore, we discuss structural features, mechanisms of activation and regulation, and cross-regulation of RRs, with a focus on the largest RR family, OmpR/PhoB, to provide a comprehensive overview of these critically important signaling molecules.

[The function of ERα in male reproductive system].

PubMed

Dong, Yu-Hang; Wei, Jin-Hua; Li, Zhen

2014-12-01

Estrogen receptors (ERs), including two sub-types ERα and ERβ, belong to the steroid hormone superfamily of nuclear receptors. ERα distributes in the male reproductive system and plays a crucial role in the regulation of male reproduction through estrogen-dependent and -independent ways. In this article, we mainly reviewed the molecular structure, mode of action and location of ERα in the male reproductive system, and explored the mechanism of ERα in regulating the male reproductive system by analyzing different animal models of disrupted ERα.

Structural Insights into Central Hypertension Regulation by Human Aminopeptidase A*

PubMed Central

Yang, Yang; Liu, Chang; Lin, Yi-Lun; Li, Fang

2013-01-01

Hypertension is regulated through both the central and systemic renin-angiotensin systems. In the central renin-angiotensin system, zinc-dependent aminopeptidase A (APA) up-regulates blood pressure by specifically cleaving the N-terminal aspartate, but not the adjacent arginine, from angiotensin II, a process facilitated by calcium. Here, we determined the crystal structures of human APA and its complexes with different ligands and identified a calcium-binding site in the S1 pocket of APA. Without calcium, the S1 pocket can bind both acidic and basic residues through formation of salt bridges with the charged side chains. In the presence of calcium, the binding of acidic residues is enhanced as they ligate the cation, whereas the binding of basic residues is no longer favorable due to charge repulsion. Of the peptidomimetic inhibitors of APA, amastatin has higher potency than bestatin by fitting better in the S1 pocket and interacting additionally with the S3′ subsite. These results explain the calcium-modulated substrate specificity of APA in central hypertension regulation and can guide the design and development of brain-targeting antihypertensive APA inhibitors. PMID:23888046

Structural insights into central hypertension regulation by human aminopeptidase A.

PubMed

Yang, Yang; Liu, Chang; Lin, Yi-Lun; Li, Fang

2013-08-30

Hypertension is regulated through both the central and systemic renin-angiotensin systems. In the central renin-angiotensin system, zinc-dependent aminopeptidase A (APA) up-regulates blood pressure by specifically cleaving the N-terminal aspartate, but not the adjacent arginine, from angiotensin II, a process facilitated by calcium. Here, we determined the crystal structures of human APA and its complexes with different ligands and identified a calcium-binding site in the S1 pocket of APA. Without calcium, the S1 pocket can bind both acidic and basic residues through formation of salt bridges with the charged side chains. In the presence of calcium, the binding of acidic residues is enhanced as they ligate the cation, whereas the binding of basic residues is no longer favorable due to charge repulsion. Of the peptidomimetic inhibitors of APA, amastatin has higher potency than bestatin by fitting better in the S1 pocket and interacting additionally with the S3' subsite. These results explain the calcium-modulated substrate specificity of APA in central hypertension regulation and can guide the design and development of brain-targeting antihypertensive APA inhibitors.

[Principles of organization and evolution of systems of regulation of functions].

PubMed

Veselkin, N P; Natochin, Iu V

2010-01-01

Evolution of living organisms is closely connected with evolution of structure of the system of regulations and its mechanisms. The functional ground of regulations is chemical signalization. As early as in unicellular organisms there is a set of signal mechanisms providing their life activity and orientation in space and time. Subsequent evolution of ways of chemical signalization followed the way of development of ways of delivery of chemical signal and development of mechanisms of its regulation. The mechanisms of chemical regulation of the signal interaction is discussed by the example of the specialized system of transduction of signal from neuron to neuron, of effect of hormone on the epithelial cell and modulation of this effect. These mechanisms are considered as the most important ways of the fine and precise adaptation of chemical signalization underlying functioning of physiological systems and organs of the living organism.

Neurobiological circuits regulating attention, cognitive control, motivation, and emotion: disruptions in neurodevelopmental psychiatric disorders.

PubMed

Arnsten, Amy F T; Rubia, Katya

2012-04-01

This article aims to review basic and clinical studies outlining the roles of prefrontal cortical (PFC) networks in the behavior and cognitive functions that are compromised in childhood neurodevelopmental disorders and how these map into the neuroimaging evidence of circuit abnormalities in these disorders. Studies of animals, normally developing children, and patients with neurodevelopmental disorders were reviewed, with focus on neuroimaging studies. The PFC provides "top-down" regulation of attention, inhibition/cognitive control, motivation, and emotion through connections with posterior cortical and subcortical structures. Dorsolateral and inferior PFC regulate attention and cognitive/inhibitory control, whereas orbital and ventromedial structures regulate motivation and affect. PFC circuitries are very sensitive to their neurochemical environment, and small changes in the underlying neurotransmitter systems, e.g. by medications, can produce large effects on mediated function. Neuroimaging studies of children with neurodevelopmental disorders show altered brain structure and function in distinctive circuits respecting this organization. Children with attention-deficit/hyperactivity disorder show prominent abnormalities in the inferior PFC and its connections to striatal, cerebellar, and parietal regions, whereas children with conduct disorder show alterations in the paralimbic system, comprising ventromedial, lateral orbitofrontal, and superior temporal cortices together with specific underlying limbic regions, regulating motivation and emotion control. Children with major depressive disorder show alterations in ventral orbital and limbic activity, particularly in the left hemisphere, mediating emotions. Finally, children with obsessive-compulsive disorder appear to have a dysregulation in orbito-fronto-striatal inhibitory control pathways, but also deficits in dorsolateral fronto-parietal systems of attention. Altogether, there is a good correspondence between anatomical circuitry mediating compromised functions and patterns of brain structure and function changes in children with neuropsychiatric disorders. Medications may optimize the neurochemical environment in PFC and associated circuitries, and improve structure and function. Copyright © 2012 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Regulation of intraocular pressure in mice: structural analysis of dopaminergic and serotonergic systems in response to cabergoline.

PubMed

Platania, Chiara Bianca Maria; Leggio, Gian Marco; Drago, Filippo; Salomone, Salvatore; Bucolo, Claudio

2013-11-01

Elevated intraocular pressure (IOP) is the main recognized risk factor of glaucoma. To investigate the contribution of dopaminergic and serotonergic systems in IOP regulation, we used cabergoline, a mixed dopamine and serotonin agonist, in C57BL/6J WT and dopamine D₃ receptor knock-out (D₃R⁻/⁻) mice with normal eye pressure or steroid-induced ocular hypertension. Furthermore, we studied the structural basis of the cabergoline-mediated activation of the dopaminergic and serotonergic systems by molecular modeling. Topical application of cabergoline, significantly decreased, in a dose-dependent manner, the intraocular pressure in WT mice, both in an ocular normotensive group (-9, -5 and -2 mmHg with 5%, 1%, and 0.1%, respectively) and an ocular hypertensive group, with a prolonged effect in this latter group. No change of intraocular pressure was observed after topical application of cabergoline in D₃R⁻/⁻ mice. We modeled and optimized, with molecular dynamics, structures of hD₃, h5HT(1A) and h5HT(2A-C) receptors; thereafter we carried out molecular docking of cabergoline. Docking revealed that binding of cabergoline into D₃ and 5HT(1A) receptors is associated with a better desolvation energy in comparison to 5HT(2A-C) binding. In conclusion, the present study support the hypothesis that dopaminergic system is pivotal to regulate IOP and that D₃R represents an intriguing target in the treatment of glaucoma. Furthermore, the structure-based computational approach adopted in this study is able to build and refine structure models of homologous dopaminergic and serotonergic receptors that may be of interest for structure-based drug discovery of ligands, with dopaminergic selectivity or with multi-pharmacological profile, potentially useful to treat optic neuropathies. Copyright © 2013 Elsevier Inc. All rights reserved.

78 FR 30231 - Defense Federal Acquisition Regulation Supplement: Clarification of “F” Orders in the Procurement...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-22

... Identification Number Structure (DFARS Case 2012-D040) AGENCY: Defense Acquisition Regulations System, Department... data by the ``F'' in 9th position does not provide a sufficiently discrete result. DoD uses other data...

Reforming insurance to support workers' rights to compensation.

PubMed

McCluskey, Martha T

2012-06-01

The structure and regulation of the insurance system for financing workers' compensation affects the costs of workers' benefits. Using the example of Maine's insurance market restructuring in response to a crisis of the early 1990s, this commentary explores how changes in insurance regulation might better support the goals of workers' compensation. The commentary analyzes how insurance and its regulation should go beyond correct pricing of risks to questions of how to structure incentives for loss control to include workers' interests as well as the interests of employers and insurers. Copyright © 2012 Wiley Periodicals, Inc.

Conserved ABC Transport System Regulated by the General Stress Response Pathways of Alpha- and Gammaproteobacteria.

PubMed

Herrou, Julien; Willett, Jonathan W; Czyż, Daniel M; Babnigg, Gyorgy; Kim, Youngchang; Crosson, Sean

2017-03-01

Brucella abortus σ E1 is an EcfG family sigma factor that regulates the transcription of dozens of genes in response to diverse stress conditions and is required for maintenance of chronic infection in a mouse model. A putative ATP-binding cassette transporter operon, bab1_0223-bab1_0226 , is among the most highly activated gene sets in the σ E1 regulon. The proteins encoded by the operon resemble quaternary ammonium-compatible solute importers but are most similar in sequence to the broadly conserved YehZYXW system, which remains largely uncharacterized. Transcription of yehZYXW is activated by the general stress sigma factor σ S in Enterobacteriaceae , which suggests a functional role for this transport system in bacterial stress response across the classes Alphaproteobacteria and Gammaproteobacteria We present evidence that B. abortus YehZYXW does not function as an importer of known compatible solutes under physiological conditions and does not contribute to the virulence defect of a σ E1 -null strain. The sole in vitro phenotype associated with genetic disruption of this putative transport system is reduced growth in the presence of high Li + ion concentrations. A crystal structure of B. abortus YehZ revealed a class II periplasmic binding protein fold with significant structural homology to Archaeoglobus fulgidus ProX, which binds glycine betaine. However, the structure of the YehZ ligand-binding pocket is incompatible with high-affinity binding to glycine betaine. This is consistent with weak measured binding of YehZ to glycine betaine and related compatible solutes. We conclude that YehZYXW is a conserved, stress-regulated transport system that is phylogenetically and functionally distinct from quaternary ammonium-compatible solute importers. IMPORTANCE Brucella abortus σ E1 regulates transcription in response to stressors encountered in its mammalian host and is necessary for maintenance of chronic infection in a mouse model. The functions of the majority of genes regulated by σ E1 remain undefined. We present a functional/structural analysis of a conserved putative membrane transport system (YehZYXW) whose expression is strongly activated by σ E1 Though annotated as a quaternary ammonium osmolyte uptake system, experimental physiological studies and measured ligand-binding properties of the periplasmic binding protein (PBP), YehZ, are inconsistent with this function. A crystal structure of B. abortus YehZ provides molecular insight into differences between bona fide quaternary ammonium osmolyte importers and YehZ-related proteins, which form a distinct phylogenetic and functional group of PBPs. Copyright © 2017 American Society for Microbiology.

5 CFR 532.203 - Structure of regular wage schedules.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Structure of regular wage schedules. 532.203 Section 532.203 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PREVAILING RATE SYSTEMS Prevailing Rate Determinations § 532.203 Structure of regular wage schedules. (a...

Almost output regulation of LFT systems via gain-scheduling control

NASA Astrophysics Data System (ADS)

Yuan, Chengzhi; Duan, Chang; Wu, Fen

2018-05-01

Output regulation of general uncertain systems is a meaningful yet challenging problem. In spite of the rich literature in the field, the problem has not yet been addressed adequately due to the lack of an effective design mechanism. In this paper, we propose a new design framework for almost output regulation of uncertain systems described in the general form of linear fractional transformation (LFT) with time-varying parametric uncertainties and unknown external perturbations. A novel semi-LFT gain-scheduling output regulator structure is proposed, such that the associated control synthesis conditions guaranteeing both output regulation and ? disturbance attenuation performance are formulated as a set of linear matrix inequalities (LMIs) plus parameter-dependent linear matrix equations, which can be solved separately. A numerical example has been used to demonstrate the effectiveness of the proposed approach.

The Chloroplast ATP Synthase Features the Characteristic Redox Regulation Machinery

PubMed Central

Sunamura, Ei-Ichiro; Kim, Yusung; Konno, Hiroki

2013-01-01

Abstract Significance: Regulation of the activity of the chloroplast ATP synthase is largely accomplished by the chloroplast thioredoxin system, the main redox regulation system in chloroplasts, which is directly coupled to the photosynthetic reaction. We review the current understanding of the redox regulation system of the chloroplast ATP synthase. Recent Advances: The thioredoxin-targeted portion of the ATP synthase consists of two cysteines located on the central axis subunit γ. The redox state of these two cysteines is under the influence of chloroplast thioredoxin, which directly controls rotation during catalysis by inducing a conformational change in this subunit. The molecular mechanism of redox regulation of the chloroplast ATP synthase has recently been determined. Critical Issues: Regulation of the activity of the chloroplast ATP synthase is critical in driving efficiency into the ATP synthesis reaction in chloroplasts. Future Directions: The molecular architecture of the chloroplast ATP synthase, which confers redox regulatory properties requires further investigation, in light of the molecular structure of the enzyme complex as well as the physiological significance of the regulation system. Antioxid. Redox Signal. 19, 1846–1854. PMID:23145525

The Structure of the Managerial System of Higher Education's Development

ERIC Educational Resources Information Center

Levina, Elena Y.; Kutuev, Ruslan A.; Balakhnina, Lidia V.; Tumarov, Konstantin B.; Chudnovskiy, Alexey D.; Shagiev, ?ulat V.

2016-01-01

The research urgency is caused by necessity of planning regulation of higher education development at all levels of management. The purpose of this article is to develop the structure of a control system of higher education development, the Foundation of which is understanding of the quality of higher education as factor for development of the…

75 FR 41097 - Homeland Security Acquisition Regulation; Lead System Integrators [HSAR Case 2009-003

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-15

... contract type and fee structure based on risks inherent in the work to be performed, in accordance with... competitive procedures, DHS takes appropriate steps to prevent any organizational conflicts of interest in the... specification of various types of contracts and fee structures that are appropriate for use with lead system...

Distribution of cocaine and amphetamine regulated transcript in ureters and urinary bladder of hypertensive rats.

PubMed

Janiuk, I; Kasacka, I

2013-01-01

Cocaine and amphetamine regulated transcript (CART), a neuropeptide of the central and peripheral nervous system plays an essential role in maintaining body homeostasis by regulating body temperature, orexia, digestive motility and blood pressure. Very few studies describe the relationship of hyperten¬sion with CART. Therefore, the present research was undertaken to identify, locate and determine the number of CART-immunopositive neuroendocrine cells (NE) and structures in the urinary bladder and ureter of rats with experimentally induced nephrogenic hypertension. The experiments were conducted on 20 Wistar rats in which hypertension was experimentally induced by applying a clamp on the left renal artery based on the two kidney, one clip experimental model (2K1C). After 6 weeks, fragments of the ureters and urinary bladder were sampled from rats with permanent hypertension. Immunohisto¬chemical analyses revealed a salient effect of renovascular hypertension on the neuroendocrine system of rat ureters and urinary bladder. Differences in the number of neuroendocrine cells and in the density of CART-positive structures were identified between the hypertensive and normotensive (control) rats. Hypertension greatly increased the number of NE cells and the density of CART- immunoreactive (IR) structures in the analysed urinary system organs.

Federal Aviation Regulations - National Aviation Regulations of Russia

NASA Astrophysics Data System (ADS)

Chernykh, O.; Bakiiev, M.

2018-03-01

Chinese Aerospace Engineering is currently developing cooperation with Russia on a wide-body airplane project that has directed the work towards better understanding of Russian airworthiness management system. The paper introduces national Aviation regulations of Russia, presents a comparison of them with worldwide recognized regulations, and highlights typical differences. They have been found to be: two general types of regulations used in Russia (Aviation Regulations and Federal Aviation Regulations), non-unified structure of regulations on Aircraft Operation management, various separate agencies responsible for regulation issuance instead of one national aviation authority, typical confusions in references. The paper also gives a list of effective Russian Regulations of both types.

Output regulation control for switched stochastic delay systems with dissipative property under error-dependent switching

NASA Astrophysics Data System (ADS)

Li, L. L.; Jin, C. L.; Ge, X.

2018-01-01

In this paper, the output regulation problem with dissipative property for a class of switched stochastic delay systems is investigated, based on an error-dependent switching law. Under the assumption that none subsystem is solvable for the problem, a sufficient condition is derived by structuring multiple Lyapunov-Krasovskii functionals with respect to multiple supply rates, via designing error feedback regulators. The condition is also established when dissipative property reduces to passive property. Finally, two numerical examples are given to demonstrate the feasibility and efficiency of the present method.

Structure and functions of internal working models of attachment and their role for emotion regulation.

PubMed

Zimmermann, P

1999-12-01

The concept of organization in the service of adaptation has been applied to attachment theory (Sroufe & Waters, 1977) as well as to a variety of life sciences (Ryan, Kuhi & Deci, 1997). Internal working models (IWMs) are postulated as providing organizing structure to the attachment behavior system controlling attachment behaviors toward caregivers and, with increasing age, autonomous individual adaptation. While many theoretical specifications have been suggested on that topic (e.g. Bretherton, 1987, 1990; Bretherton & Munholland, 1999; Main, Kaplan & Cassidy, 1985; Sroufe & Fleeson, 1986), empirical studies focusing directly on the structure or functions of internal working models are rare. Knowledge about the structure and functioning of IWMs could add to the understanding of the developmental influences of the attachment organization across the life-span. In this paper two topics will be addressed shortly and related to an empirical investigation concerning the relationship between attachment representations during late adolescence and emotion regulation patterns: (1) structure and functions of IWMs in terms of information-processing and emotion and behavior regulation; and (2) the transfer from IWMs of self-with-attachment figures to adaptive personality structures based on autonomous self-regulation.

18 CFR 1304.410 - Navigation restrictions.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., structures, land based or water use, shall not be located within the limits of safety harbors and landings established for commercial navigation. (b) Structures shall not be located in such a way as to block the... OF CONSTRUCTION IN THE TENNESSEE RIVER SYSTEM AND REGULATION OF STRUCTURES AND OTHER ALTERATIONS...

18 CFR 1304.410 - Navigation restrictions.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., structures, land based or water use, shall not be located within the limits of safety harbors and landings established for commercial navigation. (b) Structures shall not be located in such a way as to block the... OF CONSTRUCTION IN THE TENNESSEE RIVER SYSTEM AND REGULATION OF STRUCTURES AND OTHER ALTERATIONS...

78 FR 39638 - U.S. Integrated Ocean Observing System; Regulations To Certify and Integrate Regional...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-02

... become certified, RICEs must provide NOAA with information about their organizational structure and... to require RICEs to provide NOAA with certain information about their organizational structures... these eleven RICEs since FY 2005 to develop the organizational structure, operating procedures, and data...

18 CFR 1304.204 - Docks, piers, and boathouses.

Code of Federal Regulations, 2014 CFR

2014-04-01

... mesh leaves the interior of the structure open to the weather. (n) Except for nonnavigable houseboats... APPROVAL OF CONSTRUCTION IN THE TENNESSEE RIVER SYSTEM AND REGULATION OF STRUCTURES AND OTHER ALTERATIONS... structure of the maximum size, TVA shall determine the size of facility that may be approved. Applicants are...

18 CFR 1304.204 - Docks, piers, and boathouses.

Code of Federal Regulations, 2012 CFR

2012-04-01

... mesh leaves the interior of the structure open to the weather. (n) Except for nonnavigable houseboats... APPROVAL OF CONSTRUCTION IN THE TENNESSEE RIVER SYSTEM AND REGULATION OF STRUCTURES AND OTHER ALTERATIONS... structure of the maximum size, TVA shall determine the size of facility that may be approved. Applicants are...

18 CFR 1304.204 - Docks, piers, and boathouses.

Code of Federal Regulations, 2013 CFR

2013-04-01

... mesh leaves the interior of the structure open to the weather. (n) Except for nonnavigable houseboats... APPROVAL OF CONSTRUCTION IN THE TENNESSEE RIVER SYSTEM AND REGULATION OF STRUCTURES AND OTHER ALTERATIONS... structure of the maximum size, TVA shall determine the size of facility that may be approved. Applicants are...

Price regulation, new entry, and information shock on pharmaceutical market in Taiwan: a nationwide data-based study from 2001 to 2004

PubMed Central

2010-01-01

Background Using non-steroidal anti-inflammatory drugs (NSAIDs) as a case, we used Taiwan's National Health Insurance (NHI) database, to empirically explore the association between policy interventions (price regulation, new drug entry, and an information shock) and drug expenditures, utilization, and market structure between 2001 and 2004. Methods All NSAIDs prescribed in ambulatory visits in the NHI system during our study period were included and aggregated quarterly. Segmented regression analysis for interrupted time series was used to examine the associations between two price regulations, two new drug entries (cyclooxygennase-2 inhibitors) and the rofecoxib safety signal and expenditures and utilization of all NSAIDs. Herfindahl index (HHI) was applied to further examine the association between these interventions and market structure of NSAIDs. Results New entry was the only variable that was significantly correlated with changes of expenditures (positive change, p = 0.02) and market structure of the NSAIDs market in the NHI system. The correlation between price regulation (first price regulation, p = 0.62; second price regulation, p = 0.26) and information shock (p = 0.31) and drug expenditure were not statistically significant. There was no significant change in the prescribing volume of NSAIDs per rheumatoid arthritis (RA) or osteoarthritis (OA) ambulatory visit during the observational period. The market share of NSAIDs had also been largely substituted by these new drugs up to 50%, in a three-year period and resulted in a more concentrated market structure (HHI 0.17). Conclusions Our empirical study found that new drug entry was the main driving force behind escalating drug spending, especially by altering the market share. PMID:20653979

New Methodology for Evaluating Optimal Pricing for Primary Regulation of Deregulated Power Systems under Steady State Condition

NASA Astrophysics Data System (ADS)

Satyaramesh, P. V.; RadhaKrishna, C.

2013-06-01

A generalized pricing structure for procurement of power under frequency ancillary service is developed in this paper. It is a frequency linked-price model and suitable for deregulation market environment. This model takes into consideration: governor characteristics and frequency characteristics of generator as additional parameters in load flow method. The main objective of the new approach proposed in this paper is to establish bidding price structure for frequency regulation services in competitive ancillary electrical markets under steady state condition. Lot of literatures are available for calculating the frequency deviations with respect to load changes by using dynamic simulation methods. But in this paper, the model computes the frequency deviations for additional requirements of power under steady state with considering power system network topology. An attempt is also made in this paper to develop optimal bidding price structure for the frequency-regulated systems. It gives a signal to traders or bidders that the power demand can be assessed more accurately much closer to real time and helps participants bid more accurate quantities on day-ahead market. The recent trends of frequency linked-price model existing in Indian power systems issues required for attention are also dealt in this paper. Test calculations have been performed on 30-bus system. The paper also explains adoptability of 33 this model to practical Indian power system. The results presented are analyzed and useful conclusions are drawn.

48 CFR 915.404-4-70-2 - Weighted guidelines system.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Weighted guidelines system... guidelines system. (a) To properly reflect differences among contracts and the circumstances relating thereto... section. This is a structured system, referred to as weighted guidelines. Each profit factor or subfactor...

Arm-in-Arm Response Regulator Dimers Promote Intermolecular Signal Transduction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baker, Anna W.; Satyshur, Kenneth A.; Moreno Morales, Neydis

2016-02-01

ABSTRACT Bacteriophytochrome photoreceptors (BphPs) and their cognate response regulators make up two-component signal transduction systems which direct bacteria to mount phenotypic responses to changes in environmental light quality. Most of these systems utilize single-domain response regulators to transduce signals through unknown pathways and mechanisms. Here we describe the photocycle and autophosphorylation kinetics of RtBphP1, a red light-regulated histidine kinase from the desert bacteriumRamlibacter tataouinensis. RtBphP1 undergoes red to far-red photoconversion with rapid thermal reversion to the dark state. RtBphP1 is autophosphorylated in the dark; this activity is inhibited under red light. The RtBphP1 cognate response regulator, theR. tataouinensisbacteriophytochrome response regulatormore » (RtBRR), and a homolog, AtBRR fromAgrobacterium tumefaciens, crystallize unexpectedly as arm-in-arm dimers, reliant on a conserved hydrophobic motif, hFWAhL (where h is a hydrophobic M, V, L, or I residue). RtBRR and AtBRR dimerize distinctly from four structurally characterized phytochrome response regulators found in photosynthetic organisms and from all other receiver domain homodimers in the Protein Data Bank. A unique cacodylate-zinc-histidine tag metal organic framework yielded single-wavelength anomalous diffraction phases and may be of general interest. Examination of the effect of the BRR stoichiometry on signal transduction showed that phosphorylated RtBRR is accumulated more efficiently than the engineered monomeric RtBRR (RtBRR mon) in phosphotransfer reactions. Thus, we conclude that arm-in-arm dimers are a relevant signaling intermediate in this class of two-component regulatory systems. IMPORTANCEBphP histidine kinases and their cognate response regulators comprise widespread red light-sensing two-component systems. Much work on BphPs has focused on structural understanding of light sensing and on enhancing the natural infrared fluorescence of these proteins, rather than on signal transduction or the resultant phenotypes. To begin to address this knowledge gap, we solved the crystal structures of two single-domain response regulators encoded by a region immediately downstream of that encoding BphPs. We observed a previously unknown arm-in-arm dimer linkage. Monomerization via deletion of the C-terminal dimerization motif had an inhibitory effect on net response regulator phosphorylation, underlining the importance of these unusual dimers for signal transduction.« less

Conserved ABC Transport System Regulated by the General Stress Response Pathways of Alpha- and Gammaproteobacteria

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herrou, Julien; Willett, Jonathan W.; Czyż, Daniel M.

ABSTRACT Brucella abortusσ E1is an EcfG family sigma factor that regulates the transcription of dozens of genes in response to diverse stress conditions and is required for maintenance of chronic infection in a mouse model. A putative ATP-binding cassette transporter operon,bab1_0223-bab1_0226, is among the most highly activated gene sets in the σ E1regulon. The proteins encoded by the operon resemble quaternary ammonium-compatible solute importers but are most similar in sequence to the broadly conserved YehZYXW system, which remains largely uncharacterized. Transcription ofyehZYXWis activated by the general stress sigma factor σ SinEnterobacteriaceae, which suggests a functional role for this transport systemmore » in bacterial stress response across the classesAlphaproteobacteriaandGammaproteobacteria. We present evidence thatB. abortusYehZYXW does not function as an importer of known compatible solutes under physiological conditions and does not contribute to the virulence defect of a σ E1-null strain. The solein vitrophenotype associated with genetic disruption of this putative transport system is reduced growth in the presence of high Li +ion concentrations. A crystal structure ofB. abortusYehZ revealed a class II periplasmic binding protein fold with significant structural homology toArchaeoglobus fulgidusProX, which binds glycine betaine. However, the structure of the YehZ ligand-binding pocket is incompatible with high-affinity binding to glycine betaine. This is consistent with weak measured binding of YehZ to glycine betaine and related compatible solutes. We conclude that YehZYXW is a conserved, stress-regulated transport system that is phylogenetically and functionally distinct from quaternary ammonium-compatible solute importers. IMPORTANCEBrucella abortusσ E1regulates transcription in response to stressors encountered in its mammalian host and is necessary for maintenance of chronic infection in a mouse model. The functions of the majority of genes regulated by σ E1remain undefined. We present a functional/structural analysis of a conserved putative membrane transport system (YehZYXW) whose expression is strongly activated by σ E1. Though annotated as a quaternary ammonium osmolyte uptake system, experimental physiological studies and measured ligand-binding properties of the periplasmic binding protein (PBP), YehZ, are inconsistent with this function. A crystal structure ofB. abortusYehZ provides molecular insight into differences between bona fide quaternary ammonium osmolyte importers and YehZ-related proteins, which form a distinct phylogenetic and functional group of PBPs.« less

A chronometric functional sub-network in the thalamo-cortical system regulates the flow of neural information necessary for conscious cognitive processes.

PubMed

León-Domínguez, Umberto; Vela-Bueno, Antonio; Froufé-Torres, Manuel; León-Carrión, Jose

2013-06-01

The thalamo-cortical system has been defined as a neural network associated with consciousness. While there seems to be wide agreement that the thalamo-cortical system directly intervenes in vigilance and arousal, a divergence of opinion persists regarding its intervention in the control of other cognitive processes necessary for consciousness. In the present manuscript, we provide a review of recent scientific findings on the thalamo-cortical system and its role in the control and regulation of the flow of neural information necessary for conscious cognitive processes. We suggest that the axis formed by the medial prefrontal cortex and different thalamic nuclei (reticular nucleus, intralaminar nucleus, and midline nucleus), represents a core component for consciousness. This axis regulates different cerebral structures which allow basic cognitive processes like attention, arousal and memory to emerge. In order to produce a synchronized coherent response, neural communication between cerebral structures must have exact timing (chronometry). Thus, a chronometric functional sub-network within the thalamo-cortical system keeps us in an optimal and continuous functional state, allowing high-order cognitive processes, essential to awareness and qualia, to take place. Copyright © 2013 Elsevier Ltd. All rights reserved.

Sleep loss and structural plasticity.

PubMed

Areal, Cassandra C; Warby, Simon C; Mongrain, Valérie

2017-06-01

Wakefulness and sleep are dynamic states during which brain functioning is modified and shaped. Sleep loss is detrimental to many brain functions and results in structural changes localized at synapses in the nervous system. In this review, we present and discuss some of the latest observations of structural changes following sleep loss in some vertebrates and insects. We also emphasize that these changes are region-specific and cell type-specific and that, most importantly, these structural modifications have functional roles in sleep regulation and brain functions. Selected mechanisms driving structural modifications occurring with sleep loss are also discussed. Overall, recent research highlights that extending wakefulness impacts synapse number and shape, which in turn regulate sleep need and sleep-dependent learning/memory. Copyright © 2017 Elsevier Ltd. All rights reserved.

Regulation of mesenchymal stem cell 3D microenvironment: From macro to microfluidic bioreactors.

PubMed

Sart, Sébastien; Agathos, Spiros N; Li, Yan; Ma, Teng

2016-01-01

Human mesenchymal stem cells (hMSCs) have emerged as an important cell type in cell therapy and tissue engineering. In these applications, maintaining the therapeutic properties of hMSCs requires tight control of the culture environments and the structural cell organizations. Bioreactor systems are essential tools to achieve these goals in the clinical-scale expansion and tissue engineering applications. This review summarizes how different bioreactors provide cues to regulate the structure and the chemico-mechanical microenvironment of hMSCs with a focus on 3D organization. In addition to conventional bioreactors, recent advances in microfluidic bioreactors as a novel approach to better control the hMSC microenvironment are also discussed. These advancements highlight the key role of bioreactor systems in preserving hMSC's functional properties by providing dynamic and temporal regulation of in vitro cellular microenvironment. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Actin Engine in Immunological Synapse

PubMed Central

Piragyte, Indre

2012-01-01

T cell activation and function require physical contact with antigen presenting cells at a specialized junctional structure known as the immunological synapse. Once formed, the immunological synapse leads to sustained T cell receptor-mediated signalling and stabilized adhesion. High resolution microscopy indeed had a great impact in understanding the function and dynamic structure of immunological synapse. Trends of recent research are now moving towards understanding the mechanical part of immune system, expanding our knowledge in mechanosensitivity, force generation, and biophysics of cell-cell interaction. Actin cytoskeleton plays inevitable role in adaptive immune system, allowing it to bear dynamic and precise characteristics at the same time. The regulation of mechanical engine seems very complicated and overlapping, but it enables cells to be very sensitive to external signals such as surface rigidity. In this review, we focus on actin regulators and how immune cells regulate dynamic actin rearrangement process to drive the formation of immunological synapse. PMID:22916042

The Researching on Evaluation of Automatic Voltage Control Based on Improved Zoning Methodology

NASA Astrophysics Data System (ADS)

Xiao-jun, ZHU; Ang, FU; Guang-de, DONG; Rui-miao, WANG; De-fen, ZHU

2018-03-01

According to the present serious phenomenon of increasing size and structure of power system, hierarchically structured automatic voltage control(AVC) has been the researching spot. In the paper, the reduced control model is built and the adaptive reduced control model is researched to improve the voltage control effect. The theories of HCSD, HCVS, SKC and FCM are introduced and the effect on coordinated voltage regulation caused by different zoning methodologies is also researched. The generic framework for evaluating performance of coordinated voltage regulation is built. Finally, the IEEE-96 stsyem is used to divide the network. The 2383-bus Polish system is built to verify that the selection of a zoning methodology affects not only the coordinated voltage regulation operation, but also its robustness to erroneous data and proposes a comprehensive generic framework for evaluating its performance. The New England 39-bus network is used to verify the adaptive reduced control models’ performance.

The endothelial glycocalyx

PubMed Central

Yang, Yimu; Schmidt, Eric P.

2013-01-01

Once thought to be a structure of small size and uncertain significance, the endothelial glycocalyx is now known to be an important regulator of endothelial function. Studies of the systemic vasculature have demonstrated that the glycocalyx forms a substantial in vivo endothelial surface layer (ESL) critical to inflammation, barrier function and mechanotransduction. The pulmonary ESL is significantly thicker than the systemic ESL, suggesting unique physiologic function. We have recently demonstrated that the pulmonary ESL regulates exposure of endothelial surface adhesion molecules, thereby serving as a barrier to neutrophil adhesion and extravasation. While the pulmonary ESL is not a critical structural component of the endothelial barrier to fluid and protein, it serves a major role in the mechanotransduction of vascular pressure, with impact on the active regulation of endothelial permeability. It is likely that the ESL serves numerous additional functions in vascular physiology, representing a fertile area for future investigation. PMID:24073386

Proportional plus integral MIMO controller for regulation and tracking with anti-wind-up features

DOE Office of Scientific and Technical Information (OSTI.GOV)

Puleston, P.F.; Mantz, R.J.

1993-11-01

A proportional plus integral matrix control structure for MIMO systems is proposed. Based on a standard optimal control structure with integral action, it permits a greater degree of independence of the design and tuning of the regulating and tracking features, without considerably increasing the controller complexity. Fast recovery from load disturbances is achieved, while large overshoots associated with set-point changes and reset wind-up problems can be reduced. A simple effective procedure for practical tuning is introduced.

48 CFR 3016.170 - Contracts with Lead System Integrators.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 7 2012-10-01 2012-10-01 false Contracts with Lead System... Selecting Contract Types 3016.170 Contracts with Lead System Integrators. The contracting officer should... consulted to determine the appropriate contract type and fee structure for use in varied contracts with lead...

48 CFR 3016.170 - Contracts with Lead System Integrators.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 7 2013-10-01 2012-10-01 true Contracts with Lead System... Selecting Contract Types 3016.170 Contracts with Lead System Integrators. The contracting officer should... consulted to determine the appropriate contract type and fee structure for use in varied contracts with lead...

48 CFR 3016.170 - Contracts with Lead System Integrators.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 7 2014-10-01 2014-10-01 false Contracts with Lead System... Selecting Contract Types 3016.170 Contracts with Lead System Integrators. The contracting officer should... consulted to determine the appropriate contract type and fee structure for use in varied contracts with lead...

48 CFR 3016.170 - Contracts with Lead System Integrators.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 7 2011-10-01 2011-10-01 false Contracts with Lead System... Selecting Contract Types 3016.170 Contracts with Lead System Integrators. The contracting officer should... consulted to determine the appropriate contract type and fee structure for use in varied contracts with lead...

48 CFR 3016.170 - Contracts with Lead System Integrators.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Contracts with Lead System... Selecting Contract Types 3016.170 Contracts with Lead System Integrators. The contracting officer should... consulted to determine the appropriate contract type and fee structure for use in varied contracts with lead...

The Avian Proghrelin System

USDA-ARS?s Scientific Manuscript database

To understand how the proghrelin system functions in regulating growth hormone release and food intake as well as defining its pleiotropic roles in such diverse physiological processes as energy homeostasis, gastrointestinal tract function and reproduction requires detailed knowledge of the structur...

Special Medicare reimbursement and fraud and abuse considerations for management services organizations, medical foundations, and integrated delivery systems.

PubMed

DeMuro, P R; Owens, J F

1994-01-01

This chapter discusses certain Medicare reimbursement and fraud and abuse considerations for management services organizations (MSOs), medical foundations, and integrated delivery systems. It stresses the necessity of a business plan, the sources of capitalization that might be used in creating an integrated delivery system, and their effect on Medicare reimbursement. It also discusses related party principles and considerations and the Medicare "incident to" regulations. Furthermore, it discusses the application of certain Medicare safe harbor regulations on MSOs' structures and services, and those of medical foundations and integrated delivery systems.

Aircraft wing structural detail design (wing, aileron, flaps, and subsystems)

NASA Technical Reports Server (NTRS)

Downs, Robert; Zable, Mike; Hughes, James; Heiser, Terry; Adrian, Kenneth

1993-01-01

The goal of this project was to design, in detail, the wing, flaps, and ailerons for a primary flight trainer. Integrated in this design are provisions for the fuel system, the electrical system, and the fuselage/cabin carry-through interface structure. This conceptual design displays the general arrangement of all major components in the wing structure, taking into consideration the requirements set forth by the appropriate sections of Federal Aviation Regulation Part 23 (FAR23) as well as those established in the statement of work.

Educational Systems and Rising Inequality: Eastern Germany after Unification

ERIC Educational Resources Information Center

von Below, Susanne; Powell, Justin J. W.; Roberts, Lance W.

2013-01-01

Educational systems considerably influence educational opportunities and the resulting social inequalities. Contrasting institutional regulations of both structures and contents, the authors present a typology of educational system types in Germany to analyze their effects on social inequality in eastern Germany after unification. After 1990, the…

Dynamic soft variable structure control of singular systems

NASA Astrophysics Data System (ADS)

Liu, Yunlong; Zhang, Caihong; Gao, Cunchen

2012-08-01

The dynamic soft variable structure control (VSC) of singular systems is discussed in this paper. The definition of soft VSC and the design of its controller modes are given. The stability of singular systems with the dynamic soft VSC is proposed. The dynamic soft variable structure controller is designed, and the concrete algorithm on the dynamic soft VSC is given. The dynamic soft VSC of singular systems which was developed for the purpose of intentionally precluding chattering, achieving high regulation rates and shortening settling times enhanced the dynamic quality of the systems. It is illustrated the feasibility and validity of the proposed strategy by a simulation example, and an outlook on its auspicious further development is presented.

46 CFR 160.151-15 - Design and performance of inflatable liferafts.

Code of Federal Regulations, 2010 CFR

2010-10-01

...-15 Section 160.151-15 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT... structural components. (b) Seams (Regulation III/30.2.1). Each seam must be at least as strong as the weakest... is greater. (k) Painter system (Regulation III/38.6.1). The painter protruding from the liferaft...

Structural integrity and containment aspects of small gas turbine engines

NASA Astrophysics Data System (ADS)

Gupta, S. S.; Gomuc, R.

1994-03-01

Structural integrity of rotating components in gas turbine engines is very crucial since their failure implies high impact energy, which, if uncontained, could mean damage to aircraft structures, controls, and so forth, and, in the worst scenario, even loss of lives. This final consequence has led to very stringent airworthiness regulations for engine/aircraft certifications. This paper discusses the historical statistics of noncontainment events in turbofans, turboprops, and turboshafts and shows how the damage severity varies between different applications and how changes to regulations are continuing in order to improve the reliability of aircraft/rotorcraft. The paper also presents design challenges resulting from the analysis complexity of containment/noncontainment event and the way Pratt & Whitney Canada design/analysis/test system caters to all the requirements. The weight and cost impact of possible changes to current regulations are also presented.

The CpAL Quorum Sensing System Regulates Production of Hemolysins CPA and PFO To Build Clostridium perfringens Biofilms

PubMed Central

Shak, Joshua R.; Canizalez-Roman, Adrian

2015-01-01

Clostridium perfringens strains produce severe diseases, including myonecrosis and enteritis necroticans, in humans and animals. Diseases are mediated by the production of potent toxins that often damage the site of infection, e.g., skin epithelium during myonecrosis. In planktonic cultures, the regulation of important toxins, such as CPA, CPB, and PFO, is controlled by the C. perfringens Agr-like (CpAL) quorum sensing (QS) system. Strains also encode a functional LuxS/AI-2 system. Although C. perfringens strains form biofilm-like structures, the regulation of biofilm formation is poorly understood. Therefore, our studies investigated the role of CpAL and LuxS/AI-2 QS systems and of QS-regulated factors in controlling the formation of biofilms. We first demonstrate that biofilm production by reference strains differs depending on the culture medium. Increased biomass correlated with the presence of extracellular DNA in the supernatant, which was released by lysis of a fraction of the biofilm population and planktonic cells. Whereas ΔagrB mutant strains were not able to produce biofilms, a ΔluxS mutant produced wild-type levels. The transcript levels of CpAL-regulated cpa and pfoA genes, but not cpb, were upregulated in biofilms compared to planktonic cultures. Accordingly, Δcpa and ΔpfoA mutants, in type A (S13) or type C (CN3685) backgrounds, were unable to produce biofilms, whereas CN3685Δcpb made wild-type levels. Biofilm formation was restored in complemented Δcpa/cpa and ΔpfoA/pfoA strains. Confocal microscopy studies further detected CPA partially colocalizing with eDNA on the biofilm structure. Thus, CpAL regulates biofilm formation in C. perfringens by increasing levels of certain toxins required to build biofilms. PMID:25824838

The structure and function of the dopamine transporter and its role in CNS diseases.

PubMed

McHugh, Patrick C; Buckley, David A

2015-01-01

In this chapter, we explore the basic science of the dopamine transporter (DAT), an integral component of a system that regulates dopamine homeostasis. Dopamine is a key neurotransmitter for several brain functions including locomotor control and reward systems. The transporter structure, function, mechanism of action, localization, and distribution, in addition to gene regulation, are discussed. Over many years, a wealth of information concerning the DAT has been accrued and has led to increased interest in the role of the DAT in a plethora of central nervous system diseases. These DAT characteristics are explored in relation to a range of neurological and neuropsychiatric diseases, with a particular focus on the genetics of the DAT. In addition, we discuss the pharmacology of the DAT and how this relates to disease and addiction. © 2015 Elsevier Inc. All rights reserved.

A comparative analysis of biomedical research ethics regulation systems in Europe and Latin America with regard to the protection of human subjects.

PubMed

Lamas, Eugenia; Ferrer, Marcela; Molina, Alberto; Salinas, Rodrigo; Hevia, Adriana; Bota, Alexandre; Feinholz, Dafna; Fuchs, Michael; Schramm, Roland; Tealdi, Juan-Carlos; Zorrilla, Sergio

2010-12-01

The European project European and Latin American Systems of Ethics Regulation of Biomedical Research Project (EULABOR) has carried out the first comparative analysis of ethics regulation systems for biomedical research in seven countries in Europe and Latin America, evaluating their roles in the protection of human subjects. We developed a conceptual and methodological framework defining 'ethics regulation system for biomedical research' as a set of actors, institutions, codes and laws involved in overseeing the ethics of biomedical research on humans. This framework allowed us to develop comprehensive national reports by conducting semi-structured interviews to key informants. These reports were summarised and analysed in a comparative analysis. The study showed that the regulatory framework for clinical research in these countries differ in scope. It showed that despite the different political contexts, actors involved and motivations for creating the regulation, in most of the studied countries it was the government who took the lead in setting up the system. The study also showed that Europe and Latin America are similar regarding national bodies and research ethics committees, but the Brazilian system has strong and noteworthy specificities.

Regulation of Complement and Contact System Activation via C1 Inhibitor Potentiation and Factor XIIa Activity Modulation by Sulfated Glycans – Structure-Activity Relationships

PubMed Central

Schoenfeld, Ann-Kathrin; Lahrsen, Eric; Alban, Susanne

2016-01-01

The serpin C1 inhibitor (C1-INH) is the only regulator of classical complement activation as well as the major regulator of the contact system. Its importance is demonstrated by hereditary angioedema (HAE), a severe disease with potentially life-threatening attacks due to deficiency or dysfunction of C1-INH. C1-INH replacement is the therapy of choice in HAE. In addition, C1-INH showed to have beneficial effects in other diseases characterized by inappropriate complement and contact system activation. Due to some limitations of its clinical application, there is a need for improving the efficacy of therapeutically applied C1-INH or to enhance the activity of endogenous C1-INH. Given the known potentiating effect of heparin on C1-INH, sulfated glycans (SG) may be such candidates. The aim of this study was to characterize suitable SG by evaluating structure-activity relationships. For this, more than 40 structurally distinct SG were examined for their effects on C1-INH, C1s and FXIIa. The SG turned out to potentiate the C1s inhibition by C1-INH without any direct influence on C1s. Their potentiating activity proved to depend on their degree of sulfation, molecular mass as well as glycan structure. In contrast, the SG had no effect on the FXIIa inhibition by C1-INH, but structure-dependently modulated the activity of FXIIa. Among the tested SG, β-1,3-glucan sulfates with a Mr ≤ 10 000 were identified as most promising lead candidates for the development of a glycan-based C1-INH amplifier. In conclusion, the obtained information on structural characteristics of SG favoring C1-INH potentiation represent an useful elementary basis for the development of compounds improving the potency of C1-INH in diseases and clinical situations characterized by inappropriate activation of complement and contact system. PMID:27783665

Motivation, emotion regulation, and the latent structure of psychopathology: An integrative and convergent historical perspective.

PubMed

Beauchaine, Theodore P; Zisner, Aimee

2017-09-01

Motivational models of psychopathology have long been advanced by psychophysiologists, and have provided key insights into neurobiological mechanisms of a wide range of psychiatric disorders. These accounts emphasize individual differences in activity and reactivity of bottom-up, subcortical neural systems of approach and avoidance in affecting behavior. Largely independent literatures emphasize the roles of top-down, cortical deficits in emotion regulation and executive function in conferring vulnerability to psychopathology. To date however, few models effectively integrate functions performed by bottom-up emotion generation system with those performed by top-down emotion regulation systems in accounting for alternative expressions of psychopathology. In this article, we present such a model, and describe how it accommodates the well replicated bifactor structure of psychopathology. We describe how excessive approach motivation maps directly into externalizing liability, how excessive passive avoidance motivation maps directly into internalizing liability, and how emotion dysregulation and executive function map onto general liability. This approach is consistent with the Research Domain Criteria initiative, which assumes that a limited number of brain systems interact to confer vulnerability to many if not most forms of psychopathology. Copyright © 2017 Elsevier B.V. All rights reserved.

Structure of the human M2 muscarinic acetylcholine receptor bound to an antagonist

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haga, Kazuko; Kruse, Andrew C.; Asada, Hidetsugu

2012-03-15

The parasympathetic branch of the autonomic nervous system regulates the activity of multiple organ systems. Muscarinic receptors are G-protein-coupled receptors that mediate the response to acetylcholine released from parasympathetic nerves. Their role in the unconscious regulation of organ and central nervous system function makes them potential therapeutic targets for a broad spectrum of diseases. The M2 muscarinic acetylcholine receptor (M2 receptor) is essential for the physiological control of cardiovascular function through activation of G-protein-coupled inwardly rectifying potassium channels, and is of particular interest because of its extensive pharmacological characterization with both orthosteric and allosteric ligands. Here we report the structuremore » of the antagonist-bound human M2 receptor, the first human acetylcholine receptor to be characterized structurally, to our knowledge. The antagonist 3-quinuclidinyl-benzilate binds in the middle of a long aqueous channel extending approximately two-thirds through the membrane. The orthosteric binding pocket is formed by amino acids that are identical in all five muscarinic receptor subtypes, and shares structural homology with other functionally unrelated acetylcholine binding proteins from different species. A layer of tyrosine residues forms an aromatic cap restricting dissociation of the bound ligand. A binding site for allosteric ligands has been mapped to residues at the entrance to the binding pocket near this aromatic cap. The structure of the M2 receptor provides insights into the challenges of developing subtype-selective ligands for muscarinic receptors and their propensity for allosteric regulation.« less

Physiological, biochemical and molecular processes associated with gravitropism in roots of maize

NASA Astrophysics Data System (ADS)

Biermann, B.; Feldman, L. J.

1994-08-01

This research aims to characterize regulation of the principal cytosolic protein kinases in maize, cultivar `Merit' root tips, since much evidence indicates that stimuli which modulate the gravitropic response in this system act through regulation of activity of these enzymes. To this end, we have cloned a maize protein kinase belonging to a group of plant protein kinases with a catalytic domain similar in primary structure to the second messenger-regulated protein kinases known in animal and fungal systems. However, both the unique structural features conserved among plant protein kinases in this group, and lack of evidence for cyclic nucleotide signalling in plants point to operation of a novel protein kinase regulatory mechanism in plants. In order to test effects of possible regulators on protein kinase activity, we developed a sensitive method for detecting regulation of autophosphoryl labelling of protein kinases in unfractionated maize protein extracts. Regulation of protein kinase autophosphorylation in these extracts was different from that known in animals and fungi, further suggesting operation of unique protein kinase regulatory mechanisms in plants. Previous research has shown that light, or factors modulated by light, regulate plant protein kinase activity. We found that protein kinase activity was co-immunoprecipitated with the plant photoreceptor phytochrome, and was associated with phytochrome by high-affinity chemical interactions. Far-red reversibility of red-light regulation of phytochrome phosphorylation by the associated protein kinase indicates that it may modulate or transduce the light signals which lead to gravitropic sensitivity in `Merit' maize.

How Emotions Affect Learning.

ERIC Educational Resources Information Center

Sylwester, Robert

1994-01-01

Studies show our emotional system is a complex, widely distributed, and error-prone system that defines our basic personality early in life and is quite resistant to change. This article describes our emotional system's major parts (the peptides that carry emotional information and the body and brain structures that activate and regulate emotions)…

System-wide analysis of the transcriptional network of human myelomonocytic leukemia cells predicts attractor structure and phorbol-ester-induced differentiation and dedifferentiation transitions

NASA Astrophysics Data System (ADS)

Sakata, Katsumi; Ohyanagi, Hajime; Sato, Shinji; Nobori, Hiroya; Hayashi, Akiko; Ishii, Hideshi; Daub, Carsten O.; Kawai, Jun; Suzuki, Harukazu; Saito, Toshiyuki

2015-02-01

We present a system-wide transcriptional network structure that controls cell types in the context of expression pattern transitions that correspond to cell type transitions. Co-expression based analyses uncovered a system-wide, ladder-like transcription factor cluster structure composed of nearly 1,600 transcription factors in a human transcriptional network. Computer simulations based on a transcriptional regulatory model deduced from the system-wide, ladder-like transcription factor cluster structure reproduced expression pattern transitions when human THP-1 myelomonocytic leukaemia cells cease proliferation and differentiate under phorbol myristate acetate stimulation. The behaviour of MYC, a reprogramming Yamanaka factor that was suggested to be essential for induced pluripotent stem cells during dedifferentiation, could be interpreted based on the transcriptional regulation predicted by the system-wide, ladder-like transcription factor cluster structure. This study introduces a novel system-wide structure to transcriptional networks that provides new insights into network topology.

Two-Component Signal Transduction Systems That Regulate the Temporal and Spatial Expression of Myxococcus xanthus Sporulation Genes.

PubMed

Sarwar, Zaara; Garza, Anthony G

2016-02-01

When starved for nutrients, Myxococcus xanthus produces a biofilm that contains a mat of rod-shaped cells, known as peripheral rods, and aerial structures called fruiting bodies, which house thousands of dormant and stress-resistant spherical spores. Because rod-shaped cells differentiate into spherical, stress-resistant spores and spore differentiation occurs only in nascent fruiting bodies, many genes and multiple levels of regulation are required. Over the past 2 decades, many regulators of the temporal and spatial expression of M. xanthus sporulation genes have been uncovered. Of these sporulation gene regulators, two-component signal transduction circuits, which typically contain a histidine kinase sensor protein and a transcriptional regulator known as response regulator, are among the best characterized. In this review, we discuss prototypical two-component systems (Nla6S/Nla6 and Nla28S/Nla28) that regulate an early, preaggregation phase of sporulation gene expression during fruiting body development. We also discuss orphan response regulators (ActB and FruA) that regulate a later phase of sporulation gene expression, which begins during the aggregation stage of fruiting body development. In addition, we summarize the research on a complex two-component system (Esp) that is important for the spatial regulation of sporulation. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Safety and integrity of pipeline systems - philosophy and experience in Germany

DOT National Transportation Integrated Search

1997-01-01

The design, construction and operation of gas pipeline systems in Germany are subject to the Energy Act and associated regulations. This legal structure is based on a deterministic rather than a probabilistic safety philosophy, consisting of technica...

Understanding Biological Regulation Through Synthetic Biology.

PubMed

Bashor, Caleb J; Collins, James J

2018-05-20

Engineering synthetic gene regulatory circuits proceeds through iterative cycles of design, building, and testing. Initial circuit designs must rely on often-incomplete models of regulation established by fields of reductive inquiry-biochemistry and molecular and systems biology. As differences in designed and experimentally observed circuit behavior are inevitably encountered, investigated, and resolved, each turn of the engineering cycle can force a resynthesis in understanding of natural network function. Here, we outline research that uses the process of gene circuit engineering to advance biological discovery. Synthetic gene circuit engineering research has not only refined our understanding of cellular regulation but furnished biologists with a toolkit that can be directed at natural systems to exact precision manipulation of network structure. As we discuss, using circuit engineering to predictively reorganize, rewire, and reconstruct cellular regulation serves as the ultimate means of testing and understanding how cellular phenotype emerges from systems-level network function.

Colocalization properties of elementary Ca(2+) release signals with structures specific to the contractile filaments and the tubular system of intact mouse skeletal muscle fibers.

PubMed

Georgiev, Tihomir; Zapiec, Bolek; Förderer, Moritz; Fink, Rainer H A; Vogel, Martin

2015-12-01

Ca(2+) regulates several important intracellular processes. We combined second harmonic generation (SHG) and two photon excited fluorescence microscopy (2PFM) to simultaneously record the SHG signal of the myosin filaments and localized elementary Ca(2+) release signals (LCSs). We found LCSs associated with Y-shaped structures of the myosin filament pattern (YMs), so called verniers, in intact mouse skeletal muscle fibers under hypertonic treatment. Ion channels crucial for the Ca(2+) regulation are located in the tubular system, a system that is important for Ca(2+) regulation and excitation-contraction coupling. We investigated the tubular system of intact, living mouse skeletal muscle fibers using 2PFM and the fluorescent Ca(2+) indicator Fluo-4 dissolved in the external solution or the membrane dye di-8-ANEPPS. We simultaneously measured the SHG signal from the myosin filaments of the skeletal muscle fibers. We found that at least a subset of the YMs observed in SHG images are closely juxtaposed with Y-shaped structures of the transverse tubules (YTs). The distances of corresponding YMs and YTs yield values between 1.3 μm and 4.1 μm including pixel uncertainty with a mean distance of 2.52±0.10 μm (S.E.M., n=41). Additionally, we observed that some of the linear-shaped areas in the tubular system are colocalized with linear-shaped areas in the SHG images. Copyright © 2015 Elsevier Inc. All rights reserved.

System identification of the JPL micro-precision interferometer truss - Test-analysis reconciliation

NASA Technical Reports Server (NTRS)

Red-Horse, J. R.; Marek, E. L.; Levine-West, M.

1993-01-01

The JPL Micro-Precision Interferometer (MPI) is a testbed for studying the use of control-structure interaction technology in the design of space-based interferometers. A layered control architecture will be employed to regulate the interferometer optical system to tolerances in the nanometer range. An important aspect of designing and implementing the control schemes for such a system is the need for high fidelity, test-verified analytical structural models. This paper focuses on one aspect of the effort to produce such a model for the MPI structure, test-analysis model reconciliation. Pretest analysis, modal testing, and model refinement results are summarized for a series of tests at both the component and full system levels.

Regulating Cortical Neurodynamics for Past, Present and Future

NASA Astrophysics Data System (ADS)

Liljenström, Hans

2002-09-01

Behaving systems, biological as well as artificial, need to respond quickly and accurately to changes in the environment. The response is dependent on stored memories, and novel situations should be learnt for the guidance of future behavior. A highly nonlinear system dynamics is required in order to cope with a complex and changing environment, and this dynamics should be regulated to match the demands of the current situation, and to predict future behavior. In many cases the dynamics should be regulated to minimize processing time. We use computer simulations of cortical structures in order to investigate how the neurodynamics of these systems can be regulated for optimal performance in an unknown and changing environment. In particular, we study how cortical oscillations can serve to amplify weak signals and sustain an input pattern for more accurate information processing, and how chaotic-like behavior could increase the sensitivity in initial, exploratory states. We mimic regulating mechanisms based on neuromodulators, intrinsic noise levels, and various synchronizing effects. We find optimal noise levels where system performance is maximized, and neuromodulatory strategies for an efficient pattern recognition, where the anticipatory state of the system plays an important role.

76 FR 30523 - Special Conditions: Boeing Model 747-8/-8F Airplanes, Interaction of Systems and Structures

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-26

...- wire (FBW) flight control system to reduce, but not eliminate, the amplitude of the sustained... failures. The regulations do not anticipate the use of systems that control flutter modes but do not... standards that permit the use of such active flutter control systems. Discussion of Comments Notice of...

Information generation and processing systems that regulate periodontal structure and function.

PubMed

Bartold, P Mark; McCulloch, Christopher A

2013-10-01

The periodontium is a very dynamic organ that responds rapidly to mechanical and chemical stimuli. It is very complex in that it is composed of two hard tissues (cementum and bone) and two soft connective tissues (periodontal ligament and gingiva). Together these tissues are defined by the molecules expressed by the resident periodontal cells in each compartment and this determines not only the structure and function of the periodontium but also how it responds to infection and inflammation. The biological activity of these molecules is tightly regulated in time and space to preserve tissue homeostasis, influence inflammatory responses and participate in tissue regeneration. In this issue of Periodontology 2000 we explore new experimental approaches and data sets which help to understand the molecules and cells that regulate tissue form and structure in health, disease and regeneration. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

PspF-binding domain PspA1-144 and the PspA·F complex: New insights into the coiled-coil-dependent regulation of AAA+ proteins.

PubMed

Osadnik, Hendrik; Schöpfel, Michael; Heidrich, Eyleen; Mehner, Denise; Lilie, Hauke; Parthier, Christoph; Risselada, H Jelger; Grubmüller, Helmut; Stubbs, Milton T; Brüser, Thomas

2015-11-01

Phage shock protein A (PspA) belongs to the highy conserved PspA/IM30 family and is a key component of the stress inducible Psp system in Escherichia coli. One of its central roles is the regulatory interaction with the transcriptional activator of this system, the σ(54) enhancer-binding protein PspF, a member of the AAA+ protein family. The PspA/F regulatory system has been intensively studied and serves as a paradigm for AAA+ enzyme regulation by trans-acting factors. However, the molecular mechanism of how exactly PspA controls the activity of PspF and hence σ(54) -dependent expression of the psp genes is still unclear. To approach this question, we identified the minimal PspF-interacting domain of PspA, solved its structure, determined its affinity to PspF and the dissociation kinetics, identified residues that are potentially important for PspF regulation and analyzed effects of their mutation on PspF in vivo and in vitro. Our data indicate that several characteristics of AAA+ regulation in the PspA·F complex resemble those of the AAA+ unfoldase ClpB, with both proteins being regulated by a structurally highly conserved coiled-coil domain. The convergent evolution of both regulatory domains points to a general mechanism to control AAA+ activity for divergent physiologic tasks via coiled-coil domains. © 2015 John Wiley & Sons Ltd.

Cell fate control in the developing central nervous system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guérout, Nicolas; Li, Xiaofei; Barnabé-Heider, Fanie, E-mail: Fanie.Barnabe-Heider@ki.se

The principal neural cell types forming the mature central nervous system (CNS) are now understood to be diverse. This cellular subtype diversity originates to a large extent from the specification of the earlier proliferating progenitor populations during development. Here, we review the processes governing the differentiation of a common neuroepithelial cell progenitor pool into mature neurons, astrocytes, oligodendrocytes, ependymal cells and adult stem cells. We focus on studies performed in mice and involving two distinct CNS structures: the spinal cord and the cerebral cortex. Understanding the origin, specification and developmental regulators of neural cells will ultimately impact comprehension and treatmentsmore » of neurological disorders and diseases. - Highlights: • Similar mechanisms regulate cell fate in different CNS cell types and structures. • Cell fate regulators operate in a spatial–temporal manner. • Different neural cell types rely on the generation of a diversity of progenitor cells. • Cell fate decision is dictated by the integration of intrinsic and extrinsic signals.« less

[The genetic determination and function of RR-proteins--the regulators of photoperiodic reaction and circadian rhythms in plants].

PubMed

Tots'kyĭ, V M; D'iachenko, L F; Muterko, O F; Balashova, I A; Toptikov, V A

2012-01-01

The present review devoted to the analysis of recent literature on genetic determination and the domain organization of the newly discovered two-component signaling systems in pro- and eukaryotes. These structures are involved in the regulation of numerous morphological and physiological processes in plants. RR-proteins, it the key elements of signaling systems, they launch a cascade of phosphotransferase reactions and directly or indirectly regulate the transcription and activity other proteins, including enzymes, in response to hormones or environmental factors. Modern views on the molecular and genetic mechanisms of photoperiodic response, circadian rhythms and anti-stress responses in plants are set out in these positions. The relationship between gene expression and photoreceptor sensitivity of plants to photoperiod traced. We present our own data obtained on the isogenic lines of wheat, where been showed dependence expression of structural genes of enzymes on the allelic composition of individual PRR-loci and the duration action of low temperature.

What's the point of the type III secretion system needle?

PubMed Central

Blocker, Ariel J.; Deane, Janet E.; Veenendaal, Andreas K. J.; Roversi, Pietro; Hodgkinson, Julie L.; Johnson, Steven; Lea, Susan M.

2008-01-01

Recent work by several groups has significantly expanded our knowledge of the structure, regulation of assembly, and function of components of the extracellular portion of the type III secretion system (T3SS) of Gram-negative bacteria. This perspective presents a structure-informed analysis of functional data and discusses three nonmutually exclusive models of how a key aspect of T3SS biology, the sensing of host cells, may be performed. PMID:18458349

Optimization of the structural and control system for LSS with reduced-order model

NASA Technical Reports Server (NTRS)

Khot, N. S.

1989-01-01

The objective is the simultaneous design of the structural and control system for space structures. The minimum weight of the structure is the objective function, and the constraints are placed on the closed loop distribution of the frequencies and the damping parameters. The controls approach used is linear quadratic regulator with constant feedback. A reduced-order control system is used. The effect of uncontrolled modes is taken into consideration by the model error sensitivity suppression (MESS) technique which modified the weighting parameters for the control forces. For illustration, an ACOSS-FOUR structure is designed for a different number of controlled modes with specified values for the closed loop damping parameters and frequencies. The dynamic response of the optimum designs for an initial disturbance is compared.

Structural Analysis of the Regulatory Domain of ExsA, a Key Transcriptional Regulator of the Type Three Secretion System in Pseudomonas aeruginosa

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shrestha, Manisha; Xiao, Yi; Robinson, Howard

Pseudomonas aeruginosa employs a type three secretion system to facilitate infections in mammalian hosts. The operons encoding genes of structural components of the secretion machinery and associated virulence factors are all under the control of the AraC-type transcriptional activator protein, ExsA. ExsA belongs to a unique subfamily of AraC-proteins that is regulated through protein-protein contacts rather than small molecule ligands. Prior to infection, ExsA is inhibited through a direct interaction with the anti-activator ExsD. To activate ExsA upon host cell contact this interaction is disrupted by the anti-antiactivator protein ExsC. Here we report the crystal structure of the regulatory domainmore » of ExsA, which is known to mediate ExsA dimerization as well as ExsD binding. The crystal structure suggests two models for the ExsA dimer. Both models confirmed the previously shown involvement of helix α-3 in ExsA dimerization but one also suggest a role for helix α-2. These structural data are supported by the observation that a mutation in α-2 greatly diminished the ability of ExsA to activate transcription in vitro. Lastly, additional in vitro transcription studies revealed that a conserved pocket, used by AraC and the related ToxT protein for the binding of small molecule regulators, although present in ExsA is not involved in binding of ExsD.« less

Structural Analysis of the Regulatory Domain of ExsA, a Key Transcriptional Regulator of the Type Three Secretion System in Pseudomonas aeruginosa

DOE PAGES

Shrestha, Manisha; Xiao, Yi; Robinson, Howard; ...

2015-08-28

Pseudomonas aeruginosa employs a type three secretion system to facilitate infections in mammalian hosts. The operons encoding genes of structural components of the secretion machinery and associated virulence factors are all under the control of the AraC-type transcriptional activator protein, ExsA. ExsA belongs to a unique subfamily of AraC-proteins that is regulated through protein-protein contacts rather than small molecule ligands. Prior to infection, ExsA is inhibited through a direct interaction with the anti-activator ExsD. To activate ExsA upon host cell contact this interaction is disrupted by the anti-antiactivator protein ExsC. Here we report the crystal structure of the regulatory domainmore » of ExsA, which is known to mediate ExsA dimerization as well as ExsD binding. The crystal structure suggests two models for the ExsA dimer. Both models confirmed the previously shown involvement of helix α-3 in ExsA dimerization but one also suggest a role for helix α-2. These structural data are supported by the observation that a mutation in α-2 greatly diminished the ability of ExsA to activate transcription in vitro. Lastly, additional in vitro transcription studies revealed that a conserved pocket, used by AraC and the related ToxT protein for the binding of small molecule regulators, although present in ExsA is not involved in binding of ExsD.« less

Design and realization of an autonomous solar system

NASA Astrophysics Data System (ADS)

Gaga, A.; Diouri, O.; Es-sbai, N.; Errahimi, F.

2017-03-01

The aim of this work is the design and realization of an autonomous solar system, with MPPT control, a regulator charge/discharge of batteries, an H-bridge multi-level inverter with acquisition system and supervising based on a microcontroller. The proposed approach is based on developing a software platform in the LabVIEW environment which gives the system a flexible structure for controlling, monitoring and supervising the whole system in real time while providing power maximization and best quality of energy conversion from DC to AC power. The reliability of the proposed solar system is validated by the simulation results on PowerSim and experimental results achieved with a solar panel, a Lead acid battery, solar regulator and an H-bridge cascaded topology of single-phase inverter.

The brain endocannabinoid system in the regulation of energy balance.

PubMed

Richard, Denis; Guesdon, Benjamin; Timofeeva, Elena

2009-02-01

The role played by the endocannabinoid system in the regulation of energy balance is currently generating a great amount of interest among several groups of investigators. This interest in large part comes from the urgent need to develop anti-obesity and anti-cachexia drugs around target systems (such as the endocannabinoid system), which appears to be genuinely involved in energy balance regulation. When activated, the endocannabinoid system favors energy deposition through increasing energy intake and reducing energy expenditure. This system is activated in obesity and following food deprivation, which further supports its authentic function in energy balance regulation. The cannabinoid receptor type 1 (CB1), one of the two identified cannabinoid receptors, is expressed in energy-balance brain structures that are also able to readily produce or inactivate N-arachidonoyl ethanolamine (anandamide) and 2-arachidonoylglycerol (2AG), the most abundantly formed and released endocannabinoids. The brain action of endocannabinoid system on energy balance seems crucial and needs to be delineated in the context of the homeostatic and hedonic controls of food intake and energy expenditure. These controls require the coordinated interaction of the hypothalamus, brainstem and limbic system and it appears imperative to unravel those interplays. It is also critical to investigate the metabolic endocannabinoid system while considering the panoply of functions that the endocannabinoid system fulfills in the brain and other tissues. This article aims at reviewing the potential mechanisms whereby the brain endocannabinoid system influences the regulation energy balance.

The ArcB Leucine Zipper Domain Is Required for Proper ArcB Signaling

PubMed Central

Nuñez Oreza, Luis Alberto; Alvarez, Adrián F.; Arias-Olguín, Imilla I.; Torres Larios, Alfredo; Georgellis, Dimitris

2012-01-01

The Arc two-component system modulates the expression of numerous genes in response to respiratory growth conditions. This system comprises ArcA as the response regulator and ArcB as the sensor kinase. ArcB is a tripartite histidine kinase whose activity is regulated by the oxidation of two cytosol-located redox-active cysteine residues that participate in intermolecular disulfide bond formation. Here, we report that the ArcB protein segment covering residues 70–121, fulfills the molecular characteristics of a leucine zipper containing coiled coil structure. Also, mutational analyses of this segment reveal three different phenotypical effects to be distributed along the coiled coil structure of ArcB, demonstrating that this motif is essential for proper ArcB signaling. PMID:22666479

Regulating incentives: the past and present role of the state in health care systems.

PubMed

Saltman, Richard B

2002-06-01

The desire of national policymakers to encourage entrepreneurial behavior in the health sector has generated not only a new structure of market-oriented incentives, but also a new regulatory role for the State. To ensure that entrepreneurial behavior will be directed toward achieving planned market objectives, the State must shift modalities from staid bureaucratic models of command-and-control to more sensitive and sophisticated systems of oversight and supervision. Available evidence suggests that this structural transformation is currently occurring in several Northern European countries. Successful implementation of that shift will require a new, intensive, and expensive strategy for human resources development, raising questions about the financial feasibility of this incentives-plus-regulation model for less-well-off CEE/CIS and developing countries.

Carcinogenesis: alterations in reciprocal interactions of normal functional structure of biologic systems.

PubMed

Davydyan, Garri

2015-12-01

The evolution of biologic systems (BS) includes functional mechanisms that in some conditions may lead to the development of cancer. Using mathematical group theory and matrix analysis, previously, it was shown that normally functioning BS are steady functional structures regulated by three basis regulatory components: reciprocal links (RL), negative feedback (NFB) and positive feedback (PFB). Together, they form an integrative unit maintaining system's autonomy and functional stability. It is proposed that phylogenetic development of different species is implemented by the splitting of "rudimentary" characters into two relatively independent functional parts that become encoded in chromosomes. The functional correlate of splitting mechanisms is RL. Inversion of phylogenetic mechanisms during ontogenetic development leads cell differentiation until cells reach mature states. Deterioration of reciprocal structure in the genome during ontogenesis gives rise of pathological conditions characterized by unsteadiness of the system. Uncontrollable cell proliferation and invasive cell growth are the leading features of the functional outcomes of malfunctioning systems. The regulatory element responsible for these changes is RL. In matrix language, pathological regulation is represented by matrices having positive values of diagonal elements ( TrA  > 0) and also positive values of matrix determinant ( detA  > 0). Regulatory structures of that kind can be obtained if the negative entry of the matrix corresponding to RL is replaced with the positive one. To describe not only normal but also pathological states of BS, a unit matrix should be added to the basis matrices representing RL, NFB and PFB. A mathematical structure corresponding to the set of these four basis functional patterns (matrices) is a split quaternion (coquaternion). The structure and specific role of basis elements comprising four-dimensional linear space of split quaternions help to understand what changes in mechanism of cell differentiation may lead to cancer development.

Structural Determination of Biomolecules in Microfluidic Systems

NASA Astrophysics Data System (ADS)

Butler, John C.; Menard, Etienne; Rogers, John A.; Wong, Gerard C. L.

2004-03-01

Supramolecular biological complexes are often too large to be crystallized for structural studies. Here, we explore the use of microfluidic arrays to order a model self-assembled cytoskeletal system. Filamentous actin (F-actin) is a negatively charged protein rod and is a key structural component in the eukaryotic cytoskeleton. In this context, F-actin can self-assemble with actin binding proteins (ABP) in a highly regulated manner to dynamically form structures for a wide range of biomechanical functions. In this work, we will systematically study the action of 3 types of actin binding proteins (a-actinin, fimbrin, cofilin) on the self-assembled structures of F-actin that have been aligned in microfluidic arrays.

The Mannitol Operon Repressor MTIR belongs to a new class of transcription regulators in bacteria.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tan, K.; Borovilos, M.; Zhou, M

2009-12-25

Many bacteria express phosphoenolpyruvate-dependent phosphotransferase systems (PTS). The mannitol-specific PTS catalyze the uptake and phosphorylation of d-mannitol. The uptake system comprises several genes encoded in the single operon. The expression of the mannitol operon is regulated by a proposed transcriptional factor, mannitol operon repressor (MtlR) that was first studied in Escherichia coli. Here we report the first crystal structures of MtlR from Vibrio parahemeolyticus (Vp-MtlR) and its homolog YggD protein from Shigella flexneri (Sf-YggD). MtlR and YggD belong to the same protein family (Pfam05068). Although Vp-MtlR and Sf-YggD share low sequence identity (22%), their overall structures are very similar, representingmore » a novel all {alpha}-helical fold, and indicate similar function. However, their lack of any known DNA-binding structural motifs and their unfavorable electrostatic properties imply that MtlR/YggD are unlikely to bind a specific DNA operator directly as proposed earlier. This structural observation is further corroborated by in vitro DNA-binding studies of E. coli MtlR (Ec-MtlR), which detected no interaction of Ec-MtlR with the well characterized mannitol operator/promoter region. Therefore, MtlR/YggD belongs to a new class of transcription factors in bacteria that may regulate gene expression indirectly as a part of a larger transcriptional complex.« less

Generic concept to program the time domain of self-assemblies with a self-regulation mechanism.

PubMed

Heuser, Thomas; Steppert, Ann-Kathrin; Lopez, Catalina Molano; Zhu, Baolei; Walther, Andreas

2015-04-08

Nature regulates complex structures in space and time via feedback loops, kinetically controlled transformations, and under energy dissipation to allow non-equilibrium processes. Although man-made static self-assemblies realize excellent control over hierarchical structures via molecular programming, managing their temporal destiny by self-regulation is a largely unsolved challenge. Herein, we introduce a generic concept to control the time domain by programming the lifetimes of switchable self-assemblies in closed systems. We conceive dormant deactivators that, in combination with fast promoters, enable a unique kinetic balance to establish an autonomously self-regulating, transient pH-state, whose duration can be programmed over orders of magnitude-from minutes to days. Coupling this non-equilibrium state to pH-switchable self-assemblies allows predicting their assembly/disassembly fate in time, similar to a precise self-destruction mechanism. We demonstrate a platform approach by programming self-assembly lifetimes of block copolymers, nanoparticles, and peptides, enabling dynamic materials with a self-regulation functionality.

Aging and Circadian Rhythms

PubMed Central

Duffy, Jeanne F.; Zitting, Kirsi-Marja; Chinoy, Evan D.

2015-01-01

Aging is associated with numerous changes, including changes in sleep timing, duration, and quality. The circadian timing system interacts with a sleep-wake homeostatic system to regulate human sleep, including sleep timing and structure. Here, we review key features of the human circadian timing system, age-related changes in the circadian timing system, and how those changes may contribute to the observed alterations in sleep. PMID:26568120

[Disperse endocrine system and APUD concept].

PubMed

Mil'to, I V; Sukhodolo, I V; Gereng, E A; Shamardina, L A

2011-01-01

This review describes the problems of disperse endocrine system and APUD-system morphology, summarizes some debatable issues of single endocrine cell biology. The data presented refer to the history of both systems discovery, morphological methods of their study, developmental sources, their structural organization and physiological roles of their cells. The significance of single endocrine cells in the regulation of the organism functions is discussed.

Crystal Structure of PhnF, a GntR-Family Transcriptional Regulator of Phosphate Transport in Mycobacterium smegmatis

PubMed Central

Busby, Jason N.; Fritz, Georg; Moreland, Nicole J.; Cook, Gregory M.; Lott, J. Shaun; Baker, Edward N.

2014-01-01

Bacterial uptake of phosphate is usually accomplished via high-affinity transporters that are commonly regulated by two-component systems, which are activated when the concentration of phosphate is low. Mycobacterium smegmatis possesses two such transporters, the widely distributed PstSCAB system and PhnDCE, a transporter that in other bacteria mediates the uptake of alternative phosphorus sources. We previously reported that the transcriptional regulator PhnF controls the production of the Phn system, acting as a repressor under high-phosphate conditions. Here we show that the phnDCE genes are common among environmental mycobacteria, where they are often associated with phnF-like genes. In contrast, pathogenic mycobacteria were not found to encode Phn-like systems but instead were found to possess multiple copies of the pst genes. A detailed biochemical analysis of PhnF binding to its identified binding sites in the phnD-phnF intergenic region of M. smegmatis has allowed us to propose a quantitative model for repressor binding, which shows that a PhnF dimer binds independently to each site. We present the crystal structure of M. smegmatis PhnF at 1.8-Å resolution, showing a homodimer with a helix-turn-helix N-terminal domain and a C-terminal domain with a UbiC transcription regulator-associated fold. The C-terminal domain crystallized with a bound sulfate ion instead of the so far unidentified physiological ligand, allowing the identification of residues involved in effector binding. Comparison of the positioning of the DNA binding domains in PhnF with that in homologous proteins suggests that its DNA binding activity is regulated via a conformational change in the linker region, triggering a movement of the N-terminal domains. PMID:25049090

[THE INCONSISTENCIES OF REGULATION OF METABOLISM IN PHYLOGENESIS AT THREE LEVELS OF "RELATIVE BIOLOGICAL PERFECTION": ETIOLOGY OF METABOLIC PANDEMICS].

PubMed

Titov, V N

2015-11-01

The regulation of metabolism in vivo can be comprehended by considering stages of becoming inphylogenesis of humoral, hormonal, vegetative regulators separately: at the level of cells; in paracrin-regulated cenosises of cells; organs and systems under open blood circulation and closed system of blood flow. The levels of regulations formed at different stages of phylogenesis. Their completion occurred at achievement of "relative biological perfection". Only this way need of cells in functional, structural interaction and forming of multicellular developed. The development of organs and systems of organs also completed at the level of "relative biological perfection". From the same level the third stage of becoming of regulation of metabolism at the level of organism started. When three conditions of "relative biological perfection" achieved consequently at level in vivo are considered in species Homo sapiens using system approach it is detected that "relative biological perfection" in vivo is accompanied by different inconsistencies of regulation of metabolism. They are etiologic factors of "metabolic pandemics ". The inconsistencies (etiological factors) are consider as exemplified by local (at the level of paracrin-regulated cenosises of cells) and system (at the level of organism) regulation of biological reaction metabolism-microcirculation that results in dysfunction of target organs and development of pathogenesis of essential metabolic arterial hypertension. The article describes phylogenetic difference between visceral fatty cells and adpocytes, regulation of metabolism by phylogenetically late insulin, reaction of albumin at increasing of content of unesterified fatty acids in blood plasma, difference of function of resident macrophage and monocytes-macrophages in pathogenesis of atherosclerosis, metabolic syndrome, insulin resistance, obesity, under diabetes mellitus and essential metabolic arterial hypertension.

Structural Biology of Tumor Necrosis Factor Demonstrated for Undergraduates Instruction by Computer Simulation

ERIC Educational Resources Information Center

Roy, Urmi

2016-01-01

This work presents a three-dimensional (3D) modeling exercise for undergraduate students in chemistry and health sciences disciplines, focusing on a protein-group linked to immune system regulation. Specifically, the exercise involves molecular modeling and structural analysis of tumor necrosis factor (TNF) proteins, both wild type and mutant. The…

29 CFR 1926.758 - Systems-engineered metal buildings.

Code of Federal Regulations, 2014 CFR

2014-07-01

..., DEPARTMENT OF LABOR (CONTINUED) SAFETY AND HEALTH REGULATIONS FOR CONSTRUCTION Steel Erection § 1926.758... systems-engineered metal buildings except §§ 1926.755 (column anchorage) and 1926.757 (open web steel... hoisting equipment is released. (d) Construction loads shall not be placed on any structural steel...

29 CFR 1926.758 - Systems-engineered metal buildings.

Code of Federal Regulations, 2013 CFR

2013-07-01

..., DEPARTMENT OF LABOR (CONTINUED) SAFETY AND HEALTH REGULATIONS FOR CONSTRUCTION Steel Erection § 1926.758... systems-engineered metal buildings except §§ 1926.755 (column anchorage) and 1926.757 (open web steel... hoisting equipment is released. (d) Construction loads shall not be placed on any structural steel...

29 CFR 1926.758 - Systems-engineered metal buildings.

Code of Federal Regulations, 2012 CFR

2012-07-01

..., DEPARTMENT OF LABOR (CONTINUED) SAFETY AND HEALTH REGULATIONS FOR CONSTRUCTION Steel Erection § 1926.758... systems-engineered metal buildings except §§ 1926.755 (column anchorage) and 1926.757 (open web steel... hoisting equipment is released. (d) Construction loads shall not be placed on any structural steel...

Manipulation of sarcoplasmic reticulum Ca2+ release in heart failure through mechanical intervention

PubMed Central

Ibrahim, Michael; Nader, Anas; Yacoub, Magdi H; Terracciano, Cesare

2015-01-01

Left ventricular assist devices (LVADs) were developed as a means of temporary circulatory support, but the mechanical unloading they offer also results in significant reverse remodelling. In selected patients, these improvements are sufficient to allow ultimate device explantation without requiring transplantation; this represents a fundamental shift in our understanding of heart failure. Like heart failure itself, LVADs influence multiple biological systems. The transverse tubules are a system of membrane invaginations in ventricular cardiomyocytes which allow rapid propagation of the action potential throughout the cell. Through their dense concentration of L-type Ca2+ channels in close proximity to intracellular ryanodine receptors, the t-tubules enable synchronous Ca2+ release throughout the cell. The t-tubules’ structure appears to be specifically regulated by mechanical load, such that either the overload of heart failure (or the spontaneously hypertensive rat model) or the profound unloading in a chronically unloaded heart result in impaired t-tubule structure, with ineffective Ca2+ release. While there are multiple molecular pathways which underpin t-tubule regulation, Telethonin (Tcap) appears to be important in regulating the effect of altered loading on the t-tubule system. PMID:25922157

Visual Cortex Plasticity: A Complex Interplay of Genetic and Environmental Influences

PubMed Central

Maya-Vetencourt, José Fernando; Origlia, Nicola

2012-01-01

The central nervous system architecture is highly dynamic and continuously modified by sensory experience through processes of neuronal plasticity. Plasticity is achieved by a complex interplay of environmental influences and physiological mechanisms that ultimately activate intracellular signal transduction pathways regulating gene expression. In addition to the remarkable variety of transcription factors and their combinatorial interaction at specific gene promoters, epigenetic mechanisms that regulate transcription have emerged as conserved processes by which the nervous system accomplishes the induction of plasticity. Experience-dependent changes of DNA methylation patterns and histone posttranslational modifications are, in fact, recruited as targets of plasticity-associated signal transduction mechanisms. Here, we shall concentrate on structural and functional consequences of early sensory deprivation in the visual system and discuss how intracellular signal transduction pathways associated with experience regulate changes of chromatin structure and gene expression patterns that underlie these plastic phenomena. Recent experimental evidence for mechanisms of cross-modal plasticity following congenital or acquired sensory deprivation both in human and animal models will be considered as well. We shall also review different experimental strategies that can be used to achieve the recovery of sensory functions after long-term deprivation in humans. PMID:22852098

VasH Is a Transcriptional Regulator of the Type VI Secretion System Functional in Endemic and Pandemic Vibrio cholerae▿†

PubMed Central

Kitaoka, Maya; Miyata, Sarah T.; Brooks, Teresa M.; Unterweger, Daniel; Pukatzki, Stefan

2011-01-01

The Gram-negative bacterium Vibrio cholerae is the etiological agent of cholera, a disease characterized by the release of high volumes of watery diarrhea. Many medically important proteobacteria, including V. cholerae, carry one or multiple copies of the gene cluster that encodes the bacterial type VI secretion system (T6SS) to confer virulence or interspecies competitiveness. Structural similarity and sequence homology between components of the T6SS and the cell-puncturing device of T4 bacteriophage suggest that the T6SS functions as a molecular syringe to inject effector molecules into prokaryotic and eukaryotic target cells. Although our understanding of how the structural T6SS apparatus assembles is developing, little is known about how this system is regulated. Here, we report on the contribution of the activator of the alternative sigma factor 54, VasH, as a global regulator of the V. cholerae T6SS. Using bioinformatics and mutational analyses, we identified domains of the VasH polypeptide that are essential for its ability to initiate transcription of T6SS genes and established a universal role for VasH in endemic and pandemic V. cholerae strains. PMID:21949076

What Combined Measurements From Structures and Imaging Tell Us About DNA Damage Responses

PubMed Central

Brosey, Chris A.; Ahmed, Zamal; Lees-Miller, Susan P.; Tainer, John A.

2017-01-01

DNA damage outcomes depend upon the efficiency and fidelity of DNA damage responses (DDRs) for different cells and damage. As such, DDRs represent tightly regulated prototypical systems for linking nanoscale biomolecular structure and assembly to the biology of genomic regulation and cell signaling. However, the dynamic and multifunctional nature of DDR assemblies can render elusive the correlation between the structures of DDR factors and specific biological disruptions to the DDR when these structures are altered. In this chapter, we discuss concepts and strategies for combining structural, biophysical, and imaging techniques to investigate DDR recognition and regulation, and thus bridge sequence-level structural biochemistry to quantitative biological outcomes visualized in cells. We focus on representative DDR responses from PARP/PARG/AIF damage signaling in DNA single-strand break repair and nonhomologous end joining complexes in double-strand break repair. Methods with exemplary experimental results are considered with a focus on strategies for probing flexibility, conformational changes, and assembly processes that shape a predictive understanding of DDR mechanisms in a cellular context. Integration of structural and imaging measurements promises to provide foundational knowledge to rationally control and optimize DNA damage outcomes for synthetic lethality and for immune activation with resulting insights for biology and cancer interventions. PMID:28668129

Thermal Management Optimization of a Thermoelectric-Integrated Methanol Evaporator Using a Compact CFD Modeling Approach

NASA Astrophysics Data System (ADS)

Gao, Xin; Chen, Min; Snyder, G. Jeffrey; Andreasen, Søren Juhl; Kær, Søren Knudsen

2013-07-01

To better manage the magnitude and direction of the heat flux in an exchanger-based methanol evaporator of a fuel cell system, thermoelectric (TE) modules can be deployed as TE heat flux regulators (TERs). The performance of the TE-integrated evaporator is strongly influenced by its heat exchange structure. The structure transfers the fuel cell exhaust heat to the evaporation chamber to evaporate the methanol, where TE modules are installed in between to facilitate the heat regulation. In this work, firstly, a numerical study is conducted to determine the working currents and working modes of the TERs under the system working condition fluctuations and during the system cold start. A three-dimensional evaporator model is generated in ANSYS FLUENT® by combining a compact TE model with various heat exchange structure geometries. The compact TE model can dramatically improve the computational efficiency, and uses a different material property acquisition method based on module manufacturers' datasheets. Secondly, a simulation study is carried out on the novel evaporator to minimize its thermal resistance and to assess the evaporator pressure drop. The factors studied include the type of fins in the heat exchange structure, the thickness of the fins, the axial conduction penalty, etc. Results show that the TE-integrated evaporator can work more efficiently and smoothly during both load fluctuations and system cold start, offering superior performance.

[Legal aspects of the REACH regulation. The control system of the REACH regulation--new approaches in the EU chemical legislation].

PubMed

Pache, Eckhard

2008-12-01

The REACH regulation from 2006 shall overcome the deficiencies of the previously existing inconsistent legal system of chemicals and build an efficient and innovative regulation for industrial chemicals in the EU. For this purpose, the REACH regulation is not inventing a completely new legislation for chemical substances, but refers to the existing rules, regulates and structures them in a new manner and complements them. With REACH a consistent control system for chemicals in Europe has been created, which basically is managed and coordinated by the newly established European Chemicals Agency (ECHA). In the first phases of the REACH system, information about chemicals is generated and afterwards evaluated. Then this information is used in a process of authorization and restriction, to ensure adequate proliferation and safe exposure to chemical substances. Numerous duties to furnish information complement the readjustment's procedural steps, particularly with regard to the supply chain and down to the consumer. It is mainly affected by the abrogation of the determination between new and existing substances, the principle of substitution and is based on the idea that industry itself is best suited to ensure that the substances it manufactures and places on the market in the EU do not adversely affect human health or the environment.

Development and application of the modal space self-tuning regulator

NASA Astrophysics Data System (ADS)

Schultze, John Francis

The control and reduction of vibration of flexible structures is currently an area of much research and concern in the aerospace and automotive industries. Often these systems are idealized as discrete systems with a finite number of degrees of freedom. Traditional active control approaches have attempted either to identify the complete system and design an appropriate controller or; use an ad-hoc set of single degree of freedom controllers. Both methods have limitations. The former requires great computational and control design effort. This approach also attempts to reduce the vibration across the complete spectrum as opposed to applying control effort only to the problematic mode(s). The latter method is often limited by its inability to address the structural coupling inherent in these systems. The Modal Space Self Tuning Regulator (MSSTR) method proposed in this research addresses both of these problems as well as changes in the structural properties of a system. The control problem is approached in a two stage effort, decoupling and adaptive control. The structure's motion is decoupled through the Modified Reciprocal Modal Vector method. The control is then implemented in modal space as a new acceleration feedback based, single degree of freedom, form of the Self Tuning Regulator. The range of application of this controller in terms of maximum additive damping, actuator location sensitivity, and discrete and continuous system mass changes are investigated. Also, the behavior of the internal controller parameters are studied for the extension of this method to system monitoring and damage detection. Proof of the numeric stability of the controller in the ideal case is presented as well as its practical implementation issues. This control approach was shown to be effective for the cases of specified damping increases up to 10 dB, several actuator locations, three discrete mass perturbations and several continuous mass change cases. There appears to be little dependence on the actuator position until the additive damping limit is reached. The discrete mass change tests investigate both increases and reductions in the effective moving mass of the system. The controller performed well in all cases investigated achieving a minimum of 7 dB and up to 15 dB of attenuation. The continuous mass change cases, modeling tool-wear, fuel consumption, or other time varying phenomena, show good convergence behavior of the system model and the accompanying regulator law parameters. This validates the controller for its implementation in a rapidly changing system. The MSSTR performed well in several varied test cases, showing both insensitivity to actuator location and resilience to changing system parameters. Extensions to multi-input, multi-mode control appears within ready grasp.

Strategic behaviors and governance challenges in social-ecological systems

NASA Astrophysics Data System (ADS)

Muneepeerakul, Rachata; Anderies, John M.

2017-08-01

The resource management and environmental policy literature focuses on devising regulations and incentive structures to achieve desirable goals. It often presumes the existence of public infrastructure that actualizes these incentives and regulations through a process loosely referred to as `governance.' In many cases, it is not clear if and how such governance infrastructure can be created and supported. Here, we take a complex systems view in which `governance' is an emergent phenomenon generated by interactions between social, economic, and environmental (both built and natural) factors. We present a framework and formal stylized model to explore under what circumstances stable governance structures may emerge endogenously in coupled infrastructure systems comprising shared natural, social, and built infrastructures of which social-ecological systems are specific examples. The model allows us to derive general conditions for a sustainable coupled infrastructure system in which critical infrastructure (e.g., canals) is provided by a governing entity that enables resource users (e.g., farmers) to produce outputs from natural infrastructure (e.g., water) to meet their needs while supporting the governing entity.

[Organizational forms of emergency medicine in international comparison].

PubMed

Lipp, M

1993-09-01

The tasks of preclinical emergency medicine systems (PEMS) are to stabilize and maintain the vital functions and to guarantee qualified transport to the hospital. Worldwide, different structures exist as a result of historical developments. Legal regulations for PEMS have been introduced in most of the industrialized countries since 1960. More and more aspects have been subject to detailed regulations. PEMS are provided either by state-owned or by state-controlled (private) organisations. In most of the "underdeveloped" countries legal regulations do not exist and PEMS is often provided by social workers, by the army or by volunteers. In most countries, PEMS are financed by the state with a charge on the patient. In a few states PEMS are totally financed by the public health structure. Modern PEMS are controlled from dispatch centres which receive emergency calls (mostly by telephone) and send the appropriate rescue unit. In most states the staff of dispatch centres are paramedics; in some countries and in some urban areas physicians control the dispatch centre. In PEMS without physicians on the scene, an information exchange between the scene and the hospital can be observed frequently, in contrast to systems with physicians on the scene. Worldwide, ground-based PEMS are preferred, but in most countries an additional air rescue system has been established. The quality and quantity of the technical equipment of the ground-based PEMS differ widely: nationwide regulations exist, however, in the USA and Germany. Generally, there are two main concepts concerning the personnel structure: PEMS are either physician based or not. Requirements for emergency physicians differ greatly: in some countries no formal requirements exist, in others extensive practical and theoretical training is required.(ABSTRACT TRUNCATED AT 250 WORDS)

Revisiting control establishments for emerging energy hubs

NASA Astrophysics Data System (ADS)

Nasirian, Vahidreza

Emerging small-scale energy systems, i.e., microgrids and smartgrids, rely on centralized controllers for voltage regulation, load sharing, and economic dispatch. However, the central controller is a single-point-of-failure in such a design as either the controller or attached communication links failure can render the entire system inoperable. This work seeks for alternative distributed control structures to improve system reliability and help to the scalability of the system. A cooperative distributed controller is proposed that uses a noise-resilient voltage estimator and handles global voltage regulation and load sharing across a DC microgrid. Distributed adaptive droop control is also investigated as an alternative solution. A droop-free distributed control is offered to handle voltage/frequency regulation and load sharing in AC systems. This solution does not require frequency measurement and, thus, features a fast frequency regulation. Distributed economic dispatch is also studied, where a distributed protocol is designed that controls generation units to merge their incremental costs into a consensus and, thus, push the entire system to generate with the minimum cost. Experimental verifications and Hardware-in-the-Loop (HIL) simulations are used to study efficacy of the proposed control protocols.

Decoupling the Lattice Distortion and Charge Doping Effects on the Phase Transition Behavior of VO2 by Titanium (Ti4+) Doping

PubMed Central

Wu, Yanfei; Fan, Lele; Liu, Qinghua; Chen, Shi; Huang, Weifeng; Chen, Feihu; Liao, Guangming; Zou, Chongwen; Wu, Ziyu

2015-01-01

The mechanism for regulating the critical temperature (TC) of metal-insulator transition (MIT) in ions-doped VO2 systems is still a matter of debate, in particular, the unclear roles of lattice distortion and charge doping effects. To rule out the charge doping effect on the regulation of TC, we investigated Ti4+-doped VO2 (TixV1-xO2) system. It was observed that the TC of TixV1-xO2 samples first slightly decreased and then increased with increasing Ti concentration. X-ray absorption fine structure (XAFS) spectroscopy was used to explore the electronic states and local lattice structures around both Ti and V atoms in TixV1-xO2 samples. Our results revealed the local structure evolution from the initial anatase to the rutile-like structure around the Ti dopants. Furthermore, the host monoclinic VO2 lattice, specifically, the VO6 octahedra would be subtly distorted by Ti doping. The distortion of VO6 octahedra and the variation of TC showed almost the similar trend, confirming the direct effect of local structural perturbations on the phase transition behavior. By comparing other ion-doping systems, we point out that the charge doping is more effective than the lattice distortion in modulating the MIT behavior of VO2 materials. PMID:25950809

An aberrant parasympathetic response: a new perspective linking chronic stress and itch.

PubMed

Kim, Hei Sung; Yosipovitch, Gil

2013-04-01

Perceived stress has long been known to alter the dynamic equilibrium established between the nervous, endocrine and immune system and is widely recognised to trigger or enhance pruritus. However, the exact mechanism of how the major stress response systems, such as the hypothalamus-pituitary adrenal (HPA) axis and the autonomic nervous system induce or aggravate chronic itch, has not been elucidated. The limbic regions of the brain such as the prefrontal cortex and hippocampus are deeply involved in the regulation of the stress response and intersect with circuits that are responsible for memory and reward. According to the 'Polyvagal Theory', certain limbic structures that serve as a 'higher brain equivalent of the parasympathetic nervous system' play a foremost role in maintaining body homoeostasis by functioning as an active vagal brake. In addition, the limbic system has been postulated to regulate two distinct, yet related aspects of itch: (i) the sensory-discriminative aspect; and (ii) the affective-cognitive aspect. Chronic stress-induced itch is hypothesised to be caused by stress-related changes in limbic structure with subsequent rewiring of both the peripheral and central pruriceptive circuits. Herein, we review data suggesting that a dysfunctional parasympathetic nervous system associated with chronic stress may play a critical role in the regulatory control of key candidate molecules, receptors and brain structures involved in chronic itch. © 2012 John Wiley & Sons A/S.

The Labour Party's Blunkett Review: A Comprehensive Disappointment

ERIC Educational Resources Information Center

Lichman, Keith

2014-01-01

David Blunkett's "Review of Education Structures" for the Labour Party recognises that there is a chaotic and unsatisfactory situation in the English education system but its response is ambiguous and self-contradictory. Its proposals seek to normalise and regulate rather than remedy a system in which lack of democratic accountability,…

The Educational System of Venezuela. Education around the World.

ERIC Educational Resources Information Center

Nemeth, Edward J.

History, structure, legal bases, and planned reforms of the educational system of Venezuela are discussed. The conflicting roles of church and state in administering education have been reconciled within the past two decades, with resultant increases in enrollment and government financing. Curriculum regulation, coordination, and supervision are…

Maturing Glycoproteomics Technologies Provide Unique Structural Insights into the N-glycoproteome and Its Regulation in Health and Disease*

PubMed Central

Packer, Nicolle H.; Schulz, Benjamin L.

2016-01-01

The glycoproteome remains severely understudied because of significant analytical challenges associated with glycoproteomics, the system-wide analysis of intact glycopeptides. This review introduces important structural aspects of protein N-glycosylation and summarizes the latest technological developments and applications in LC-MS/MS-based qualitative and quantitative N-glycoproteomics. These maturing technologies provide unique structural insights into the N-glycoproteome and its synthesis and regulation by complementing existing methods in glycoscience. Modern glycoproteomics is now sufficiently mature to initiate efforts to capture the molecular complexity displayed by the N-glycoproteome, opening exciting opportunities to increase our understanding of the functional roles of protein N-glycosylation in human health and disease. PMID:26929216

Neural signatures of cognitive and emotional biases in depression

PubMed Central

Fossati, Philippe

2008-01-01

Functional brain imaging studies suggest that depression is a system-level disorder affecting discrete but functionally linked cortical and limbic structures, with abnormalities in the anterior cingulate, lateral, ami medial prefrontal cortex, amygdala, ami hippocampus. Within this circuitry, abnormal corticolimbic interactions underlie cognitive deficits ami emotional impairment in depression. Depression involves biases toward processing negative emotional information and abnormal self-focus in response to emotional stimuli. These biases in depression could reflect excessive analytical self-focus in depression, as well as impaired cognitive control of emotional response to negative stimuli. By combining structural and functional investigations, brain imaging studies mav help to generate novel antidepressant treatments that regulate structural and factional plasticity within the neural network regulating mood and affective behavior.

[Current legislation in the healthcare system 2015/2016].

PubMed

Martenstein, I; Wienke, A

2016-03-01

The energy of the legislator in the healthcare system was barely stoppable in 2015. Many new laws have been brought into force and legal initiatives have also been implemented. The Hospital Structure Act, the Treatment Enhancement Act, amendments of the official medical fee schedules for physicians, the Prevention Act, the E-Health Act, the Anti-corruption Act, the hospital admission guidelines and amendments of the model specialty training regulations are just some of the essential alterations that lie ahead of the medical community. This article gives a review of the most important new legislative regulations in the healthcare system and presents the fundamental consequences for the practice.

[Current legislation in the healthcare system 2015/2016].

PubMed

Martenstein, I; Wienke, A

2016-05-01

The energy of the legislator in the healthcare system was barely stoppable in 2015. Many new laws have been brought into force and legal initiatives have also been implemented. The Hospital Structure Act, the Treatment Enhancement Act, amendments of the official medical fee schedules for physicians, the Prevention Act, the E-Health Act, the Anti-corruption Act, the hospital admission guidelines and amendments of the model specialty training regulations are just some of the essential alterations that lie ahead of the medical community. This article gives a review of the most important new legislative regulations in the healthcare system and presents the fundamental consequences for the practice.

The CpAL quorum sensing system regulates production of hemolysins CPA and PFO to build Clostridium perfringens biofilms.

PubMed

Vidal, Jorge E; Shak, Joshua R; Canizalez-Roman, Adrian

2015-06-01

Clostridium perfringens strains produce severe diseases, including myonecrosis and enteritis necroticans, in humans and animals. Diseases are mediated by the production of potent toxins that often damage the site of infection, e.g., skin epithelium during myonecrosis. In planktonic cultures, the regulation of important toxins, such as CPA, CPB, and PFO, is controlled by the C. perfringens Agr-like (CpAL) quorum sensing (QS) system. Strains also encode a functional LuxS/AI-2 system. Although C. perfringens strains form biofilm-like structures, the regulation of biofilm formation is poorly understood. Therefore, our studies investigated the role of CpAL and LuxS/AI-2 QS systems and of QS-regulated factors in controlling the formation of biofilms. We first demonstrate that biofilm production by reference strains differs depending on the culture medium. Increased biomass correlated with the presence of extracellular DNA in the supernatant, which was released by lysis of a fraction of the biofilm population and planktonic cells. Whereas ΔagrB mutant strains were not able to produce biofilms, a ΔluxS mutant produced wild-type levels. The transcript levels of CpAL-regulated cpa and pfoA genes, but not cpb, were upregulated in biofilms compared to planktonic cultures. Accordingly, Δcpa and ΔpfoA mutants, in type A (S13) or type C (CN3685) backgrounds, were unable to produce biofilms, whereas CN3685Δcpb made wild-type levels. Biofilm formation was restored in complemented Δcpa/cpa and ΔpfoA/pfoA strains. Confocal microscopy studies further detected CPA partially colocalizing with eDNA on the biofilm structure. Thus, CpAL regulates biofilm formation in C. perfringens by increasing levels of certain toxins required to build biofilms. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Cooling Water Intakes

EPA Pesticide Factsheets

Industries use large volumes of water for cooling. The water intakes pull large numbers of fish and other organisms into the cooling systems. EPA issues regulations on intake structures in order to minimize adverse environmental impacts.

K-Cl cotransporters, cell volume homeostasis, and neurological disease

PubMed Central

Kahle, Kristopher T.; Khanna, Arjun R.; Alper, Seth L.; Adragna, Norma C.; Lauf, Peter K.; Sun, Dandan; Delpire, Eric

2016-01-01

K+-Cl− cotransporters (KCCs) were originally characterized as regulators of red blood cell (RBC) volume. Since then, four distinct KCCs have been cloned, and their importance for volume regulation has been demonstrated in other cell types. Genetic models of certain KCCs, such as KCC3, and their inhibitory WNK-STE20/SPS1-related proline/alanine-rich kinase (SPAK) serine-threonine kinases, have demonstrated the evolutionary necessity of these molecules for nervous system cell volume regulation, structure, and function, and their involvement in neurological disease. The recent characterization of a swelling-activated dephosphorylation mechanism that potently stimulates the KCCs has pinpointed a potentially druggable switch of KCC activity. An improved understanding of WNK/SPAK-mediated KCC cell volume regulation in the nervous system might reveal novel avenues for the treatment of multiple neurological diseases. PMID:26142773

K-Cl cotransporters, cell volume homeostasis, and neurological disease.

PubMed

Kahle, Kristopher T; Khanna, Arjun R; Alper, Seth L; Adragna, Norma C; Lauf, Peter K; Sun, Dandan; Delpire, Eric

2015-08-01

K(+)-Cl(-) cotransporters (KCCs) were originally characterized as regulators of red blood cell (RBC) volume. Since then, four distinct KCCs have been cloned, and their importance for volume regulation has been demonstrated in other cell types. Genetic models of certain KCCs, such as KCC3, and their inhibitory WNK-STE20/SPS1-related proline/alanine-rich kinase (SPAK) serine-threonine kinases, have demonstrated the evolutionary necessity of these molecules for nervous system cell volume regulation, structure, and function, and their involvement in neurological disease. The recent characterization of a swelling-activated dephosphorylation mechanism that potently stimulates the KCCs has pinpointed a potentially druggable switch of KCC activity. An improved understanding of WNK/SPAK-mediated KCC cell volume regulation in the nervous system might reveal novel avenues for the treatment of multiple neurological diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

Molecular dynamics-based model of VEGF-A and its heparin interactions.

PubMed

Uciechowska-Kaczmarzyk, Urszula; Babik, Sándor; Zsila, Ferenc; Bojarski, Krzysztof Kamil; Beke-Somfai, Tamás; Samsonov, Sergey A

2018-06-01

We present a computational model of the Vascular Endothelial Growth Factor (VEGF), an important regulator of blood vessels formation, which function is affected by its heparin interactions. Although structures of a receptor binding (RBD) and a heparin binding domain (HBD) of VEGF are known, there are structural data neither on the 12 amino acids interdomain linker nor on its complexes with heparin. We apply molecular docking and molecular dynamics techniques combined with circular dichroism spectroscopy to model the full structure of the dimeric VEGF and to propose putative molecular mechanisms underlying the function of VEGF/VEGF receptors/heparin system. We show that both the conformational flexibility of the linker and the formation of HBD-heparin-HBD sandwich-like structures regulate the mutual disposition of HBDs and so affect the VEGF-mediated signalling. Copyright © 2018 Elsevier Inc. All rights reserved.

Patterns of synchrony for feed-forward and auto-regulation feed-forward neural networks.

PubMed

Aguiar, Manuela A D; Dias, Ana Paula S; Ferreira, Flora

2017-01-01

We consider feed-forward and auto-regulation feed-forward neural (weighted) coupled cell networks. In feed-forward neural networks, cells are arranged in layers such that the cells of the first layer have empty input set and cells of each other layer receive only inputs from cells of the previous layer. An auto-regulation feed-forward neural coupled cell network is a feed-forward neural network where additionally some cells of the first layer have auto-regulation, that is, they have a self-loop. Given a network structure, a robust pattern of synchrony is a space defined in terms of equalities of cell coordinates that is flow-invariant for any coupled cell system (with additive input structure) associated with the network. In this paper, we describe the robust patterns of synchrony for feed-forward and auto-regulation feed-forward neural networks. Regarding feed-forward neural networks, we show that only cells in the same layer can synchronize. On the other hand, in the presence of auto-regulation, we prove that cells in different layers can synchronize in a robust way and we give a characterization of the possible patterns of synchrony that can occur for auto-regulation feed-forward neural networks.

State of the APC/C: Organization, function, and structure

PubMed Central

McLean, Janel R.; Chaix, Denis; Ohi, Melanie D.; Gould, Kathleen L.

2016-01-01

The ubiquitin-proteasome protein degradation system is involved in many essential cellular processes including cell cycle regulation, cell differentiation, and the unfolded protein response.The anaphase-promoting complex/cyclosome (APC/C), an evolutionary conserved E3 ubiquitin ligase, was discovered 15 years ago because of its pivotal role in cyclin degradation and mitotic progression. Since then, we have learned that the APC/C is a very large, complex E3 ligase composed of 13 subunits, yielding a molecular machine of approximately 1 MDa. The intricate regulation of the APC/C is mediated by the Cdc20 family of activators, pseudosubstrate inhibitors, protein kinases and phosphatases and the spindle assembly checkpoint. The large size, complexity, and dynamic nature of the APC/C represent significant obstacles toward high-resolution structural techniques; however, over the last decade, there have been a number of lower resolution APC/C structures determined using single particle electron microscopy. These structures, when combined with data generated from numerous genetic and biochemical studies, have begun to shed light on how APC/C activity is regulated. Here, we discuss the most recent developments in the APC/C field concerning structure, substrate recognition, and catalysis. PMID:21261459

Investigation of structure in the modular light pipe component for LED automotive lamp

NASA Astrophysics Data System (ADS)

Chen, Hsi-Chao; Zhou, Yang; Huang, Chien-Sheng; Jhong, Wan-Ling; Cheng, Bo-Wei; Jhang, Jhe-Ming

2014-09-01

Light-Emitting Diodes (LEDs) have the advantages of small length, long lifetime, fast response time (μs), low voltage, good mechanical properties and environmental protection. Furthermore, LEDs could replace the halogen lamps to avoid the mercury pollution and economize the use of energy. Therefore, the LEDs could instead of the traditional lamp in the future and became an important light source. The proposal of this study was to investigate the effects of the structure and length of the reflector component for a LED automotive lamp. The novel LED automotive lamp was assembled by several different modularization columnar. The optimized design of the different structure and the length to the reflector was simulated by software TracePro. The design result must met the vehicle regulation of United Nations Economic Commission for Europe (UNECE) such as ECE-R19 etc. The structure of the light pipe could be designed by two steps structure. Then constitute the proper structure and choose different power LED to meet the luminous intensity of the vehicle regulation. The simulation result shows the proper structure and length has the best total luminous flux and a high luminous efficiency for the system. Also, the stray light could meet the vehicle regulation of ECE R19. Finally, the experimental result of the selected structure and length of the light pipe could match the simulation result above 80%.

Treatment of Depression From a Self-Regulation Perspective: Basic Concepts and Applied Strategies in Self-System Therapy.

PubMed

Strauman, Timothy J; Eddington, Kari M

2017-02-01

Self-regulation models of psychopathology provide a theory-based, empirically supported framework for developing psychotherapeutic interventions that complement and extend current cognitive-behavioral models. However, many clinicians are only minimally familiar with the psychology of self-regulation. The aim of the present manuscript is twofold. First, we provide an overview of self-regulation as a motivational process essential to well-being and introduce two related theories of self-regulation which have been applied to depression. Second, we describe how self-regulatory concepts and processes from those two theories have been translated into psychosocial interventions, focusing specifically on self-system therapy (SST), a brief structured treatment for depression that targets personal goal pursuit. Two randomized controlled trials have shown that SST is superior to cognitive therapy for depressed clients with specific self-regulatory deficits, and both studies found evidence that SST works in part by restoring adaptive self-regulation. Self-regulation-based psychotherapeutic approaches to depression hold significant promise for enhancing treatment efficacy and ultimately may provide an individualizable framework for treatment planning.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herrou, Julien; Willett, Jonathan W.; Czyż, Daniel M.

ABSTRACT Brucella abortusσ E1is an EcfG family sigma factor that regulates the transcription of dozens of genes in response to diverse stress conditions and is required for maintenance of chronic infection in a mouse model. A putative ATP-binding cassette transporter operon,bab1_0223-bab1_0226, is among the most highly activated gene sets in the σ E1regulon. The proteins encoded by the operon resemble quaternary ammonium-compatible solute importers but are most similar in sequence to the broadly conserved YehZYXW system, which remains largely uncharacterized. Transcription ofyehZYXWis activated by the general stress sigma factor σ SinEnterobacteriaceae, which suggests a functional role for this transport systemmore » in bacterial stress response across the classesAlphaproteobacteriaandGammaproteobacteria. We present evidence thatB. abortusYehZYXW does not function as an importer of known compatible solutes under physiological conditions and does not contribute to the virulence defect of a σ E1-null strain. The solein vitrophenotype associated with genetic disruption of this putative transport system is reduced growth in the presence of high Li +ion concentrations. A crystal structure ofB. abortusYehZ revealed a class II periplasmic binding protein fold with significant structural homology toArchaeoglobus fulgidusProX, which binds glycine betaine. However, the structure of the YehZ ligand-binding pocket is incompatible with high-affinity binding to glycine betaine. This is consistent with weak measured binding of YehZ to glycine betaine and related compatible solutes. We conclude that YehZYXW is a conserved, stress-regulated transport system that is phylogenetically and functionally distinct from quaternary ammonium-compatible solute importers. IMPORTANCEBrucella abortusσ E1regulates transcription in response to stressors encountered in its mammalian host and is necessary for maintenance of chronic infection in a mouse model. The functions of the majority of genes regulated by σ E1remain undefined. We present a functional/structural analysis of a conserved putative membrane transport system (YehZYXW) whose expression is strongly activated by σ E1. Though annotated as a quaternary ammonium osmolyte uptake system, experimental physiological studies and measured ligand-binding properties of the periplasmic binding protein (PBP), YehZ, are inconsistent with this function. A crystal structure ofB. abortusYehZ provides molecular insight into differences between bona fide quaternary ammonium osmolyte importers and YehZ-related proteins, which form a distinct phylogenetic and functional group of PBPs.« less

24 CFR 200.926 - Minimum property standards for one and two family dwellings.

Code of Federal Regulations, 2011 CFR

2011-04-01

... units in a structure where the units are located side-by-side in town house fashion. Section 200.926d(c... the subarea for seismic design (see § 200.926a(c)(5)), or if it fails to regulate subareas in more..., structural loads and seismic design, foundation systems, materials standards, construction components, glass...

24 CFR 200.926 - Minimum property standards for one and two family dwellings.

Code of Federal Regulations, 2010 CFR

2010-04-01

... units in a structure where the units are located side-by-side in town house fashion. Section 200.926d(c... the subarea for seismic design (see § 200.926a(c)(5)), or if it fails to regulate subareas in more..., structural loads and seismic design, foundation systems, materials standards, construction components, glass...

Mechanistic Implications of the Unique Structural Features and Dimerization of the Cytoplasmic Domain of the Pseudomonas Sigma Regulator, PupR

DOE PAGES

Jensen, Jaime L.; Balbo, Andrea; Neau, David B.; ...

2015-09-29

Gram-negative bacteria tightly regulate intracellular levels of iron, an essential nutrient. To ensure this tight regulation, some outer membrane TonB-dependent transporters (TBDTs) that are responsible for iron import stimulate their own transcription in response to extracellular binding by an iron-laden siderophore. This process is mediated by an inner membrane sigma regulator protein (an anti-sigma factor) that transduces an unknown periplasmic signal from the TBDT to release an intracellular sigma factor from the inner membrane, which ultimately upregulates TBDT transcription. Here we use the Pseudomonas putida ferric-pseudobactin BN7/BN8 sigma regulator, PupR, as a model system to understand the molecular mechanism ofmore » this conserved class of sigma regulators. We have determined the X-ray crystal structure of the cytoplasmic anti-sigma domain (ASD) of PupR to 2.0 Å. Size exclusion chromatography, small angle X-ray scattering, and sedimentation velocity analytical ultracentrifugation, all indicate that in contrast to other ASDs, the PupR-ASD exists as a dimer in solution. Mutagenesis of residues at the dimer interface identified from the crystal structure disrupts dimerization and protein stability, as determined by sedimentation velocity analytical ultracentrifugation and thermal denaturation circular dichroism spectroscopy. Lastly, these combined results suggest that this type of inner membrane sigma regulator may utilize an unusual mechanism to sequester their cognate sigma factors and prevent transcription activation.« less

Mechanistic Implications of the Unique Structural Features and Dimerization of the Cytoplasmic Domain of the Pseudomonas Sigma Regulator, PupR

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jensen, Jaime L.; Balbo, Andrea; Neau, David B.

Gram-negative bacteria tightly regulate intracellular levels of iron, an essential nutrient. To ensure this tight regulation, some outer membrane TonB-dependent transporters (TBDTs) that are responsible for iron import stimulate their own transcription in response to extracellular binding by an iron-laden siderophore. This process is mediated by an inner membrane sigma regulator protein (an anti-sigma factor) that transduces an unknown periplasmic signal from the TBDT to release an intracellular sigma factor from the inner membrane, which ultimately upregulates TBDT transcription. Here we use the Pseudomonas putida ferric-pseudobactin BN7/BN8 sigma regulator, PupR, as a model system to understand the molecular mechanism ofmore » this conserved class of sigma regulators. We have determined the X-ray crystal structure of the cytoplasmic anti-sigma domain (ASD) of PupR to 2.0 Å. Size exclusion chromatography, small angle X-ray scattering, and sedimentation velocity analytical ultracentrifugation, all indicate that in contrast to other ASDs, the PupR-ASD exists as a dimer in solution. Mutagenesis of residues at the dimer interface identified from the crystal structure disrupts dimerization and protein stability, as determined by sedimentation velocity analytical ultracentrifugation and thermal denaturation circular dichroism spectroscopy. Lastly, these combined results suggest that this type of inner membrane sigma regulator may utilize an unusual mechanism to sequester their cognate sigma factors and prevent transcription activation.« less

The leptin system and its expression at different nutritional and pregnant stages in lined seahorse (Hippocampus erectus).

PubMed

Zhang, Huixian; Qin, Geng; Zhang, Yanhong; Li, Shuisheng; Lin, Qiang

2016-10-15

Leptin is an essential hormone for the regulation of energy metabolism and food intake in vertebrate animals. To better understand the physiological roles of leptin in nutrient regulation in paternal ovoviviparous fish (family Syngnathidae), the present study cloned the full-length of leptin-a and leptin receptor (lepr) genes in lined seahorse (Hippocampus erectus). Results showed that there was a 576-bp intron between two exons in leptin-a gene but no leptin-b gene in seahorse. Although the primary amino acid sequence conservation of seahorse leptin-a was very low, the 3-D structure modeling of seahorse leptin-a revealed strong conservation of tertiary structure with other vertebrates. Seahorse leptin-a mRNA was highly expressed in brain, whereas lepr mRNA was mainly expressed in ovary and gill. Interestingly, both leptin-a and lepr mRNA were expressed in the brood pouch of male seahorse, suggesting the leptin system plays a role during the male pregnancy. Physiological experiments showed that the expression of hepatic leptin-a and lepr mRNA in unfed seahorses was significantly higher than that in those fed 100%, as well as 60%, of their food during the fasting stage, showing that seahorse might initiate the leptin system to regulate its energy metabolism while starving. Moreover, the expression of leptin-a in the brood pouch of pregnant seahorse was significantly upregulated compared with non-pregnant seahorse, whereas the expression of lepr was downregulated, suggesting that the leptin system might be involved in the male pregnancy. In conclusion, the leptin system plays a role in the energy metabolism and food intake, and might provide new insights into molecular regulation of male pregnancy in seahorse. © 2016. Published by The Company of Biologists Ltd.

The leptin system and its expression at different nutritional and pregnant stages in lined seahorse (Hippocampus erectus)

PubMed Central

Zhang, Huixian; Qin, Geng; Zhang, Yanhong; Li, Shuisheng

2016-01-01

ABSTRACT Leptin is an essential hormone for the regulation of energy metabolism and food intake in vertebrate animals. To better understand the physiological roles of leptin in nutrient regulation in paternal ovoviviparous fish (family Syngnathidae), the present study cloned the full-length of leptin-a and leptin receptor (lepr) genes in lined seahorse (Hippocampus erectus). Results showed that there was a 576-bp intron between two exons in leptin-a gene but no leptin-b gene in seahorse. Although the primary amino acid sequence conservation of seahorse leptin-a was very low, the 3-D structure modeling of seahorse leptin-a revealed strong conservation of tertiary structure with other vertebrates. Seahorse leptin-a mRNA was highly expressed in brain, whereas lepr mRNA was mainly expressed in ovary and gill. Interestingly, both leptin-a and lepr mRNA were expressed in the brood pouch of male seahorse, suggesting the leptin system plays a role during the male pregnancy. Physiological experiments showed that the expression of hepatic leptin-a and lepr mRNA in unfed seahorses was significantly higher than that in those fed 100%, as well as 60%, of their food during the fasting stage, showing that seahorse might initiate the leptin system to regulate its energy metabolism while starving. Moreover, the expression of leptin-a in the brood pouch of pregnant seahorse was significantly upregulated compared with non-pregnant seahorse, whereas the expression of lepr was downregulated, suggesting that the leptin system might be involved in the male pregnancy. In conclusion, the leptin system plays a role in the energy metabolism and food intake, and might provide new insights into molecular regulation of male pregnancy in seahorse. PMID:27628034

From early family systems to internalizing symptoms: The role of emotion regulation and peer relations.

PubMed

Lindblom, Jallu; Vänskä, Mervi; Flykt, Marjo; Tolvanen, Asko; Tiitinen, Aila; Tulppala, Maija; Punamäki, Raija-Leena

2017-04-01

Research has demonstrated the importance of early family characteristics, such as the quality of caregiving, on children's later mental health. Information is, however, needed about the role of more holistic family systems and specific child-related socioemotional mechanisms. In this study, we conceptualize families as dynamic family system types, consisting of both marital and parenting trajectories over the transition to parenthood. First, we examine how early family system types predict children's anxiety, depression, peer exclusion, and emotion regulation. Second, we test whether couples' infertility history and other family related contextual factors moderate the effects of family system types on child outcomes. Third, we test whether children's emotion regulation and peer exclusion mediate the effects of family system types on anxiety and depression. The participants were 452 families representing cohesive, distant, authoritative, enmeshed, and discrepant family types, identified on the basis of relationship autonomy and intimacy from pregnancy to the child's age of 2 and 12 months. Children's anxiety, depression, emotion regulation, and peer exclusion were assessed at the age of 7-8 years. Structural equation modeling showed that distant, enmeshed, and discrepant families similarly predicted children's heightened anxiety and depression. Infertility history, parental education, and parity moderated the associations between certain family system types and child outcomes. Finally, emotion regulation, but not peer exclusion, was a common mediating mechanism between distant and enmeshed families and children's depression. The results emphasize the importance of early family environments on children's emotion regulation development and internalizing psychopathology. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

H-NS regulates the Vibrio parahaemolyticus type VI secretion system 1

PubMed Central

Salomon, Dor; Klimko, John A.

2014-01-01

The marine bacterium Vibrio parahaemolyticus, a major cause of food-borne gastroenteritis, employs a type VI secretion system 1 (T6SS1), a recently discovered protein secretion system, to combat competing bacteria. Environmental signals such as temperature, salinity, cell density and surface sensing, as well as the quorum-sensing master regulator OpaR, were previously reported to regulate T6SS1 activity and expression. In this work, we set out to identify additional transcription regulators that control the tightly regulated T6SS1 activity. To this end, we determined the effect of deletions in several known virulence regulators and in two regulators encoded within the T6SS1 gene cluster on expression and secretion of the core T6SS component Hcp1 and on T6SS1-mediated anti-bacterial activity. We report that VP1391 and VP1407, transcriptional regulators encoded within the T6SS1 gene cluster, are essential for T6SS1 activity. Moreover, we found that H-NS, a bacterial histone-like nucleoid structuring protein, which mediates transcription silencing of horizontally acquired genes, serves as a repressor of T6SS1. We also show that activation of surface sensing and high salt conditions alleviate the H-NS-mediated repression. Our results shed light on the complex network of environmental signals and transcription regulators that govern the tight regulation over T6SS1 activity. PMID:24987102

Yersinia Type III Secretion System Master Regulator LcrF

PubMed Central

Schwiesow, Leah; Lam, Hanh

2015-01-01

Many Gram-negative pathogens express a type III secretion (T3SS) system to enable growth and survival within a host. The three human-pathogenic Yersinia species, Y. pestis, Y. pseudotuberculosis, and Y. enterocolitica, encode the Ysc T3SS, whose expression is controlled by an AraC-like master regulator called LcrF. In this review, we discuss LcrF structure and function as well as the environmental cues and pathways known to regulate LcrF expression. Similarities and differences in binding motifs and modes of action between LcrF and the Pseudomonas aeruginosa homolog ExsA are summarized. In addition, we present a new bioinformatics analysis that identifies putative LcrF binding sites within Yersinia target gene promoters. PMID:26644429

Golgi-Resident GTPase Rab30 Promotes the Biogenesis of Pathogen-Containing Autophagosomes

PubMed Central

Oda, Seiichiro; Nozawa, Takashi; Nozawa-Minowa, Atsuko; Tanaka, Misako; Aikawa, Chihiro; Harada, Hiroyuki; Nakagawa, Ichiro

2016-01-01

Autophagy acts as a host-defense system against pathogenic microorganisms such as Group A Streptococcus (GAS). Autophagy is a membrane-mediated degradation system that is regulated by intracellular membrane trafficking regulators, including small GTPase Rab proteins. Here, we identified Rab30 as a novel regulator of GAS-containing autophagosome-like vacuoles (GcAVs). We found that Rab30, a Golgi-resident Rab, was recruited to GcAVs in response to autophagy induction by GAS infection in epithelial cells. Rab30 recruitment was dependent upon its GTPase activity. In addition, the knockdown of Rab30 expression significantly reduced GcAV formation efficiency and impaired intracellular GAS degradation. Rab30 normally functions to maintain the structural integrity of the Golgi complex, but GcAV formation occurred even when the Golgi apparatus was disrupted. Although Rab30 also colocalized with a starvation-induced autophagosome, Rab30 was not required for autophagosome formation during starvation. These results suggest that Rab30 mediates autophagy against GAS independently of its normal cellular role in the structural maintenance of the Golgi apparatus, and autophagosome biogenesis during bacterial infection involves specific Rab GTPases. PMID:26771875

Structure-function analyses reveal the molecular architecture and neutralization mechanism of a bacterial HEPN-MNT toxin-antitoxin system.

PubMed

Jia, Xuanyan; Yao, Jianyun; Gao, Zengqiang; Liu, Guangfeng; Dong, Yu-Hui; Wang, Xiaoxue; Zhang, Heng

2018-05-04

Toxin-antitoxin (TA) loci in bacteria are small genetic modules that regulate various cellular activities, including cell growth and death. The two-gene module encoding a HEPN (higher eukaryotes and prokaryotes nucleotide-binding) domain and a cognate MNT (minimal nucleotidyltransferase) domain have been predicted to represent a novel type II TA system prevalent in archaea and bacteria. However, the neutralization mechanism and cellular targets of the TA family remain unclear. The toxin SO_3166 having a HEPN domain and its cognate antitoxin SO_3165 with an MNT domain constitute a typical type II TA system that regulates cell motility and confers plasmid stability in the bacterium Shewanella oneidensis Here, we report the crystal structure and solution conformation of the SO_3166-SO_3165 pair, representing the first complex structures in this TA family. The structures revealed that SO_3165 and SO_3166 form a tight heterooctamer (at a 2:6 ratio), an organization that is very rare in other TA systems. We also observed that SO_3166 dimerization enables the formation of a deep cleft at the HEPN-domain interface harboring a composite R X 4-6H active site that functions as an RNA-cleaving RNase. SO_3165 bound SO_3166 mainly through its two α-helices (α2 and α4), functioning as molecular recognition elements. Moreover, their insertion into the SO_3166 cleft sterically blocked the R X 4-6H site or narrowed the cleft to inhibit RNA substrate binding. Structure-based mutagenesis confirmed the important roles of these α-helices in SO_3166 binding and inhibition. Our structure-function analysis provides first insights into the neutralization mechanism of the HEPN-MNT TA family. © 2018 Jia et al.

Gap junctions in cells of the immune system: structure, regulation and possible functional roles.

PubMed

Sáez, J C; Brañes, M C; Corvalán, L A; Eugenín, E A; González, H; Martínez, A D; Palisson, F

2000-04-01

Gap junction channels are sites of cytoplasmic communication between contacting cells. In vertebrates, they consist of protein subunits denoted connexins (Cxs) which are encoded by a gene family. According to their Cx composition, gap junction channels show different gating and permeability properties that define which ions and small molecules permeate them. Differences in Cx primary sequences suggest that channels composed of different Cxs are regulated differentially by intracellular pathways under specific physiological conditions. Functional roles of gap junction channels could be defined by the relative importance of permeant substances, resulting in coordination of electrical and/or metabolic cellular responses. Cells of the native and specific immune systems establish transient homo- and heterocellular contacts at various steps of the immune response. Morphological and functional studies reported during the last three decades have revealed that many intercellular contacts between cells in the immune response present gap junctions or "gap junction-like" structures. Partial characterization of the molecular composition of some of these plasma membrane structures and regulatory mechanisms that control them have been published recently. Studies designed to elucidate their physiological roles suggest that they might permit coordination of cellular events which favor the effective and timely response of the immune system.

Dawn of the in vivo RNA structurome and interactome.

PubMed

Kwok, Chun Kit

2016-10-15

RNA is one of the most fascinating biomolecules in living systems given its structural versatility to fold into elaborate architectures for important biological functions such as gene regulation, catalysis, and information storage. Knowledge of RNA structures and interactions can provide deep insights into their functional roles in vivo For decades, RNA structural studies have been conducted on a transcript-by-transcript basis. The advent of next-generation sequencing (NGS) has enabled the development of transcriptome-wide structural probing methods to profile the global landscape of RNA structures and interactions, also known as the RNA structurome and interactome, which transformed our understanding of the RNA structure-function relationship on a transcriptomic scale. In this review, molecular tools and NGS methods used for RNA structure probing are presented, novel insights uncovered by RNA structurome and interactome studies are highlighted, and perspectives on current challenges and potential future directions are discussed. A more complete understanding of the RNA structures and interactions in vivo will help illuminate the novel roles of RNA in gene regulation, development, and diseases. © 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

MicroRNA miR-328 Regulates Zonation Morphogenesis by Targeting CD44 Expression

PubMed Central

Wang, Chia-Hui; Lee, Daniel Y.; Deng, Zhaoqun; Jeyapalan, Zina; Lee, Shao-Chen; Kahai, Shireen; Lu, Wei-Yang; Zhang, Yaou; Yang, Burton B.

2008-01-01

Morphogenesis is crucial to initiate physiological development and tumor invasion. Here we show that a microRNA controls zonation morphogenesis by targeting hyaluronan receptor CD44. We have developed a novel system to study microRNA functions by generating constructs expressing pre-miRNAs and mature miRNAs. Using this system, we have demonstrated that expression of miR-328 reduced cell adhesion, aggregation, and migration, and regulated formation of capillary structure. Protein analysis indicated that miR-328 repressed CD44 expression. Activities of luciferase constructs harboring the target site in CD44, but not the one containing mutation, were repressed by miR-328. Zonation morphogenesis appeared in cells transfected by miR-328: miR-328-transfected cells were present on the surface of zonating structures while the control cells stayed in the middle. MiR-328-mediated CD44 actions was validated by anti-CD44 antibody, hyaluronidase, CD44 siRNA, and CD44 expression constructs. In vivo experiments showed that CD44-silencing cells appeared as layers on the surfaces of nodules or zonating structures. Immuno-histochemistry also exhibited CD44-negative cells on the surface layers of normal rat livers and the internal zones of Portal veins. Our results demonstrate that miR-328 targets CD44, which is essential in regulating zonation morphogenesis: silencing of CD44 expression is essential in sealing the zonation structures to facilitate their extension and to inhibit complex expansion. PMID:18560585

MicroRNA miR-328 regulates zonation morphogenesis by targeting CD44 expression.

PubMed

Wang, Chia-Hui; Lee, Daniel Y; Deng, Zhaoqun; Jeyapalan, Zina; Lee, Shao-Chen; Kahai, Shireen; Lu, Wei-Yang; Zhang, Yaou; Yang, Burton B

2008-06-18

Morphogenesis is crucial to initiate physiological development and tumor invasion. Here we show that a microRNA controls zonation morphogenesis by targeting hyaluronan receptor CD44. We have developed a novel system to study microRNA functions by generating constructs expressing pre-miRNAs and mature miRNAs. Using this system, we have demonstrated that expression of miR-328 reduced cell adhesion, aggregation, and migration, and regulated formation of capillary structure. Protein analysis indicated that miR-328 repressed CD44 expression. Activities of luciferase constructs harboring the target site in CD44, but not the one containing mutation, were repressed by miR-328. Zonation morphogenesis appeared in cells transfected by miR-328: miR-328-transfected cells were present on the surface of zonating structures while the control cells stayed in the middle. MiR-328-mediated CD44 actions was validated by anti-CD44 antibody, hyaluronidase, CD44 siRNA, and CD44 expression constructs. In vivo experiments showed that CD44-silencing cells appeared as layers on the surfaces of nodules or zonating structures. Immuno-histochemistry also exhibited CD44-negative cells on the surface layers of normal rat livers and the internal zones of Portal veins. Our results demonstrate that miR-328 targets CD44, which is essential in regulating zonation morphogenesis: silencing of CD44 expression is essential in sealing the zonation structures to facilitate their extension and to inhibit complex expansion.

Zebrafish E-cadherin: expression during early embryogenesis and regulation during brain development.

PubMed

Babb, S G; Barnett, J; Doedens, A L; Cobb, N; Liu, Q; Sorkin, B C; Yelick, P C; Raymond, P A; Marrs, J A

2001-06-01

Zebrafish E-cadherin (cdh1) cell adhesion molecule cDNAs were cloned. We investigated spatial and temporal expression of cdh1 during early embryogenesis. Expression was observed in blastomeres, the anterior mesoderm during gastrulation, and developing epithelial structures. In the developing nervous system, cdh1 was detected at the pharyngula stage (24 hpf) in the midbrain-hindbrain boundary (MHB). Developmental regulation of MHB formation involves wnt1 and pax2.1. wnt1 expression preceded cdh1 expression during MHB formation, and cdh1 expression in the MHB was dependent on normal development of this structure. Copyright 2001 Wiley-Liss, Inc.

Cytoskeleton Molecular Motors: Structures and Their Functions in Neuron.

PubMed

Xiao, Qingpin; Hu, Xiaohui; Wei, Zhiyi; Tam, Kin Yip

2016-01-01

Cells make use of molecular motors to transport small molecules, macromolecules and cellular organelles to target region to execute biological functions, which is utmost important for polarized cells, such as neurons. In particular, cytoskeleton motors play fundamental roles in neuron polarization, extension, shape and neurotransmission. Cytoskeleton motors comprise of myosin, kinesin and cytoplasmic dynein. F-actin filaments act as myosin track, while kinesin and cytoplasmic dynein move on microtubules. Cytoskeleton motors work together to build a highly polarized and regulated system in neuronal cells via different molecular mechanisms and functional regulations. This review discusses the structures and working mechanisms of the cytoskeleton motors in neurons.

Oxytocin Receptor Genetic and Epigenetic Variations: Association with Child Abuse and Adult Psychiatric Symptoms

ERIC Educational Resources Information Center

Smearman, Erica L.; Almli, Lynn M.; Conneely, Karen N.; Brody, Gene H.; Sales, Jessica M.; Bradley, Bekh; Ressler, Kerry J.; Smith, Alicia K.

2016-01-01

Childhood abuse can alter biological systems and increase risk for adult psychopathology. Epigenetic mechanisms, alterations in DNA structure that regulate the gene expression, are a potential mechanism underlying this risk. While abuse associates with methylation of certain genes, particularly those in the stress response system, no study to date…

Decentralized regulation of dynamic systems. [for controlling large scale linear systems

NASA Technical Reports Server (NTRS)

Chu, K. C.

1975-01-01

A special class of decentralized control problem is discussed in which the objectives of the control agents are to steer the state of the system to desired levels. Each agent is concerned about certain aspects of the state of the entire system. The state and control equations are given for linear time-invariant systems. Stability and coordination, and the optimization of decentralized control are analyzed, and the information structure design is presented.

Exploring New Thermal Fog and Ultra-Low Volume Technologies to Improve Indoor Control of the Dengue Vector, Aedes aegypti (Diptera: Culicidae)

DTIC Science & Technology

2014-07-01

urban structures. An insect growth regulator was also applied to determine howwell each sprayer delivered lethal doses of active ingredient to indoor...vector suppressionwhencombinedwith aneffective insect growth regulator. However, during a dengue outbreak, either delivery system should provide an...sion(Morrisonetal. 2008,Eisenetal. 2009). Successful control programs rely on a combination of intradomi- ciliary adulticide application, larvicidal

From the endoplasmic reticulum to the plasma membrane: mechanisms of CFTR folding and trafficking.

PubMed

Farinha, Carlos M; Canato, Sara

2017-01-01

CFTR biogenesis starts with its co-translational insertion into the membrane of endoplasmic reticulum and folding of the cytosolic domains, towards the acquisition of a fully folded compact native structure. Efficiency of this process is assessed by the ER quality control system that allows the exit of folded proteins but targets unfolded/misfolded CFTR to degradation. If allowed to leave the ER, CFTR is modified at the Golgi and reaches the post-Golgi compartments to be delivered to the plasma membrane where it functions as a cAMP- and phosphorylation-regulated chloride/bicarbonate channel. CFTR residence at the membrane is a balance of membrane delivery, endocytosis, and recycling. Several adaptors, motor, and scaffold proteins contribute to the regulation of CFTR stability and are involved in continuously assessing its structure through peripheral quality control systems. Regulation of CFTR biogenesis and traffic (and its dysregulation by mutations, such as the most common F508del) determine its overall activity and thus contribute to the fine modulation of chloride secretion and hydration of epithelial surfaces. This review covers old and recent knowledge on CFTR folding and trafficking from its synthesis to the regulation of its stability at the plasma membrane and highlights how several of these steps can be modulated to promote the rescue of mutant CFTR.

A systems biology approach toward understanding seed composition in soybean.

PubMed

Li, Ling; Hur, Manhoi; Lee, Joon-Yong; Zhou, Wenxu; Song, Zhihong; Ransom, Nick; Demirkale, Cumhur Yusuf; Nettleton, Dan; Westgate, Mark; Arendsee, Zebulun; Iyer, Vidya; Shanks, Jackie; Nikolau, Basil; Wurtele, Eve Syrkin

2015-01-01

The molecular, biochemical, and genetic mechanisms that regulate the complex metabolic network of soybean seed development determine the ultimate balance of protein, lipid, and carbohydrate stored in the mature seed. Many of the genes and metabolites that participate in seed metabolism are unknown or poorly defined; even more remains to be understood about the regulation of their metabolic networks. A global omics analysis can provide insights into the regulation of seed metabolism, even without a priori assumptions about the structure of these networks. With the future goal of predictive biology in mind, we have combined metabolomics, transcriptomics, and metabolic flux technologies to reveal the global developmental and metabolic networks that determine the structure and composition of the mature soybean seed. We have coupled this global approach with interactive bioinformatics and statistical analyses to gain insights into the biochemical programs that determine soybean seed composition. For this purpose, we used Plant/Eukaryotic and Microbial Metabolomics Systems Resource (PMR, http://www.metnetdb.org/pmr, a platform that incorporates metabolomics data to develop hypotheses concerning the organization and regulation of metabolic networks, and MetNet systems biology tools http://www.metnetdb.org for plant omics data, a framework to enable interactive visualization of metabolic and regulatory networks. This combination of high-throughput experimental data and bioinformatics analyses has revealed sets of specific genes, genetic perturbations and mechanisms, and metabolic changes that are associated with the developmental variation in soybean seed composition. Researchers can explore these metabolomics and transcriptomics data interactively at PMR.

Chloroplast Translation: Structural and Functional Organization, Operational Control, and Regulation[OPEN

PubMed Central

2018-01-01

Chloroplast translation is essential for cellular viability and plant development. Its positioning at the intersection of organellar RNA and protein metabolism makes it a unique point for the regulation of gene expression in response to internal and external cues. Recently obtained high-resolution structures of plastid ribosomes, the development of approaches allowing genome-wide analyses of chloroplast translation (i.e., ribosome profiling), and the discovery of RNA binding proteins involved in the control of translational activity have greatly increased our understanding of the chloroplast translation process and its regulation. In this review, we provide an overview of the current knowledge of the chloroplast translation machinery, its structure, organization, and function. In addition, we summarize the techniques that are currently available to study chloroplast translation and describe how translational activity is controlled and which cis-elements and trans-factors are involved. Finally, we discuss how translational control contributes to the regulation of chloroplast gene expression in response to developmental, environmental, and physiological cues. We also illustrate the commonalities and the differences between the chloroplast and bacterial translation machineries and the mechanisms of protein biosynthesis in these two prokaryotic systems. PMID:29610211

Posttranslational Modifications Regulate the Postsynaptic Localization of PSD-95.

PubMed

Vallejo, Daniela; Codocedo, Juan F; Inestrosa, Nibaldo C

2017-04-01

The postsynaptic density (PSD) consists of a lattice-like array of interacting proteins that organizes and stabilizes synaptic receptors, ion channels, structural proteins, and signaling molecules required for normal synaptic transmission and synaptic function. The scaffolding and hub protein postsynaptic density protein-95 (PSD-95) is a major element of central chemical synapses and interacts with glutamate receptors, cell adhesion molecules, and cytoskeletal elements. In fact, PSD-95 can regulate basal synaptic stability as well as the activity-dependent structural plasticity of the PSD and, therefore, of the excitatory chemical synapse. Several studies have shown that PSD-95 is highly enriched at excitatory synapses and have identified multiple protein structural domains and protein-protein interactions that mediate PSD-95 function and trafficking to the postsynaptic region. PSD-95 is also a target of several signaling pathways that induce posttranslational modifications, including palmitoylation, phosphorylation, ubiquitination, nitrosylation, and neddylation; these modifications determine the synaptic stability and function of PSD-95 and thus regulate the fates of individual dendritic spines in the nervous system. In the present work, we review the posttranslational modifications that regulate the synaptic localization of PSD-95 and describe their functional consequences. We also explore the signaling pathways that induce such changes.

Extracellular matrix control of dendritic spine and synapse structure and plasticity in adulthood

PubMed Central

Levy, Aaron D.; Omar, Mitchell H.; Koleske, Anthony J.

2014-01-01

Dendritic spines are the receptive contacts at most excitatory synapses in the central nervous system. Spines are dynamic in the developing brain, changing shape as they mature as well as appearing and disappearing as they make and break connections. Spines become much more stable in adulthood, and spine structure must be actively maintained to support established circuit function. At the same time, adult spines must retain some plasticity so their structure can be modified by activity and experience. As such, the regulation of spine stability and remodeling in the adult animal is critical for normal function, and disruption of these processes is associated with a variety of late onset diseases including schizophrenia and Alzheimer’s disease. The extracellular matrix (ECM), composed of a meshwork of proteins and proteoglycans, is a critical regulator of spine and synapse stability and plasticity. While the role of ECM receptors in spine regulation has been extensively studied, considerably less research has focused directly on the role of specific ECM ligands. Here, we review the evidence for a role of several brain ECM ligands and remodeling proteases in the regulation of dendritic spine and synapse formation, plasticity, and stability in adults. PMID:25368556

Reverse engineering the gap gene network of Drosophila melanogaster.

PubMed

Perkins, Theodore J; Jaeger, Johannes; Reinitz, John; Glass, Leon

2006-05-01

A fundamental problem in functional genomics is to determine the structure and dynamics of genetic networks based on expression data. We describe a new strategy for solving this problem and apply it to recently published data on early Drosophila melanogaster development. Our method is orders of magnitude faster than current fitting methods and allows us to fit different types of rules for expressing regulatory relationships. Specifically, we use our approach to fit models using a smooth nonlinear formalism for modeling gene regulation (gene circuits) as well as models using logical rules based on activation and repression thresholds for transcription factors. Our technique also allows us to infer regulatory relationships de novo or to test network structures suggested by the literature. We fit a series of models to test several outstanding questions about gap gene regulation, including regulation of and by hunchback and the role of autoactivation. Based on our modeling results and validation against the experimental literature, we propose a revised network structure for the gap gene system. Interestingly, some relationships in standard textbook models of gap gene regulation appear to be unnecessary for or even inconsistent with the details of gap gene expression during wild-type development.

Crystal Structures of the Receiver Domain of the Response Regulator PhoP from Escherichia coli in the Absence and Presence of the Phosphoryl Analog Beryllofluoride▿

PubMed Central

Bachhawat, Priti; Stock, Ann M.

2007-01-01

The response regulator PhoP is part of the PhoQ/PhoP two-component system involved in responses to depletion of extracellular Mg2+. Here, we report the crystal structures of the receiver domain of Escherichia coli PhoP determined in the absence and presence of the phosphoryl analog beryllofluoride. In the presence of beryllofluoride, the active receiver domain forms a twofold symmetric dimer similar to that seen in structures of other regulatory domains from the OmpR/PhoB family, providing further evidence that members of this family utilize a common mode of dimerization in the active state. In the absence of activating agents, the PhoP receiver domain crystallizes with a similar structure, consistent with the previous observation that high concentrations can promote an active state of PhoP independent of phosphorylation. PMID:17545283

[Medical Devices Law for pain therapists].

PubMed

Regner, M; Sabatowski, R

2016-08-01

Medical Devices Law is a relatively new legal system, which has replaced the Medical Devices Regulations still well-known in Germany. German Medical Devices Law is based on European directives, which are, in turn, incorporated into national law by the Medical Devices Act. The Medical Devices Act is a framework law and covers a number of regulations that address specific topics within Medical Devices Law. In turn, in individual regulations, reference is made to guidelines, recommendations, etc. from other sources that provide detailed technical information on specific topics. Medical Devices Law is a very complex legal system, which needs to be permanently observed due to constant updating and adjustment. In the current article, the design and the structure of the system will be described, but special emphasis will be laid on important problem areas that need to be considered when applying and operating medical products, in this case by pain therapists in particular.

Modulation of electronic structures of bases through DNA recognition of protein.

PubMed

Hagiwara, Yohsuke; Kino, Hiori; Tateno, Masaru

2010-04-21

The effects of environmental structures on the electronic states of functional regions in a fully solvated DNA·protein complex were investigated using combined ab initio quantum mechanics/molecular mechanics calculations. A complex of a transcriptional factor, PU.1, and the target DNA was used for the calculations. The effects of solvent on the energies of molecular orbitals (MOs) of some DNA bases strongly correlate with the magnitude of masking of the DNA bases from the solvent by the protein. In the complex, PU.1 causes a variation in the magnitude among DNA bases by means of directly recognizing the DNA bases through hydrogen bonds and inducing structural changes of the DNA structure from the canonical one. Thus, the strong correlation found in this study is the first evidence showing the close quantitative relationship between recognition modes of DNA bases and the energy levels of the corresponding MOs. Thus, it has been revealed that the electronic state of each base is highly regulated and organized by the DNA recognition of the protein. Other biological macromolecular systems can be expected to also possess similar modulation mechanisms, suggesting that this finding provides a novel basis for the understanding for the regulation functions of biological macromolecular systems.

Integration of structural health monitoring solutions onto commercial aircraft via the Federal Aviation Administration structural health monitoring research program

NASA Astrophysics Data System (ADS)

Swindell, Paul; Doyle, Jon; Roach, Dennis

2017-02-01

The Federal Aviation Administration (FAA) started a research program in structural health monitoring (SHM) in 2011. The program's goal was to understand the technical gaps of implementing SHM on commercial aircraft and the potential effects on FAA regulations and guidance. The program evolved into a demonstration program consisting of a team from Sandia National Labs Airworthiness Assurance NDI Center (AANC), the Boeing Corporation, Delta Air Lines, Structural Monitoring Systems (SMS), Anodyne Electronics Manufacturing Corp (AEM) and the FAA. This paper will discuss the program from the selection of the inspection problem, the SHM system (Comparative Vacuum Monitoring-CVM) that was selected as the inspection solution and the testing completed to provide sufficient data to gain the first approved use of an SHM system for routine maintenance on commercial US aircraft.

Structure and Dynamics of the tRNA-like Structure Domain of Brome Mosaic Virus

NASA Astrophysics Data System (ADS)

Vieweger, Mario; Nesbitt, David

2014-03-01

Conformational switching is widely accepted as regulatory mechanism in gene expression in bacterial systems. More recently, similar regulation mechanisms are emerging for viral systems. One of the most abundant and best studied systems is the tRNA-like structure domain that is found in a number of plant viruses across eight genera. In this work, the folding dynamics of the tRNA-like structure domain of Brome Mosaic Virus are investigated using single-molecule Fluorescence Resonance Energy Transfer techniques. In particular, Burst fluorescence is applied to observe metal-ion induced folding in freely diffusing RNA constructs resembling the 3'-terminal 169nt of BMV RNA3. Histograms of EFRET probabilities reveal a complex equilibrium of three distinct populations. A step-wise kinetic model for TLS folding is developed in accord with the evolution of conformational populations and structural information in the literature. In this mechanism, formation of functional TLS domains from unfolded RNAs requires two consecutive steps; 1) hybridization of a long-range stem interaction followed by 2) formation of a 3' pseudoknot. This three-state equilibrium is well described by step-wise dissociation constants K1(328(30) μM) and K2(1092(183) μM) for [Mg2+] and K1(74(6) mM) and K2(243(52) mM) for [Na+]-induced folding. The kinetic model is validated by oligo competition with the STEM interaction. Implications of this conformational folding mechanism are discussed in regards to regulation of virus replication.

The Extracellular Environment of the CNS: Influence on Plasticity, Sprouting, and Axonal Regeneration after Spinal Cord Injury

PubMed Central

Forbes, Lindsey H.

2018-01-01

The extracellular environment of the central nervous system (CNS) becomes highly structured and organized as the nervous system matures. The extracellular space of the CNS along with its subdomains plays a crucial role in the function and stability of the CNS. In this review, we have focused on two components of the neuronal extracellular environment, which are important in regulating CNS plasticity including the extracellular matrix (ECM) and myelin. The ECM consists of chondroitin sulfate proteoglycans (CSPGs) and tenascins, which are organized into unique structures called perineuronal nets (PNNs). PNNs associate with the neuronal cell body and proximal dendrites of predominantly parvalbumin-positive interneurons, forming a robust lattice-like structure. These developmentally regulated structures are maintained in the adult CNS and enhance synaptic stability. After injury, however, CSPGs and tenascins contribute to the structure of the inhibitory glial scar, which actively prevents axonal regeneration. Myelin sheaths and mature adult oligodendrocytes, despite their important role in signal conduction in mature CNS axons, contribute to the inhibitory environment existing after injury. As such, unlike the peripheral nervous system, the CNS is unable to revert to a “developmental state” to aid neuronal repair. Modulation of these external factors, however, has been shown to promote growth, regeneration, and functional plasticity after injury. This review will highlight some of the factors that contribute to or prevent plasticity, sprouting, and axonal regeneration after spinal cord injury. PMID:29849554

Asymmetric activation mechanism of a homodimeric red light regulated photoreceptor.

PubMed

Gourinchas, Geoffrey; Heintz, Udo; Winkler, Andreas

2018-06-05

Organisms adapt to environmental cues using diverse signaling networks. In order to sense and integrate light for regulating various biological functions, photoreceptor proteins have evolved in a modular way. This modularity is targeted in the development of optogenetic tools enabling the control of cellular events with high spatiotemporal precision. However, the limited understanding of signaling mechanisms impedes the rational design of innovative photoreceptor-effector couples. Here we reveal molecular details of signal transduction in phytochrome-regulated diguanylyl-cyclases. Asymmetric structural changes of the full-length homodimer result in a functional heterodimer featuring two different photoactivation states. Structural changes around the cofactors result in a quasi-translational rearrangement of the distant coiled-coil sensor-effector linker. Eventually, this regulates enzymatic activity by modulating the dimer interface of the output domains. Considering the importance of phytochrome heterodimerization in plant signaling, our mechanistic details of asymmetric photoactivation in a bacterial system reveal novel aspects of the evolutionary adaptation of phytochromes. © 2018, Gourinchas et al.

Hierarchical regulation of photosynthesis gene expression by the oxygen-responsive PrrBA and AppA-PpsR systems of Rhodobacter sphaeroides.

PubMed

Gomelsky, Larissa; Moskvin, Oleg V; Stenzel, Rachel A; Jones, Denise F; Donohue, Timothy J; Gomelsky, Mark

2008-12-01

In the facultatively phototrophic proteobacterium Rhodobacter sphaeroides, formation of the photosynthetic apparatus is oxygen dependent. When oxygen tension decreases, the response regulator PrrA of the global two-component PrrBA system is believed to directly activate transcription of the puf, puh, and puc operons, encoding structural proteins of the photosynthetic complexes, and to indirectly upregulate the photopigment biosynthesis genes bch and crt. Decreased oxygen also results in inactivation of the photosynthesis-specific repressor PpsR, bringing about derepression of the puc, bch, and crt operons. We uncovered a hierarchical relationship between these two regulatory systems, earlier thought to function independently. We also more accurately assessed the spectrum of gene targets of the PrrBA system. First, expression of the appA gene, encoding the PpsR antirepressor, is PrrA dependent, which establishes one level of hierarchical dominance of the PrrBA system over AppA-PpsR. Second, restoration of the appA transcript to the wild-type level is insufficient for rescuing phototrophic growth impairment of the prrA mutant, whereas inactivation of ppsR is sufficient. This suggests that in addition to controlling appA transcription, PrrA affects the activity of the AppA-PpsR system via an as yet unidentified mechanism(s). Third, PrrA directly activates several bch and crt genes, traditionally considered to be the PpsR targets. Therefore, in R. sphaeroides, the global PrrBA system regulates photosynthesis gene expression (i) by rigorous control over the photosynthesis-specific AppA-PpsR regulatory system and (ii) by extensive direct transcription activation of genes encoding structural proteins of photosynthetic complexes as well as genes encoding photopigment biosynthesis enzymes.

The RNA Helicase DeaD Stimulates ExsA Translation To Promote Expression of the Pseudomonas aeruginosa Type III Secretion System

PubMed Central

Intile, Peter J.; Balzer, Grant J.; Wolfgang, Matthew C.

2015-01-01

ABSTRACT The Pseudomonas aeruginosa type III secretion system (T3SS) is a primary virulence factor important for phagocytic avoidance, disruption of host cell signaling, and host cell cytotoxicity. ExsA is the master regulator of T3SS transcription. The expression, synthesis, and activity of ExsA is tightly regulated by both intrinsic and extrinsic factors. Intrinsic regulation consists of the well-characterized ExsECDA partner-switching cascade, while extrinsic factors include global regulators that alter exsA transcription and/or translation. To identify novel extrinsic regulators of ExsA, we conducted a transposon mutagenesis screen in the absence of intrinsic control. Transposon disruptions within gene PA2840, which encodes a homolog of the Escherichia coli RNA-helicase DeaD, significantly reduced T3SS gene expression. Recent studies indicate that E. coli DeaD can promote translation by relieving inhibitory secondary structures within target mRNAs. We report here that PA2840, renamed DeaD, stimulates ExsA synthesis at the posttranscriptional level. Genetic experiments demonstrate that the activity of an exsA translational fusion is reduced in a deaD mutant. In addition, exsA expression in trans fails to restore T3SS gene expression in a deaD mutant. We hypothesized that DeaD relaxes mRNA secondary structure to promote exsA translation and found that altering the mRNA sequence of exsA or the native exsA Shine-Dalgarno sequence relieved the requirement for DeaD in vivo. Finally, we show that purified DeaD promotes ExsA synthesis using in vitro translation assays. Together, these data reveal a novel regulatory mechanism for P. aeruginosa DeaD and add to the complexity of global regulation of T3SS. IMPORTANCE Although members of the DEAD box family of RNA helicases are appreciated for their roles in mRNA degradation and ribosome biogenesis, an additional role in gene regulation is now emerging in bacteria. By relaxing secondary structures in mRNAs, DEAD box helicases are now thought to promote translation by enhancing ribosomal recruitment. We identify here an RNA helicase that plays a critical role in promoting ExsA synthesis, the central regulator of the Pseudomonas aeruginosa type III secretion system, and provide additional evidence that DEAD box helicases directly stimulate translation of target genes. The finding that DeaD stimulates exsA translation adds to a growing list of transcriptional and posttranscriptional regulatory mechanisms that control type III gene expression. PMID:26055113

A Testosterone-Related Structural Brain Phenotype Predicts Aggressive Behavior From Childhood to Adulthood

PubMed Central

Nguyen, Tuong-Vi; McCracken, James T; Albaugh, Matthew D; Botteron, Kelly N.; Hudziak, James J; Ducharme, Simon

2015-01-01

Structural covariance, the examination of anatomic correlations between brain regions, has emerged recently as a valid and useful measure of developmental brain changes. Yet the exact biological processes leading to changes in covariance, and the relation between such covariance and behavior, remain largely unexplored. The steroid hormone testosterone represents a compelling mechanism through which this structural covariance may be developmentally regulated in humans. Although steroid hormone receptors can be found throughout the central nervous system, the amygdala represents a key target for testosterone-specific effects, given its high density of androgen receptors. In addition, testosterone has been found to impact cortical thickness (CTh) across the whole brain, suggesting that it may also regulate the structural relationship, or covariance, between the amygdala and CTh. Here we examined testosterone-related covariance between amygdala volumes and whole-brain CTh, as well as its relationship to aggression levels, in a longitudinal sample of children, adolescents, and young adults 6 to 22 years old. We found: (1) testosterone-specific modulation of the covariance between the amygdala and medial prefrontal cortex (mPFC); (2) a significant relationship between amygdala-mPFC covariance and levels of aggression; and (3) mediation effects of amygdala-mPFC covariance on the relationship between testosterone and aggression. These effects were independent of sex, age, pubertal stage, estradiol levels and anxious-depressed symptoms. These findings are consistent with prior evidence that testosterone targets the neural circuits regulating affect and impulse regulation, and show, for the first time in humans, how androgen-dependent organizational effects may regulate a very specific, aggression-related structural brain phenotype from childhood to young adulthood. PMID:26431805

A testosterone-related structural brain phenotype predicts aggressive behavior from childhood to adulthood.

PubMed

Nguyen, Tuong-Vi; McCracken, James T; Albaugh, Matthew D; Botteron, Kelly N; Hudziak, James J; Ducharme, Simon

2016-01-01

Structural covariance, the examination of anatomic correlations between brain regions, has emerged recently as a valid and useful measure of developmental brain changes. Yet the exact biological processes leading to changes in covariance, and the relation between such covariance and behavior, remain largely unexplored. The steroid hormone testosterone represents a compelling mechanism through which this structural covariance may be developmentally regulated in humans. Although steroid hormone receptors can be found throughout the central nervous system, the amygdala represents a key target for testosterone-specific effects, given its high density of androgen receptors. In addition, testosterone has been found to impact cortical thickness (CTh) across the whole brain, suggesting that it may also regulate the structural relationship, or covariance, between the amygdala and CTh. Here, we examined testosterone-related covariance between amygdala volumes and whole-brain CTh, as well as its relationship to aggression levels, in a longitudinal sample of children, adolescents, and young adults 6-22 years old. We found: (1) testosterone-specific modulation of the covariance between the amygdala and medial prefrontal cortex (mPFC); (2) a significant relationship between amygdala-mPFC covariance and levels of aggression; and (3) mediation effects of amygdala-mPFC covariance on the relationship between testosterone and aggression. These effects were independent of sex, age, pubertal stage, estradiol levels and anxious-depressed symptoms. These findings are consistent with prior evidence that testosterone targets the neural circuits regulating affect and impulse regulation, and show, for the first time in humans, how androgen-dependent organizational effects may regulate a very specific, aggression-related structural brain phenotype from childhood to young adulthood. Copyright © 2015 Elsevier Ltd. All rights reserved.

Complex fluids with mobile charge-regulating macro-ions

NASA Astrophysics Data System (ADS)

Markovich, Tomer; Andelman, David; Podgornik, Rudi

2017-10-01

We generalize the concept of charge regulation of ionic solutions, and apply it to complex fluids with mobile macro-ions having internal non-electrostatic degrees of freedom. The suggested framework provides a convenient tool for investigating systems where mobile macro-ions can self-regulate their charge (e.g., proteins). We show that even within a simplified charge-regulation model, the charge dissociation equilibrium results in different and notable properties. Consequences of the charge regulation include a positional dependence of the effective charge of the macro-ions, a non-monotonic dependence of the effective Debye screening length on the concentration of the monovalent salt, a modification of the electric double-layer structure, and buffering by the macro-ions of the background electrolyte.

RNA-Binding Proteins in Trichomonas vaginalis: Atypical Multifunctional Proteins.

PubMed

Figueroa-Angulo, Elisa E; Calla-Choque, Jaeson S; Mancilla-Olea, Maria Inocente; Arroyo, Rossana

2015-11-26

Iron homeostasis is highly regulated in vertebrates through a regulatory system mediated by RNA-protein interactions between the iron regulatory proteins (IRPs) that interact with an iron responsive element (IRE) located in certain mRNAs, dubbed the IRE-IRP regulatory system. Trichomonas vaginalis, the causal agent of trichomoniasis, presents high iron dependency to regulate its growth, metabolism, and virulence properties. Although T. vaginalis lacks IRPs or proteins with aconitase activity, possesses gene expression mechanisms of iron regulation at the transcriptional and posttranscriptional levels. However, only one gene with iron regulation at the transcriptional level has been described. Recently, our research group described an iron posttranscriptional regulatory mechanism in the T. vaginalis tvcp4 and tvcp12 cysteine proteinase mRNAs. The tvcp4 and tvcp12 mRNAs have a stem-loop structure in the 5'-coding region or in the 3'-UTR, respectively that interacts with T. vaginalis multifunctional proteins HSP70, α-Actinin, and Actin under iron starvation condition, causing translation inhibition or mRNA stabilization similar to the previously characterized IRE-IRP system in eukaryotes. Herein, we summarize recent progress and shed some light on atypical RNA-binding proteins that may participate in the iron posttranscriptional regulation in T. vaginalis.

Biological life-support systems

NASA Technical Reports Server (NTRS)

Shepelev, Y. Y.

1975-01-01

The establishment of human living environments by biologic methods, utilizing the appropriate functions of autotrophic and heterotrophic organisms is examined. Natural biologic systems discussed in terms of modeling biologic life support systems (BLSS), the structure of biologic life support systems, and the development of individual functional links in biologic life support systems are among the factors considered. Experimental modeling of BLSS in order to determine functional characteristics, mechanisms by which stability is maintained, and principles underlying control and regulation is also discussed.

Structural basis for complement evasion by Lyme disease pathogen Borrelia burgdorferi.

PubMed

Bhattacharjee, Arnab; Oeemig, Jesper S; Kolodziejczyk, Robert; Meri, Taru; Kajander, Tommi; Lehtinen, Markus J; Iwaï, Hideo; Jokiranta, T Sakari; Goldman, Adrian

2013-06-28

Borrelia burgdorferi spirochetes that cause Lyme borreliosis survive for a long time in human serum because they successfully evade the complement system, an important arm of innate immunity. The outer surface protein E (OspE) of B. burgdorferi is needed for this because it recruits complement regulator factor H (FH) onto the bacterial surface to evade complement-mediated cell lysis. To understand this process at the molecular level, we used a structural approach. First, we solved the solution structure of OspE by NMR, revealing a fold that has not been seen before in proteins involved in complement regulation. Next, we solved the x-ray structure of the complex between OspE and the FH C-terminal domains 19 and 20 (FH19-20) at 2.83 Å resolution. The structure shows that OspE binds FH19-20 in a way similar to, but not identical with, that used by endothelial cells to bind FH via glycosaminoglycans. The observed interaction of OspE with FH19-20 allows the full function of FH in down-regulation of complement activation on the bacteria. This reveals the molecular basis for how B. burgdorferi evades innate immunity and suggests how OspE could be used as a potential vaccine antigen.

Rational Modular RNA Engineering Based on In Vivo Profiling of Structural Accessibility.

PubMed

Leistra, Abigail N; Amador, Paul; Buvanendiran, Aishwarya; Moon-Walker, Alex; Contreras, Lydia M

2017-12-15

Bacterial small RNAs (sRNAs) have been established as powerful parts for controlling gene expression. However, development and application of engineered sRNAs has primarily focused on regulating novel synthetic targets. In this work, we demonstrate a rational modular RNA engineering approach that uses in vivo structural accessibility measurements to tune the regulatory activity of a multisubstrate sRNA for differential control of its native target network. Employing the CsrB global sRNA regulator as a model system, we use published in vivo structural accessibility data to infer the contribution of its local structures (substructures) to function and select a subset for engineering. We then modularly recombine the selected substructures, differentially representing those of presumed high or low functional contribution, to build a library of 21 CsrB variants. Using fluorescent translational reporter assays, we demonstrate that the CsrB variants achieve a 5-fold gradient of control of well-characterized Csr network targets. Interestingly, results suggest that less conserved local structures within long, multisubstrate sRNAs may represent better targets for rational engineering than their well-conserved counterparts. Lastly, mapping the impact of sRNA variants on a signature Csr network phenotype indicates the potential of this approach for tuning the activity of global sRNA regulators in the context of metabolic engineering applications.

Molecular Force Spectroscopy on Cells

NASA Astrophysics Data System (ADS)

Liu, Baoyu; Chen, Wei; Zhu, Cheng

2015-04-01

Molecular force spectroscopy has become a powerful tool to study how mechanics regulates biology, especially the mechanical regulation of molecular interactions and its impact on cellular functions. This force-driven methodology has uncovered a wealth of new information of the physical chemistry of molecular bonds for various biological systems. The new concepts, qualitative and quantitative measures describing bond behavior under force, and structural bases underlying these phenomena have substantially advanced our fundamental understanding of the inner workings of biological systems from the nanoscale (molecule) to the microscale (cell), elucidated basic molecular mechanisms of a wide range of important biological processes, and provided opportunities for engineering applications. Here, we review major force spectroscopic assays, conceptual developments of mechanically regulated kinetics of molecular interactions, and their biological relevance. We also present current challenges and highlight future directions.

A quality system for PET: An industry perspective

NASA Astrophysics Data System (ADS)

Zigler, Steven S.; Breslow, Kenneth; Nazerias, Michael

2005-12-01

Quality systems have been employed in a variety of industries to develop and supply products that meet customer expectations and regulatory requirements. Most quality systems address organizational structure, design controls, production, complaints, audits, corrective actions and preventive actions. This paper describes PETNET's efforts to develop a quality system for use in the production of PET tracers. Our goal is to ensure quality products and to facilitate compliance with impending PET good manufacturing practice (GMP) regulations.

Overexpression of neurofilament H disrupts normal cell structure and function

NASA Technical Reports Server (NTRS)

Szebenyi, Gyorgyi; Smith, George M.; Li, Ping; Brady, Scott T.

2002-01-01

Studying exogenously expressed tagged proteins in live cells has become a standard technique for evaluating protein distribution and function. Typically, expression levels of experimentally introduced proteins are not regulated, and high levels are often preferred to facilitate detection. However, overexpression of many proteins leads to mislocalization and pathologies. Therefore, for normative studies, moderate levels of expression may be more suitable. To understand better the dynamics of intermediate filament formation, transport, and stability in a healthy, living cell, we inserted neurofilament heavy chain (NFH)-green fluorescent protein (GFP) fusion constructs in adenoviral vectors with tetracycline (tet)-regulated promoters. This system allows for turning on or off the synthesis of NFH-GFP at a selected time, for a defined period, in a dose-dependent manner. We used this inducible system for live cell imaging of changes in filament structure and cell shape, motility, and transport associated with increasing NFH-GFP expression. Cells with low to intermediate levels of NFH-GFP were structurally and functionally similar to neighboring, nonexpressing cells. In contrast, overexpression led to pathological alterations in both filament organization and cell function. Copyright 2002 Wiley-Liss, Inc.

[Competition in healthcare--political intentions].

PubMed

Knieps, Franz

2009-01-01

Over the last 20 years strategies introducing regulated competition have gradually been implemented in the corporatistically structured German healthcare system. In particular, this applies to the structure of health insurance organisation where the corporatively organised allocation system has deliberately been transformed to ensure health insurance choice. Accordingly, the laws governing membership, health insurance premiums and health benefits have been adapted and new rules for public finance including a risk structure compensation scheme encompassing the different kinds of health insurances have been established. The options for competition arising in the area of health service provision do not only affect the health insurance companies themselves, but also the relations to the providers of healthcare as well as their relationship with each other. This holds especially true of the role and function of the (regional) physicians' associations. The relation between collective agreements and individual contracts is still unclear. With the further development of strategies introducing regulated competition the possibilities and limitations of competition will have to be explored and many details--such as, for example, the implementation of the responsibility for ensuring the provision of healthcare services--need to be resolved.

Mathematic Model of Digital Control System with PID Regulator and Regular Step of Quantization with Information Transfer via the Channel of Plural Access

NASA Astrophysics Data System (ADS)

Abramov, G. V.; Emeljanov, A. E.; Ivashin, A. L.

Theoretical bases for modeling a digital control system with information transfer via the channel of plural access and a regular quantization cycle are submitted. The theory of dynamic systems with random changes of the structure including elements of the Markov random processes theory is used for a mathematical description of a network control system. The characteristics of similar control systems are received. Experimental research of the given control systems is carried out.

Space construction base control system

NASA Technical Reports Server (NTRS)

Kaczynski, R. F.

1979-01-01

Several approaches for an attitude control system are studied and developed for a large space construction base that is structurally flexible. Digital simulations were obtained using the following techniques: (1) the multivariable Nyquist array method combined with closed loop pole allocation, (2) the linear quadratic regulator method. Equations for the three-axis simulation using the multilevel control method were generated and are presented. Several alternate control approaches are also described. A technique is demonstrated for obtaining the dynamic structural properties of a vehicle which is constructed of two or more submodules of known dynamic characteristics.

The School Principal in Sweden: A Boss or a Leader? Implications for the Competence of School Principals.

ERIC Educational Resources Information Center

Nytell, Ulf

Management and leadership as a consequence of organizational tasks and structure are discussed in this paper, with a focus on the application of leadership theories from market-oriented organizations to more regulated organizations such as the Swedish school system. The Swedish educational system, according to Berg's (1988) "cross…

The Domestic Telecommunications Carrier Industry. Part I. President's Task Force on Communications Policy. Staff Paper Five.

ERIC Educational Resources Information Center

Rostow, Eugene V.

A staff paper submitted to the President's Task Force on Communications Policy recommends that public policy ensure an integrated structure in the telecommunications industry, while fostering limited competition to keep the system responsive to new technology and to consumer demands. The present system of regulated monopoly for companies supplying…

The Troll HSE Risk Management System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wiig, E.; Berthelsen, I.; Donovan, K.

1996-12-31

The Petroleum Act and Internal Control regulations in Norway lay down requirements for how HSE shall be Managed and documented. To comply with the Norwegian legislation the Troll Project has developed an HSE Risk Management System (RMS) structured around Hazards and Effects Management. The resulting quality, technical and operating integrity, and HSE performance are an endorsement of the power of RMS.

Structural insights into NHEJ: building up an integrated picture of the dynamic DSB repair super complex, one component and interaction at a time

PubMed Central

Williams, Gareth J.; Hammel, Michal; Radhakrishnan, Sarvan Kumar; Ramsden, Dale; Lees-Miller, Susan P.; Tainer, John A.

2014-01-01

Non-homologous end joining (NHEJ) is the major pathway for repair of DNA double-strand breaks (DSBs) in human cells. NHEJ is also needed for V(D)J recombination and the development of T and B cells in vertebrate immune systems, and acts in both the generation and prevention of non-homologous chromosomal translocations, a hallmark of genomic instability and many human cancers. X-ray crystal structures, cryo-electron microscopy envelopes, and small angle X-ray scattering (SAXS) solution conformations and assemblies are defining most of the core protein components for NHEJ: Ku70/Ku80 heterodimer; the DNA dependent protein kinase catalytic subunit (DNA-PKcs); the structure-specific endonuclease Artemis along with polynucleotide kinase/phosphatase (PNKP), aprataxin and PNKP related protein (APLF); the scaffolding proteins XRCC4 and XLF (XRCC4-like factor); DNA polymerases, and DNA ligase IV (Lig IV). The dynamic assembly of multi-protein NHEJ complexes at DSBs is regulated in part by protein phosphorylation. The basic steps of NHEJ have been biochemically defined to require: 1) DSB detection by the Ku heterodimer with subsequent DNA-PKcs tethering to form the DNA-PKcs-Ku-DNA complex (termed DNA-PK), 2) lesion processing, and 3) DNA end ligation by Lig IV, which functions in complex with XRCC4 and XLF. The current integration of structures by combined methods is resolving puzzles regarding the mechanisms, coordination and regulation of these three basic steps. Overall, structural results suggest the NHEJ system forms a flexing scaffold with the DNA-PKcs HEAT repeats acting as compressible macromolecular springs suitable to store and release conformational energy to apply forces to regulate NHEJ complexes and the DNA substrate for DNA end protection, processing, and ligation. PMID:24656613

Attitude control of the space construction base: A modular approach

NASA Technical Reports Server (NTRS)

Oconnor, D. A.

1982-01-01

A planar model of a space base and one module is considered. For this simplified system, a feedback controller which is compatible with the modular construction method is described. The systems dynamics are decomposed into two parts corresponding to base and module. The information structure of the problem is non-classical in that not all system information is supplied to each controller. The base controller is designed to accommodate structural changes that occur as the module is added and the module controller is designed to regulate its own states and follow commands from the base. Overall stability of the system is checked by Liapunov analysis and controller effectiveness is verified by computer simulation.

Mechanism of the pH-Induced Conformational Change in the Sensor Domain of the DraK Histidine Kinase via the E83, E105, and E107 Residues

PubMed Central

Jee, Jun-Goo; Lee, Jae Kyoung; Kim, Hyo Jeong; Park, Jin-Wan; Kim, Eun-Hee; Hwang, Eunha; Kim, Sang-Yoon; Lee, Eun-Gyeong; Kwon, Ohsuk; Cheong, Hae-Kap

2014-01-01

The DraR/DraK two-component system was found to be involved in the differential regulation of antibiotic biosynthesis in a medium-dependent manner; however, its function and signaling and sensing mechanisms remain unclear. Here, we describe the solution structure of the extracellular sensor domain of DraK and suggest a mechanism for the pH-dependent conformational change of the protein. The structure contains a mixed alpha-beta fold, adopting a fold similar to the ubiquitous sensor domain of histidine kinase. A biophysical study demonstrates that the E83, E105, and E107 residues have abnormally high pKa values and that they drive the pH-dependent conformational change for the extracellular sensor domain of DraK. We found that a triple mutant (E83L/E105L/E107A) is pH independent and mimics the low pH structure. An in vivo study showed that DraK is essential for the recovery of the pH of Streptomyces coelicolor growth medium after acid shock. Our findings suggest that the DraR/DraK two-component system plays an important role in the pH regulation of S. coelicolor growth medium. This study provides a foundation for the regulation and the production of secondary metabolites in Streptomyces. PMID:25203403

Mechanism of the pH-induced conformational change in the sensor domain of the DraK Histidine kinase via the E83, E105, and E107 residues.

PubMed

Yeo, Kwon Joo; Hong, Young-Soo; Jee, Jun-Goo; Lee, Jae Kyoung; Kim, Hyo Jeong; Park, Jin-Wan; Kim, Eun-Hee; Hwang, Eunha; Kim, Sang-Yoon; Lee, Eun-Gyeong; Kwon, Ohsuk; Cheong, Hae-Kap

2014-01-01

The DraR/DraK two-component system was found to be involved in the differential regulation of antibiotic biosynthesis in a medium-dependent manner; however, its function and signaling and sensing mechanisms remain unclear. Here, we describe the solution structure of the extracellular sensor domain of DraK and suggest a mechanism for the pH-dependent conformational change of the protein. The structure contains a mixed alpha-beta fold, adopting a fold similar to the ubiquitous sensor domain of histidine kinase. A biophysical study demonstrates that the E83, E105, and E107 residues have abnormally high pKa values and that they drive the pH-dependent conformational change for the extracellular sensor domain of DraK. We found that a triple mutant (E83L/E105L/E107A) is pH independent and mimics the low pH structure. An in vivo study showed that DraK is essential for the recovery of the pH of Streptomyces coelicolor growth medium after acid shock. Our findings suggest that the DraR/DraK two-component system plays an important role in the pH regulation of S. coelicolor growth medium. This study provides a foundation for the regulation and the production of secondary metabolites in Streptomyces.

[The Influence of the Functioning of Brain Regulatory Systems onto the Voluntary Regulation of Cognitive Performance in Children. Report 2. Neuropsychological and Electrophysiological Assessment of Brain Regulatory Functions in Children Aged 10-12 with Learning Difficulties].

PubMed

Semenova, O A; Machinskaya, R I

2015-01-01

A total number of 172 children aged 10-12 were electrophysiologically and neuropsychologically assessed in order to analyze the influence of the functioning of brain regulatory systems onto the voluntary regulation of cognitive performance during the preteen years. EEG patterns associated with the nonoptimal functioning of brain regulatory systems, particularly fronto-thalamic, limbic and fronto-striatal structures were significantly more often observed in children with learning and behavioral difficulties, as compared to the control group. Neuropsychological assessment showed that the nonoptimal functioning of different brain regulatory systems specifically affect the voluntary regulation of cognitive performance. Children with EEG patterns of fronto-thalamic nonoptimal functioning demonstrated poor voluntary regulation such as impulsiveness and difficulties in continuing the same algorithms. Children with EEG patterns of limbic nonoptimal functioning showed a less pronounced executive dysfunction manifested only in poor switching between program units within a task. Children with EEG patterns of fronto-striatal nonoptimal functioning struggled with such executive dysfunctions as motor and tactile perseverations and emotional-motivational deviations such as poor motivation and communicative skills.

Structure analysis of the global metabolic regulator Crc from Pseudomonas aeruginosa.

PubMed

Wei, Yong; Zhang, Heng; Gao, Zeng-Qiang; Xu, Jian-Hua; Liu, Quan-Sheng; Dong, Yu-Hui

2013-01-01

The global metabolic regulator catabolite repression control (Crc) has recently been found to modulate the susceptibility to antibiotics and virulence in the opportunistic pathogen Pseudomonas aeruginosa and been suggested as a nonlethal target for novel antimicrobials. In P. aeruginosa, Crc couples with the CA motifs from the small RNA CrcZ to form a post-transcriptional regulator system and is removed from the 5'-end of the target mRNAs. In this study, we first reported the crystal structure of Crc from P. aeruginosa refined to 2.20 Å. The structure showed that it consists of two halves with similar overall topology and there are 11 β strands surrounded by 13 helices, forming a four-layered α/β-sandwich. The circular dichroism spectroscopy revealed that it is thermostable in solution and shares similar characteristics to that in crystal. Comprehensive structural analysis and comparison with the homologies of Crc showed high similarity with several known nucleases and consequently may be classified into a member exodeoxyribonuclease III. However, it shows distinct substrate specificity (RNA as the preferred substrate) compared to these DNA endonucleases. Structural comparisons also revealed potential RNA recognition and binding region mainly consisting of five flexible loops. Our structure study provided the basis for the future application of Crc as a target to develop new antibiotics. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.

Taiwan Regulation of Biobanks.

PubMed

Fan, Chien-Te; Hung, Tzu-Hsun; Yeh, Chan-Kun

2015-01-01

This paper introduces legal framework and governance structure in relation to the management and development of biobanks in Taiwan. At first, we briefly describe Taiwan's population, political system and health care system. Secondly, this research introduces biobanking framework of Taiwan including 25 biobanks established with the approval of the Ministry of Health and Welfare. In those biobanks, "Taiwan Biobank" is the first and the largest government-supported biobank which comprises population-based cohort study and disease- oriented study. Since the collection of information, data, and biological specimen of biobanks often involve highly sensitive personal information, in the legal framework of Taiwan, there is a specific regulation, "Human Biobank Management Act" (HBMA), which plays an important role in regulating biobanks in Taiwan. HBMA, the Personal Information Act and other regulations constitute a comprehensive legal and regulatory privacy framework of biobanks. Through the introduction and analysis of the current legal framework applicable to biobanks, we found that there are several challenges that need to be solved appropriately that involve duplicate review systems, the obstacles in the international collaboration, and data sharing between biobanks in Taiwan. © 2015 American Society of Law, Medicine & Ethics, Inc.

Molecular and functional characterization of riboflavin specific transport system in rat brain capillary endothelial cells.

PubMed

Patel, Mitesh; Vadlapatla, Ramya Krishna; Pal, Dhananjay; Mitra, Ashim K

2012-08-15

Riboflavin is an important water soluble vitamin (B2) required for metabolic reactions, normal cellular growth, differentiation and function. Mammalian brain cells cannot synthesize riboflavin and must import from systemic circulation. However, the uptake mechanism, cellular translocation and intracellular trafficking of riboflavin in brain capillary endothelial cells are poorly understood. The primary objective of this study is to investigate the existence of a riboflavin-specific transport system and delineate the uptake and intracellular regulation of riboflavin in immortalized rat brain capillary endothelial cells (RBE4). The uptake of [3H]-riboflavin is sodium, temperature and energy dependent but pH independent. [3H]-Riboflavin uptake is saturable with K(m) and V(max) values of 19 ± 3 μM and 0.235 ± 0.012 pmol/min/mg protein, respectively. The uptake process is inhibited by unlabelled structural analogs (lumiflavin, lumichrome) but not by structurally unrelated vitamins. Ca(++)/calmodulin and protein kinase A (PKA) pathways are found to play an important role in the intracellular regulation of [3H]-riboflavin. Apical and baso-lateral uptake of [3H]-riboflavin clearly indicates that a riboflavin specific transport system is predominantly localized on the apical side of RBE4 cells. A 628 bp band corresponding to a riboflavin transporter is revealed in RT-PCR analysis. These findings, for the first time report the existence of a specialized and high affinity transport system for riboflavin in RBE4 cells. The blood-brain barrier (BBB) is a major obstacle limiting drug transport inside the brain as it regulates drug permeation from systemic circulation. This transporter can be utilized for targeted delivery in enhancing brain permeation of highly potent drugs on systemic administration. Copyright © 2012 Elsevier B.V. All rights reserved.

The Normative Structure of Knowledge Production and Utilization in Education. Volume 2. Case Studies of the Infrastructure of Educational R and D.

ERIC Educational Resources Information Center

Markley, O. W.

This is the second volume of a report on a study that (1) investigated the "normative structure" (the governance system) of knowledge production and utilization (KPU) activities in education, (2) developed an analytical framework through which to understand how formal policy acts as a "regulator" of activities in KPU, (3) described the major…

Molecular mechanisms of floral organ specification by MADS domain proteins.

PubMed

Yan, Wenhao; Chen, Dijun; Kaufmann, Kerstin

2016-02-01

Flower development is a model system to understand organ specification in plants. The identities of different types of floral organs are specified by homeotic MADS transcription factors that interact in a combinatorial fashion. Systematic identification of DNA-binding sites and target genes of these key regulators show that they have shared and unique sets of target genes. DNA binding by MADS proteins is not based on 'simple' recognition of a specific DNA sequence, but depends on DNA structure and combinatorial interactions. Homeotic MADS proteins regulate gene expression via alternative mechanisms, one of which may be to modulate chromatin structure and accessibility in their target gene promoters. Copyright © 2015 Elsevier Ltd. All rights reserved.

Bifurcation analysis of nephron pressure and flow regulation

NASA Astrophysics Data System (ADS)

Barfred, Mikael; Mosekilde, Erik; Holstein-Rathlou, Niels-Henrik

1996-09-01

One- and two-dimensional continuation techniques are applied to study the bifurcation structure of a model of renal flow and pressure control. Integrating the main physiological mechanisms by which the individual nephron regulates the incoming blood flow, the model describes the interaction between the tubuloglomerular feedback and the response of the afferent arteriole. It is shown how a Hopf bifurcation leads the system to perform self-sustained oscillations if the feedback gain becomes sufficiently strong, and how a further increase of this parameter produces a folded structure of overlapping period-doubling cascades. Similar phenomena arise in response to increasing blood pressure. The numerical analyses are supported by existing experimental results on anesthetized rats.

Actors involved in the regulation of clinical research: comparison of Finland to England, Canada, and the USA.

PubMed

Hemminki, Elina

2015-04-07

The relevance and quantity of clinical research has caused concern and regulation is claimed to hinder clinical research. This paper compares clinical research regulations in Finland to those of England, Canada, and the USA around 2010-2011. Several approaches and data sources were used, including semi- or unstructured interviews of experts. For the analysis, a theoretical framework was made, data from various sources was synthesized, and features of the systems were simplified and classified. The various specific names and terms used in the data were changed into general ones. Common structures for the regulation existed in all four countries, but the details and scope varied. The research regulated within the main system was determined by research type (Finland), the financer of the health system (England), or research site (Canada, USA). Only Finland had specific legislation on medical research. The overriding impression of the regulatory systems was one of complexity. All countries had extra regulation for drug research. The types of drug research covered varied from trials with unlicensed (new) products or new indications (USA and Canada), to all types of interventional drug research (England), where 'interventional' was interpreted broadly (Finland). The complexity of regulations had led to the creation of various big and small businesses to help researchers and sponsors. There was notable variation in the role played by the public research funder. The role played by health care was difficult to study and seemed to involve varying interests as researchers were also health care employees. Research ethics committees were important and their tasks also included aspects other than ethics. This study revealed that a comparison between countries can provide useful insights into the distinctive aspects of each country's system, as well as identifying common features that require international action.

Airway smooth muscle contraction - perspectives on past, present and future.

PubMed

Mitchell, H W

2009-10-01

Past and contemporary views of airway smooth muscle (ASM) have led to a high level of understanding of the control and intracellular regulation of force or shortening of ASM and of its possible role in airway disease. As well as the multitude of cellular mechanisms that regulate ASM contraction, a number of structural and mechanical factors, which are only present at the airway and lung level, provide overriding control over ASM. With new knowledge about the cellular physiology and biology of ASM, there is increasing need to understand how ASM contraction is regulated and expressed at these airway and system levels.

Wired for behaviors: from development to function of innate limbic system circuitry

PubMed Central

Sokolowski, Katie; Corbin, Joshua G.

2012-01-01

The limbic system of the brain regulates a number of behaviors that are essential for the survival of all vertebrate species including humans. The limbic system predominantly controls appropriate responses to stimuli with social, emotional, or motivational salience, which includes innate behaviors such as mating, aggression, and defense. Activation of circuits regulating these innate behaviors begins in the periphery with sensory stimulation (primarily via the olfactory system in rodents), and is then processed in the brain by a set of delineated structures that primarily includes the amygdala and hypothalamus. While the basic neuroanatomy of these connections is well-established, much remains unknown about how information is processed within innate circuits and how genetic hierarchies regulate development and function of these circuits. Utilizing innovative technologies including channel rhodopsin-based circuit manipulation and genetic manipulation in rodents, recent studies have begun to answer these central questions. In this article we review the current understanding of how limbic circuits regulate sexually dimorphic behaviors and how these circuits are established and shaped during pre- and post-natal development. We also discuss how understanding developmental processes of innate circuit formation may inform behavioral alterations observed in neurodevelopmental disorders, such as autism spectrum disorders, which are characterized by limbic system dysfunction. PMID:22557946

Critical Assessment of the Foundations of Power Transmission and Distribution Reliability Metrics and Standards.

PubMed

Nateghi, Roshanak; Guikema, Seth D; Wu, Yue Grace; Bruss, C Bayan

2016-01-01

The U.S. federal government regulates the reliability of bulk power systems, while the reliability of power distribution systems is regulated at a state level. In this article, we review the history of regulating electric service reliability and study the existing reliability metrics, indices, and standards for power transmission and distribution networks. We assess the foundations of the reliability standards and metrics, discuss how they are applied to outages caused by large exogenous disturbances such as natural disasters, and investigate whether the standards adequately internalize the impacts of these events. Our reflections shed light on how existing standards conceptualize reliability, question the basis for treating large-scale hazard-induced outages differently from normal daily outages, and discuss whether this conceptualization maps well onto customer expectations. We show that the risk indices for transmission systems used in regulating power system reliability do not adequately capture the risks that transmission systems are prone to, particularly when it comes to low-probability high-impact events. We also point out several shortcomings associated with the way in which regulators require utilities to calculate and report distribution system reliability indices. We offer several recommendations for improving the conceptualization of reliability metrics and standards. We conclude that while the approaches taken in reliability standards have made considerable advances in enhancing the reliability of power systems and may be logical from a utility perspective during normal operation, existing standards do not provide a sufficient incentive structure for the utilities to adequately ensure high levels of reliability for end-users, particularly during large-scale events. © 2015 Society for Risk Analysis.

Development of functional ectopic compound eyes in scarabaeid beetles by knockdown of orthodenticle.

PubMed

Zattara, Eduardo E; Macagno, Anna L M; Busey, Hannah A; Moczek, Armin P

2017-11-07

Complex traits like limbs, brains, or eyes form through coordinated integration of diverse cell fates across developmental space and time, yet understanding how complexity and integration emerge from uniform, undifferentiated precursor tissues remains limited. Here, we use ectopic eye formation as a paradigm to investigate the emergence and integration of novel complex structures following massive ontogenetic perturbation. We show that down-regulation via RNAi of a single head patterning gene- orthodenticle -induces ectopic structures externally resembling compound eyes at the middorsal adult head of both basal and derived scarabaeid beetle species (Onthophagini and Oniticellini). Scanning electron microscopy documents ommatidial organization of these induced structures, while immunohistochemistry reveals the presence of rudimentary ommatidial lenses, crystalline cones, and associated neural-like tissue within them. Further, RNA-sequencing experiments show that after orthodenticle down-regulation, the transcriptional signature of the middorsal head-the location of ectopic eye induction-converges onto that of regular compound eyes, including up-regulation of several retina-specific genes. Finally, a light-aversion behavioral assay to assess functionality reveals that ectopic compound eyes can rescue the ability to respond to visual stimuli when wild-type eyes are surgically removed. Combined, our results show that knockdown of a single gene is sufficient for the middorsal head to acquire the competence to ectopically generate a functional compound eye-like structure. These findings highlight the buffering capacity of developmental systems, allowing massive genetic perturbations to be channeled toward orderly and functional developmental outcomes, and render ectopic eye formation a widely accessible paradigm to study the evolution of complex systems. Published under the PNAS license.

Histofluorescent labelling of catecholaminergic structures in rotifers (Aschelminthes). II. Males of Brachionus plicatilis and structures from sectioned females.

PubMed

Keshmirian, J; Nogrady, T

1988-01-01

1. Catecholaminergic structures in the male Brachionus plicatilis were investigated, using aqueous dansylpropranolol as fluorescent label of neurotransmitter receptors. 2. All major organs of the male are innervated by catecholaminergic systems, that may also be involved in the regulation of copulatory behavior. 3. Cryostat-sectioned preparations of the female B. plicatilis were also investigated. They provided additional information to findings on whole animals reported in our previous paper (Keshmirian and Nogrady 1987 a).

[Nonnative guidelines for allocating human resources in child and adolescent psychiatry using average values under convergence conditions instead of price determination - analysis of the data of university hospitals in Germany concerning the costs of calculating day and minute values according to Psych-PV and PEPP-System].

PubMed

Barufka, Steffi; Heller, Michael; Prayon, Valeria; Fegert, Jörg M

2015-11-01

Despite substantial opposition in the practical field, based on an amendment to the Hospital Financing Act (KHG). the so-called PEPP-System was introduced in child and adolescent psychiatry as a new calculation model. The 2-year moratorium, combined with the rescheduling of the repeal of the psychiatry personnel regulation (Psych-PV) and a convergence phase, provided the German Federal Ministry of Health with additional time to enter a structured dialogue with professional associations. Especially the perspective concerning the regulatory framework is presently unclear. In light of this debate, this article provides calculations to illustrate the transformation of the previous personnel regulation into the PEPP-System by means of the data of §21 KHEntgG stemming from the 22 university hospitals of child and adolescent psychiatry and psychotherapy in Germany. In 2013 there was a total of 7,712 cases and 263,694 calculation days. In order to identify a necessary basic reimbursement value th1\\t would guarantee a constant quality of patient care, the authors utilize outcomes, cost structures, calculation days, and minute values for individual professional groups according to both systems (Psych-PV and PEPP) based on data from 2013 and the InEK' s analysis of the calculation datasets. The authors propose a normative agreement on the basic reimbursement value between 270 and 285 EUR. This takes into account the concentration phenomenon and the expansion of services that has occurred since the introduction of the Psych-PV system. Such a normative agreement on structural quality could provide a verifiable framework for the allocation of human resources corresponding to the previous regulations of Psych-PV.

The engine fuel system fault analysis

NASA Astrophysics Data System (ADS)

Zhang, Yong; Song, Hanqiang; Yang, Changsheng; Zhao, Wei

2017-05-01

For improving the reliability of the engine fuel system, the typical fault factor of the engine fuel system was analyzed from the point view of structure and functional. The fault character was gotten by building the fuel system fault tree. According the utilizing of fault mode effect analysis method (FMEA), several factors of key component fuel regulator was obtained, which include the fault mode, the fault cause, and the fault influences. All of this made foundation for next development of fault diagnosis system.

A General Precipitation-limited L X–T–R Relation among Early-type Galaxies

NASA Astrophysics Data System (ADS)

Voit, G. Mark; Ma, C. P.; Greene, J.; Goulding, A.; Pandya, V.; Donahue, M.; Sun, M.

2018-01-01

The relation between X-ray luminosity (L X) and ambient gas temperature (T) among massive galactic systems is an important cornerstone of both observational cosmology and galaxy-evolution modeling. In the most massive galaxy clusters, the relation is determined primarily by cosmological structure formation. In less massive systems, it primarily reflects the feedback response to radiative cooling of circumgalactic gas. Here we present a simple but powerful model for the L X–T relation as a function of physical aperture R within which those measurements are made. The model is based on the precipitation framework for AGN feedback and assumes that the circumgalactic medium is precipitation-regulated at small radii and limited by cosmological structure formation at large radii. We compare this model with many different data sets and show that it successfully reproduces the slope and upper envelope of the L X–T–R relation over the temperature range from ∼0.2 keV through ≳ 10 {keV}. Our findings strongly suggest that the feedback mechanisms responsible for regulating star formation in individual massive galaxies have much in common with the precipitation-triggered feedback that appears to regulate galaxy-cluster cores.

Australia's private health insurance industry: structure, competition, regulation and role in a less than 'ideal world'.

PubMed

Shamsullah, Ardel

2011-02-01

Australia's private health insurance funds have been prominent participants in the nation's health system for 60 years. Yet there is relatively little public awareness of the distinctive origins of the health funds, the uncharacteristic organisational nature of these commercial enterprises and the peculiarly regulated nature of their industry. The conventional corporate responsibility to shareholders was, until recently, completely irrelevant, and remains marginal to the sector. However, their purported answerability to contributors, styled as 'members', was always doubtful for most health funds. After a long period of remarkable stability in the sector, despite significant shifts in health funding policy, recent years have brought notable changes, with mergers, acquisitions and exits from the industry. The research is based on the detailed study of the private health funds, covering their history, organisational character and industry structure. It argues that the funds have always been divorced from the disciplines of the competitive market and generally have operated complacently within a system of comprehensive regulation and generous subsidy. The prospect of the private health funds enjoying an expanded role under a form of 'social insurance', as suggested by the National Health and Hospitals Reform Commission, is not supported.

Flight training efforts would benefit from more flexible aviation regulatory structures.

PubMed

Bent, J

1996-10-01

Training and regulatory issues related to modern flight deck systems are reviewed. Philosophical differences in regulatory bodies in the United States and Europe are highlighted. Methods of changing regulations in Europe and the United States are discussed.

Quiet Clean Short-haul Experimental Engine (QCSEE) whirl test of cam/harmonic pitch change actuation system

NASA Technical Reports Server (NTRS)

1976-01-01

A variable pitch fan actuation system, which incorporates a remote nacelle mounted blade angle regulator, was tested. The regulator drives a rotating fan mounted mechanical actuator through a flexible shaft and differential gear train. The actuator incorporates a high ratio harmonic drive attached to a multitrack spherical cam which changes blade pitch through individual cam follower arms attached to each blade trunnion. Testing of the actuator on a whirl rig, is reported. Results of tests conducted to verify that the unit satisfied the design requirements and was structurally adequate for use in an engine test are presented.

Ca2+-Regulated Photoproteins: Effective Immunoassay Reporters

PubMed Central

Frank, Ludmila A.

2010-01-01

Ca2+-regulated photoproteins of luminous marine coelenterates are of interest and a challenge for researchers as a unique bioluminescent system and as a promising analytical instrument for both in vivo and in vitro applications. The proteins are comprehensively studied as to biochemical properties, tertiary structures, bioluminescence mechanism, etc. This knowledge, along with available recombinant proteins serves the basis for development of unique bioluminescent detection systems that are “self-contained”, triggerable, fast, highly sensitive, and non-hazardous. In the paper, we focus on the use of photoproteins as reporters in binding assays based on immunological recognition element—bioluminescent immunoassay and hybridization immunoassay, their advantages and prospects. PMID:22163526

Is the regulation of the electronic properties of organic molecules by polynuclear superhalogens more effective than that by mononuclear superhalogens? A high-level ab initio case study.

PubMed

Li, Miao-Miao; Li, Jin-Feng; Bai, Hongcun; Sun, Yin-Yin; Li, Jian-Li; Yin, Bing

2015-08-21

The regulation of the electronic properties of organic molecules induced by polynuclear superhalogens is theoretically explored here for sixteen composite structures. It is clearly indicated by the higher vertical electron detachment energy (VDE) that polynuclear superhalogens are more effective in regulating the electronic properties than mononuclear structures. However, this enhanced regulation is not only determined by superhalogens themselves but also related to the distribution of the extra electron of the final composites. The composites, in which the extra electron is mainly aggregated into the superhalogen moiety, will possess higher VDE values, as reported in the case of C1', 7.12 eV at the CCSD(T) level. This is probably due to the fact that, compared with organic molecules, superhalogens possess stronger attraction towards the extra electron and thus should lead to lower energies of the extra electrons and to higher VDE values eventually. Compared with CCSD(T), the Outer Valence Green's Function (OVGF) method fails completely for composite structures containing Cl atoms, while MP2 results are generally consistent in terms of the relative order of VDEs. Actually if the extra electron distribution of the systems could be approximated by the HOMO, the results at the OVGF level will be consistent with the CCSD(T) results. Conversely, the difference in VDEs between OVGF and CCSD(T) is significantly large. Besides superhalogen properties, the structures, relative stabilities and thermodynamic stabilities with respect to various fragmentation channels were also investigated for all the composite structures.

The structurally related auxin and melatonin tryptophan-derivatives and their roles in Arabidopsis thaliana and in the human malaria parasite Plasmodium falciparum.

PubMed

Koyama, Fernanda C; Carvalho, Thais L G; Alves, Eduardo; da Silva, Henrique B; de Azevedo, Mauro F; Hemerly, Adriana S; Garcia, Célia R S

2013-01-01

Indole compounds are involved in a range of functions in many organisms. In the human malaria parasite Plasmodium falciparum, melatonin and other tryptophan derivatives are able to modulate its intraerythrocytic cycle, increasing the schizont population as well as parasitemia, likely through ubiquitin-proteasome system (UPS) gene regulation. In plants, melatonin regulates root development, in a similar way to that described for indoleacetic acid, suggesting that melatonin and indoleacetic acid could co-participate in some physiological processes due to structural similarities. In the present work, we evaluate whether the chemical structure similarity found in indoleacetic acid and melatonin can lead to similar effects in Arabidopsis thaliana lateral root formation and P. falciparum cell cycle modulation, as well as in the UPS of gene regulation, by qRT-PCR. Our data show that P. falciparum is not able to respond to indoleacetic acid either in the modulation of the intraerythrocytic cycle or in the gene regulation mediated by the UPS as observed for melatonin. The similarities of these indole compounds are not sufficient to confer synergistic functions in P. falciparum cell cycle modulation, but could interplay in A. thaliana lateral root formation. © 2013 The Author(s) Journal of Eukaryotic Microbiology © 2013 International Society of Protistologists.

Lipid Processing in the Brain: A Key Regulator of Systemic Metabolism

PubMed Central

Bruce, Kimberley D.; Zsombok, Andrea; Eckel, Robert H.

2017-01-01

Metabolic disorders, particularly aberrations in lipid homeostasis, such as obesity, type 2 diabetes mellitus, and hypertriglyceridemia often manifest together as the metabolic syndrome (MetS). Despite major advances in our understanding of the pathogenesis of these disorders, the prevalence of the MetS continues to rise. It is becoming increasingly apparent that intermediary metabolism within the central nervous system is a major contributor to the regulation of systemic metabolism. In particular, lipid metabolism within the brain is tightly regulated to maintain neuronal structure and function and may signal nutrient status to modulate metabolism in key peripheral tissues such as the liver. There is now a growing body of evidence to suggest that fatty acid (FA) sensing in hypothalamic neurons via accumulation of FAs or FA metabolites may signal nutritional sufficiency and may decrease hepatic glucose production, lipogenesis, and VLDL-TG secretion. In addition, recent studies have highlighted the existence of liver-related neurons that have the potential to direct such signals through parasympathetic and sympathetic nervous system activity. However, to date whether these liver-related neurons are FA sensitive remain to be determined. The findings discussed in this review underscore the importance of the autonomic nervous system in the regulation of systemic metabolism and highlight the need for further research to determine the key features of FA neurons, which may serve as novel therapeutic targets for the treatment of metabolic disorders. PMID:28421037

RNA polymerase III transcription - regulated by chromatin structure and regulator of nuclear chromatin organization.

PubMed

Pascali, Chiara; Teichmann, Martin

2013-01-01

RNA polymerase III (Pol III) transcription is regulated by modifications of the chromatin. DNA methylation and post-translational modifications of histones, such as acetylation, phosphorylation and methylation have been linked to Pol III transcriptional activity. In addition to being regulated by modifications of DNA and histones, Pol III genes and its transcription factors have been implicated in the organization of nuclear chromatin in several organisms. In yeast, the ability of the Pol III transcription system to contribute to nuclear organization seems to be dependent on direct interactions of Pol III genes and/or its transcription factors TFIIIC and TFIIIB with the structural maintenance of chromatin (SMC) protein-containing complexes cohesin and condensin. In human cells, Pol III genes and transcription factors have also been shown to colocalize with cohesin and the transcription regulator and genome organizer CCCTC-binding factor (CTCF). Furthermore, chromosomal sites have been identified in yeast and humans that are bound by partial Pol III machineries (extra TFIIIC sites - ETC; chromosome organizing clamps - COC). These ETCs/COC as well as Pol III genes possess the ability to act as boundary elements that restrict spreading of heterochromatin.

miR-132 Regulates Dendritic Spine Structure by Direct Targeting of Matrix Metalloproteinase 9 mRNA.

PubMed

Jasińska, Magdalena; Miłek, Jacek; Cymerman, Iwona A; Łęski, Szymon; Kaczmarek, Leszek; Dziembowska, Magdalena

2016-09-01

Mir-132 is a neuronal activity-regulated microRNA that controls the morphology of dendritic spines and neuronal transmission. Similar activities have recently been attributed to matrix metalloproteinase-9 (MMP-9), an extrasynaptic protease. In the present study, we provide evidence that miR-132 directly regulates MMP-9 mRNA in neurons to modulate synaptic plasticity. With the use of luciferase reporter system, we show that miR-132 binds to the 3'UTR of MMP-9 mRNA to regulate its expression in neurons. The overexpression of miR-132 in neurons reduces the level of endogenous MMP-9 protein secretion. In synaptoneurosomes, metabotropic glutamate receptor (mGluR)-induced signaling stimulates the dissociation of miR-132 from polyribosomal fractions and shifts it towards the messenger ribonucleoprotein (mRNP)-containing fraction. Furthermore, we demonstrate that the overexpression of miR-132 in the cultured hippocampal neurons from Fmr1 KO mice that have increased synaptic MMP-9 level provokes enlargement of the dendritic spine heads, a process previously implicated in enhanced synaptic plasticity. We propose that activity-dependent miR-132 regulates structural plasticity of dendritic spines through matrix metalloproteinase 9.

Artificial Symmetry-Breaking for Morphogenetic Engineering Bacterial Colonies.

PubMed

Nuñez, Isaac N; Matute, Tamara F; Del Valle, Ilenne D; Kan, Anton; Choksi, Atri; Endy, Drew; Haseloff, Jim; Rudge, Timothy J; Federici, Fernan

2017-02-17

Morphogenetic engineering is an emerging field that explores the design and implementation of self-organized patterns, morphologies, and architectures in systems composed of multiple agents such as cells and swarm robots. Synthetic biology, on the other hand, aims to develop tools and formalisms that increase reproducibility, tractability, and efficiency in the engineering of biological systems. We seek to apply synthetic biology approaches to the engineering of morphologies in multicellular systems. Here, we describe the engineering of two mechanisms, symmetry-breaking and domain-specific cell regulation, as elementary functions for the prototyping of morphogenetic instructions in bacterial colonies. The former represents an artificial patterning mechanism based on plasmid segregation while the latter plays the role of artificial cell differentiation by spatial colocalization of ubiquitous and segregated components. This separation of patterning from actuation facilitates the design-build-test-improve engineering cycle. We created computational modules for CellModeller representing these basic functions and used it to guide the design process and explore the design space in silico. We applied these tools to encode spatially structured functions such as metabolic complementation, RNAPT7 gene expression, and CRISPRi/Cas9 regulation. Finally, as a proof of concept, we used CRISPRi/Cas technology to regulate cell growth by controlling methionine synthesis. These mechanisms start from single cells enabling the study of morphogenetic principles and the engineering of novel population scale structures from the bottom up.

Self-regulating chemo-mechano-chemical systems

DOEpatents

Aizenberg, Joanna; He, Ximin; Aizenberg, Michael

2017-05-16

A chemo-mechano-chemical (C.sub.1-M-C.sub.2) system includes a base supporting an actuatable structure, said structure comprising a functionalized portion and being embedded in an environmentally responsive gel capable of volume change in response to an environmental stimulus; a first fluid layer disposed over the base and in contact with the actuatable structure, said first fluid layer comprising the environmentally responsive gel; and a second fluid layer in contact with the actuatable structure, wherein the layers are positioned such that the functionalized portion is in contact with the second layer in a first relaxed state and in contact with the first layer in a second actuated state and wherein the functionalized portion interacts with at least one of the layers to provide a chemical or physical response.

Mutational analysis of Kaposica reveals that bridging of MG2 and CUB domains of target protein is crucial for the cofactor activity of RCA proteins

PubMed Central

Gautam, Avneesh Kumar; Panse, Yogesh; Ghosh, Payel; Reza, Malik Johid; Mullick, Jayati; Sahu, Arvind

2015-01-01

The complement system has evolved to annul pathogens, but its improper regulation is linked with diseases. Efficient regulation of the system is primarily provided by a family of proteins termed regulators of complement activation (RCA). The knowledge of precise structural determinants of RCA proteins critical for imparting the regulatory activities and the molecular events underlying the regulatory processes, nonetheless, is still limited. Here, we have dissected the structural requirements of RCA proteins that are crucial for one of their two regulatory activities, the cofactor activity (CFA), by using the Kaposi’s sarcoma-associated herpesvirus RCA homolog Kaposica as a model protein. We have scanned the entire Kaposica molecule by sequential mutagenesis using swapping and site-directed mutagenesis, which identified residues critical for its interaction with C3b and factor I. Mapping of these residues onto the modeled structure of C3b–Kaposica–factor I complex supported the mutagenesis data. Furthermore, the model suggested that the C3b-interacting residues bridge the CUB (complement C1r-C1s, Uegf, Bmp1) and MG2 (macroglobulin-2) domains of C3b. Thus, it seems that stabilization of the CUB domain with respect to the core of the C3b molecule is central for its CFA. Identification of CFA-critical regions in Kaposica guided experiments in which the equivalent regions of membrane cofactor protein were swapped into decay-accelerating factor. This strategy allowed CFA to be introduced into decay-accelerating factor, suggesting that viral and human regulators use a common mechanism for CFA. PMID:26420870

Structural basis for serotonergic regulation of neural circuits in the mouse olfactory bulb.

PubMed

Suzuki, Yoshinori; Kiyokage, Emi; Sohn, Jaerin; Hioki, Hiroyuki; Toida, Kazunori

2015-02-01

Olfactory processing is well known to be regulated by centrifugal afferents from other brain regions, such as noradrenergic, acetylcholinergic, and serotonergic neurons. Serotonergic neurons widely innervate and regulate the functions of various brain regions. In the present study, we focused on serotonergic regulation of the olfactory bulb (OB), one of the most structurally and functionally well-defined brain regions. Visualization of a single neuron among abundant and dense fibers is essential to characterize and understand neuronal circuits. We accomplished this visualization by successfully labeling and reconstructing serotonin (5-hydroxytryptamine: 5-HT) neurons by infection with sindbis and adeno-associated virus into dorsal raphe nuclei (DRN) of mice. 5-HT synapses were analyzed by correlative confocal laser microscopy and serial-electron microscopy (EM) study. To further characterize 5-HT neuronal and network function, we analyzed whether glutamate was released from 5-HT synaptic terminals using immuno-EM. Our results are the first visualizations of complete 5-HT neurons and fibers projecting from DRN to the OB with bifurcations. We found that a single 5-HT axon can form synaptic contacts to both type 1 and 2 periglomerular cells within a single glomerulus. Through immunolabeling, we also identified vesicular glutamate transporter 3 in 5-HT neurons terminals, indicating possible glutamatergic transmission. Our present study strongly implicates the involvement of brain regions such as the DRN in regulation of the elaborate mechanisms of olfactory processing. We further provide a structure basis of the network for coordinating or linking olfactory encoding with other neural systems, with special attention to serotonergic regulation. © 2014 Wiley Periodicals, Inc.

[Network structures in biological systems].

PubMed

Oleskin, A V

2013-01-01

Network structures (networks) that have been extensively studied in the humanities are characterized by cohesion, a lack of a central control unit, and predominantly fractal properties. They are contrasted with structures that contain a single centre (hierarchies) as well as with those whose elements predominantly compete with one another (market-type structures). As far as biological systems are concerned, their network structures can be subdivided into a number of types involving different organizational mechanisms. Network organization is characteristic of various structural levels of biological systems ranging from single cells to integrated societies. These networks can be classified into two main subgroups: (i) flat (leaderless) network structures typical of systems that are composed of uniform elements and represent modular organisms or at least possess manifest integral properties and (ii) three-dimensional, partly hierarchical structures characterized by significant individual and/or intergroup (intercaste) differences between their elements. All network structures include an element that performs structural, protective, and communication-promoting functions. By analogy to cell structures, this element is denoted as the matrix of a network structure. The matrix includes a material and an immaterial component. The material component comprises various structures that belong to the whole structure and not to any of its elements per se. The immaterial (ideal) component of the matrix includes social norms and rules regulating network elements' behavior. These behavioral rules can be described in terms of algorithms. Algorithmization enables modeling the behavior of various network structures, particularly of neuron networks and their artificial analogs.

Waterborne fluoride exposure changed the structure and the expressions of steroidogenic-related genes in gonads of adult zebrafish (Danio rerio).

PubMed

Li, MeiYan; Cao, Jinling; Chen, Jianjie; Song, Jie; Zhou, Bingrui; Feng, Cuiping; Wang, Jundong

2016-02-01

Excessive fluoride in natural water ecosystem has been demonstrated to have adverse effects on reproductive system in humans and mammals, while the most vulnerable aquatic organisms were ignored. In this study, the effects of waterborne fluoride on growth performance, sex steroid hormone, histological structure, and the transcriptional profiles of sex steroid related genes were examined in both female and male zebrafish exposed to different concentrations of 0.79, 18.60, 36.83 mg L(-1) of fluoride for 30 and 60 d to investigate the effects of fluoride on reproductive system and the underlying toxic mechanisms caused by fluoride. The results showed that the body weight was remarkably decreased, the structure of ovary and testis were serious injured, and the T and E2 levels were significantly reduced in male zebrafish. The transcriptional profiles of steroidogenic related genes displayed phenomenal alterations, the expressions of pgr and cyp19a1a were significantly up-regulated, while the transcriptional levels of er, ar and hsd3β were decreased both in the ovary and testis, and hsd17β8 were down-regulated just in males. Taken together, these results demonstrated that fluoride could significantly inhibit the growth of zebrafish, and notably affect the reproductive system in both sex zebrafish by impairing the structure of ovary and testis, altering steroid hormone levels and steroidogenic genes expression related to the synthesis of sex hormones in zebrafish. Copyright © 2015 Elsevier Ltd. All rights reserved.

Crystal structure of Bacillus anthracis virulence regulator AtxA and effects of phosphorylated histidines on multimerization and activity

PubMed Central

Hammerstrom, Troy G.; Horton, Lori B.; Swick, Michelle C.; Joachimiak, Andrzej; Osipiuk, Jerzy; Koehler, Theresa M.

2015-01-01

Summary The Bacillus anthracis virulence regulator AtxA controls transcription of the anthrax toxin genes and capsule biosynthesis operon. AtxA activity is elevated during growth in media containing glucose and CO2/bicarbonate, and there is a positive correlation between the CO2/bicarbonate signal, AtxA activity, and homomultimerization. AtxA activity is also affected by phosphorylation at specific histidines. We show that AtxA crystallizes as a dimer. Distinct folds associated with predicted DNA-binding domains (HTH1 and HTH2) and phosphoenolpyruvate: carbohydrate phosphotransferase system-regulated domains (PRD1 and PRD2) are apparent. We tested AtxA variants containing single and double phosphomimetic (His → Asp) and phosphoablative (His → Ala) amino acid changes for activity in B. anthracis cultures and for protein-protein interactions in cell lysates. Reduced activity of AtxA H199A, lack of multimerization and activity of AtxAH379D variants, and predicted structural changes associated with phosphorylation support a model for control of AtxA function. We propose that (1) in the AtxA dimer, phosphorylation of H199 in PRD1 affects HTH2 positioning, influencing DNA-binding; and (2) phosphorylation of H379 in PRD2 disrupts dimer formation. The AtxA structure is the first reported high-resolution full-length structure of a PRD-containing regulator and can serve as a model for proteins of this family, especially those that link virulence to bacterial metabolism. PMID:25402841

Crystal structure of Bacillus anthracis virulence regulator AtxA and effects of phosphorylated histidines on multimerization and activity.

PubMed

Hammerstrom, Troy G; Horton, Lori B; Swick, Michelle C; Joachimiak, Andrzej; Osipiuk, Jerzy; Koehler, Theresa M

2015-02-01

The Bacillus anthracis virulence regulator AtxA controls transcription of the anthrax toxin genes and capsule biosynthetic operon. AtxA activity is elevated during growth in media containing glucose and CO(2)/bicarbonate, and there is a positive correlation between the CO(2)/bicarbonate signal, AtxA activity and homomultimerization. AtxA activity is also affected by phosphorylation at specific histidines. We show that AtxA crystallizes as a dimer. Distinct folds associated with predicted DNA-binding domains (HTH1 and HTH2) and phosphoenolpyruvate: carbohydrate phosphotransferase system-regulated domains (PRD1 and PRD2) are apparent. We tested AtxA variants containing single and double phosphomimetic (His→Asp) and phosphoablative (His→Ala) amino acid changes for activity in B. anthracis cultures and for protein-protein interactions in cell lysates. Reduced activity of AtxA H199A, lack of multimerization and activity of AtxAH379D variants, and predicted structural changes associated with phosphorylation support a model for control of AtxA function. We propose that (i) in the AtxA dimer, phosphorylation of H199 in PRD1 affects HTH2 positioning, influencing DNA-binding; and (ii) phosphorylation of H379 in PRD2 disrupts dimer formation. The AtxA structure is the first reported high-resolution full-length structure of a PRD-containing regulator, and can serve as a model for proteins of this family, especially those that link virulence to bacterial metabolism. © 2014 John Wiley & Sons Ltd.

[Health protection and health promotion in formal structures of executive county authorities and executive offices of municipalities having the county status].

PubMed

Nosko, Jan; Marcinkiewicz, Andrzej

2009-01-01

An analysis of the role of public administration in the Polish health system, essential for the effectiveness of health protection and health promotion, is a very important and urgent task faced by scholars. This issue also concerns the authorities of counties (powiaty) and municipalities having the county status (MHCS), and these structures were chosen as the subject of our study. The aim of the study was to analyze whether health related rules and regulations of these administrative structures comply with the requirements of relevant Polish legislation acts. The survey, performed in 2008, covered all the 378 counties and municipalities having the county status. On the basis of 171 Acts reviewed, a list of 11 groups of obligations and duties assigned to county and municipality units were prepared and used as a research tool. It was found that the provisions of the Health Care Institutions Act of 1991 were most evidently (87%) reflected in the rules and regulations of the studies structures; more than a half (57%) refer to prophylaxis and health promotion, however, the most important Act as far as health protection and health promotion are concerned, i.e., the Act of 2004 was reflected in only 11.6%. Also the presence of some outdated regulations was discovered. The results of the study may indicate that the mechanisms, by which the execution of legal regulations on health protection and health promotion tasks should be supervised, are insufficient.

Protein Export According to Schedule: Architecture, Assembly, and Regulation of Type III Secretion Systems from Plant- and Animal-Pathogenic Bacteria

PubMed Central

2012-01-01

Summary: Flagellar and translocation-associated type III secretion (T3S) systems are present in most Gram-negative plant- and animal-pathogenic bacteria and are often essential for bacterial motility or pathogenicity. The architectures of the complex membrane-spanning secretion apparatuses of both systems are similar, but they are associated with different extracellular appendages, including the flagellar hook and filament or the needle/pilus structures of translocation-associated T3S systems. The needle/pilus is connected to a bacterial translocon that is inserted into the host plasma membrane and mediates the transkingdom transport of bacterial effector proteins into eukaryotic cells. During the last 3 to 5 years, significant progress has been made in the characterization of membrane-associated core components and extracellular structures of T3S systems. Furthermore, transcriptional and posttranscriptional regulators that control T3S gene expression and substrate specificity have been described. Given the architecture of the T3S system, it is assumed that extracellular components of the secretion apparatus are secreted prior to effector proteins, suggesting that there is a hierarchy in T3S. The aim of this review is to summarize our current knowledge of T3S system components and associated control proteins from both plant- and animal-pathogenic bacteria. PMID:22688814

TRP channels in calcium homeostasis: from hormonal control to structure-function relationship of TRPV5 and TRPV6.

PubMed

van Goor, Mark K C; Hoenderop, Joost G J; van der Wijst, Jenny

2017-06-01

Maintaining plasma calcium levels within a narrow range is of vital importance for many physiological functions. Therefore, calcium transport processes in the intestine, bone and kidney are tightly regulated to fine-tune the rate of absorption, storage and excretion. The TRPV5 and TRPV6 calcium channels are viewed as the gatekeepers of epithelial calcium transport. Several calciotropic hormones control the channels at the level of transcription, membrane expression, and function. Recent technological advances have provided the first near-atomic resolution structural models of several TRPV channels, allowing insight into their architecture. While this field is still in its infancy, it has increased our understanding of molecular channel regulation and holds great promise for future structure-function studies of these ion channels. This review will summarize the mechanisms that control the systemic calcium balance, as well as extrapolate structural views to the molecular functioning of TRPV5/6 channels in epithelial calcium transport. Copyright © 2016. Published by Elsevier B.V.

Change in single cystathionine β-synthase domain-containing protein from a bent to flat conformation upon adenosine monophosphate binding.

PubMed

Jeong, Byung-Cheon; Park, Si Hoon; Yoo, Kyoung Shin; Shin, Jeong Sheop; Song, Hyun Kyu

2013-07-01

Cystathionine β-synthase (CBS) domains are small intracellular modules that can act as binding domains for adenosine derivatives, and they may regulate the activity of associated enzymes or other functional domains. Among these, the single CBS domain-containing proteins, CBSXs, from Arabidopsis thaliana, have recently been identified as redox regulators of the thioredoxin system. Here, the crystal structure of CBSX2 in complex with adenosine monophosphate (AMP) is reported at 2.2Å resolution. The structure of dimeric CBSX2 with bound-AMP is shown to be approximately flat, which is in stark contrast to the bent form of apo-CBSXs. This conformational change in quaternary structure is triggered by a local structural change of the unique α5 helix, and by moving each loop P into an open conformation to accommodate incoming ligands. Furthermore, subtle rearrangement of the dimer interface triggers movement of all subunits, and consequently, the bent structure of the CBSX2 dimer becomes a flat structure. This reshaping of the structure upon complex formation with adenosine-containing ligand provides evidence that ligand-induced conformational reorganization of antiparallel CBS domains is an important regulatory mechanism. Copyright © 2013 Elsevier Inc. All rights reserved.

Understanding congestion in China's medical market: an incentive structure perspective.

PubMed

Sun, Zesheng; Wang, Shuhong; Barnes, Stephen R

2016-04-01

Congestion has become one of the most important factors leading to patient dissatisfaction and doctor-patient conflicts in the medical market of China. In this study, we explore the causes and effects of structural congestion in the Chinese medical market from an incentive structure perspective. Our analysis reveals that prior medical system reforms with price regulation in China have induced hospitals to establish incentives for capital-intensive investments, while ignoring human capital, and have driven medical staff and patients to higher-level hospitals, reinforcing an incentive structure in which congestion in higher-level hospitals and idle resources in lower-level hospitals coexist. The existing incentive structure has led to cost increases and degradation of human capital and specific factor effects. Recent reforms to reduce congestion in the Chinese medical market were not effective. Most of them had no impact on and did not involve the existing distorted incentive structure. Future reforms should consider rebalancing expectations for medical quality, free flow of human capital and price regulation reforms to rebuild a new incentive structure. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Implementing International Health Regulation (2005) in the Brazilian legal-administrative system.

PubMed

Lima, Yara Oyram Ramos; Costa, Ediná Alves

2015-06-01

The scope of this study was to analyze how the International Sanitary Regulation (ISR 2005)has been incorporated into the Brazilian legal-administrative system, in relation to sanitary control measures involving freight, means of transportation and travelers and possible alterations to health surveillance activities, competencies and procedures. This case study has been undertaken using a qualitative approach, of a descriptive and exploratory nature, using institutional data sources and interviews with key-informants involved in implementing ISR (2005). Alterations to the Brazilian legal-administrative system resulting from ISR (2005) were identified, in relation to standards, special competencies and procedures relating to sanitary controls for freight, modes of transportation and travelers. In its present form, the International Sanitary Regulation is an instrument that, in addition to introducing new international and national sanitary control concepts and elements, also helps to clarify questions that are helpful on a national level, relating to the specific competencies and procedures which will, to a certain extent, put pressure on administrative structures in the areas of sanitary control and surveillance.

Extremely high boron tolerance in Puccinellia distans (Jacq.) Parl. related to root boron exclusion and a well-regulated antioxidant system.

PubMed

Hamurcu, Mehmet; Hakki, Erdogan E; Demiral Sert, Tijen; Özdemir, Canan; Minareci, Ersin; Avsaroglu, Zuhal Z; Gezgin, Sait; Ali Kayis, Seyit; Bell, Richard W

Recent studies indicate an extremely high level of tolerance to boron (B) toxicity in Puccinellia distans (Jacq.) Parl. but the mechanistic basis is not known. Puccinellia distans was exposed to B concentrations of up to 1000 mg B L-1 and root B uptake, growth parameters, B and N contents, H2O2 accumulation and ·OH-scavenging activity were measured. Antioxidant enzyme activities including superoxide dismutase (SOD), ascorbate peroxidase, catalase, peroxidase and glutathione reductase, and lipid peroxidation products were determined. B appears to be actively excluded from roots. Excess B supply caused structural deformations in roots and leaves, H2O2 accumulation and simultaneous up-regulation of the antioxidative system, which prevented lipid peroxidation even at the highest B concentrations. Thus, P. distans has an efficient root B-exclusion capability and, in addition, B tolerance in shoots is achieved by a well-regulated antioxidant defense system.

RNA-Binding Proteins in Trichomonas vaginalis: Atypical Multifunctional Proteins Involved in a Posttranscriptional Iron Regulatory Mechanism

PubMed Central

Figueroa-Angulo, Elisa E.; Calla-Choque, Jaeson S.; Mancilla-Olea, Maria Inocente; Arroyo, Rossana

2015-01-01

Iron homeostasis is highly regulated in vertebrates through a regulatory system mediated by RNA-protein interactions between the iron regulatory proteins (IRPs) that interact with an iron responsive element (IRE) located in certain mRNAs, dubbed the IRE-IRP regulatory system. Trichomonas vaginalis, the causal agent of trichomoniasis, presents high iron dependency to regulate its growth, metabolism, and virulence properties. Although T. vaginalis lacks IRPs or proteins with aconitase activity, possesses gene expression mechanisms of iron regulation at the transcriptional and posttranscriptional levels. However, only one gene with iron regulation at the transcriptional level has been described. Recently, our research group described an iron posttranscriptional regulatory mechanism in the T. vaginalis tvcp4 and tvcp12 cysteine proteinase mRNAs. The tvcp4 and tvcp12 mRNAs have a stem-loop structure in the 5'-coding region or in the 3'-UTR, respectively that interacts with T. vaginalis multifunctional proteins HSP70, α-Actinin, and Actin under iron starvation condition, causing translation inhibition or mRNA stabilization similar to the previously characterized IRE-IRP system in eukaryotes. Herein, we summarize recent progress and shed some light on atypical RNA-binding proteins that may participate in the iron posttranscriptional regulation in T. vaginalis. PMID:26703754

Regulation of planar growth by the Arabidopsis AGC protein kinase UNICORN.

PubMed

Enugutti, Balaji; Kirchhelle, Charlotte; Oelschner, Maxi; Torres Ruiz, Ramón Angel; Schliebner, Ivo; Leister, Dario; Schneitz, Kay

2012-09-11

The spatial coordination of growth is of central importance for the regulation of plant tissue architecture. Individual layers, such as the epidermis, are clonally propagated and structurally maintained by symmetric cell divisions that are oriented along the plane of the layer. The developmental control of this process is poorly understood. The simple cellular basis and sheet-like structure of Arabidopsis integuments make them an attractive model system to address planar growth. Here we report on the characterization of the Arabidopsis UNICORN (UCN) gene. Analysis of ucn integuments reveals localized distortion of planar growth, eventually resulting in an ectopic multicellular protrusion. In addition, ucn mutants exhibit ectopic growth in filaments and petals, as well as aberrant embryogenesis. We further show that UCN encodes an active AGC VIII kinase. Genetic, biochemical, and cell biological data suggest that UCN suppresses ectopic growth in integuments by directly repressing the KANADI transcription factor ABERRANT TESTA SHAPE. Our findings indicate that UCN represents a unique plant growth regulator that maintains planar growth of integuments by repressing a developmental regulator involved in the control of early integument growth and polarity.

Regulator-dependent mechanisms of C3b processing by factor I allow differentiation of immune responses.

PubMed

Xue, Xiaoguang; Wu, Jin; Ricklin, Daniel; Forneris, Federico; Di Crescenzio, Patrizia; Schmidt, Christoph Q; Granneman, Joke; Sharp, Thomas H; Lambris, John D; Gros, Piet

2017-08-01

The complement system labels microbes and host debris for clearance. Degradation of surface-bound C3b is pivotal to direct immune responses and protect host cells. How the serine protease factor I (FI), assisted by regulators, cleaves either two or three distant peptide bonds in the CUB domain of C3b remains unclear. We present a crystal structure of C3b in complex with FI and regulator factor H (FH; domains 1-4 with 19-20). FI binds C3b-FH between FH domains 2 and 3 and a reoriented C3b C-terminal domain and docks onto the first scissile bond, while stabilizing its catalytic domain for proteolytic activity. One cleavage in C3b does not affect its overall structure, whereas two cleavages unfold CUB and dislodge the thioester-containing domain (TED), affecting binding of regulators and thereby determining the number of cleavages. These data explain how FI generates late-stage opsonins iC3b or C3dg in a context-dependent manner, to react to foreign, danger or healthy self signals.

The neuroendocrine immunomodulatory axis-like pathway mediated by circulating haemocytes in pacific oyster Crassostrea gigas.

PubMed

Liu, Zhaoqun; Zhou, Zhi; Jiang, Qiufen; Wang, Lingling; Yi, Qilin; Qiu, Limei; Song, Linsheng

2017-01-01

The neuroendocrine-immune (NEI) regulatory network is a complex system, which plays an indispensable role in the immunity of host. In this study, a neuroendocrine immunomodulatory axis (NIA)-like pathway mediated by the nervous system and haemocytes was characterized in the oyster Crassostrea gigas Once invaded pathogen was recognized by the host, the nervous system would temporally release neurotransmitters to modulate the immune response. Instead of acting passively, oyster haemocytes were able to mediate neuronal immunomodulation promptly by controlling the expression of specific neurotransmitter receptors on cell surface and modulating their binding sensitivities, thus regulating intracellular concentration of Ca 2+ This neural immunomodulation mediated by the nervous system and haemocytes could influence cellular immunity in oyster by affecting mRNA expression level of TNF genes, and humoral immunity by affecting the activities of key immune-related enzymes. In summary, though simple in structure, the 'nervous-haemocyte' NIA-like pathway regulates both cellular and humoral immunity in oyster, meaning a world to the effective immune regulation of the NEI network. © 2017 The Authors.

Tropomodulin Capping of Actin Filaments in Striated Muscle Development and Physiology

PubMed Central

Gokhin, David S.; Fowler, Velia M.

2011-01-01

Efficient striated muscle contraction requires precise assembly and regulation of diverse actin filament systems, most notably the sarcomeric thin filaments of the contractile apparatus. By capping the pointed ends of actin filaments, tropomodulins (Tmods) regulate actin filament assembly, lengths, and stability. Here, we explore the current understanding of the expression patterns, localizations, and functions of Tmods in both cardiac and skeletal muscle. We first describe the mechanisms by which Tmods regulate myofibril assembly and thin filament lengths, as well as the roles of closely related Tmod family variants, the leiomodins (Lmods), in these processes. We also discuss emerging functions for Tmods in the sarcoplasmic reticulum. This paper provides abundant evidence that Tmods are key structural regulators of striated muscle cytoarchitecture and physiology. PMID:22013379

[Advances in the study of neuroendocrinological regulation of kisspeptin in fish reproduction].

PubMed

Zhuo, Qi

2013-10-01

Kisspeptin, a key factor in the neuroendocrinological regulation of animal reproduction, is a peptide product encoded by kiss genes, which act as the natural ligand of GPR54. Over the last decade, multiple functional molecular forms of kisspeptin have been found in vertebrate species. In fish, the major molecular structural form is kisspeptin-10. The kisspeptin/GPR54 system has multiple important functions in reproduction. This review provides an overview of our current knowledge on kisspeptin and its role in regulating fish reproductive, including the distribution and location of kisspeptin neurons in the brain, the molecular polymorphism of fish kisspeptin, functional diversity, the molecular mechanism of fish reproductive regulation, and the molecular evolution of kisspeptin as well as the co-regulation of fish reproduction by kisspeptin and other functional molecules. Perspectives on the future of kisspeptin regulation in fish reproduction are also highlighted.

On issue of increasing profitability of automated energy technology complexes for preparation and combustion of water-coal suspensions

NASA Astrophysics Data System (ADS)

Brylina, O. G.; Osintsev, K. V.; Prikhodko, YU S.; Savosteenko, N. V.

2018-03-01

The article considers the issues of energy technological complexes economy increase on the existing techniques of water-coal suspensions preparation and burning basis due to application of highly effective control systems of electric drives and neurocontrol. The automated control system structure for the main boiler components is given. The electric drive structure is disclosed by the example of pumps (for transfer of coal-water mash and / or suspension). A system for controlling and diagnosing a heat and power complex based on a multi-zone regulator is proposed. The possibility of using neural networks for implementing the control algorithms outlined in the article is considered.

Applying an Equity Lens to the Child Care Setting.

PubMed

Scott, Krista; Looby, Anna Ayers; Hipp, Janie Simms; Frost, Natasha

2017-03-01

In the current landscape, child care is increasingly being seen as a place for early education, and systems are largely bundling child care in the Early Care and Education sphere through funding and quality measures. As states define school readiness and quality, they often miss critical elements, such as equitable access to quality and cultural traditions. This article provides a summary of the various definitions and structures of child care. It also discusses how the current child care policy conversation can and ought to be infused with a framework grounded in the context of institutional racism and trauma. Models and examples will explore the differences between state government regulations, and how those differ than the regulation and structure of child care in Indian Country.

A mutually exclusive stem–loop arrangement in roX2 RNA is essential for X-chromosome regulation in Drosophila

PubMed Central

Ilik, Ibrahim Avsar; Maticzka, Daniel; Georgiev, Plamen; Gutierrez, Noel Marie; Backofen, Rolf; Akhtar, Asifa

2017-01-01

The X chromosome provides an ideal model system to study the contribution of RNA–protein interactions in epigenetic regulation. In male flies, roX long noncoding RNAs (lncRNAs) harbor several redundant domains to interact with the ubiquitin ligase male-specific lethal 2 (MSL2) and the RNA helicase Maleless (MLE) for X-chromosomal regulation. However, how these interactions provide the mechanics of spreading remains unknown. By using the uvCLAP (UV cross-linking and affinity purification) methodology, which provides unprecedented information about RNA secondary structures in vivo, we identified the minimal functional unit of roX2 RNA. By using wild-type and various MLE mutant derivatives, including a catalytically inactive MLE derivative, MLEGET, we show that the minimal roX RNA contains two mutually exclusive stem–loops that exist in a peculiar structural arrangement: When one stem–loop is unwound by MLE, an alternate structure can form, likely trapping MLE in this perpetually structured region. We show that this functional unit is necessary for dosage compensation, as mutations that disrupt this formation lead to male lethality. Thus, we propose that roX2 lncRNA contains an MLE-dependent affinity switch to enable reversible interactions of the MSL complex to allow dosage compensation of the X chromosome. PMID:29066499

Profiling the array of Ca(v)3.1 variants from the human T-type calcium channel gene CACNA1G: alternative structures, developmental expression, and biophysical variations.

PubMed

Emerick, Mark C; Stein, Rebecca; Kunze, Robin; McNulty, Megan M; Regan, Melissa R; Hanck, Dorothy A; Agnew, William S

2006-08-01

We describe the regulated transcriptome of CACNA1G, a human gene for T-type Ca(v)3.1 calcium channels that is subject to extensive alternative RNA splicing. Fifteen sites of transcript variation include 2 alternative 5'-UTR promoter sites, 2 alternative 3'-UTR polyadenylation sites, and 11 sites of alternative splicing within the open reading frame. A survey of 1580 fetal and adult human brain full-length complementary DNAs reveals a family of 30 distinct transcripts, including multiple functional forms that vary in expression with development. Statistical analyses of fetal and adult transcript populations reveal patterns of linkages among intramolecular splice site configurations that change dramatically with development. A shift from nearly independent, biased splicing in fetal transcripts to strongly concerted splicing in adult transcripts suggests progressive activation of multiple "programs" of splicing regulation that reorganize molecular structures in differentiating cells. Patch-clamp studies of nine selected variants help relate splicing regulation to permutations of the gating parameters most likely to modify T-channel physiology in expressing neurons. Gating behavior reflects combinatorial interactions between variable domains so that molecular phenotype depends on ensembles of coselected domains, consistent with the observed emergence of concerted splicing during development. We conclude that the structural gene and networks of splicing regulatory factors define an integrated system for the phenotypic variation of Ca(v)3.1 biophysics during nervous system development. Copyright 2006 Wiley-Liss, Inc.

Structural and mechanical heterogeneity of the erythrocyte membrane reveals hallmarks of membrane stability.

PubMed

Picas, Laura; Rico, Félix; Deforet, Maxime; Scheuring, Simon

2013-02-26

The erythrocyte membrane, a metabolically regulated active structure that comprises lipid molecules, junctional complexes, and the spectrin network, enables the cell to undergo large passive deformations when passing through the microvascular system. Here we use atomic force microscopy (AFM) imaging and quantitative mechanical mapping at nanometer resolution to correlate structure and mechanics of key components of the erythrocyte membrane, crucial for cell integrity and function. Our data reveal structural and mechanical heterogeneity modulated by the metabolic state at unprecedented nanometer resolution. ATP-depletion, reducing skeletal junction phosphorylation in RBC cells, leads to membrane stiffening. Analysis of ghosts and shear-force opened erythrocytes show that, in the absence of cytosolic kinases, spectrin phosphorylation results in membrane stiffening at the extracellular face and a reduced junction remodeling in response to loading forces. Topography and mechanical mapping of single components at the cytoplasmic face reveal that, surprisingly, spectrin phosphorylation by ATP softens individual filaments. Our findings suggest that, besides the mechanical signature of each component, the RBC membrane mechanics is regulated by the metabolic state and the assembly of its structural elements.

Neuronal and molecular mechanisms of sleep homeostasis.

PubMed

Donlea, Jeffrey M

2017-12-01

Sleep is necessary for survival, and prolonged waking causes a homeostatic increase in the need for recovery sleep. Homeostasis is a core component of sleep regulation and has been tightly conserved across evolution from invertebrates to man. Homeostatic sleep regulation was first identified among insects in cockroaches several decades ago, but the characterization of sleep rebound in Drosophila melanogaster opened the use of insect model species to understand homeostatic functions and regulation of sleep. This review describes circuits in two neuropil structures, the central complex and mushroom bodies, that influence sleep homeostasis and neuromodulatory systems that influence the accrual of homeostatic sleep need. Copyright © 2017 Elsevier Inc. All rights reserved.

Benefits and entitlements in the Hungarian health care system.

PubMed

Gaal, Peter

2005-12-01

This contribution considers entitlements and benefits in the Hungarian health care system. After a brief introduction to the organizational structure of the system the decision-making processes are discussed in detail, including the most important actors, types and pieces of legislation, formal structures, decision-making criteria, and outputs in terms of benefit catalogues. Within the two main public financing systems (social insurance and tax-funded services) there are four types of regulatory regimes: (a) traditional political decision making, (b) price negotiations, (c) updating of classification systems for payment purposes, and (d) the procedure for the inclusion of registered medicines in the scope of the social health insurance system. As an example we discuss the benefit regulations and benefit catalogues in the category of services of curative care (HC.1) of the OECD classification of health services.

Benefits and entitlements in the Hungarian health care system

PubMed Central

2005-01-01

This contribution considers entitlements and benefits in the Hungarian health care system. After a brief introduction to the organizational structure of the system the decision-making processes are discussed in detail, including the most important actors, types and pieces of legislation, formal structures, decision-making criteria, and outputs in terms of benefit catalogues. Within the two main public financing systems (social insurance and tax-funded services) there are four types of regulatory regimes: (a) traditional political decision making, (b) price negotiations, (c) updating of classification systems for payment purposes, and (d) the procedure for the inclusion of registered medicines in the scope of the social health insurance system. As an example we discuss the benefit regulations and benefit catalogues in the category of services of curative care (HC.1) of the OECD classification of health services. PMID:16267656

18 CFR 1304.412 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-04-01

... CONSTRUCTION IN THE TENNESSEE RIVER SYSTEM AND REGULATION OF STRUCTURES AND OTHER ALTERATIONS Miscellaneous... targeted elevation to which TVA plans to fill each reservoir during its annual operating cycle. Applicants... summer pool elevation for the reservoir in question at the time the application is submitted. Land-based...

The air transportation/energy system

NASA Technical Reports Server (NTRS)

1973-01-01

The changing pattern of transportation is discussed, and the energy intensiveness of various modes of transportation is also analyzed. Sociopsychological data affecting why people travel by air are presented, along with governmental regulation and air transportation economics. The aviation user tax structure is shown in tabular form.

Opportunities and questions for the fundamental biological sciences in space

NASA Technical Reports Server (NTRS)

Sharp, Joseph C.; Vernikos, Joan

1992-01-01

The nature of biological issues which can be addressed during long-term space missions is briefly discussed. These issues include structure, from cell to organ to organism; function, the regulation of systems such as immunology, neural sciences, and behavior; and reproduction and development.

18 CFR 1304.412 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-04-01

... CONSTRUCTION IN THE TENNESSEE RIVER SYSTEM AND REGULATION OF STRUCTURES AND OTHER ALTERATIONS Miscellaneous... targeted elevation to which TVA plans to fill each reservoir during its annual operating cycle. Applicants... summer pool elevation for the reservoir in question at the time the application is submitted. Land-based...

7 CFR 650.4 - Definition of terms.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Regulations of the Department of Agriculture (Continued) NATURAL RESOURCES CONSERVATION SERVICE, DEPARTMENT OF... group considers structure and function of natural resource systems, complexity of problems, and the... action, significance usually depends on the effects in the locale rather than in the world as a whole...

7 CFR 650.4 - Definition of terms.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Regulations of the Department of Agriculture (Continued) NATURAL RESOURCES CONSERVATION SERVICE, DEPARTMENT OF... group considers structure and function of natural resource systems, complexity of problems, and the... action, significance usually depends on the effects in the locale rather than in the world as a whole...

7 CFR 650.4 - Definition of terms.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Regulations of the Department of Agriculture (Continued) NATURAL RESOURCES CONSERVATION SERVICE, DEPARTMENT OF... group considers structure and function of natural resource systems, complexity of problems, and the... action, significance usually depends on the effects in the locale rather than in the world as a whole...

Chapter Seven - When Phosphorylation Encounters Ubiquitination: A Balanced Perspective on IGF-1R Signaling.

PubMed

Girnita, L; Takahashi, S-I; Crudden, C; Fukushima, T; Worrall, C; Furuta, H; Yoshihara, H; Hakuno, F; Girnita, A

2016-01-01

Cell-surface receptors govern the critical information passage from outside to inside the cell and hence control important cellular decisions such as survival, growth, and differentiation. These receptors, structurally grouped into different families, utilize common intracellular signaling-proteins and pathways, yet promote divergent biological consequences. In rapid processing of extracellular signals to biological outcomes, posttranslational modifications offer a repertoire of protein processing options. Protein ubiquitination was originally identified as a signal for protein degradation through the proteasome system. It is now becoming increasingly recognized that both ubiquitin and ubiquitin-like proteins, all evolved from a common ubiquitin structural superfold, are used extensively by the cell and encompass signal tags for many different cellular fates. In this chapter we examine the current understanding of the ubiquitin regulation surrounding the insulin-like growth factor and insulin signaling systems, major members of the larger family of receptor tyrosine kinases (RTKs) and key regulators of fundamental physiological and pathological states. Copyright © 2016 Elsevier Inc. All rights reserved.

Gaps, inexperience, inconsistencies, and overlaps: crisis in the regulation of genetically modified plants and animals.

PubMed

Mandal, Gregory N

2004-04-01

The regulation of genetically modified products pursuant to statutes enacted decades prior to the advent of biotechnology has created a regulatory system that is passive rather than proactive about risks, has difficulty adapting to biotechnology advances, and is highly fractured and inefficient--transgenic plants and animals are governed by at least twelve different statutes and five different agencies or services. The deficiencies resulting from this piecemeal approach to regulation unnecessarily expose society and the environment to adverse risks of biotechnology and introduce numerous inefficiencies into the regulatory system. These risks and inefficiencies include gaps in regulation, duplicative and inconsistent regulation, unnecessary increases in the cost of and delay in the development and commercialization of new biotechnology products. These deficiencies also increase the risk of further unnecessary biotechnology scares, which may cause public overreaction against biotechnology products, preventing the maximization of social welfare. With science and society poised to soar from first-generation biotechnology (focused on crops modified for agricultural benefit), to next-generation developments (including transgenic fish, insects, and livestock, and pharmaceutical-producing and industrial compound-producing plants and animals), it is necessary to establish a comprehensive, efficient, and scientifically rigorous regulatory system. This Article details how to achieve such a result through fixing the deficiencies in, and risks created by, the current regulatory structure. Ignoring many details, the solutions can be summarized in two categories. First, statutory and regulatory gaps that are identified must be closed with new legislation and regulation. Second, regulation of genetically modified products must be shifted from a haphazard model based on statutes not intended to cover biotechnology to a system based upon agency expertise in handling particular types of risks.

Passively Adaptive Inflatable Structure for the Shooting Star Experiment

NASA Technical Reports Server (NTRS)

Tinker, Michael L..

1998-01-01

An inflatable structural system is described for the Shooting Star Experiment that is a technology demonstrator flight for solar thermal propulsion. The inflatable structure is a pressurized assembly used in orbit to support a fresnel lens for focusing sunlight into a thermal storage engine. When the engine temperature reaches a preset level, the propellant is injected into the storage engine, absorbs heat from a heat exchanger, and is expanded through the nozzle to produce thrust. The inflatable structure is an adaptive system in that a regulator and relief valve are utilized to maintain pressure within design limits during the full range of orbital conditions. Further, the polyimide film material used for construction of the inflatable is highly nonlinear, with modulus varying as a function of frequency, temperature, and level of excitation. A series of tests is described for characterizing the structure in response to various operating conditions.

Linear regulator design for stochastic systems by a multiple time scales method

NASA Technical Reports Server (NTRS)

Teneketzis, D.; Sandell, N. R., Jr.

1976-01-01

A hierarchically-structured, suboptimal controller for a linear stochastic system composed of fast and slow subsystems is considered. The controller is optimal in the limit as the separation of time scales of the subsystems becomes infinite. The methodology is illustrated by design of a controller to suppress the phugoid and short period modes of the longitudinal dynamics of the F-8 aircraft.

[Plant hormones, plant growth regulators].

PubMed

Végvári, György; Vidéki, Edina

2014-06-29

Plants seem to be rather defenceless, they are unable to do motion, have no nervous system or immune system unlike animals. Besides this, plants do have hormones, though these substances are produced not in glands. In view of their complexity they lagged behind animals, however, plant organisms show large scale integration in their structure and function. In higher plants, such as in animals, the intercellular communication is fulfilled through chemical messengers. These specific compounds in plants are called phytohormones, or in a wide sense, bioregulators. Even a small quantity of these endogenous organic compounds are able to regulate the operation, growth and development of higher plants, and keep the connection between cells, tissues and synergy between organs. Since they do not have nervous and immume systems, phytohormones play essential role in plants' life.

Systematic comparison of the response properties of protein and RNA mediated gene regulatory motifs.

PubMed

Iyengar, Bharat Ravi; Pillai, Beena; Venkatesh, K V; Gadgil, Chetan J

2017-05-30

We present a framework enabling the dissection of the effects of motif structure (feedback or feedforward), the nature of the controller (RNA or protein), and the regulation mode (transcriptional, post-transcriptional or translational) on the response to a step change in the input. We have used a common model framework for gene expression where both motif structures have an activating input and repressing regulator, with the same set of parameters, to enable a comparison of the responses. We studied the global sensitivity of the system properties, such as steady-state gain, overshoot, peak time, and peak duration, to parameters. We find that, in all motifs, overshoot correlated negatively whereas peak duration varied concavely with peak time. Differences in the other system properties were found to be mainly dependent on the nature of the controller rather than the motif structure. Protein mediated motifs showed a higher degree of adaptation i.e. a tendency to return to baseline levels; in particular, feedforward motifs exhibited perfect adaptation. RNA mediated motifs had a mild regulatory effect; they also exhibited a lower peaking tendency and mean overshoot. Protein mediated feedforward motifs showed higher overshoot and lower peak time compared to the corresponding feedback motifs.

Growing Out of Stress: The Role of Cell- and Organ-Scale Growth Control in Plant Water-Stress Responses[OPEN

PubMed Central

Robbins, Neil E.

2016-01-01

Water is the most limiting resource on land for plant growth, and its uptake by plants is affected by many abiotic stresses, such as salinity, cold, heat, and drought. While much research has focused on exploring the molecular mechanisms underlying the cellular signaling events governing water-stress responses, it is also important to consider the role organismal structure plays as a context for such responses. The regulation of growth in plants occurs at two spatial scales: the cell and the organ. In this review, we focus on how the regulation of growth at these different spatial scales enables plants to acclimate to water-deficit stress. The cell wall is discussed with respect to how the physical properties of this structure affect water loss and how regulatory mechanisms that affect wall extensibility maintain growth under water deficit. At a higher spatial scale, the architecture of the root system represents a highly dynamic physical network that facilitates access of the plant to a heterogeneous distribution of water in soil. We discuss the role differential growth plays in shaping the structure of this system and the physiological implications of such changes. PMID:27503468

Multifunctional glial support by Semper cells in the Drosophila retina

PubMed Central

Charlton-Perkins, Mark A.

2017-01-01

Glial cells play structural and functional roles central to the formation, activity and integrity of neurons throughout the nervous system. In the retina of vertebrates, the high energetic demand of photoreceptors is sustained in part by Müller glia, an intrinsic, atypical radial glia with features common to many glial subtypes. Accessory and support glial cells also exist in invertebrates, but which cells play this function in the insect retina is largely undefined. Using cell-restricted transcriptome analysis, here we show that the ommatidial cone cells (aka Semper cells) in the Drosophila compound eye are enriched for glial regulators and effectors, including signature characteristics of the vertebrate visual system. In addition, cone cell-targeted gene knockdowns demonstrate that such glia-associated factors are required to support the structural and functional integrity of neighboring photoreceptors. Specifically, we show that distinct support functions (neuronal activity, structural integrity and sustained neurotransmission) can be genetically separated in cone cells by down-regulating transcription factors associated with vertebrate gliogenesis (pros/Prox1, Pax2/5/8, and Oli/Olig1,2, respectively). Further, we find that specific factors critical for glial function in other species are also critical in cone cells to support Drosophila photoreceptor activity. These include ion-transport proteins (Na/K+-ATPase, Eaat1, and Kir4.1-related channels) and metabolic homeostatic factors (dLDH and Glut1). These data define genetically distinct glial signatures in cone/Semper cells that regulate their structural, functional and homeostatic interactions with photoreceptor neurons in the compound eye of Drosophila. In addition to providing a new high-throughput model to study neuron-glia interactions, the fly eye will further help elucidate glial conserved "support networks" between invertebrates and vertebrates. PMID:28562601

Lignin Down-regulation of Zea mays via dsRNAi and Klason Lignin Analysis

PubMed Central

Park, Sang-Hyuck; Ong, Rebecca Garlock; Mei, Chuansheng; Sticklen, Mariam

2014-01-01

To facilitate the use of lignocellulosic biomass as an alternative bioenergy resource, during biological conversion processes, a pretreatment step is needed to open up the structure of the plant cell wall, increasing the accessibility of the cell wall carbohydrates. Lignin, a polyphenolic material present in many cell wall types, is known to be a significant hindrance to enzyme access. Reduction in lignin content to a level that does not interfere with the structural integrity and defense system of the plant might be a valuable step to reduce the costs of bioethanol production. In this study, we have genetically down-regulated one of the lignin biosynthesis-related genes, cinnamoyl-CoA reductase (ZmCCR1) via a double stranded RNA interference technique. The ZmCCR1_RNAi construct was integrated into the maize genome using the particle bombardment method. Transgenic maize plants grew normally as compared to the wild-type control plants without interfering with biomass growth or defense mechanisms, with the exception of displaying of brown-coloration in transgenic plants leaf mid-ribs, husks, and stems. The microscopic analyses, in conjunction with the histological assay, revealed that the leaf sclerenchyma fibers were thinned but the structure and size of other major vascular system components was not altered. The lignin content in the transgenic maize was reduced by 7-8.7%, the crystalline cellulose content was increased in response to lignin reduction, and hemicelluloses remained unchanged. The analyses may indicate that carbon flow might have been shifted from lignin biosynthesis to cellulose biosynthesis. This article delineates the procedures used to down-regulate the lignin content in maize via RNAi technology, and the cell wall compositional analyses used to verify the effect of the modifications on the cell wall structure. PMID:25080235

Lignin down-regulation of Zea mays via dsRNAi and klason lignin analysis.

PubMed

Park, Sang-Hyuck; Ong, Rebecca Garlock; Mei, Chuansheng; Sticklen, Mariam

2014-07-23

To facilitate the use of lignocellulosic biomass as an alternative bioenergy resource, during biological conversion processes, a pretreatment step is needed to open up the structure of the plant cell wall, increasing the accessibility of the cell wall carbohydrates. Lignin, a polyphenolic material present in many cell wall types, is known to be a significant hindrance to enzyme access. Reduction in lignin content to a level that does not interfere with the structural integrity and defense system of the plant might be a valuable step to reduce the costs of bioethanol production. In this study, we have genetically down-regulated one of the lignin biosynthesis-related genes, cinnamoyl-CoA reductase (ZmCCR1) via a double stranded RNA interference technique. The ZmCCR1_RNAi construct was integrated into the maize genome using the particle bombardment method. Transgenic maize plants grew normally as compared to the wild-type control plants without interfering with biomass growth or defense mechanisms, with the exception of displaying of brown-coloration in transgenic plants leaf mid-ribs, husks, and stems. The microscopic analyses, in conjunction with the histological assay, revealed that the leaf sclerenchyma fibers were thinned but the structure and size of other major vascular system components was not altered. The lignin content in the transgenic maize was reduced by 7-8.7%, the crystalline cellulose content was increased in response to lignin reduction, and hemicelluloses remained unchanged. The analyses may indicate that carbon flow might have been shifted from lignin biosynthesis to cellulose biosynthesis. This article delineates the procedures used to down-regulate the lignin content in maize via RNAi technology, and the cell wall compositional analyses used to verify the effect of the modifications on the cell wall structure.

History, anatomical nomenclature, comparative anatomy and functions of the hippocampal formation.

PubMed

El-Falougy, H; Benuska, J

2006-01-01

The complex structures in the cerebral hemispheres is included under one term, the limbic system. Our conception of this system and its special functions rises from the comparative neuroanatomical and neurophysiological studies. The components of the limbic system are the hippocampus, gyrus parahippocampalis, gyrus dentatus, gyrus cinguli, corpus amygdaloideum, nuclei anteriores thalami, hypothalamus and gyrus paraterminalis Because of its unique macroscopic and microscopic structure, the hippocampus is a conspicuous part of the limbic system. During phylogenetic development, the hippocampus developed from a simple cortical plate in amphibians into complex three-dimensional convoluted structure in mammals. In the last few decades, structures of the limbic system were extensively studied. Attention was directed to the physiological functions and pathological changes of the hippocampus. Experimental studies proved that the hippocampus has a very important role in the process of learning and memory. Another important functions of the hippocampus as a part of the limbic system is its role in regulation of sexual and emotional behaviour. The term "hippocampal formation" is defined as the complex of six structures: gyrus dentatus, hippocampus proprius, subiculum proprium, presubiculum, parasubiculum and area entorhinalis In this work we attempt to present a brief review of knowledge about the hippocampus from the point of view of history, anatomical nomenclature, comparative anatomy and functions (Tab. 1, Fig. 2, Ref. 33).

Fundamental Aspects on Conductive Textiles Implemented in Intelligent System

NASA Astrophysics Data System (ADS)

Manea, L. R.; Hristian, L.; Ene, D.; Amariei, N.; Popa, A.

2017-06-01

Conductive fibers, which are electrically conductive elements having the structure of a fiber, have a fairly long history and have been used for applications in electronic textiles as well as for aesthetics, anti-static and shielding purposes. Electrically conducting textile fibers, such as gold-coated threads, were produced in antiquity for aesthetic purposes, before the discovery of electricity, using various manufacturing methods. The textile intelligent systems, which comprise conducting textile structures (electroconducting wires or structures), present a dynamic behavior which favors the self regulation of the thermal insulation and vapor permeability with the purpose to maintain the thermo-physiological balance; the clothing assembly aims at monitoring the biologic potential, used only in critical situation (ex. accidents, falling down in a precipice etc.).

Golden ratio: A subtle regulator in our body and cardiovascular system?

PubMed

Ozturk, Selcuk; Yalta, Kenan; Yetkin, Ertan

2016-11-15

Golden ratio, which is an irrational number and also named as the Greek letter Phi (φ), is defined as the ratio between two lines of unequal length, where the ratio of the lengths of the shorter to the longer is the same as the ratio between the lengths of the longer and the sum of the lengths. The so-called formula is a mathematical ratio and there exist a variety of examples in natural and man-made structures of great beauty. Moreover, golden ratio is expressed throughout the human body in some ways, including digits, uterus, teeth, and cardiovascular system. Although the association of Fibonacci series or golden ratio with systems and organs of human being has not been assessed in depth yet, the mainstream regulation of cardiovascular system seems to be associated with golden ratio. This raises the idea that there might have been a fine and subtle regulator in our body. In this article, we aimed to elaborate the relationship between the existence of golden ratio and the human body and to discuss the golden ratio and its association with cardiovascular system. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Experimental Systems to Study Yeast Pexophagy.

PubMed

Yamashita, Shun-Ichi; Oku, Masahide; Sakai, Yasuyoshi; Fujiki, Yukio

2017-01-01

Peroxisome abundance is tightly regulated according to the physiological contexts, through regulations of both proliferation and degradation of the organelles. Here, we describe detailed methods to analyze processes for autophagic degradation of peroxisomes, termed pexophagy, in yeast organisms. The assay systems include a method for biochemical detection of pexophagy completion, and one for microscopic visualization of specialized membrane structures acting in pexophagy. As a model yeast organism utilized in studies of pexophagy, the methylotrophic yeast Komagataella phaffii (Pichia pastoris) is referred to in this chapter and related information on the studies with baker's yeast (Saccharomyces cerevisiae) is also included. The described techniques facilitate elucidation of molecular machineries for pexophagy and understanding of peroxisome-selective autophagic pathways.

Distributed software framework and continuous integration in hydroinformatics systems

NASA Astrophysics Data System (ADS)

Zhou, Jianzhong; Zhang, Wei; Xie, Mengfei; Lu, Chengwei; Chen, Xiao

2017-08-01

When encountering multiple and complicated models, multisource structured and unstructured data, complex requirements analysis, the platform design and integration of hydroinformatics systems become a challenge. To properly solve these problems, we describe a distributed software framework and it’s continuous integration process in hydroinformatics systems. This distributed framework mainly consists of server cluster for models, distributed database, GIS (Geographic Information System) servers, master node and clients. Based on it, a GIS - based decision support system for joint regulating of water quantity and water quality of group lakes in Wuhan China is established.

Output Feedback Pole-Placement in the Design of Compensators for Suboptimal Linear Quadratic Regulators.

DTIC Science & Technology

1979-06-01

also extended to the class of stabilizable systems and the required compensator shown to possess a separation property. Finally the design methodology...Page 1.1. Block diagram of transfer function given in (1.28) ........... 15 3.3.1. Compensator structure for controllable and stabilizable systems ...response will be stable. The implemented output feedback control law will stabilize the total closed loop system . n nn Let [uin and iJi= 1 be the

Regulation of humoral immunity by complement.

PubMed

Carroll, Michael C; Isenman, David E

2012-08-24

The complement system of innate immunity is important in regulating humoral immunity largely through the complement receptor CR2, which forms a coreceptor on B cells during antigen-induced activation. However, CR2 also retains antigens on follicular dendritic cells (FDCs). Display of antigen on FDCs is critical for clonal selection and affinity maturation of activated B cells. This review will discuss the role of complement in adaptive immunity in general with a focus on the interplay between CR2-associated antigen on B cells with CR2 expressed on FDCs. This latter interaction provides an opportunity for memory B cells to sample antigen over prolonged periods. The cocrystal structure of CR2 with its ligand C3d provides insight into how the complement system regulates access of antigen by B cells with implications for therapeutic manipulations to modulate aberrant B cell responses in the case of autoimmunity. Copyright © 2012 Elsevier Inc. All rights reserved.

Conformational dynamism for DNA interaction in the Salmonella RcsB response regulator

PubMed Central

Miguel-Romero, Laura; Huesa, Juanjo; García, Pablo; García-del Portillo, Francisco

2018-01-01

Abstract The RcsCDB phosphorelay system controls an extremely large regulon in Enterobacteriaceae that involves processes such as biofilm formation, flagella production, synthesis of extracellular capsules and cell division. Therefore, fine-tuning of this system is essential for virulence in pathogenic microorganisms of this group. The final master effector of the RcsCDB system is the response regulator (RR) RcsB, which activates or represses multiple genes by binding to different promoter regions. This regulatory activity of RcsB can be done alone or in combination with additional transcriptional factors in phosphorylated or dephosphorylated states. The capacity of RcsB to interact with multiple promoters and partners, either dephosphorylated or phosphorylated, suggests an extremely conformational dynamism for this RR. To shed light on the activation mechanism of RcsB and its implication on promoter recognition, we solved the crystal structure of full-length RcsB from Salmonella enterica serovar Typhimurium in the presence and absence of a phosphomimetic molecule BeF3−. These two novel structures have guided an extensive site-directed mutagenesis study at the structural and functional level that confirms RcsB conformational plasticity and dynamism. Our data allowed us to propose a β5-T switch mechanism where phosphorylation is coupled to alternative DNA binding ways and which highlights the conformational dynamism of RcsB to be so pleiotropic. PMID:29186528

Long-Term Effects of Acute Stress on the Prefrontal-Limbic System in the Healthy Adult

PubMed Central

Wei, Dongtao; Du, Xue; Zhang, Qinglin; Liu, Guangyuan; Qiu, Jiang

2017-01-01

Most people are exposed to at least one traumatic event during the course of their lives, but large numbers of people do not develop posttraumatic stress disorders. Although previous studies have shown that repeated and chronic stress change the brain’s structure and function, few studies have focused on the long-term effects of acute stressful exposure in a nonclinical sample, especially the morphology and functional connectivity changes in brain regions implicated in emotional reactivity and emotion regulation. Forty-one months after the 5/12 Wenchuan earthquake, we investigated the effects of trauma exposure on the structure and functional connectivity of the brains of trauma-exposed healthy individuals compared with healthy controls matched for age, sex, and education. We then used machine-learning algorithms with the brain structural features to distinguish between the two groups at an individual level. In the trauma-exposed healthy individuals, our results showed greater gray matter density in prefrontal-limbic brain systems, including the dorsal anterior cingulate cortex, medial prefrontal cortex, amygdala and hippocampus, than in the controls. Further analysis showed stronger amygdala-hippocampus functional connectivity in the trauma-exposed healthy compared to the controls. Our findings revealed that survival of traumatic experiences, without developing PTSD, was associated with greater gray matter density in the prefrontal-limbic systems related to emotional regulation. PMID:28045980

Planning for Competency-Based Teacher Education at the State Level.

ERIC Educational Resources Information Center

Roth, Robert A.

There are eight areas which require attention in planning for state implementation of performance-based teacher education (PBTE): (a) initiation action, (b) goal statement formulation, (c) state role identification, (d) certification pattern design, (e) delivery system structure, (f) support mechanism organization, (g) regulation changes…

Genetics and Population Structure of Heterobasidion annosum with Special Reference to Western North America

Treesearch

Thomas E. Chase

1989-01-01

Recent advances in the genetics and population biology of Heterobasidion annosum are reviewed. H. annosum is a heterothallic (outbreeding) basidiomycete with a unifactorial, multiallelic incompatibility system which regulates mating. H. annosum in western North America consists of two intersterility groups (...

48 CFR 1615.404-4 - Profit.

Code of Federal Regulations, 2011 CFR

2011-10-01

... contracts by use of a weighted guidelines structured approach. The service charge so determined will be the... 1615.404-4 Federal Acquisition Regulations System OFFICE OF PERSONNEL MANAGEMENT FEDERAL EMPLOYEES... Contract Pricing 1615.404-4 Profit. (a) When the pricing of FEHB Program contracts is determined by cost...

48 CFR 1615.404-4 - Profit.

Code of Federal Regulations, 2010 CFR

2010-10-01

... contracts by use of a weighted guidelines structured approach. The service charge so determined will be the... 1615.404-4 Federal Acquisition Regulations System OFFICE OF PERSONNEL MANAGEMENT FEDERAL EMPLOYEES... Contract Pricing 1615.404-4 Profit. (a) When the pricing of FEHB Program contracts is determined by cost...

A Long-Term Study of the Microbial Community Structure in a Simulated Chloraminated Drinking Water Distribution System - abstract

EPA Science Inventory

Many US water treatment facilities use chloramination to limit regulated disinfectant by-product formation. However, chloramination has been shown to promote nitrifying bacteria, and 30 to 63% of water utilities using secondary chloramine disinfection experience nitrification ep...

A novel statistical approach for identification of the master regulator transcription factor.

PubMed

Sikdar, Sinjini; Datta, Susmita

2017-02-02

Transcription factors are known to play key roles in carcinogenesis and therefore, are gaining popularity as potential therapeutic targets in drug development. A 'master regulator' transcription factor often appears to control most of the regulatory activities of the other transcription factors and the associated genes. This 'master regulator' transcription factor is at the top of the hierarchy of the transcriptomic regulation. Therefore, it is important to identify and target the master regulator transcription factor for proper understanding of the associated disease process and identifying the best therapeutic option. We present a novel two-step computational approach for identification of master regulator transcription factor in a genome. At the first step of our method we test whether there exists any master regulator transcription factor in the system. We evaluate the concordance of two ranked lists of transcription factors using a statistical measure. In case the concordance measure is statistically significant, we conclude that there is a master regulator. At the second step, our method identifies the master regulator transcription factor, if there exists one. In the simulation scenario, our method performs reasonably well in validating the existence of a master regulator when the number of subjects in each treatment group is reasonably large. In application to two real datasets, our method ensures the existence of master regulators and identifies biologically meaningful master regulators. An R code for implementing our method in a sample test data can be found in http://www.somnathdatta.org/software . We have developed a screening method of identifying the 'master regulator' transcription factor just using only the gene expression data. Understanding the regulatory structure and finding the master regulator help narrowing the search space for identifying biomarkers for complex diseases such as cancer. In addition to identifying the master regulator our method provides an overview of the regulatory structure of the transcription factors which control the global gene expression profiles and consequently the cell functioning.

Closed-loop control of renal perfusion pressure in physiological experiments.

PubMed

Campos-Delgado, D U; Bonilla, I; Rodríguez-Martínez, M; Sánchez-Briones, M E; Ruiz-Hernández, E

2013-07-01

This paper presents the design, experimental modeling, and control of a pump-driven renal perfusion pressure (RPP)-regulatory system to implement precise and relatively fast RPP regulation in rats. The mechatronic system is a simple, low-cost, and reliable device to automate the RPP regulation process based on flow-mediated occlusion. Hence, the regulated signal is the RPP measured in the left femoral artery of the rat, and the manipulated variable is the voltage applied to a dc motor that controls the occlusion of the aorta. The control system is implemented in a PC through the LabView software, and a data acquisition board NI USB-6210. A simple first-order linear system is proposed to approximate the dynamics in the experiment. The parameters of the model are chosen to minimize the error between the predicted and experimental output averaged from eight input/output datasets at different RPP operating conditions. A closed-loop servocontrol system based on a pole-placement PD controller plus dead-zone compensation was proposed for this purpose. First, the feedback structure was validated in simulation by considering parameter uncertainty, and constant and time-varying references. Several experimental tests were also conducted to validate in real time the closed-loop performance for stepwise and fast switching references, and the results show the effectiveness of the proposed automatic system to regulate the RPP in the rat, in a precise, accurate (mean error less than 2 mmHg) and relatively fast mode (10-15 s of response time).

The Metabolic Core and Catalytic Switches Are Fundamental Elements in the Self-Regulation of the Systemic Metabolic Structure of Cells

PubMed Central

De la Fuente, Ildefonso M.; Cortes, Jesus M.; Perez-Pinilla, Martin B.; Ruiz-Rodriguez, Vicente; Veguillas, Juan

2011-01-01

Background Experimental observations and numerical studies with dissipative metabolic networks have shown that cellular enzymatic activity self-organizes spontaneously leading to the emergence of a metabolic core formed by a set of enzymatic reactions which are always active under all environmental conditions, while the rest of catalytic processes are only intermittently active. The reactions of the metabolic core are essential for biomass formation and to assure optimal metabolic performance. The on-off catalytic reactions and the metabolic core are essential elements of a Systemic Metabolic Structure which seems to be a key feature common to all cellular organisms. Methodology/Principal Findings In order to investigate the functional importance of the metabolic core we have studied different catalytic patterns of a dissipative metabolic network under different external conditions. The emerging biochemical data have been analysed using information-based dynamic tools, such as Pearson's correlation and Transfer Entropy (which measures effective functionality). Our results show that a functional structure of effective connectivity emerges which is dynamical and characterized by significant variations of bio-molecular information flows. Conclusions/Significance We have quantified essential aspects of the metabolic core functionality. The always active enzymatic reactions form a hub –with a high degree of effective connectivity- exhibiting a wide range of functional information values being able to act either as a source or as a sink of bio-molecular causal interactions. Likewise, we have found that the metabolic core is an essential part of an emergent functional structure characterized by catalytic modules and metabolic switches which allow critical transitions in enzymatic activity. Both, the metabolic core and the catalytic switches in which also intermittently-active enzymes are involved seem to be fundamental elements in the self-regulation of the Systemic Metabolic Structure. PMID:22125607

Cis-regulatory underpinnings of human GLI3 expression in embryonic craniofacial structures and internal organs.

PubMed

Abbasi, Amir A; Minhas, Rashid; Schmidt, Ansgar; Koch, Sabine; Grzeschik, Karl-Heinz

2013-10-01

The zinc finger transcription factor Gli3 is an important mediator of Sonic hedgehog (Shh) signaling. During early embryonic development Gli3 participates in patterning and growth of the central nervous system, face, skeleton, limb, tooth and gut. Precise regulation of the temporal and spatial expression of Gli3 is crucial for the proper specification of these structures in mammals and other vertebrates. Previously we reported a set of human intronic cis-regulators controlling almost the entire known repertoire of endogenous Gli3 expression in mouse neural tube and limbs. However, the genetic underpinning of GLI3 expression in other embryonic domains such as craniofacial structures and internal organs remain elusive. Here we demonstrate in a transgenic mice assay the potential of a subset of human/fish conserved non-coding sequences (CNEs) residing within GLI3 intronic intervals to induce reporter gene expression at known regions of endogenous Gli3 transcription in embryonic domains other than central nervous system (CNS) and limbs. Highly specific reporter expression was observed in craniofacial structures, eye, gut, and genitourinary system. Moreover, the comparison of expression patterns directed by these intronic cis-acting regulatory elements in mouse and zebrafish embryos suggests that in accordance with sequence conservation, the target site specificity of a subset of these elements remains preserved among these two lineages. Taken together with our recent investigations, it is proposed here that during vertebrate evolution the Gli3 expression control acquired multiple, independently acting, intronic enhancers for spatiotemporal patterning of CNS, limbs, craniofacial structures and internal organs. © 2013 The Authors Development, Growth & Differentiation © 2013 Japanese Society of Developmental Biologists.

Function of fusion regulatory proteins (FRPs) in immune cells and virus-infected cells.

PubMed

Tsurudome, M; Ito, Y

2000-01-01

Two molecules that regulate cell fusion have been identified and designated fusion regulatory protein-1 (FRP-1) and FRP-2. FRP-1 is a complex composed of a glycosylated heavy chain and a nonglycosylated light chain that are disulfide linked. FRP-1 heavy chain is identical to 4F2/CD98 heavy chain, whereas FRP-2 is identical to integrin alpha3 subunit. The FRP-1 heavy chain is a multifunctional molecule: that is, fusion regulator, amino acid transporter, integrin regulator, comitogenic factor, Na+-Ca2+ exchanger, oncogenic protein, and so on. Several aspects of the structure and function of the FRP-1 system are reviewed: fusion regulatory molecular mechanisms, cross-talk between the FRP-1 and integrin, the FRP-1 system as amino acid transporter, and FRP-1-mediated T-cell activation. The FRP-1 system is involved in virus-mediated cell fusion and multinucleated giant cell formation of blood monocytes. Monoclonal antibodies against human FRP-1 heavy chain induce polykaryocytes that have properties as osteoclasts. Multiple steps participate in molecular mechanisms regulating cell fusion. The FRP-1 heavy chain supports amino acid transport activity and the FRP-1 light chains have recently been cloned as amino acid transporters that require association with the heavy chain to exhibit their activity. Novel pathways for monocyte-dependent regulation of T-cell activation have recently been found that are mediated by the FRP-1 system. In conclusion, the FRP-1 molecules are essential factors for basic cellular functions.

Regulation of body growth by microRNAs.

PubMed

Lui, Julian C

2017-11-15

Regulation of body growth remains a fascinating and unresolved biological mystery. One key component of body growth is skeletal and longitudinal bone growth. Children grow taller because their bones grew longer, and the predominant driver of longitudinal bone growth is a cartilaginous structure found near the ends of long bone named the growth plate. Numerous recent studies have started to unveil the importance of microRNAs in regulation of growth plate functions, therefore contributing to regulation of linear growth. In addition to longitudinal growth, other organs in our body need to increase in size and cell number as we grow, and the regulation of organ growth involves both systemic factors like hormones; and other intrinsic mechanisms, which we are just beginning to understand. This review aims to summarize some recent important findings on how microRNAs are involved in both of these processes: the regulation of longitudinal bone growth, and the regulation of organs and overall body growth. Published by Elsevier B.V.

Causality, randomness, intelligibility, and the epistemology of the cell.

PubMed

Dougherty, Edward R; Bittner, Michael L

2010-06-01

Because the basic unit of biology is the cell, biological knowledge is rooted in the epistemology of the cell, and because life is the salient characteristic of the cell, its epistemology must be centered on its livingness, not its constituent components. The organization and regulation of these components in the pursuit of life constitute the fundamental nature of the cell. Thus, regulation sits at the heart of biological knowledge of the cell and the extraordinary complexity of this regulation conditions the kind of knowledge that can be obtained, in particular, the representation and intelligibility of that knowledge. This paper is essentially split into two parts. The first part discusses the inadequacy of everyday intelligibility and intuition in science and the consequent need for scientific theories to be expressed mathematically without appeal to commonsense categories of understanding, such as causality. Having set the backdrop, the second part addresses biological knowledge. It briefly reviews modern scientific epistemology from a general perspective and then turns to the epistemology of the cell. In analogy with a multi-faceted factory, the cell utilizes a highly parallel distributed control system to maintain its organization and regulate its dynamical operation in the face of both internal and external changes. Hence, scientific knowledge is constituted by the mathematics of stochastic dynamical systems, which model the overall relational structure of the cell and how these structures evolve over time, stochasticity being a consequence of the need to ignore a large number of factors while modeling relatively few in an extremely complex environment.

International medical law and its impact on the ukrainian health care legislation.

PubMed

Pashkov, Vitalii; Udovyka, Larysa; Dichko, Hanna

2018-01-01

Introduction: The Ukrainian state has an urgent necessity of rapid search for essentially new legal and organizational forms of the healthcare system, reform of the legal regulation of healthcare services provision. In the context of European integration, the advancement of the medical industry reform is closely related to consideration of international standards and norms of health care. The aim: To study the impact of international medical law on the Ukrainian health care legislation. Materials and methods: International and Ukrainian regulations and documents on health care were used in the research. System and structural, functional and legal comparative methods as well as systematization, analysis and synthesis were determinative in the research process. Review: Systematization of international documents on health care was made. The major problems in the Ukrainian health care legislation were determined in terms of their conformity with the international legislative norms. The expediency of the Medical Code adoption was grounded and its structure was defined. Conclusions: Most health care international acts are ratified by Ukraine and their provisions are implemented in the legislation. Simultaneously, there is a row of problems, which hinder the Ukrainian health care development and place obstacles in the way of European integration. To remove these obstacles, it is expedient to create a codified act - the Medical Code, which would systematize the provisions of the current medical laws and regulations and fill in the existing gaps in the legal regulation of health care.

A Stable Human-Cell System Overexpressing Cystic Fibrosis Transmembrane Conductance Regulator Recombinant Protein at the Cell Surface

PubMed Central

Dai, Qun; Aleksandrov, Andrei A.; Bajrami, Bekim; Diego, Pamela Ann; Wu, Xing; Ray, Marjorie; Naren, Anjaparavanda P.; Riordan, John R.; Yao, Xudong; DeLucas, Lawrence J.; Urbatsch, Ina L.; Kappes, John C.

2015-01-01

Recent human clinical trials results demonstrated successful treatment for certain genetic forms of cystic fibrosis (CF). To extend treatment opportunities to those afflicted with other genetic forms of CF disease, structural and biophysical characterization of CF transmembrane conductance regulator (CFTR) is urgently needed. In this study, CFTR was modified with various tags, including a His10 purification tag, the SUMOstar (SUMO*) domain, an extracellular FLAG epitope, or an enhanced green fluorescent protein (EGFP), each alone or in various combinations. Expressed in HEK293 cells, recombinant CFTR proteins underwent complex glycosylation, compartmentalized with the plasma membrane, and exhibited regulated chloride-channel activity with only modest alterations in channel conductance and gating kinetics. Surface CFTR expression level was enhanced by the presence of SUMO* on the N-terminus. Quantitative mass-spectrometric analysis indicated approximately 10% of the total recombinant CFTR (SUMO*-CFTRFLAG-EGFP) localized to the plasma membrane. Trial purification using dodecylmaltoside for membrane protein extraction reproducibly recovered 178 ± 56 μg SUMO*-CFTRFLAG-EGFP per billion cells at 80% purity. Fluorescence size-exclusion chromatography indicated purified CFTR was monodisperse. These findings demonstrate a stable mammalian cell expression system capable of producing human CFTR of sufficient quality and quantity to augment futrure CF drug discovery efforts, including biophysical and structural studies. PMID:25577540

Design and implementation of a synthetic pre-miR switch for controlling miRNA biogenesis in mammals

PubMed Central

Atanasov, Janina; Groher, Florian

2017-01-01

Abstract Synthetic RNA-based systems have increasingly been used for the regulation of eukaryotic gene expression. Due to their structural properties, riboregulators provide a convenient basis for the development of ligand-dependent controllable systems. Here, we demonstrate reversible conditional control of miRNA biogenesis with an aptamer domain as a sensing unit connected to a natural miRNA precursor for the first time. For the design of the pre-miR switch, we replaced the natural terminal loop with the TetR aptamer. Thus, the TetR aptamer was positioned close to the Dicer cleavage sites, which allowed sterical control over pre-miR processing by Dicer. Our design proved to be highly versatile, allowing us to regulate the biogenesis of three structurally different miRNAs: miR-126, -34a and -199a. Dicer cleavage was inhibited up to 143-fold via co-expression of the TetR protein, yet could be completely restored upon addition of doxycycline. Moreover, we showed the functionality of the pre-miR switches for gene regulation through the interaction of the respective miRNA with its specific target sequence. Our designed device is capable of robust and reversible control of miRNA abundance. Thus, we offer a novel investigational tool for functional miRNA analysis. PMID:29036355

Somatostatin signaling and the regulation of growth and metabolism in fish.

PubMed

Klein, Sarah E; Sheridan, Mark A

2008-05-14

The study of the somatostatins (SS) signaling system in fish has provided important information about the structure, function, and evolution of SSs and their receptors. The SS signaling system elicits widespread biological actions via multiple hormone variants, numerous receptor subtypes, and a variety of signal transduction pathways. SSs alter growth via both direct and indirect actions, including inhibiting growth hormone release at the pituitary, decreasing hepatic GH sensitivity, and lowering plasma IGF-I levels. Metabolism also is significantly influenced by SSs. SSs stimulate the breakdown of energy stores and influences digestion, food intake, nutrient absorption, and food conversion both directly and through the modulation of other hormonal systems. The study of fish, which display a diversity of habitat types and life history forms, reveals that the SS signaling system helps regulate energy partitioning and integrate metabolism with growth and other biological processes.

Structure of Salmonella FlhE, conserved member of a flagellar Type III secretion operon

DOE PAGES

Lee, Jaemin; Monzingo, Arthur F.; Keatinge-Clay, Adrian T.; ...

2014-12-26

In this paper, the bacterial flagellum is assembled by a multicomponent transport apparatus categorized as a type III secretion system. The secretion of proteins that assemble into the flagellum is driven by the proton motive force. The periplasmic protein FlhE is a member of the flhBAE operon in the majority of bacteria where FlhE is found. FlhA and FlhB are established components of the flagellar type III secretion system. The absence of FlhE results in a proton leak through the flagellar system, inappropriate secretion patterns, and cell death, indicating that FlhE regulates an important aspect of proper flagellar biosynthesis. Wemore » isolated FlhE from the periplasm of Salmonella and solved its structure to 1.5 Å resolution. The structure reveals a β-sandwich fold, with no close structural homologs. Finally, possible roles of FlhE, including that of a chaperone, are discussed.« less

Structure of Salmonella FlhE, conserved member of a flagellar Type III secretion operon

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Jaemin; Monzingo, Arthur F.; Keatinge-Clay, Adrian T.

In this paper, the bacterial flagellum is assembled by a multicomponent transport apparatus categorized as a type III secretion system. The secretion of proteins that assemble into the flagellum is driven by the proton motive force. The periplasmic protein FlhE is a member of the flhBAE operon in the majority of bacteria where FlhE is found. FlhA and FlhB are established components of the flagellar type III secretion system. The absence of FlhE results in a proton leak through the flagellar system, inappropriate secretion patterns, and cell death, indicating that FlhE regulates an important aspect of proper flagellar biosynthesis. Wemore » isolated FlhE from the periplasm of Salmonella and solved its structure to 1.5 Å resolution. The structure reveals a β-sandwich fold, with no close structural homologs. Finally, possible roles of FlhE, including that of a chaperone, are discussed.« less

On the role of the central nervous system in regulating the mineralisation of inner-ear otoliths of fish.

PubMed

Anken, Ralf H

2006-12-01

Stato- or otoliths are calcified structures in the organ of balance and equilibrium of vertebrates, the inner ear, where they enhance its sensitivity to gravity. The compact otoliths of fish are composed of the calcium carbonate polymorph aragonite and a small fraction of organic molecules. The latter form a protein skeleton which determines the morphology of an otolith as well as its crystal lattice structure. This short review addresses findings according to which the brain obviously plays a prominent role in regulating the mineralisation of fish otoliths and depends on the gravity vector. Overall, otolith mineralisation has thus been identified to be a unique, neuronally guided biomineralisation process. The following is a hypothetical model for regulation of calcification by efferent vestibular neurons: (1) release of calcium at tight junctions in the macular epithelia, (2) macular carbonic anhydrase activity (which in turn is responsible for carbonate deposition), (3) chemical composition of matrix proteins. The rationale and evidence that support this model are discussed.

Isolating causal pathways between flow and fish in the regulated river hierarchy

DOE Office of Scientific and Technical Information (OSTI.GOV)

McManamay, Ryan A.; Peoples, Brandon K.; Orth, Donald J.

Unregulated river systems are organized in a hierarchy in which large-scale factors (i.e., landscape and segment scales) influence local habitats (i.e., reach, meso-, and microhabitat scales), and both differentially exert selective pressures on biota. Dams, however, create discontinua in these processes and change the hierarchical structure. We examined the relative roles of hydrology and other instream factors, within a hierarchical landscape context, in organizing fish communities in regulated and unregulated tributaries to the Upper Tennessee River, USA. We also used multivariate regression trees to identify factors that partition fish assemblages based on trait similarities, irrespective of spatial scale. Then, wemore » used classical path analysis and structural equation modeling to evaluate the most plausible hierarchical causal structure of specific trait-based community components, given the data. Both statistical approaches suggested that river regulation affects stream fishes through a variety of reach-scale variables, not always through hydrology itself. Though we observed different changes in flow, temperature, and biotic responses according to regulation types, the most predominant path in which dam regulation affected biota was via temperature alterations. Diversion dams had the strongest effects on fish assemblages. Diversion dams reduced flow magnitudes, leading to declines in fish richness but increased temperatures, leading to lower abundances in equilibrium species and nest guarders. Peaking and run-of-river dams increased flow variability, leading to lower abundances in nest-guarding fishes. Flow displayed direct relationships with biotic responses; however, results indicated that changes in temperature and substrate had equal, if not stronger, effects on fish assemblage composition. The strength and nature of relationships depended on whether flow metrics were standardized for river size. Here, we suggest that restoration efforts in regulated rivers focus on improving flow conditions in conjunction with temperature and substrate restoration.« less

Isolating causal pathways between flow and fish in the regulated river hierarchy

DOE PAGES

McManamay, Ryan A.; Peoples, Brandon K.; Orth, Donald J.; ...

2015-07-07

Unregulated river systems are organized in a hierarchy in which large-scale factors (i.e., landscape and segment scales) influence local habitats (i.e., reach, meso-, and microhabitat scales), and both differentially exert selective pressures on biota. Dams, however, create discontinua in these processes and change the hierarchical structure. We examined the relative roles of hydrology and other instream factors, within a hierarchical landscape context, in organizing fish communities in regulated and unregulated tributaries to the Upper Tennessee River, USA. We also used multivariate regression trees to identify factors that partition fish assemblages based on trait similarities, irrespective of spatial scale. Then, wemore » used classical path analysis and structural equation modeling to evaluate the most plausible hierarchical causal structure of specific trait-based community components, given the data. Both statistical approaches suggested that river regulation affects stream fishes through a variety of reach-scale variables, not always through hydrology itself. Though we observed different changes in flow, temperature, and biotic responses according to regulation types, the most predominant path in which dam regulation affected biota was via temperature alterations. Diversion dams had the strongest effects on fish assemblages. Diversion dams reduced flow magnitudes, leading to declines in fish richness but increased temperatures, leading to lower abundances in equilibrium species and nest guarders. Peaking and run-of-river dams increased flow variability, leading to lower abundances in nest-guarding fishes. Flow displayed direct relationships with biotic responses; however, results indicated that changes in temperature and substrate had equal, if not stronger, effects on fish assemblage composition. The strength and nature of relationships depended on whether flow metrics were standardized for river size. Here, we suggest that restoration efforts in regulated rivers focus on improving flow conditions in conjunction with temperature and substrate restoration.« less

Extracellular Matrix as a Regulator of Epidermal Stem Cell Fate.

PubMed

Chermnykh, Elina; Kalabusheva, Ekaterina; Vorotelyak, Ekaterina

2018-03-27

Epidermal stem cells reside within the specific anatomic location, called niche, which is a microenvironment that interacts with stem cells to regulate their fate. Regulation of many important processes, including maintenance of stem cell quiescence, self-renewal, and homeostasis, as well as the regulation of division and differentiation, are common functions of the stem cell niche. As it was shown in multiple studies, extracellular matrix (ECM) contributes a lot to stem cell niches in various tissues, including that of skin. In epidermis, ECM is represented, primarily, by a highly specialized ECM structure, basement membrane (BM), which separates the epidermal and dermal compartments. Epidermal stem cells contact with BM, but when they lose the contact and migrate to the overlying layers, they undergo terminal differentiation. When considering all of these factors, ECM is of fundamental importance in regulating epidermal stem cells maintenance, proper mobilization, and differentiation. Here, we summarize the remarkable progress that has recently been made in the research of ECM role in regulating epidermal stem cell fate, paying special attention to the hair follicle stem cell niche. We show that the destruction of ECM components impairs epidermal stem cell morphogenesis and homeostasis. A deep understanding of ECM molecular structure as well as the development of in vitro system for stem cell maintaining by ECM proteins may bring us to developing new approaches for regenerative medicine.

Active control of acoustic pressure fields using smart material technologies

NASA Technical Reports Server (NTRS)

Banks, H. T.; Smith, R. C.

1993-01-01

An overview describing the use of piezoceramic patches in reducing noise in a structural acoustics setting is presented. The passive and active contributions due to patches which are bonded to an Euler-Bernoulli beam or thin shell are briefly discussed and the results are incorporated into a 2-D structural acoustics model. In this model, an exterior noise source causes structural vibrations which in turn lead to interior noise as a result of nonlinear fluid/structure coupling mechanism. Interior sound pressure levels are reduced via patches bonded to the flexible boundary (a beam in this case) which generate pure bending moments when an out-of-phase voltage is applied. Well-posedness results for the infinite dimensional system are discussed and a Galerkin scheme for approximating the system dynamics is outlined. Control is implemented by using linear quadratic regulator (LQR) optimal control theory to calculate gains for the linearized system and then feeding these gains back into the nonlinear system of interest. The effectiveness of this strategy for this problem is illustrated in an example.

The TubR-centromere complex adopts a double-ring segrosome structure in Type III partition systems.

PubMed

Martín-García, Bárbara; Martín-González, Alejandro; Carrasco, Carolina; Hernández-Arriaga, Ana M; Ruíz-Quero, Rubén; Díaz-Orejas, Ramón; Aicart-Ramos, Clara; Moreno-Herrero, Fernando; Oliva, María A

2018-05-14

In prokaryotes, the centromere is a specialized segment of DNA that promotes the assembly of the segrosome upon binding of the Centromere Binding Protein (CBP). The segrosome structure exposes a specific surface for the interaction of the CBP with the motor protein that mediates DNA movement during cell division. Additionally, the CBP usually controls the transcriptional regulation of the segregation system as a cell cycle checkpoint. Correct segrosome functioning is therefore indispensable for accurate DNA segregation. Here, we combine biochemical reconstruction and structural and biophysical analysis to bring light to the architecture of the segrosome complex in Type III partition systems. We present the particular features of the centromere site, tubC, of the model system encoded in Clostridium botulinum prophage c-st. We find that the split centromere site contains two different iterons involved in the binding and spreading of the CBP, TubR. The resulting nucleoprotein complex consists of a novel double-ring structure that covers part of the predicted promoter. Single molecule data provides a mechanism for the formation of the segrosome structure based on DNA bending and unwinding upon TubR binding.

Mechanical stress and network structure drive protein dynamics during cytokinesis.

PubMed

Srivastava, Vasudha; Robinson, Douglas N

2015-03-02

Cell-shape changes associated with processes like cytokinesis and motility proceed on several-second timescales but are derived from molecular events, including protein-protein interactions, filament assembly, and force generation by molecular motors, all of which occur much faster [1-4]. Therefore, defining the dynamics of such molecular machinery is critical for understanding cell-shape regulation. In addition to signaling pathways, mechanical stresses also direct cytoskeletal protein accumulation [5-7]. A myosin-II-based mechanosensory system controls cellular contractility and shape during cytokinesis and under applied stress [6, 8]. In Dictyostelium, this system tunes myosin II accumulation by feedback through the actin network, particularly through the crosslinker cortexillin I. Cortexillin-binding IQGAPs are major regulators of this system. Here, we defined the short timescale dynamics of key cytoskeletal proteins during cytokinesis and under mechanical stress, using fluorescence recovery after photobleaching and fluorescence correlation spectroscopy, to examine the dynamic interplay between these proteins. Equatorially enriched proteins including cortexillin I, IQGAP2, and myosin II recovered much more slowly than actin and polar crosslinkers. The mobility of equatorial proteins was greatly reduced at the furrow compared to the interphase cortex, suggesting their stabilization during cytokinesis. This mobility shift did not arise from a single biochemical event, but rather from a global inhibition of protein dynamics by mechanical-stress-associated changes in the cytoskeletal structure. Mechanical tuning of contractile protein dynamics provides robustness to the cytoskeletal framework responsible for regulating cell shape and contributes to cytokinesis fidelity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Circuits regulating pleasure and happiness: the evolution of reward-seeking and misery-fleeing behavioral mechanisms in vertebrates.

PubMed

Loonen, Anton J M; Ivanova, Svetlana A

2015-01-01

The very first free-moving animals in the oceans over 540 million years ago must have been able to obtain food, territory, and shelter, as well as reproduce. Therefore, they would have needed regulatory mechanisms to induce movements enabling achievement of these prerequisites for survival. It can be useful to consider these mechanisms in primitive chordates, which represent our earliest ancestors, to develop hypotheses addressing how these essential parts of human behavior are regulated and relate to more sophisticated behavioral manifestations such as mood. An animal comparable to lampreys was the earliest known vertebrate with a modern forebrain consisting of old and new cortical parts. Lampreys have a separate dorsal pallium, the forerunner of the most recently developed part of the cerebral cortex. In addition, the lamprey extrapyramidal system (EPS), which regulates movement, is modern. However, in lampreys and their putative forerunners, the hagfishes, the striatum, which is the input part of this EPS, probably corresponds to the human centromedial amygdala, which in higher vertebrates is part of a system mediating fear and anxiety. Both animals have well-developed nuclear habenulae, which are involved in several critical behaviors; in lampreys this system regulates the reward system that reinforces appetitive-seeking behavior or the avoidance system that reinforces flight behavior resulting from negative inputs. Lampreys also have a distinct glutamatergic nucleus, the so-called habenula-projection globus pallidus, which receives input from glutamatergic and GABAergic signals and gives output to the lateral habenula. Via this route, this nucleus influences midbrain monoaminergic nuclei and regulates the food acquisition system. These various structures involved in motor regulation in the lampreys may be conserved in humans and include two complementary mechanisms for reward reinforcement and avoidance behaviors. The first system is associated with experiencing pleasure and the second with happiness. The activities of these mechanisms are regulated by a tract running via the habenula to the upper brainstem. Identifying the human correlate of the lamprey habenula-projecting globus pallidus may help in elucidating the mechanism of the antidepressant effects of glutamatergic drugs.

De novo design of a synthetic riboswitch that regulates transcription termination

PubMed Central

Wachsmuth, Manja; Findeiß, Sven; Weissheimer, Nadine; Stadler, Peter F.; Mörl, Mario

2013-01-01

Riboswitches are regulatory RNA elements typically located in the 5′-untranslated region of certain mRNAs and control gene expression at the level of transcription or translation. These elements consist of a sensor and an adjacent actuator domain. The sensor usually is an aptamer that specifically interacts with a ligand. The actuator contains an intrinsic terminator or a ribosomal binding site for transcriptional or translational regulation, respectively. Ligand binding leads to structural rearrangements of the riboswitch and to presentation or masking of these regulatory elements. Based on this modular organization, riboswitches are an ideal target for constructing synthetic regulatory systems for gene expression. Although riboswitches for translational control have been designed successfully, attempts to construct synthetic elements regulating transcription have failed so far. Here, we present an in silico pipeline for the rational design of synthetic riboswitches that regulate gene expression at the transcriptional level. Using the well-characterized theophylline aptamer as sensor, we designed the actuator part as RNA sequences that can fold into functional intrinsic terminator structures. In the biochemical characterization, several of the designed constructs show ligand-dependent control of gene expression in Escherichia coli, demonstrating that it is possible to engineer riboswitches not only for translational but also for transcriptional regulation. PMID:23275562

L-type Ca2+ channels in the heart: structure and regulation.

PubMed

Treinys, Rimantas; Jurevicius, Jonas

2008-01-01

This review analyzes the structure and regulation mechanisms of voltage-dependent L-type Ca(2+) channel in the heart. L-type Ca(2+) channels in the heart are composed of four different polypeptide subunits, and the pore-forming subunit alpha(1) is the most important part of the channel. In cardiac myocytes, Ca(2+) enter cell cytoplasm from extracellular space mainly through L-type Ca(2+) channels; these channels are very important system in heart Ca(2+) uptake regulation. L-type Ca(2+) channels are responsible for the activation of sarcoplasmic reticulum channels (RyR2) and force of muscle contraction generation in heart; hence, activity of the heart depends on L-type Ca(2+) channels. Phosphorylation of channel-forming subunits by different kinases is one of the most important ways to change the activity of L-type Ca(2+) channel. Additionally, the activity of L-type Ca(2+) channels depends on Ca(2+) concentration in cytoplasm. Ca(2+) current in cardiac cells can facilitate, and this process is regulated by phosphorylation of L-type Ca(2+) channels and intracellular Ca(2+) concentration. Disturbances in cellular Ca(2+) transport and regulation of L-type Ca(2+) channels are directly related to heart diseases, life quality, and life span.

POMC Neurons: From Birth to Death

PubMed Central

Toda, Chitoku; Santoro, Anna; Kim, Jung Dae

2017-01-01

The hypothalamus is an evolutionarily conserved brain structure that regulates an organism’s basic functions, such as homeostasis and reproduction. Several hypothalamic nuclei and neuronal circuits have been the focus of many studies to understand their role in regulating these basic functions. Within the hypothalamic neuronal populations, the arcuate melanocortin system plays a major role in controlling homeostatic functions. The arcuate pro-opiomelanocortin (POMC) neurons in particular have been shown to be critical regulators of metabolism and reproduction because of their projections to several brain areas both in and outside of the hypothalamus, such as autonomic regions of the brain stem and spinal cord. Here, we review and discuss the current understanding of POMC neurons from their development and intracellular regulators to their physiological functions and pathological dysregulation. PMID:28192062

Ferredoxin:thioredoxin reductase (FTR) links the regulation of oxygenic photosynthesis to deeply rooted bacteria.

PubMed

Balsera, Monica; Uberegui, Estefania; Susanti, Dwi; Schmitz, Ruth A; Mukhopadhyay, Biswarup; Schürmann, Peter; Buchanan, Bob B

2013-02-01

Uncovered in studies on photosynthesis 35 years ago, redox regulation has been extended to all types of living cells. We understand a great deal about the occurrence, function, and mechanism of action of this mode of regulation, but we know little about its origin and its evolution. To help fill this gap, we have taken advantage of available genome sequences that make it possible to trace the phylogenetic roots of members of the system that was originally described for chloroplasts-ferredoxin, ferredoxin:thioredoxin reductase (FTR), and thioredoxin as well as target enzymes. The results suggest that: (1) the catalytic subunit, FTRc, originated in deeply rooted microaerophilic, chemoautotrophic bacteria where it appears to function in regulating CO(2) fixation by the reverse citric acid cycle; (2) FTRc was incorporated into oxygenic photosynthetic organisms without significant structural change except for addition of a variable subunit (FTRv) seemingly to protect the Fe-S cluster against oxygen; (3) new Trxs and target enzymes were systematically added as evolution proceeded from bacteria through the different types of oxygenic photosynthetic organisms; (4) an oxygenic type of regulation preceded classical light-dark regulation in the regulation of enzymes of CO(2) fixation by the Calvin-Benson cycle; (5) FTR is not universally present in oxygenic photosynthetic organisms, and in certain early representatives is seemingly functionally replaced by NADP-thioredoxin reductase; and (6) FTRc underwent structural diversification to meet the ecological needs of a variety of bacteria and archaea.

Dynamics and Emergent Structures in Active Fluids

NASA Astrophysics Data System (ADS)

Baskaran, Aparna

2014-03-01

In this talk, we consider an active fluid of colloidal sized particles, with the primary manifestation of activity being a self-replenishing velocity along one body axis of the particle. This is a minimal model for varied systems such as bacterial colonies, cytoskeletal filament motility assays vibrated granular particles and self propelled diffusophoretic colloids, depending on the nature of interaction among the particles. Using microscopic Brownian dynamics simulations, coarse-graining using the tools of non-equilibrium statistical mechanics and analysis of macroscopic hydrodynamic theories, we characterize emergent structures seen in these systems, which are determined by the symmetry of the interactions among the active units, such as propagating density waves, dense stationary bands, asters and phase separated isotropic clusters. We identify a universal mechanism, termed ``self-regulation,'' as the underlying physics that leads to these structures in diverse systems. Support from NSF through DMR-1149266 and DMR-0820492.

A variable structure approach to robust control of VTOL aircraft

NASA Technical Reports Server (NTRS)

Calise, A. J.; Kramer, F.

1982-01-01

This paper examines the application of variable structure control theory to the design of a flight control system for the AV-8A Harrier in a hover mode. The objective in variable structure design is to confine the motion to a subspace of the total state space. The motion in this subspace is insensitive to system parameter variations and external disturbances that lie in the range space of the control. A switching type of control law results from the design procedure. The control system was designed to track a vector velocity command defined in the body frame. For comparison purposes, a proportional controller was designed using optimal linear regulator theory. Both control designs were first evaluated for transient response performance using a linearized model, then a nonlinear simulation study of a hovering approach to landing was conducted. Wind turbulence was modeled using a 1052 destroyer class air wake model.

NASA Requirements for Ground-Based Pressure Vessels and Pressurized Systems (PVS). Revision C

NASA Technical Reports Server (NTRS)

Greulich, Owen Rudolf

2017-01-01

The purpose of this document is to ensure the structural integrity of PVS through implementation of a minimum set of requirements for ground-based PVS in accordance with this document, NASA Policy Directive (NPD) 8710.5, NASA Safety Policy for Pressure Vessels and Pressurized Systems, NASA Procedural Requirements (NPR) 8715.3, NASA General Safety Program Requirements, applicable Federal Regulations, and national consensus codes and standards (NCS).

Crystal structure of Bacillus anthracis virulence regulator AtxA and effects of phosphorylated histidines on multimerization and activity

DOE PAGES

Hammerstrom, Troy G.; Horton, Lori B.; Swick, Michelle C.; ...

2014-12-30

The Bacillus anthracis virulence regulator AtxA controls transcription of the anthrax toxin genes and capsule biosynthesis operon. AtxA activity is elevated during growth in media containing glucose and CO 2/bicarbonate, and there is a positive correlation between the CO 2/bicarbonate signal, AtxA activity, and homomultimerization. AtxA activity is also affected by phosphorylation at specific histidines. We show that AtxA crystallizes as a dimer. Distinct folds associated with predicted DNA-binding domains (HTH1 and HTH2) and phosphoenolpyruvate: carbohydrate phosphotransferase system-regulated domains (PRD1 and PRD2) are apparent. We tested AtxA variants containing single and double phosphomimetic (His → Asp) and phosphoablative (His →more » Ala) amino acid changes for activity in B. anthracis cultures and for protein-protein interactions in cell lysates. Reduced activity of AtxA H199A, lack of multimerization and activity of AtxAH379D variants, and predicted structural changes associated with phosphorylation support a model for control of AtxA function. We propose that (1) in the AtxA dimer, phosphorylation of H199 in PRD1 affects HTH2 positioning, influencing DNA-binding; and (2) phosphorylation of H379 in PRD2 disrupts dimer formation. In conclusion, the AtxA structure is the first reported high-resolution full-length structure of a PRD-containing regulator and can serve as a model for proteins of this family, especially those that link virulence to bacterial metabolism.« less

Crystal structure of Bacillus anthracis virulence regulator AtxA and effects of phosphorylated histidines on multimerization and activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hammerstrom, Troy G.; Horton, Lori B.; Swick, Michelle C.

The Bacillus anthracis virulence regulator AtxA controls transcription of the anthrax toxin genes and capsule biosynthesis operon. AtxA activity is elevated during growth in media containing glucose and CO 2/bicarbonate, and there is a positive correlation between the CO 2/bicarbonate signal, AtxA activity, and homomultimerization. AtxA activity is also affected by phosphorylation at specific histidines. We show that AtxA crystallizes as a dimer. Distinct folds associated with predicted DNA-binding domains (HTH1 and HTH2) and phosphoenolpyruvate: carbohydrate phosphotransferase system-regulated domains (PRD1 and PRD2) are apparent. We tested AtxA variants containing single and double phosphomimetic (His → Asp) and phosphoablative (His →more » Ala) amino acid changes for activity in B. anthracis cultures and for protein-protein interactions in cell lysates. Reduced activity of AtxA H199A, lack of multimerization and activity of AtxAH379D variants, and predicted structural changes associated with phosphorylation support a model for control of AtxA function. We propose that (1) in the AtxA dimer, phosphorylation of H199 in PRD1 affects HTH2 positioning, influencing DNA-binding; and (2) phosphorylation of H379 in PRD2 disrupts dimer formation. In conclusion, the AtxA structure is the first reported high-resolution full-length structure of a PRD-containing regulator and can serve as a model for proteins of this family, especially those that link virulence to bacterial metabolism.« less

Crystal structure of B acillus anthracis virulence regulator AtxA and effects of phosphorylated histidines on multimerization and activity: AtxA multimerization, phosphorylation and activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hammerstrom, Troy G.; Horton, Lori B.; Swick, Michelle C.

2014-12-30

The Bacillus anthracis virulence regulator AtxA controls transcription of the anthrax toxin genes and capsule biosynthetic operon. AtxA activity is elevated during growth in media containing glucose and CO2/bicarbonate, and there is a positive correlation between the CO2/bicarbonate signal, AtxA activity and homomultimerization. AtxA activity is also affected by phosphorylation at specific histidines. We show that AtxA crystallizes as a dimer. Distinct folds associated with predicted DNA-binding domains (HTH1 and HTH2) and phosphoenolpyruvate: carbohydrate phosphotransferase system-regulated domains (PRD1 and PRD2) are apparent. We tested AtxA variants containing single and double phosphomimetic (HisAsp) and phosphoablative (HisAla) amino acid changes for activitymore » in B.anthracis cultures and for protein-protein interactions in cell lysates. Reduced activity of AtxA H199A, lack of multimerization and activity of AtxAH379D variants, and predicted structural changes associated with phosphorylation support a model for control of AtxA function. We propose that (i) in the AtxA dimer, phosphorylation of H199 in PRD1 affects HTH2 positioning, influencing DNA-binding; and (ii) phosphorylation of H379 in PRD2 disrupts dimer formation. The AtxA structure is the first reported high-resolution full-length structure of a PRD-containing regulator, and can serve as a model for proteins of this family, especially those that link virulence to bacterial metabolism.« less

Performance evaluation of functioning of natural-industrial system of mining-processing complex with help of analytical and mathematical models

NASA Astrophysics Data System (ADS)

Bosikov, I. I.; Klyuev, R. V.; Revazov, V. Ch; Pilieva, D. E.

2018-03-01

The article describes research and analysis of hazardous processes occurring in the natural-industrial system and effectiveness assessment of its functioning using mathematical models. Studies of the functioning regularities of the natural and industrial system are becoming increasingly relevant in connection with the formulation of the task of modernizing production and the economy of Russia as a whole. In connection with a significant amount of poorly structured data, it is complicated by regulations for the effective functioning of production processes, social and natural complexes, under which a sustainable development of the natural-industrial system of the mining and processing complex would be ensured. Therefore, the scientific and applied problems, the solution of which allows one to formalize the hidden structural functioning patterns of the natural-industrial system and to make managerial decisions of organizational and technological nature to improve the efficiency of the system, are very relevant.

Angiotensin (1-7) ameliorates the structural and biochemical alterations of ovariectomy-induced osteoporosis in rats via activation of ACE-2/Mas receptor axis.

PubMed

Abuohashish, Hatem M; Ahmed, Mohammed M; Sabry, Dina; Khattab, Mahmoud M; Al-Rejaie, Salim S

2017-05-23

The local and systemic renin angiotensin system (RAS) influences the skeletal system micro-structure and metabolism. Studies suggested angiotensin 1-7 (Ang(1-7)) as the beneficial RAS molecule via Mas receptor activation. This study examines the function of Ang(1-7) in bone micro-architecture and metabolism in an ovariectomized (OVX) rodent model of osteoporosis. OVX rats showed structural and bone metabolic degeneration in parallel with suppressed expressions of the angiotensin converting enzyme-2 (ACE-2)/Ang(1-7)/Mas components. The infusion of Ang(1-7) markedly alleviated the altered bone metabolism and significantly enhanced both trabecular (metaphyseal) and cortical (metaphyseal-diaphyseal) morphometry. Urinary and bones minerals were also improved in OVX rats by Ang(1-7). The infusion of the heptapeptide enhanced ACE-2/Mas receptor expressions, while down-regulated AngII, ACE, and AngII type-1 receptor (AT1R) in OVX animals. Moreover, Ang(1-7) markedly improved osteoprotegerin (OPG) and lowered receptor activator NF-κB ligand (RANKL) expressions. The defensive properties of Ang(1-7) on bone metabolism, structure and minerals were considerably eradicated after blockage of Mas receptor with A-779. Ang(1-7)-induced up-regulated ACE-2/Ang(1-7)/Mas cascade and OPG expressions were abolished and the expressions of ACE/AngII/AT1R and RANKL were provoked by A-779. These findings shows for the first time the novel valuable therapeutic role of Ang(1-7) on bone health and metabolism through the ACE-2/Mas cascade.

Design of distributed systems of hydrolithosphere processes management. A synthesis of distributed management systems

NASA Astrophysics Data System (ADS)

Pershin, I. M.; Pervukhin, D. A.; Ilyushin, Y. V.; Afanaseva, O. V.

2017-10-01

The paper considers an important problem of designing distributed systems of hydrolithosphere processes management. The control actions on the hydrolithosphere processes under consideration are implemented by a set of extractive wells. The article shows the method of defining the approximation links for description of the dynamic characteristics of hydrolithosphere processes. The structure of distributed regulators, used in the management systems by the considered processes, is presented. The paper analyses the results of the synthesis of the distributed management system and the results of modelling the closed-loop control system by the parameters of the hydrolithosphere process.

The desmoplakin–intermediate filament linkage regulates cell mechanics

PubMed Central

Broussard, Joshua A.; Yang, Ruiguo; Huang, Changjin; Nathamgari, S. Shiva P.; Beese, Allison M.; Godsel, Lisa M.; Hegazy, Marihan H.; Lee, Sherry; Zhou, Fan; Sniadecki, Nathan J.; Green, Kathleen J.; Espinosa, Horacio D.

2017-01-01

The translation of mechanical forces into biochemical signals plays a central role in guiding normal physiological processes during tissue development and homeostasis. Interfering with this process contributes to cardiovascular disease, cancer progression, and inherited disorders. The actin-based cytoskeleton and its associated adherens junctions are well-established contributors to mechanosensing and transduction machinery; however, the role of the desmosome–intermediate filament (DSM–IF) network is poorly understood in this context. Because a force balance among different cytoskeletal systems is important to maintain normal tissue function, knowing the relative contributions of these structurally integrated systems to cell mechanics is critical. Here we modulated the interaction between DSMs and IFs using mutant forms of desmoplakin, the protein bridging these structures. Using micropillar arrays and atomic force microscopy, we demonstrate that strengthening the DSM–IF interaction increases cell–substrate and cell–cell forces and cell stiffness both in cell pairs and sheets of cells. In contrast, disrupting the interaction leads to a decrease in these forces. These alterations in cell mechanics are abrogated when the actin cytoskeleton is dismantled. These data suggest that the tissue-specific variability in DSM–IF network composition provides an opportunity to differentially regulate tissue mechanics by balancing and tuning forces among cytoskeletal systems. PMID:28495795

Trends in the Restructuring of German Universities

ERIC Educational Resources Information Center

Pritchard, Rosalind

2006-01-01

What happens when a highly regulated educational system--one featuring academic freedom, a national outlook, and an input-oriented, state-run bureaucracy--attempts to internationalize and introduce management structures that are outcome-oriented, deregulated, and more efficient? In the case of Germany, examined in this article, it has long been…

Vocational Education in Japan and Texas. Policy Research Project Report 100.

ERIC Educational Resources Information Center

Texas Univ., Austin. Lyndon B. Johnson School of Public Affairs.

The divergent cultural patterns, philosophies of education, and basic structures of government in Japan and the United States have resulted in distinct differences between the educational systems of the two countries. The national government strictly regulates all aspects of Japanese education (including student achievement levels and the…

Production and regulation of functional amyloid curli fimbriae by Shiga toxin-producing Escherichia coli

USDA-ARS?s Scientific Manuscript database

Functional amyloid, in the form of adhesive fimbrial proteins termed curli, was first described in Salmonella and Escherichia coli. Curli fibers adhere to various host cells and structural proteins, interact with components of the host immune system, and participate in biofilm formation. Shiga toxin...

48 CFR 1436.570 - Prohibition against use of lead-based paint.

Code of Federal Regulations, 2012 CFR

2012-10-01

... lead-based paint. 1436.570 Section 1436.570 Federal Acquisition Regulations System DEPARTMENT OF THE... 1436.570 Prohibition against use of lead-based paint. (a) Definitions. As used in this section... of Lead-Based Paint, in solicitations and contracts when construction of residential structures or...

48 CFR 1436.570 - Prohibition against use of lead-based paint.

Code of Federal Regulations, 2014 CFR

2014-10-01

... lead-based paint. 1436.570 Section 1436.570 Federal Acquisition Regulations System DEPARTMENT OF THE... 1436.570 Prohibition against use of lead-based paint. (a) Definitions. As used in this section... of Lead-Based Paint, in solicitations and contracts when construction of residential structures or...

48 CFR 1436.570 - Prohibition against use of lead-based paint.

Code of Federal Regulations, 2013 CFR

2013-10-01

... lead-based paint. 1436.570 Section 1436.570 Federal Acquisition Regulations System DEPARTMENT OF THE... 1436.570 Prohibition against use of lead-based paint. (a) Definitions. As used in this section... of Lead-Based Paint, in solicitations and contracts when construction of residential structures or...

48 CFR 1436.570 - Prohibition against use of lead-based paint.

Code of Federal Regulations, 2011 CFR

2011-10-01

... lead-based paint. 1436.570 Section 1436.570 Federal Acquisition Regulations System DEPARTMENT OF THE... 1436.570 Prohibition against use of lead-based paint. (a) Definitions. As used in this section... of Lead-Based Paint, in solicitations and contracts when construction of residential structures or...

26 CFR 1.263(a)-0 - Outline of regulations under section 263(a).

Code of Federal Regulations, 2014 CFR

2014-04-01

... amounts paid for improvements. (e) Determining the unit of property. (1) In general. (2) Building. (i) In general. (ii) Application of improvement rules to a building. (A) Building structure. (B) Building system. (iii) Condominium. (A) In general. (B) Application of improvement rules to a condominium. (iv...

18 CFR 1304.409 - Indefinite or temporary moorage of recreational vessels.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 18 Conservation of Power and Water Resources 2 2010-04-01 2010-04-01 false Indefinite or temporary... TENNESSEE VALLEY AUTHORITY APPROVAL OF CONSTRUCTION IN THE TENNESSEE RIVER SYSTEM AND REGULATION OF STRUCTURES AND OTHER ALTERATIONS Miscellaneous § 1304.409 Indefinite or temporary moorage of recreational...

[Convergence of healthcare regulation in the Americas: history, development, and new challenges].

PubMed

Silva, Ana Paula Jucá; Tagliari, Patrícia Oliveira Pereira

2016-05-01

The present article describes the changing relationship among healthcare regulatory authorities in various international settings, with special emphasis on the Americas. As other sectors, healthcare also faces the need to regulate international practices, while at the same time taking into consideration the specific realities of each country. Regulatory convergence - a movement towards technical alignment to enable the adoption of local regulatory mechanisms that take into account internationally recognized standards and principles to promote a single sanitary goal - has emerged as a means to address this challenge. Organizations that already use this tool, such as the International Conference of Drug Regulatory Authorities (ICDRA), Pan American Network for Drug Regulatory Harmonization (PANDRH), International Generic Drug Regulators Programme (IGDRP), and the International Medical Device Regulators Forum (IMDRF), among others, are currently working to gather knowledge, data, and specialists from different countries to build an international technical and scientific standard that can be used for decision-making by local regulators. This would ensure convergence of national regulations despite the need to adapt international standards to local needs, structure, and capacities. The most recent resolutions issued by the World Health Organization recognize the need to bring regulatory systems closer to the reality of national healthcare systems, and underscore the advantages of using existing local guidelines as input for cooperation with regulatory authorities.

A role for the ESCRT system in cell division in archaea.

PubMed

Samson, Rachel Y; Obita, Takayuki; Freund, Stefan M; Williams, Roger L; Bell, Stephen D

2008-12-12

Archaea are prokaryotic organisms that lack endomembrane structures. However, a number of hyperthermophilic members of the Kingdom Crenarchaea, including members of the Sulfolobus genus, encode homologs of the eukaryotic endosomal sorting system components Vps4 and ESCRT-III (endosomal sorting complex required for transport-III). We found that Sulfolobus ESCRT-III and Vps4 homologs underwent regulation of their expression during the cell cycle. The proteins interacted and we established the structural basis of this interaction. Furthermore, these proteins specifically localized to the mid-cell during cell division. Overexpression of a catalytically inactive mutant Vps4 in Sulfolobus resulted in the accumulation of enlarged cells, indicative of failed cell division. Thus, the archaeal ESCRT system plays a key role in cell division.

Receptor for advanced glycation endproducts (RAGE) maintains pulmonary structure and regulates the response to cigarette smoke.

PubMed

Wolf, Lisa; Herr, Christian; Niederstraßer, Julia; Beisswenger, Christoph; Bals, Robert

2017-01-01

The receptor for advanced glycation endproducts (RAGE) is highly expressed in the lung but its physiological functions in this organ is still not completely understood. To determine the contribution of RAGE to physiological functions of the lung, we analyzed pulmonary mechanics and structure of wildtype and RAGE deficient (RAGE-/-) mice. RAGE deficiency spontaneously resulted in a loss of lung structure shown by an increased mean chord length, increased respiratory system compliance, decreased respiratory system elastance and increased concentrations of serum protein albumin in bronchoalveolar lavage fluids. Pulmonary expression of RAGE was mainly localized on alveolar epithelial cells and alveolar macrophages. Primary murine alveolar epithelial cells isolated from RAGE-/- mice revealed an altered differentiation and defective barrier formation under in vitro conditions. Stimulation of interferone-y (IFNy)-activated alveolar macrophages deficient for RAGE with Toll-like receptor (TLR) ligands resulted in significantly decreased release of proinflammatory cytokines and chemokines. Exposure to chronic cigarette smoke did not affect emphysema-like changes in lung parenchyma in RAGE-/- mice. Acute cigarette smoke exposure revealed a modified inflammatory response in RAGE-/- mice that was characterized by an influx of macrophages and a decreased keratinocyte-derived chemokine (KC) release. Our data suggest that RAGE regulates the differentiation of alveolar epithelial cells and impacts on the development and maintenance of pulmonary structure. In cigarette smoke-induced lung pathology, RAGE mediates inflammation that contributes to lung damage.

EHD proteins: Key conductors of endocytic transport

PubMed Central

Naslavsky, Naava; Caplan, Steve

2010-01-01

Regulation of endocytic transport is controlled by an elaborate network of proteins. Rab GTP-binding proteins and their effectors have well-defined roles in mediating specific endocytic transport steps, but until recently, less was known about the four mammalian dynamin-like C-terminal Eps15 Homology Domain (EHD) proteins that also regulate endocytic events. In recent years, however, great strides have been made in understanding the structure and function of these unique proteins. Indeed, a growing body of literature addresses EHD protein structure, interactions with binding partners, functions in mammalian cells, and the generation of various new model systems. Accordingly, this is now an opportune time to pause and review the function and mechanisms of action of EHD proteins, and to highlight some of the challenges and future directions for the field. PMID:21067929

Computational Study of the Genomic and Epigenomic Phenomena

NASA Astrophysics Data System (ADS)

Yang, Wenjing

Biological systems are perhaps the ultimate complex systems, uniquely capable of processing and communicating information, reproducing in their lifetimes, and adapting in evolutionary time scales. My dissertation research focuses on using computational approaches to understand the biocomplexity manifested in the multitude of length scales and time scales. At the molecular and cellular level, central to the complex behavior of a biological system is the regulatory network. My research study focused on epigenetics, which is essential for multicellular organisms to establish cellular identity during development or in response to intracellular and environmental stimuli. My computational study of epigenomics is greatly facilitated by recent advances in high-throughput sequencing technology, which enables high-resolution snapshots of epigenomes and transcriptomes. Using human CD4+ T cell as a model system, the dynamical changes in epigenome and transcriptome pertinent to T cell activation were investigated at the genome scale. Going beyond traditional focus on transcriptional regulation, I provided evidences that post-transcriptional regulation may serve as a major component of the regulatory network. In addition, I explored alternative polyadenylation, another novel aspect of gene regulation, and how it cross-talks with the local chromatin structure. As the renowned theoretical biologist Theodosius Dobzhansky said eloquently, "Nothing in biology makes sense except in the light of evolution''. To better understand this ubiquitous driving force in the biological world, I went beyond molecular events in a single organism, and investigated the dynamical changes of population structure along the evolutionary time scale. To this end, we used HIV virus population dynamics in the host immune system as a model system. The evolution of HIV viral population plays a key role in AIDS immunopathogenesis with its exceptionally high mutation rate. However, the theoretical studies of the effect of recombination have been rather limited. Given the phylogenetic and experimental evidences for the high recombination rate and its important role in HIV evolution and epidemics, I established a mathematical model to study the effect of recombination, and explored the complex behavior of this dynamics system.

On decentralized control of large-scale systems

NASA Technical Reports Server (NTRS)

Siljak, D. D.

1978-01-01

A scheme is presented for decentralized control of large-scale linear systems which are composed of a number of interconnected subsystems. By ignoring the interconnections, local feedback controls are chosen to optimize each decoupled subsystem. Conditions are provided to establish compatibility of the individual local controllers and achieve stability of the overall system. Besides computational simplifications, the scheme is attractive because of its structural features and the fact that it produces a robust decentralized regulator for large dynamic systems, which can tolerate a wide range of nonlinearities and perturbations among the subsystems.

Public Policy and Health Informatics.

PubMed

Bell, Katherine

2018-05-01

To provide an overview of the history of electronic health policy and identify significant laws that influence health informatics. US Department of Health and Human Services. The development of health information technology has influenced the process for delivering health care. Public policy and regulations are an important part of health informatics and establish the structure of electronic health systems. Regulatory bodies of the government initiate policies to ease the execution of electronic health record implementation. These same bureaucratic entities regulate the system to protect the rights of the patients and providers. Nurses should have an overall understanding of the system behind health informatics and be able to advocate for change. Nurses can utilize this information to optimize the use of health informatics and campaign for safe, effective, and efficient health information technology. Copyright © 2018 Elsevier Inc. All rights reserved.

Project WISH: The Emerald City

NASA Technical Reports Server (NTRS)

Oz, Hayrani; Dunne, Jim; Butchar, Stan; George, Tommy; Hellstrom, Rob; Kringen, Tricia; Owens, George; Perrea, Mike; Semeraro, Paul; Thorndike, Phil

1992-01-01

Phase 3 of Project WISH saw the evolution of the Emerald City (E-City) from a collection of specialized independent analyses and ideas to a working structural design integrated with major support systems and analyses. Emphasis was placed on comparing and contrasting the closed and open cycle gas core nuclear rocket engines to further determine the optimum propulsive system for the E-City. Power and thermal control requirements were then defined and the question of how to meet these requirements was addressed. Software was developed to automate the mission/system/configuration analysis so changes dictated by various subsystem constraints could be managed efficiently and analyzed interactively. In addition, the liquid hydrogen propellant tank was statically designed for minimum mass and shape optimization using a finite element modeling package called SDRC I-DEAS. Spoke and shaft cross-sectional areas were optimized on ASTROS (Automated Structural Optimization System) for mass minimization. A structural dynamic analysis of the optimal structure also conducted using ASTROS enabled a study of the modes, frequencies, displacements, and accelerations of the E-City. Finally, the attitude control system design began with an initial mass moment of inertia analysis and was then designed and optimized using linear quadratic regulator control theory.

Analysis of Regulatory Guidance for Health Monitoring

NASA Technical Reports Server (NTRS)

Munns, Thomas E.; Beard, Richard E.; Culp, Aubrey M.; Murphy, Dennis A.; Kent, Renee M.; Cooper, Eric G. (Technical Monitor)

2000-01-01

The purpose of this study was to assess the connection between current FAA regulations and the incorporation of Health Management (HM) systems into commercial aircraft. To address the overall objectives ARINC: (1) investigated FAA regulatory guidance, (2) investigated airline maintenance practices, (3) systematically identified regulations and practices that would be affected or could act as barriers to the introduction of HM technology, and (4) assessed regulatory and operational tradeoffs that should be considered for implementation. The assessment procedure was validated on a postulated structural HM capability for the B757 horizontal stabilizer.

Modal Filtering for Control of Flexible Aircraft

NASA Technical Reports Server (NTRS)

Suh, Peter M.; Mavris, Dimitri N.

2013-01-01

Modal regulators and deformation trackers are designed for an open-loop fluttering wing model. The regulators are designed with modal coordinate and accelerometer inputs respectively. The modal coordinates are estimated with simulated fiber optics. The robust stability of the closed-loop systems is compared in a structured singular-value vector analysis. Performance is evaluated and compared in a gust alleviation and flutter suppression simulation. For the same wing and flight condition two wing-shape-tracking control architectures are presented, which achieve deformation control at any point on the wing.

Modify the Histone to Win the Battle: Chromatin Dynamics in Plant–Pathogen Interactions

PubMed Central

Ramirez-Prado, Juan S.; Piquerez, Sophie J. M.; Bendahmane, Abdelhafid; Hirt, Heribert; Raynaud, Cécile; Benhamed, Moussa

2018-01-01

Relying on an immune system comes with a high energetic cost for plants. Defense responses in these organisms are therefore highly regulated and fine-tuned, permitting them to respond pertinently to the attack of a microbial pathogen. In recent years, the importance of the physical modification of chromatin, a highly organized structure composed of genomic DNA and its interacting proteins, has become evident in the research field of plant–pathogen interactions. Several processes, including DNA methylation, changes in histone density and variants, and various histone modifications, have been described as regulators of various developmental and defense responses. Herein, we review the state of the art in the epigenomic aspects of plant immunity, focusing on chromatin modifications, chromatin modifiers, and their physiological consequences. In addition, we explore the exciting field of understanding how plant pathogens have adapted to manipulate the plant epigenomic regulation in order to weaken their immune system and thrive in their host, as well as how histone modifications in eukaryotic pathogens are involved in the regulation of their virulence. PMID:29616066

Medication advertising in Brazil. Can it be regulated?

PubMed

Nascimento, Alvaro César

2009-01-01

The regulation of medication advertising in Brazil has four weak points. Inspection and punishment of irregularities is carried out a posteriori to the infraction being committed (when the population has already been exposed to a sanitary risk). The fines charged by the Brazilian Sanitary Surveillance Agency (Anvisa) have a derisory value compared to investments in advertising. There is no mechanism that prevents fines from being transferred to prices. The phrase 'If symptoms persist, consult your doctor', rather than warning about the risks of self-medication, encourages using at least the first medication without a prescription, advising a visit to the doctor only if symptoms persist. Anvisa data and academic studies reveal that 90% to 100% of advertising shown in the media contains irregularities. Thus, the Anvisa Collegiate Board of Directors Resolution 102/2000, which seeks to regulate the sector, makes up a system that benefits the infractor and keeps the population at risk. This work analyses alternative regulation, looking at advertising's previous compliance statute through the surveillance system; it studies international statutes and proposes an alteration in the structure of the current model, inserting the logic of sanitary risk prevention.

The Orphan Nuclear Receptor TR4 Is a Vitamin A-activated Nuclear Receptor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, X. Edward; Suino-Powell, Kelly M.; Xu, Yong

2015-11-30

Testicular receptors 2 and 4 (TR2/4) constitute a subgroup of orphan nuclear receptors that play important roles in spermatogenesis, lipid and lipoprotein regulation, and the development of the central nervous system. Currently, little is known about the structural features and the ligand regulation of these receptors. Here we report the crystal structure of the ligand-free TR4 ligand binding domain, which reveals an autorepressed conformation. The ligand binding pocket of TR4 is filled by the C-terminal half of helix 10, and the cofactor binding site is occupied by the AF-2 helix, thus preventing ligand-independent activation of the receptor. However, TR4 exhibitsmore » constitutive transcriptional activity on multiple promoters, which can be further potentiated by nuclear receptor coactivators. Mutations designed to disrupt cofactor binding, dimerization, or ligand binding substantially reduce the transcriptional activity of this receptor. Importantly, both retinol and retinoic acid are able to promote TR4 to recruit coactivators and to activate a TR4-regulated reporter. These findings demonstrate that TR4 is a ligand-regulated nuclear receptor and suggest that retinoids might have a much wider regulatory role via activation of orphan receptors such as TR4.« less

Structure-guided design and functional characterization of an artificial red light-regulated guanylate/adenylate cyclase for optogenetic applications.

PubMed

Etzl, Stefan; Lindner, Robert; Nelson, Matthew D; Winkler, Andreas

2018-06-08

Genetically targeting biological systems to control cellular processes with light is the concept of optogenetics. Despite impressive developments in this field, underlying molecular mechanisms of signal transduction of the employed photoreceptor modules are frequently not sufficiently understood to rationally design new optogenetic tools. Here, we investigate the requirements for functional coupling of red light-sensing phytochromes with non-natural enzymatic effectors by creating a series of constructs featuring the Deinococcus radiodurans bacteriophytochrome linked to a Synechocystis guanylate/adenylate cyclase. Incorporating characteristic structural elements important for cyclase regulation in our designs, we identified several red light-regulated fusions with promising properties. We provide details of one light-activated construct with low dark-state activity and high dynamic range that outperforms previous optogenetic tools in vitro and expands our in vivo toolkit, as demonstrated by manipulation of Caenorhabditis elegans locomotor activity. The full-length crystal structure of this phytochrome-linked cyclase revealed molecular details of photoreceptor-effector coupling, highlighting the importance of the regulatory cyclase element. Analysis of conformational dynamics by hydrogen-deuterium exchange in different functional states enriched our understanding of phytochrome signaling and signal integration by effectors. We found that light-induced conformational changes in the phytochrome destabilize the coiled-coil sensor-effector linker, which releases the cyclase regulatory element from an inhibited conformation, increasing cyclase activity of this artificial system. Future designs of optogenetic functionalities may benefit from our work, indicating that rational considerations for the effector improve the rate of success of initial designs to obtain optogenetic tools with superior properties. © 2018 Etzl et al.

Feline coronavirus: Insights into viral pathogenesis based on the spike protein structure and function.

PubMed

Jaimes, Javier A; Whittaker, Gary R

2018-04-01

Feline coronavirus (FCoV) is an etiological agent that causes a benign enteric illness and the fatal systemic disease feline infectious peritonitis (FIP). The FCoV spike (S) protein is considered the viral regulator for binding and entry to the cell. This protein is also involved in FCoV tropism and virulence, as well as in the switch from enteric disease to FIP. This regulation is carried out by spike's major functions: receptor binding and virus-cell membrane fusion. In this review, we address important aspects in FCoV genetics, replication and pathogenesis, focusing on the role of S. To better understand this, FCoV S protein models were constructed, based on the human coronavirus NL63 (HCoV-NL63) S structure. We describe the specific structural characteristics of the FCoV S, in comparison with other coronavirus spikes. We also revise the biochemical events needed for FCoV S activation and its relation to the structural features of the protein. Copyright © 2018 Elsevier Inc. All rights reserved.

Control of complex networks requires both structure and dynamics

NASA Astrophysics Data System (ADS)

Gates, Alexander J.; Rocha, Luis M.

2016-04-01

The study of network structure has uncovered signatures of the organization of complex systems. However, there is also a need to understand how to control them; for example, identifying strategies to revert a diseased cell to a healthy state, or a mature cell to a pluripotent state. Two recent methodologies suggest that the controllability of complex systems can be predicted solely from the graph of interactions between variables, without considering their dynamics: structural controllability and minimum dominating sets. We demonstrate that such structure-only methods fail to characterize controllability when dynamics are introduced. We study Boolean network ensembles of network motifs as well as three models of biochemical regulation: the segment polarity network in Drosophila melanogaster, the cell cycle of budding yeast Saccharomyces cerevisiae, and the floral organ arrangement in Arabidopsis thaliana. We demonstrate that structure-only methods both undershoot and overshoot the number and which sets of critical variables best control the dynamics of these models, highlighting the importance of the actual system dynamics in determining control. Our analysis further shows that the logic of automata transition functions, namely how canalizing they are, plays an important role in the extent to which structure predicts dynamics.

Parallel firing strategy on Petri nets: A review

NASA Astrophysics Data System (ADS)

Mavlankulov, Gairatzhan; Turaev, Sherzod; Zhumabaeva, Laula; Zhukabayeva, Tamara

2015-05-01

In this paper we review the recent results related on Petri net controlled grammars and the close related topics. Though the theme of regulated grammars is one of the classic topics in formal language theory, a Petri net controlled grammar is still interesting subject for the investigation for many reasons. This type of grammars can successfully be used in modeling new problems emerging in manufacturing systems, systems biology and other areas. Moreover, the graphically illustrability, the ability to represent both a grammar and its control in one structure, and the possibility to unify different regulated rewritings make this formalization attractive for the study. We also summarize the obtained results and propose a new conception such as parallel firing strategy on Petri Nets.

Structural and regulatory mutations in Vibrio parahaemolyticus type III secretion systems display variable effects on virulence.

PubMed

Calder, Thomas; de Souza Santos, Marcela; Attah, Victoria; Klimko, John; Fernandez, Jessie; Salomon, Dor; Krachler, Anne-Marie; Orth, Kim

2014-12-01

The Gram-negative bacterium, Vibrio parahaemolyticus, is a major cause of seafood-derived food poisoning throughout the world. The pathogenicity of V. parahaemolyticus is attributed to several virulence factors, including two type III secretion systems (T3SS), T3SS1 and T3SS2. Herein, we compare the virulence of V. parahaemolyticus POR strains, which harbor a mutation in the T3SS needle apparatus of either system, to V. parahaemolyticus CAB strains, which harbor mutations in positive transcriptional regulators of either system. These strains are derived from the clinical RIMD 2210633 strain. We demonstrate that each mutation affects the virulence of the bacterium in a different manner. POR and CAB strains exhibited similar levels of swarming motility and T3SS effector production and secretion, but the CAB3 and CAB4 strains, which harbor a mutation in the T3SS2 master regulator gene, formed reduced biofilm growth under T3SS2 inducing conditions. Additionally, while the cytotoxicity of the POR and CAB strains was similar, the CAB2 (T3SS1 regulatory mutant) strain was strikingly more invasive than the comparable POR2 (T3SS1 structural mutant) strain. In summary, creating structural or regulatory mutations in either T3SS1 or T3SS2 causes differential downstream effects on other virulence systems. Understanding the biological differences of strains created from a clinical isolate is critical for interpreting and understanding the pathogenic nature of V. parahaemolyticus. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Mathematical model of alternative mechanism of telomere length maintenance

NASA Astrophysics Data System (ADS)

Kollár, Richard; Bod'ová, Katarína; Nosek, Jozef; Tomáška, L'ubomír

2014-03-01

Biopolymer length regulation is a complex process that involves a large number of biological, chemical, and physical subprocesses acting simultaneously across multiple spatial and temporal scales. An illustrative example important for genomic stability is the length regulation of telomeres—nucleoprotein structures at the ends of linear chromosomes consisting of tandemly repeated DNA sequences and a specialized set of proteins. Maintenance of telomeres is often facilitated by the enzyme telomerase but, particularly in telomerase-free systems, the maintenance of chromosomal termini depends on alternative lengthening of telomeres (ALT) mechanisms mediated by recombination. Various linear and circular DNA structures were identified to participate in ALT, however, dynamics of the whole process is still poorly understood. We propose a chemical kinetics model of ALT with kinetic rates systematically derived from the biophysics of DNA diffusion and looping. The reaction system is reduced to a coagulation-fragmentation system by quasi-steady-state approximation. The detailed treatment of kinetic rates yields explicit formulas for expected size distributions of telomeres that demonstrate the key role played by the J factor, a quantitative measure of bending of polymers. The results are in agreement with experimental data and point out interesting phenomena: an appearance of very long telomeric circles if the total telomere density exceeds a critical value (excess mass) and a nonlinear response of the telomere size distributions to the amount of telomeric DNA in the system. The results can be of general importance for understanding dynamics of telomeres in telomerase-independent systems as this mode of telomere maintenance is similar to the situation in tumor cells lacking telomerase activity. Furthermore, due to its universality, the model may also serve as a prototype of an interaction between linear and circular DNA structures in various settings.

[Biotechnological functional systems].

PubMed

Bokser, O Ia

1999-01-01

Based on the theory of functional systems and a concept of the quantum system of behavior, studies of the quantumsystems were conducted. Their structure, the interaction of biological and technical sections were analyzed. Mathematical, biophysical, and experimental models were designed. The paper shows that biotechnical quantumsystems are involved in the formation of biological feedback. A system with imperative feedback from the programmed and introduced current results of efforts has been developed and put into practice for the self-regulation of muscle tension. Training by using this biological feedback system causes a stable increase in the perception rate of proprioceptive stimulus in examinees (operates, sportsmen, neurological patients).

Iron, copper, zinc, and manganese transport and regulation in pathogenic Enterobacteria: correlations between strains, site of infection and the relative importance of the different metal transport systems for virulence

PubMed Central

Porcheron, Gaëlle; Garénaux, Amélie; Proulx, Julie; Sabri, Mourad; Dozois, Charles M.

2013-01-01

For all microorganisms, acquisition of metal ions is essential for survival in the environment or in their infected host. Metal ions are required in many biological processes as components of metalloproteins and serve as cofactors or structural elements for enzymes. However, it is critical for bacteria to ensure that metal uptake and availability is in accordance with physiological needs, as an imbalance in bacterial metal homeostasis is deleterious. Indeed, host defense strategies against infection either consist of metal starvation by sequestration or toxicity by the highly concentrated release of metals. To overcome these host strategies, bacteria employ a variety of metal uptake and export systems and finely regulate metal homeostasis by numerous transcriptional regulators, allowing them to adapt to changing environmental conditions. As a consequence, iron, zinc, manganese, and copper uptake systems significantly contribute to the virulence of many pathogenic bacteria. However, during the course of our experiments on the role of iron and manganese transporters in extraintestinal Escherichia coli (ExPEC) virulence, we observed that depending on the strain tested, the importance of tested systems in virulence may be different. This could be due to the different set of systems present in these strains, but literature also suggests that as each pathogen must adapt to the particular microenvironment of its site of infection, the role of each acquisition system in virulence can differ from a particular strain to another. In this review, we present the systems involved in metal transport by Enterobacteria and the main regulators responsible for their controlled expression. We also discuss the relative role of these systems depending on the pathogen and the tissues they infect. PMID:24367764

Accountability in the UK Healthcare System: An Overview

PubMed Central

Peckham, Stephen

2014-01-01

Recent changes in the English National Health Service (NHS) have introduced new complexities into the accountability arrangements for healthcare services. This commentary describes how the new organizational structures have challenged the traditional centralized accountability structures by creating a more dispersed system of governance for local health-care commissioners. It sets the context of discussions about accountability in the UK NHS and then describes the key changes in England following the implementation of the NHS reforms in April 2013. The commentary concludes that while there is increased complexity of accountability within a more decentralized and fragmented healthcare system, the government's goal of achieving increased local autonomy and greater control by general practitioners (GPs) will probably not be realized. In particular, the system will continue to have strongly centralized aspects, with increased regulation and central political responsibility. PMID:25305399

Drosophila-Cdh1 (Rap/Fzr) a regulatory subunit of APC/C is required for synaptic morphology, synaptic transmission and locomotion.

PubMed

Wise, Alexandria; Schatoff, Emma; Flores, Julian; Hua, Shao-Ying; Ueda, Atsushi; Wu, Chun-Fang; Venkatesh, Tadmiri

2013-11-01

The assembly of functional synapses requires the orchestration of the synthesis and degradation of a multitude of proteins. Protein degradation and modification by the conserved ubiquitination pathway has emerged as a key cellular regulatory mechanism during nervous system development and function (Kwabe and Brose, 2011). The anaphase promoting complex/cyclosome (APC/C) is a multi-subunit ubiquitin ligase complex primarily characterized for its role in the regulation of mitosis (Peters, 2002). In recent years, a role for APC/C in nervous system development and function has been rapidly emerging (Stegmuller and Bonni, 2005; Li et al., 2008). In the mammalian central nervous system the activator subunit, APC/C-Cdh1, has been shown to be a regulator of axon growth and dendrite morphogenesis (Konishi et al., 2004). In the Drosophila peripheral nervous system (PNS), APC2, a ligase subunit of the APC/C complex has been shown to regulate synaptic bouton size and activity (van Roessel et al., 2004). To investigate the role of APC/C-Cdh1 at the synapse we examined loss-of-function mutants of Rap/Fzr (Retina aberrant in pattern/Fizzy related), a Drosophila homolog of the mammalian Cdh1 during the development of the larval neuromuscular junction in Drosophila. Our cell biological, ultrastructural, electrophysiological, and behavioral data showed that rap/fzr loss-of-function mutations lead to changes in synaptic structure and function as well as locomotion defects. Data presented here show changes in size and morphology of synaptic boutons, and, muscle tissue organization. Electrophysiological experiments show that loss-of-function mutants exhibit increased frequency of spontaneous miniature synaptic potentials, indicating a higher rate of spontaneous synaptic vesicle fusion events. In addition, larval locomotion and peristaltic movement were also impaired. These findings suggest a role for Drosophila APC/C-Cdh1 mediated ubiquitination in regulating synaptic morphology, function and integrity of muscle structure in the peripheral nervous system. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.

Delayed effects of flood control on a flood-dependent riparian forest

USGS Publications Warehouse

Katz, Gabrielle L.; Friedman, Jonathan M.; Beatty, Susan W.

2005-01-01

The downstream effects of dams on riparian forests are strongly mediated by the character and magnitude of adjustment of the fluvial–geomorphic system. To examine the effects of flow regulation on sand-bed streams in eastern Colorado, we studied the riparian forest on three river segments, the dam-regulated South Fork Republican River downstream of Bonny Dam, the unregulated South Fork Republican River upstream of Bonny Dam, and the unregulated Arikaree River. Although Bonny Dam significantly reduced peak and mean discharge downstream since 1951, there was little difference in forest structure between the regulated and unregulated segments. On all river segments, the riparian forest was dominated by the native pioneer tree, Populus deltoides, which became established during a period of channel narrowing beginning after the 1935 flood of record and ending by 1965. The nonnative Elaeagnus angustifolia was present on all river segments, with recruitment ongoing. The lack of contrast in forest structure between regulated and unregulated reaches resulted primarily from the fact that no large floods occurred on any of the study segments since dam construction. Most of the riparian forest in the study area was located on the broad narrowing terrace, which was rarely inundated on the unregulated segments, resulting in little contrast with the regulated segment. A minor dam effect occurred on the small modern floodplain, which was actively disturbed on the unregulated segments, but not on the regulated segments. Although Bonny Dam had the potential to significantly influence downstream riparian ecosystems, this influence had not been expressed, and may never be if a large flood does not occur within the lifetime of the dam. Minor dam effects to riparian systems can be expected downstream of large dams in some settings, including the present example in which there was insufficient time for the dam effects to by fully expressed.

Structural and legal implications of e-health.

PubMed

Terry, N P

2000-01-01

Web and attendant e-Commerce phenomena are irretrievably at odds with the traditional structure and hence legal regulation of health delivery. E-Health delivers healthcare information, diagnosis, treatment, care, and prescribing of drugs in a nonlinear, nonhierarchical manner that encourages patients to "enter" the system at an infinite number of points, thus defying current regulatory constructs. Similarly, e-Commerce fundamentals such as disintermediation and disaggregation result in medical information being delivered through unfamiliar channels, creating immensely difficult questions for health lawyers.

Environmental-stress-induced Chromatin Regulation and its Heritability

PubMed Central

Fang, Lei; Wuptra, Kenly; Chen, Danqi; Li, Hongjie; Huang, Shau-Ku; Jin, Chunyuan; Yokoyama, Kazunari K

2014-01-01

Chromatin is subject to proofreading and repair mechanisms during the process of DNA replication, as well as repair to maintain genetic and epigenetic information and genome stability. The dynamic structure of chromatin modulates various nuclear processes, including transcription and replication, by altering the accessibility of the DNA to regulatory factors. Structural changes in chromatin are affected by the chemical modification of histone proteins and DNA, remodeling of nucleosomes, incorporation of variant histones, noncoding RNAs, and nonhistone DNA-binding proteins. Phenotypic diversity and fidelity can be balanced by controlling stochastic switching of chromatin structure and dynamics in response to the environmental disruptors and endogenous stresses. The dynamic chromatin remodeling can, therefore, serve as a sensor, through which environmental and/or metabolic agents can alter gene expression, leading to global cellular changes involving multiple interactive networks. Furthermore its recent evidence also suggests that the epigenetic changes are heritable during the development. This review will discuss the environmental sensing system for chromatin regulation and genetic and epigenetic controls from developmental perspectives. PMID:25045581

The Structure of Sucrose Synthase-1 from Arabidopsis thaliana and Its Functional Implications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, Yi; Anderson, Spencer; Zhang, Yanfeng

2014-10-02

Sucrose transport is the central system for the allocation of carbon resources in vascular plants. During growth and development, plants control carbon distribution by coordinating sites of sucrose synthesis and cleavage in different plant organs and different cellular locations. Sucrose synthase, which reversibly catalyzes sucrose synthesis and cleavage, provides a direct and reversible means to regulate sucrose flux. Depending on the metabolic environment, sucrose synthase alters its cellular location to participate in cellulose, callose, and starch biosynthesis through its interactions with membranes, organelles, and cytoskeletal actin. The x-ray crystal structure of sucrose synthase isoform 1 from Arabidopsis thaliana (AtSus1) hasmore » been determined as a complex with UDP-glucose and as a complex with UDP and fructose, at 2.8- and 2.85-{angstrom} resolutions, respectively. The AtSus1 structure provides insights into sucrose catalysis and cleavage, as well as the regulation of sucrose synthase and its interactions with cellular targets.« less

Application of Contraction Mappings to the Control of Nonlinear Systems. Ph.D. Thesis

NASA Technical Reports Server (NTRS)

Killingsworth, W. R., Jr.

1972-01-01

The theoretical and applied aspects of successive approximation techniques are considered for the determination of controls for nonlinear dynamical systems. Particular emphasis is placed upon the methods of contraction mappings and modified contraction mappings. It is shown that application of the Pontryagin principle to the optimal nonlinear regulator problem results in necessary conditions for optimality in the form of a two point boundary value problem (TPBVP). The TPBVP is represented by an operator equation and functional analytic results on the iterative solution of operator equations are applied. The general convergence theorems are translated and applied to those operators arising from the optimal regulation of nonlinear systems. It is shown that simply structured matrices and similarity transformations may be used to facilitate the calculation of the matrix Green functions and the evaluation of the convergence criteria. A controllability theory based on the integral representation of TPBVP's, the implicit function theorem, and contraction mappings is developed for nonlinear dynamical systems. Contraction mappings are theoretically and practically applied to a nonlinear control problem with bounded input control and the Lipschitz norm is used to prove convergence for the nondifferentiable operator. A dynamic model representing community drug usage is developed and the contraction mappings method is used to study the optimal regulation of the nonlinear system.

Cardiac system bioenergetics: metabolic basis of the Frank-Starling law

PubMed Central

Saks, Valdur; Dzeja, Petras; Schlattner, Uwe; Vendelin, Marko; Terzic, Andre; Wallimann, Theo

2006-01-01

The fundamental principle of cardiac behaviour is described by the Frank-Starling law relating force of contraction during systole with end-diastolic volume. While both work and respiration rates increase linearly with imposed load, the basis of mechano-energetic coupling in heart muscle has remained a long-standing enigma. Here, we highlight advances made in understanding of complex cellular and molecular mechanisms that orchestrate coupling of mitochondrial oxidative phosphorylation with ATP utilization for muscle contraction. Cardiac system bioenergetics critically depends on an interrelated metabolic infrastructure regulating mitochondrial respiration and energy fluxes throughout cellular compartments. The data reviewed indicate the significance of two interrelated systems regulating mitochondrial respiration and energy fluxes in cells: (1) the creatine kinase, adenylate kinase and glycolytic pathways that communicate flux changes generated by cellular ATPases within structurally organized enzymatic modules and networks; and (2) a secondary system based on mitochondrial participation in cellular calcium cycle, which adjusts substrate oxidation and energy-transducing processes to meet increasing cellular energy demands. By conveying energetic signals to metabolic sensors, coupled phosphotransfer reactions provide a high-fidelity regulation of the excitation–contraction cycle. Such integration of energetics with calcium signalling systems provides the basis for ‘metabolic pacing’, synchronizing the cellular electrical and mechanical activities with energy supply processes. PMID:16410283

A non-ideal portal frame energy harvester controlled using a pendulum

NASA Astrophysics Data System (ADS)

Iliuk, I.; Balthazar, J. M.; Tusset, A. M.; Piqueira, J. R. C.; Rodrigues de Pontes, B.; Felix, J. L. P.; Bueno, Á. M.

2013-09-01

A model of energy harvester based on a simple portal frame structure is presented. The system is considered to be non-ideal system (NIS) due to interaction with the energy source, a DC motor with limited power supply and the system structure. The nonlinearities present in the piezoelectric material are considered in the piezoelectric coupling mathematical model. The system is a bi-stable Duffing oscillator presenting a chaotic behavior. Analyzing the average power variation, and bifurcation diagrams, the value of the control variable that optimizes power or average value that stabilizes the chaotic system in the periodic orbit is determined. The control sensitivity is determined to parametric errors in the damping and stiffness parameters of the portal frame. The proposed passive control technique uses a simple pendulum to tuned to the vibration of the structure to improve the energy harvesting. The results show that with the implementation of the control strategy it is possible to eliminate the need for active or semi active control, usually more complex. The control also provides a way to regulate the energy captured to a desired operating frequency.

Inverse problem studies of biochemical systems with structure identification of S-systems by embedding training functions in a genetic algorithm.

PubMed

Sarode, Ketan Dinkar; Kumar, V Ravi; Kulkarni, B D

2016-05-01

An efficient inverse problem approach for parameter estimation, state and structure identification from dynamic data by embedding training functions in a genetic algorithm methodology (ETFGA) is proposed for nonlinear dynamical biosystems using S-system canonical models. Use of multiple shooting and decomposition approach as training functions has been shown for handling of noisy datasets and computational efficiency in studying the inverse problem. The advantages of the methodology are brought out systematically by studying it for three biochemical model systems of interest. By studying a small-scale gene regulatory system described by a S-system model, the first example demonstrates the use of ETFGA for the multifold aims of the inverse problem. The estimation of a large number of parameters with simultaneous state and network identification is shown by training a generalized S-system canonical model with noisy datasets. The results of this study bring out the superior performance of ETFGA on comparison with other metaheuristic approaches. The second example studies the regulation of cAMP oscillations in Dictyostelium cells now assuming limited availability of noisy data. Here, flexibility of the approach to incorporate partial system information in the identification process is shown and its effect on accuracy and predictive ability of the estimated model are studied. The third example studies the phenomenological toy model of the regulation of circadian oscillations in Drosophila that follows rate laws different from S-system power-law. For the limited noisy data, using a priori information about properties of the system, we could estimate an alternate S-system model that showed robust oscillatory behavior with predictive abilities. Copyright © 2016 Elsevier Inc. All rights reserved.

The Hard Work of Interpretation: The National Politics of PISA Reception in Hungary and Romania

ERIC Educational Resources Information Center

Neumann, Eszter; Kiss, Adel; Fejes, Ildiko

2012-01-01

This article discusses the dynamic interaction between global policy and knowledge flows and two post-communist education systems--Hungary and Romania--with special attention to the appropriation of post-bureaucratic regulation tools and the structural changes enhanced by the knowledge transmitted by the Programme for International Student…

An AlgU-regulated antisense transcript encoded within the Pseudomonas syringae fleQ gene has a positive effect on motility

USDA-ARS?s Scientific Manuscript database

Bacterial flagella production is controlled by a multi-tiered regulatory system that coordinates expression of 40-50 subunits and correct assembly of these complicated structures. Flagellar expression is environmentally controlled, presumably to optimize the benefits and liabilities of flagellar ex...

Economics (A High School One Semester Course). Instructional Materials/Resources for Social Studies.

ERIC Educational Resources Information Center

Jackstadt, Stephen L.; And Others

Designed to aid teachers of a high school economics course, this curriculum guide is presented in self-contained units of study. Thirteen units, each with specific lessons, cover economic problems, the market system, market structure, market imperfections, government regulation, the national economy, aggregate supply and demand, the business…

36 CFR 13.1904 - Kennecott Mines National Historic Landmark (KNHL).

Code of Federal Regulations, 2011 CFR

2011-07-01

..., DEPARTMENT OF THE INTERIOR NATIONAL PARK SYSTEM UNITS IN ALASKA Special Regulations-Wrangell-St. Elias... and other mine openings; (c) Camping in or on any historic structure; and (d) Camping within the mill... center; and (e) Lighting or maintaining a fire within the mill site as defined in paragraph (d) of this...

Fire and the Design of Educational Buildings. Building Bulletin 7. Sixth Edition.

ERIC Educational Resources Information Center

Department of Education and Science, London (England).

This bulletin offers guidance on English school premises regulations applying to safety protection against fires in the following general areas: means of escape in case of fire; precautionary measures to prevent fire; fire warning systems and fire fighting; fire spreading speed; structures and materials resistant to fires; and damage control. It…

Two-component signal transduction systems of Xanthomonas spp.: a lesson from genomics.

PubMed

Qian, Wei; Han, Zhong-Ji; He, Chaozu

2008-02-01

The two-component signal transduction systems (TCSTSs), consisting of a histidine kinase sensor (HK) and a response regulator (RR), are the dominant molecular mechanisms by which prokaryotes sense and respond to environmental stimuli. Genomes of Xanthomonas generally contain a large repertoire of TCSTS genes (approximately 92 to 121 for each genome), which encode diverse structural groups of HKs and RRs. Among them, although a core set of 70 TCSTS genes (about two-thirds in total) which accumulates point mutations with a slow rate are shared by these genomes, the other genes, especially hybrid HKs, experienced extensive genetic recombination, including genomic rearrangement, gene duplication, addition or deletion, and fusion or fission. The recombinations potentially promote the efficiency and complexity of TCSTSs in regulating gene expression. In addition, our analysis suggests that a co-evolutionary model, rather than a selfish operon model, is the major mechanism for the maintenance and microevolution of TCSTS genes in the genomes of Xanthomonas. Genomic annotation, secondary protein structure prediction, and comparative genomic analyses of TCSTS genes reviewed here provide insights into our understanding of signal networks in these important phytopathogenic bacteria.

Role of Endogenous Sulfur Dioxide in Regulating Vascular Structural Remodeling in Hypertension

PubMed Central

Chen, Selena; Tang, Chaoshu

2016-01-01

Sulfur dioxide (SO2), an emerging gasotransmitter, was discovered to be endogenously generated in the cardiovascular system. Recently, the physiological effects of endogenous SO2 were confirmed. Vascular structural remodeling (VSR), an important pathological change in many cardiovascular diseases, plays a crucial role in the pathogenesis of the diseases. Here, the authors reviewed the research progress of endogenous SO2 in regulating VSR by searching the relevant data from PubMed and Medline. In spontaneously hypertensive rats (SHRs) and pulmonary hypertensive rats, SO2/aspartate aminotransferase (AAT) pathway was significantly altered. SO2 inhibited vascular smooth muscle cell (VSMC) proliferation, promoted apoptosis, inhibited the synthesis of extracellular collagen but promoted its degradation, and enhanced antioxidative capacity, thereby playing a significant role in attenuating VSR. However, the detailed mechanisms needed to be further explored. Further studies in this field would be important for the better understanding of the pathogenesis of systemic hypertension and pulmonary hypertension. Also, clinical trials are needed to demonstrate if SO2 would be a potential therapeutic target in cardiovascular diseases. PMID:27721913

The Relationship between Structure-Related Food Parenting Practices and Children's Heightened Levels of Self-Regulation in Eating.

PubMed

Frankel, Leslie A; Powell, Elisabeth; Jansen, Elena

Food parenting practices influence children's eating behaviors and weight status. Food parenting practices also influence children's self-regulatory abilities around eating, which has important implications for children's eating behaviors. The purpose of the following study is to examine use of structure-related food parenting practices and the potential impact on children's ability to self-regulate energy intake. Parents (n = 379) of preschool age children (M = 4.10 years, SD = 0.92) were mostly mothers (68.6%), Non-White (54.5%), and overweight/obese (50.1%). Hierarchical Multiple Regression was conducted to predict child self-regulation in eating from structure-related food parenting practices (structured meal setting, structured meal timing, family meal setting), while accounting for child weight status, parent age, gender, BMI, race, and yearly income. Hierarchical Multiple Regression results indicated that structure-related feeding practices (structured meal setting and family meal setting, but not structured meal timing) are associated with children's heightened levels of self-regulation in eating. Models examining the relationship within children who were normal weight and overweight/obese indicated the following: a relationship between structured meal setting and heightened self-regulation in eating for normal-weight children and a relationship between family meal setting and heightened self-regulation in eating for overweight/obese children. Researchers should further investigate these potentially modifiable parent feeding behaviors as a protective parenting technique, which possibly contributes to a healthy weight development by enhancing self-regulation in eating.

Causality, Randomness, Intelligibility, and the Epistemology of the Cell

PubMed Central

Dougherty, Edward R; Bittner, Michael L

2010-01-01

Because the basic unit of biology is the cell, biological knowledge is rooted in the epistemology of the cell, and because life is the salient characteristic of the cell, its epistemology must be centered on its livingness, not its constituent components. The organization and regulation of these components in the pursuit of life constitute the fundamental nature of the cell. Thus, regulation sits at the heart of biological knowledge of the cell and the extraordinary complexity of this regulation conditions the kind of knowledge that can be obtained, in particular, the representation and intelligibility of that knowledge. This paper is essentially split into two parts. The first part discusses the inadequacy of everyday intelligibility and intuition in science and the consequent need for scientific theories to be expressed mathematically without appeal to commonsense categories of understanding, such as causality. Having set the backdrop, the second part addresses biological knowledge. It briefly reviews modern scientific epistemology from a general perspective and then turns to the epistemology of the cell. In analogy with a multi-faceted factory, the cell utilizes a highly parallel distributed control system to maintain its organization and regulate its dynamical operation in the face of both internal and external changes. Hence, scientific knowledge is constituted by the mathematics of stochastic dynamical systems, which model the overall relational structure of the cell and how these structures evolve over time, stochasticity being a consequence of the need to ignore a large number of factors while modeling relatively few in an extremely complex environment. PMID:21119887

Conformational dynamism for DNA interaction in the Salmonella RcsB response regulator.

PubMed

Casino, Patricia; Miguel-Romero, Laura; Huesa, Juanjo; García, Pablo; García-Del Portillo, Francisco; Marina, Alberto

2018-01-09

The RcsCDB phosphorelay system controls an extremely large regulon in Enterobacteriaceae that involves processes such as biofilm formation, flagella production, synthesis of extracellular capsules and cell division. Therefore, fine-tuning of this system is essential for virulence in pathogenic microorganisms of this group. The final master effector of the RcsCDB system is the response regulator (RR) RcsB, which activates or represses multiple genes by binding to different promoter regions. This regulatory activity of RcsB can be done alone or in combination with additional transcriptional factors in phosphorylated or dephosphorylated states. The capacity of RcsB to interact with multiple promoters and partners, either dephosphorylated or phosphorylated, suggests an extremely conformational dynamism for this RR. To shed light on the activation mechanism of RcsB and its implication on promoter recognition, we solved the crystal structure of full-length RcsB from Salmonella enterica serovar Typhimurium in the presence and absence of a phosphomimetic molecule BeF3-. These two novel structures have guided an extensive site-directed mutagenesis study at the structural and functional level that confirms RcsB conformational plasticity and dynamism. Our data allowed us to propose a β5-T switch mechanism where phosphorylation is coupled to alternative DNA binding ways and which highlights the conformational dynamism of RcsB to be so pleiotropic. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Systems Mechanobiology: Tension-Inhibited Protein Turnover Is Sufficient to Physically Control Gene Circuits

PubMed Central

Dingal, P.C. Dave P.; Discher, Dennis E.

2014-01-01

Mechanotransduction pathways convert forces that stress and strain structures within cells into gene expression levels that impact development, homeostasis, and disease. The levels of some key structural proteins in the nucleus, cytoskeleton, or extracellular matrix have been recently reported to scale with tissue- and cell-level forces or mechanical properties such as stiffness, and so the mathematics of mechanotransduction becomes important to understand. Here, we show that if a given structural protein positively regulates its own gene expression, then stresses need only inhibit degradation of that protein to achieve stable, mechanosensitive gene expression. This basic use-it-or-lose-it module is illustrated by application to meshworks of nuclear lamin A, minifilaments of myosin II, and extracellular matrix collagen fibers—all of which possess filamentous coiled-coil/supercoiled structures. Past experiments not only suggest that tension suppresses protein degradation mediated and/or initiated by various enzymes but also that transcript levels vary with protein levels because key transcription factors are regulated by these structural proteins. Coupling between modules occurs within single cells and between cells in tissue, as illustrated during embryonic heart development where cardiac fibroblasts make collagen that cardiomyocytes contract. With few additional assumptions, the basic module has sufficient physics to control key structural genes in both development and disease. PMID:25468352

Hotspots for allosteric regulation on protein surfaces

PubMed Central

Reynolds, Kimberly A.; McLaughlin, Richard N.; Ranganathan, Rama

2012-01-01

Recent work indicates a general architecture for proteins in which sparse networks of physically contiguous and co-evolving amino acids underlie basic aspects of structure and function. These networks, termed sectors, are spatially organized such that active sites are linked to many surface sites distributed throughout the structure. Using the metabolic enzyme dihydrofolate reductase as a model system, we show that (1) the sector is strongly correlated to a network of residues undergoing millisecond conformational fluctuations associated with enzyme catalysis and (2) sector-connected surface sites are statistically preferred locations for the emergence of allosteric control in vivo. Thus, sectors represent an evolutionarily conserved “wiring” mechanism that can enable perturbations at specific surface positions to rapidly initiate conformational control over protein function. These findings suggest that sectors enable the evolution of intermolecular communication and regulation. PMID:22196731

New Exoskeleton Arm Concept Design And Actuation For Haptic Interaction With Virtual Objects

NASA Astrophysics Data System (ADS)

Chakarov, D.; Veneva, I.; Tsveov, M.; Tiankov, T.

2014-12-01

In the work presented in this paper the conceptual design and actuation of one new exoskeleton of the upper limb is presented. The device is designed for application where both motion tracking and force feedback are required, such as human interaction with virtual environment or rehabilitation tasks. The choice is presented of mechanical structure kinematical equivalent to the structure of the human arm. An actuation system is selected based on braided pneumatic muscle actuators. Antagonistic drive system for each joint is shown, using pulley and cable transmissions. Force/displacement diagrams are presented of two antagonistic acting muscles. Kinematics and dynamic estimations are performed of the system exoskeleton and upper limb. Selected parameters ensure in the antagonistic scheme joint torque regulation and human arm range of motion.

Self-organization and feedback effects in the shock compressed media

NASA Astrophysics Data System (ADS)

Khantuleva, Tatyana

2005-07-01

New theoretical approach to the transport in condensed matter far from equilibrium combines methods of statistical mechanics and cybernetic physics in order to construct closed mathematical model of a system with self-organization and self-regulation. Mesoscopic effects are considered as a result of the structure formation and the feedback effects in an open system under dynamic loading. Nonequilibrium state equations had been involved to incorporate the velocity dispersion. Integrodifferential balance equations describe both wave and dissipative transport properties. Boundary conditions determine the internal scale spectra. The model is completed by the feedback that introduces the structure evolution basing the methods of cybernetic physics. The obtained results open a wide prospective for the control methods in applications to new technologies, intellectual systems and prediction of catastrophic phenomena.

Translational neurocardiology: preclinical models and cardioneural integrative aspects

PubMed Central

Andresen, M. C.; Armour, J. A.; Billman, G. E.; Chen, P.‐S.; Foreman, R. D.; Herring, N.; O'Leary, D. S.; Sabbah, H. N.; Schultz, H. D.; Sunagawa, K.; Zucker, I. H.

2016-01-01

Abstract Neuronal elements distributed throughout the cardiac nervous system, from the level of the insular cortex to the intrinsic cardiac nervous system, are in constant communication with one another to ensure that cardiac output matches the dynamic process of regional blood flow demand. Neural elements in their various ‘levels’ become differentially recruited in the transduction of sensory inputs arising from the heart, major vessels, other visceral organs and somatic structures to optimize neuronal coordination of regional cardiac function. This White Paper will review the relevant aspects of the structural and functional organization for autonomic control of the heart in normal conditions, how these systems remodel/adapt during cardiac disease, and finally how such knowledge can be leveraged in the evolving realm of autonomic regulation therapy for cardiac therapeutics. PMID:27098459

Moving HAIRS: Towards adaptive, homeostatic materials

NASA Astrophysics Data System (ADS)

Aizenberg, Joanna

Dynamic structures that respond reversibly to changes in their environment are central to self-regulating thermal and lighting systems, targeted drug delivery, sensors, and self-propelled locomotion. Since an adaptive change requires energy input, an ideal strategy would be to design materials that harvest energy directly from the environment and use it to drive an appropriate response. This lecture will present the design of a novel class of reconfigurable materials that use surfaces bearing arrays of nanostructures put in motion by environment-responsive gels. Their unique hybrid architecture, and chemical and mechanical properties can be optimized to confer a wide range of adaptive behaviors. Using both experimental and modeling approaches, we are developing these hydrogel-actuated integrated responsive systems (HAIRS) as new materials with reversible optical and wetting properties, as a multifunctional platform for controlling cell differentiation and function, and as a first homeostatic system with autonomous self-regulation.

Leukemia inhibitory factor: part of a large ingathering family.

PubMed

Taupin, J L; Pitard, V; Dechanet, J; Miossec, V; Gualde, N; Moreau, J F

1998-01-01

Leukemia Inhibitory Factor (LIF) has a wide variety of biological activities. It regulates the differentiation of embryonic stem cells, neural cells, osteoblasts, adipocytes, hepatocytes and kidney epithelial cells. It also triggers the proliferation of myoblasts, primordial germ cells and some endothelial cells. Many of these biological functions parallel those of interleukin-6, Oncostatin M, ciliary neurotrophic factor, interleukin-11 and cardiotrophin-1. These structurally related cytokines also share subunits of their receptors which could partially explain the redundancy in this system of soluble mediators. In vivo LIF proves important in regulating the inflammatory response by fine tuning of the delicate balance of at least four systems in the body, namely the immune, the hematopoietic, the nervous and the endocrine systems. Although we are far from its therapeutic applications, the fast increasing knowledge in this field may bring new insights for the understanding of the cytokine biology in general.

Quorum Sensing Influences Burkholderia thailandensis Biofilm Development and Matrix Production.

PubMed

Tseng, Boo Shan; Majerczyk, Charlotte D; Passos da Silva, Daniel; Chandler, Josephine R; Greenberg, E Peter; Parsek, Matthew R

2016-10-01

Members of the genus Burkholderia are known to be adept at biofilm formation, which presumably assists in the survival of these organisms in the environment and the host. Biofilm formation has been linked to quorum sensing (QS) in several bacterial species. In this study, we characterized Burkholderia thailandensis biofilm development under flow conditions and sought to determine whether QS contributes to this process. B. thailandensis biofilm formation exhibited an unusual pattern: the cells formed small aggregates and then proceeded to produce mature biofilms characterized by "dome" structures filled with biofilm matrix material. We showed that this process was dependent on QS. B. thailandensis has three acyl-homoserine lactone (AHL) QS systems (QS-1, QS-2, and QS-3). An AHL-negative strain produced biofilms consisting of cell aggregates but lacking the matrix-filled dome structures. This phenotype was rescued via exogenous addition of the three AHL signals. Of the three B. thailandensis QS systems, we show that QS-1 is required for proper biofilm development, since a btaR1 mutant, which is defective in QS-1 regulation, forms biofilms without these dome structures. Furthermore, our data show that the wild-type biofilm biomass, as well as the material inside the domes, stains with a fucose-binding lectin. The btaR1 mutant biofilms, however, are negative for fucose staining. This suggests that the QS-1 system regulates the production of a fucose-containing exopolysaccharide in wild-type biofilms. Finally, we present data showing that QS ability during biofilm development produces a biofilm that is resistant to dispersion under stress conditions. The saprophyte Burkholderia thailandensis is a close relative of the pathogenic bacterium Burkholderia pseudomallei, the causative agent of melioidosis, which is contracted from its environmental reservoir. Since most bacteria in the environment reside in biofilms, B. thailandensis is an ideal model organism for investigating questions in Burkholderia physiology. In this study, we characterized B. thailandensis biofilm development and sought to determine if quorum sensing (QS) contributes to this process. Our work shows that B. thailandensis produces biofilms with unusual dome structures under flow conditions. Our findings suggest that these dome structures are filled with a QS-regulated, fucose-containing exopolysaccharide that may be involved in the resilience of B. thailandensis biofilms against changes in the nutritional environment. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Tenascin-C and mechanotransduction in the development and diseases of cardiovascular system

PubMed Central

Imanaka-Yoshida, Kyoko; Aoki, Hiroki

2014-01-01

Living tissue is composed of cells and extracellular matrix (ECM). In the heart and blood vessels, which are constantly subjected to mechanical stress, ECM molecules form well-developed fibrous frameworks to maintain tissue structure. ECM is also important for biological signaling, which influences various cellular functions in embryonic development, and physiological/pathological responses to extrinsic stimuli. Among ECM molecules, increased attention has been focused on matricellular proteins. Matricellular proteins are a growing group of non-structural ECM proteins highly up-regulated at active tissue remodeling, serving as biological mediators. Tenascin-C (TNC) is a typical matricellular protein, which is highly expressed during embryonic development, wound healing, inflammation, and cancer invasion. The expression is tightly regulated, dependent on the microenvironment, including various growth factors, cytokines, and mechanical stress. In the heart, TNC appears in a spatiotemporal-restricted manner during early stages of development, sparsely detected in normal adults, but transiently re-expressed at restricted sites associated with tissue injury and inflammation. Similarly, in the vascular system, TNC is strongly up-regulated during embryonic development and under pathological conditions with an increase in hemodynamic stress. Despite its intriguing expression pattern, cardiovascular system develops normally in TNC knockout mice. However, deletion of TNC causes acute aortic dissection (AAD) under strong mechanical and humoral stress. Accumulating reports suggest that TNC may modulate the inflammatory response and contribute to elasticity of the tissue, so that it may protect cardiovascular tissue from destructive stress responses. TNC may be a key molecule to control cellular activity during development, adaptation, or pathological tissue remodeling. PMID:25120494

[Drug Dependence and Cytotoxicity of Law-evading Drugs: Their Identities Explored from Basic Research].

PubMed

Funada, Masahiko

2016-01-01

  Cases of people experiencing disturbed consciousness or dyspnea, causing traffic accidents, or requiring ambulance transport to hospital due to abuse of law-evading chemical substances have become a serious social problem in Japan. Most law-evading herbal products are marketed as incense or herbs and consist of finely chopped, dry vegetative matter mixed with chemical substances (drugs). Analysis of the chemical substances in these herbal products has demonstrated that they contain synthetic cannabinoids. Because there are many cannabinoid compounds, even if a particular drug is regulated, similar compounds that differ only slightly in structure may be added in their place. Therefore a cat-and-mouse game exists between regulations on chemical substances and their propagation. This paper summarizes the pharmacological actions and dangers of chemical substances contained in law-evading herbal products by focusing on synthetic cannabinoids, as a group of chemical substances contained in these products. Furthermore, comprehensive designations of synthetic cannabinoids have been introduced as a new method of regulation that emphasizes the similarity of chemical structures; this paper also outlines the comprehensive designations. We established a psychic-dependence liability and cytotoxicity screening system for synthetic cannabinoids using animals (behavioral analysis in vivo) and cell cultures (cytotoxicity analysis in vitro). With our drug-screening system, we were able rapidly to evaluate and quantify psychic-dependence liabilities and cytotoxicity of synthetic cannabinoids contained in law-evading herbal products. These scientific data using our screening system contributed to the establishment of legislation for comprehensive designations of synthetic cannabinoids.

Analysis 320 coal mine accidents using structural equation modeling with unsafe conditions of the rules and regulations as exogenous variables.

PubMed

Zhang, Yingyu; Shao, Wei; Zhang, Mengjia; Li, Hejun; Yin, Shijiu; Xu, Yingjun

2016-07-01

Mining has been historically considered as a naturally high-risk industry worldwide. Deaths caused by coal mine accidents are more than the sum of all other accidents in China. Statistics of 320 coal mine accidents in Shandong province show that all accidents contain indicators of "unsafe conditions of the rules and regulations" with a frequency of 1590, accounting for 74.3% of the total frequency of 2140. "Unsafe behaviors of the operator" is another important contributory factor, which mainly includes "operator error" and "venturing into dangerous places." A systems analysis approach was applied by using structural equation modeling (SEM) to examine the interactions between the contributory factors of coal mine accidents. The analysis of results leads to three conclusions. (i) "Unsafe conditions of the rules and regulations," affect the "unsafe behaviors of the operator," "unsafe conditions of the equipment," and "unsafe conditions of the environment." (ii) The three influencing factors of coal mine accidents (with the frequency of effect relation in descending order) are "lack of safety education and training," "rules and regulations of safety production responsibility," and "rules and regulations of supervision and inspection." (iii) The three influenced factors (with the frequency in descending order) of coal mine accidents are "venturing into dangerous places," "poor workplace environment," and "operator error." Copyright © 2016 Elsevier Ltd. All rights reserved.

Regulating plant physiology with organic electronics.

PubMed

Poxson, David J; Karady, Michal; Gabrielsson, Roger; Alkattan, Aziz Y; Gustavsson, Anna; Doyle, Siamsa M; Robert, Stéphanie; Ljung, Karin; Grebe, Markus; Simon, Daniel T; Berggren, Magnus

2017-05-02

The organic electronic ion pump (OEIP) provides flow-free and accurate delivery of small signaling compounds at high spatiotemporal resolution. To date, the application of OEIPs has been limited to delivery of nonaromatic molecules to mammalian systems, particularly for neuroscience applications. However, many long-standing questions in plant biology remain unanswered due to a lack of technology that precisely delivers plant hormones, based on cyclic alkanes or aromatic structures, to regulate plant physiology. Here, we report the employment of OEIPs for the delivery of the plant hormone auxin to induce differential concentration gradients and modulate plant physiology. We fabricated OEIP devices based on a synthesized dendritic polyelectrolyte that enables electrophoretic transport of aromatic substances. Delivery of auxin to transgenic Arabidopsis thaliana seedlings in vivo was monitored in real time via dynamic fluorescent auxin-response reporters and induced physiological responses in roots. Our results provide a starting point for technologies enabling direct, rapid, and dynamic electronic interaction with the biochemical regulation systems of plants.

Regulating plant physiology with organic electronics

PubMed Central

Poxson, David J.; Karady, Michal; Alkattan, Aziz Y.; Gustavsson, Anna; Robert, Stéphanie; Grebe, Markus; Berggren, Magnus

2017-01-01

The organic electronic ion pump (OEIP) provides flow-free and accurate delivery of small signaling compounds at high spatiotemporal resolution. To date, the application of OEIPs has been limited to delivery of nonaromatic molecules to mammalian systems, particularly for neuroscience applications. However, many long-standing questions in plant biology remain unanswered due to a lack of technology that precisely delivers plant hormones, based on cyclic alkanes or aromatic structures, to regulate plant physiology. Here, we report the employment of OEIPs for the delivery of the plant hormone auxin to induce differential concentration gradients and modulate plant physiology. We fabricated OEIP devices based on a synthesized dendritic polyelectrolyte that enables electrophoretic transport of aromatic substances. Delivery of auxin to transgenic Arabidopsis thaliana seedlings in vivo was monitored in real time via dynamic fluorescent auxin-response reporters and induced physiological responses in roots. Our results provide a starting point for technologies enabling direct, rapid, and dynamic electronic interaction with the biochemical regulation systems of plants. PMID:28420793

Investigating neuronal function with optically controllable proteins

PubMed Central

Zhou, Xin X.; Pan, Michael; Lin, Michael Z.

2015-01-01

In the nervous system, protein activities are highly regulated in space and time. This regulation allows for fine modulation of neuronal structure and function during development and adaptive responses. For example, neurite extension and synaptogenesis both involve localized and transient activation of cytoskeletal and signaling proteins, allowing changes in microarchitecture to occur rapidly and in a localized manner. To investigate the role of specific protein regulation events in these processes, methods to optically control the activity of specific proteins have been developed. In this review, we focus on how photosensory domains enable optical control over protein activity and have been used in neuroscience applications. These tools have demonstrated versatility in controlling various proteins and thereby cellular functions, and possess enormous potential for future applications in nervous systems. Just as optogenetic control of neuronal firing using opsins has changed how we investigate the function of cellular circuits in vivo, optical control may yet yield another revolution in how we study the circuitry of intracellular signaling in the brain. PMID:26257603

Structure, signaling mechanism and regulation of the natriuretic peptide receptor guanylate cyclase.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Misono, K. S.; Philo, J. S.; Arakawa, T.

2011-06-01

Atrial natriuretic peptide (ANP) and the homologous B-type natriuretic peptide are cardiac hormones that dilate blood vessels and stimulate natriuresis and diuresis, thereby lowering blood pressure and blood volume. ANP and B-type natriuretic peptide counterbalance the actions of the renin-angiotensin-aldosterone and neurohormonal systems, and play a central role in cardiovascular regulation. These activities are mediated by natriuretic peptide receptor-A (NPRA), a single transmembrane segment, guanylyl cyclase (GC)-linked receptor that occurs as a homodimer. Here, we present an overview of the structure, possible chloride-mediated regulation and signaling mechanism of NPRA and other receptor GCs. Earlier, we determined the crystal structures ofmore » the NPRA extracellular domain with and without bound ANP. Their structural comparison has revealed a novel ANP-induced rotation mechanism occurring in the juxtamembrane region that apparently triggers transmembrane signal transduction. More recently, the crystal structures of the dimerized catalytic domain of green algae GC Cyg12 and that of cyanobacterium GC Cya2 have been reported. These structures closely resemble that of the adenylyl cyclase catalytic domain, consisting of a C1 and C2 subdomain heterodimer. Adenylyl cyclase is activated by binding of G{sub s}{alpha} to C2 and the ensuing 7{sup o} rotation of C1 around an axis parallel to the central cleft, thereby inducing the heterodimer to adopt a catalytically active conformation. We speculate that, in NPRA, the ANP-induced rotation of the juxtamembrane domains, transmitted across the transmembrane helices, may induce a similar rotation in each of the dimerized GC catalytic domains, leading to the stimulation of the GC catalytic activity.« less

Modelling of flow processes of the structured two-phase disperse systems (solid phase-liquid medium).

PubMed

Uriev, N B; Kuchin, I V

2007-10-31

A review of the basic theories and models of shear flow of suspensions is presented and the results of modeling of structured suspensions under flow conditions. The physical backgrounds and conditions of macroscopic discontinuity in the behaviour of high-concentrated systems are analyzed. The use of surfactants and imposed vibration for regulation of rheological properties of suspensions are considered. A review of the recent approaches and methods of computer simulation of concentrated suspensions is undertaken and results of computer simulation of suspensions are presented. Formation and destruction of the structure of suspension under static and dynamic conditions (including imposed combined shear and orthogonal oscillations) are discussed. The influence of interaction of particles as well as of some parameters characterizing a type and intensity of external perturbations on suspensions behavior is demonstrated.

Genetic variations in the serotonergic system contribute to amygdala volume in humans.

PubMed

Li, Jin; Chen, Chunhui; Wu, Karen; Zhang, Mingxia; Zhu, Bi; Chen, Chuansheng; Moyzis, Robert K; Dong, Qi

2015-01-01

The amygdala plays a critical role in emotion processing and psychiatric disorders associated with emotion dysfunction. Accumulating evidence suggests that amygdala structure is modulated by serotonin-related genes. However, there is a gap between the small contributions of single loci (less than 1%) and the reported 63-65% heritability of amygdala structure. To understand the "missing heritability," we systematically explored the contribution of serotonin genes on amygdala structure at the gene set level. The present study of 417 healthy Chinese volunteers examined 129 representative polymorphisms in genes from multiple biological mechanisms in the regulation of serotonin neurotransmission. A system-level approach using multiple regression analyses identified that nine SNPs collectively accounted for approximately 8% of the variance in amygdala volume. Permutation analyses showed that the probability of obtaining these findings by chance was low (p = 0.043, permuted for 1000 times). Findings showed that serotonin genes contribute moderately to individual differences in amygdala volume in a healthy Chinese sample. These results indicate that the system-level approach can help us to understand the genetic basis of a complex trait such as amygdala structure.

Institutions, incentives and the future of fisheries

PubMed Central

Hilborn, Ray; Orensanz, J. M. (Lobo); Parma, Ana M.

2005-01-01

Fisheries around the world are managed with a broad range of institutional structures. Some of these have been quite disastrous, whereas others have proven both biologically and economically successful. Unsuccessful systems have generally involved either open access, attempts at top-down control with poor ability to monitor and implement regulations, or reliance on consensus. Successful systems range from local cooperatives to strong governmental control, to various forms of property rights, but usually involve institutional systems that provide incentives to individual operators that lead to behaviour consistent with conservation. PMID:15744918

Examination of Csr regulatory circuitry using epistasis analysis with RNA-seq (Epi-seq) confirms that CsrD affects gene expression via CsrA, CsrB and CsrC.

PubMed

Potts, Anastasia H; Leng, Yuanyuan; Babitzke, Paul; Romeo, Tony

2018-03-29

The Csr global regulatory system coordinates gene expression in response to metabolic status. This system utilizes the RNA binding protein CsrA to regulate gene expression by binding to transcripts of structural and regulatory genes, thus affecting their structure, stability, translation, and/or transcription elongation. CsrA activity is controlled by sRNAs, CsrB and CsrC, which sequester CsrA away from other transcripts. CsrB/C levels are partly determined by their rates of turnover, which requires CsrD to render them susceptible to RNase E cleavage. Previous epistasis analysis suggested that CsrD affects gene expression through the other Csr components, CsrB/C and CsrA. However, those conclusions were based on a limited analysis of reporters. Here, we reassessed the global behavior of the Csr circuitry using epistasis analysis with RNA seq (Epi-seq). Because CsrD effects on mRNA levels were entirely lost in the csrA mutant and largely eliminated in a csrB/C mutant under our experimental conditions, while the majority of CsrA effects persisted in the absence of csrD, the original model accounts for the global behavior of the Csr system. Our present results also reflect a more nuanced role of CsrA as terminal regulator of the Csr system than has been recognized.

Information processing in the primate visual system - An integrated systems perspective

NASA Technical Reports Server (NTRS)

Van Essen, David C.; Anderson, Charles H.; Felleman, Daniel J.

1992-01-01

The primate visual system contains dozens of distinct areas in the cerebral cortex and several major subcortical structures. These subdivisions are extensively interconnected in a distributed hierarchical network that contains several intertwined processing streams. A number of strategies are used for efficient information processing within this hierarchy. These include linear and nonlinear filtering, passage through information bottlenecks, and coordinated use of multiple types of information. In addition, dynamic regulation of information flow within and between visual areas may provide the computational flexibility needed for the visual system to perform a broad spectrum of tasks accurately and at high resolution.

Expression of multidrug resistance efflux pump gene norA is iron responsive in Staphylococcus aureus.

PubMed

Deng, Xin; Sun, Fei; Ji, Quanjiang; Liang, Haihua; Missiakas, Dominique; Lan, Lefu; He, Chuan

2012-04-01

Staphylococcus aureus utilizes efflux transporter NorA to pump out a wide range of structurally dissimilar drugs, conferring low-level multidrug resistance. The regulation of norA expression has yet to be fully understood although past studies have revealed that this gene is under the control of the global transcriptional regulator MgrA and the two-component system ArlRS. To identify additional regulators of norA, we screened a transposon library in strain Newman expressing the transcriptional fusion norA-lacZ for altered β-galactosidase activity. We identify a transposon insertion in fhuB, a gene that encodes a ferric hydroxamate uptake system permease, and propose that the norA transcription is iron responsive. In agreement with this observation, addition of FeCl(3) repressed the induction of norA-lacZ, suggesting that bacterial iron uptake plays an important role in regulating norA transcription. In addition, a fur (ferric uptake regulator) deletion exhibited compromised norA transcription and reduced resistance to quinolone compared to the wild-type strain, indicating that fur functions as a positive regulator of norA. A putative Fur box identified in the promoter region of norA was confirmed by electrophoretic mobility shift and DNase I footprint assays. Finally, by employing a siderophore secretion assay, we reveal that NorA may contribute to the export of siderophores. Collectively, our experiments uncover some novel interactions between cellular iron level and norA regulation in S. aureus.

Expression of Multidrug Resistance Efflux Pump Gene norA Is Iron Responsive in Staphylococcus aureus

PubMed Central

Deng, Xin; Sun, Fei; Ji, Quanjiang; Liang, Haihua; Missiakas, Dominique; Lan, Lefu

2012-01-01

Staphylococcus aureus utilizes efflux transporter NorA to pump out a wide range of structurally dissimilar drugs, conferring low-level multidrug resistance. The regulation of norA expression has yet to be fully understood although past studies have revealed that this gene is under the control of the global transcriptional regulator MgrA and the two-component system ArlRS. To identify additional regulators of norA, we screened a transposon library in strain Newman expressing the transcriptional fusion norA-lacZ for altered β-galactosidase activity. We identify a transposon insertion in fhuB, a gene that encodes a ferric hydroxamate uptake system permease, and propose that the norA transcription is iron responsive. In agreement with this observation, addition of FeCl3 repressed the induction of norA-lacZ, suggesting that bacterial iron uptake plays an important role in regulating norA transcription. In addition, a fur (ferric uptake regulator) deletion exhibited compromised norA transcription and reduced resistance to quinolone compared to the wild-type strain, indicating that fur functions as a positive regulator of norA. A putative Fur box identified in the promoter region of norA was confirmed by electrophoretic mobility shift and DNase I footprint assays. Finally, by employing a siderophore secretion assay, we reveal that NorA may contribute to the export of siderophores. Collectively, our experiments uncover some novel interactions between cellular iron level and norA regulation in S. aureus. PMID:22267518

Integrated carboxylic carbon nanotube pathways with membranes for voltage-activated humidity detection and microclimate regulation.

PubMed

Pingitore, V; Miriello, D; Drioli, E; Gugliuzza, A

2015-06-14

This work describes some single walled carboxylic carbon nanotubes with outstanding transport properties when assembled in a 3D microarray working like a humidity membrane-sensor and an adjustable moisture regulator. Combined nano-assembly approaches are used to build up a better quality pathway through which assisted-charge and mass transport synchronically takes place. The structure-electrical response relationship is found, while controllable and tunable donor-acceptor interactions established at material interfaces are regarded as key factors for the accomplishment of charge transportation, enhanced electrical responses and adjustable moisture exchange. Raman and infrared spectroscopy provides indications about the fine structural and chemical features of the hybrid-composite membranes, resulting in perfect agreement with related morphology and electrical properties. Enhanced and modular electrical response to changes in the surrounding atmosphere is concerned with doping events, while assisted moisture regulation is discussed in relation to swelling and hopping actions. The electro-activated hybrid-composite membrane proposed in this work can be regarded as an attractive 'sense-to-act' precursor for smart long-distance monitoring systems with capability to adapt itself and provide local comfortable microenvironments.

Dynamic Characterization of an Inflatable Concentrator for Solar Thermal Propulsion

NASA Technical Reports Server (NTRS)

Leigh, Larry; Hamidzadeh, Hamid; Tinker, Michael L.; Rodriguez, Pedro I. (Technical Monitor)

2001-01-01

An inflatable structural system that is a technology demonstrator for solar thermal propulsion and other applications is characterized for structural dynamic behavior both experimentally and computationally. The inflatable structure is a pressurized assembly developed for use in orbit to support a Fresnel lens or inflatable lenticular element for focusing sunlight into a solar thermal rocket engine. When the engine temperature reaches a pre-set level, the propellant is injected into the engine, absorbs heat from an exchanger, and is expanded through the nozzle to produce thrust. The inflatable structure is a passively adaptive system in that a regulator and relief valve are utilized to maintain pressure within design limits during the full range of orbital conditions. Modeling and test activities are complicated by the fact that the polyimide film material used for construction of the inflatable is nonlinear, with modulus varying as a function of frequency, temperature, and level of excitation. Modal vibration testing and finite element modeling are described in detail in this paper. The test database is used for validation and modification of the model. This work is highly significant because of the current interest in inflatable structures for space application, and because of the difficulty in accurately modeling such systems.

Eliciting Reciprocal Peer-Tutoring Groups' Metacognitive Regulation through Structuring and Problematizing Scaffolds

ERIC Educational Resources Information Center

De Backer, Liesje; Van Keer, Hilde; Valcke, Martin

2016-01-01

The study examines whether structuring (SS) versus problematising scaffolds (PS) differently affect reciprocal peer-tutoring (RPT) groups' adoption of particular regulation skills, deep-level regulation, and tutee-initiated regulation. A quasi-experimental design involving two experimental groups (SS versus PS condition) was adopted. The first,…

European regulations and their impact on tissue banking.

PubMed

Tatarenko, Alina

2006-01-01

Extensive CoE-EU cooperation ensures coherence and complementarities between the principles of the CoE guides which can be regarded as recommendations on best practice, and the technical requirements of the EU directives which set out legally binding requirements. This means that the same standards now exist throughout European continent. Having a common set of standards facilitates cooperation between different healthcare systems, especially in cases of emergencies, and the export-import issues. Adoption of the same quality management and traceability systems helps to minimise the risks and prevent disease transmissions. It reassures patients who undergo treatments outside of their countries. The tissue establishments need to introduce technical and structural changes to adhere to the new regulations which ultimately results in saving and improving of lives of many patients.

Paraspeckles: Where Long Noncoding RNA Meets Phase Separation.

PubMed

Fox, Archa H; Nakagawa, Shinichi; Hirose, Tetsuro; Bond, Charles S

2018-02-01

Long noncoding RNA (lncRNA) molecules are some of the newest and least understood players in gene regulation. Hence, we need good model systems with well-defined RNA and protein components. One such system is paraspeckles - protein-rich nuclear organelles built around a specific lncRNA scaffold. New discoveries show how paraspeckles are formed through multiple RNA-protein and protein-protein interactions, some of which involve extensive polymerization, and others with multivalent interactions driving phase separation. Once formed, paraspeckles influence gene regulation through sequestration of component proteins and RNAs, with subsequent depletion in other compartments. Here we focus on the dual aspects of paraspeckle structure and function, revealing an emerging role for these dynamic bodies in a multitude of cellular settings. Copyright © 2017 Elsevier Ltd. All rights reserved.

An adaptive learning control system for large flexible structures

NASA Technical Reports Server (NTRS)

Thau, F. E.

1985-01-01

The objective of the research has been to study the design of adaptive/learning control systems for the control of large flexible structures. In the first activity an adaptive/learning control methodology for flexible space structures was investigated. The approach was based on using a modal model of the flexible structure dynamics and an output-error identification scheme to identify modal parameters. In the second activity, a least-squares identification scheme was proposed for estimating both modal parameters and modal-to-actuator and modal-to-sensor shape functions. The technique was applied to experimental data obtained from the NASA Langley beam experiment. In the third activity, a separable nonlinear least-squares approach was developed for estimating the number of excited modes, shape functions, modal parameters, and modal amplitude and velocity time functions for a flexible structure. In the final research activity, a dual-adaptive control strategy was developed for regulating the modal dynamics and identifying modal parameters of a flexible structure. A min-max approach was used for finding an input to provide modal parameter identification while not exceeding reasonable bounds on modal displacement.

Hierarchical, Three-Dimensional Measurement System for Crime Scene Scanning.

PubMed

Marcin, Adamczyk; Maciej, Sieniło; Robert, Sitnik; Adam, Woźniak

2017-07-01

We present a new generation of three-dimensional (3D) measuring systems, developed for the process of crime scene documentation. This measuring system facilitates the preparation of more insightful, complete, and objective documentation for crime scenes. Our system reflects the actual requirements for hierarchical documentation, and it consists of three independent 3D scanners: a laser scanner for overall measurements, a situational structured light scanner for more minute measurements, and a detailed structured light scanner for the most detailed parts of tscene. Each scanner has its own spatial resolution, of 2.0, 0.3, and 0.05 mm, respectively. The results of interviews we have conducted with technicians indicate that our developed 3D measuring system has significant potential to become a useful tool for forensic technicians. To ensure the maximum compatibility of our measuring system with the standards that regulate the documentation process, we have also performed a metrological validation and designated the maximum permissible length measurement error E MPE for each structured light scanner. In this study, we present additional results regarding documentation processes conducted during crime scene inspections and a training session. © 2017 American Academy of Forensic Sciences.

Multi-level and hybrid modelling approaches for systems biology.

PubMed

Bardini, R; Politano, G; Benso, A; Di Carlo, S

2017-01-01

During the last decades, high-throughput techniques allowed for the extraction of a huge amount of data from biological systems, unveiling more of their underling complexity. Biological systems encompass a wide range of space and time scales, functioning according to flexible hierarchies of mechanisms making an intertwined and dynamic interplay of regulations. This becomes particularly evident in processes such as ontogenesis, where regulative assets change according to process context and timing, making structural phenotype and architectural complexities emerge from a single cell, through local interactions. The information collected from biological systems are naturally organized according to the functional levels composing the system itself. In systems biology, biological information often comes from overlapping but different scientific domains, each one having its own way of representing phenomena under study. That is, the different parts of the system to be modelled may be described with different formalisms. For a model to have improved accuracy and capability for making a good knowledge base, it is good to comprise different system levels, suitably handling the relative formalisms. Models which are both multi-level and hybrid satisfy both these requirements, making a very useful tool in computational systems biology. This paper reviews some of the main contributions in this field.

Transcriptional Control of the Lateral-Flagellar Genes of Bradyrhizobium diazoefficiens.

PubMed

Mongiardini, Elías J; Quelas, J Ignacio; Dardis, Carolina; Althabegoiti, M Julia; Lodeiro, Aníbal R

2017-08-01

Bradyrhizobium diazoefficiens , a soybean N 2 -fixing symbiont, possesses a dual flagellar system comprising a constitutive subpolar flagellum and inducible lateral flagella. Here, we analyzed the genomic organization and biosynthetic regulation of the lateral-flagellar genes. We found that these genes are located in a single genomic cluster, organized in two monocistronic transcriptional units and three operons, one possibly containing an internal transcription start site. Among the monocistronic units is blr6846, homologous to the class IB master regulators of flagellum synthesis in Brucella melitensis and Ensifer meliloti and required for the expression of all the lateral-flagellar genes except lafA2 , whose locus encodes a single lateral flagellin. We therefore named blr6846 lafR ( la teral- f lagellar r egulator). Despite its similarity to two-component response regulators and its possession of a phosphorylatable Asp residue, lafR behaved as an orphan response regulator by not requiring phosphorylation at this site. Among the genes induced by lafR is flbT L , a class III regulator. We observed different requirements for FlbT L in the synthesis of each flagellin subunit. Although the accumulation of lafA1 , but not lafA2 , transcripts required FlbT L , the production of both flagellin polypeptides required FlbT L Moreover, the regulation cascade of this lateral-flagellar regulon appeared to be not as strictly ordered as those found in other bacterial species. IMPORTANCE Bacterial motility seems essential for the free-living style in the environment, and therefore these microorganisms allocate a great deal of their energetic resources to the biosynthesis and functioning of flagella. Despite energetic costs, some bacterial species possess dual flagellar systems, one of which is a primary system normally polar or subpolar, and the other is a secondary, lateral system that is produced only under special circumstances. Bradyrhizobium diazoefficiens , an N 2 -fixing symbiont of soybean plants, possesses dual flagellar systems, including the lateral system that contributes to swimming in wet soil and competition for nodulation and is expressed under high energy availability, as well as under requirement for high torque by the flagella. The structural organization and transcriptional regulation of the 41 genes that comprise this secondary flagellar system seem adapted to adjust bacterial energy expenditures for motility to the soil's environmental dynamics. Copyright © 2017 American Society for Microbiology.

Paleo-Immunology: Evidence Consistent with Insertion of a Primordial Herpes Virus-Like Element in the Origins of Acquired Immunity

PubMed Central

Dreyfus, David H.

2009-01-01

Background The RAG encoded proteins, RAG-1 and RAG-2 regulate site-specific recombination events in somatic immune B- and T-lymphocytes to generate the acquired immune repertoire. Catalytic activities of the RAG proteins are related to the recombinase functions of a pre-existing mobile DNA element in the DDE recombinase/RNAse H family, sometimes termed the “RAG transposon”. Methodology/Principal Findings Novel to this work is the suggestion that the DDE recombinase responsible for the origins of acquired immunity was encoded by a primordial herpes virus, rather than a “RAG transposon.” A subsequent “arms race” between immunity to herpes infection and the immune system obscured primary amino acid similarities between herpes and immune system proteins but preserved regulatory, structural and functional similarities between the respective recombinase proteins. In support of this hypothesis, evidence is reviewed from previous published data that a modern herpes virus protein family with properties of a viral recombinase is co-regulated with both RAG-1 and RAG-2 by closely linked cis-acting co-regulatory sequences. Structural and functional similarity is also reviewed between the putative herpes recombinase and both DDE site of the RAG-1 protein and another DDE/RNAse H family nuclease, the Argonaute protein component of RISC (RNA induced silencing complex). Conclusions/Significance A “co-regulatory” model of the origins of V(D)J recombination and the acquired immune system can account for the observed linked genomic structure of RAG-1 and RAG-2 in non-vertebrate organisms such as the sea urchin that lack an acquired immune system and V(D)J recombination. Initially the regulated expression of a viral recombinase in immune cells may have been positively selected by its ability to stimulate innate immunity to herpes virus infection rather than V(D)J recombination Unlike the “RAG-transposon” hypothesis, the proposed model can be readily tested by comparative functional analysis of herpes virus replication and V(D)J recombination. PMID:19492059

[A role of the autonomic nervous system in cerebro-cardiac disorders].

PubMed

Basantsova, N Yu; Tibekina, L M; Shishkin, A N

The authors consider anatomical/physiological characteristics and a role of different autonomic CNS regions, including insula cortex, amygdala complex, anterior cingulate cortex, ventral medial prefrontal cortex, hypothalamus and epiphysis, involved in the regulation of cardiovascular activity. The damage of these structures, e.g., due to the acute disturbance of cerebral blood circulation, led to arrhythmia, including fatal arrhythmia, in previously intact myocardium; systolic and diastolic dysfunction, ischemic changes considered in the frames of cerebro-cardial syndrome. On the cellular level, the disturbance of autonomic regulation resulted in catechol amine excitotoxicity, oxidative stress and free radical myocardium injury.

[Natriuretic peptides. History of discovery, chemical structure, mechanism of action and the removal routes. Basis of diagnostic and therapeutic use].

PubMed

Stryjewski, Piotr J; Nessler, Bohdan; Cubera, Katarzyna; Nessler, Jadwiga

2013-01-01

Natriuretic peptides (NP) are the group of proteins synthesized and secreted by the mammalian heart. All the NP are synthesized from prohormones and have 17-amino acid cyclic structures containing two cysteine residues linked by internal disulphide bond. They are characterized by a wide range of actions, mainly through their membrane receptors. The NP regulate the water and electrolyte balance, blood pressure through their diuretic, natriuretic, and relaxating the vascular smooth muscles effects. They also affect the endocrine system and the nervous system. The neurohormonal regulation of blood circulation results are mainly based on antagonism with renin--angiotensin--aldosterone system. The NP representatives are: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), urodilatine and (DNP) Dendroaspis natriuretic peptide, not found in the human body. According to the guidelines of the European Society of Cardiology determination of NT-proBNP level have found a use in the diagnosis of acute and chronic heart failure, risk stratification in acute coronary syndromes and pulmonary embolism. There are reports found in the literature, that demonstrate the usefulness of NT-proBNP determination in valvular, atrial fibrillation, and syncopes. Recombinant human ANP--Carperitid and BNP--Nesiritid, have already found a use in the adjunctive therapy of dyspnea in acute heart failure.

Control of Bone Remodeling by the Peripheral Sympathetic Nervous System

PubMed Central

Campbell, Preston; Ma, Yun

2013-01-01

The skeleton is no longer seen as a static, isolated, and mostly structural organ. Over the last two decades, a more complete picture of the multiple functions of the skeleton has emerged, and its interactions with a growing number of apparently unrelated organs have become evident. The skeleton not only reacts to mechanical loading and inflammatory, hormonal, and mineral challenges, but also acts of its own accord by secreting factors controlling the function of other tissues, including the kidney and possibly the pancreas and gonads. It is thus becoming widely recognized that it is by nature an endocrine organ, in addition to a structural organ and site of mineral storage and hematopoiesis. Consequently and by definition, bone homeostasis must be tightly regulated and integrated with the biology of other organs to maintain whole body homeostasis, and data uncovering the involvement of the central nervous system (CNS) in the control of bone remodeling support this concept. The sympathetic nervous system (SNS) represents one of the main links between the CNS and the skeleton, based on a number of anatomic, pharmacologic, and genetic studies focused on β-adrenergic receptor (βAR) signaling in bone cells. The goal of this report was to review the data supporting the role of the SNS and βAR signaling in the regulation of skeletal homeostasis. PMID:23765388

Cap-and-Trade Modeling and Analysis: Congested Electricity Market Equilibrium

NASA Astrophysics Data System (ADS)

Limpaitoon, Tanachai

This dissertation presents an equilibrium framework for analyzing the impact of cap-and-trade regulation on transmission-constrained electricity market. The cap-and-trade regulation of greenhouse gas emissions has gained momentum in the past decade. The impact of the regulation and its efficacy in the electric power industry depend on interactions of demand elasticity, transmission network, market structure, and strategic behavior of firms. I develop an equilibrium model of an oligopoly electricity market in conjunction with a market for tradable emissions permits to study the implications of such interactions. My goal is to identify inefficiencies that may arise from policy design elements and to avoid any unintended adverse consequences on the electric power sector. I demonstrate this modeling framework with three case studies examining the impact of carbon cap-and-trade regulation. In the first case study, I study equilibrium results under various scenarios of resource ownership and emission targets using a 24-bus IEEE electric transmission system. The second and third case studies apply the equilibrium model to a realistic electricity market, Western Electricity Coordinating Council (WECC) 225-bus system with a detailed representation of the California market. In the first and second case studies, I examine oligopoly in electricity with perfect competition in the permit market. I find that under a stringent emission cap and a high degree of concentration of non-polluting firms, the electricity market is subject to potential abuses of market power. Also, market power can occur in the procurement of non-polluting energy through the permit market when non-polluting resources are geographically concentrated in a transmission-constrained market. In the third case study, I relax the competitive market structure assumption of the permit market by allowing oligopolistic competition in the market through a conjectural variation approach. A short-term equilibrium analysis of the joint markets in the presence of market power reveals that strategic permit trading can play a vital role in determining economic outcomes in the electricity market. In particular, I find that a firm with more efficient technologies can employ strategic withholding of permits, which allows for its increase in output share in the electricity market at the expense of other less efficient firms. In addition, strategic permit trading can influence patterns of transmission congestion. These results illustrate that market structure and transmission congestion can have a significant impact on the market performance and environmental outcome of the regulation while the interactions of such factors can lead to unintended consequences. The proposed approach is proven useful as a tool for market monitoring purposes in the short run from the perspective of a system operator, whose responsibility has become indirectly intertwined with emission trading regulation.

Conceptual Model of Supply Chain Structure Mapping - A Case of Subsidized LPG Commodity in Yogyakarta

NASA Astrophysics Data System (ADS)

Sulistio, Joko; Thoif, Afifuddin; Fitri Alindira, Aulia

2016-01-01

— In 2007, the government launched a conversion program of kerosene to LPG by issuing a Presidential Regulation No. 104/2007 on Supply, Distribution and Pricing LPG 3 Kg. Article 2 on the regulation says that setting the supply, distribution, and pricing of LPG 3 Kg include planning an annual sales volume of enterprises, the reference price and the retail price and conditions of export and import of LPG 3 Kg in order to reduce subsidies Kerosene especially to divert the use of kerosene according to government policy. In principle, the purpose of this policy is to reduce energy subsidies on commodities, especially Kerosene. Although the government claimed the conversion program is success, there are few problems arising from conversion program. In 2014, many scarcity and high price of LPG 3 Kg were reported. In this case, Pertamina was given full authority to manage all supply chain and distribution. Because the root of the problem of scarcity that occurred in the supply chain system has not been explained, the proposed solutions will also be partial and not comprehensive. Thus, this research will build a structural map of the causes of supply chain system LPG 3 Kg, as well as providing a comprehensive picture of system dynamics of LPG 3 Kg supply chain system which applied in Indonesia. And the result is expected as in form of Causal Loop Diagram of supply chain system.

Multi-agent electricity market modeling with EMCAS.

DOE Office of Scientific and Technical Information (OSTI.GOV)

North, M.; Macal, C.; Conzelmann, G.

2002-09-05

Electricity systems are a central component of modern economies. Many electricity markets are transitioning from centrally regulated systems to decentralized markets. Furthermore, several electricity markets that have recently undergone this transition have exhibited extremely unsatisfactory results, most notably in California. These high stakes transformations require the introduction of largely untested regulatory structures. Suitable tools that can be used to test these regulatory structures before they are applied to real systems are required. Multi-agent models can provide such tools. To better understand the requirements such as tool, a live electricity market simulation was created. This experience helped to shape the developmentmore » of the multi-agent Electricity Market Complex Adaptive Systems (EMCAS) model. To explore EMCAS' potential, several variations of the live simulation were created. These variations probed the possible effects of changing power plant outages and price setting rules on electricity market prices.« less

Plant-soil-microbe interactions regulating soil C storage

NASA Astrophysics Data System (ADS)

Hofmockel, K. S.; Bach, E.; Williams, R.

2016-12-01

Integration across disciplines is required to identify the emergent microbial scale properties that regulate the release or occlusion of plant inputs in soil organic matter. To investigate how micro-scale processes influence soil carbon cycling, we measured microbial community composition and activity within soil aggregates monthly over two growing seasons of a long-term bioenergy field experiment. Using a biologically sensitive sieving technique, soil aggregates were isolated and microbial community activity and composition were measured. This aggregate approach revealed biogeochemical processes regulating C cycling that are not detected using whole soil approaches. Soil aggregation influenced microbe-substrate interactions, where diversified perennial grassland systems supported greater aggregation and reduced severity of aggregate turnover compared to corn systems. Aggregate turnover and concurrent increases in activity resulted in greater microbial biomass and physical protection of soil organic matter in prairie systems, especially fertilized prairies. Fertilized prairie enhanced microbial biomass, enzyme activity, and soil aggregation despite greater root biomass in unfertilized prairie. Independent of ecosystem or sampling date, N-acetyl-glucosaminidase activity and Nitrospirae abundance was greatest in large macroaggregates (>2000 µm), which harbored the highest C:N; cellobiohydrolase activity and Acidobacteria abundance was greatest in microaggregates (<250 µm) which had the lowest C:N. Aggregate fractions differed in microbial community composition (bacteria, archaea, and fungi) and potential enzyme activity, independent of cropping system. Microaggregates harbored significantly greater microbial diversity and richness across all bioenergy cropping systems. Together these results suggest that by mediating access to substrates, soil structure (aggregates) can influence the microbial community composition and extracellular enzyme activity to regulate ecosystem scale decomposition of soil organic matter.

Inference of time-delayed gene regulatory networks based on dynamic Bayesian network hybrid learning method

PubMed Central

Yu, Bin; Xu, Jia-Meng; Li, Shan; Chen, Cheng; Chen, Rui-Xin; Wang, Lei; Zhang, Yan; Wang, Ming-Hui

2017-01-01

Gene regulatory networks (GRNs) research reveals complex life phenomena from the perspective of gene interaction, which is an important research field in systems biology. Traditional Bayesian networks have a high computational complexity, and the network structure scoring model has a single feature. Information-based approaches cannot identify the direction of regulation. In order to make up for the shortcomings of the above methods, this paper presents a novel hybrid learning method (DBNCS) based on dynamic Bayesian network (DBN) to construct the multiple time-delayed GRNs for the first time, combining the comprehensive score (CS) with the DBN model. DBNCS algorithm first uses CMI2NI (conditional mutual inclusive information-based network inference) algorithm for network structure profiles learning, namely the construction of search space. Then the redundant regulations are removed by using the recursive optimization algorithm (RO), thereby reduce the false positive rate. Secondly, the network structure profiles are decomposed into a set of cliques without loss, which can significantly reduce the computational complexity. Finally, DBN model is used to identify the direction of gene regulation within the cliques and search for the optimal network structure. The performance of DBNCS algorithm is evaluated by the benchmark GRN datasets from DREAM challenge as well as the SOS DNA repair network in Escherichia coli, and compared with other state-of-the-art methods. The experimental results show the rationality of the algorithm design and the outstanding performance of the GRNs. PMID:29113310

Inference of time-delayed gene regulatory networks based on dynamic Bayesian network hybrid learning method.

PubMed

Yu, Bin; Xu, Jia-Meng; Li, Shan; Chen, Cheng; Chen, Rui-Xin; Wang, Lei; Zhang, Yan; Wang, Ming-Hui

2017-10-06

Gene regulatory networks (GRNs) research reveals complex life phenomena from the perspective of gene interaction, which is an important research field in systems biology. Traditional Bayesian networks have a high computational complexity, and the network structure scoring model has a single feature. Information-based approaches cannot identify the direction of regulation. In order to make up for the shortcomings of the above methods, this paper presents a novel hybrid learning method (DBNCS) based on dynamic Bayesian network (DBN) to construct the multiple time-delayed GRNs for the first time, combining the comprehensive score (CS) with the DBN model. DBNCS algorithm first uses CMI2NI (conditional mutual inclusive information-based network inference) algorithm for network structure profiles learning, namely the construction of search space. Then the redundant regulations are removed by using the recursive optimization algorithm (RO), thereby reduce the false positive rate. Secondly, the network structure profiles are decomposed into a set of cliques without loss, which can significantly reduce the computational complexity. Finally, DBN model is used to identify the direction of gene regulation within the cliques and search for the optimal network structure. The performance of DBNCS algorithm is evaluated by the benchmark GRN datasets from DREAM challenge as well as the SOS DNA repair network in Escherichia coli , and compared with other state-of-the-art methods. The experimental results show the rationality of the algorithm design and the outstanding performance of the GRNs.

Effect of guided, structured, writing program on self-harm ideations and emotion regulation.

PubMed

Fukumori, Takaki; Kuroda, Hiromi; Ito, Masaya; Kashimura, Masami

2017-01-01

This study investigated the efficacy of structured writing on reducing self-harm ideations and enhancing emotion regulation. Japanese university students (N=22) participated in the study. Participants were randomly assigned to the structured writing group (n=10; 70% female), or an assessment only control group (n=12; 67% female). For three consecutive days, participants in the intervention group performed structured writing that included psycho-education and self-reflection about emotions. The Self-Harm Ideation Scale, the Generalized Expectancy for Negative Mood Regulation Scale, and the Acceptance and Action Questionnaire-II were used to assess outcomes. Structured writing had a short-term effect on expectancies for self-regulation of negative moods and acceptance of negative emotions, but had a limited effect on self-harm ideations. This study presents preliminary evidence that increasing awareness, learning, and reflection about emotions resulting from using a structured writing program is particularly useful for regulating emotions. J. Med. Invest. 64: 74-78, February, 2017.

48 CFR 215.404-70 - DD Form 1547, Record of Weighted Guidelines Method Application.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false DD Form 1547, Record of... TYPES CONTRACTING BY NEGOTIATION Contract Pricing 215.404-70 DD Form 1547, Record of Weighted Guidelines Method Application. Follow the procedures at PGI 215.404-70 for use of DD Form 1547 whenever a structured...

Long-Range Educational Policy Planning and the Demand for Educated Manpower in Times of Uncertainty.

ERIC Educational Resources Information Center

Bakke, E. K.

1984-01-01

There is no good method of regulating the educational system based on specific, numerical measurements of labor requirements, and it will be important to integrate uncertainty into future forecasts. Adjustments in demand and supply of educated labor in Norway require a decentralized authority structure providing incentives for institutions and the…

Interaction of structural core protein of Classical Swine Fever Virus with endoplasmic reticulum-associated degradation pathway protein OS9

USDA-ARS?s Scientific Manuscript database

Classical Swine Fever Virus (CSFV) Core protein is involved in virus RNA protection, transcription regulation and virus virulence. To discover additional Core protein functions a yeast two-hybrid system was used to identify host proteins that interact with Core. Among the identified host proteins, t...

A case history of all-age management

Treesearch

Richard M. Godman; Gilbert A. Mattson

1992-01-01

Single-tree selection "works" in sugar maple stands in the Lake States. This system of all-age management has been used for 31 years on the Argonne Experimental Forest. In 1953, researchers found that cutting according to basal area guides is both a convenient and effective way to regulate a stand. Later experience showed that achieving good stand structure...

Isolating causal pathways between flow and fish in the regulated river hierarchy

Treesearch

Ryan McManamay; Donald J. Orth; Charles A. Dolloff; David C. Mathews

2015-01-01

Unregulated river systems are organized in a hierarchy in which large scale factors (i.e. landscape and segment scales) influence local habitats (i.e. reach, meso- and microhabitat scales), and both differentially exert selective pressures on biota. Dams, however, create discontinua in these processes and change the hierarchical structure. We examined the relative...

Structuring injustice: partisan politics in the making and unmaking of James Madison University's equal opportunity policy.

PubMed

Robinson, Christine M; Spivey, Sue E

2011-01-01

This analysis contributes to LGBT campus climate research on the quality of campus life in higher education in the United States. We argue that public education institutions in different states face divergent impediments to improving campus climate, and that more research is needed identifying structural factors affecting campus climate. Using a social systems analysis of policymaking at one university as a case study, we illustrate how partisan politics and state regulation make Virginia colleges and universities more vulnerable to political scrutiny and control. Finally, we propose a social justice-oriented policy agenda to address structural inequalities.

Autocatalytic microtubule nucleation determines the size and mass of Xenopus laevis egg extract spindles

PubMed Central

Decker, Franziska; Oriola, David; Dalton, Benjamin

2018-01-01

Regulation of size and growth is a fundamental problem in biology. A prominent example is the formation of the mitotic spindle, where protein concentration gradients around chromosomes are thought to regulate spindle growth by controlling microtubule nucleation. Previous evidence suggests that microtubules nucleate throughout the spindle structure. However, the mechanisms underlying microtubule nucleation and its spatial regulation are still unclear. Here, we developed an assay based on laser ablation to directly probe microtubule nucleation events in Xenopus laevis egg extracts. Combining this method with theory and quantitative microscopy, we show that the size of a spindle is controlled by autocatalytic growth of microtubules, driven by microtubule-stimulated microtubule nucleation. The autocatalytic activity of this nucleation system is spatially regulated by the limiting amounts of active microtubule nucleators, which decrease with distance from the chromosomes. This mechanism provides an upper limit to spindle size even when resources are not limiting. PMID:29323637

Study of a control strategy for grid side converter in doubly- fed wind power system

NASA Astrophysics Data System (ADS)

Zhu, D. J.; Tan, Z. L.; Yuan, F.; Wang, Q. Y.; Ding, M.

2016-08-01

The grid side converter is an important part of the excitation system of doubly-fed asynchronous generator used in wind power system. As a three-phase voltage source PWM converter, it can not only transfer slip power in the form of active power, but also adjust the reactive power of the grid. This paper proposed a control approach for improving its performance. In this control approach, the dc voltage is regulated by a sliding mode variable structure control scheme and current by a variable structure controller based on the input output linearization. The theoretical bases of the sliding mode variable structure control were introduced, and the stability proof was presented. Switching function of the system has been deduced, sliding mode voltage controller model has been established, and the output of the outer voltage loop is the instruction of the inner current loop. Affine nonlinear model of two input two output equations on d-q axis for current has been established its meeting conditions of exact linearization were proved. In order to improve the anti-jamming capability of the system, a variable structure control was added in the current controller, the control law was deduced. The dual-loop control with sliding mode control in outer voltage loop and linearization variable structure control in inner current loop was proposed. Simulation results demonstrate the effectiveness of the proposed control strategy even during the dc reference voltage and system load variation.

Post-transcriptional trafficking and regulation of neuronal gene expression.

PubMed

Goldie, Belinda J; Cairns, Murray J

2012-02-01

Intracellular messenger RNA (mRNA) traffic and translation must be highly regulated, both temporally and spatially, within eukaryotic cells to support the complex functional partitioning. This capacity is essential in neurons because it provides a mechanism for rapid input-restricted activity-dependent protein synthesis in individual dendritic spines. While this feature is thought to be important for synaptic plasticity, the structures and mechanisms that support this capability are largely unknown. Certainly specialized RNA binding proteins and binding elements in the 3' untranslated region (UTR) of translationally regulated mRNA are important, but the subtlety and complexity of this system suggests that an intermediate "specificity" component is also involved. Small non-coding microRNA (miRNA) are essential for CNS development and may fulfill this role by acting as the guide strand for mediating complex patterns of post-transcriptional regulation. In this review we examine post-synaptic gene regulation, mRNA trafficking and the emerging role of post-transcriptional gene silencing in synaptic plasticity.

Examining the link between price regulation and pharmaceutical R&D investment.

PubMed

Vernon, John A

2005-01-01

This paper examines the link between price regulation and pharmaceutical research and development (R&D) investment. I identify two mechanisms through which price regulation may exert an influence on R&D: an expected-profit effect and a cash-flow effect. Using established models of the determinants of pharmaceutical R&D, I exploit a unique fact to quantify firm exposure to pharmaceutical price regulation: relative to the rest of the world, the U.S. pharmaceutical market is largely unregulated with respect to price. Using this fact within the context of a system of quasi-structural equations, I simulate how a new policy regulating pharmaceutical prices in the U.S. will affect R&D investment. I find that such a policy will lead to a decline in industry R&D by between 23.4 and 32.7%. This prediction, however, is accompanied by several caveats. Moreover, it says nothing about the implications for social welfare; therefore, these issues are also discussed. Copyright 2004 John Wiley & Sons, Ltd.

Evolution of Osteocrin as an activity-regulated factor in the primate brain

PubMed Central

Ataman, Bulent; Boulting, Gabriella L.; Harmin, David A.; Yang, Marty G.; Baker-Salisbury, Mollie; Yap, Ee-Lynn; Malik, Athar N.; Mei, Kevin; Rubin, Alex A.; Spiegel, Ivo; Durresi, Ershela; Sharma, Nikhil; Hu, Linda S.; Pletikos, Mihovil; Griffith, Eric C.; Partlow, Jennifer N.; Stevens, Christine R.; Adli, Mazhar; Chahrour, Maria; Sestan, Nenad; Walsh, Christopher A.; Berezovskii, Vladimir K.; Livingstone, Margaret S.; Greenberg, Michael E.

2017-01-01

Sensory stimuli drive the maturation and function of the mammalian nervous system in part through the activation of gene expression networks that regulate synapse development and plasticity. These networks have primarily been studied in mice, and it is not known whether there are species- or clade-specific activity-regulated genes that control features of brain development and function. Here we use transcriptional profiling of human fetal brain cultures to identify an activity-dependent secreted factor, Osteocrin (OSTN), that is induced by membrane depolarization of human but not mouse neurons. We find that OSTN has been repurposed in primates through the evolutionary acquisition of DNA regulatory elements that bind the activity-regulated transcription factor MEF2. In addition, we demonstrate that OSTN is expressed in primate neocortex and restricts activity-dependent dendritic growth in human neurons. These findings suggest that, in response to sensory input, OSTN regulates features of neuronal structure and function that are unique to primates. PMID:27830782

Cell fate regulation governed by a repurposed bacterial histidine kinase

DOE PAGES

Childers, W. Seth; Xu, Qingping; Mann, Thomas H.; ...

2014-10-28

One of the simplest organisms to divide asymmetrically is the bacterium Caulobacter crescentus. The DivL pseudo-histidine kinase, positioned at one cell pole, regulates cell-fate by controlling the activation of the global transcription factor CtrA via an interaction with the response regulator (RR) DivK. DivL uniquely contains a tyrosine at the histidine phosphorylation site, and can achieve these regulatory functions in vivo without kinase activity. Determination of the DivL crystal structure and biochemical analysis of wild-type and site-specific DivL mutants revealed that the DivL PAS domains regulate binding specificity for DivK~P over DivK, which is modulated by an allosteric intramolecular interactionmore » between adjacent domains. We discovered that DivL's catalytic domains have been repurposed as a phosphospecific RR input sensor, thereby reversing the flow of information observed in conventional histidine kinase (HK)-RR systems and coupling a complex network of signaling proteins for cell-fate regulation.« less

The Effect of Environmental Regulation on Employment in Resource-Based Areas of China-An Empirical Research Based on the Mediating Effect Model.

PubMed

Cao, Wenbin; Wang, Hui; Ying, Huihui

2017-12-19

While environmental pollution is becoming more and more serious, many countries are adopting policies to control pollution. At the same time, the environmental regulation will inevitably affect economic and social development, especially employment growth. The environmental regulation will not only affect the scale of employment directly, but it will also have indirect effects by stimulating upgrades in the industrial structure and in technological innovation. This paper examines the impact of environmental regulation on employment, using a mediating model based on the data from five typical resource-based provinces in China from 2000 to 2015. The estimation is performed based on the system GMM (Generalized Method of Moments) estimator. The results show that the implementation of environmental regulation in resource-based areas has both a direct effect and a mediating effect on employment. These findings provide policy implications for these resource-based areas to promote the coordinating development between the environment and employment.

The Effect of Environmental Regulation on Employment in Resource-Based Areas of China—An Empirical Research Based on the Mediating Effect Model

PubMed Central

Cao, Wenbin; Wang, Hui; Ying, Huihui

2017-01-01

While environmental pollution is becoming more and more serious, many countries are adopting policies to control pollution. At the same time, the environmental regulation will inevitably affect economic and social development, especially employment growth. The environmental regulation will not only affect the scale of employment directly, but it will also have indirect effects by stimulating upgrades in the industrial structure and in technological innovation. This paper examines the impact of environmental regulation on employment, using a mediating model based on the data from five typical resource-based provinces in China from 2000 to 2015. The estimation is performed based on the system GMM (Generalized Method of Moments) estimator. The results show that the implementation of environmental regulation in resource-based areas has both a direct effect and a mediating effect on employment. These findings provide policy implications for these resource-based areas to promote the coordinating development between the environment and employment. PMID:29257068

Cobalamin in inflammation III — glutathionylcobalamin and methylcobalamin/adenosylcobalamin coenzymes: the sword in the stone? How cobalamin may directly regulate the nitric oxide synthases

PubMed Central

Wheatley, Carmen

2007-01-01

Several mysteries surround the structure and function of the nitric oxide synthases (NOS). The NOS oxygenase domain structure is unusually open with a large area of solvent that could accommodate an unidentified ligand. The exact mechanism of the two-step five-electron monoxygenation of arginine to NG-hydroxy-L-arginine, thence to citrulline and nitric oxide (NO), is not clear, particularly as arginine/NG-hydroxy-L-arginine is bound at a great distance to the supposed catalytic heme Fe [III], as the anti-stereoisomer. The Return of the Scarlet Pimpernel Paper proposed that cobalamin is a primary indirect regulator of the NOS. An additional direct regulatory effect of the ‘base-off’ dimethylbenzimidazole of glutathionylcobalamin (GSCbl), which may act as a sixth ligand to the heme iron, promote Co-oriented, BH4/BH3 radical catalysed oxidation of L-arginine to NO, and possibly regulate the rate of inducible NOS/NO production by the NOS dimers, is further advanced. The absence of homology between the NOS and methionine synthase/methylmalonyl CoA mutase may enable GSCbl to regulate both sets of enzymes simultaneously by completely separate mechanisms. Thus, cobalamin may exert central control over both pro-and anti-inflammatory systems. PMID:18923642

Regulation of cellular plasticity and resilience by mood stabilizers: the role of AMPA receptor trafficking

PubMed Central

Du, Jing; Quiroz, Jorge A.; Gray, Neil A.; Szabo, Steve T.; Zarate Jr, Carlos A.; Manji, Husseini K.

2004-01-01

There is increasing evidence from a variety of sources that severe mood disorders are associated with regional reductions in brain volume, as well as reductions in the number, size, and density of glia and neurons in discrete brain areas. Although the precise pathophysiology underlying these morphometric changes remains to be fully elucidated, the data suggest that severe mood disorders are associated with impairments of structural plasticity and cellular resilience. In this context, it is noteworthy that a growing body of data suggests that the glutamaiergic system (which is known to play a major role in neuronal plasticity and cellular resilience) may be involved in the pathophysiology and treatment of mood disorders. Glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) GluR1 receptor trafficking plays a critical role in regulating various forms of neural plasticity. It is thus noteworthy that recent studies have shown that structurally dissimilar mood stabilizers lithium and valproate regulate GluR1 receptor subunit trafficking and localization at synapses. These studies suggest that regulation of glutamatergically mediated synaptic plasticity may play a role in the treatment of mood disorders, and raises the possibility that agents more directly affecting synaptic GluR1 represent novel therapies for these devastating illnesses. PMID:22034247

Structural Code Considerations for Solar Rooftop Installations.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dwyer, Stephen F.; Dwyer, Brian P.; Sanchez, Alfred

2014-12-01

Residential rooftop solar panel installations are limited in part by the high cost of structural related code requirements for field installation. Permitting solar installations is difficult because there is a belief among residential permitting authorities that typical residential rooftops may be structurally inadequate to support the additional load associated with a photovoltaic (PV) solar installation. Typical engineering methods utilized to calculate stresses on a roof structure involve simplifying assumptions that render a complex non-linear structure to a basic determinate beam. This method of analysis neglects the composite action of the entire roof structure, yielding a conservative analysis based on amore » rafter or top chord of a truss. Consequently, the analysis can result in an overly conservative structural analysis. A literature review was conducted to gain a better understanding of the conservative nature of the regulations and codes governing residential construction and the associated structural system calculations.« less

Living in the branches: population dynamics and ecological processes in dendritic networks

USGS Publications Warehouse

Grant, E.H.C.; Lowe, W.H.; Fagan, W.F.

2007-01-01

Spatial structure regulates and modifies processes at several levels of ecological organization (e.g. individual/genetic, population and community) and is thus a key component of complex systems, where knowledge at a small scale can be insufficient for understanding system behaviour at a larger scale. Recent syntheses outline potential applications of network theory to ecological systems, but do not address the implications of physical structure for network dynamics. There is a specific need to examine how dendritic habitat structure, such as that found in stream, hedgerow and cave networks, influences ecological processes. Although dendritic networks are one type of ecological network, they are distinguished by two fundamental characteristics: (1) both the branches and the nodes serve as habitat, and (2) the specific spatial arrangement and hierarchical organization of these elements interacts with a species' movement behaviour to alter patterns of population distribution and abundance, and community interactions. Here, we summarize existing theory relating to ecological dynamics in dendritic networks, review empirical studies examining the population- and community-level consequences of these networks, and suggest future research integrating spatial pattern and processes in dendritic systems.

Predictive Feedback and Feedforward Control for Systems with Unknown Disturbances

NASA Technical Reports Server (NTRS)

Juang, Jer-Nan; Eure, Kenneth W.

1998-01-01

Predictive feedback control has been successfully used in the regulation of plate vibrations when no reference signal is available for feedforward control. However, if a reference signal is available it may be used to enhance regulation by incorporating a feedforward path in the feedback controller. Such a controller is known as a hybrid controller. This paper presents the theory and implementation of the hybrid controller for general linear systems, in particular for structural vibration induced by acoustic noise. The generalized predictive control is extended to include a feedforward path in the multi-input multi-output case and implemented on a single-input single-output test plant to achieve plate vibration regulation. There are cases in acoustic-induce vibration where the disturbance signal is not available to be used by the hybrid controller, but a disturbance model is available. In this case the disturbance model may be used in the feedback controller to enhance performance. In practice, however, neither the disturbance signal nor the disturbance model is available. This paper presents the theory of identifying and incorporating the noise model into the feedback controller. Implementations are performed on a test plant and regulation improvements over the case where no noise model is used are demonstrated.

An ideal-typical model for comparing interprofessional relations and skill mix in health care.

PubMed

Schönfelder, Walter; Nilsen, Elin Anita

2016-11-08

Comparisons of health system performance, including the regulations of interprofessional relations and the skill mix between health professions are challenging. National strategies for regulating interprofessional relations vary widely across European health care systems. Unambiguously defined and generally accepted performance indicators have to remain generic, with limited power for recognizing the organizational structures regulating interprofessional relations in different health systems. A coherent framework for in-depth comparisons of different models for organizing interprofessional relations and the skill mix between professional groups is currently not available. This study aims to develop an ideal-typical framework for categorizing skill mix and interprofessional relations in health care, and to assess the potential impact for different ideal types on care coordination and integrated service delivery. A document analysis of the Health Systems in Transition (HiT) reports published by the European Observatory on Health Systems and Policies was conducted. The HiT reports to 31 European health systems were analyzed using a qualitative content analysis and a process of meaning condensation. The educational tracks available to nurses have an impact on the professional autonomy for nurses, the hierarchy between professional groups, the emphasis given to negotiating skill mix, interdisciplinary teamwork and the extent of cooperation across the health and social service interface. Based on the results of the document analysis, three ideal types for regulating interprofessional relations and skill mix in health care are delimited. For each ideal type, outcomes on service coordination and holistic service delivery are described. Comparisons of interprofessional relations are necessary for proactive health human resource policies. The proposed ideal-typical framework provides the means for in-depth comparisons of interprofessional relations in the health care workforce beyond of what is possible with directly comparable, but generic performance indicators.

Alternative modes of client binding enable functional plasticity of Hsp70

NASA Astrophysics Data System (ADS)

Mashaghi, Alireza; Bezrukavnikov, Sergey; Minde, David P.; Wentink, Anne S.; Kityk, Roman; Zachmann-Brand, Beate; Mayer, Matthias P.; Kramer, Günter; Bukau, Bernd; Tans, Sander J.

2016-11-01

The Hsp70 system is a central hub of chaperone activity in all domains of life. Hsp70 performs a plethora of tasks, including folding assistance, protection against aggregation, protein trafficking, and enzyme activity regulation, and interacts with non-folded chains, as well as near-native, misfolded, and aggregated proteins. Hsp70 is thought to achieve its many physiological roles by binding peptide segments that extend from these different protein conformers within a groove that can be covered by an ATP-driven helical lid. However, it has been difficult to test directly how Hsp70 interacts with protein substrates in different stages of folding and how it affects their structure. Moreover, recent indications of diverse lid conformations in Hsp70-substrate complexes raise the possibility of additional interaction mechanisms. Addressing these issues is technically challenging, given the conformational dynamics of both chaperone and client, the transient nature of their interaction, and the involvement of co-chaperones and the ATP hydrolysis cycle. Here, using optical tweezers, we show that the bacterial Hsp70 homologue (DnaK) binds and stabilizes not only extended peptide segments, but also partially folded and near-native protein structures. The Hsp70 lid and groove act synergistically when stabilizing folded structures: stabilization is abolished when the lid is truncated and less efficient when the groove is mutated. The diversity of binding modes has important consequences: Hsp70 can both stabilize and destabilize folded structures, in a nucleotide-regulated manner; like Hsp90 and GroEL, Hsp70 can affect the late stages of protein folding; and Hsp70 can suppress aggregation by protecting partially folded structures as well as unfolded protein chains. Overall, these findings in the DnaK system indicate an extension of the Hsp70 canonical model that potentially affects a wide range of physiological roles of the Hsp70 system.

Application of the principles of systems biology and Wiener's cybernetics for analysis of regulation of energy fluxes in muscle cells in vivo.

PubMed

Guzun, Rita; Saks, Valdur

2010-03-08

The mechanisms of regulation of respiration and energy fluxes in the cells are analyzed based on the concepts of systems biology, non-equilibrium steady state kinetics and applications of Wiener's cybernetic principles of feedback regulation. Under physiological conditions cardiac function is governed by the Frank-Starling law and the main metabolic characteristic of cardiac muscle cells is metabolic homeostasis, when both workload and respiration rate can be changed manifold at constant intracellular level of phosphocreatine and ATP in the cells. This is not observed in skeletal muscles. Controversies in theoretical explanations of these observations are analyzed. Experimental studies of permeabilized fibers from human skeletal muscle vastus lateralis and adult rat cardiomyocytes showed that the respiration rate is always an apparent hyperbolic but not a sigmoid function of ADP concentration. It is our conclusion that realistic explanations of regulation of energy fluxes in muscle cells require systemic approaches including application of the feedback theory of Wiener's cybernetics in combination with detailed experimental research. Such an analysis reveals the importance of limited permeability of mitochondrial outer membrane for ADP due to interactions of mitochondria with cytoskeleton resulting in quasi-linear dependence of respiration rate on amplitude of cyclic changes in cytoplasmic ADP concentrations. The system of compartmentalized creatine kinase (CK) isoenzymes functionally coupled to ANT and ATPases, and mitochondrial-cytoskeletal interactions separate energy fluxes (mass and energy transfer) from signalling (information transfer) within dissipative metabolic structures - intracellular energetic units (ICEU). Due to the non-equilibrium state of CK reactions, intracellular ATP utilization and mitochondrial ATP regeneration are interconnected by the PCr flux from mitochondria. The feedback regulation of respiration occurring via cyclic fluctuations of cytosolic ADP, Pi and Cr/PCr ensures metabolic stability necessary for normal function of cardiac cells.

[Hormonal regulation of metabolism in the human body in microgravity and during simulation of its physiological effects].

PubMed

Larina, I M

2003-01-01

The paper presents results of investigations into the effects of space flight and simulation experiments of various length on the hormonal regulation of metabolism in the human body. Microgravity was shown to instigate shifts on different levels of the hormonal regulation and consequent adjustment of metabolism to this new environment. For instance, adaptation occurs on the level of basal secretory activity resulting in altered metabolism and formation of a pool of hormones. Metabolism readaptation to the Earth's gravity is dependent on polymorphic processes in the system of hormonal regulation developing in the course of time. Trends in the hormonal regulation of water-electrolyte metabolism during early adaptation point to inequality of contributions of the antidiuretic hormone, natriuretic peptide, and the renin-angiotensin-aldosterone system. In the ground-based simulations responses of the hormonal regulation of water-electrolyte metabolism differ in intensity and types of hormones involved. Temperature variation can modify reactions of the comosis and volume regulating hormones at the beginning of adaptation. Physical-chemical regulation of calcium homeostasis in microgravity reveals itself by a rapid decline of the calcium-binding ability of blood buffers and, later on, degradation of the relative ability of extraplasmic structures to bind calcium. Qualitative and quantitative changes in the diurnal rhythm of the suprarenal steroidogenesis are indicative of modification of intensity of reactions of the main biosynthetic sequences. Countermeasures used by test-subjects in these investigations loosened significantly the aldosterone-secreting biosynthetic sequences but were favorable to the synthesis of testosterone and hydrocortisone. Some of the highly variable processes of hormonal regulation were mute to the diurnal rhythms in the pre-flight and preexperimental periods.

ATP regulation of the ligand-binding properties in temperate and cold-adapted haemoglobins. X-ray structure and ligand-binding kinetics in the sub-Antarctic fish Eleginops maclovinus.

PubMed

Coppola, Daniela; Abbruzzetti, Stefania; Nicoletti, Francesco; Merlino, Antonello; Gambacurta, Alessandra; Giordano, Daniela; Howes, Barry D; De Sanctis, Giampiero; Vitagliano, Luigi; Bruno, Stefano; di Prisco, Guido; Mazzarella, Lelio; Smulevich, Giulietta; Coletta, Massimo; Viappiani, Cristiano; Vergara, Alessandro; Verde, Cinzia

2012-10-30

The major haemoglobin of the sub-Antarctic fish Eleginops maclovinus was structurally and functionally characterised with the aim to compare molecular environmental adaptations in the O(2)-transport system of sub-Antarctic fishes of the suborder Notothenioidei with those of their high-latitude relatives. Ligand-binding kinetics of the major haemoglobin of E. maclovinus indicated strong stabilisation of the liganded quaternary T state, enhanced in the presence of the physiological allosteric effector ATP, compared to that of high-Antarctic Trematomus bernacchii. The activation enthalpy for O(2) dissociation was dramatically lower than that in T. bernacchii haemoglobin, suggesting remarkable differences in temperature sensitivity and structural changes associated with O(2) release and exit from the protein. The haemoglobin functional properties, together with the X-ray structure of the CO form at 1.49 Å resolution, the first of a temperate notothenioid, strongly support the hypothesis that in E. maclovinus, whose life-style varies according to changes in habitat, the mechanisms that regulate O(2) affinity and the ATP-induced Root effect differ from those of high-Antarctic Notothenioids.

Effect of the SH3-SH2 domain linker sequence on the structure of Hck kinase.

PubMed

Meiselbach, Heike; Sticht, Heinrich

2011-08-01

The coordination of activity in biological systems requires the existence of different signal transduction pathways that interact with one another and must be precisely regulated. The Src-family tyrosine kinases, which are found in many signaling pathways, differ in their physiological function despite their high overall structural similarity. In this context, the differences in the SH3-SH2 domain linkers might play a role for differential regulation, but the structural consequences of linker sequence remain poorly understood. We have therefore performed comparative molecular dynamics simulations of wildtype Hck and of a mutant Hck in which the SH3-SH2 domain linker is replaced by the corresponding sequence from the homologous kinase Lck. These simulations reveal that linker replacement not only affects the orientation of the SH3 domain itself, but also leads to an alternative conformation of the activation segment in the Hck kinase domain. The sequence of the SH3-SH2 domain linker thus exerts a remote effect on the active site geometry and might therefore play a role in modulating the structure of the inactive kinase or in fine-tuning the activation process itself.

Utility Rate Equations of Group Population Dynamics in Biological and Social Systems

PubMed Central

Yukalov, Vyacheslav I.; Yukalova, Elizaveta P.; Sornette, Didier

2013-01-01

We present a novel system of equations to describe the evolution of self-organized structured societies (biological or human) composed of several trait groups. The suggested approach is based on the combination of ideas employed in the theory of biological populations, system theory, and utility theory. The evolution equations are defined as utility rate equations, whose parameters are characterized by the utility of each group with respect to the society as a whole and by the mutual utilities of groups with respect to each other. We analyze in detail the cases of two groups (cooperators and defectors) and of three groups (cooperators, defectors, and regulators) and find that, in a self-organized society, neither defectors nor regulators can overpass the maximal fractions of about each. This is in agreement with the data for bee and ant colonies. The classification of societies by their distance from equilibrium is proposed. We apply the formalism to rank the countries according to the introduced metric quantifying their relative stability, which depends on the cost of defectors and regulators as well as their respective population fractions. We find a remarkable concordance with more standard economic ranking based, for instance, on GDP per capita. PMID:24386163

Utility rate equations of group population dynamics in biological and social systems.

PubMed

Yukalov, Vyacheslav I; Yukalova, Elizaveta P; Sornette, Didier

2013-01-01

We present a novel system of equations to describe the evolution of self-organized structured societies (biological or human) composed of several trait groups. The suggested approach is based on the combination of ideas employed in the theory of biological populations, system theory, and utility theory. The evolution equations are defined as utility rate equations, whose parameters are characterized by the utility of each group with respect to the society as a whole and by the mutual utilities of groups with respect to each other. We analyze in detail the cases of two groups (cooperators and defectors) and of three groups (cooperators, defectors, and regulators) and find that, in a self-organized society, neither defectors nor regulators can overpass the maximal fractions of about [Formula: see text] each. This is in agreement with the data for bee and ant colonies. The classification of societies by their distance from equilibrium is proposed. We apply the formalism to rank the countries according to the introduced metric quantifying their relative stability, which depends on the cost of defectors and regulators as well as their respective population fractions. We find a remarkable concordance with more standard economic ranking based, for instance, on GDP per capita.

The role of sleep in regulating structural plasticity and synaptic strength: Implications for memory and cognitive function.

PubMed

Raven, Frank; Van der Zee, Eddy A; Meerlo, Peter; Havekes, Robbert

2018-06-01

Dendritic spines are the major sites of synaptic transmission in the central nervous system. Alterations in the strength of synaptic connections directly affect the neuronal communication, which is crucial for brain function as well as the processing and storage of information. Sleep and sleep loss bidirectionally alter structural plasticity, by affecting spine numbers and morphology, which ultimately can affect the functional output of the brain in terms of alertness, cognition, and mood. Experimental data from studies in rodents suggest that sleep deprivation may impact structural plasticity in different ways. One of the current views, referred to as the synaptic homeostasis hypothesis, suggests that wake promotes synaptic potentiation whereas sleep facilitates synaptic downscaling. On the other hand, several studies have now shown that sleep deprivation can reduce spine density and attenuate synaptic efficacy in the hippocampus. These data are the basis for the view that sleep promotes hippocampal structural plasticity critical for memory formation. Altogether, the impact of sleep and sleep loss may vary between regions of the brain. A better understanding of the role that sleep plays in regulating structural plasticity may ultimately lead to novel therapeutic approaches for brain disorders that are accompanied by sleep disturbances and sleep loss. Copyright © 2017 Elsevier Ltd. All rights reserved.

Budding yeast chromatin is dispersed in a crowded nucleoplasm in vivo

PubMed Central

Chen, Chen; Lim, Hong Hwa; Shi, Jian; Tamura, Sachiko; Maeshima, Kazuhiro; Surana, Uttam; Gan, Lu

2016-01-01

Chromatin organization has an important role in the regulation of eukaryotic systems. Although recent studies have refined the three-dimensional models of chromatin organization with high resolution at the genome sequence level, little is known about how the most fundamental units of chromatin—nucleosomes—are positioned in three dimensions in vivo. Here we use electron cryotomography to study chromatin organization in the budding yeast Saccharomyces cerevisiae. Direct visualization of yeast nuclear densities shows no evidence of 30-nm fibers. Aside from preribosomes and spindle microtubules, few nuclear structures are larger than a tetranucleosome. Yeast chromatin does not form compact structures in interphase or mitosis and is consistent with being in an “open” configuration that is conducive to high levels of transcription. From our study and those of others, we propose that yeast can regulate its transcription using local nucleosome–nucleosome associations. PMID:27605704

Functional Dynamics within the Human Ribosome Regulate the Rate of Active Protein Synthesis.

PubMed

Ferguson, Angelica; Wang, Leyi; Altman, Roger B; Terry, Daniel S; Juette, Manuel F; Burnett, Benjamin J; Alejo, Jose L; Dass, Randall A; Parks, Matthew M; Vincent, C Theresa; Blanchard, Scott C

2015-11-05

The regulation of protein synthesis contributes to gene expression in both normal physiology and disease, yet kinetic investigations of the human translation mechanism are currently lacking. Using single-molecule fluorescence imaging methods, we have quantified the nature and timing of structural processes in human ribosomes during single-turnover and processive translation reactions. These measurements reveal that functional complexes exhibit dynamic behaviors and thermodynamic stabilities distinct from those observed for bacterial systems. Structurally defined sub-states of pre- and post-translocation complexes were sensitive to specific inhibitors of the eukaryotic ribosome, demonstrating the utility of this platform to probe drug mechanism. The application of three-color single-molecule fluorescence resonance energy transfer (smFRET) methods further revealed a long-distance allosteric coupling between distal tRNA binding sites within ribosomes bearing three tRNAs, which contributed to the rate of processive translation. Copyright © 2015 Elsevier Inc. All rights reserved.

Frequency-Dependent Activation of Glucose Utilization in the Superior Cervical Ganglion by Electrical Stimulation of Cervical Sympathetic Trunk

NASA Astrophysics Data System (ADS)

Yarowsky, Paul; Kadekaro, Massako; Sokoloff, Louis

1983-07-01

Electrical stimulation of the distal stump of the transected cervical sympathetic trunk produces a frequency-dependent activation of glucose utilization, measured by the deoxy[14C]glucose method, in the superior cervical ganglion of the urethane-anesthetized rat. The frequency dependence falls between 0-15 Hz; at 20 Hz the activation of glucose utilization is no greater than at 15 Hz. Deafferentation of the superior cervical ganglion by transection of the cervical sympathetic trunk does not diminish the rate of glucose utilization in the ganglion in the urethane-anesthetized rat. These results indicate that the rate of energy metabolism in an innervated neural structure is, at least in part, regulated by the impulse frequency of the electrical input to the structure, and this regulation may be an essential component of the mechanism of the coupling of metabolic activity to functional activity in the nervous system.

Functional dynamics within the human ribosome regulate the rate of active protein synthesis

PubMed Central

Ferguson, Angelica; Wang, Leyi; Altman, Roger B.; Terry, Daniel S.; Juette, Manuel F.; Burnett, Benjamin J.; Alejo, Jose L.; Dass, Randall A.; Parks, Matthew M.; Vincent, Theresa C.; Blanchard, Scott C.

2015-01-01

SUMMARY The regulation of protein synthesis contributes to gene expression in both normal physiology and disease, yet kinetic investigations of the human translation mechanism are currently lacking. Using single-molecule fluorescence imaging methods, we have quantified the nature and timing of structural processes in human ribosomes during single-turnover and processive translation reactions. These measurements reveal that functional complexes exhibit dynamic behaviors and thermodynamic stabilities distinct from those observed for bacterial systems. Structurally defined sub-states of pre- and post-translocation complexes were sensitive to specific inhibitors of the eukaryotic ribosome demonstrating the utility of this platform to probe drug mechanism. The application of three-color single-molecule FRET methods further revealed a long-distance allosteric coupling between distal tRNA binding sites within ribosomes bearing three tRNAs, which contributed to the rate of processive translation. PMID:26593721

Structure and Function of the 26S Proteasome.

PubMed

Bard, Jared A M; Goodall, Ellen A; Greene, Eric R; Jonsson, Erik; Dong, Ken C; Martin, Andreas

2018-06-20

As the endpoint for the ubiquitin-proteasome system, the 26S proteasome is the principal proteolytic machine responsible for regulated protein degradation in eukaryotic cells. The proteasome's cellular functions range from general protein homeostasis and stress response to the control of vital processes such as cell division and signal transduction. To reliably process all the proteins presented to it in the complex cellular environment, the proteasome must combine high promiscuity with exceptional substrate selectivity. Recent structural and biochemical studies have shed new light on the many steps involved in proteasomal substrate processing, including recognition, deubiquitination, and ATP-driven translocation and unfolding. In addition, these studies revealed a complex conformational landscape that ensures proper substrate selection before the proteasome commits to processive degradation. These advances in our understanding of the proteasome's intricate machinery set the stage for future studies on how the proteasome functions as a major regulator of the eukaryotic proteome.

Structural analysis of a Petri net model of oxidative stress in atherosclerosis.

PubMed

Kozak, Adam; Formanowicz, Dorota; Formanowicz, Piotr

2018-06-01

Atherosclerosis is a complex process of gathering sub-endothelial plaques decreasing lumen of the blood vessels. This disorder affects people of all ages, but its progression is asymptomatic for many years. It is regulated by many typical and atypical factors including the immune system response, a chronic kidney disease, a diet rich in lipids, a local inflammatory process and a local oxidative stress that is here one of the key factors. In this study, a Petri net model of atherosclerosis regulation is presented. This model includes also some information about stoichiometric relationships between its components and covers all mentioned factors. For the model, a structural analysis based on invariants was made and biological conclusions are presented. Since the model contains inhibitor arcs, a heuristic method for analysis of such cases is presented. This method can be used to extend the concept of feasible t -invariants.

The Affective Neuroscience of Aging

PubMed Central

Mather, Mara

2018-01-01

While aging is associated with clear declines in physical and cognitive processes, emotional functioning fares relatively well. Consistent with this behavioral profile, two core emotional brain regions, the amygdala and ventromedial prefrontal cortex, show little structural and functional decline in aging, compared with other regions. However, emotional processes depend on interacting systems of neurotransmitters and brain regions that go beyond these structures. This review examines how age-related brain changes influence processes such as attending to and remembering emotional stimuli, regulating emotion, recognizing emotional expressions, empathy, risk taking, impulsivity, behavior change and attentional focus. PMID:26436717

Teaching resources. Protein phosphatases.

PubMed

Salton, Stephen R

2005-03-01

This Teaching Resource provides lecture notes and slides for a class covering the structure and function of protein phosphatases and is part of the course "Cell Signaling Systems: A Course for Graduate Students." The lecture begins with a discussion of the importance of phosphatases in physiology, recognized by the award of a Nobel Prize in 1992, and then proceeds to describe the two types of protein phosphatases: serine/threonine and tyrosine phosphatases. The information covered includes the structure, regulation, and substrate specificity of protein phosphatases, with an emphasis on their importance in disease and clinical settings.

[Mediator processes in the brain structures in the late periods after external and combined exposure to ionizing radiation].

PubMed

Taĭts, M Iu; Dudina, T V; Kandybo, T S; Elkina, A I

1990-01-01

In experiments with mature Wistar male rats it was shown that X-radiation of 12.9 mCi/kg and the combined effect of X-rays and 131I of 6.5 mCi/kg changed the rate of mediator processes in the structures responsible for the hypothalamic function regulation. At remote times (6 months) following irradiation differences were observed in the discoordination of mediator interrelations associated with the peculiarities of the indirect effect of external and combined irradiation implemented via endocrine mechanism system.

The Affective Neuroscience of Aging.

PubMed

Mather, Mara

2016-01-01

Although aging is associated with clear declines in physical and cognitive processes, emotional functioning fares relatively well. Consistent with this behavioral profile, two core emotional brain regions, the amygdala and ventromedial prefrontal cortex, show little structural and functional decline in aging, compared with other regions. However, emotional processes depend on interacting systems of neurotransmitters and brain regions that go beyond these structures. This review examines how age-related brain changes influence processes such as attending to and remembering emotional stimuli, regulating emotion, and recognizing emotional expressions, as well as empathy, risk taking, impulsivity, behavior change, and attentional focus.

Regulation of glycan structures in murine embryonic stem cells: combined transcript profiling of glycan-related genes and glycan structural analysis.

PubMed

Nairn, Alison V; Aoki, Kazuhiro; dela Rosa, Mitche; Porterfield, Mindy; Lim, Jae-Min; Kulik, Michael; Pierce, J Michael; Wells, Lance; Dalton, Stephen; Tiemeyer, Michael; Moremen, Kelley W

2012-11-02

The abundance and structural diversity of glycans on glycoproteins and glycolipids are highly regulated and play important roles during vertebrate development. Because of the challenges associated with studying glycan regulation in vertebrate embryos, we have chosen to study mouse embryonic stem (ES) cells as they differentiate into embryoid bodies (EBs) or into extraembryonic endodermal (ExE) cells as a model for cellular differentiation. We profiled N- and O-glycan structures isolated from these cell populations and examined transcripts encoding the corresponding enzymatic machinery for glycan biosynthesis in an effort to probe the mechanisms that drive the regulation of glycan diversity. During differentiation from mouse ES cells to either EBs or ExE cells, general trends were detected. The predominance of high mannose N-glycans in ES cells shifted to an equal abundance of complex and high mannose structures, increased sialylation, and increased α-Gal termination in the differentiated cell populations. Whereas core 1 O-glycan structures predominated in all three cell populations, increased sialylation and increased core diversity characterized the O-glycans of both differentiated cell types. Increased polysialylation was also found in both differentiated cell types. Differences between the two differentiated cell types included greater sialylation of N-glycans in EBs, whereas α-Gal-capped structures were more prevalent in ExE cells. Changes in glycan structures generally, but not uniformly, correlated with alterations in transcript abundance for the corresponding biosynthetic enzymes, suggesting that transcriptional regulation contributes significantly to the regulation of glycan expression. Knowledge of glycan structural diversity and transcript regulation should provide greater understanding of the roles of protein glycosylation in vertebrate development.

Translational neurocardiology: preclinical models and cardioneural integrative aspects.

PubMed

Ardell, J L; Andresen, M C; Armour, J A; Billman, G E; Chen, P-S; Foreman, R D; Herring, N; O'Leary, D S; Sabbah, H N; Schultz, H D; Sunagawa, K; Zucker, I H

2016-07-15

Neuronal elements distributed throughout the cardiac nervous system, from the level of the insular cortex to the intrinsic cardiac nervous system, are in constant communication with one another to ensure that cardiac output matches the dynamic process of regional blood flow demand. Neural elements in their various 'levels' become differentially recruited in the transduction of sensory inputs arising from the heart, major vessels, other visceral organs and somatic structures to optimize neuronal coordination of regional cardiac function. This White Paper will review the relevant aspects of the structural and functional organization for autonomic control of the heart in normal conditions, how these systems remodel/adapt during cardiac disease, and finally how such knowledge can be leveraged in the evolving realm of autonomic regulation therapy for cardiac therapeutics. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Progress in fuel systems to meet new fuel economy and emissions standards

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1995-12-31

This publication includes information describing the latest developments within the automotive industry on fuel system hardware and control strategies. Contents include: Slow heating process of a heated pintle-type gasoline fuel injector; Mixture preparation measurements; Study of fuel flow rate change in injector for methanol fueled S.I. engine; Flow and structural analysis for fuel pressure regulator performance; A new method to analyze fuel behavior in a spark ignition engine; Throttle body at engine idle -- tolerance effect on flow rate; and more.

A Disintegrin and Metalloprotease 17 in the Cardiovascular and Central Nervous Systems.

PubMed

Xu, Jiaxi; Mukerjee, Snigdha; Silva-Alves, Cristiane R A; Carvalho-Galvão, Alynne; Cruz, Josiane C; Balarini, Camille M; Braga, Valdir A; Lazartigues, Eric; França-Silva, Maria S

2016-01-01

ADAM17 is a metalloprotease and disintegrin that lodges in the plasmatic membrane of several cell types and is able to cleave a wide variety of cell surface proteins. It is somatically expressed in mammalian organisms and its proteolytic action influences several physiological and pathological processes. This review focuses on the structure of ADAM17, its signaling in the cardiovascular system and its participation in certain disorders involving the heart, blood vessels, and neural regulation of autonomic and cardiovascular modulation.

Linear-Quadratic-Gaussian Regulator Developed for a Magnetic Bearing

NASA Technical Reports Server (NTRS)

Choi, Benjamin B.

2002-01-01

Linear-Quadratic-Gaussian (LQG) control is a modern state-space technique for designing optimal dynamic regulators. It enables us to trade off regulation performance and control effort, and to take into account process and measurement noise. The Structural Mechanics and Dynamics Branch at the NASA Glenn Research Center has developed an LQG control for a fault-tolerant magnetic bearing suspension rig to optimize system performance and to reduce the sensor and processing noise. The LQG regulator consists of an optimal state-feedback gain and a Kalman state estimator. The first design step is to seek a state-feedback law that minimizes the cost function of regulation performance, which is measured by a quadratic performance criterion with user-specified weighting matrices, and to define the tradeoff between regulation performance and control effort. The next design step is to derive a state estimator using a Kalman filter because the optimal state feedback cannot be implemented without full state measurement. Since the Kalman filter is an optimal estimator when dealing with Gaussian white noise, it minimizes the asymptotic covariance of the estimation error.

Hindered disulfide bonds to regulate release rate of model drug from mesoporous silica.

PubMed

Nadrah, Peter; Maver, Uroš; Jemec, Anita; Tišler, Tatjana; Bele, Marjan; Dražić, Goran; Benčina, Mojca; Pintar, Albin; Planinšek, Odon; Gaberšček, Miran

2013-05-01

With the advancement of drug delivery systems based on mesoporous silica nanoparticles (MSNs), a simple and efficient method regulating the drug release kinetics is needed. We developed redox-responsive release systems with three levels of hindrance around the disulfide bond. A model drug (rhodamine B dye) was loaded into MSNs' mesoporous voids. The pore opening was capped with β-cyclodextrin in order to prevent leakage of drug. Indeed, in absence of a reducing agent the systems exhibited little leakage, while the addition of dithiothreitol cleaved the disulfide bonds and enabled the release of cargo. The release rate and the amount of released dye were tuned by the level of hindrance around disulfide bonds, with the increased hindrance causing a decrease in the release rate as well as in the amount of released drug. Thus, we demonstrated the ability of the present mesoporous systems to intrinsically control the release rate and the amount of the released cargo by only minor structural variations. Furthermore, an in vivo experiment on zebrafish confirmed that the present model delivery system is nonteratogenic.

Role of substance P in the cardiovascular system.

PubMed

Mistrova, Eliska; Kruzliak, Peter; Chottova Dvorakova, Magdalena

2016-08-01

This article provides an overview of the structure and function of substance P signalling system and its involvement in the cardiovascular regulation. Substance P is an undecapeptide originating from TAC1 gen and belonging to the tachykinin family. The biological actions of substance P are mainly mediated through neurokinin receptor 1 since substance P is the ligand with the highest affinity to neurokinin receptor 1. Substance P is widely distributed within the central and peripheral nervous systems as well as in the cardiovascular system. Substance P is involved in the regulation of heart frequency, blood pressure and in the stretching of vessels. Substance P plays an important role in ischemia and reperfusion and cardiovascular response to stress. Additionally, it has been also implicated in angiogenesis, pain transmission and inflammation. The substance P/neurokinin receptor 1 receptor system is involved in the molecular bases of many human pathological processes. Antagonists of neurokinin receptor 1 receptor could provide clinical solutions for a variety of diseases. Neurokinin receptor 1 antagonists are already used in the prevention of chemotherapy induced nausea and vomiting. Copyright © 2015 Elsevier Ltd. All rights reserved.

Multi-Omics and Integrated Network Analyses Reveal New Insights into the Systems Relationships between Metabolites, Structural Genes, and Transcriptional Regulators in Developing Grape Berries (Vitis vinifera L.) Exposed to Water Deficit.

PubMed

Savoi, Stefania; Wong, Darren C J; Degu, Asfaw; Herrera, Jose C; Bucchetti, Barbara; Peterlunger, Enrico; Fait, Aaron; Mattivi, Fulvio; Castellarin, Simone D

2017-01-01

Grapes are one of the major fruit crops and they are cultivated in many dry environments. This study comprehensively characterizes the metabolic response of grape berries exposed to water deficit at different developmental stages. Increases of proline, branched-chain amino acids, phenylpropanoids, anthocyanins, and free volatile organic compounds have been previously observed in grape berries exposed to water deficit. Integrating RNA-sequencing analysis of the transcriptome with large-scale analysis of central and specialized metabolites, we reveal that these increases occur via a coordinated regulation of key structural pathway genes. Water deficit-induced up-regulation of flavonoid genes is also coordinated with the down-regulation of many stilbene synthases and a consistent decrease in stilbenoid concentration. Water deficit activated both ABA-dependent and ABA-independent signal transduction pathways by modulating the expression of several transcription factors. Gene-gene and gene-metabolite network analyses showed that water deficit-responsive transcription factors such as bZIPs, AP2/ERFs, MYBs, and NACs are implicated in the regulation of stress-responsive metabolites. Enrichment of known and novel cis -regulatory elements in the promoters of several ripening-specific/water deficit-induced modules further affirms the involvement of a transcription factor cross-talk in the berry response to water deficit. Together, our integrated approaches show that water deficit-regulated gene modules are strongly linked to key fruit-quality metabolites and multiple signal transduction pathways may be critical to achieve a balance between the regulation of the stress-response and the berry ripening program. This study constitutes an invaluable resource for future discoveries and comparative studies, in grapes and other fruits, centered on reproductive tissue metabolism under abiotic stress.

Molecular Basis for Modulation of Metabotropic Glutamate Receptors and Their Drug Actions by Extracellular Ca2+

PubMed Central

Zou, Juan; Jiang, Jason Y.; Yang, Jenny J.

2017-01-01

Metabotropic glutamate receptors (mGluRs) associated with the slow phase of the glutamatergic signaling pathway in neurons of the central nervous system have gained importance as drug targets for chronic neurodegenerative diseases. While extracellular Ca2+ was reported to exhibit direct activation and modulation via an allosteric site, the identification of those binding sites was challenged by weak binding. Herein, we review the discovery of extracellular Ca2+ in regulation of mGluRs, summarize the recent developments in probing Ca2+ binding and its co-regulation of the receptor based on structural and biochemical analysis, and discuss the molecular basis for Ca2+ to regulate various classes of drug action as well as its importance as an allosteric modulator in mGluRs. PMID:28335551

Intelligent Chatter Bot for Regulation Search

NASA Astrophysics Data System (ADS)

De Luise, María Daniela López; Pascal, Andrés; Saad, Ben; Álvarez, Claudia; Pescio, Pablo; Carrilero, Patricio; Malgor, Rafael; Díaz, Joaquín

2016-01-01

This communication presents a functional prototype, named PTAH, implementing a linguistic model focused on regulations in Spanish. Its global architecture, the reasoning model and short statistics are provided for the prototype. It is mainly a conversational robot linked to an Expert System by a module with many intelligent linguistic filters, implementing the reasoning model of an expert. It is focused on bylaws, regulations, jurisprudence and customized background representing entity mission, vision and profile. This Structure and model are generic enough to self-adapt to any regulatory environment, but as a first step, it was limited to an academic field. This way it is possible to limit the slang and data numbers. The foundations of the linguistic model are also outlined and the way the architecture implements the key features of the behavior.

Computational study of RNA folding kinetics and thermodynamics

NASA Astrophysics Data System (ADS)

Morgan, Steven Robert

RNA in its many forms is involved in the processes of protein manufacture, gene splicing, catalysis and gene regulation. It is also the store of genetic information in some viruses. The function of the RNA is determined by its structure, and it is the purpose of this thesis to investigate kinetic and thermodynamic properties of RNA secondary structures in order to obtain a better understanding of their formation and function. Our main tenet is that kinetic formation of RNA structure is necessary to explain features found in natural RNA structures, as well as aspects of the biological function of RNA. Firstly we show that examination of the energies of fragments of RNA secondary structure provides evidence for kinetic formation of structure. Local regions of RNA of length less than about 100 nucleotides adopt a conformation with energy near or equal to the minimum possible for those regions, whilst the energies of larger domains are much further from the their respective minima. This is consistent with the patterns that would be expected if RNA structure is folded Idneticatic during transcription. A Monte-Carlo algorithm is then used to model the kinetic folding of RNA during transcriptional growth. The algorithm is capable of finding the correct structure of a natural RNA for which the minimum free energy approach is unsuccessful. In the viral phage MS2 Idneticatic formed RNA structure plays an important role in the regulation of gene expression. The folding algorithm can accurately model this by IdneticaUy controlling access to the gene initiation region. The algorithm is also successfully used to model the control of replication in the ColEl plasmid. Taking a different approach, we then use a simplified model of RNA secondary structure to investigate the size of energy barriers between degenerate minimum energy structures. This model has much in common with physical systems such as spin glasses, and in fact shows similar behaviour to these systems in that energy barriers between structures grow quickly with the length of the RNA sequence. These barriers will serve to trap RNA in non-optimal structures. Together these studies demonstrate the necessity of studying RNA secondary structure from a kinetic point of view, and provide clear directions in which further work may be taken. Kinetic models of RNA secondary structure should continue to prove useful in modelling the structure and function of RNA.

Structural and Mechanistic Roles of Novel Chemical Ligands on the SdiA Quorum-Sensing Transcription Regulator

DOE PAGES

Nguyen, Y.; Nguyen, Nam X.; Rogers, Jamie L.; ...

2015-05-19

Bacteria engage in chemical signaling, termed quorum sensing (QS), to mediate intercellular communication, mimicking multicellular organisms. The LuxR family of QS transcription factors regulates gene expression, coordinating population behavior by sensing endogenous acyl homoserine lactones (AHLs). However, some bacteria (such as Escherichia coli) do not produce AHLs. These LuxR orphans sense exogenous AHLs but also regulate transcription in the absence of AHLs. Importantly, this AHL-independent regulatory mechanism is still largely unknown. Here we present several structures of one such orphan LuxR-type protein, SdiA, from enterohemorrhagic E. coli (EHEC), in the presence and absence of AHL. SdiA is actually not inmore » an apo state without AHL but is regulated by a previously unknown endogenous ligand, 1-octanoyl-rac-glycerol (OCL), which is ubiquitously found throughout the tree of life and serves as an energy source, signaling molecule, and substrate for membrane biogenesis. While exogenous AHL renders to SdiA higher stability and DNA binding affinity, OCL may function as a chemical chaperone placeholder that stabilizes SdiA, allowing for basal activity. Structural comparison between SdiA-AHL and SdiA-OCL complexes provides crucial mechanistic insights into the ligand regulation of AHL-dependent and -independent function of LuxR-type proteins. Importantly, in addition to its contribution to basic science, this work has implications for public health, inasmuch as the SdiA signaling system aids the deadly human pathogen EHEC to adapt to a commensal lifestyle in the gastrointestinal (GI) tract of cattle, its main reservoir. These studies open exciting and novel avenues to control shedding of this human pathogen in the environment. IMPORTANCE Quorum sensing refers to bacterial chemical signaling. The QS acyl homoserine lactone (AHL) signals are recognized by LuxR-type receptors that regulate gene transcription. However, some bacteria have orphan LuxR-type receptors and do not produce AHLs, sensing them from other bacteria. We solved three structures of the E. coli SdiA orphan, in the presence and absence of AHL. SdiA with no AHL is not in an apo state but is regulated by a previously unknown endogenous ligand, 1-octanoyl-rac-glycerol (OCL). OCL is ubiquitously found in prokaryotes and eukaryotes and is a phospholipid precursor for membrane biogenesis and a signaling molecule. While AHL renders to SdiA higher stability and DNA-binding affinity, OCL functions as a chemical chaperone placeholder, stabilizing SdiA and allowing for basal activity. Our studies provide crucial mechanistic insights into the ligand regulation of SdiA activity.« less

Network analyses based on comprehensive molecular interaction maps reveal robust control structures in yeast stress response pathways

PubMed Central

Kawakami, Eiryo; Singh, Vivek K; Matsubara, Kazuko; Ishii, Takashi; Matsuoka, Yukiko; Hase, Takeshi; Kulkarni, Priya; Siddiqui, Kenaz; Kodilkar, Janhavi; Danve, Nitisha; Subramanian, Indhupriya; Katoh, Manami; Shimizu-Yoshida, Yuki; Ghosh, Samik; Jere, Abhay; Kitano, Hiroaki

2016-01-01

Cellular stress responses require exquisite coordination between intracellular signaling molecules to integrate multiple stimuli and actuate specific cellular behaviors. Deciphering the web of complex interactions underlying stress responses is a key challenge in understanding robust biological systems and has the potential to lead to the discovery of targeted therapeutics for diseases triggered by dysregulation of stress response pathways. We constructed large-scale molecular interaction maps of six major stress response pathways in Saccharomyces cerevisiae (baker’s or budding yeast). Biological findings from over 900 publications were converted into standardized graphical formats and integrated into a common framework. The maps are posted at http://www.yeast-maps.org/yeast-stress-response/ for browse and curation by the research community. On the basis of these maps, we undertook systematic analyses to unravel the underlying architecture of the networks. A series of network analyses revealed that yeast stress response pathways are organized in bow–tie structures, which have been proposed as universal sub-systems for robust biological regulation. Furthermore, we demonstrated a potential role for complexes in stabilizing the conserved core molecules of bow–tie structures. Specifically, complex-mediated reversible reactions, identified by network motif analyses, appeared to have an important role in buffering the concentration and activity of these core molecules. We propose complex-mediated reactions as a key mechanism mediating robust regulation of the yeast stress response. Thus, our comprehensive molecular interaction maps provide not only an integrated knowledge base, but also a platform for systematic network analyses to elucidate the underlying architecture in complex biological systems. PMID:28725465

Project Wish: The Emerald City, phase 3

NASA Technical Reports Server (NTRS)

1992-01-01

Phase 3 of Project Wish saw the evolution of the Emerald City (E-City) from a collection of specialized independent analyses and ideas to a working structural design integrated with major support systems and analyses. Emphasis was placed on comparing and contrasting the closed and open cycle gas core nuclear rocket engines to further determine the optimum propulsive system for the C-City. Power and thermal control requirements were then defined and the question of how to meet these requirements was addressed. Software was developed to automate the mission/system/configuration analysis so changes dictated by various subsystems constraints could be managed efficiently and analyzed interactively. In addition, the liquid hydrogen propellant tank was statically designed for minimum mass and shape optimization using a finite element modeling package called SDRC I-DEAS while spoke and shaft cross-sectional areas were optimized on ASTROS (Automated Structural Optimization System). A structural dynamic analysis also conducted using ASTROS enabled a study of the displacements, accelerations, modes and frequencies of the C-City. Finally, the attitude control system design began with an initial mass moment of inertia analysis and was then designed and optimized using linear quadratic regulator control theory.

Contribution of α-smooth muscle actin and extracellular matrix to the in vitro reorganization of cardiomyocyte contractile system.

PubMed

Bildyug, Natalya; Bozhokina, Ekaterina; Khaitlina, Sofia

2016-04-01

Cardiomyocytes in culture undergo reversible rearrangement of their contractile apparatus with the conversion of typical myofibrils into the structures of non-muscle type and the loss of contractility. Along with these transformations, the cardiomyocytes gain the capacity to synthesize extracellular matrix. Here we show that during cultivation of rat neonatal cardiomyocytes, the inherent α-cardiac actin isoform is transiently replaced by α-smooth-muscle actin, whose expression is accompanied by transformation of myofibrils into stress-fiber-like structures. The following down-regulation of α-smooth muscle actin parallels restoration of myofibrillar system and correlates with the accumulation of extracellular collagen and laminin, initially missing from the cardiomyocytes culture. © 2016 International Federation for Cell Biology.

Adaptive management of rangeland systems

USGS Publications Warehouse

Allen, Craig R.; Angeler, David G.; Fontaine, Joseph J.; Garmestani, Ahjond S.; Hart, Noelle M.; Pope, Kevin L.; Twidwell, Dirac

2017-01-01

Adaptive management is an approach to natural resource management that uses structured learning to reduce uncertainties for the improvement of management over time. The origins of adaptive management are linked to ideas of resilience theory and complex systems. Rangeland management is particularly well suited for the application of adaptive management, having sufficient controllability and reducible uncertainties. Adaptive management applies the tools of structured decision making and requires monitoring, evaluation, and adjustment of management. Adaptive governance, involving sharing of power and knowledge among relevant stakeholders, is often required to address conflict situations. Natural resource laws and regulations can present a barrier to adaptive management when requirements for legal certainty are met with environmental uncertainty. However, adaptive management is possible, as illustrated by two cases presented in this chapter. Despite challenges and limitations, when applied appropriately adaptive management leads to improved management through structured learning, and rangeland management is an area in which adaptive management shows promise and should be further explored.

Interrogating viral capsid assembly with ion mobility-mass spectrometry

NASA Astrophysics Data System (ADS)

Uetrecht, Charlotte; Barbu, Ioana M.; Shoemaker, Glen K.; van Duijn, Esther; Heck, Albert J. R.

2011-02-01

Most proteins fulfil their function as part of large protein complexes. Surprisingly, little is known about the pathways and regulation of protein assembly. Several viral coat proteins can spontaneously assemble into capsids in vitro with morphologies identical to the native virion and thus resemble ideal model systems for studying protein complex formation. Even for these systems, the mechanism for self-assembly is still poorly understood, although it is generally thought that smaller oligomeric structures form key intermediates. This assembly nucleus and larger viral assembly intermediates are typically low abundant and difficult to monitor. Here, we characterised small oligomers of Hepatitis B virus (HBV) and norovirus under equilibrium conditions using native ion mobility mass spectrometry. This data in conjunction with computational modelling enabled us to elucidate structural features of these oligomers. Instead of more globular shapes, the intermediates exhibit sheet-like structures suggesting that they are assembly competent. We propose pathways for the formation of both capsids.

Identical phosphatase mechanisms achieved through distinct modes of binding phosphoprotein substrate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pazy, Y.; Motaleb, M.A.; Guarnieri, M.T.

2010-04-05

Two-component signal transduction systems are widespread in prokaryotes and control numerous cellular processes. Extensive investigation of sensor kinase and response regulator proteins from many two-component systems has established conserved sequence, structural, and mechanistic features within each family. In contrast, the phosphatases which catalyze hydrolysis of the response regulator phosphoryl group to terminate signal transduction are poorly understood. Here we present structural and functional characterization of a representative of the CheC/CheX/FliY phosphatase family. The X-ray crystal structure of Borrelia burgdorferi CheX complexed with its CheY3 substrate and the phosphoryl analogue BeF{sub 3}{sup -} reveals a binding orientation between a response regulatormore » and an auxiliary protein different from that shared by every previously characterized example. The surface of CheY3 containing the phosphoryl group interacts directly with a long helix of CheX which bears the conserved (E - X{sub 2} - N) motif. Conserved CheX residues Glu96 and Asn99, separated by a single helical turn, insert into the CheY3 active site. Structural and functional data indicate that CheX Asn99 and CheY3 Thr81 orient a water molecule for hydrolytic attack. The catalytic residues of the CheX-CheY3 complex are virtually superimposable on those of the Escherichia coli CheZ phosphatase complexed with CheY, even though the active site helices of CheX and CheZ are oriented nearly perpendicular to one other. Thus, evolution has found two structural solutions to achieve the same catalytic mechanism through different helical spacing and side chain lengths of the conserved acid/amide residues in CheX and CheZ.« less

Structural and Biochemical Characterization of Spa47 Provides Mechanistic Insight into Type III Secretion System ATPase Activation and Shigella Virulence Regulation.

PubMed

Burgess, Jamie L; Burgess, R Alan; Morales, Yalemi; Bouvang, Jenna M; Johnson, Sean J; Dickenson, Nicholas E

2016-12-09

Like many Gram-negative pathogens, Shigella rely on a complex type III secretion system (T3SS) to inject effector proteins into host cells, take over host functions, and ultimately establish infection. Despite these critical roles, the energetics and regulatory mechanisms controlling the T3SS and pathogen virulence remain largely unclear. In this study, we present a series of high resolution crystal structures of Spa47 and use the structures to model an activated Spa47 oligomer, finding that ATP hydrolysis may be supported by specific side chain contributions from adjacent protomers within the complex. Follow-up mutagenesis experiments targeting the predicted active site residues validate the oligomeric model and determined that each of the tested residues are essential for Spa47 ATPase activity, although they are not directly responsible for stable oligomer formation. Although N-terminal domain truncation was necessary for crystal formation, it resulted in strictly monomeric Spa47 that is unable to hydrolyze ATP, despite maintaining the canonical ATPase core structure and active site residues. Coupled with studies of ATPase inactive full-length Spa47 point mutants, we find that Spa47 oligomerization and ATP hydrolysis are needed for complete T3SS apparatus formation, a proper translocator secretion profile, and Shigella virulence. This work represents the first structure-function characterization of Spa47, uniquely complementing the multitude of included Shigella T3SS phenotype assays and providing a more complete understanding of T3SS ATPase-mediated pathogen virulence. Additionally, these findings provide a strong platform for follow-up studies evaluating regulation of Spa47 oligomerization in vivo as a much needed means of treating and perhaps preventing shigellosis. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Selectively catalytic activity of metal–organic frameworks depending on the N-position within the pyridine ring of their building blocks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, Haitao, E-mail: xuhaitao@ecust.edu.cn; Gou, Yongxia; Ye, Jing

2016-05-15

Iron metal–organic frameworks (MOFs) [Fe(L){sub 2}(SCN){sub 2}]{sub ∝} (L1: 4-bpdh=2,5-bis(4-pyridyl)-3,4-diaza-2,4-hexadiene for 1Fe; and L2: 3-bpdh=2,5-bis(3-pyridyl)-3,4-diaza-2,4-hexadiene for 2Fe) were assembled in a MeOH–H{sub 2}O solvent system. 1Fe exhibits a two-dimensional extended-grid network, whereas 2Fe exhibits a stair-like double-chain; the N-position within the pyridine ring of the complexes was observed to regulate the MOF structure as layers or chains. Furthermore, selectively catalytic activity was observed for the layered MOF but not the chain-structured MOF; micro/nanoparticles of the layered MOF were therefore investigated for new potential applications of micro/nano MOFs. - Graphical abstract: Iron metal–organic frameworks (MOFs) [Fe(L){sub 2}(SCN){sub 2}]{sub ∝} (L1: 4-bpdh=2,5-bis(4-pyridyl)-3,4-diaza-2,4-hexadienemore » for 1Fe; and L2: 3-bpdh=2,5-bis(3-pyridyl)-3,4-diaza-2,4-hexadiene for 2Fe) were assembled in a MeOH–H{sub 2}O solvent system. The N-position within the pyridine ring of the complexes was observed to regulate the MOF structure as layers or chains. Selectively catalytic activity was observed for the layered MOF but not the chain-structured MOF. - Highlights: • Synthesis and structure of metal–organic framework [Fe(L){sub 2}(SCN){sub 2}]{sub ∝}. • Selectively catalytic activity depending on the N-position within the pyridine ring. • The degradation and conversion of methyl orange.« less

Structural and Biochemical Characterization of Spa47 Provides Mechanistic Insight into Type III Secretion System ATPase Activation and Shigella Virulence Regulation*

PubMed Central

Burgess, Jamie L.; Burgess, R. Alan; Morales, Yalemi; Bouvang, Jenna M.; Johnson, Sean J.; Dickenson, Nicholas E.

2016-01-01

Like many Gram-negative pathogens, Shigella rely on a complex type III secretion system (T3SS) to inject effector proteins into host cells, take over host functions, and ultimately establish infection. Despite these critical roles, the energetics and regulatory mechanisms controlling the T3SS and pathogen virulence remain largely unclear. In this study, we present a series of high resolution crystal structures of Spa47 and use the structures to model an activated Spa47 oligomer, finding that ATP hydrolysis may be supported by specific side chain contributions from adjacent protomers within the complex. Follow-up mutagenesis experiments targeting the predicted active site residues validate the oligomeric model and determined that each of the tested residues are essential for Spa47 ATPase activity, although they are not directly responsible for stable oligomer formation. Although N-terminal domain truncation was necessary for crystal formation, it resulted in strictly monomeric Spa47 that is unable to hydrolyze ATP, despite maintaining the canonical ATPase core structure and active site residues. Coupled with studies of ATPase inactive full-length Spa47 point mutants, we find that Spa47 oligomerization and ATP hydrolysis are needed for complete T3SS apparatus formation, a proper translocator secretion profile, and Shigella virulence. This work represents the first structure-function characterization of Spa47, uniquely complementing the multitude of included Shigella T3SS phenotype assays and providing a more complete understanding of T3SS ATPase-mediated pathogen virulence. Additionally, these findings provide a strong platform for follow-up studies evaluating regulation of Spa47 oligomerization in vivo as a much needed means of treating and perhaps preventing shigellosis. PMID:27770024

The content of our cooperation, not the color of our skin: an alliance detection system regulates categorization by coalition and race, but not sex.

PubMed

Pietraszewski, David; Cosmides, Leda; Tooby, John

2014-01-01

Humans in all societies form and participate in cooperative alliances. To successfully navigate an alliance-laced world, the human mind needs to detect new coalitions and alliances as they emerge, and predict which of many potential alliance categories are currently organizing an interaction. We propose that evolution has equipped the mind with cognitive machinery that is specialized for performing these functions: an alliance detection system. In this view, racial categories do not exist because skin color is perceptually salient; they are constructed and regulated by the alliance system in environments where race predicts social alliances and divisions. Early tests using adversarial alliances showed that the mind spontaneously detects which individuals are cooperating against a common enemy, implicitly assigning people to rival alliance categories based on patterns of cooperation and competition. But is social antagonism necessary to trigger the categorization of people by alliance--that is, do we cognitively link A and B into an alliance category only because they are jointly in conflict with C and D? We report new studies demonstrating that peaceful cooperation can trigger the detection of new coalitional alliances and make race fade in relevance. Alliances did not need to be marked by team colors or other perceptually salient cues. When race did not predict the ongoing alliance structure, behavioral cues about cooperative activities up-regulated categorization by coalition and down-regulated categorization by race, sometimes eliminating it. Alliance cues that sensitively regulated categorization by coalition and race had no effect on categorization by sex, eliminating many alternative explanations for the results. The results support the hypothesis that categorizing people by their race is a reversible product of a cognitive system specialized for detecting alliance categories and regulating their use. Common enemies are not necessary to erase important social boundaries; peaceful cooperation can have the same effect.

The Content of Our Cooperation, Not the Color of Our Skin: An Alliance Detection System Regulates Categorization by Coalition and Race, but Not Sex

PubMed Central

Pietraszewski, David; Cosmides, Leda; Tooby, John

2014-01-01

Humans in all societies form and participate in cooperative alliances. To successfully navigate an alliance-laced world, the human mind needs to detect new coalitions and alliances as they emerge, and predict which of many potential alliance categories are currently organizing an interaction. We propose that evolution has equipped the mind with cognitive machinery that is specialized for performing these functions: an alliance detection system. In this view, racial categories do not exist because skin color is perceptually salient; they are constructed and regulated by the alliance system in environments where race predicts social alliances and divisions. Early tests using adversarial alliances showed that the mind spontaneously detects which individuals are cooperating against a common enemy, implicitly assigning people to rival alliance categories based on patterns of cooperation and competition. But is social antagonism necessary to trigger the categorization of people by alliance—that is, do we cognitively link A and B into an alliance category only because they are jointly in conflict with C and D? We report new studies demonstrating that peaceful cooperation can trigger the detection of new coalitional alliances and make race fade in relevance. Alliances did not need to be marked by team colors or other perceptually salient cues. When race did not predict the ongoing alliance structure, behavioral cues about cooperative activities up-regulated categorization by coalition and down-regulated categorization by race, sometimes eliminating it. Alliance cues that sensitively regulated categorization by coalition and race had no effect on categorization by sex, eliminating many alternative explanations for the results. The results support the hypothesis that categorizing people by their race is a reversible product of a cognitive system specialized for detecting alliance categories and regulating their use. Common enemies are not necessary to erase important social boundaries; peaceful cooperation can have the same effect. PMID:24520394

[Agricultural eco-economic system coupling in Zhifanggou watershed in hilly-gully region of Loess Plateau].

PubMed

Wang, Ji-Jun

2009-11-01

Agricultural eco-economic system coupling is an organic unit formed by the inherent interaction between agricultural ecosystem and economic system, and regulated and controlled by mankind moderate interference. Its status can be expressed by the circular chain-net structure of agricultural resources and agricultural industry. The agricultural eco-economic system in Zhifanggou watershed has gone through the process of system coupling, system conflict, system coupling, and partial conflict in high leverage, which is caused by the farmers' requirement and the state's macro-policy, economic means, and administrative means. To cope with the problems of agricultural eco-economics system coupling in Zhifanggou watershed, the optimal coupling model should be established, with tree-grass resources and related industries as the core.

Structural analysis of the Quaking homodimerization interface

PubMed Central

Beuck, Christine; Qu, Song; Fagg, W. Samuel; Ares, Manuel; Williamson, James R.

2012-01-01

Quaking is a prototypical member of the STAR protein family, which plays key roles in posttranscriptional gene regulation by controlling mRNA translation, stability and splicing. QkI-5 has been shown to regulate mRNA expression in the central nervous system, but little is known about its roles in other tissues. STAR proteins function as dimers and bind to bipartite RNA sequences, however, the structural and functional roles of homo- and hetero-dimerization are still unclear. Here, we present the crystal structure of the QkI dimerization domain, which adopts a similar stacked helix-turn-helix arrangement as its homologs GLD-1 and Sam68, but differs by an additional helix inserted in the dimer interface. Variability of the dimer interface residues likely ensures selective homodimerization by preventing association with non-cognate STAR family proteins in the cell. Mutations that inhibit dimerization also significantly impair RNA binding in vitro, alter QkI-5 protein levels, and impair QkI function in a splicing assay in vivo. Together our results indicate that a functional Qua1 homodimerization domain is required for QkI-5 function in mammalian cells. PMID:22982292