Technologies and Approaches to Elucidate and Model the Virulence Program of Salmonella.

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

McDermott, Jason E.; Yoon, Hyunjin; Nakayasu, Ernesto S.

Salmonella is a primary cause of enteric diseases in a variety of animals. During its evolution into a pathogenic bacterium, Salmonella acquired an elaborate regulatory network that responds to multiple environmental stimuli within host animals and integrates them resulting in fine regulation of the virulence program. The coordinated action by this regulatory network involves numerous virulence regulators, necessitating genome-wide profiling analysis to assess and combine efforts from multiple regulons. In this review we discuss recent high-throughput analytic approaches to understand the regulatory network of Salmonella that controls virulence processes. Application of high-throughput analyses have generated a large amount of datamore » and driven development of computational approaches required for data integration. Therefore, we also cover computer-aided network analyses to infer regulatory networks, and demonstrate how genome-scale data can be used to construct regulatory and metabolic systems models of Salmonella pathogenesis. Genes that are coordinately controlled by multiple virulence regulators under infectious conditions are more likely to be important for pathogenesis. Thus, reconstructing the global regulatory network during infection or, at the very least, under conditions that mimic the host cellular environment not only provides a bird’s eye view of Salmonella survival strategy in response to hostile host environments but also serves as an efficient means to identify novel virulence factors that are essential for Salmonella to accomplish systemic infection in the host.« less

Small heterodimer partner (NROB2) coordinates nutrient signaling and the circadian clock in mice

USDA-ARS?s Scientific Manuscript database

Circadian rhythm regulates multiple metabolic processes and in turn is readily entrained by feeding-fasting cycles. However, the molecular mechanisms by which the peripheral clock senses nutrition availability remain largely unknown. Bile acids are under circadian control and also increase postprand...

Statistical significance of combinatorial regulations

PubMed Central

Terada, Aika; Okada-Hatakeyama, Mariko; Tsuda, Koji; Sese, Jun

2013-01-01

More than three transcription factors often work together to enable cells to respond to various signals. The detection of combinatorial regulation by multiple transcription factors, however, is not only computationally nontrivial but also extremely unlikely because of multiple testing correction. The exponential growth in the number of tests forces us to set a strict limit on the maximum arity. Here, we propose an efficient branch-and-bound algorithm called the “limitless arity multiple-testing procedure” (LAMP) to count the exact number of testable combinations and calibrate the Bonferroni factor to the smallest possible value. LAMP lists significant combinations without any limit, whereas the family-wise error rate is rigorously controlled under the threshold. In the human breast cancer transcriptome, LAMP discovered statistically significant combinations of as many as eight binding motifs. This method may contribute to uncover pathways regulated in a coordinated fashion and find hidden associations in heterogeneous data. PMID:23882073

The Mediator complex: a master coordinator of transcription and cell lineage development.

PubMed

Yin, Jing-wen; Wang, Gang

2014-03-01

Mediator is a multiprotein complex that is required for gene transcription by RNA polymerase II. Multiple subunits of the complex show specificity in relaying information from signals and transcription factors to the RNA polymerase II machinery, thus enabling control of the expression of specific genes. Recent studies have also provided novel mechanistic insights into the roles of Mediator in epigenetic regulation, transcriptional elongation, termination, mRNA processing, noncoding RNA activation and super enhancer formation. Based on these specific roles in gene regulation, Mediator has emerged as a master coordinator of development and cell lineage determination. Here, we describe the most recent advances in understanding the mechanisms of Mediator function, with an emphasis on its role during development and disease.

The C. elegans RSA complex localizes protein phosphatase 2A to centrosomes and regulates mitotic spindle assembly.

PubMed

Schlaitz, Anne-Lore; Srayko, Martin; Dammermann, Alexander; Quintin, Sophie; Wielsch, Natalie; MacLeod, Ian; de Robillard, Quentin; Zinke, Andrea; Yates, John R; Müller-Reichert, Thomas; Shevchenko, Andrei; Oegema, Karen; Hyman, Anthony A

2007-01-12

Microtubule behavior changes during the cell cycle and during spindle assembly. However, it remains unclear how these changes are regulated and coordinated. We describe a complex that targets the Protein Phosphatase 2A holoenzyme (PP2A) to centrosomes in C. elegans embryos. This complex includes Regulator of Spindle Assembly 1 (RSA-1), a targeting subunit for PP2A, and RSA-2, a protein that binds and recruits RSA-1 to centrosomes. In contrast to the multiple functions of the PP2A catalytic subunit, RSA-1 and RSA-2 are specifically required for microtubule outgrowth from centrosomes and for spindle assembly. The centrosomally localized RSA-PP2A complex mediates these functions in part by regulating two critical mitotic effectors: the microtubule destabilizer KLP-7 and the C. elegans regulator of spindle assembly TPXL-1. By regulating a subset of PP2A functions at the centrosome, the RSA complex could therefore provide a means of coordinating microtubule outgrowth from centrosomes and kinetochore microtubule stability during mitotic spindle assembly.

Effects of adenosine triphosphate concentration on motor force regulation during skeletal muscle contraction

NASA Astrophysics Data System (ADS)

Wei, J.; Dong, C.; Chen, B.

2017-04-01

We employ a mechanical model of sarcomere to quantitatively investigate how adenosine triphosphate (ATP) concentration affects motor force regulation during skeletal muscle contraction. Our simulation indicates that there can be negative cross-bridges resisting contraction within the sarcomere and higher ATP concentration would decrease the resistance force from negative cross-bridges by promoting their timely detachment. It is revealed that the motor force is well regulated only when ATP concentration is above a certain level. These predictions may provide insights into the role of ATP in regulating coordination among multiple motors.

cAMP/PKA signaling balances respiratory activity with mitochondria dependent apoptosis via transcriptional regulation

PubMed Central

2010-01-01

Background Appropriate control of mitochondrial function, morphology and biogenesis are crucial determinants of the general health of eukaryotic cells. It is therefore imperative that we understand the mechanisms that co-ordinate mitochondrial function with environmental signaling systems. The regulation of yeast mitochondrial function in response to nutritional change can be modulated by PKA activity. Unregulated PKA activity can lead to the production of mitochondria that are prone to the production of ROS, and an apoptotic form of cell death. Results We present evidence that mitochondria are sensitive to the level of cAMP/PKA signaling and can respond by modulating levels of respiratory activity or committing to self execution. The inappropriate activation of one of the yeast PKA catalytic subunits, Tpk3p, is sufficient to commit cells to an apoptotic death through transcriptional changes that promote the production of dysfunctional, ROS producing mitochondria. Our data implies that cAMP/PKA regulation of mitochondrial function that promotes apoptosis engages the function of multiple transcription factors, including HAP4, SOK2 and SCO1. Conclusions We propose that in yeast, as is the case in mammalian cells, mitochondrial function and biogenesis are controlled in response to environmental change by the concerted regulation of multiple transcription factors. The visualization of cAMP/TPK3 induced cell death within yeast colonies supports a model that PKA regulation plays a physiological role in coordinating respiratory function and cell death with nutritional status in budding yeast. PMID:21108829

Multiscale Models in the Biomechanics of Plant Growth

PubMed Central

Fozard, John A.

2015-01-01

Plant growth occurs through the coordinated expansion of tightly adherent cells, driven by regulated softening of cell walls. It is an intrinsically multiscale process, with the integrated properties of multiple cell walls shaping the whole tissue. Multiscale models encode physical relationships to bring new understanding to plant physiology and development. PMID:25729061

Structural basis for regulation of rhizobial nodulation and symbiosis gene expression by the regulatory NolR

USDA-ARS?s Scientific Manuscript database

The symbiosis between rhizobial microbes and host plants involves the coordinated expression of multiple genes, which leads to nodule formation and nitrogen fixation. As part of the transcriptional machinery for nodulation and symbiosis across a range of Rhizobium, NolR serves as a global regulatory...

Amplified Rate Acceleration by Simultaneous Up-Regulation of Multiple Active Sites in an Endo-Functionalized Porous Capsule.

PubMed

Kopilevich, Sivil; Müller, Achim; Weinstock, Ira A

2015-10-14

Using the hydrolysis of epoxides in water as a model reaction, the effect of multiple active sites on Michaelis-Menten compliant rate accelerations in a porous capsule is demonstrated. The capsule is a water-soluble Ih-symmetry Keplerate-type complex of the form, [{Mo(VI)6O21(H2O)6}12{Mo(V)2O4(L)}30](42-), in which 12 pentagonal "ligands," {(Mo(VI))Mo(VI)5O21(H2O)6}(6-), are coordinated to 30 dimolybdenum sites, {Mo(V)2O4L}(1+) (L = an endohedrally coordinated η(2)-bound carboxylate anion), resulting in 20 Mo9O9 pores. When "up-regulated" by removal of ca. one-third of the blocking ligands, L, an equal number of dimolybdenum sites are activated, and the newly freed-up space allows for encapsulation of nearly twice as many substrate guests, leading to a larger effective molarity (amplification), and an increase in the rate acceleration (k(cat)/k(uncat)) from 16,000 to an enzyme-like value of 182,800.

The metazoan Mediator co-activator complex as an integrative hub for transcriptional regulation.

PubMed

Malik, Sohail; Roeder, Robert G

2010-11-01

The Mediator is an evolutionarily conserved, multiprotein complex that is a key regulator of protein-coding genes. In metazoan cells, multiple pathways that are responsible for homeostasis, cell growth and differentiation converge on the Mediator through transcriptional activators and repressors that target one or more of the almost 30 subunits of this complex. Besides interacting directly with RNA polymerase II, Mediator has multiple functions and can interact with and coordinate the action of numerous other co-activators and co-repressors, including those acting at the level of chromatin. These interactions ultimately allow the Mediator to deliver outputs that range from maximal activation of genes to modulation of basal transcription to long-term epigenetic silencing.

Stress and serial adult metamorphosis: multiple roles for the stress axis in socially regulated sex change.

PubMed

Solomon-Lane, Tessa K; Crespi, Erica J; Grober, Matthew S

2013-01-01

Socially regulated sex change in teleost fishes is a striking example of social status information regulating biological function in the service of reproductive success. The establishment of social dominance in sex changing species is translated into a cascade of changes in behavior, physiology, neuroendocrine function, and morphology that transforms a female into a male, or vice versa. The hypothalamic-pituitary-interrenal axis (HPI, homologous to HP-adrenal axis in mammals and birds) has been hypothesized to play a mechanistic role linking status to sex change. The HPA/I axis responds to environmental stressors by integrating relevant external and internal cues and coordinating biological responses including changes in behavior, energetics, physiology, and morphology (i.e., metamorphosis). Through actions of both corticotropin-releasing factor and glucocorticoids, the HPA/I axis has been implicated in processes central to sex change, including the regulation of agonistic behavior, social status, energetic investment, and life history transitions. In this paper, we review the hypothesized roles of the HPA/I axis in the regulation of sex change and how those hypotheses have been tested to date. We include original data on sex change in the bluebanded goby (Lythyrpnus dalli), a highly social fish capable of bidirectional sex change. We then propose a model for HPA/I involvement in sex change and discuss how these ideas might be tested in the future. Understanding the regulation of sex change has the potential to elucidate evolutionarily conserved mechanisms responsible for translating pertinent information about the environment into coordinated biological changes along multiple body axes.

Stress and serial adult metamorphosis: multiple roles for the stress axis in socially regulated sex change

PubMed Central

Solomon-Lane, Tessa K.; Crespi, Erica J.; Grober, Matthew S.

2013-01-01

Socially regulated sex change in teleost fishes is a striking example of social status information regulating biological function in the service of reproductive success. The establishment of social dominance in sex changing species is translated into a cascade of changes in behavior, physiology, neuroendocrine function, and morphology that transforms a female into a male, or vice versa. The hypothalamic-pituitary-interrenal axis (HPI, homologous to HP-adrenal axis in mammals and birds) has been hypothesized to play a mechanistic role linking status to sex change. The HPA/I axis responds to environmental stressors by integrating relevant external and internal cues and coordinating biological responses including changes in behavior, energetics, physiology, and morphology (i.e., metamorphosis). Through actions of both corticotropin-releasing factor and glucocorticoids, the HPA/I axis has been implicated in processes central to sex change, including the regulation of agonistic behavior, social status, energetic investment, and life history transitions. In this paper, we review the hypothesized roles of the HPA/I axis in the regulation of sex change and how those hypotheses have been tested to date. We include original data on sex change in the bluebanded goby (Lythyrpnus dalli), a highly social fish capable of bidirectional sex change. We then propose a model for HPA/I involvement in sex change and discuss how these ideas might be tested in the future. Understanding the regulation of sex change has the potential to elucidate evolutionarily conserved mechanisms responsible for translating pertinent information about the environment into coordinated biological changes along multiple body axes. PMID:24265604

Systems Biophysics of Gene Expression

PubMed Central

Vilar, Jose M.G.; Saiz, Leonor

2013-01-01

Gene expression is a process central to any form of life. It involves multiple temporal and functional scales that extend from specific protein-DNA interactions to the coordinated regulation of multiple genes in response to intracellular and extracellular changes. This diversity in scales poses fundamental challenges to the use of traditional approaches to fully understand even the simplest gene expression systems. Recent advances in computational systems biophysics have provided promising avenues to reliably integrate the molecular detail of biophysical process into the system behavior. Here, we review recent advances in the description of gene regulation as a system of biophysical processes that extend from specific protein-DNA interactions to the combinatorial assembly of nucleoprotein complexes. There is now basic mechanistic understanding on how promoters controlled by multiple, local and distal, DNA binding sites for transcription factors can actively control transcriptional noise, cell-to-cell variability, and other properties of gene regulation, including precision and flexibility of the transcriptional responses. PMID:23790365

Genotet: An Interactive Web-based Visual Exploration Framework to Support Validation of Gene Regulatory Networks.

PubMed

Yu, Bowen; Doraiswamy, Harish; Chen, Xi; Miraldi, Emily; Arrieta-Ortiz, Mario Luis; Hafemeister, Christoph; Madar, Aviv; Bonneau, Richard; Silva, Cláudio T

2014-12-01

Elucidation of transcriptional regulatory networks (TRNs) is a fundamental goal in biology, and one of the most important components of TRNs are transcription factors (TFs), proteins that specifically bind to gene promoter and enhancer regions to alter target gene expression patterns. Advances in genomic technologies as well as advances in computational biology have led to multiple large regulatory network models (directed networks) each with a large corpus of supporting data and gene-annotation. There are multiple possible biological motivations for exploring large regulatory network models, including: validating TF-target gene relationships, figuring out co-regulation patterns, and exploring the coordination of cell processes in response to changes in cell state or environment. Here we focus on queries aimed at validating regulatory network models, and on coordinating visualization of primary data and directed weighted gene regulatory networks. The large size of both the network models and the primary data can make such coordinated queries cumbersome with existing tools and, in particular, inhibits the sharing of results between collaborators. In this work, we develop and demonstrate a web-based framework for coordinating visualization and exploration of expression data (RNA-seq, microarray), network models and gene-binding data (ChIP-seq). Using specialized data structures and multiple coordinated views, we design an efficient querying model to support interactive analysis of the data. Finally, we show the effectiveness of our framework through case studies for the mouse immune system (a dataset focused on a subset of key cellular functions) and a model bacteria (a small genome with high data-completeness).

Bimanual motor coordination controlled by cooperative interactions in intrinsic and extrinsic coordinates.

PubMed

Sakurada, Takeshi; Ito, Koji; Gomi, Hiroaki

2016-01-01

Although strong motor coordination in intrinsic muscle coordinates has frequently been reported for bimanual movements, coordination in extrinsic visual coordinates is also crucial in various bimanual tasks. To explore the bimanual coordination mechanisms in terms of the frame of reference, here we characterized implicit bilateral interactions in visuomotor tasks. Visual perturbations (finger-cursor gain change) were applied while participants performed a rhythmic tracking task with both index fingers under an in-phase or anti-phase relationship in extrinsic coordinates. When they corrected the right finger's amplitude, the left finger's amplitude unintentionally also changed [motor interference (MI)], despite the instruction to keep its amplitude constant. Notably, we observed two specificities: one was large MI and low relative-phase variability (PV) under the intrinsic in-phase condition, and the other was large MI and high PV under the extrinsic in-phase condition. Additionally, using a multiple-interaction model, we successfully decomposed MI into intrinsic components caused by motor correction and extrinsic components caused by visual-cursor mismatch of the right finger's movements. This analysis revealed that the central nervous system facilitates MI by combining intrinsic and extrinsic components in the condition with in-phases in both intrinsic and extrinsic coordinates, and that under-additivity of the effects is explained by the brain's preference for the intrinsic interaction over extrinsic interaction. In contrast, the PV was significantly correlated with the intrinsic component, suggesting that the intrinsic interaction dominantly contributed to bimanual movement stabilization. The inconsistent features of MI and PV suggest that the central nervous system regulates multiple levels of bilateral interactions for various bimanual tasks. © 2015 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

29 CFR 31.12 - Effect on other regulations; supervision and coordination.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 1 2011-07-01 2011-07-01 false Effect on other regulations; supervision and coordination... on other regulations; supervision and coordination. (a) Effect on other regulations. All regulations... inapplicable, or prohibits discrimination on any other ground. (b) Supervision and coordination. (1) The...

29 CFR 31.12 - Effect on other regulations; supervision and coordination.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 29 Labor 1 2012-07-01 2012-07-01 false Effect on other regulations; supervision and coordination... on other regulations; supervision and coordination. (a) Effect on other regulations. All regulations... inapplicable, or prohibits discrimination on any other ground. (b) Supervision and coordination. (1) The...

29 CFR 31.12 - Effect on other regulations; supervision and coordination.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 29 Labor 1 2013-07-01 2013-07-01 false Effect on other regulations; supervision and coordination... on other regulations; supervision and coordination. (a) Effect on other regulations. All regulations... inapplicable, or prohibits discrimination on any other ground. (b) Supervision and coordination. (1) The...

29 CFR 31.12 - Effect on other regulations; supervision and coordination.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 1 2010-07-01 2010-07-01 true Effect on other regulations; supervision and coordination... on other regulations; supervision and coordination. (a) Effect on other regulations. All regulations... inapplicable, or prohibits discrimination on any other ground. (b) Supervision and coordination. (1) The...

Dynamic ubiquitin signaling in cell cycle regulation

PubMed Central

Gilberto, Samuel

2017-01-01

The cell division cycle is driven by a collection of enzymes that coordinate DNA duplication and separation, ensuring that genomic information is faithfully and perpetually maintained. The activity of the effector proteins that perform and coordinate these biological processes oscillates by regulated expression and/or posttranslational modifications. Ubiquitylation is a cardinal cellular modification and is long known for driving cell cycle transitions. In this review, we emphasize emerging concepts of how ubiquitylation brings the necessary dynamicity and plasticity that underlie the processes of DNA replication and mitosis. New studies, often focusing on the regulation of chromosomal proteins like DNA polymerases or kinetochore kinases, are demonstrating that ubiquitylation is a versatile modification that can be used to fine-tune these cell cycle events, frequently through processes that do not involve proteasomal degradation. Understanding how the increasing variety of identified ubiquitin signals are transduced will allow us to develop a deeper mechanistic perception of how the multiple factors come together to faithfully propagate genomic information. Here, we discuss these and additional conceptual challenges that are currently under study toward understanding how ubiquitin governs cell cycle regulation. PMID:28684425

Dynamic ubiquitin signaling in cell cycle regulation.

PubMed

Gilberto, Samuel; Peter, Matthias

2017-08-07

The cell division cycle is driven by a collection of enzymes that coordinate DNA duplication and separation, ensuring that genomic information is faithfully and perpetually maintained. The activity of the effector proteins that perform and coordinate these biological processes oscillates by regulated expression and/or posttranslational modifications. Ubiquitylation is a cardinal cellular modification and is long known for driving cell cycle transitions. In this review, we emphasize emerging concepts of how ubiquitylation brings the necessary dynamicity and plasticity that underlie the processes of DNA replication and mitosis. New studies, often focusing on the regulation of chromosomal proteins like DNA polymerases or kinetochore kinases, are demonstrating that ubiquitylation is a versatile modification that can be used to fine-tune these cell cycle events, frequently through processes that do not involve proteasomal degradation. Understanding how the increasing variety of identified ubiquitin signals are transduced will allow us to develop a deeper mechanistic perception of how the multiple factors come together to faithfully propagate genomic information. Here, we discuss these and additional conceptual challenges that are currently under study toward understanding how ubiquitin governs cell cycle regulation. © 2017 Gilberto and Peter.

Functionally specific renal sympathetic nerve fibers: role in cardiovascular regulation.

PubMed

DiBona, G F

2001-06-01

The sympathetic nervous system provides differentiated regulation of the functions of various organs. This differentiated regulation occurs through mechanisms that operate at multiple sites within the classic reflex arc: peripherally at the level of afferent input stimuli to various reflex pathways, centrally at the level of interconnections between various central neuron pools, and peripherally at the level of efferent fibers targeted to various effectors within the organ. In the kidney, increased renal sympathetic nerve activity regulates the functions of the intrarenal effectors: the tubules, the blood vessels, and the juxtaglomerular granular cells. This enables a physiologically appropriate coordination between the circulatory, filtration, reabsorptive, excretory, and renin secretory contributions to overall renal function. Anatomically, each of these effectors has a dual pattern of innervation consisting of a specific and selective innervation by unmyelinated slowly conducting C-type renal sympathetic nerve fibers and an innervation that is shared among all the effectors. This arrangement facilitates maximum flexibility in the coordination of the tubules, the blood vessels, and the juxtaglomerular granular cells so as to produce physiologically appropriate responses to a variety of homeostatic requirements.

Endocytosis-dependent coordination of multiple actin regulators is required for wound healing

PubMed Central

Matsubayashi, Yutaka; Coulson-Gilmer, Camilla

2015-01-01

The ability to heal wounds efficiently is essential for life. After wounding of an epithelium, the cells bordering the wound form dynamic actin protrusions and/or a contractile actomyosin cable, and these actin structures drive wound closure. Despite their importance in wound healing, the molecular mechanisms that regulate the assembly of these actin structures at wound edges are not well understood. In this paper, using Drosophila melanogaster embryos, we demonstrate that Diaphanous, SCAR, and WASp play distinct but overlapping roles in regulating actin assembly during wound healing. Moreover, we show that endocytosis is essential for wound edge actin assembly and wound closure. We identify adherens junctions (AJs) as a key target of endocytosis during wound healing and propose that endocytic remodeling of AJs is required to form “signaling centers” along the wound edge that control actin assembly. We conclude that coordination of actin assembly, AJ remodeling, and membrane traffic is required for the construction of a motile leading edge during wound healing. PMID:26216900

Emergence of multiple synchronization modes in hydrodynamically-coupled cilia

NASA Astrophysics Data System (ADS)

Guo, Hanliang; Kanso, Eva

2016-11-01

Motile cilia and flagella exhibit different phase coordinations. For example, closely swimming spermatozoa are observed to synchronize together; bi-flagellates Chlamydomonas regulate the flagella in a "breast-stroke" fashion; cilia on the surface of Paramecium beat in a fixed phase lag in an orchestrated wave like fashion. Experimental evidence suggests that phase coordinations can be achieved solely via hydrodynamical interactions. However, the exact mechanisms behind it remain illusive. Here, adapting a "geometric switch" model, we observe different synchronization modes in pairs of hydrodynamically-coupled cilia by changing physical parameters such as the strength of the cilia internal motor and the separation distance between cilia. Interestingly, we find regions in the parameter space where the coupled cilia reach stable phase coordinations and regions where the phase coordinations are sensitive to perturbations. We also find that leaning into the fluid reduces the sensitivity to perturbations, and produces stable phase coordination that is neither in-phase nor anti-phase, which could explain the origin of metachronal waves in large cilia populations.

Widespread promoter-mediated coordination of transcription and mRNA degradation

PubMed Central

2012-01-01

Background Previous work showed that mRNA degradation is coordinated with transcription in yeast, and in several genes the control of mRNA degradation was linked to promoter elements through two different mechanisms. Here we show at the genomic scale that the coordination of transcription and mRNA degradation is promoter-dependent in yeast and is also observed in humans. Results We first demonstrate that swapping upstream cis-regulatory sequences between two yeast species affects both transcription and mRNA degradation and suggest that while some cis-regulatory elements control either transcription or degradation, multiple other elements enhance both processes. Second, we show that adjacent yeast genes that share a promoter (through divergent orientation) have increased similarity in their patterns of mRNA degradation, providing independent evidence for the promoter-mediated coupling of transcription to mRNA degradation. Finally, analysis of the differences in mRNA degradation rates between mammalian cell types or mammalian species suggests a similar coordination between transcription and mRNA degradation in humans. Conclusions Our results extend previous studies and suggest a pervasive promoter-mediated coordination between transcription and mRNA degradation in yeast. The diverse genes and regulatory elements associated with this coordination suggest that it is generated by a global mechanism of gene regulation and modulated by gene-specific mechanisms. The observation of a similar coupling in mammals raises the possibility that coupling of transcription and mRNA degradation may reflect an evolutionarily conserved phenomenon in gene regulation. PMID:23237624

Potential Mechanisms Underlying Intercortical Signal Regulation via Cholinergic Neuromodulators

PubMed Central

Whittington, Miles A.; Kopell, Nancy J.

2015-01-01

The dynamical behavior of the cortex is extremely complex, with different areas and even different layers of a cortical column displaying different temporal patterns. A major open question is how the signals from different layers and different brain regions are coordinated in a flexible manner to support function. Here, we considered interactions between primary auditory cortex and adjacent association cortex. Using a biophysically based model, we show how top-down signals in the beta and gamma regimes can interact with a bottom-up gamma rhythm to provide regulation of signals between the cortical areas and among layers. The flow of signals depends on cholinergic modulation: with only glutamatergic drive, we show that top-down gamma rhythms may block sensory signals. In the presence of cholinergic drive, top-down beta rhythms can lift this blockade and allow signals to flow reciprocally between primary sensory and parietal cortex. SIGNIFICANCE STATEMENT Flexible coordination of multiple cortical areas is critical for complex cognitive functions, but how this is accomplished is not understood. Using computational models, we studied the interactions between primary auditory cortex (A1) and association cortex (Par2). Our model is capable of replicating interaction patterns observed in vitro and the simulations predict that the coordination between top-down gamma and beta rhythms is central to the gating process regulating bottom-up sensory signaling projected from A1 to Par2 and that cholinergic modulation allows this coordination to occur. PMID:26558772

Coordinated regulation of intracellular pH by two glucose-sensing pathways in yeast.

PubMed

Isom, Daniel G; Page, Stephani C; Collins, Leonard B; Kapolka, Nicholas J; Taghon, Geoffrey J; Dohlman, Henrik G

2018-02-16

The yeast Saccharomyces cerevisiae employs multiple pathways to coordinate sugar availability and metabolism. Glucose and other sugars are detected by a G protein-coupled receptor, Gpr1, as well as a pair of transporter-like proteins, Rgt2 and Snf3. When glucose is limiting, however, an ATP-driven proton pump (Pma1) is inactivated, leading to a marked decrease in cytoplasmic pH. Here we determine the relative contribution of the two sugar-sensing pathways to pH regulation. Whereas cytoplasmic pH is strongly dependent on glucose abundance and is regulated by both glucose-sensing pathways, ATP is largely unaffected and therefore cannot account for the changes in Pma1 activity. These data suggest that the pH is a second messenger of the glucose-sensing pathways. We show further that different sugars differ in their ability to control cellular acidification, in the manner of inverse agonists. We conclude that the sugar-sensing pathways act via Pma1 to invoke coordinated changes in cellular pH and metabolism. More broadly, our findings support the emerging view that cellular systems have evolved the use of pH signals as a means of adapting to environmental stresses such as those caused by hypoxia, ischemia, and diabetes. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

GPS-Free Localization Algorithm for Wireless Sensor Networks

PubMed Central

Wang, Lei; Xu, Qingzheng

2010-01-01

Localization is one of the most fundamental problems in wireless sensor networks, since the locations of the sensor nodes are critical to both network operations and most application level tasks. A GPS-free localization scheme for wireless sensor networks is presented in this paper. First, we develop a standardized clustering-based approach for the local coordinate system formation wherein a multiplication factor is introduced to regulate the number of master and slave nodes and the degree of connectivity among master nodes. Second, using homogeneous coordinates, we derive a transformation matrix between two Cartesian coordinate systems to efficiently merge them into a global coordinate system and effectively overcome the flip ambiguity problem. The algorithm operates asynchronously without a centralized controller; and does not require that the location of the sensors be known a priori. A set of parameter-setting guidelines for the proposed algorithm is derived based on a probability model and the energy requirements are also investigated. A simulation analysis on a specific numerical example is conducted to validate the mathematical analytical results. We also compare the performance of the proposed algorithm under a variety multiplication factor, node density and node communication radius scenario. Experiments show that our algorithm outperforms existing mechanisms in terms of accuracy and convergence time. PMID:22219694

Regulation of alternative splicing in Drosophila by 56 RNA binding proteins

DOE PAGES

Brooks, Angela N.; Duff, Michael O.; May, Gemma; ...

2015-08-20

Alternative splicing is regulated by RNA binding proteins (RBPs) that recognize pre-mRNA sequence elements and activate or repress adjacent exons. Here, we used RNA interference and RNA-seq to identify splicing events regulated by 56 Drosophila proteins, some previously unknown to regulate splicing. Nearly all proteins affected alternative first exons, suggesting that RBPs play important roles in first exon choice. Half of the splicing events were regulated by multiple proteins, demonstrating extensive combinatorial regulation. We observed that SR and hnRNP proteins tend to act coordinately with each other, not antagonistically. We also identified a cross-regulatory network where splicing regulators affected themore » splicing of pre-mRNAs encoding other splicing regulators. In conclusion, this large-scale study substantially enhances our understanding of recent models of splicing regulation and provides a resource of thousands of exons that are regulated by 56 diverse RBPs.« less

The coordination of ploidy and cell size differs between cell layers in leaves

PubMed Central

Katagiri, Yohei; Hasegawa, Junko; Fujikura, Ushio; Hoshino, Rina; Matsunaga, Sachihiro; Tsukaya, Hirokazu

2016-01-01

Growth and developmental processes are occasionally accompanied by multiple rounds of DNA replication, known as endoreduplication. Coordination between endoreduplication and cell size regulation often plays a crucial role in proper organogenesis and cell differentiation. Here, we report that the level of correlation between ploidy and cell volume is different in the outer and inner cell layers of leaves of Arabidopsis thaliana using a novel imaging technique. Although there is a well-known, strong correlation between ploidy and cell volume in pavement cells of the epidermis, this correlation was extremely weak in palisade mesophyll cells. Induction of epidermis cell identity based on the expression of the homeobox gene ATML1 in mesophyll cells enhanced the level of correlation between ploidy and cell volume to near that of wild-type epidermal cells. We therefore propose that the correlation between ploidy and cell volume is regulated by cell identity. PMID:26903507

Reactive oxygen species-dependent wound responses in animals and plants.

PubMed

Suzuki, Nobuhiro; Mittler, Ron

2012-12-15

Animals and plants evolved sophisticated mechanisms that regulate their responses to mechanical injury. Wound response in animals mainly promotes wound healing processes, nerve cell regeneration, and immune system responses at the vicinity of the wound site. In contrast, wound response in plants is primarily directed at sealing the wound site via deposition of various compounds and generating systemic signals that activate multiple defense mechanisms in remote tissues. Despite these differences between animals and plants, recent studies have shown that reactive oxygen species (ROS) play very common signaling and coordination roles in the wound responses of both systems. This review provides an update on recent findings related to ROS-regulated coordination of intercellular communications and signal transduction during wound response in plants and animals. In particular, differences and similarities in H2O2-dependent long-distance signaling between zebrafish and Arabidopsis thaliana are discussed. Published by Elsevier Inc.

Phosphoinositide 3-Kinase Regulates Glycolysis through Mobilization of Aldolase from the Actin Cytoskeleton.

PubMed

Hu, Hai; Juvekar, Ashish; Lyssiotis, Costas A; Lien, Evan C; Albeck, John G; Oh, Doogie; Varma, Gopal; Hung, Yin Pun; Ullas, Soumya; Lauring, Josh; Seth, Pankaj; Lundquist, Mark R; Tolan, Dean R; Grant, Aaron K; Needleman, Daniel J; Asara, John M; Cantley, Lewis C; Wulf, Gerburg M

2016-01-28

The phosphoinositide 3-kinase (PI3K) pathway regulates multiple steps in glucose metabolism and also cytoskeletal functions, such as cell movement and attachment. Here, we show that PI3K directly coordinates glycolysis with cytoskeletal dynamics in an AKT-independent manner. Growth factors or insulin stimulate the PI3K-dependent activation of Rac, leading to disruption of the actin cytoskeleton, release of filamentous actin-bound aldolase A, and an increase in aldolase activity. Consistently, PI3K inhibitors, but not AKT, SGK, or mTOR inhibitors, cause a significant decrease in glycolysis at the step catalyzed by aldolase, while activating PIK3CA mutations have the opposite effect. These results point toward a master regulatory function of PI3K that integrates an epithelial cell's metabolism and its form, shape, and function, coordinating glycolysis with the energy-intensive dynamics of actin remodeling. Copyright © 2016 Elsevier Inc. All rights reserved.

Phosphoinositide 3-Kinase Regulates Glycolysis through Mobilization of Aldolase from the Actin cytoskeleton

PubMed Central

Hu, Hai; Juvekar, Ashish; Lyssiotis, Costas A.; Lien, Evan C.; Albeck, John G.; Oh, Doogie; Varma, Gopal; Hung, Yin Pun; Ullas, Soumya; Lauring, Josh; Seth, Pankaj; Lundquist, Mark R.; Tolan, Dean R.; Grant, Aaron K.; Needleman, Daniel J.; Asara, John M.; Cantley, Lewis C.

2016-01-01

Summary The Phosphoinositide 3-Kinase (PI3K) pathway regulates multiple steps in glucose metabolism but also cytoskeletal functions, such as cell movement and attachment. Here we show that PI3K directly coordinates glycolysis with cytoskeletal dynamics in an AKT-independent manner. Growth factors or insulin stimulate the PI3K-dependent activation of Rac, leading to disruption of the actin cytoskeleton, release of filamentous actin-bound aldolase A and an increase in aldolase activity. Consistently, PI3K-, but not AKT-, SGK- or mTOR-inhibitors, cause a significant decrease in glycolysis at the step catalyzed by aldolase, while activating PIK3CA mutations have the opposite effect. These results point towards a master regulatory function of PI3K that integrates an epithelial cell’s metabolism and its form, shape and function, coordinating glycolysis with the energy-intensive dynamics of actin remodeling. PMID:26824656

Regulation of Amino Acid, Nucleotide, and Phosphate Metabolism in Saccharomyces cerevisiae

PubMed Central

Ljungdahl, Per O.; Daignan-Fornier, Bertrand

2012-01-01

Ever since the beginning of biochemical analysis, yeast has been a pioneering model for studying the regulation of eukaryotic metabolism. During the last three decades, the combination of powerful yeast genetics and genome-wide approaches has led to a more integrated view of metabolic regulation. Multiple layers of regulation, from suprapathway control to individual gene responses, have been discovered. Constitutive and dedicated systems that are critical in sensing of the intra- and extracellular environment have been identified, and there is a growing awareness of their involvement in the highly regulated intracellular compartmentalization of proteins and metabolites. This review focuses on recent developments in the field of amino acid, nucleotide, and phosphate metabolism and provides illustrative examples of how yeast cells combine a variety of mechanisms to achieve coordinated regulation of multiple metabolic pathways. Importantly, common schemes have emerged, which reveal mechanisms conserved among various pathways, such as those involved in metabolite sensing and transcriptional regulation by noncoding RNAs or by metabolic intermediates. Thanks to the remarkable sophistication offered by the yeast experimental system, a picture of the intimate connections between the metabolomic and the transcriptome is becoming clear. PMID:22419079

Low pH, aluminum and phosphorus coordinately regulate malate exudation through GmALMT1 to improve soybean adaptation to acid soils

USDA-ARS?s Scientific Manuscript database

Low pH, aluminum (Al) toxicity and low phosphorus (P) often coexist in acid soils where crops need to cope with these multiple limiting factors. In this study we found that P addition to acid soils alleviates Al toxicity and enhanced soybean adaptation to acid soils, especially for the P-efficient g...

Massive quantum regions for simulations on bio-nanomaterials: synthetic ferritin nanocages.

PubMed

Torras, Juan; Alemán, Carlos

2018-02-22

QM/MM molecular dynamics simulations on the 4His-ΔC* protein cage have been performed using multiple active zones (up to 86 quantum regions). The regulation and nanocage stability exerted by the divalent transition metal ions in the monomer-to-cage conversion have been understood by comparing high level quantum trajectories obtained using Cu 2+ and Ni 2+ coordination ions.

Coordinated Control Method of Voltage and Reactive Power for Active Distribution Networks Based on Soft Open Point

DOE PAGES

Li, Peng; Ji, Haoran; Wang, Chengshan; ...

2017-03-22

The increasing penetration of distributed generators (DGs) exacerbates the risk of voltage violations in active distribution networks (ADNs). The conventional voltage regulation devices limited by the physical constraints are difficult to meet the requirement of real-time voltage and VAR control (VVC) with high precision when DGs fluctuate frequently. But, soft open point (SOP), a flexible power electronic device, can be used as the continuous reactive power source to realize the fast voltage regulation. Considering the cooperation of SOP and multiple regulation devices, this paper proposes a coordinated VVC method based on SOP for ADNs. Firstly, a time-series model of coordi-natedmore » VVC is developed to minimize operation costs and eliminate voltage violations of ADNs. Then, by applying the linearization and conic relaxation, the original nonconvex mixed-integer non-linear optimization model is converted into a mixed-integer second-order cone programming (MISOCP) model which can be efficiently solved to meet the requirement of voltage regulation rapidity. Here, we carried out some case studies on the IEEE 33-node system and IEEE 123-node system to illustrate the effectiveness of the proposed method.« less

Coordinated Control Method of Voltage and Reactive Power for Active Distribution Networks Based on Soft Open Point

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

Li, Peng; Ji, Haoran; Wang, Chengshan

The increasing penetration of distributed generators (DGs) exacerbates the risk of voltage violations in active distribution networks (ADNs). The conventional voltage regulation devices limited by the physical constraints are difficult to meet the requirement of real-time voltage and VAR control (VVC) with high precision when DGs fluctuate frequently. But, soft open point (SOP), a flexible power electronic device, can be used as the continuous reactive power source to realize the fast voltage regulation. Considering the cooperation of SOP and multiple regulation devices, this paper proposes a coordinated VVC method based on SOP for ADNs. Firstly, a time-series model of coordi-natedmore » VVC is developed to minimize operation costs and eliminate voltage violations of ADNs. Then, by applying the linearization and conic relaxation, the original nonconvex mixed-integer non-linear optimization model is converted into a mixed-integer second-order cone programming (MISOCP) model which can be efficiently solved to meet the requirement of voltage regulation rapidity. Here, we carried out some case studies on the IEEE 33-node system and IEEE 123-node system to illustrate the effectiveness of the proposed method.« less

Neural control of the kidney: functionally specific renal sympathetic nerve fibers.

PubMed

DiBona, G F

2000-11-01

The sympathetic nervous system provides differentiated regulation of the functions of various organs. This differentiated regulation occurs via mechanisms that operate at multiple sites within the classic reflex arc: peripherally at the level of afferent input stimuli to various reflex pathways, centrally at the level of interconnections between various central neuron pools, and peripherally at the level of efferent fibers targeted to various effectors within the organ. In the kidney, increased renal sympathetic nerve activity regulates the functions of the intrarenal effectors: the tubules, the blood vessels, and the juxtaglomerular granular cells. This enables a physiologically appropriate coordination between the circulatory, filtration, reabsorptive, excretory, and renin secretory contributions to overall renal function. Anatomically, each of these effectors has a dual pattern of innervation consisting of a specific and selective innervation by unmyelinated slowly conducting C-type renal sympathetic nerve fibers in addition to an innervation that is shared among all the effectors. This arrangement permits the maximum flexibility in the coordination of physiologically appropriate responses of the tubules, the blood vessels, and the juxtaglomerular granular cells to a variety of homeostatic requirements.

Coordinated Acetylcholine Release in Prefrontal Cortex and Hippocampus Is Associated with Arousal and Reward on Distinct Timescales.

PubMed

Teles-Grilo Ruivo, Leonor M; Baker, Keeley L; Conway, Michael W; Kinsley, Peter J; Gilmour, Gary; Phillips, Keith G; Isaac, John T R; Lowry, John P; Mellor, Jack R

2017-01-24

Cholinergic neurotransmission throughout the neocortex and hippocampus regulates arousal, learning, and attention. However, owing to the poorly characterized timing and location of acetylcholine release, its detailed behavioral functions remain unclear. Using electrochemical biosensors chronically implanted in mice, we made continuous measurements of the spatiotemporal dynamics of acetylcholine release across multiple behavioral states. We found that tonic levels of acetylcholine release were coordinated between the prefrontal cortex and hippocampus and maximal during training on a rewarded working memory task. Tonic release also increased during REM sleep but was contingent on subsequent wakefulness. In contrast, coordinated phasic acetylcholine release occurred only during the memory task and was strongly localized to reward delivery areas without being contingent on trial outcome. These results show that coordinated acetylcholine release between the prefrontal cortex and hippocampus is associated with reward and arousal on distinct timescales, providing dual mechanisms to support learned behavior acquisition during cognitive task performance. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Wheat leaf lipids during heat stress: II. Lipids experiencing coordinated metabolism are detected by analysis of lipid co-occurrence.

PubMed

Narayanan, Sruthi; Prasad, P V Vara; Welti, Ruth

2016-03-01

Identifying lipids that experience coordinated metabolism during heat stress would provide information regarding lipid dynamics under stress conditions and assist in developing heat-tolerant wheat varieties. We hypothesized that co-occurring lipids, which are up-regulated or down-regulated together through time during heat stress, represent groups that can be explained by coordinated metabolism. Wheat plants (Triticum aestivum L.) were subjected to 12 days of high day and/or night temperature stress, followed by a 4-day recovery period. Leaves were sampled at four time points, and 165 lipids were measured by electrospray ionization-tandem mass spectrometry. Correlation analysis of lipid levels in 160 leaf samples from each of two wheat genotypes revealed 13 groups of lipids. Lipids within each group co-occurred through the high day and night temperature stress treatments. The lipid groups can be broadly classified as groups containing extraplastidic phospholipids, plastidic glycerolipids, oxidized glycerolipids, triacylglycerols, acylated sterol glycosides and sterol glycosides. Current knowledge of lipid metabolism suggests that the lipids in each group co-occur because they are regulated by the same enzyme(s). The results suggest that increases in activities of desaturating, oxidizing, glycosylating and acylating enzymes lead to simultaneous changes in levels of multiple lipid species during high day and night temperature stress in wheat. © 2015 John Wiley & Sons Ltd.

Genomics screens for metastasis genes

PubMed Central

Yan, Jinchun; Huang, Qihong

2014-01-01

Metastasis is responsible for most cancer mortality. The process of metastasis is complex, requiring the coordinated expression and fine regulation of many genes in multiple pathways in both the tumor and host tissues. Identification and characterization of the genetic programs that regulate metastasis is critical to understanding the metastatic process and discovering molecular targets for the prevention and treatment of metastasis. Genomic approaches and functional genomic analyses can systemically discover metastasis genes. In this review, we summarize the genetic tools and methods that have been used to identify and characterize the genes that play critical roles in metastasis. PMID:22684367

Cell and plastid division are coordinated through the prereplication factor AtCDT1

PubMed Central

Raynaud, Cécile; Perennes, Claudette; Reuzeau, Christophe; Catrice, Olivier; Brown, Spencer; Bergounioux, Catherine

2005-01-01

The cell division cycle involves nuclear and cytoplasmic events, namely organelle multiplication and distribution between the daughter cells. Until now, plastid and plant cell division have been considered as independent processes because they can be uncoupled. Here, down-regulation of AtCDT1a and AtCDT1b, members of the prereplication complex, is shown to alter both nuclear DNA replication and plastid division in Arabidopsis thaliana. These data constitute molecular evidence for relationships between the cell-cycle and plastid division. Moreover, the severe developmental defects observed in AtCDT1-RNA interference (RNAi) plants underline the importance of coordinated cell and organelle division for plant growth and morphogenesis. PMID:15928083

Single-Molecule Studies of Actin Assembly and Disassembly Factors

PubMed Central

Smith, Benjamin A.; Gelles, Jeff; Goode, Bruce L.

2014-01-01

The actin cytoskeleton is very dynamic and highly regulated by multiple associated proteins in vivo. Understanding how this system of proteins functions in the processes of actin network assembly and disassembly requires methods to dissect the mechanisms of activity of individual factors and of multiple factors acting in concert. The advent of single-filament and single-molecule fluorescence imaging methods has provided a powerful new approach to discovering actin-regulatory activities and obtaining direct, quantitative insights into the pathways of molecular interactions that regulate actin network architecture and dynamics. Here we describe techniques for acquisition and analysis of single-molecule data, applied to the novel challenges of studying the filament assembly and disassembly activities of actin-associated proteins in vitro. We discuss the advantages of single-molecule analysis in directly visualizing the order of molecular events, measuring the kinetic rates of filament binding and dissociation, and studying the coordination among multiple factors. The methods described here complement traditional biochemical approaches in elucidating actin-regulatory mechanisms in reconstituted filamentous networks. PMID:24630103

The Zymomonas mobilis regulator hfq contributes to tolerance against multiple lignocellulosic pretreatment inhibitors

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

Yang, Shihui; Pelletier, Dale A; Lu, Tse-Yuan

Zymomonas mobilis produces near theoretical yields of ethanol and recombinant strains are candidate industrial microorganisms. To date, few studies have examined its responses to various stresses at the gene level. Hfq is a conserved bacterial member of the Sm-like family of RNA-binding proteins, coordinating a broad array of responses including multiple stress responses. In a previous study, we observed Z. mobilis ZM4 gene ZMO0347 showed higher expression under anaerobic, stationary phase compared to that of aerobic, stationary conditions. We have shown the utility of the pKNOCK suicide plasmid for mutant construction in Z. mobilis, and constructed a Gateway compatible expressionmore » plasmid for use in Z. mobilis for the first time. We have also used genetics to show Z. mobilis Hfq and S. cerevisiae Lsm proteins play important roles in resisting multiple, important industrially relevant inhibitors. The conserved nature of this global regulator offers the potential to apply insights from these fundamental studies for further industrial strain development.« less

18 CFR 1302.12 - Effect on other regulations; supervision and coordination.

Code of Federal Regulations, 2013 CFR

2013-04-01

... regulations; supervision and coordination. 1302.12 Section 1302.12 Conservation of Power and Water Resources... OF THE CIVIL RIGHTS ACT OF 1964 § 1302.12 Effect on other regulations; supervision and coordination...) Supervision and coordination. TVA may from time to time assign to officials of other departments or agencies...

48 CFR 1604.7001 - Coordination of benefits clause.

Code of Federal Regulations, 2011 CFR

2011-10-01

... FEDERAL EMPLOYEES HEALTH BENEFITS ACQUISITION REGULATION GENERAL ADMINISTRATIVE MATTERS Coordination of Benefits 1604.7001 Coordination of benefits clause. OPM expects all FEHBP plans to coordinate benefits... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false Coordination of benefits...

48 CFR 1604.7001 - Coordination of benefits clause.

Code of Federal Regulations, 2012 CFR

2012-10-01

... FEDERAL EMPLOYEES HEALTH BENEFITS ACQUISITION REGULATION GENERAL ADMINISTRATIVE MATTERS Coordination of Benefits 1604.7001 Coordination of benefits clause. OPM expects all FEHBP plans to coordinate benefits... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false Coordination of benefits...

48 CFR 1604.7001 - Coordination of benefits clause.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 6 2013-10-01 2013-10-01 false Coordination of benefits clause. 1604.7001 Section 1604.7001 Federal Acquisition Regulations System OFFICE OF PERSONNEL MANAGEMENT FEDERAL EMPLOYEES HEALTH BENEFITS ACQUISITION REGULATION GENERAL ADMINISTRATIVE MATTERS Coordination of...

48 CFR 1604.7001 - Coordination of benefits clause.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false Coordination of benefits clause. 1604.7001 Section 1604.7001 Federal Acquisition Regulations System OFFICE OF PERSONNEL MANAGEMENT FEDERAL EMPLOYEES HEALTH BENEFITS ACQUISITION REGULATION GENERAL ADMINISTRATIVE MATTERS Coordination of...

48 CFR 1604.7001 - Coordination of benefits clause.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Coordination of benefits clause. 1604.7001 Section 1604.7001 Federal Acquisition Regulations System OFFICE OF PERSONNEL MANAGEMENT FEDERAL EMPLOYEES HEALTH BENEFITS ACQUISITION REGULATION GENERAL ADMINISTRATIVE MATTERS Coordination of...

The coordination of ploidy and cell size differs between cell layers in leaves.

PubMed

Katagiri, Yohei; Hasegawa, Junko; Fujikura, Ushio; Hoshino, Rina; Matsunaga, Sachihiro; Tsukaya, Hirokazu

2016-04-01

Growth and developmental processes are occasionally accompanied by multiple rounds of DNA replication, known as endoreduplication. Coordination between endoreduplication and cell size regulation often plays a crucial role in proper organogenesis and cell differentiation. Here, we report that the level of correlation between ploidy and cell volume is different in the outer and inner cell layers of leaves of Arabidopsis thaliana using a novel imaging technique. Although there is a well-known, strong correlation between ploidy and cell volume in pavement cells of the epidermis, this correlation was extremely weak in palisade mesophyll cells. Induction of epidermis cell identity based on the expression of the homeobox gene ATML1 in mesophyll cells enhanced the level of correlation between ploidy and cell volume to near that of wild-type epidermal cells. We therefore propose that the correlation between ploidy and cell volume is regulated by cell identity. © 2016. Published by The Company of Biologists Ltd.

Enhancements Needed in GE Crop and Food Regulation in the U.S.

PubMed Central

Benbrook, Charles

2016-01-01

Genetically engineered (GE) crops, multi-ingredient foods derived from one or more GE ingredients, and GE agricultural inputs are regulated in the United States under a “Coordinated Framework” that was literally cobbled together in the early 1990s. Via this Framework, responsibility is spread across three federal agencies for the assessment and management of potential risks arising from the planting of GE crops, the raising of GE animals, or uses of GE inputs. The Framework was incomplete and conceptually flawed from the beginning. Despite multiple, piecemeal efforts to update aspects of GE risk assessment and regulatory policy, the Coordinated Framework survives to this day largely unchanged. Its shortcomings are recognized in both the scientific and legal communities, but meaningful reforms thus far remain out of reach, blocked by the intense controversy now surrounding all things biotech. Five generic reforms and another five specific initiatives are described to create a more robust, science-driven GE regulatory infrastructure in the U.S. PMID:27066473

DNA-dependent protein kinase in nonhomologous end joining: a lock with multiple keys?

PubMed

Weterings, Eric; Chen, David J

2007-10-22

The DNA-dependent protein kinase (DNA-PK) is one of the central enzymes involved in DNA double-strand break (DSB) repair. It facilitates proper alignment of the two ends of the broken DNA molecule and coordinates access of other factors to the repair complex. We discuss the latest findings on DNA-PK phosphorylation and offer a working model for the regulation of DNA-PK during DSB repair.

Regulations in the field of Geo-Information

NASA Astrophysics Data System (ADS)

Felus, Y.; Keinan, E.; Regev, R.

2013-10-01

The geomatics profession has gone through a major revolution during the last two decades with the emergence of advanced GNSS, GIS and Remote Sensing technologies. These technologies have changed the core principles and working procedures of geomatics professionals. For this reason, surveying and mapping regulations, standards and specifications should be updated to reflect these changes. In Israel, the "Survey Regulations" is the principal document that regulates the professional activities in four key areas geodetic control, mapping, cadastre and Georaphic information systems. Licensed Surveyors and mapping professionals in Israel are required to work according to those regulations. This year a new set of regulations have been published and include a few major amendments as follows: In the Geodesy chapter, horizontal control is officially based on the Israeli network of Continuously Operating GNSS Reference Stations (CORS). The regulations were phrased in a manner that will allow minor datum changes to the CORS stations due to Earth Crustal Movements. Moreover, the regulations permit the use of GNSS for low accuracy height measurements. In the Cadastre chapter, the most critical change is the move to Coordinate Based Cadastre (CBC). Each parcel corner point is ranked according to its quality (accuracy and clarity of definition). The highest ranking for a parcel corner is 1. A point with a rank of 1 is defined by its coordinates alone. Any other contradicting evidence is inferior to the coordinates values. Cadastral Information is stored and managed via the National Cadastral Databases. In the Mapping and GIS chapter; the traditional paper maps (ranked by scale) are replaced by digital maps or spatial databases. These spatial databases are ranked by their quality level. Quality level is determined (similar to the ISO19157 Standard) by logical consistency, completeness, positional accuracy, attribute accuracy, temporal accuracy and usability. Metadata is another critical component of any spatial database. Every component in a map should have a metadata identification, even if the map was compiled from multiple resources. The regulations permit the use of advanced sensors and mapping techniques including LIDAR and digita l cameras that have been certified and meet the defined criteria. The article reviews these new regulations and the decision that led to them.

Dynamical modelling of coordinated multiple robot systems

NASA Technical Reports Server (NTRS)

Hayati, Samad

1987-01-01

The state of the art in the modeling of the dynamics of coordinated multiple robot manipulators is summarized and various problems related to this subject are discussed. It is recognized that dynamics modeling is a component used in the design of controllers for multiple cooperating robots. As such, the discussion addresses some problems related to the control of multiple robots. The techniques used to date in the modeling of closed kinematic chains are summarized. Various efforts made to date for the control of coordinated multiple manipulators is summarized.

Regulation of DNA Alkylation Damage Repair: Lessons and Therapeutic Opportunities

PubMed Central

Soll, Jennifer M.; Sobol, Robert W.; Mosammaparast, Nima

2016-01-01

Alkylation chemotherapy is one of the most widely used systemic therapies for cancer. While somewhat effective, clinical responses and toxicities of these agents are highly variable. A major contributing factor for this variability is the numerous distinct lesions that are created upon alkylation damage. These adducts activate multiple repair pathways. There is mounting evidence that the individual pathways function cooperatively, suggesting that coordinated regulation of alkylation repair is critical to prevent toxicity. Furthermore, some alkylating agents produce adducts that overlap with newly discovered methylation marks, making it difficult to distinguish between bona fide damaged bases and so called ‘epigenetic’ adducts. We discuss new efforts aimed at deciphering the mechanisms that regulate these repair pathways, emphasizing their implications for cancer chemotherapy. PMID:27816326

Coordination of meristem and boundary functions by transcription factors in the SHOOT MERISTEMLESS regulatory network.

PubMed

Scofield, Simon; Murison, Alexander; Jones, Angharad; Fozard, John; Aida, Mitsuhiro; Band, Leah R; Bennett, Malcolm; Murray, James A H

2018-04-30

The Arabidopsis homeodomain transcription factor SHOOT MERISTEMLESS (STM) is crucial for shoot apical meristem (SAM) function, yet the components and structure of the STM gene regulatory network (GRN) are largely unknown. Here, we show that transcriptional regulators are overrepresented among STM-regulated genes and, using these as GRN components in Bayesian network analysis, we infer STM GRN associations and reveal regulatory relationships between STM and factors involved in multiple aspects of SAM function. These include hormone regulation, TCP-mediated control of cell differentiation, AIL/PLT-mediated regulation of pluripotency and phyllotaxis, and specification of meristem-organ boundary zones via CUC1. We demonstrate a direct positive transcriptional feedback loop between STM and CUC1, despite their distinct expression patterns in the meristem and organ boundary, respectively. Our further finding that STM activates expression of the CUC1-targeting microRNA miR164c combined with mathematical modelling provides a potential solution for this apparent contradiction, demonstrating that these proposed regulatory interactions coupled with STM mobility could be sufficient to provide a mechanism for CUC1 localisation at the meristem-organ boundary. Our findings highlight the central role for the STM GRN in coordinating SAM functions. © 2018. Published by The Company of Biologists Ltd.

Determination of the core promoter regions of the Saccharomyces cerevisiae RPS3 gene.

PubMed

Joo, Yoo Jin; Kim, Jin-Ha; Baek, Joung Hee; Seong, Ki Moon; Lee, Jae Yung; Kim, Joon

2009-01-01

Ribosomal protein genes (RPG), which are scattered throughout the genomes of all eukaryotes, are subjected to coordinated expression. In yeast, the expression of RPGs is highly regulated, mainly at the transcriptional level. Recent research has found that many ribosomal proteins (RPs) function in multiple processes in addition to protein synthesis. Therefore, detailed knowledge of promoter architecture as well as gene regulation is important in understanding the multiple cellular processes mediated by RPGs. In this study, we investigated the functional architecture of the yeast RPS3 promoter and identified many putative cis-elements. Using beta-galactosidase reporter analysis and EMSA, the core promoter of RPS3 containing UASrpg and T-rich regions was corroborated. Moreover, the promoter occupancy of RPS3 by three transcription factors was confirmed. Taken together, our results further the current understanding of the promoter architecture and trans-elements of the Saccharomyces cerevisiae RPS3 gene.

Research on growth factors in periodontology.

PubMed

Smith, Patricio C; Martínez, Constanza; Cáceres, Mónica; Martínez, Jorge

2015-02-01

Growth factors play critical roles in periodontal repair through the regulation of cell behavior. Many of the cell responses regulated by these proteins include cell adhesion, migration, proliferation and differentiation. Periodontal regeneration involves an organized response of different cells, tissues and growth factors implicated in the coordination of these events. However, periodontal tissue reconstruction is an extremely difficult task. Multiple studies have been performed to understand the specific role of growth factors in periodontal wound healing. In the present review we analyze the evidence that supports the roles of growth factors in periodontal wound healing and regeneration. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Guaranteeing a captive audience: coordinated regulation of gene transfer agent (GTA) production and recipient capability by cellular regulators.

PubMed

Westbye, Alexander B; Beatty, J Thomas; Lang, Andrew S

2017-08-01

Gene transfer agents (GTAs) are bacteriophage-like particles produced by many prokaryotes. Several members of the Alphaproteobacteria produce a class of genetically-related GTAs that is best studied in Rhodobacter capsulatus. DNA transfer by the R. capsulatus GTA (RcGTA) combines aspects of both transduction and natural transformation, as recipient cells require a natural transformation-like system to incorporate donated DNA. The genes involved in RcGTA production and recipient capability are located at multiple loci in the bacterial genome; however, a conserved phosphorelay containing the response regulator CtrA and a quorum sensing system regulate both RcGTA production and recipient capability. This review highlights recent discoveries in RcGTA biology, and focuses on the co-regulation of genes involved in RcGTA production and recipient capability. Copyright © 2017 Elsevier Ltd. All rights reserved.

Catch-slip bonds can be dispensable for motor force regulation during skeletal muscle contraction

NASA Astrophysics Data System (ADS)

Dong, Chenling; Chen, Bin

2015-07-01

It is intriguing how multiple molecular motors can perform coordinated and synchronous functions, which is essential in various cellular processes. Recent studies on skeletal muscle might have shed light on this issue, where rather precise motor force regulation was partly attributed to the specific stochastic features of a single attached myosin motor. Though attached motors can randomly detach from actin filaments either through an adenosine triphosphate (ATP) hydrolysis cycle or through "catch-slip bond" breaking, their respective contribution in motor force regulation has not been clarified. Here, through simulating a mechanical model of sarcomere with a coupled Monte Carlo method and finite element method, we find that the stochastic features of an ATP hydrolysis cycle can be sufficient while those of catch-slip bonds can be dispensable for motor force regulation.

Long range epigenetic silencing is a trans-species mechanism that results in cancer specific deregulation by overriding the chromatin domains of normal cells.

PubMed

Forn, Marta; Muñoz, Mar; Tauriello, Daniele V F; Merlos-Suárez, Anna; Rodilla, Verónica; Bigas, Anna; Batlle, Eduard; Jordà, Mireia; Peinado, Miguel A

2013-12-01

DNA methylation and chromatin remodeling are frequently implicated in the silencing of genes involved in carcinogenesis. Long Range Epigenetic Silencing (LRES) is a mechanism of gene inactivation that affects multiple contiguous CpG islands and has been described in different human cancer types. However, it is unknown whether there is a coordinated regulation of the genes embedded in these regions in normal cells and in early stages of tumor progression. To better characterize the molecular events associated with the regulation and remodeling of these regions we analyzed two regions undergoing LRES in human colon cancer in the mouse model. We demonstrate that LRES also occurs in murine cancer in vivo and mimics the molecular features of the human phenomenon, namely, downregulation of gene expression, acquisition of inactive histone marks, and DNA hypermethylation of specific CpG islands. The genes embedded in these regions showed a dynamic and autonomous regulation during mouse intestinal cell differentiation, indicating that, in the framework considered here, the coordinated regulation in LRES is restricted to cancer. Unexpectedly, benign adenomas in Apc(Min/+) mice showed overexpression of most of the genes affected by LRES in cancer, which suggests that the repressive remodeling of the region is a late event. Chromatin immunoprecipitation analysis of the transcriptional insulator CTCF in mouse colon cancer cells revealed disrupted chromatin domain boundaries as compared with normal cells. Malignant regression of cancer cells by in vitro differentiation resulted in partial reversion of LRES and gain of CTCF binding. We conclude that genes in LRES regions are plastically regulated in cell differentiation and hyperproliferation, but are constrained to a coordinated repression by abolishing boundaries and the autonomous regulation of chromatin domains in cancer cells. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Coordinated Regulation of Virulence during Systemic Infection of Salmonella enterica serovar Typhimurium

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

Yoon, Hyunjin; McDermott, Jason E.; Porwollik, Steffen

Salmonella must respond to a myriad of environmental cues during infection of a mouse and express specific subsets of genes in a temporal and spatial manner to subvert the host defense mechanisms but these regulatory pathways are poorly established. To unravel how micro-environmental signals are processed and integrated into coordinated action, we constructed in-frame non-polar deletions of 84 regulators inferred to play a role in Salmonella typhimurium virulence and tested them in three virulence assays (intraperitoneal (i.p.), and intragastric (i.g.) infection in BALB/c mice, and persistence in SvJ129 mice). Overall 36 regulators were identified that were less virulent in atmore » least one assay, and of those, 15 regulators were required for systemic mouse infection in an acute infection model. As a first step towards understanding the interplay between a pathogen and its host from a systems biology standpoint we focused on these 15 genes. Transcriptional profiles were obtained for each of these 15 regulators from strains grown under four different environmental conditions. These results as well as publicly available transcriptional profiles were analyzed using both network inference and cluster analysis algorithms. The analysis predicts a regulatory network in which all 15 regulators control a specific set of genes necessary for Salmonella to cause systemic infection. We tested the regulatory model by expressing a subset of the regulators in trans and monitoring transcription of 7 known virulence factors located within Salmonella pathogenicity island 2 (SPI-2). These experiments validated the regulatory model and showed that, for these 7 genes, the response regulator SsrB and the marR type regulator SlyA co-regulate in a regulatory cascade by integrating multiple signals.« less

Wheat leaf lipids during heat stress: II. Lipids experiencing coordinated metabolism are detected by analysis of lipid co-occurrence

PubMed Central

Narayanan, Sruthi; Prasad, P.V. Vara; Welti, Ruth

2016-01-01

Identifying lipids that experience coordinated metabolism during heat stress would provide information regarding lipid dynamics under stress conditions and assist in developing heat-tolerant wheat varieties. We hypothesized that co-occurring lipids, which are up-or-down-regulated together through time during heat stress, represent groups that can be explained by coordinated metabolism. Wheat plants (Triticum aestivum L.) were subjected to 12 days of high day and/or night temperature stress, followed by a 4-day recovery period. Leaves were sampled at four time points, and 165 lipids were measured by electrospray ionization-tandem mass spectrometry. Correlation analysis of lipid levels in 160 leaf samples from each of two wheat genotypes revealed 13 groups of lipids. Lipids within each group co-occurred through the high day and night temperature stress treatments. The lipid groups can be broadly classified as groups containing: extraplastidic phospholipids, plastidic glycerolipids, oxidized glycerolipids, triacylglycerols, acylated sterol glycosides, and sterol glycosides. Current knowledge of lipid metabolism suggests that the lipids in each group co-occur because they are regulated by the same enzyme(s). The results suggest that increases in activities of desaturating, oxidizing, glycosylating, and acylating enzymes lead to simultaneous changes in levels of multiple lipid species during high day and night temperature stress in wheat. PMID:26436445

Modeling and Optimization of Coordinative Operation of Hydro-wind-photovoltaic Considering Power Generation and Output Fluctuation

NASA Astrophysics Data System (ADS)

Wang, Xianxun; Mei, Yadong

2017-04-01

Coordinative operation of hydro-wind-photovoltaic is the solution of mitigating the conflict of power generation and output fluctuation of new energy and conquering the bottleneck of new energy development. Due to the deficiencies of characterizing output fluctuation, depicting grid construction and disposal of power abandon, the research of coordinative mechanism is influenced. In this paper, the multi-object and multi-hierarchy model of coordinative operation of hydro-wind-photovoltaic is built with the aim of maximizing power generation and minimizing output fluctuation and the constraints of topotaxy of power grid and balanced disposal of power abandon. In the case study, the comparison of uncoordinative and coordinative operation is carried out with the perspectives of power generation, power abandon and output fluctuation. By comparison from power generation, power abandon and output fluctuation between separate operation and coordinative operation of multi-power, the coordinative mechanism is studied. Compared with running solely, coordinative operation of hydro-wind-photovoltaic can gain the compensation benefits. Peak-alternation operation reduces the power abandon significantly and maximizes resource utilization effectively by compensating regulation of hydropower. The Pareto frontier of power generation and output fluctuation is obtained through multiple-objective optimization. It clarifies the relationship of mutual influence between these two objects. When coordinative operation is taken, output fluctuation can be markedly reduced at the cost of a slight decline of power generation. The power abandon also drops sharply compared with operating separately. Applying multi-objective optimization method to optimize the coordinate operation, Pareto optimal solution set of power generation and output fluctuation is achieved.

Enhancer of polycomb coordinates multiple signaling pathways to promote both cyst and germline stem cell differentiation in the Drosophila adult testis

PubMed Central

Feng, Lijuan; Shi, Zhen; Chen, Xin

2017-01-01

Stem cells reside in a particular microenvironment known as a niche. The interaction between extrinsic cues originating from the niche and intrinsic factors in stem cells determines their identity and activity. Maintenance of stem cell identity and stem cell self-renewal are known to be controlled by chromatin factors. Herein, we use the Drosophila adult testis which has two adult stem cell lineages, the germline stem cell (GSC) lineage and the cyst stem cell (CySC) lineage, to study how chromatin factors regulate stem cell differentiation. We find that the chromatin factor Enhancer of Polycomb [E(Pc)] acts in the CySC lineage to negatively control transcription of genes associated with multiple signaling pathways, including JAK-STAT and EGF, to promote cellular differentiation in the CySC lineage. E(Pc) also has a non-cell-autonomous role in regulating GSC lineage differentiation. When E(Pc) is specifically inactivated in the CySC lineage, defects occur in both germ cell differentiation and maintenance of germline identity. Furthermore, compromising Tip60 histone acetyltransferase activity in the CySC lineage recapitulates loss-of-function phenotypes of E(Pc), suggesting that Tip60 and E(Pc) act together, consistent with published biochemical data. In summary, our results demonstrate that E(Pc) plays a central role in coordinating differentiation between the two adult stem cell lineages in Drosophila testes. PMID:28196077

Setting standards at the forefront of delivery system reform: aligning care coordination quality measures for multiple chronic conditions.

PubMed

DuGoff, Eva H; Dy, Sydney; Giovannetti, Erin R; Leff, Bruce; Boyd, Cynthia M

2013-01-01

The primary study objective is to assess how three major health reform care coordination initiatives (Accountable Care Organizations, Independence at Home, and Community-Based Care Transitions) measure concepts critical to care coordination for people with multiple chronic conditions. We find that there are major differences in quality measurement across these three large and politically important programs. Quality measures currently used or proposed for these new health reform-related programs addressing care coordination primarily capture continuity of care. Other key areas of care coordination, such as care transitions, patient-centeredness, and cross-cutting care across multiple conditions are infrequently addressed. The lack of a comprehensive and consistent measure set for care coordination will pose challenges for healthcare providers and policy makers who seek, respectively, to provide and reward well-coordinated care. In addition, this heterogeneity in measuring care coordination quality will generate new information, but will inhibit comparisons between these care coordination programs. © 2013 National Association for Healthcare Quality.

Setting Standards at the Forefront of Delivery System Reform: Aligning Care Coordination Quality Measures for Multiple Chronic Conditions

PubMed Central

DuGoff, Eva H.; Dy, Sydney; Giovannetti, Erin R.; Leff, Bruce; Boyd, Cynthia M.

2015-01-01

The primary study objective is to assess how three major health reform care coordination initiatives (Accountable Care Organizations, Independence at Home, and Community-based Care Transitions) measure concepts critical to care coordination for people with multiple chronic conditions. We find that there are major differences in quality measurement across these three large and politically important programs. Quality measures currently used or proposed for these new health reform-related programs addressing care coordination primarily capture continuity of care. Other key areas of care coordination, such as care transitions, patient-centeredness, and cross-cutting care across multiple conditions are infrequently addressed. The lack of a comprehensive and consistent measure set for care coordination will pose challenges for health care providers and policymakers who seek, respectively, to provide and reward well-coordinated care. In addition, this heterogeneity in measuring care coordination quality will generate new information, but will inhibit comparisons between these care coordination programs. PMID:24004040

22 CFR 209.12 - Effect on other regulations; supervision and coordination.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Effect on other regulations; supervision and... OF THE CIVIL RIGHTS ACT OF 1964 § 209.12 Effect on other regulations; supervision and coordination... other ground. (b) Supervision and coordination. The Administrator may from time to time assign to...

22 CFR 209.12 - Effect on other regulations; supervision and coordination.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Effect on other regulations; supervision and... OF THE CIVIL RIGHTS ACT OF 1964 § 209.12 Effect on other regulations; supervision and coordination... other ground. (b) Supervision and coordination. The Administrator may from time to time assign to...

5 CFR 179.213 - Coordinating salary offset with other agencies.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Coordinating salary offset with other... REGULATIONS CLAIMS COLLECTION STANDARDS Salary Offset § 179.213 Coordinating salary offset with other agencies... intent of this regulation. (2) The designated salary offset coordinator will be responsible for: (i...

Vehicle coordinated transportation dispatching model base on multiple crisis locations

NASA Astrophysics Data System (ADS)

Tian, Ran; Li, Shanwei; Yang, Guoying

2018-05-01

Many disastrous events are often caused after unconventional emergencies occur, and the requirements of disasters are often different. It is difficult for a single emergency resource center to satisfy such requirements at the same time. Therefore, how to coordinate the emergency resources stored by multiple emergency resource centers to various disaster sites requires the coordinated transportation of emergency vehicles. In this paper, according to the problem of emergency logistics coordination scheduling, based on the related constraints of emergency logistics transportation, an emergency resource scheduling model based on multiple disasters is established.

DNA Double-Strand Breaks Coupled with PARP1 and HNRNPA2B1 Binding Sites Flank Coordinately Expressed Domains in Human Chromosomes

PubMed Central

Fedoseeva, Daria M.; Sosin, Dmitri V.; Grachev, Sergei A.; Serebraykova, Marina V.; Romanenko, Svetlana A.; Vorobieva, Nadezhda V.; Kravatsky, Yuri V.

2013-01-01

Genome instability plays a key role in multiple biological processes and diseases, including cancer. Genome-wide mapping of DNA double-strand breaks (DSBs) is important for understanding both chromosomal architecture and specific chromosomal regions at DSBs. We developed a method for precise genome-wide mapping of blunt-ended DSBs in human chromosomes, and observed non-random fragmentation and DSB hot spots. These hot spots are scattered along chromosomes and delimit protected 50–250 kb DNA domains. We found that about 30% of the domains (denoted forum domains) possess coordinately expressed genes and that PARP1 and HNRNPA2B1 specifically bind DNA sequences at the forum domain termini. Thus, our data suggest a novel type of gene regulation: a coordinated transcription or silencing of gene clusters delimited by DSB hot spots as well as PARP1 and HNRNPa2B1 binding sites. PMID:23593027

Spinal Locomotor Circuits Develop Using Hierarchical Rules Based on Motorneuron Position and Identity.

PubMed

Hinckley, Christopher A; Alaynick, William A; Gallarda, Benjamin W; Hayashi, Marito; Hilde, Kathryn L; Driscoll, Shawn P; Dekker, Joseph D; Tucker, Haley O; Sharpee, Tatyana O; Pfaff, Samuel L

2015-09-02

The coordination of multi-muscle movements originates in the circuitry that regulates the firing patterns of spinal motorneurons. Sensory neurons rely on the musculotopic organization of motorneurons to establish orderly connections, prompting us to examine whether the intraspinal circuitry that coordinates motor activity likewise uses cell position as an internal wiring reference. We generated a motorneuron-specific GCaMP6f mouse line and employed two-photon imaging to monitor the activity of lumbar motorneurons. We show that the central pattern generator neural network coordinately drives rhythmic columnar-specific motorneuron bursts at distinct phases of the locomotor cycle. Using multiple genetic strategies to perturb the subtype identity and orderly position of motorneurons, we found that neurons retained their rhythmic activity-but cell position was decoupled from the normal phasing pattern underlying flexion and extension. These findings suggest a hierarchical basis of motor circuit formation that relies on increasingly stringent matching of neuronal identity and position. Copyright © 2015 Elsevier Inc. All rights reserved.

Dishevelled links basal body docking and orientation in ciliated epithelial cells

PubMed Central

Vladar, Eszter K.; Axelrod, Jeffrey D.

2014-01-01

Some epithelia contain cells with multiple, motile cilia that beat in a concerted fashion. New tools and experimental systems have facilitated molecular studies of cilium biogenesis and of the coordinated planar polarization of cilia that leads to their concerted motility. Recent, elegant work by Park and colleagues, using embryonic frog epidermis, demonstrates that Dishevelled (Dvl), a key regulator of both the Wnt/β-catenin and Planar Cell Polarity (PCP) pathways, controls both the docking and planar polarization of ciliary basal bodies. PMID:18819800

AMYGDALA MICROCIRCUITS CONTROLLING LEARNED FEAR

PubMed Central

Duvarci, Sevil; Pare, Denis

2014-01-01

We review recent work on the role of intrinsic amygdala networks in the regulation of classically conditioned defensive behaviors, commonly known as conditioned fear. These new developments highlight how conditioned fear depends on far more complex networks than initially envisioned. Indeed, multiple parallel inhibitory and excitatory circuits are differentially recruited during the expression versus extinction of conditioned fear. Moreover, shifts between expression and extinction circuits involve coordinated interactions with different regions of the medial prefrontal cortex. However, key areas of uncertainty remain, particularly with respect to the connectivity of the different cell types. Filling these gaps in our knowledge is important because much evidence indicates that human anxiety disorders results from an abnormal regulation of the networks supporting fear learning. PMID:24908482

BORC Functions Upstream of Kinesins 1 and 3 to Coordinate Regional Movement of Lysosomes along Different Microtubule Tracks.

PubMed

Guardia, Carlos M; Farías, Ginny G; Jia, Rui; Pu, Jing; Bonifacino, Juan S

2016-11-15

The multiple functions of lysosomes are critically dependent on their ability to undergo bidirectional movement along microtubules between the center and the periphery of the cell. Centrifugal and centripetal movement of lysosomes is mediated by kinesin and dynein motors, respectively. We recently described a multi-subunit complex named BORC that recruits the small GTPase Arl8 to lysosomes to promote their kinesin-dependent movement toward the cell periphery. Here, we show that BORC and Arl8 function upstream of two structurally distinct kinesin types: kinesin-1 (KIF5B) and kinesin-3 (KIF1Bβ and KIF1A). Remarkably, KIF5B preferentially moves lysosomes on perinuclear tracks enriched in acetylated α-tubulin, whereas KIF1Bβ and KIF1A drive lysosome movement on more rectilinear, peripheral tracks enriched in tyrosinated α-tubulin. These findings establish BORC as a master regulator of lysosome positioning through coupling to different kinesins and microtubule tracks. Common regulation by BORC enables coordinate control of lysosome movement in different regions of the cell. Published by Elsevier Inc.

BORC Functions Upstream of Kinesins 1 and 3 to Coordinate Regional Movement of Lysosomes Along Different Microtubule Tracks

PubMed Central

Guardia, Carlos M.; Farías, Ginny G.; Jia, Rui; Pu, Jing; Bonifacino, Juan S.

2016-01-01

Summary The multiple functions of lysosomes are critically dependent on their ability to undergo bidirectional movement along microtubules between the center and the periphery of the cell. Centrifugal and centripetal movement of lysosomes is mediated by kinesin and dynein motors, respectively. We recently described a multisubunit complex named BORC that recruits the small GTPase Arl8 to lysosomes to promote their kinesin-dependent movement toward the cell periphery. Here we show that BORC and Arl8 function upstream of two structurally distinct kinesin types: kinesin-1 (KIF5B) and kinesin-3 (KIF1Bβ and KIF1A). Remarkably, KIF5B preferentially moves lysosomes on perinuclear tracks enriched in acetylated α-tubulin, whereas KIF1Bβ and KIF1A drive lysosome movement on more rectilinear, peripheral tracks enriched in tyrosinated α-tubulin. These findings establish BORC as a master regulator of lysosome positioning through coupling to different kinesins and microtubule tracks. Common regulation by BORC enables coordinate control of lysosome movement in different regions of the cell. PMID:27851960

Requirements for efficient cell-type proportioning: regulatory timescales, stochasticity and lateral inhibition

NASA Astrophysics Data System (ADS)

Pfeuty, B.; Kaneko, K.

2016-04-01

The proper functioning of multicellular organisms requires the robust establishment of precise proportions between distinct cell types. This developmental differentiation process typically involves intracellular regulatory and stochastic mechanisms to generate cell-fate diversity as well as intercellular signaling mechanisms to coordinate cell-fate decisions at tissue level. We thus surmise that key insights about the developmental regulation of cell-type proportion can be captured by the modeling study of clustering dynamics in population of inhibitory-coupled noisy bistable systems. This general class of dynamical system is shown to exhibit a very stable two-cluster state, but also metastability, collective oscillations or noise-induced state hopping, which can prevent from timely and reliably reaching a robust and well-proportioned clustered state. To circumvent these obstacles or to avoid fine-tuning, we highlight a general strategy based on dual-time positive feedback loops, such as mediated through transcriptional versus epigenetic mechanisms, which improves proportion regulation by coordinating early and flexible lineage priming with late and firm commitment. This result sheds new light on the respective and cooperative roles of multiple regulatory feedback, stochasticity and lateral inhibition in developmental dynamics.

Multiple structure-intrinsic disorder interactions regulate and coordinate Hox protein function

NASA Astrophysics Data System (ADS)

Bondos, Sarah

During animal development, Hox transcription factors determine fate of developing tissues to generate diverse organs and appendages. Hox proteins are famous for their bizarre mutant phenotypes, such as replacing antennae with legs. Clearly, the functions of individual Hox proteins must be distinct and reliable in vivo, or the organism risks malformation or death. However, within the Hox protein family, the DNA-binding homeodomains are highly conserved and the amino acids that contact DNA are nearly invariant. These observations raise the question: How do different Hox proteins correctly identify their distinct target genes using a common DNA binding domain? One possible means to modulate DNA binding is through the influence of the non-homeodomain protein regions, which differ significantly among Hox proteins. However genetic approaches never detected intra-protein interactions, and early biochemical attempts were hindered because the special features of ``intrinsically disordered'' sequences were not appreciated. We propose the first-ever structural model of a Hox protein to explain how specific contacts between distant, intrinsically disordered regions of the protein and the homeodomain regulate DNA binding and coordinate this activity with other Hox molecular functions.

Mechanism of synergistic activation of Arp2/3 complex by cortactin and N-WASP

PubMed Central

Helgeson, Luke A; Nolen, Brad J

2013-01-01

Nucleation promoting factors (NPFs) initiate branched actin network assembly by activating Arp2/3 complex, a branched actin filament nucleator. Cellular actin networks contain multiple NPFs, but how they coordinately regulate Arp2/3 complex is unclear. Cortactin is an NPF that activates Arp2/3 complex weakly on its own, but with WASP/N-WASP, another class of NPFs, potently activates. We dissect the mechanism of synergy and propose a model in which cortactin displaces N-WASP from nascent branches as a prerequisite for nucleation. Single-molecule imaging revealed that unlike WASP/N-WASP, cortactin remains bound to junctions during nucleation, and specifically targets junctions with a ∼160-fold increased on rate over filament sides. N-WASP must be dimerized for potent synergy, and targeted mutations indicate release of dimeric N-WASP from nascent branches limits nucleation. Mathematical modeling shows cortactin-mediated displacement but not N-WASP recycling or filament recruitment models can explain synergy. Our results provide a molecular basis for coordinate Arp2/3 complex regulation. DOI: http://dx.doi.org/10.7554/eLife.00884.001 PMID:24015358

Constant change: dynamic regulation of membrane transport by calcium signalling networks keeps plants in tune with their environment.

PubMed

Kleist, Thomas J; Luan, Sheng

2016-03-01

Despite substantial variation and irregularities in their environment, plants must conform to spatiotemporal demands on the molecular composition of their cytosol. Cell membranes are the major interface between organisms and their environment and the basis for controlling the contents and intracellular organization of the cell. Membrane transport proteins (MTPs) govern the flow of molecules across membranes, and their activities are closely monitored and regulated by cell signalling networks. By continuously adjusting MTP activities, plants can mitigate the effects of environmental perturbations, but effective implementation of this strategy is reliant on precise coordination among transport systems that reside in distinct cell types and membranes. Here, we examine the role of calcium signalling in the coordination of membrane transport, with an emphasis on potassium transport. Potassium is an exceptionally abundant and mobile ion in plants, and plant potassium transport has been intensively studied for decades. Classic and recent studies have underscored the importance of calcium in plant environmental responses and membrane transport regulation. In reviewing recent advances in our understanding of the coding and decoding of calcium signals, we highlight established and emerging roles of calcium signalling in coordinating membrane transport among multiple subcellular locations and distinct transport systems in plants, drawing examples from the CBL-CIPK signalling network. By synthesizing classical studies and recent findings, we aim to provide timely insights on the role of calcium signalling networks in the modulation of membrane transport and its importance in plant environmental responses. © 2015 John Wiley & Sons Ltd.

Parallel Allostery by cAMP and PDE Coordinates Activation and Termination Phases in cAMP Signaling.

PubMed

Krishnamurthy, Srinath; Tulsian, Nikhil Kumar; Chandramohan, Arun; Anand, Ganesh S

2015-09-15

The second messenger molecule cAMP regulates the activation phase of the cAMP signaling pathway through high-affinity interactions with the cytosolic cAMP receptor, the protein kinase A regulatory subunit (PKAR). Phosphodiesterases (PDEs) are enzymes responsible for catalyzing hydrolysis of cAMP to 5' AMP. It was recently shown that PDEs interact with PKAR to initiate the termination phase of the cAMP signaling pathway. While the steps in the activation phase are well understood, steps in the termination pathway are unknown. Specifically, the binding and allosteric networks that regulate the dynamic interplay between PKAR, PDE, and cAMP are unclear. In this study, PKAR and PDE from Dictyostelium discoideum (RD and RegA, respectively) were used as a model system to monitor complex formation in the presence and absence of cAMP. Amide hydrogen/deuterium exchange mass spectrometry was used to monitor slow conformational transitions in RD, using disordered regions as conformational probes. Our results reveal that RD regulates its interactions with cAMP and RegA at distinct loci by undergoing slow conformational transitions between two metastable states. In the presence of cAMP, RD and RegA form a stable ternary complex, while in the absence of cAMP they maintain transient interactions. RegA and cAMP each bind at orthogonal sites on RD with resultant contrasting effects on its dynamics through parallel allosteric relays at multiple important loci. RD thus serves as an integrative node in cAMP termination by coordinating multiple allosteric relays and governing the output signal response. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

50 CFR 402.44 - Advance coordination for FIFRA actions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED Counterpart Regulations Governing Actions... Act § 402.44 Advance coordination for FIFRA actions. (a) Advance coordination. EPA may request the...

50 CFR 402.44 - Advance coordination for FIFRA actions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED Counterpart Regulations Governing Actions... Act § 402.44 Advance coordination for FIFRA actions. (a) Advance coordination. EPA may request the...

50 CFR 402.44 - Advance coordination for FIFRA actions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED Counterpart Regulations Governing Actions... Act § 402.44 Advance coordination for FIFRA actions. (a) Advance coordination. EPA may request the...

50 CFR 402.44 - Advance coordination for FIFRA actions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED Counterpart Regulations Governing Actions... Act § 402.44 Advance coordination for FIFRA actions. (a) Advance coordination. EPA may request the...

50 CFR 402.44 - Advance coordination for FIFRA actions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED Counterpart Regulations Governing Actions... Act § 402.44 Advance coordination for FIFRA actions. (a) Advance coordination. EPA may request the...

Transcripts of sulphur metabolic genes are co-ordinately regulated in developing seeds of common bean lacking phaseolin and major lectins

PubMed Central

Marsolais, Frédéric

2012-01-01

The lack of phaseolin and phytohaemagglutinin in common bean (dry bean, Phaseolus vulgaris) is associated with an increase in total cysteine and methionine concentrations by 70% and 10%, respectively, mainly at the expense of an abundant non-protein amino acid, S-methyl-cysteine. Transcripts were profiled between two genetically related lines differing for this trait at four stages of seed development using a high density microarray designed for common bean. Transcripts of multiple sulphur-rich proteins were elevated, several previously identified by proteomics, including legumin, basic 7S globulin, albumin-2, defensin, albumin-1, the Bowman–Birk type proteinase inhibitor, the double-headed trypsin inhibitor, and the Kunitz trypsin inhibitor. A co-ordinated regulation of transcripts coding for sulphate transporters, sulphate assimilatory enzymes, serine acetyltransferases, cystathionine β-lyase, homocysteine S-methyltransferase and methionine gamma-lyase was associated with changes in cysteine and methionine concentrations. Differential gene expression of sulphur-rich proteins preceded that of sulphur metabolic enzymes, suggesting a regulation by demand from the protein sink. Up-regulation of SERAT1;1 and -1;2 expression revealed an activation of cytosolic O-acetylserine biosynthesis. Down-regulation of SERAT2;1 suggested that cysteine and S-methyl-cysteine biosynthesis may be spatially separated in different subcellular compartments. Analysis of free amino acid profiles indicated that enhanced cysteine biosynthesis was correlated with a depletion of O-acetylserine. These results contribute to our understanding of the regulation of sulphur metabolism in developing seed in response to a change in the composition of endogenous proteins. PMID:23066144

Transcripts of sulphur metabolic genes are co-ordinately regulated in developing seeds of common bean lacking phaseolin and major lectins.

PubMed

Liao, Dengqun; Pajak, Agnieszka; Karcz, Steven R; Chapman, B Patrick; Sharpe, Andrew G; Austin, Ryan S; Datla, Raju; Dhaubhadel, Sangeeta; Marsolais, Frédéric

2012-10-01

The lack of phaseolin and phytohaemagglutinin in common bean (dry bean, Phaseolus vulgaris) is associated with an increase in total cysteine and methionine concentrations by 70% and 10%, respectively, mainly at the expense of an abundant non-protein amino acid, S-methyl-cysteine. Transcripts were profiled between two genetically related lines differing for this trait at four stages of seed development using a high density microarray designed for common bean. Transcripts of multiple sulphur-rich proteins were elevated, several previously identified by proteomics, including legumin, basic 7S globulin, albumin-2, defensin, albumin-1, the Bowman-Birk type proteinase inhibitor, the double-headed trypsin inhibitor, and the Kunitz trypsin inhibitor. A co-ordinated regulation of transcripts coding for sulphate transporters, sulphate assimilatory enzymes, serine acetyltransferases, cystathionine β-lyase, homocysteine S-methyltransferase and methionine gamma-lyase was associated with changes in cysteine and methionine concentrations. Differential gene expression of sulphur-rich proteins preceded that of sulphur metabolic enzymes, suggesting a regulation by demand from the protein sink. Up-regulation of SERAT1;1 and -1;2 expression revealed an activation of cytosolic O-acetylserine biosynthesis. Down-regulation of SERAT2;1 suggested that cysteine and S-methyl-cysteine biosynthesis may be spatially separated in different subcellular compartments. Analysis of free amino acid profiles indicated that enhanced cysteine biosynthesis was correlated with a depletion of O-acetylserine. These results contribute to our understanding of the regulation of sulphur metabolism in developing seed in response to a change in the composition of endogenous proteins.

Analysis of the ERK1,2 transcriptome in mammary epithelial cells

PubMed Central

Grill, Constance; Gheyas, Ferdous; Dayananth, Priya; Jin, Weihong; Ding, Wei; Qiu, Ping; Wang, Luquan; Doll, Ronald J.; English, Jessie M.

2004-01-01

MAPK (mitogen-activated protein kinase) pathways constitute major regulators of cellular transcriptional programmes. We analysed the ERK1,2 (extracellular-signal-regulated kinase 1,2) transcriptome in a non-transformed MEC (mammary epithelial cell) line, MCF-12A, utilizing rAd MEK1EE, a recombinant adenovirus encoding constitutively active MEK1 (MAPK/ERK kinase 1). rAd MEK1EE infection induced morphological changes and DNA synthesis which were inhibited by the MEK1,2 inhibitor PD184352. Hierarchical clustering of data derived from seven time points over 24 h identified 430 and 305 co-ordinately up-regulated and down-regulated genes respectively. c-Myc binding sites were identified in the promoters of most of these up-regulated genes. A total of 46 candidate effectors of the Raf/MEK/ERK1,2 pathway in MECs were identified by comparing our dataset with previously reported Raf-1-regulated genes. These analyses led to the identification of a suite of growth factors co-ordinately induced by MEK1EE, including multiple ErbB ligands, vascular endothelial growth factor and PHRP (parathyroid hormone-related protein). PHRP is the primary mediator of humoral hypercalcaemia of malignancy, and has been implicated in metastasis to bone. We demonstrate that PHRP is secreted by MEK1EE-expressing cells. This secretion is inhibited by PD184352, but not by ErbB inhibitors. Our results suggest that, in addition to anti-proliferative properties, MEK1,2 inhibitors may be anti-angiogenic and possess therapeutic utility in the treatment of PHRP-positive tumours. PMID:15109307

A Bir1p–Sli15p Kinetochore Passenger Complex Regulates Septin Organization during Anaphase

PubMed Central

Thomas, Scott

2007-01-01

Kinetochore–passenger complexes in metazoans have been proposed to coordinate the segregation of chromosomes in anaphase with the induction of cytokinesis. Passenger protein homologues in the budding yeast Saccharomyces cerevisiae play a critical role early in mitosis, ensuring proper biorientation of kinetochore–microtubule attachments. Our recent work has implicated the passenger protein Bir1p (Survivin) and the inner kinetochore complex centromere binding factor 3 (CBF3) in the regulation of septin dynamics during anaphase. Here, we present data that is consistent with there being multiple passenger protein complexes. Our data show that Bir1p links together a large passenger complex containing Ndc10p, Sli15p (INCENP), and Ipl1p (Aurora B) and that the interaction between Bir1p and Sli15p is specifically involved in regulating septin dynamics during anaphase. Neither conditional alleles nor mutants of BIR1 that disrupt the interaction between Bir1p and Sli15p resulted in mono-attached kinetochores, suggesting that the Bir1p–Sli15p complex functions in anaphase and independently from Sli15p–Ipl1p complexes. We present a model for how discrete passenger complexes coordinate distinct aspects of mitosis. PMID:17652458

Teaching High School Biology Students to Coordinate Text and Diagrams: Relations with Transfer, Effort, and Spatial Skill

ERIC Educational Resources Information Center

Bergey, Bradley W.; Cromley, Jennifer G.; Newcombe, Nora S.

2015-01-01

There is growing evidence that targeted instruction can improve diagram comprehension, yet one of the skills identified in the diagram comprehension literature--coordinating multiple representations--has rarely been directly taught to students and tested as a classroom intervention. We created a Coordinating Multiple Representation (CMR)…

Coordinating Multiple Representations in a Reform Calculus Textbook

ERIC Educational Resources Information Center

Chang, Briana L.; Cromley, Jennifer G.; Tran, Nhi

2015-01-01

Coordination of multiple representations (CMR) is widely recognized as a critical skill in mathematics and is frequently demanded in reform calculus textbooks. However, little is known about the prevalence of coordination tasks in such textbooks. We coded 707 instances of CMR in a widely used reform calculus textbook and analyzed the distributions…

Coordinating Multiple Representations in a Reform Calculus Textbook

ERIC Educational Resources Information Center

Chang, Briana L.; Cromley, Jennifer G.; Tran, Nhi

2016-01-01

Coordination of multiple representations (CMR) is widely recognized as a critical skill in mathematics and is frequently demanded in reform calculus textbooks. However, little is known about the prevalence of coordination tasks in such textbooks. We coded 707 instances of CMR in a widely used reform calculus textbook and analyzed the distributions…

Bidirectional Coupling between Astrocytes and Neurons Mediates Learning and Dynamic Coordination in the Brain: A Multiple Modeling Approach

PubMed Central

Wade, John J.; McDaid, Liam J.; Harkin, Jim; Crunelli, Vincenzo; Kelso, J. A. Scott

2011-01-01

In recent years research suggests that astrocyte networks, in addition to nutrient and waste processing functions, regulate both structural and synaptic plasticity. To understand the biological mechanisms that underpin such plasticity requires the development of cell level models that capture the mutual interaction between astrocytes and neurons. This paper presents a detailed model of bidirectional signaling between astrocytes and neurons (the astrocyte-neuron model or AN model) which yields new insights into the computational role of astrocyte-neuronal coupling. From a set of modeling studies we demonstrate two significant findings. Firstly, that spatial signaling via astrocytes can relay a “learning signal” to remote synaptic sites. Results show that slow inward currents cause synchronized postsynaptic activity in remote neurons and subsequently allow Spike-Timing-Dependent Plasticity based learning to occur at the associated synapses. Secondly, that bidirectional communication between neurons and astrocytes underpins dynamic coordination between neuron clusters. Although our composite AN model is presently applied to simplified neural structures and limited to coordination between localized neurons, the principle (which embodies structural, functional and dynamic complexity), and the modeling strategy may be extended to coordination among remote neuron clusters. PMID:22242121

NOVEL ROLES FOR INSULIN RECEPTOR (IR) IN ADIPOCYTES AND SKELETAL MUSCLE CELLS VIA NEW AND UNEXPECTED SUBSTRATES

PubMed Central

Ramalingam, Latha; Oh, Eunjin; Thurmond, Debbie C.

2012-01-01

The insulin signaling pathway regulates whole-body glucose homeostasis by transducing extracellular signals from the insulin receptor (IR) to downstream intracellular targets, thus coordinating a multitude of biological functions. Dysregulation of IR or its signal transduction is associated with insulin resistance, which may culminate in type 2 diabetes (T2D). Following initial stimulation of IR, insulin signaling diverges into different pathways, activating multiple substrates which have roles in various metabolic and cellular processes. The integration of multiple pathways arising from IR activation continues to expand as new IR substrates are identified and characterized. Accordingly, our review will focus on roles for IR substrates as they pertain to three primary areas: Metabolism/glucose uptake, Mitogenesis/growth, and Aging/Longevity. While IR functions in a seemingly pleotropic manner in many cell types, through these three main roles in fat and skeletal muscle cells, IR multi-tasks to regulate whole-body glucose homeostasis to impact healthspan and lifespan. PMID:23052216

Circadian expression profiles of chromatin remodeling factor genes in Arabidopsis.

PubMed

Lee, Hong Gil; Lee, Kyounghee; Jang, Kiyoung; Seo, Pil Joon

2015-01-01

The circadian clock is a biological time keeper mechanism that regulates biological rhythms to a period of approximately 24 h. The circadian clock enables organisms to anticipate environmental cycles and coordinates internal cellular physiology with external environmental cues. In plants, correct matching of the clock with the environment confers fitness advantages to plant survival and reproduction. Therefore, circadian clock components are regulated at multiple layers to fine-tune the circadian oscillation. Epigenetic regulation provides an additional layer of circadian control. However, little is known about which chromatin remodeling factors are responsible for circadian control. In this work, we analyzed circadian expression of 109 chromatin remodeling factor genes and identified 17 genes that display circadian oscillation. In addition, we also found that a candidate interacts with a core clock component, supporting that clock activity is regulated in part by chromatin modification. As an initial attempt to elucidate the relationship between chromatin modification and circadian oscillation, we identified novel regulatory candidates that provide a platform for future investigations of chromatin regulation of the circadian clock.

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.

Drosophila nemo is an essential gene involved in the regulation of programmed cell death.

PubMed

Mirkovic, Ivana; Charish, Kristi; Gorski, Sharon M; McKnight, Kristen; Verheyen, Esther M

2002-11-01

Nemo-like kinases define a novel family of serine/threonine kinases that are involved in integrating multiple signaling pathways. They are conserved regulators of Wnt/Wingless pathways, which may coordinate Wnt with TGFbeta-mediated signaling. Drosophila nemo was identified through its involvement in epithelial planar polarity, a process regulated by a non-canonical Wnt pathway. We have previously found that ectopic expression of Nemo using the Gal4-UAS system resulted in embryonic lethality associated with defects in patterning and head development. In this study we present our analyses of the phenotypes of germline clone-derived embryos. We observe lethality associated with head defects and reduction of programmed cell death and conclude that nmo is an essential gene. We also present data showing that nmo is involved in regulating apoptosis during eye development, based on both loss of function phenotypes and on genetic interactions with the pro-apoptotic gene reaper. Finally, we present genetic data from the adult wing that suggest the activity of ectopically expressed Nemo can be modulated by Jun N-terminal kinase (JNK) signaling. Such an observation supports the model that there is cross-talk between Wnt, TGFbeta and JNK signaling at multiple stages of development. Copyright 2002 Elsevier Science Ireland Ltd.

MicroRNA-182 drives metastasis of primary sarcomas by targeting multiple genes

PubMed Central

Sachdeva, Mohit; Mito, Jeffrey K.; Lee, Chang-Lung; Zhang, Minsi; Li, Zhizhong; Dodd, Rebecca D.; Cason, David; Luo, Lixia; Ma, Yan; Van Mater, David; Gladdy, Rebecca; Lev, Dina C.; Cardona, Diana M.; Kirsch, David G.

2014-01-01

Metastasis causes most cancer deaths, but is incompletely understood. MicroRNAs can regulate metastasis, but it is not known whether a single miRNA can regulate metastasis in primary cancer models in vivo. We compared the expression of miRNAs in metastatic and nonmetastatic primary mouse sarcomas and found that microRNA-182 (miR-182) was markedly overexpressed in some tumors that metastasized to the lungs. By utilizing genetically engineered mice with either deletion of or overexpression of miR-182 in primary sarcomas, we discovered that deletion of miR-182 substantially decreased, while overexpression of miR-182 considerably increased, the rate of lung metastasis after amputation of the tumor-bearing limb. Additionally, deletion of miR-182 decreased circulating tumor cells (CTCs), while overexpression of miR-182 increased CTCs, suggesting that miR-182 regulates intravasation of cancer cells into the circulation. We identified 4 miR-182 targets that inhibit either the migration of tumor cells or the degradation of the extracellular matrix. Notably, restoration of any of these targets in isolation did not alter the metastatic potential of sarcoma cells injected orthotopically, but the simultaneous restoration of all 4 targets together substantially decreased the number of metastases. These results demonstrate that a single miRNA can regulate metastasis of primary tumors in vivo by coordinated regulation of multiple genes. PMID:25180607

MMSET is dynamically regulated during cell-cycle progression and promotes normal DNA replication.

PubMed

Evans, Debra L; Zhang, Haoxing; Ham, Hyoungjun; Pei, Huadong; Lee, SeungBaek; Kim, JungJin; Billadeau, Daniel D; Lou, Zhenkun

2016-01-01

The timely and precise duplication of cellular DNA is essential for maintaining genome integrity and is thus tightly-regulated. During mitosis and G1, the Origin Recognition Complex (ORC) binds to future replication origins, coordinating with multiple factors to load the minichromosome maintenance (MCM) complex onto future replication origins as part of the pre-replication complex (pre-RC). The pre-RC machinery, in turn, remains inactive until the subsequent S phase when it is required for replication fork formation, thereby initiating DNA replication. Multiple myeloma SET domain-containing protein (MMSET, a.k.a. WHSC1, NSD2) is a histone methyltransferase that is frequently overexpressed in aggressive cancers and is essential for normal human development. Several studies have suggested a role for MMSET in cell-cycle regulation; however, whether MMSET is itself regulated during cell-cycle progression has not been examined. In this study, we report that MMSET is degraded during S phase in a cullin-ring ligase 4-Cdt2 (CRL4(Cdt2)) and proteasome-dependent manner. Notably, we also report defects in DNA replication and a decreased association of pre-RC factors with chromatin in MMSET-depleted cells. Taken together, our results suggest a dynamic regulation of MMSET levels throughout the cell cycle, and further characterize the role of MMSET in DNA replication and cell-cycle progression.

Coordinating Multiple Spacecraft Assets for Joint Science Campaigns

NASA Technical Reports Server (NTRS)

Estlin, Tara; Chien, Steve; Castano, Rebecca; Gaines, Daniel; de Granville, Charles; Doubleday, Josh; Anderson, Robert C.; Knight, Russell; Bornstein, Benjamin; Rabideau, Gregg;

Central genes, pathways and modules that regulate bone mass.

PubMed

Quiros-Gonzalez, Isabel; Yadav, Vijay K

2014-11-01

Bones are structures that give the shape and defined features to vertebrates, protect several soft organs and perform multiple endocrine influences on other organs. To achieve these functions bones are first modeled early during life and then constantly remodeled throughout life. The process of bone (re)modeling happens simultaneously at multitude of locations in the skeleton and ensures that vertebrates have a mechanically strong yet a flexible skeleton to the most part of their life. Given the extent of its occurrence in the body, bone remodeling is a highly energy demanding process and is co-ordinated with other physiological processes as diverse as energy metabolism, sleep-wake cycle and reproduction. Neuronal circuits in the brain play a very important role in the coordination of bone remodeling with other organ system functions, and perform this function in sync with environmental and peripheral hormonal cues. In this review, we will focus on the roles of hormonal signals and neural circuits that originate in, or impinge on, the brain in the regulation of bone mass. We will provide herein an updated view of how advances in molecular genetics have refined the neural circuits involved in the regulation of bone mass, from the whole brain level to the specific neuronal populations and their neurotransmitters. This will help to understand the mechanisms whereby vertebrate brain regulates bone mass by fine-tuning metabolic signals that originate in the brain or elsewhere in the body. Copyright © 2014 Elsevier Inc. All rights reserved.

Cell- and virus-mediated regulation of the barrier-to-autointegration factor's phosphorylation state controls its DNA binding, dimerization, subcellular localization, and antipoxviral activity.

PubMed

Jamin, Augusta; Wicklund, April; Wiebe, Matthew S

2014-05-01

Barrier-to-autointegration factor (BAF) is a DNA binding protein with multiple cellular functions, including the ability to act as a potent defense against vaccinia virus infection. This antiviral function involves BAF's ability to condense double-stranded DNA and subsequently prevent viral DNA replication. In recent years, it has become increasingly evident that dynamic phosphorylation involving the vaccinia virus B1 kinase and cellular enzymes is likely a key regulator of multiple BAF functions; however, the precise mechanisms are poorly understood. Here we analyzed how phosphorylation impacts BAF's DNA binding, subcellular localization, dimerization, and antipoxviral activity through the characterization of BAF phosphomimetic and unphosphorylatable mutants. Our studies demonstrate that increased phosphorylation enhances BAF's mobilization from the nucleus to the cytosol, while dephosphorylation restricts BAF to the nucleus. Phosphorylation also impairs both BAF's dimerization and its DNA binding activity. Furthermore, our studies of BAF's antiviral activity revealed that hyperphosphorylated BAF is unable to suppress viral DNA replication or virus production. Interestingly, the unphosphorylatable BAF mutant, which is capable of binding DNA but localizes predominantly to the nucleus, was also incapable of suppressing viral replication. Thus, both DNA binding and localization are important determinants of BAF's antiviral function. Finally, our examination of how phosphatases are involved in regulating BAF revealed that PP2A dephosphorylates BAF during vaccinia infection, thus counterbalancing the activity of the B1 kinase. Altogether, these data demonstrate that phosphoregulation of BAF by viral and cellular enzymes modulates this protein at multiple molecular levels, thus determining its effectiveness as an antiviral factor and likely other functions as well. The barrier-to-autointegration factor (BAF) contributes to cellular genomic integrity in multiple ways, the best characterized of which are as a host defense against cytoplasmic DNA and as a regulator of mitotic nuclear reassembly. Although dynamic phosphorylation involving both viral and cellular enzymes is likely a key regulator of multiple BAF functions, the precise mechanisms involved are poorly understood. Here we demonstrate that phosphorylation coordinately regulates BAF's DNA binding, subcellular localization, dimerization, and antipoxviral activity. Overall, our findings provide new insights into how phosphoregulation of BAF modulates this protein at multiple levels and governs its effectiveness as an antiviral factor against foreign DNA.

Synergistic role of Sprouty2 inactivation and c-Met up-regulation in mouse and human hepatocarcinogenesis.

PubMed

Lee, Susie A; Ladu, Sara; Evert, Matthias; Dombrowski, Frank; De Murtas, Valentina; Chen, Xin; Calvisi, Diego F

2010-08-01

Sprouty2 (Spry2), a negative feedback regulator of the Ras/mitogen-activated protein kinase (MAPK) pathway, is frequently down-regulated in human hepatocellular carcinoma (HCC). We tested the hypothesis that loss of Spry2 cooperates with unconstrained activation of the c-Met protooncogene to induce hepatocarcinogenesis via in vitro and in vivo approaches. We found coordinated down-regulation of Spry2 protein expression and activation of c-Met as well as its downstream effectors extracellular signal-regulated kinase (ERK) and v-akt murine thymoma viral oncogene homolog (AKT) in a subset of human HCC samples with poor outcome. Mechanistic studies revealed that Spry2 function is disrupted in human HCC via multiple mechanisms at both transcriptional and post-transcriptional level, including promoter hypermethylation, loss of heterozygosity, and proteosomal degradation by neural precursor cell expressed, developmentally down-regulated 4 (NEDD4). In HCC cell lines, Spry2 overexpression inhibits c-Met-induced cell proliferation as well as ERK and AKT activation, whereas loss of Spry2 potentiates c-Met signaling. Most importantly, we show that blocking Spry2 activity via a dominant negative form of Spry2 cooperates with c-Met to promote hepatocarcinogenesis in the mouse liver by sustaining proliferation and angiogenesis. The tumors exhibited high levels of activated ERK and AKT, recapitulating the subgroup of human HCC with a clinically aggressive phenotype. The occurrence of frequent genetic, epigenetic, and biochemical events leading to Spry2 inactivation provides solid evidence that Spry2 functions as a tumor suppressor gene in liver cancer. Coordinated deregulation of Spry2 and c-Met signaling may be a pivotal oncogenic mechanism responsible for unrestrained activation of ERK and AKT pathways in human hepatocarcinogenesis.

Genetic evidence for the coordinated regulation of collagen fibrillogenesis in the cornea by decorin and biglycan.

PubMed

Zhang, Guiyun; Chen, Shoujun; Goldoni, Silvia; Calder, Bennett W; Simpson, Holly C; Owens, Rick T; McQuillan, David J; Young, Marian F; Iozzo, Renato V; Birk, David E

2009-03-27

Decorin and biglycan are class I small leucine-rich proteoglycans (SLRPs) involved in regulation of collagen fibril and matrix assembly. We hypothesize that tissue-specific matrix assembly, such as in the cornea, requires a coordinate regulation involving multiple SLRPs. To this end, we investigated the expression of decorin and biglycan in the cornea of mice deficient in either SLRP gene and in double-mutant mice. Decorin and biglycan exhibited overlapping spatial expression patterns throughout the corneal stroma with differential temporal expression. Whereas decorin was expressed at relatively high levels in all developmental stages, biglycan expression was high early, decreased during development, and was present at very low levels in the mature cornea. Ultrastructural analyses demonstrated comparable fibril structure in the decorin- and biglycan-null corneas compared with wild-type controls. We found a compensatory up-regulation of biglycan gene expression in the decorin-deficient mice, but not the reverse. Notably, the corneas of compound decorin/biglycan-null mice showed severe disruption in fibril structure and organization, especially affecting the posterior corneal regions, corroborating the idea that biglycan compensates for the loss of decorin. Fibrillogenesis assays using recombinant decorin and biglycan confirmed a functional compensation, with both having similar effects at high SLRP/collagen ratios. However, at low ratios decorin was a more efficient regulator. The use of proteoglycan or protein core yielded comparable results. These findings provide firm genetic evidence for an interaction of decorin and biglycan during corneal development and further suggest that decorin has a primary role in regulating fibril assembly, a function that can be fine-tuned by biglycan during early development.

Sgol2 provides a regulatory platform that coordinates essential cell cycle processes during meiosis I in oocytes

PubMed Central

Rattani, Ahmed; Wolna, Magda; Ploquin, Mickael; Helmhart, Wolfgang; Morrone, Seamus; Mayer, Bernd; Godwin, Jonathan; Xu, Wenqing; Stemmann, Olaf; Pendas, Alberto; Nasmyth, Kim

2013-01-01

Accurate chromosome segregation depends on coordination between cohesion resolution and kinetochore-microtubule interactions (K-fibers), a process regulated by the spindle assembly checkpoint (SAC). How these diverse processes are coordinated remains unclear. We show that in mammalian oocytes Shugoshin-like protein 2 (Sgol2) in addition to protecting cohesin, plays an important role in turning off the SAC, in promoting the congression and bi-orientation of bivalents on meiosis I spindles, in facilitating formation of K-fibers and in limiting bivalent stretching. Sgol2’s ability to protect cohesin depends on its interaction with PP2A, as is its ability to silence the SAC, with the latter being mediated by direct binding to Mad2. In contrast, its effect on bivalent stretching and K-fiber formation is independent of PP2A and mediated by recruitment of MCAK and inhibition of Aurora C kinase activity respectively. By virtue of its multiple interactions, Sgol2 links many of the processes essential for faithful chromosome segregation. DOI: http://dx.doi.org/10.7554/eLife.01133.001 PMID:24192037

48 CFR 1652.204-71 - Coordination of Benefits.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false Coordination of Benefits. 1652.204-71 Section 1652.204-71 Federal Acquisition Regulations System OFFICE OF PERSONNEL MANAGEMENT FEDERAL EMPLOYEES HEALTH BENEFITS ACQUISITION REGULATION CLAUSES AND FORMS CONTRACT CLAUSES Texts of FEHBP...

48 CFR 1652.204-71 - Coordination of Benefits.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false Coordination of Benefits. 1652.204-71 Section 1652.204-71 Federal Acquisition Regulations System OFFICE OF PERSONNEL MANAGEMENT FEDERAL EMPLOYEES HEALTH BENEFITS ACQUISITION REGULATION CLAUSES AND FORMS CONTRACT CLAUSES Texts of FEHBP...

Beclin 1 Is Required for Neuron Viability and Regulates Endosome Pathways via the UVRAG-VPS34 Complex

PubMed Central

Wold, Mitchell S.; Gong, Shiaoching; Phillips, Greg R.; Dou, Zhixun; Zhao, Yanxiang; Heintz, Nathaniel; Zong, Wei-Xing; Yue, Zhenyu

2014-01-01

Deficiency of autophagy protein beclin 1 is implicated in tumorigenesis and neurodegenerative diseases, but the molecular mechanism remains elusive. Previous studies showed that Beclin 1 coordinates the assembly of multiple VPS34 complexes whose distinct phosphatidylinositol 3-kinase III (PI3K-III) lipid kinase activities regulate autophagy at different steps. Recent evidence suggests a function of beclin 1 in regulating multiple VPS34-mediated trafficking pathways beyond autophagy; however, the precise role of beclin 1 in autophagy-independent cellular functions remains poorly understood. Herein we report that beclin 1 regulates endocytosis, in addition to autophagy, and is required for neuron viability in vivo. We find that neuronal beclin 1 associates with endosomes and regulates EEA1/early endosome localization and late endosome formation. Beclin 1 maintains proper cellular phosphatidylinositol 3-phosphate (PI(3)P) distribution and total levels, and loss of beclin 1 causes a disruption of active Rab5 GTPase-associated endosome formation and impairment of endosome maturation, likely due to a failure of Rab5 to recruit VPS34. Furthermore, we find that Beclin 1 deficiency causes complete loss of the UVRAG-VPS34 complex and associated lipid kinase activity. Interestingly, beclin 1 deficiency impairs p40phox-linked endosome formation, which is rescued by overexpressed UVRAG or beclin 1, but not by a coiled-coil domain-truncated beclin 1 (a UVRAG-binding mutant), Atg14L or RUBICON. Thus, our study reveals the essential role for beclin 1 in neuron survival involving multiple membrane trafficking pathways including endocytosis and autophagy, and suggests that the UVRAG-beclin 1 interaction underlies beclin 1's function in endocytosis. PMID:25275521

34 CFR 412.5 - What regulations apply?

Code of Federal Regulations, 2010 CFR

2010-07-01

..., DEPARTMENT OF EDUCATION NATIONAL NETWORK FOR CURRICULUM COORDINATION IN VOCATIONAL AND TECHNICAL EDUCATION... Curriculum Coordination in Vocational and Technical Education: (a) The regulations in this part 412. (b) The...

Emerging role of the brain in the homeostatic regulation of energy and glucose metabolism.

PubMed

Roh, Eun; Song, Do Kyeong; Kim, Min-Seon

2016-03-11

Accumulated evidence from genetic animal models suggests that the brain, particularly the hypothalamus, has a key role in the homeostatic regulation of energy and glucose metabolism. The brain integrates multiple metabolic inputs from the periphery through nutrients, gut-derived satiety signals and adiposity-related hormones. The brain modulates various aspects of metabolism, such as food intake, energy expenditure, insulin secretion, hepatic glucose production and glucose/fatty acid metabolism in adipose tissue and skeletal muscle. Highly coordinated interactions between the brain and peripheral metabolic organs are critical for the maintenance of energy and glucose homeostasis. Defective crosstalk between the brain and peripheral organs contributes to the development of obesity and type 2 diabetes. Here we comprehensively review the above topics, discussing the main findings related to the role of the brain in the homeostatic regulation of energy and glucose metabolism.

Emerging role of the brain in the homeostatic regulation of energy and glucose metabolism

PubMed Central

Roh, Eun; Song, Do Kyeong; Kim, Min-Seon

2016-01-01

Accumulated evidence from genetic animal models suggests that the brain, particularly the hypothalamus, has a key role in the homeostatic regulation of energy and glucose metabolism. The brain integrates multiple metabolic inputs from the periphery through nutrients, gut-derived satiety signals and adiposity-related hormones. The brain modulates various aspects of metabolism, such as food intake, energy expenditure, insulin secretion, hepatic glucose production and glucose/fatty acid metabolism in adipose tissue and skeletal muscle. Highly coordinated interactions between the brain and peripheral metabolic organs are critical for the maintenance of energy and glucose homeostasis. Defective crosstalk between the brain and peripheral organs contributes to the development of obesity and type 2 diabetes. Here we comprehensively review the above topics, discussing the main findings related to the role of the brain in the homeostatic regulation of energy and glucose metabolism. PMID:26964832

Sugar and Glycerol Transport in Saccharomyces cerevisiae.

PubMed

Bisson, Linda F; Fan, Qingwen; Walker, Gordon A

2016-01-01

In Saccharomyces cerevisiae the process of transport of sugar substrates into the cell comprises a complex network of transporters and interacting regulatory mechanisms. Members of the large family of hexose (HXT) transporters display uptake efficiencies consistent with their environmental expression and play physiological roles in addition to feeding the glycolytic pathway. Multiple glucose-inducing and glucose-independent mechanisms serve to regulate expression of the sugar transporters in yeast assuring that expression levels and transporter activity are coordinated with cellular metabolism and energy needs. The expression of sugar transport activity is modulated by other nutritional and environmental factors that may override glucose-generated signals. Transporter expression and activity is regulated transcriptionally, post-transcriptionally and post-translationally. Recent studies have expanded upon this suite of regulatory mechanisms to include transcriptional expression fine tuning mediated by antisense RNA and prion-based regulation of transcription. Much remains to be learned about cell biology from the continued analysis of this dynamic process of substrate acquisition.

Coordinated regulation of photosynthesis in rice increases yield and tolerance to environmental stress

PubMed Central

Ambavaram, Madana M. R.; Basu, Supratim; Krishnan, Arjun; Ramegowda, Venkategowda; Batlang, Utlwang; Rahman, Lutfor; Baisakh, Niranjan; Pereira, Andy

2014-01-01

Plants capture solar energy and atmospheric carbon dioxide (CO2) through photosynthesis, which is the primary component of crop yield, and needs to be increased considerably to meet the growing global demand for food. Environmental stresses, which are increasing with climate change, adversely affect photosynthetic carbon metabolism (PCM) and limit yield of cereals such as rice (Oryza sativa) that feeds half the world. To study the regulation of photosynthesis, we developed a rice gene regulatory network and identified a transcription factor HYR (HIGHER YIELD RICE) associated with PCM, which on expression in rice enhances photosynthesis under multiple environmental conditions, determining a morpho-physiological programme leading to higher grain yield under normal, drought and high-temperature stress conditions. We show HYR is a master regulator, directly activating photosynthesis genes, cascades of transcription factors and other downstream genes involved in PCM and yield stability under drought and high-temperature environmental stress conditions. PMID:25358745

Genetic perturbations that impair functional trait interactions lead to reduced bone strength and increased fragility in mice

PubMed Central

Smith, Lauren M.; Bigelow, Erin M.R.; Nolan, Bonnie T.; Faillace, Meghan E.; Nadeau, Joseph H.; Jepsen, Karl J.

2014-01-01

Functional adaptation may complicate the choice of phenotype used in genetic studies that seek to identify genes contributing to fracture susceptibility. Often, genetic variants affecting one trait are compensated by coordinated changes in other traits. Bone fracture is a prototypic example because mechanical function of long bones (stiffness and strength) depends on how the system coordinately adjusts the amount (cortical area) and quality (tissue-mineral density, TMD) of bone tissue to mechanically offset the natural variation in bone robustness (total area/length). We propose that efforts aimed at identifying genes regulating fracture resistance will benefit from better understanding how functional adaptation contributes to the genotype-phenotype relationship. We analyzed the femurs of C57BL/6J – ChrA/J/NaJ Chromosome Substitution Strains (CSSs) to systemically interrogate the mouse genome for chromosomes harboring genes that regulate mechanical function. These CSSs (CSS-i, i = the substituted chromosome) showed changes in mechanical function on the order of -26.6 to 11.5% relative to the B6 reference strain after adjusting for body size. Seven substitutions showed altered robustness, cortical area, or TMD, but no effect on mechanical function (CSS-4, 5, 8, 9, 17, 18, 19); six substitutions showed altered robustness, cortical area, or TMD, and reduced mechanical function (CSS-1, 2, 6, 10, 12, 15); and one substitution also showed reduced mechanical function but exhibited no significant changes in the three physical traits analyzed in this study (CSS-3). A key feature that distinguished CSSs that maintained function from those with reduced function was whether the system adjusted cortical area and TMD to the levels needed to compensate for the natural variation in bone robustness. These results provide a novel biomechanical mechanism linking genotype with phenotype, indicating that genes control function not only by regulating individual traits, but also by regulating how the system coordinately adjusts multiple traits to establish function. PMID:25003813

An Architecture for Controlling Multiple Robots

NASA Technical Reports Server (NTRS)

Aghazarian, Hrand; Pirjanian, Paolo; Schenker, Paul; Huntsberger, Terrance

2004-01-01

The Control Architecture for Multirobot Outpost (CAMPOUT) is a distributed-control architecture for coordinating the activities of multiple robots. In the CAMPOUT, multiple-agent activities and sensor-based controls are derived as group compositions and involve coordination of more basic controllers denoted, for present purposes, as behaviors. The CAMPOUT provides basic mechanistic concepts for representation and execution of distributed group activities. One considers a network of nodes that comprise behaviors (self-contained controllers) augmented with hyper-links, which are used to exchange information between the nodes to achieve coordinated activities. Group behavior is guided by a scripted plan, which encodes a conditional sequence of single-agent activities. Thus, higher-level functionality is composed by coordination of more basic behaviors under the downward task decomposition of a multi-agent planner

Adaptor protein complex 2-mediated endocytosis is crucial for male reproductive organ development in Arabidopsis.

PubMed

Kim, Soo Youn; Xu, Zheng-Yi; Song, Kyungyoung; Kim, Dae Heon; Kang, Hyangju; Reichardt, Ilka; Sohn, Eun Ju; Friml, Jirí; Juergens, Gerd; Hwang, Inhwan

2013-08-01

Fertilization in flowering plants requires the temporal and spatial coordination of many developmental processes, including pollen production, anther dehiscence, ovule production, and pollen tube elongation. However, it remains elusive as to how this coordination occurs during reproduction. Here, we present evidence that endocytosis, involving heterotetrameric adaptor protein complex 2 (AP-2), plays a crucial role in fertilization. An Arabidopsis thaliana mutant ap2m displays multiple defects in pollen production and viability, as well as elongation of staminal filaments and pollen tubes, all of which are pivotal processes needed for fertilization. Of these abnormalities, the defects in elongation of staminal filaments and pollen tubes were partially rescued by exogenous auxin. Moreover, DR5rev:GFP (for green fluorescent protein) expression was greatly reduced in filaments and anthers in ap2m mutant plants. At the cellular level, ap2m mutants displayed defects in both endocytosis of N-(3-triethylammonium-propyl)-4-(4-diethylaminophenylhexatrienyl) pyridinium dibromide, a lypophilic dye used as an endocytosis marker, and polar localization of auxin-efflux carrier PIN FORMED2 (PIN2) in the stamen filaments. Moreover, these defects were phenocopied by treatment with Tyrphostin A23, an inhibitor of endocytosis. Based on these results, we propose that AP-2-dependent endocytosis plays a crucial role in coordinating the multiple developmental aspects of male reproductive organs by modulating cellular auxin level through the regulation of the amount and polarity of PINs.

Adaptor Protein Complex 2–Mediated Endocytosis Is Crucial for Male Reproductive Organ Development in Arabidopsis[W

PubMed Central

Kim, Soo Youn; Xu, Zheng-Yi; Song, Kyungyoung; Kim, Dae Heon; Kang, Hyangju; Reichardt, Ilka; Sohn, Eun Ju; Friml, Jiří; Juergens, Gerd; Hwang, Inhwan

2013-01-01

Fertilization in flowering plants requires the temporal and spatial coordination of many developmental processes, including pollen production, anther dehiscence, ovule production, and pollen tube elongation. However, it remains elusive as to how this coordination occurs during reproduction. Here, we present evidence that endocytosis, involving heterotetrameric adaptor protein complex 2 (AP-2), plays a crucial role in fertilization. An Arabidopsis thaliana mutant ap2m displays multiple defects in pollen production and viability, as well as elongation of staminal filaments and pollen tubes, all of which are pivotal processes needed for fertilization. Of these abnormalities, the defects in elongation of staminal filaments and pollen tubes were partially rescued by exogenous auxin. Moreover, DR5rev:GFP (for green fluorescent protein) expression was greatly reduced in filaments and anthers in ap2m mutant plants. At the cellular level, ap2m mutants displayed defects in both endocytosis of N-(3-triethylammonium-propyl)-4-(4-diethylaminophenylhexatrienyl) pyridinium dibromide, a lypophilic dye used as an endocytosis marker, and polar localization of auxin-efflux carrier PIN FORMED2 (PIN2) in the stamen filaments. Moreover, these defects were phenocopied by treatment with Tyrphostin A23, an inhibitor of endocytosis. Based on these results, we propose that AP-2–dependent endocytosis plays a crucial role in coordinating the multiple developmental aspects of male reproductive organs by modulating cellular auxin level through the regulation of the amount and polarity of PINs. PMID:23975898

Neuronal CRTC-1 governs systemic mitochondrial metabolism and lifespan via a catecholamine signal.

PubMed

Burkewitz, Kristopher; Morantte, Ianessa; Weir, Heather J M; Yeo, Robin; Zhang, Yue; Huynh, Frank K; Ilkayeva, Olga R; Hirschey, Matthew D; Grant, Ana R; Mair, William B

2015-02-26

Low energy states delay aging in multiple species, yet mechanisms coordinating energetics and longevity across tissues remain poorly defined. The conserved energy sensor AMP-activated protein kinase (AMPK) and its corresponding phosphatase calcineurin modulate longevity via the CREB regulated transcriptional coactivator (CRTC)-1 in C. elegans. We show that CRTC-1 specifically uncouples AMPK/calcineurin-mediated effects on lifespan from pleiotropic side effects by reprogramming mitochondrial and metabolic function. This pro-longevity metabolic state is regulated cell nonautonomously by CRTC-1 in the nervous system. Neuronal CRTC-1/CREB regulates peripheral metabolism antagonistically with the functional PPARα ortholog, NHR-49, drives mitochondrial fragmentation in distal tissues, and suppresses the effects of AMPK on systemic mitochondrial metabolism and longevity via a cell-nonautonomous catecholamine signal. These results demonstrate that while both local and distal mechanisms combine to modulate aging, distal regulation overrides local contribution. Targeting central perception of energetic state is therefore a potential strategy to promote healthy aging. Copyright © 2015 Elsevier Inc. All rights reserved.

Neuronal CRTC-1 governs systemic mitochondrial metabolism and lifespan via a catecholamine signal

PubMed Central

Burkewitz, Kristopher; Morantte, Ianessa; Weir, Heather J.M.; Yeo, Robin; Zhang, Yue; Huynh, Frank K.; Ilkayeva, Olga R.; Hirschey, Matthew D.; Grant, Ana R.; Mair, William B.

2015-01-01

SUMMARY Low energy states delay aging in multiple species, yet mechanisms coordinating energetics and longevity across tissues remain poorly defined. The conserved energy sensor AMP-activated protein kinase (AMPK) and its corresponding phosphatase calcineurin modulate longevity via the CREB regulated transcriptional coactivator (CRTC)-1 in C. elegans. We show that CRTC-1 specifically uncouples AMPK/calcineurin-mediated effects on lifespan from pleiotropic side effects by reprogramming mitochondrial and metabolic function. This pro-longevity metabolic state is regulated cell-nonautonomously by CRTC-1 in the nervous system. Neuronal CRTC-1/CREB regulates peripheral metabolism antagonistically with the functional PPARα ortholog, NHR-49, drives mitochondrial fragmentation in distal tissues, and suppresses the effects of AMPK on systemic mitochondrial metabolism and longevity via a cell-nonautonomous catecholamine signal. These results demonstrate that while both local and distal mechanisms combine to modulate aging, distal regulation overrides local contribution. Targeting central perception of energetic state is therefore a potential strategy to promote healthy aging. PMID:25723162

Modulation of gastrointestinal vagal neurocircuits by hyperglycemia

PubMed Central

Browning, Kirsteen N.

2013-01-01

Glucose sensing within autonomic neurocircuits is critical for the effective integration and regulation of a variety of physiological homeostatic functions including the co-ordination of vagally-mediated reflexes regulating gastrointestinal (GI) functions. Glucose regulates GI functions via actions at multiple sites of action, from modulating the activity of enteric neurons, endocrine cells, and glucose transporters within the intestine, to regulating the activity and responsiveness of the peripheral terminals, cell bodies and central terminals of vagal sensory neurons, to modifying both the activity and synaptic responsiveness of central brainstem neurons. Unsurprisingly, significant impairment in GI functions occurs in pathophysiological states where glucose levels are dysregulated, such as diabetes. A substantial obstacle to the development of new therapies to modify the disease, rather than treat the symptoms, are the gaps in our understanding of the mechanisms by which glucose modulates GI functions, particularly vagally-mediated responses and a more complete understanding of disease-related plasticity within these neurocircuits may open new avenues and targets for research. PMID:24324393

Large clusters of co-expressed genes in the Drosophila genome.

PubMed

Boutanaev, Alexander M; Kalmykova, Alla I; Shevelyov, Yuri Y; Nurminsky, Dmitry I

2002-12-12

Clustering of co-expressed, non-homologous genes on chromosomes implies their co-regulation. In lower eukaryotes, co-expressed genes are often found in pairs. Clustering of genes that share aspects of transcriptional regulation has also been reported in higher eukaryotes. To advance our understanding of the mode of coordinated gene regulation in multicellular organisms, we performed a genome-wide analysis of the chromosomal distribution of co-expressed genes in Drosophila. We identified a total of 1,661 testes-specific genes, one-third of which are clustered on chromosomes. The number of clusters of three or more genes is much higher than expected by chance. We observed a similar trend for genes upregulated in the embryo and in the adult head, although the expression pattern of individual genes cannot be predicted on the basis of chromosomal position alone. Our data suggest that the prevalent mechanism of transcriptional co-regulation in higher eukaryotes operates with extensive chromatin domains that comprise multiple genes.

Cell identity regulators link development and stress responses in the Arabidopsis root.

PubMed

Iyer-Pascuzzi, Anjali S; Jackson, Terry; Cui, Hongchang; Petricka, Jalean J; Busch, Wolfgang; Tsukagoshi, Hironaka; Benfey, Philip N

2011-10-18

Stress responses in plants are tightly coordinated with developmental processes, but interaction of these pathways is poorly understood. We used genome-wide assays at high spatiotemporal resolution to understand the processes that link development and stress in the Arabidopsis root. Our meta-analysis finds little evidence for a universal stress response. However, common stress responses appear to exist with many showing cell type specificity. Common stress responses may be mediated by cell identity regulators because mutations in these genes resulted in altered responses to stress. Evidence for a direct role for cell identity regulators came from genome-wide binding profiling of the key regulator SCARECROW, which showed binding to regulatory regions of stress-responsive genes. Coexpression in response to stress was used to identify genes involved in specific developmental processes. These results reveal surprising linkages between stress and development at cellular resolution, and show the power of multiple genome-wide data sets to elucidate biological processes. Copyright © 2011 Elsevier Inc. All rights reserved.

Nucleocytoplasmic Shuttling of the Golgi Phosphatidylinositol 4-Kinase Pik1 Is Regulated by 14-3-3 Proteins and Coordinates Golgi Function with Cell Growth

PubMed Central

Demmel, Lars; Beck, Mike; Klose, Christian; Schlaitz, Anne-Lore; Gloor, Yvonne; Hsu, Peggy P.; Havlis, Jan; Shevchenko, Andrej; Krause, Eberhard; Kalaidzidis, Yannis

2008-01-01

The yeast phosphatidylinositol 4-kinase Pik1p is essential for proliferation, and it controls Golgi homeostasis and transport of newly synthesized proteins from this compartment. At the Golgi, phosphatidylinositol 4-phosphate recruits multiple cytosolic effectors involved in formation of post-Golgi transport vesicles. A second pool of catalytically active Pik1p localizes to the nucleus. The physiological significance and regulation of this dual localization of the lipid kinase remains unknown. Here, we show that Pik1p binds to the redundant 14-3-3 proteins Bmh1p and Bmh2p. We provide evidence that nucleocytoplasmic shuttling of Pik1p involves phosphorylation and that 14-3-3 proteins bind Pik1p in the cytoplasm. Nutrient deprivation results in relocation of Pik1p from the Golgi to the nucleus and increases the amount of Pik1p–14-3-3 complex, a process reversed upon restored nutrient supply. These data suggest a role of Pik1p nucleocytoplasmic shuttling in coordination of biosynthetic transport from the Golgi with nutrient signaling. PMID:18172025

Coordinated transcriptional regulation patterns associated with infertility phenotypes in men

PubMed Central

Ellis, Peter J I; Furlong, Robert A; Conner, Sarah J; Kirkman‐Brown, Jackson; Afnan, Masoud; Barratt, Christopher; Griffin, Darren K; Affara, Nabeel A

2007-01-01

Introduction Microarray gene‐expression profiling is a powerful tool for global analysis of the transcriptional consequences of disease phenotypes. Understanding the genetic correlates of particular pathological states is important for more accurate diagnosis and screening of patients, and thus for suggesting appropriate avenues of treatment. As yet, there has been little research describing gene‐expression profiling of infertile and subfertile men, and thus the underlying transcriptional events involved in loss of spermatogenesis remain unclear. Here we present the results of an initial screen of 33 patients with differing spermatogenic phenotypes. Methods Oligonucleotide array expression profiling was performed on testis biopsies for 33 patients presenting for testicular sperm extraction. Significantly regulated genes were selected using a mixed model analysis of variance. Principle components analysis and hierarchical clustering were used to interpret the resulting dataset with reference to the patient history, clinical findings and histological composition of the biopsies. Results Striking patterns of coordinated gene expression were found. The most significant contains multiple germ cell‐specific genes and corresponds to the degree of successful spermatogenesis in each patient, whereas a second pattern corresponds to inflammatory activity within the testis. Smaller‐scale patterns were also observed, relating to unique features of the individual biopsies. PMID:17496197

Intelligent multiagent coordination based on reinforcement hierarchical neuro-fuzzy models.

PubMed

Mendoza, Leonardo Forero; Vellasco, Marley; Figueiredo, Karla

2014-12-01

This paper presents the research and development of two hybrid neuro-fuzzy models for the hierarchical coordination of multiple intelligent agents. The main objective of the models is to have multiple agents interact intelligently with each other in complex systems. We developed two new models of coordination for intelligent multiagent systems, which integrates the Reinforcement Learning Hierarchical Neuro-Fuzzy model with two proposed coordination mechanisms: the MultiAgent Reinforcement Learning Hierarchical Neuro-Fuzzy with a market-driven coordination mechanism (MA-RL-HNFP-MD) and the MultiAgent Reinforcement Learning Hierarchical Neuro-Fuzzy with graph coordination (MA-RL-HNFP-CG). In order to evaluate the proposed models and verify the contribution of the proposed coordination mechanisms, two multiagent benchmark applications were developed: the pursuit game and the robot soccer simulation. The results obtained demonstrated that the proposed coordination mechanisms greatly improve the performance of the multiagent system when compared with other strategies.

Functional Organization of Neuronal and Humoral Signals Regulating Feeding Behavior

PubMed Central

Schwartz, Gary J.; Zeltser, Lori M.

2014-01-01

Energy homeostasis- ensuring that energy availability matches energy requirements- is essential for survival. One way that energy balance is achieved is through coordinated action of neural and neuroendocrine feeding circuits, which promote energy intake when energy supply is limited. Feeding behavior engages multiple somatic and visceral tissues distributed throughout the body – contraction of skeletal and smooth muscles in the head and along the upper digestive tract required to consume and digest food, as well as stimulation of endocrine and exocrine secretions from a wide range of organs. Accordingly, neurons that contribute to feeding behaviors are localized to central, peripheral and enteric nervous systems. To promote energy balance, feeding circuits must be able to identify and respond to energy requirements, as well as the amount of energy available from internal and external sources, and then direct appropriate coordinated responses throughout the body. PMID:23642202

[The effects of Cardiodoron on cardio-respiratory coordination--a literature review].

PubMed

Cysarz, D; Heckmann, C; Kümmell, H C

2002-10-01

In healthy subjects self-regulation of the organism establishes the order of rhythmical functions. This self-regulation is altered in patients suffering from idiopathic orthostatic syndrome resulting from disturbances of functional aspects only. Thus the cardio-respiratory coordination, which may serve as the representative of the order of rhythmical functions, is modified. In the case of idiopathic orthostatic syndrome the anthroposophic medicine offers the medicament Cardiodoron(r). Does it stimulate self-regulation in order to normalise the cardio-respiratory coordination? This claim is analysed by a systematic review of the literature. Only those publications were considered where the cardio-respiratory coordination was analysed in studies with patients or healthy subjects. The methods of the studies with patients and healthy subjects vary strongly. Nevertheless, a normalisation of the cardio-respiratory coordination could be found in studies with patients suffering from idiopathic orthostatic syndrome as well as in studies with healthy subjects. The studies show that the use of the medicament results in a normalisation of the cardiorespiratory coordination. By stimulating the self-regulation the medicament leads to an improvement of the order of rhythmical functions in the human organism. Copyright 2002 S. Karger GmbH, Freiburg

Evolutionary Analysis of DELLA-Associated Transcriptional Networks.

PubMed

Briones-Moreno, Asier; Hernández-García, Jorge; Vargas-Chávez, Carlos; Romero-Campero, Francisco J; Romero, José M; Valverde, Federico; Blázquez, Miguel A

2017-01-01

DELLA proteins are transcriptional regulators present in all land plants which have been shown to modulate the activity of over 100 transcription factors in Arabidopsis, involved in multiple physiological and developmental processes. It has been proposed that DELLAs transduce environmental information to pre-wired transcriptional circuits because their stability is regulated by gibberellins (GAs), whose homeostasis largely depends on environmental signals. The ability of GAs to promote DELLA degradation coincides with the origin of vascular plants, but the presence of DELLAs in other land plants poses at least two questions: what regulatory properties have DELLAs provided to the behavior of transcriptional networks in land plants, and how has the recruitment of DELLAs by GA signaling affected this regulation. To address these issues, we have constructed gene co-expression networks of four different organisms within the green lineage with different properties regarding DELLAs: Arabidopsis thaliana and Solanum lycopersicum (both with GA-regulated DELLA proteins), Physcomitrella patens (with GA-independent DELLA proteins) and Chlamydomonas reinhardtii (a green alga without DELLA), and we have examined the relative evolution of the subnetworks containing the potential DELLA-dependent transcriptomes. Network analysis indicates a relative increase in parameters associated with the degree of interconnectivity in the DELLA-associated subnetworks of land plants, with a stronger effect in species with GA-regulated DELLA proteins. These results suggest that DELLAs may have played a role in the coordination of multiple transcriptional programs along evolution, and the function of DELLAs as regulatory 'hubs' became further consolidated after their recruitment by GA signaling in higher plants.

RPA-coated single-stranded DNA as a platform for post-translational modifications in the DNA damage response

PubMed Central

Maréchal, Alexandre; Zou, Lee

2015-01-01

The Replication Protein A (RPA) complex is an essential regulator of eukaryotic DNA metabolism. RPA avidly binds to single-stranded DNA (ssDNA) through multiple oligonucleotide/oligosaccharide-binding folds and coordinates the recruitment and exchange of genome maintenance factors to regulate DNA replication, recombination and repair. The RPA-ssDNA platform also constitutes a key physiological signal which activates the master ATR kinase to protect and repair stalled or collapsed replication forks during replication stress. In recent years, the RPA complex has emerged as a key target and an important regulator of post-translational modifications in response to DNA damage, which is critical for its genome guardian functions. Phosphorylation and SUMOylation of the RPA complex, and more recently RPA-regulated ubiquitination, have all been shown to control specific aspects of DNA damage signaling and repair by modulating the interactions between RPA and its partners. Here, we review our current understanding of the critical functions of the RPA-ssDNA platform in the maintenance of genome stability and its regulation through an elaborate network of covalent modifications. PMID:25403473

RPA-coated single-stranded DNA as a platform for post-translational modifications in the DNA damage response.

PubMed

Maréchal, Alexandre; Zou, Lee

2015-01-01

The Replication Protein A (RPA) complex is an essential regulator of eukaryotic DNA metabolism. RPA avidly binds to single-stranded DNA (ssDNA) through multiple oligonucleotide/oligosaccharide-binding folds and coordinates the recruitment and exchange of genome maintenance factors to regulate DNA replication, recombination and repair. The RPA-ssDNA platform also constitutes a key physiological signal which activates the master ATR kinase to protect and repair stalled or collapsed replication forks during replication stress. In recent years, the RPA complex has emerged as a key target and an important regulator of post-translational modifications in response to DNA damage, which is critical for its genome guardian functions. Phosphorylation and SUMOylation of the RPA complex, and more recently RPA-regulated ubiquitination, have all been shown to control specific aspects of DNA damage signaling and repair by modulating the interactions between RPA and its partners. Here, we review our current understanding of the critical functions of the RPA-ssDNA platform in the maintenance of genome stability and its regulation through an elaborate network of covalent modifications.

Evolutionary Agent-based Models to design distributed water management strategies

NASA Astrophysics Data System (ADS)

Giuliani, M.; Castelletti, A.; Reed, P. M.

2012-12-01

There is growing awareness in the scientific community that the traditional centralized approach to water resources management, as described in much of the water resources literature, provides an ideal optimal solution, which is certainly useful to quantify the best physically achievable performance, but is generally inapplicable. Most real world water resources management problems are indeed characterized by the presence of multiple, distributed and institutionally-independent decision-makers. Multi-Agent Systems provide a potentially more realistic alternative framework to model multiple and self-interested decision-makers in a credible context. Each decision-maker can be represented by an agent who, being self-interested, acts according to local objective functions and produces negative externalities on system level objectives. Different levels of coordination can potentially be included in the framework by designing coordination mechanisms to drive the current decision-making structure toward the global system efficiency. Yet, the identification of effective coordination strategies can be particularly complex in modern institutional contexts and current practice is dependent on largely ad-hoc coordination strategies. In this work we propose a novel Evolutionary Agent-based Modeling (EAM) framework that enables a mapping of fully uncoordinated and centrally coordinated solutions into their relative "many-objective" tradeoffs using multiobjective evolutionary algorithms. Then, by analysing the conflicts between local individual agent and global system level objectives it is possible to more fully understand the causes, consequences, and potential solution strategies for coordination failures. Game-theoretic criteria have value for identifying the most interesting alternatives from a policy making point of view as well as the coordination mechanisms that can be applied to obtain these interesting solutions. The proposed approach is numerically tested on a synthetic case study, representing a Y-shaped system composed by two regulated lakes, whose releases merge just upstream of a city. Each reservoir is operated by an agent in order to prevent floods along the lake shores (local objective). However, the optimal operation of the reservoirs with respect to the local objectives is conflicting with the minimization of floods in the city (global objective). The evolution of the Agent-based Model from individualistic management strategies of the reservoirs toward a global compromise that reduces the costs for the city is analysed.

Hippo circuitry and the redox modulation of hippo components in cancer cell fate decisions.

PubMed

Ashraf, Asma; Pervaiz, Shazib

2015-12-01

Meticulous and precise control of organ size is undoubtedly one of the most pivotal processes in mammalian development and regeneration along with cell differentiation, morphogenesis and programmed cell death. These processes are strictly regulated by complex and highly coordinated mechanisms to maintain a steady growth state. There are a number of extrinsic and intrinsic factors that dictate the total number and/or size of cells by influencing growth, proliferation, differentiation and cell death. Multiple pathways, such as those involved in promoting organ size and others that restrict disproportionate tissue growth act simultaneously to maintain cellular and tissue homeostasis. Aberrations at any level in these organ size-regulating processes can lead to various pathological states with cancers being the most formidable one (Yin and Zhang, 2011). Extensive research in the realm of growth control has led to the identification of the Hippo-signaling pathway as a critical network in modulating tissue growth via its effect on multiple signaling pathways and through intricate crosstalk with proteins that regulate cell polarity, adhesion and cell-cell interactions (Zhao et al., 2011b). The Hippo pathway controls cell number and organ size by transducing signals from the plasma membrane to the nucleus to regulate the expression of genes involved in cell fate determination (Shi et al., 2015). In this review, we summarize the recent discoveries concerning Hippo pathway, its diversiform regulation in mammals as well as its implications in cancers, and highlight the possible role of oxidative stress in Hippo pathway regulation. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

A Kinome RNAi Screen in Drosophila Identifies Novel Genes Interacting with Lgl, aPKC, and Crb Cell Polarity Genes in Epithelial Tissues.

PubMed

Parsons, Linda M; Grzeschik, Nicola A; Amaratunga, Kasun; Burke, Peter; Quinn, Leonie M; Richardson, Helena E

2017-08-07

In both Drosophila melanogaster and mammalian systems, epithelial structure and underlying cell polarity are essential for proper tissue morphogenesis and organ growth. Cell polarity interfaces with multiple cellular processes that are regulated by the phosphorylation status of large protein networks. To gain insight into the molecular mechanisms that coordinate cell polarity with tissue growth, we screened a boutique collection of RNAi stocks targeting the kinome for their capacity to modify Drosophila "cell polarity" eye and wing phenotypes. Initially, we identified kinase or phosphatase genes whose depletion modified adult eye phenotypes associated with the manipulation of cell polarity complexes (via overexpression of Crb or aPKC). We next conducted a secondary screen to test whether these cell polarity modifiers altered tissue overgrowth associated with depletion of Lgl in the wing. These screens identified Hippo, Jun kinase (JNK), and Notch signaling pathways, previously linked to cell polarity regulation of tissue growth. Furthermore, novel pathways not previously connected to cell polarity regulation of tissue growth were identified, including Wingless (Wg/Wnt), Ras, and lipid/Phospho-inositol-3-kinase (PI3K) signaling pathways. Additionally, we demonstrated that the "nutrient sensing" kinases Salt Inducible Kinase 2 and 3 ( SIK2 and 3 ) are potent modifiers of cell polarity phenotypes and regulators of tissue growth. Overall, our screen has revealed novel cell polarity-interacting kinases and phosphatases that affect tissue growth, providing a platform for investigating molecular mechanisms coordinating cell polarity and tissue growth during development. Copyright © 2017 Parsons et al.

Three 1-Aminocyclopropane-1-Carboxylate Synthase Genes Regulated by Primary and Secondary Pollination Signals in Orchid Flowers1

PubMed Central

Bui, Anhthu Q.; Neill, Sharman D. O'

1998-01-01

The temporal and spatial expression patterns of three 1-aminocyclopropane-1-carboxylate (ACC) synthase genes were investigated in pollinated orchid (Phalaenopsis spp.) flowers. Pollination signals initiate a cascade of development events in multiple floral organs, including the induction of ethylene biosynthesis, which coordinates several postpollination developmental responses. The initiation and propagation of ethylene biosynthesis is regulated by the coordinated expression of three distinct ACC synthase genes in orchid flowers. One ACC synthase gene (Phal-ACS1) is regulated by ethylene and participates in amplification and interorgan transmission of the pollination signal, as we have previously described in a related orchid genus. Two additional ACC synthase genes (Phal-ACS2 and Phal-ACS3) are expressed primarily in the stigma and ovary of pollinated orchid flowers. Phal-ACS2 mRNA accumulated in the stigma within 1 h after pollination, whereas Phal-ACS1 mRNA was not detected until 6 h after pollination. Similar to the expression of Phal-ACS2, the Phal-ACS3 gene was expressed within 2 h after pollination in the ovary. Exogenous application of auxin, but not ACC, mimicked pollination by stimulating a rapid increase in ACC synthase activity in the stigma and ovary and inducing Phal-ACS2 and Phal-ACS3 mRNA accumulation in the stigma and ovary, respectively. These results provide the basis for an expanded model of interorgan regulation of three ACC synthase genes that respond to both primary (Phal-ACS2 and Phal-ACS3) and secondary (Phal-ACS1) pollination signals. PMID:9449850

O-GlcNAcylation of master growth repressor DELLA by SECRET AGENT modulates multiple signaling pathways in Arabidopsis

PubMed Central

Zentella, Rodolfo; Hu, Jianhong; Hsieh, Wen-Ping; Matsumoto, Peter A.; Dawdy, Andrew; Barnhill, Benjamin; Oldenhof, Harriëtte; Hartweck, Lynn M.; Maitra, Sushmit; Thomas, Stephen G.; Cockrell, Shelley; Boyce, Michael; Shabanowitz, Jeffrey; Hunt, Donald F.; Olszewski, Neil E.; Sun, Tai-ping

2016-01-01

The DELLA family of transcription regulators functions as master growth repressors in plants by inhibiting phytohormone gibberellin (GA) signaling in response to developmental and environmental cues. DELLAs also play a central role in mediating cross-talk between GA and other signaling pathways via antagonistic direct interactions with key transcription factors. However, how these crucial protein–protein interactions can be dynamically regulated during plant development remains unclear. Here, we show that DELLAs are modified by the O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) SECRET AGENT (SEC) in Arabidopsis. O-GlcNAcylation of the DELLA protein REPRESSOR OF ga1-3 (RGA) inhibits RGA binding to four of its interactors—PHYTOCHROME-INTERACTING FACTOR3 (PIF3), PIF4, JASMONATE-ZIM DOMAIN1, and BRASSINAZOLE-RESISTANT1 (BZR1)—that are key regulators in light, jasmonate, and brassinosteroid signaling pathways, respectively. Consistent with this, the sec-null mutant displayed reduced responses to GA and brassinosteroid and showed decreased expression of several common target genes of DELLAs, BZR1, and PIFs. Our results reveal a direct role of OGT in repressing DELLA activity and indicate that O-GlcNAcylation of DELLAs provides a fine-tuning mechanism in coordinating multiple signaling activities during plant development. PMID:26773002

O-GlcNAcylation of master growth repressor DELLA by SECRET AGENT modulates multiple signaling pathways in Arabidopsis.

PubMed

Zentella, Rodolfo; Hu, Jianhong; Hsieh, Wen-Ping; Matsumoto, Peter A; Dawdy, Andrew; Barnhill, Benjamin; Oldenhof, Harriëtte; Hartweck, Lynn M; Maitra, Sushmit; Thomas, Stephen G; Cockrell, Shelley; Boyce, Michael; Shabanowitz, Jeffrey; Hunt, Donald F; Olszewski, Neil E; Sun, Tai-Ping

2016-01-15

The DELLA family of transcription regulators functions as master growth repressors in plants by inhibiting phytohormone gibberellin (GA) signaling in response to developmental and environmental cues. DELLAs also play a central role in mediating cross-talk between GA and other signaling pathways via antagonistic direct interactions with key transcription factors. However, how these crucial protein-protein interactions can be dynamically regulated during plant development remains unclear. Here, we show that DELLAs are modified by the O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) SECRET AGENT (SEC) in Arabidopsis. O-GlcNAcylation of the DELLA protein REPRESSOR OF ga1-3 (RGA) inhibits RGA binding to four of its interactors-PHYTOCHROME-INTERACTING FACTOR3 (PIF3), PIF4, JASMONATE-ZIM DOMAIN1, and BRASSINAZOLE-RESISTANT1 (BZR1)-that are key regulators in light, jasmonate, and brassinosteroid signaling pathways, respectively. Consistent with this, the sec-null mutant displayed reduced responses to GA and brassinosteroid and showed decreased expression of several common target genes of DELLAs, BZR1, and PIFs. Our results reveal a direct role of OGT in repressing DELLA activity and indicate that O-GlcNAcylation of DELLAs provides a fine-tuning mechanism in coordinating multiple signaling activities during plant development. © 2016 Zentella et al.; Published by Cold Spring Harbor Laboratory Press.

Accurate Encoding and Decoding by Single Cells: Amplitude Versus Frequency Modulation

PubMed Central

Micali, Gabriele; Aquino, Gerardo; Richards, David M.; Endres, Robert G.

2015-01-01

Cells sense external concentrations and, via biochemical signaling, respond by regulating the expression of target proteins. Both in signaling networks and gene regulation there are two main mechanisms by which the concentration can be encoded internally: amplitude modulation (AM), where the absolute concentration of an internal signaling molecule encodes the stimulus, and frequency modulation (FM), where the period between successive bursts represents the stimulus. Although both mechanisms have been observed in biological systems, the question of when it is beneficial for cells to use either AM or FM is largely unanswered. Here, we first consider a simple model for a single receptor (or ion channel), which can either signal continuously whenever a ligand is bound, or produce a burst in signaling molecule upon receptor binding. We find that bursty signaling is more accurate than continuous signaling only for sufficiently fast dynamics. This suggests that modulation based on bursts may be more common in signaling networks than in gene regulation. We then extend our model to multiple receptors, where continuous and bursty signaling are equivalent to AM and FM respectively, finding that AM is always more accurate. This implies that the reason some cells use FM is related to factors other than accuracy, such as the ability to coordinate expression of multiple genes or to implement threshold crossing mechanisms. PMID:26030820

The Role of Heparan Sulfate Proteoglycans in Optic Disc and Stalk Morphogenesis

PubMed Central

Cai, Zhigang; Grobe, Kay; Zhang, Xin

2014-01-01

Background Heparan sulfate proteoglycans (HSPG) are important for embryonic development via the regulation of gradient formation and signaling of multiple growth factors and morphogens. Previous studies have shown that Bmp/Shh/Fgf signaling are required for the regionalization of the optic vesicle (OV) and for the closure of the optic fissure (OF), the disturbance of which underlie ocular anomalies such as microphthalmia, coloboma and optic nerve hypoplasia. Results To study HSPG-dependent coordination of these signaling pathways during mammalian visual system development, we have generated a series of OV-specific mutations in the heparan sulfate (HS) N-sulfotransferase genes (Ndst1 and Ndst2) and HS O-sulfotransferase genes (Hs2st, Hs6st1 and Hs6st2) in mice. Interestingly, the resulting HS undersulfation still allowed for normal retinal neurogenesis and optic fissure closure, but led to defective optic disc and stalk development. The adult mutant animals further developed optic nerve aplasia/hypoplasia and displayed retinal degeneration. We observed that MAPK/ERK signaling was down-regulated in Ndst mutants, and consistent with this, HS-related optic nerve morphogenesis defects in mutant mice could partially be rescued by constitutive Kras activation. Conclusions These results suggest that HSPGs, depending on their HS sulfation pattern, regulate multiple signaling pathways in optic disc and stalk morphogenesis. PMID:24753163

Driving Skills of Young Adults with Developmental Coordination Disorder: Regulating Speed and Coping with Distraction

ERIC Educational Resources Information Center

de Oliveira, Rita F.; Wann, John P.

2011-01-01

In two experiments, we used an automatic car simulator to examine the steering control, speed regulation and response to hazards of young adults with developmental coordination disorder (DCD) and limited driving experience. In Experiment 1 participants either used the accelerator pedal to regulate their speed, or used the brake pedal when they…

Keep meaning in conversational coordination

PubMed Central

Cuffari, Elena C.

2014-01-01

Coordination is a widely employed term across recent quantitative and qualitative approaches to intersubjectivity, particularly approaches that give embodiment and enaction central explanatory roles. With a focus on linguistic and bodily coordination in conversational contexts, I review the operational meaning of coordination in recent empirical research and related theorizing of embodied intersubjectivity. This discussion articulates what must be involved in treating linguistic meaning as dynamic processes of coordination. The coordination approach presents languaging as a set of dynamic self-organizing processes and actions on multiple timescales and across multiple modalities that come about and work in certain domains (those jointly constructed in social, interactive, high-order sense-making). These processes go beyond meaning at the level that is available to first-person experience. I take one crucial consequence of this to be the ubiquitously moral nature of languaging with others. Languaging coordinates experience, among other levels of behavior and event. Ethical effort is called for by the automatic autonomy-influencing forces of languaging as coordination. PMID:25520693

Reprogramming of gene expression during compression wood formation in pine: Coordinated modulation of S-adenosylmethionine, lignin and lignan related genes

PubMed Central

2012-01-01

Background Transcript profiling of differentiating secondary xylem has allowed us to draw a general picture of the genes involved in wood formation. However, our knowledge is still limited about the regulatory mechanisms that coordinate and modulate the different pathways providing substrates during xylogenesis. The development of compression wood in conifers constitutes an exceptional model for these studies. Although differential expression of a few genes in differentiating compression wood compared to normal or opposite wood has been reported, the broad range of features that distinguish this reaction wood suggest that the expression of a larger set of genes would be modified. Results By combining the construction of different cDNA libraries with microarray analyses we have identified a total of 496 genes in maritime pine (Pinus pinaster, Ait.) that change in expression during differentiation of compression wood (331 up-regulated and 165 down-regulated compared to opposite wood). Samples from different provenances collected in different years and geographic locations were integrated into the analyses to mitigate the effects of multiple sources of variability. This strategy allowed us to define a group of genes that are consistently associated with compression wood formation. Correlating with the deposition of a thicker secondary cell wall that characterizes compression wood development, the expression of a number of genes involved in synthesis of cellulose, hemicellulose, lignin and lignans was up-regulated. Further analysis of a set of these genes involved in S-adenosylmethionine metabolism, ammonium recycling, and lignin and lignans biosynthesis showed changes in expression levels in parallel to the levels of lignin accumulation in cells undergoing xylogenesis in vivo and in vitro. Conclusions The comparative transcriptomic analysis reported here have revealed a broad spectrum of coordinated transcriptional modulation of genes involved in biosynthesis of different cell wall polymers associated with within-tree variations in pine wood structure and composition. In particular, we demonstrate the coordinated modulation at transcriptional level of a gene set involved in S-adenosylmethionine synthesis and ammonium assimilation with increased demand for coniferyl alcohol for lignin and lignan synthesis, enabling a better understanding of the metabolic requirements in cells undergoing lignification. PMID:22747794

Hmga2 regulates self-renewal of retinal progenitors.

PubMed

Parameswaran, Sowmya; Xia, Xiaohuan; Hegde, Ganapati; Ahmad, Iqbal

2014-11-01

In vertebrate retina, histogenesis occurs over an extended period. To sustain the temporal generation of diverse cell types, retinal progenitor cells (RPCs) must self-renew. However, self-renewal and regulation of RPCs remain poorly understood. Here, we demonstrate that cell-extrinsic factors coordinate with the epigenetic regulator high-mobility group AT-hook 2 (Hmga2) to regulate self-renewal of late retinal progenitor cells (RPCs). We observed that a small subset of RPCs was capable of clonal propagation and retained multipotentiality of parents in the presence of endothelial cells (ECs), known self-renewal regulators in various stem cell niches. The self-renewing effects, also observed in vivo, involve multiple intercellular signaling pathways, engaging Hmga2. As progenitors exhaust during retinal development, expression of Hmga2 progressively decreases. Analyses of Hmga2-expression perturbation, in vitro and in vivo, revealed that Hmga2 functionally helps to mediate cell-extrinsic influences on late-retinal progenitor self-renewal. Our results provide a framework for integrating the diverse intercellular influences elicited by epigenetic regulators for self-renewal in a dynamic stem cell niche: the developing vertebrate retina. © 2014. Published by The Company of Biologists Ltd.

Tricolor White-Light-Emitting Carbon Dots with Multiple-Cores@Shell Structure for WLED Application.

PubMed

Zhang, Tianyi; Zhao, Feifei; Li, Li; Qi, Bin; Zhu, Dongxia; Lü, Jianhua; Lü, Changli

2018-06-13

The past few years have witnessed the rapid development of carbon dots (CDs) due to their outstanding optical properties and a wide range of applications. However, the design and control of CDs with long-wavelength multicolor emission are still huge challenges to be addressed for their practical use in different fields. Here, novel nitrogen-doped multiple-core@shell-structured AC-CDs with tricolor emissions of red, green, and blue were constructed via one-pot hydrothermal method from 5-amino-1,10-phenanthroline and citric acid as reactants and the growth process of AC-CDs was monitored with the reaction time in the synthetic system. The origin of different fluorescence emissions was explored using the unique coordination ability of the surface groups of AC-CDs. An obvious concentration dependence of fluorescent properties was observed for the as-prepared AC-CDs, and a highly fluorescent quantum yield (QY) of 67% for red emission at 630 nm can be obtained by adjusting concentration of AC-CDs. The pure white-light emission (0.33, 0.33; Commission Internationale de l'Elcairage coordinate) was carried out from single carbon dot with QY of 29% through regulation of the excitation and concentration of multiple-core@shell-structured AC-CDs. In addition, because of their excellent photoluminescent properties, the white-emitting AC-CDs as emitting phosphor can be easily used in the fabrication of white-light-emitting diode with good anti-photobleaching and temperature stability.

Translating Theory Into Practice: Implementing a Program of Assessment.

PubMed

Hauer, Karen E; O'Sullivan, Patricia S; Fitzhenry, Kristen; Boscardin, Christy

2018-03-01

A program of assessment addresses challenges in learner assessment using a centrally planned, coordinated approach that emphasizes assessment for learning. This report describes the steps taken to implement a program of assessment framework within a medical school. A literature review on best practices in assessment highlighted six principles that guided implementation of the program of assessment in 2016-2017: (1) a centrally coordinated plan for assessment aligns with and supports a curricular vision; (2) multiple assessment tools used longitudinally generate multiple data points; (3) learners require ready access to information-rich feedback to promote reflection and informed self-assessment; (4) mentoring is essential to facilitate effective data use for reflection and learning planning; (5) the program of assessment fosters self-regulated learning behaviors; and (6) expert groups make summative decisions about grades and readiness for advancement. Implementation incorporated stakeholder engagement, use of multiple assessment tools, design of a coaching program, and creation of a learner performance dashboard. The assessment team monitors adherence to principles defining the program of assessment and gathers and responds to regular feedback from key stakeholders, including faculty, staff, and students. Next steps include systematically collecting evidence for validity of individual assessments and the program overall. Iterative review of student performance data informs curricular improvements. The program of assessment also highlights technology needs that will be addressed with information technology experts. The outcome ultimately will entail showing evidence of validity that the program produces physicians who engage in lifelong learning and provide high-quality patient care.

Power System Decomposition for Practical Implementation of Bulk-Grid Voltage Control Methods

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

Vallem, Mallikarjuna R.; Vyakaranam, Bharat GNVSR; Holzer, Jesse T.

Power system algorithms such as AC optimal power flow and coordinated volt/var control of the bulk power system are computationally intensive and become difficult to solve in operational time frames. The computational time required to run these algorithms increases exponentially as the size of the power system increases. The solution time for multiple subsystems is less than that for solving the entire system simultaneously, and the local nature of the voltage problem lends itself to such decomposition. This paper describes an algorithm that can be used to perform power system decomposition from the point of view of the voltage controlmore » problem. Our approach takes advantage of the dominant localized effect of voltage control and is based on clustering buses according to the electrical distances between them. One of the contributions of the paper is to use multidimensional scaling to compute n-dimensional Euclidean coordinates for each bus based on electrical distance to perform algorithms like K-means clustering. A simple coordinated reactive power control of photovoltaic inverters for voltage regulation is used to demonstrate the effectiveness of the proposed decomposition algorithm and its components. The proposed decomposition method is demonstrated on the IEEE 118-bus system.« less

Ants regulate colony spatial organization using multiple chemical road-signs

PubMed Central

Heyman, Yael; Shental, Noam; Brandis, Alexander; Hefetz, Abraham; Feinerman, Ofer

2017-01-01

Communication provides the basis for social life. In ant colonies, the prevalence of local, often chemically mediated, interactions introduces strong links between communication networks and the spatial distribution of ants. It is, however, unknown how ants identify and maintain nest chambers with distinct functions. Here, we combine individual tracking, chemical analysis and machine learning to decipher the chemical signatures present on multiple nest surfaces. We present evidence for several distinct chemical ‘road-signs' that guide the ants' movements within the dark nest. These chemical signatures can be used to classify nest chambers with different functional roles. Using behavioural manipulations, we demonstrate that at least three of these chemical signatures are functionally meaningful and allow ants from different task groups to identify their specific nest destinations, thus facilitating colony coordination and stabilization. The use of multiple chemicals that assist spatiotemporal guidance, segregation and pattern formation is abundant in multi-cellular organisms. Here, we provide a rare example for the use of these principles in the ant colony. PMID:28569746

Ants regulate colony spatial organization using multiple chemical road-signs.

PubMed

Heyman, Yael; Shental, Noam; Brandis, Alexander; Hefetz, Abraham; Feinerman, Ofer

2017-06-01

Communication provides the basis for social life. In ant colonies, the prevalence of local, often chemically mediated, interactions introduces strong links between communication networks and the spatial distribution of ants. It is, however, unknown how ants identify and maintain nest chambers with distinct functions. Here, we combine individual tracking, chemical analysis and machine learning to decipher the chemical signatures present on multiple nest surfaces. We present evidence for several distinct chemical 'road-signs' that guide the ants' movements within the dark nest. These chemical signatures can be used to classify nest chambers with different functional roles. Using behavioural manipulations, we demonstrate that at least three of these chemical signatures are functionally meaningful and allow ants from different task groups to identify their specific nest destinations, thus facilitating colony coordination and stabilization. The use of multiple chemicals that assist spatiotemporal guidance, segregation and pattern formation is abundant in multi-cellular organisms. Here, we provide a rare example for the use of these principles in the ant colony.

Temporal Coordination and Adaptation to Rate Change in Music Performance

ERIC Educational Resources Information Center

Loehr, Janeen D.; Large, Edward W.; Palmer, Caroline

2011-01-01

People often coordinate their actions with sequences that exhibit temporal variability and unfold at multiple periodicities. We compared oscillator- and timekeeper-based accounts of temporal coordination by examining musicians' coordination of rhythmic musical sequences with a metronome that gradually changed rate at the end of a musical phrase…

Mediator independently orchestrates multiple steps of preinitiation complex assembly in vivo

PubMed Central

Eyboulet, Fanny; Wydau-Dematteis, Sandra; Eychenne, Thomas; Alibert, Olivier; Neil, Helen; Boschiero, Claire; Nevers, Marie-Claire; Volland, Hervé; Cornu, David; Redeker, Virginie; Werner, Michel; Soutourina, Julie

2015-01-01

Mediator is a large multiprotein complex conserved in all eukaryotes, which has a crucial coregulator function in transcription by RNA polymerase II (Pol II). However, the molecular mechanisms of its action in vivo remain to be understood. Med17 is an essential and central component of the Mediator head module. In this work, we utilised our large collection of conditional temperature-sensitive med17 mutants to investigate Mediator's role in coordinating preinitiation complex (PIC) formation in vivo at the genome level after a transfer to a non-permissive temperature for 45 minutes. The effect of a yeast mutation proposed to be equivalent to the human Med17-L371P responsible for infantile cerebral atrophy was also analyzed. The ChIP-seq results demonstrate that med17 mutations differentially affected the global presence of several PIC components including Mediator, TBP, TFIIH modules and Pol II. Our data show that Mediator stabilizes TFIIK kinase and TFIIH core modules independently, suggesting that the recruitment or the stability of TFIIH modules is regulated independently on yeast genome. We demonstrate that Mediator selectively contributes to TBP recruitment or stabilization to chromatin. This study provides an extensive genome-wide view of Mediator's role in PIC formation, suggesting that Mediator coordinates multiple steps of a PIC assembly pathway. PMID:26240385

50 CFR 401.5 - Coordination with States.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A ANADROMOUS FISHERIES... 50 Wildlife and Fisheries 7 2010-10-01 2010-10-01 false Coordination with States. 401.5 Section 401.5 Wildlife and Fisheries JOINT REGULATIONS (UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF...

Histone chaperones: an escort network regulating histone traffic.

PubMed

De Koning, Leanne; Corpet, Armelle; Haber, James E; Almouzni, Geneviève

2007-11-01

In eukaryotes, DNA is organized into chromatin in a dynamic manner that enables it to be accessed for processes such as transcription and repair. Histones, the chief protein component of chromatin, must be assembled, replaced or exchanged to preserve or change this organization according to cellular needs. Histone chaperones are key actors during histone metabolism. Here we classify known histone chaperones and discuss how they build a network to escort histone proteins. Molecular interactions with histones and their potential specificity or redundancy are also discussed in light of chaperone structural properties. The multiplicity of histone chaperone partners, including histone modifiers, nucleosome remodelers and cell-cycle regulators, is relevant to their coordination with key cellular processes. Given the current interest in chromatin as a source of epigenetic marks, we address the potential contributions of histone chaperones to epigenetic memory and genome stability.

Intrinsic, Functional, and Structural Properties of β-Thymosins and β-Thymosin/WH2 Domains in the Regulation and Coordination of Actin Self-Assembly Dynamics and Cytoskeleton Remodeling.

PubMed

Renault, L

2016-01-01

β-Thymosins are a family of heat-stable multifunctional polypeptides that are expressed as small proteins of about 5kDa (~45 amino acids) almost exclusively in multicellular animals. They were first isolated from the thymus. As full-length or truncated polypeptides, they appear to stimulate a broad range of extracellular activities in various signaling pathways, including tissue repair and regeneration, inflammation, cell migration, and immune defense. However, their cell surface receptors and structural mechanisms of regulations in these multiple pathways remain still poorly understood. Besides their extracellular activities, they belong to a larger family of small, intrinsically disordered actin-binding domains called WH2/β-thymosin domains that have been identified in more than 1800 multidomain proteins found in different taxonomic domains of life and involved in various actin-based motile processes including cell morphogenesis, motility, adhesions, tissue development, intracellular trafficking, or pathogen infections. This review briefly surveys the main recent findings to understand how these small, intrinsically disordered but functional domains can interact with many unrelated partners and can thus integrate and coordinate various intracellular activities in actin self-assembly dynamics and cell signaling pathways linked to their cytoskeleton remodeling. © 2016 Elsevier Inc. All rights reserved.

Units Coordination and the Construction of Improper Fractions: A Revision of the Splitting Hypothesis

ERIC Educational Resources Information Center

Hackenberg, Amy J.

2007-01-01

This article communicates findings from a year-long constructivist teaching experiment about the relationship between four sixth-grade students' multiplicative structures and their construction of improper fractions. Students' multiplicative structures are the units coordinations that they can take as given prior to activity--i.e., the units…

15 CFR 921.52 - Promotion and coordination of estuarine research.

Code of Federal Regulations, 2010 CFR

2010-01-01

... estuarine research. 921.52 Section 921.52 Commerce and Foreign Trade Regulations Relating to Commerce and... AND COASTAL RESOURCE MANAGEMENT NATIONAL ESTUARINE RESEARCH RESERVE SYSTEM REGULATIONS Special Research Projects § 921.52 Promotion and coordination of estuarine research. (a) NOAA will promote and...

Multiple Phosphatases Regulate Carbon Source-Dependent Germination and Primary Metabolism in Aspergillus nidulans

PubMed Central

de Assis, Leandro José; Ries, Laure Nicolas Annick; Savoldi, Marcela; Dinamarco, Taisa Magnani; Goldman, Gustavo Henrique; Brown, Neil Andrew

2015-01-01

Aspergillus nidulans is an important mold and a model system for the study of fungal cell biology. In addition, invasive A. nidulans pulmonary infections are common in humans with chronic granulomatous disease. The morphological and biochemical transition from dormant conidia into active, growing, filamentous hyphae requires the coordination of numerous biosynthetic, developmental, and metabolic processes. The present study exhibited the diversity of roles performed by seven phosphatases in regulating cell cycle, development, and metabolism in response to glucose and alternative carbon sources. The identified phosphatases highlighted the importance of several signaling pathways regulating filamentous growth, the action of the pyruvate dehydrogenase complex as a metabolic switch controlling carbon usage, and the identification of the key function performed by the α-ketoglutarate dehydrogenase during germination. These novel insights into the fundamental roles of numerous phosphatases in germination and carbon sensing have provided new avenues of research into the identification of inhibitors of fungal germination, with implications for the food, feed, and pharmaceutical industries. PMID:25762568

Cell-autonomous regulation of Mu-opioid receptor recycling by substance P.

PubMed

Bowman, Shanna L; Soohoo, Amanda L; Shiwarski, Daniel J; Schulz, Stefan; Pradhan, Amynah A; Puthenveedu, Manojkumar A

2015-03-24

How neurons coordinate and reprogram multiple neurotransmitter signals is an area of broad interest. Here, we show that substance P (SP), a neuropeptide associated with inflammatory pain, reprograms opioid receptor recycling and signaling. SP, through activation of the neurokinin 1 (NK1R) receptor, increases the post-endocytic recycling of the mu-opioid receptor (MOR) in trigeminal ganglion (TG) neurons in an agonist-selective manner. SP-mediated protein kinase C (PKC) activation is both required and sufficient for increasing recycling of exogenous and endogenous MOR in TG neurons. The target of this cross-regulation is MOR itself, given that mutation of either of two PKC phosphorylation sites on MOR abolishes the SP-induced increase in recycling and resensitization. Furthermore, SP enhances the resensitization of fentanyl-induced, but not morphine-induced, antinociception in mice. Our results define a physiological pathway that cross-regulates opioid receptor recycling via direct modification of MOR and suggest a mode of homeostatic interaction between the pain and analgesic systems.

The regulation of vascular endothelial growth factor-induced microvascular permeability requires Rac and reactive oxygen species.

PubMed

Monaghan-Benson, Elizabeth; Burridge, Keith

2009-09-18

Vascular permeability is a complex process involving the coordinated regulation of multiple signaling pathways in the endothelial cell. It has long been documented that vascular endothelial growth factor (VEGF) greatly enhances microvascular permeability; however, the molecular mechanisms controlling VEGF-induced permeability remain unknown. Treatment of microvascular endothelial cells with VEGF led to an increase in reactive oxygen species (ROS) production. ROS are required for VEGF-induced permeability as treatment with the free radical scavenger, N-acetylcysteine, inhibited this effect. Additionally, treatment with VEGF caused ROS-dependent tyrosine phosphorylation of both vascular-endothelial (VE)-cadherin and beta-catenin. Rac1 was required for the VEGF-induced increase in permeability and adherens junction protein phosphorylation. Knockdown of Rac1 inhibited VEGF-induced ROS production consistent with Rac lying upstream of ROS in this pathway. Collectively, these data suggest that VEGF leads to a Rac-mediated generation of ROS, which, in turn, elevates the tyrosine phosphorylation of VE-cadherin and beta-catenin, ultimately regulating adherens junction integrity.

MYOCARDIAL AKT: THE OMNIPRESENT NEXUS

PubMed Central

Sussman, Mark A.; Völkers, Mirko; Fischer, Kimberlee; Bailey, Brandi; Cottage, Christopher T.; Din, Shabana; Gude, Natalie; Avitabile, Daniele; Alvarez, Roberto; Sundararaman, Balaji; Quijada, Pearl; Mason, Matt; Konstandin, Mathias H.; Malhowski, Amy; Cheng, Zhaokang; Khan, Mohsin; McGregor, Michael

2013-01-01

One of the greatest examples of integrated signal transduction is revealed by examination of effects mediated by AKT kinase in myocardial biology. Positioned at the intersection of multiple afferent and efferent signals, AKT exemplifies a molecular sensing node that coordinates dynamic responses of the cell in literally every aspect of biological responses. The balanced and nuanced nature of homeostatic signaling is particularly essential within the myocardial context, where regulation of survival, energy production, contractility, and response to pathological stress all flow through the nexus of AKT activation or repression. Equally important, the loss of regulated AKT activity is primarily the cause or consequence of pathological conditions leading to remodeling of the heart and eventual decompensation. This review presents an overview compendium of the complex world of myocardial AKT biology gleaned from more than a decade of research. Summarization of the widespread influence that AKT exerts upon myocardial responses leaves no doubt that the participation of AKT in molecular signaling will need to be reckoned with as a seemingly omnipresent regulator of myocardial molecular biological responses. PMID:21742795

Cell-Autonomous Regulation of Mu-Opioid Receptor Recycling by Substance P

PubMed Central

Bowman, Shanna L.; Soohoo, Amanda L.; Shiwarski, Daniel J.; Schulz, Stefan; Pradhan, Amynah A.; Puthenveedu, Manojkumar A.

2015-01-01

SUMMARY How neurons coordinate and reprogram multiple neurotransmitter signals is an area of broad interest. Here, we show that substance P (SP), a neuropep-tide associated with inflammatory pain, reprograms opioid receptor recycling and signaling. SP, through activation of the neurokinin 1 (NK1R) receptor, increases the post-endocytic recycling of the muopioid receptor (MOR) in trigeminal ganglion (TG) neurons in an agonist-selective manner. SP-mediated protein kinase C (PKC) activation is both required and sufficient for increasing recycling of exogenous and endogenous MOR in TG neurons. The target of this cross-regulation is MOR itself, given that mutation of either of two PKC phosphorylation sites on MOR abolishes the SP-induced increase in recycling and resensitization. Furthermore, SP enhances the resensitization of fentanyl-induced, but not morphine-induced, antinociception in mice. Our results define a physiological pathway that cross-regulates opioid receptor recycling via direct modification of MOR and suggest a mode of homeo-static interaction between the pain and analgesic systems. PMID:25801029

The politics and strategy of industry self-regulation: the pharmaceutical industry's principles for ethical direct-to-consumer advertising as a deceptive blocking strategy.

PubMed

Arnold, Denis G; Oakley, James L

2013-06-01

As the pharmaceutical industry lobbies European regulators to permit direct-to-consumer advertising (DTCA) of prescription drugs in the European Union, we found that five leading companies violated industry-developed and -promulgated standards for ethical advertising in the United States. Utilizing multiple data sources and methods, we demonstrate a consistent failure by companies that market erectile dysfunction drugs to comply with the industry's guiding principles for ethical DTCA over a four-year period despite pledges of compliance by company leaders. Noncompliance resulted in children being exposed to sexually themed promotional messages more than 100 billion times. We argue that the guidelines are a coordinated effort by the industry to prevent unwanted federal regulation, and we introduce the concept of a blocking strategy to explain company behavior and to advance theoretical understanding of firms' public affairs strategies. We recommend policy responses to prevent deceptive practices, protect children from adult content, and promote genuine health care education.

Hippo, TGF-β, and Src-MAPK pathways regulate transcription of the upd3 cytokine in Drosophila enterocytes upon bacterial infection.

PubMed

Houtz, Philip; Bonfini, Alessandro; Liu, Xi; Revah, Jonathan; Guillou, Aurélien; Poidevin, Mickael; Hens, Korneel; Huang, Hsin-Yi; Deplancke, Bart; Tsai, Yu-Chen; Buchon, Nicolas

2017-11-01

Cytokine signaling is responsible for coordinating conserved epithelial regeneration and immune responses in the digestive tract. In the Drosophila midgut, Upd3 is a major cytokine, which is induced in enterocytes (EC) and enteroblasts (EB) upon oral infection, and initiates intestinal stem cell (ISC) dependent tissue repair. To date, the genetic network directing upd3 transcription remains largely uncharacterized. Here, we have identified the key infection-responsive enhancers of the upd3 gene and show that distinct enhancers respond to various stresses. Furthermore, through functional genetic screening, bioinformatic analyses and yeast one-hybrid screening, we determined that the transcription factors Scalloped (Sd), Mothers against dpp (Mad), and D-Fos are principal regulators of upd3 expression. Our study demonstrates that upd3 transcription in the gut is regulated by the activation of multiple pathways, including the Hippo, TGF-β/Dpp, and Src, as well as p38-dependent MAPK pathways. Thus, these essential pathways, which are known to control ISC proliferation cell-autonomously, are also activated in ECs to promote tissue turnover the regulation of upd3 transcription.

SFPQ associates to LSD1 and regulates the migration of newborn pyramidal neurons in the developing cerebral cortex.

PubMed

Saud, K; Cánovas, J; Lopez, C I; Berndt, F A; López, E; Maass, J C; Barriga, A; Kukuljan, M

2017-04-01

The development of the cerebral cortex requires the coordination of multiple processes ranging from the proliferation of progenitors to the migration and establishment of connectivity of the newborn neurons. Epigenetic regulation carried out by the COREST/LSD1 complex has been identified as a mechanism that regulates the development of pyramidal neurons of the cerebral cortex. We now identify the association of the multifunctional RNA-binding protein SFPQ to LSD1 during the development of the cerebral cortex. In vivo reduction of SFPQ dosage by in utero electroporation of a shRNA results in impaired radial migration of newborn pyramidal neurons, in a similar way to that observed when COREST or LSD1 expressions are decreased. Diminished SFPQ expression also associates to decreased proliferation of progenitor cells, while it does not affect the acquisition of neuronal fate. These results are compatible with the idea that SFPQ, plays an important role regulating proliferation and migration during the development of the cerebral cortex. Copyright © 2016 ISDN. Published by Elsevier Ltd. All rights reserved.

Direct Measurement of Charge Regulation in Metalloprotein Electron Transfer.

PubMed

Zahler, Collin T; Zhou, Hongyu; Abdolvahabi, Alireza; Holden, Rebecca L; Rasouli, Sanaz; Tao, Peng; Shaw, Bryan F

2018-05-04

Determining whether a protein regulates its net electrostatic charge during electron transfer (ET) will deepen our mechanistic understanding of how polypeptides tune rates and free energies of ET (e.g., by affecting reorganization energy, and/or redox potential). Charge regulation during ET has never been measured for proteins because few tools exist to measure the net charge of a folded protein in solution at different oxidation states. Herein, we used a niche analytical tool (protein charge ladders analyzed with capillary electrophoresis) to determine that the net charges of myoglobin, cytochrome c, and azurin change by 0.62±0.06, 1.19±0.02, and 0.51±0.04 units upon single ET. Computational analysis predicts that these fluctuations in charge arise from changes in the pK a  values of multiple non-coordinating residues (predominantly histidine) that involve between 0.42-0.90 eV. These results suggest that ionizable residues can tune the reactivity of redox centers by regulating the net charge of the entire protein-cofactor-solvent complex. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Quadrupedal gaits in hexapod animals - inter-leg coordination in free-walking adult stick insects.

PubMed

Grabowska, Martyna; Godlewska, Elzbieta; Schmidt, Joachim; Daun-Gruhn, Silvia

2012-12-15

The analysis of inter-leg coordination in insect walking is generally a study of six-legged locomotion. For decades, the stick insect Carausius morosus has been instrumental for unravelling the rules and mechanisms that control leg coordination in hexapeds. We analysed inter-leg coordination in C. morosus that freely walked on straight paths on plane surfaces with different slopes. Consecutive 1.7 s sections were assigned inter-leg coordination patterns (which we call gaits) based on footfall patterns. Regular gaits, i.e. wave, tetrapod or tripod gaits, occurred in different proportions depending on surface slopes. Tetrapod gaits were observed most frequently, wave gaits only occurred on 90 deg inclining slopes and tripod gaits occurred most often on 15 deg declining slopes, i.e. in 40% of the sections. Depending on the slope, 36-66% of the sections were assigned irregular gaits. Irregular gaits were mostly due to multiple stepping by the front legs, which is perhaps probing behaviour, not phase coupled to the middle legs' cycles. In irregular gaits, middle leg and hindleg coordination was regular, related to quadrupedal walk and wave gaits. Apparently, front legs uncouple from and couple to the walking system without compromising middle leg and hindleg coordination. In front leg amputees, the remaining legs were strictly coordinated. In hindleg and middle leg amputees, the front legs continued multiple stepping. The coordination of middle leg amputees was maladapted, with front legs and hindlegs performing multiple steps or ipsilateral legs being in simultaneous swing. Thus, afferent information from middle legs might be necessary for a regular hindleg stepping pattern.

Growth and stress response mechanisms underlying post-feeding regenerative organ growth in the Burmese python.

PubMed

Andrew, Audra L; Perry, Blair W; Card, Daren C; Schield, Drew R; Ruggiero, Robert P; McGaugh, Suzanne E; Choudhary, Amit; Secor, Stephen M; Castoe, Todd A

2017-05-02

Previous studies examining post-feeding organ regeneration in the Burmese python (Python molurus bivittatus) have identified thousands of genes that are significantly differentially regulated during this process. However, substantial gaps remain in our understanding of coherent mechanisms and specific growth pathways that underlie these rapid and extensive shifts in organ form and function. Here we addressed these gaps by comparing gene expression in the Burmese python heart, liver, kidney, and small intestine across pre- and post-feeding time points (fasted, one day post-feeding, and four days post-feeding), and by conducting detailed analyses of molecular pathways and predictions of upstream regulatory molecules across these organ systems. Identified enriched canonical pathways and upstream regulators indicate that while downstream transcriptional responses are fairly tissue specific, a suite of core pathways and upstream regulator molecules are shared among responsive tissues. Pathways such as mTOR signaling, PPAR/LXR/RXR signaling, and NRF2-mediated oxidative stress response are significantly differentially regulated in multiple tissues, indicative of cell growth and proliferation along with coordinated cell-protective stress responses. Upstream regulatory molecule analyses identify multiple growth factors, kinase receptors, and transmembrane receptors, both within individual organs and across separate tissues. Downstream transcription factors MYC and SREBF are induced in all tissues. These results suggest that largely divergent patterns of post-feeding gene regulation across tissues are mediated by a core set of higher-level signaling molecules. Consistent enrichment of the NRF2-mediated oxidative stress response indicates this pathway may be particularly important in mediating cellular stress during such extreme regenerative growth.

Estimating Accurate Target Coordinates with Magnetic Resonance Images by Using Multiple Phase-Encoding Directions during Acquisition.

PubMed

Kim, Minsoo; Jung, Na Young; Park, Chang Kyu; Chang, Won Seok; Jung, Hyun Ho; Chang, Jin Woo

2018-06-01

Stereotactic procedures are image guided, often using magnetic resonance (MR) images limited by image distortion, which may influence targets for stereotactic procedures. The aim of this work was to assess methods of identifying target coordinates for stereotactic procedures with MR in multiple phase-encoding directions. In 30 patients undergoing deep brain stimulation, we acquired 5 image sets: stereotactic brain computed tomography (CT), T2-weighted images (T2WI), and T1WI in both right-to-left (RL) and anterior-to-posterior (AP) phase-encoding directions. Using CT coordinates as a reference, we analyzed anterior commissure and posterior commissure coordinates to identify any distortion relating to phase-encoding direction. Compared with CT coordinates, RL-directed images had more positive x-axis values (0.51 mm in T1WI, 0.58 mm in T2WI). AP-directed images had more negative y-axis values (0.44 mm in T1WI, 0.59 mm in T2WI). We adopted 2 methods to predict CT coordinates with MR image sets: parallel translation and selective choice of axes according to phase-encoding direction. Both were equally effective at predicting CT coordinates using only MR; however, the latter may be easier to use in clinical settings. Acquiring MR in multiple phase-encoding directions and selecting axes according to the phase-encoding direction allows identification of more accurate coordinates for stereotactic procedures. © 2018 S. Karger AG, Basel.

Free energy from molecular dynamics with multiple constraints

NASA Astrophysics Data System (ADS)

den Otter, W. K.; Briels, W. J.

In molecular dynamics simulations of reacting systems, the key step to determining the equilibrium constant and the reaction rate is the calculation of the free energy as a function of the reaction coordinate. Intuitively the derivative of the free energy is equal to the average force needed to constrain the reaction coordinate to a constant value, but the metric tensor effect of the constraint on the sampled phase space distribution complicates this relation. The appropriately corrected expression for the potential of mean constraint force method (PMCF) for systems in which only the reaction coordinate is constrained was published recently. Here we will consider the general case of a system with multiple constraints. This situation arises when both the reaction coordinate and the 'hard' coordinates are constrained, and also in systems with several reaction coordinates. The obvious advantage of this method over the established thermodynamic integration and free energy perturbation methods is that it avoids the cumbersome introduction of a full set of generalized coordinates complementing the constrained coordinates. Simulations of n -butane and n -pentane in vacuum illustrate the method.

33 CFR 209.141 - Coordination of hydroelectric power operations with power marketing agencies.

Code of Federal Regulations, 2010 CFR

2010-07-01

... power operations with power marketing agencies. 209.141 Section 209.141 Navigation and Navigable Waters... Coordination of hydroelectric power operations with power marketing agencies. (a) Purpose. This regulation... generating facilities with the power marketing agencies. (b) Applicability. This regulation applies to all...

Low pH, Aluminum, and Phosphorus Coordinately Regulate Malate Exudation through GmALMT1 to Improve Soybean Adaptation to Acid Soils1[W][OA

PubMed Central

Liang, Cuiyue; Piñeros, Miguel A.; Tian, Jiang; Yao, Zhufang; Sun, Lili; Liu, Jiping; Shaff, Jon; Coluccio, Alison; Kochian, Leon V.; Liao, Hong

2013-01-01

Low pH, aluminum (Al) toxicity, and low phosphorus (P) often coexist and are heterogeneously distributed in acid soils. To date, the underlying mechanisms of crop adaptation to these multiple factors on acid soils remain poorly understood. In this study, we found that P addition to acid soils could stimulate Al tolerance, especially for the P-efficient genotype HN89. Subsequent hydroponic studies demonstrated that solution pH, Al, and P levels coordinately altered soybean (Glycine max) root growth and malate exudation. Interestingly, HN89 released more malate under conditions mimicking acid soils (low pH, +P, and +Al), suggesting that root malate exudation might be critical for soybean adaptation to both Al toxicity and P deficiency on acid soils. GmALMT1, a soybean malate transporter gene, was cloned from the Al-treated root tips of HN89. Like root malate exudation, GmALMT1 expression was also pH dependent, being suppressed by low pH but enhanced by Al plus P addition in roots of HN89. Quantitative real-time PCR, transient expression of a GmALMT1-yellow fluorescent protein chimera in Arabidopsis protoplasts, and electrophysiological analysis of Xenopus laevis oocytes expressing GmALMT1 demonstrated that GmALMT1 encodes a root cell plasma membrane transporter that mediates malate efflux in an extracellular pH-dependent and Al-independent manner. Overexpression of GmALMT1 in transgenic Arabidopsis, as well as overexpression and knockdown of GmALMT1 in transgenic soybean hairy roots, indicated that GmALMT1-mediated root malate efflux does underlie soybean Al tolerance. Taken together, our results suggest that malate exudation is an important component of soybean adaptation to acid soils and is coordinately regulated by three factors, pH, Al, and P, through the regulation of GmALMT1 expression and GmALMT1 function. PMID:23341359

Low pH, aluminum, and phosphorus coordinately regulate malate exudation through GmALMT1 to improve soybean adaptation to acid soils.

PubMed

Liang, Cuiyue; Piñeros, Miguel A; Tian, Jiang; Yao, Zhufang; Sun, Lili; Liu, Jiping; Shaff, Jon; Coluccio, Alison; Kochian, Leon V; Liao, Hong

2013-03-01

Low pH, aluminum (Al) toxicity, and low phosphorus (P) often coexist and are heterogeneously distributed in acid soils. To date, the underlying mechanisms of crop adaptation to these multiple factors on acid soils remain poorly understood. In this study, we found that P addition to acid soils could stimulate Al tolerance, especially for the P-efficient genotype HN89. Subsequent hydroponic studies demonstrated that solution pH, Al, and P levels coordinately altered soybean (Glycine max) root growth and malate exudation. Interestingly, HN89 released more malate under conditions mimicking acid soils (low pH, +P, and +Al), suggesting that root malate exudation might be critical for soybean adaptation to both Al toxicity and P deficiency on acid soils. GmALMT1, a soybean malate transporter gene, was cloned from the Al-treated root tips of HN89. Like root malate exudation, GmALMT1 expression was also pH dependent, being suppressed by low pH but enhanced by Al plus P addition in roots of HN89. Quantitative real-time PCR, transient expression of a GmALMT1-yellow fluorescent protein chimera in Arabidopsis protoplasts, and electrophysiological analysis of Xenopus laevis oocytes expressing GmALMT1 demonstrated that GmALMT1 encodes a root cell plasma membrane transporter that mediates malate efflux in an extracellular pH-dependent and Al-independent manner. Overexpression of GmALMT1 in transgenic Arabidopsis, as well as overexpression and knockdown of GmALMT1 in transgenic soybean hairy roots, indicated that GmALMT1-mediated root malate efflux does underlie soybean Al tolerance. Taken together, our results suggest that malate exudation is an important component of soybean adaptation to acid soils and is coordinately regulated by three factors, pH, Al, and P, through the regulation of GmALMT1 expression and GmALMT1 function.

Systems Level Analyses Reveal Multiple Regulatory Activities of CodY Controlling Metabolism, Motility and Virulence in Listeria monocytogenes

PubMed Central

Lobel, Lior; Herskovits, Anat A.

2016-01-01

Bacteria sense and respond to many environmental cues, rewiring their regulatory network to facilitate adaptation to new conditions/niches. Global transcription factors that co-regulate multiple pathways simultaneously are essential to this regulatory rewiring. CodY is one such global regulator, controlling expression of both metabolic and virulence genes in Gram-positive bacteria. Branch chained amino acids (BCAAs) serve as a ligand for CodY and modulate its activity. Classically, CodY was considered to function primarily as a repressor under rich growth conditions. However, our previous studies of the bacterial pathogen Listeria monocytogenes revealed that CodY is active also when the bacteria are starved for BCAAs. Under these conditions, CodY loses the ability to repress genes (e.g., metabolic genes) and functions as a direct activator of the master virulence regulator gene, prfA. This observation raised the possibility that CodY possesses multiple functions that allow it to coordinate gene expression across a wide spectrum of metabolic growth conditions, and thus better adapt bacteria to the mammalian niche. To gain a deeper understanding of CodY’s regulatory repertoire and identify direct target genes, we performed a genome wide analysis of the CodY regulon and DNA binding under both rich and minimal growth conditions, using RNA-Seq and ChIP-Seq techniques. We demonstrate here that CodY is indeed active (i.e., binds DNA) under both conditions, serving as a repressor and activator of different genes. Further, we identified new genes and pathways that are directly regulated by CodY (e.g., sigB, arg, his, actA, glpF, gadG, gdhA, poxB, glnR and fla genes), integrating metabolism, stress responses, motility and virulence in L. monocytogenes. This study establishes CodY as a multifaceted factor regulating L. monocytogenes physiology in a highly versatile manner. PMID:26895237

Tellurium-containing polymer micelles: competitive-ligand-regulated coordination responsive systems.

PubMed

Cao, Wei; Gu, Yuwei; Meineck, Myriam; Li, Tianyu; Xu, Huaping

2014-04-02

Nanomaterials capable of achieving tunable cargo release kinetics are of significance in a fundamental sense and various biological or medical applications. We report a competitive coordination system based on a novel tellurium-containing polymer and its ligand-regulated release manners. Tellurium was introduced to water-soluble polymers for the first time as drug delivery vehicles. The coordination chemistry between platinum and tellurium was designed to enable the load of platinum-based drugs. Through the competitive coordination of biomolecules, the drugs could be released in a controlled manner. Furthermore, the release kinetics could be modulated by the competitive ligands involved due to their different coordination ability. This tellurium-containing polymer may enrich the family of delivery systems and provide a new platform for future biomedical nanotechnologies.

HES factors regulate specific aspects of chondrogenesis and chondrocyte hypertrophy during cartilage development

PubMed Central

Rutkowski, Timothy P.; Kohn, Anat; Sharma, Deepika; Ren, Yinshi; Mirando, Anthony J.

2016-01-01

ABSTRACT RBPjκ-dependent Notch signaling regulates multiple processes during cartilage development, including chondrogenesis, chondrocyte hypertrophy and cartilage matrix catabolism. Select members of the HES- and HEY-families of transcription factors are recognized Notch signaling targets that mediate specific aspects of Notch function during development. However, whether particular HES and HEY factors play any role(s) in the processes during cartilage development is unknown. Here, for the first time, we have developed unique in vivo genetic models and in vitro approaches demonstrating that the RBPjκ-dependent Notch targets HES1 and HES5 suppress chondrogenesis and promote the onset of chondrocyte hypertrophy. HES1 and HES5 might have some overlapping function in these processes, although only HES5 directly regulates Sox9 transcription to coordinate cartilage development. HEY1 and HEYL play no discernable role in regulating chondrogenesis or chondrocyte hypertrophy, whereas none of the HES or HEY factors appear to mediate Notch regulation of cartilage matrix catabolism. This work identifies important candidates that might function as downstream mediators of Notch signaling both during normal skeletal development and in Notch-related skeletal disorders. PMID:27160681

Systems analysis of multiple regulator perturbations allows discovery of virulence factors in Salmonella

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

Yoon, Hyunjin; Ansong, Charles; McDermott, Jason E.

Background: Systemic bacterial infections are highly regulated and complex processes that are orchestrated by numerous virulence factors. Genes that are coordinately controlled by the set of regulators required for systemic infection are potentially required for pathogenicity. Results: In this study we present a systems biology approach in which sample-matched multi-omic measurements of fourteen virulence-essential regulator mutants were coupled with computational network analysis to efficiently identify Salmonella virulence factors. Immunoblot experiments verified network-predicted virulence factors and a subset was determined to be secreted into the host cytoplasm, suggesting that they are virulence factors directly interacting with host cellular components. Two ofmore » these, SrfN and PagK2, were required for full mouse virulence and were shown to be translocated independent of either of the type III secretion systems in Salmonella or the type III injectisome-related flagellar mechanism. Conclusions: Integrating multi-omic datasets from Salmonella mutants lacking virulence regulators not only identified novel virulence factors but also defined a new class of translocated effectors involved in pathogenesis. The success of this strategy at discovery of known and novel virulence factors suggests that the approach may have applicability for other bacterial pathogens.« less

Plant hormone signaling in flowering: An epigenetic point of view.

PubMed

Campos-Rivero, Gerardo; Osorio-Montalvo, Pedro; Sánchez-Borges, Rafael; Us-Camas, Rosa; Duarte-Aké, Fátima; De-la-Peña, Clelia

2017-07-01

Reproduction is one of the most important phases in an organism's lifecycle. In the case of angiosperm plants, flowering provides the major developmental transition from the vegetative to the reproductive stage, and requires genetic and epigenetic reprogramming to ensure the success of seed production. Flowering is regulated by a complex network of genes that integrate multiple environmental cues and endogenous signals so that flowering occurs at the right time; hormone regulation, signaling and homeostasis are very important in this process. Working alone or in combination, hormones are able to promote flowering by epigenetic regulation. Some plant hormones, such as gibberellins, jasmonic acid, abscisic acid and auxins, have important effects on chromatin compaction mediated by DNA methylation and histone posttranslational modifications, which hints at the role that epigenetic regulation may play in flowering through hormone action. miRNAs have been viewed as acting independently from DNA methylation and histone modification, ignoring their potential to interact with hormone signaling - including the signaling of auxins, gibberellins, ethylene, jasmonic acid, salicylic acid and others - to regulate flowering. Therefore, in this review we examine new findings about interactions between epigenetic mechanisms and key players in hormone signaling to coordinate flowering. Copyright © 2017 Elsevier GmbH. All rights reserved.

Multiresource allocation and scheduling for periodic soft real-time applications

NASA Astrophysics Data System (ADS)

Gopalan, Kartik; Chiueh, Tzi-cker

2001-12-01

Real-time applications that utilize multiple system resources, such as CPU, disks, and network links, require coordinated scheduling of these resources in order to meet their end-to-end performance requirements. Most state-of-the-art operating systems support independent resource allocation and deadline-driven scheduling but lack coordination among multiple heterogeneous resources. This paper describes the design and implementation of an Integrated Real-time Resource Scheduler (IRS) that performs coordinated allocation and scheduling of multiple heterogeneous resources on the same machine for periodic soft real-time application. The principal feature of IRS is a heuristic multi-resource allocation algorithm that reserves multiple resources for real-time applications in a manner that can maximize the number of applications admitted into the system in the long run. At run-time, a global scheduler dispatches the tasks of the soft real-time application to individual resource schedulers according to the precedence constraints between tasks. The individual resource schedulers, which could be any deadline based schedulers, can make scheduling decisions locally and yet collectively satisfy a real-time application's performance requirements. The tightness of overall timing guarantees is ultimately determined by the properties of individual resource schedulers. However, IRS maximizes overall system resource utilization efficiency by coordinating deadline assignment across multiple tasks in a soft real-time application.

A let-7-to-miR-125 MicroRNA Switch Regulates Neuronal Integrity and Lifespan in Drosophila

PubMed Central

Chawla, Geetanjali; Deosthale, Padmini; Childress, Sue; Wu, Yen-chi; Sokol, Nicholas S.

2016-01-01

Messenger RNAs (mRNAs) often contain binding sites for multiple, different microRNAs (miRNAs). However, the biological significance of this feature is unclear, since such co-targeting miRNAs could function coordinately, independently, or redundantly with one another. Here, we show that two co-transcribed Drosophila miRNAs, let-7 and miR-125, non-redundantly regulate a common target, the transcription factor Chronologically Inappropriate Morphogenesis (Chinmo). We first characterize novel adult phenotypes associated with loss of both let-7 and miR-125, which are derived from a common, polycistronic transcript that also encodes a third miRNA, miR-100. Consistent with the coordinate upregulation of all three miRNAs in aging flies, these phenotypes include brain degeneration and shortened lifespan. However, transgenic rescue analysis reveal separable roles for these miRNAs: adult miR-125 but not let-7 mutant phenotypes are associated with ectopic Chinmo expression in adult brains and are suppressed by chinmo reduction. In contrast, let-7 is predominantly responsible for regulating chinmo during nervous system formation. These results indicate that let-7 and miR-125 function during two distinct stages, development and adulthood, rather than acting at the same time. These different activities are facilitated by an increased rate of processing of let-7 during development and a lower rate of decay of the accumulated miR-125 in the adult nervous system. Thus, this work not only establishes a key role for the highly conserved miR-125 in aging. It also demonstrates that two co-transcribed miRNAs function independently during distinct stages to regulate a common target, raising the possibility that such biphasic control may be a general feature of clustered miRNAs. PMID:27508495

78 FR 17066 - Indirect Stock Transfers and Coordination Rule Exceptions; Transfers of Stock or Securities in...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-19

... Indirect Stock Transfers and Coordination Rule Exceptions; Transfers of Stock or Securities in Outbound... issue of the Federal Register, the IRS and the Treasury Department are issuing temporary regulations... stock transfers for certain outbound asset reorganizations. The temporary regulations also modify the...

48 CFR 750.7110-2 - Office of General Counsel coordination.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Office of General Counsel coordination. 750.7110-2 Section 750.7110-2 Federal Acquisition Regulations System AGENCY FOR INTERNATIONAL DEVELOPMENT CONTRACT MANAGEMENT EXTRAORDINARY CONTRACTUAL ACTIONS Extraordinary Contractual Actions To Protect Foreign Policy Interests of th...

75 FR 57690 - Acquisition Regulation: Sustainable Acquisition

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-22

... coordinate its activities with and submit required reports through the Environmental Sustainability... reports directly to the Prime Contractor's Environmental Sustainability Coordinator at the supported... reports through the Environmental Sustainability Coordinator or equivalent position. Reporting under this...

49 CFR 613.300 - Coordination of Federal and federally assisted programs and projects.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 7 2012-10-01 2012-10-01 false Coordination of Federal and federally assisted programs and projects. 613.300 Section 613.300 Transportation Other Regulations Relating to Transportation... Coordination of Federal and Federally Assisted Programs and Projects § 613.300 Coordination of Federal and...

Mitigating regulatory impact: the case of partial price controls on metformin in India.

PubMed

Bhaskarabhatla, Ajay; Chatterjee, Chirantan; Anurag, Priyatam; Pennings, Enrico

2017-03-01

The use of drug price controls is a contentious issue globally. Low- and middle-income countries use direct price controls to improve access to essential drugs. But such price controls have little meaning if they are not designed and implemented well, and the extent to which firms coordinate in these countries to weaken price controls has been largely overlooked. In mid-2013, India adopted partial price-cap regulation for some, but not all, formulations of several essential medicines. Using data on sales and prices of the out-of-patent oral antidiabetic drug Metformin—considered essential by WHO since 1998—and employing the differences-in-differences methodology, we examine the impact of the regulation on curbing prices. We find that firms coordinated to increase the price of the regulated formulation in the period before regulation, which led to a higher ceiling price. We also find, using triple-differences analyses, that the coordination is stronger among larger firms and for time-release formulations. We present anecdotal evidence to suggest that pharmaceutical trade associations facilitated coordination among firms, and we conclude that partial price control of Metformin in India is, at best, a modest improvement over no regulation.

A Safe Cooperative Framework for Atmospheric Science Missions with Multiple Heterogeneous UAS using Piecewise Bezier Curves

NASA Technical Reports Server (NTRS)

Mehdi, S. Bilal; Puig-Navarro, Javier; Choe, Ronald; Cichella, Venanzio; Hovakimyan, Naira; Chandarana, Meghan; Trujillo, Anna; Rothhaar, Paul M.; Tran, Loc; Neilan, James H.;

Circulating microRNAs as Potential Biomarkers of Infectious Disease

PubMed Central

Correia, Carolina N.; Nalpas, Nicolas C.; McLoughlin, Kirsten E.; Browne, John A.; Gordon, Stephen V.; MacHugh, David E.; Shaughnessy, Ronan G.

2017-01-01

microRNAs (miRNAs) are a class of small non-coding endogenous RNA molecules that regulate a wide range of biological processes by post-transcriptionally regulating gene expression. Thousands of these molecules have been discovered to date, and multiple miRNAs have been shown to coordinately fine-tune cellular processes key to organismal development, homeostasis, neurobiology, immunobiology, and control of infection. The fundamental regulatory role of miRNAs in a variety of biological processes suggests that differential expression of these transcripts may be exploited as a novel source of molecular biomarkers for many different disease pathologies or abnormalities. This has been emphasized by the recent discovery of remarkably stable miRNAs in mammalian biofluids, which may originate from intracellular processes elsewhere in the body. The potential of circulating miRNAs as biomarkers of disease has mainly been demonstrated for various types of cancer. More recently, however, attention has focused on the use of circulating miRNAs as diagnostic/prognostic biomarkers of infectious disease; for example, human tuberculosis caused by infection with Mycobacterium tuberculosis, sepsis caused by multiple infectious agents, and viral hepatitis. Here, we review these developments and discuss prospects and challenges for translating circulating miRNA into novel diagnostics for infectious disease. PMID:28261201

Cysteine-rich peptides (CRPs) mediate diverse aspects of cell-cell communication in plant reproduction and development.

PubMed

Marshall, Eleanor; Costa, Liliana M; Gutierrez-Marcos, Jose

2011-03-01

Cell-cell communication in plants is essential for the correct co-ordination of reproduction, growth, and development. Studies to dissect this mode of communication have previously focussed primarily on the action of plant hormones as mediators of intercellular signalling. In animals, peptide signalling is a well-documented intercellular communication system, however, relatively little is known about this system in plants. In recent years, numerous reports have emerged about small, secreted peptides controlling different aspects of plant reproduction. Interestingly, most of these peptides are cysteine-rich, and there is convincing evidence suggesting multiple roles for related cysteine-rich peptides (CRPs) as signalling factors in developmental patterning as well as during plant pathogen responses and symbiosis. In this review, we discuss how CRPs are emerging as key signalling factors in regulating multiple aspects of vegetative growth and reproductive development in plants.

Shutoff of Host Gene Expression in Influenza A Virus and Herpesviruses: Similar Mechanisms and Common Themes

PubMed Central

Rivas, Hembly G.; Schmaling, Summer K.; Gaglia, Marta M.

2016-01-01

The ability to shut off host gene expression is a shared feature of many viral infections, and it is thought to promote viral replication by freeing host cell machinery and blocking immune responses. Despite the molecular differences between viruses, an emerging theme in the study of host shutoff is that divergent viruses use similar mechanisms to enact host shutoff. Moreover, even viruses that encode few proteins often have multiple mechanisms to affect host gene expression, and we are only starting to understand how these mechanisms are integrated. In this review we discuss the multiplicity of host shutoff mechanisms used by the orthomyxovirus influenza A virus and members of the alpha- and gamma-herpesvirus subfamilies. We highlight the surprising similarities in their mechanisms of host shutoff and discuss how the different mechanisms they use may play a coordinated role in gene regulation. PMID:27092522

Motion and force control for multiple cooperative manipulators

NASA Technical Reports Server (NTRS)

Wen, John T.; Kreutz, Kenneth

1989-01-01

The motion and force control of multiple robot arms manipulating a commonly held object is addressed. A general control paradigm that decouples the motion and force control problems is introduced. For motion control, there are three natural choices: (1) joint torques, (2) arm-tip force vectors, and (3) the acceleration of a generalized coordinate. Choice (1) allows a class of relatively model-independent control laws by exploiting the Hamiltonian structure of the open-loop system; (2) and (3) require the full model information but produce simpler problems. To resolve the nonuniqueness of the joint torques, two methods are introduced. If the arm and object models are available, the allocation of the desired end-effector control force to the joint actuators can be optimized; otherwise the internal force can be controlled about some set point. It is shown that effective force regulation can be achieved even if little model information is available.

Dual Coordination of Post Translational Modifications in Human Protein Networks

PubMed Central

Woodsmith, Jonathan; Kamburov, Atanas; Stelzl, Ulrich

2013-01-01

Post-translational modifications (PTMs) regulate protein activity, stability and interaction profiles and are critical for cellular functioning. Further regulation is gained through PTM interplay whereby modifications modulate the occurrence of other PTMs or act in combination. Integration of global acetylation, ubiquitination and tyrosine or serine/threonine phosphorylation datasets with protein interaction data identified hundreds of protein complexes that selectively accumulate each PTM, indicating coordinated targeting of specific molecular functions. A second layer of PTM coordination exists in these complexes, mediated by PTM integration (PTMi) spots. PTMi spots represent very dense modification patterns in disordered protein regions and showed an equally high mutation rate as functional protein domains in cancer, inferring equivocal importance for cellular functioning. Systematic PTMi spot identification highlighted more than 300 candidate proteins for combinatorial PTM regulation. This study reveals two global PTM coordination mechanisms and emphasizes dataset integration as requisite in proteomic PTM studies to better predict modification impact on cellular signaling. PMID:23505349

Analysis of model replication origins in Drosophila reveals new aspects of the chromatin landscape and its relationship to origin activity and the prereplicative complex

PubMed Central

Liu, Jun; McConnell, Kristopher; Dixon, Michael; Calvi, Brian R.

2012-01-01

Epigenetic regulation exerts a major influence on origins of DNA replication during development. The mechanisms for this regulation, however, are poorly defined. We showed previously that acetylation of nucleosomes regulates the origins that mediate developmental gene amplification during Drosophila oogenesis. Here we show that developmental activation of these origins is associated with acetylation of multiple histone lysines. Although these modifications are not unique to origin loci, we find that the level of acetylation is higher at the active origins and quantitatively correlated with the number of times these origins initiate replication. All of these acetylation marks were developmentally dynamic, rapidly increasing with origin activation and rapidly declining when the origins shut off and neighboring promoters turn on. Fine-scale analysis of the origins revealed that both hyperacetylation of nucleosomes and binding of the origin recognition complex (ORC) occur in a broad domain and that acetylation is highest on nucleosomes adjacent to one side of the major site of replication initiation. It was surprising to find that acetylation of some lysines depends on binding of ORC to the origin, suggesting that multiple histone acetyltransferases may be recruited during origin licensing. Our results reveal new insights into the origin epigenetic landscape and lead us to propose a chromatin switch model to explain the coordination of origin and promoter activity during development. PMID:22049023

Soft Regulation with Crowd Recommendation: Coordinating Self-Interested Agents in Sociotechnical Systems under Imperfect Information.

PubMed

Luo, Yu; Iyengar, Garud; Venkatasubramanian, Venkat

2016-01-01

Regulating emerging industries is challenging, even controversial at times. Under-regulation can result in safety threats to plant personnel, surrounding communities, and the environment. Over-regulation may hinder innovation, progress, and economic growth. Since one typically has limited understanding of, and experience with, the novel technology in practice, it is difficult to accomplish a properly balanced regulation. In this work, we propose a control and coordination policy called soft regulation that attempts to strike the right balance and create a collective learning environment. In soft regulation mechanism, individual agents can accept, reject, or partially accept the regulator's recommendation. This non-intrusive coordination does not interrupt normal operations. The extent to which an agent accepts the recommendation is mediated by a confidence level (from 0 to 100%). Among all possible recommendation methods, we investigate two in particular: the best recommendation wherein the regulator is completely informed and the crowd recommendation wherein the regulator collects the crowd's average and recommends that value. We show by analysis and simulations that soft regulation with crowd recommendation performs well. It converges to optimum, and is as good as the best recommendation for a wide range of confidence levels. This work sheds a new theoretical perspective on the concept of the wisdom of crowds.

Self-Healing Gelatin Hydrogels Cross-Linked by Combining Multiple Hydrogen Bonding and Ionic Coordination.

PubMed

Zhang, Guangzhao; Lv, Lei; Deng, Yonghong; Wang, Chaoyang

2017-06-01

Self-healing hydrogels have been studied by many researchers via multiple cross-linking approaches including physical and chemical interactions. It is an interesting project in multifunctional hydrogel exploration that a water soluble polymer matrix is cross-linked by combining the ionic coordination and the multiple hydrogen bonds to fabricate self-healing hydrogels with injectable property. This study introduces a general procedure of preparing the hydrogels (termed gelatin-UPy-Fe) cross-linked by both ionic coordination of Fe 3+ and carboxyl group from the gelatin and the quadruple hydrogen bonding interaction from the ureido-pyrimidinone (UPy) dimers. The gelatin-UPy-Fe hydrogels possess an excellent self-healing property. The effects of the ionic coordination of Fe 3+ and quadruple hydrogen bonding of UPy on the formation and mechanical behavior of the prepared hydrogels are investigated. In vitro drug release of the gelatin-UPy-Fe hydrogels is also observed, giving an intriguing glimpse into possible biological applications. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

An Overview of Seafood Supply, Food Safety and Regulation in New South Wales, Australia.

PubMed

Hussain, Malik A; Saputra, Themy; Szabo, Elizabeth A; Nelan, Bruce

2017-07-19

Seafood consumption is increasing in Australia, especially in New South Wales (NSW). Average per capita seafood consumption in NSW is higher than the national average. Seafood supply in NSW comes from domestic (wild catch and aquaculture) and overseas (seafood imports) sources. The contribution of wild catch and aquaculture in domestic seafood production (2012-2013) was 73.42% and 26.52%, respectively. Seafood-associated foodborne illness outbreaks are not common and on an average four outbreaks occur each year in NSW. Most of the outbreaks in 2015 and 2016 were related to ciguatera poisoning. The regulation of the seafood industry and the management of food safety is an example of the coordinated work of multiple government agencies and organizations in which NSW Food Authority is responsible for managing the overall risks through the Seafood Safety Scheme. Overall, seafood supply in NSW is of high quality and poses low food safety risk to consumers.

Regulation of podocalyxin trafficking by Rab small GTPases in epithelial cells

PubMed Central

Mrozowska, Paulina S.; Fukuda, Mitsunori

2016-01-01

ABSTRACT The characteristic feature of polarity establishment in MDCK II cells is transcytosis of apical glycoprotein podocalyxin (PCX) from the outer plasma membrane to the newly formed apical domain. This transcytotic event consists of multiple steps, including internalization from the plasma membrane, transport through early endosomes and Rab11-positive recycling endosomes, and delivery to the apical membrane. These steps are known to be tightly coordinated by Rab small GTPases, which act as molecular switches cycling between active GTP-bound and inactive GDP-bound states. However, our knowledge regarding which sets of Rabs regulate particular steps of PCX trafficking was rather limited. Recently, we have performed a comprehensive analysis of Rab GTPase engagement in the transcytotic pathway of PCX during polarity establishment in 2-dimensional (2D) and 3-dimensional (3D) MDCK II cell cultures. In this Commentary we summarize our findings and set them in the context of previous reports. PMID:27463697

Coordinating Known and Unknown Quantities in a Multiplicative Context: Problem Conceptualization, Affordances and Constraints

ERIC Educational Resources Information Center

Ramful, Ajay

2012-01-01

In line with continuing efforts to explain the demanding nature of multiplicative reasoning among middle-school students, this study explores the fine-grained knowledge elements that two pairs of 7th and 8th graders deployed in their attempt to coordinate the known and unknown quantities in the gear-wheel problem. Failure to conceptualize the…

I have my own lease-So why the service plan again? Perspectives on service planning in supportive housing.

PubMed

Choy-Brown, Mimi; Hamovitch, Emily K; Cuervo, Carolina; Stanhope, Victoria

2016-12-01

This study aimed to understand multiple stakeholder perspectives implementing a recovery-oriented approach to service planning in supportive housing programs serving people with lived experience of mental illnesses. Multiple stakeholders (N = 57) were recruited to participate in focus groups (N = 8), including 4 with tenants, 2 with service coordinators, 1 with supervisors, and 1 with leadership. Supportive housing programs were purposively sampled from a recovery-oriented organization serving 1,500 people annually. Stakeholders' experiences with service planning and implementing a recovery-oriented approach to service planning were explored. The authors conducted inductive thematic analyses combined with a conceptual matrix, which yielded themes across and within multiple stakeholder focus groups. Three themes emerged: (a) an institutional reminder-service planning experiences elicited negative emotions and served to remind people of experiences in institutional settings, (b) one-size-fits-all service planning-stakeholders perceived the use of quality assurance tools within the planning process as rigid to others' interests beyond their own, and (c) rules and regulations-reconciling funder requirements (e.g., completion dates) while also tailoring services to tenants' particular situations challenged providers. Even in a recovery-oriented organization, findings suggest that service planning in supportive housing has limitations in responding to each tenant's iterative recovery process. Further, in this context where people can make their home, stakeholders questioned whether the very presence of ongoing service planning activities is problematic. However, tenant-service coordinator relationships predicated on mutual respect and esteem overcame some service planning limitations. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Telerobotic management system: coordinating multiple human operators with multiple robots

NASA Astrophysics Data System (ADS)

King, Jamie W.; Pretty, Raymond; Brothers, Brendan; Gosine, Raymond G.

2003-09-01

This paper describes an application called the Tele-robotic management system (TMS) for coordinating multiple operators with multiple robots for applications such as underground mining. TMS utilizes several graphical interfaces to allow the user to define a partially ordered plan for multiple robots. This plan is then converted to a Petri net for execution and monitoring. TMS uses a distributed framework to allow robots and operators to easily integrate with the applications. This framework allows robots and operators to join the network and advertise their capabilities through services. TMS then decides whether tasks should be dispatched to a robot or a remote operator based on the services offered by the robots and operators.

Automation of Coordinated Planning Between Observatories: The Visual Observation Layout Tool (VOLT)

NASA Technical Reports Server (NTRS)

Maks, Lori; Koratkar, Anuradha; Kerbel, Uri; Pell, Vince

2002-01-01

Fulfilling the promise of the era of great observatories, NASA now has more than three space-based astronomical telescopes operating in different wavebands. This situation provides astronomers with the unique opportunity of simultaneously observing a target in multiple wavebands with these observatories. Currently scheduling multiple observatories simultaneously, for coordinated observations, is highly inefficient. Coordinated observations require painstaking manual collaboration among the observatory staff at each observatory. Because they are time-consuming and expensive to schedule, observatories often limit the number of coordinated observations that can be conducted. In order to exploit new paradigms for observatory operation, the Advanced Architectures and Automation Branch of NASA's Goddard Space Flight Center has developed a tool called the Visual Observation Layout Tool (VOLT). The main objective of VOLT is to provide a visual tool to automate the planning of coordinated observations by multiple astronomical observatories. Four of NASA's space-based astronomical observatories - the Hubble Space Telescope (HST), Far Ultraviolet Spectroscopic Explorer (FUSE), Rossi X-ray Timing Explorer (RXTE) and Chandra - are enthusiastically pursuing the use of VOLT. This paper will focus on the purpose for developing VOLT, as well as the lessons learned during the infusion of VOLT into the planning and scheduling operations of these observatories.

Ghrelin: an emerging player in the regulation of reproduction in non-mammalian vertebrates.

PubMed

Unniappan, Suraj

2010-07-01

The endocrine regulation of vertebrate reproduction is achieved by the coordinated actions of multiple endocrine factors mainly produced from the brain, pituitary, and gonads. In addition to these, several other tissues including the fat and gut produce factors that have reproductive effects. Ghrelin is one such gut/brain hormone with species-specific effects in the regulation of mammalian reproduction. Recent studies have shown that ghrelin and ghrelin receptor mRNAs, and protein are expressed in the ovary and testis of mammals, indicating a direct effect for ghrelin in the control of reproduction. Ghrelin regulates mammalian reproduction by modulating hormone secretion from the brain and pituitary, and by acting directly on the gonads to influence reproductive tissue development and steroid hormone release. Based on the studies reported so far, ghrelin seems to have a predominantly inhibitory role on mammalian reproduction. The presence of ghrelin and ghrelin receptor has been found in the brain, pituitary and gonads of several non-mammalian vertebrates. In contrast to mammals, ghrelin seems to have a stimulatory role in the regulation of non-mammalian reproduction. The main objective of this review is to do a perspective analysis of the comparative aspects of ghrelin regulation of reproduction. (c) 2009 Elsevier Inc. All rights reserved.

Soft Regulation with Crowd Recommendation: Coordinating Self-Interested Agents in Sociotechnical Systems under Imperfect Information

PubMed Central

2016-01-01

Regulating emerging industries is challenging, even controversial at times. Under-regulation can result in safety threats to plant personnel, surrounding communities, and the environment. Over-regulation may hinder innovation, progress, and economic growth. Since one typically has limited understanding of, and experience with, the novel technology in practice, it is difficult to accomplish a properly balanced regulation. In this work, we propose a control and coordination policy called soft regulation that attempts to strike the right balance and create a collective learning environment. In soft regulation mechanism, individual agents can accept, reject, or partially accept the regulator’s recommendation. This non-intrusive coordination does not interrupt normal operations. The extent to which an agent accepts the recommendation is mediated by a confidence level (from 0 to 100%). Among all possible recommendation methods, we investigate two in particular: the best recommendation wherein the regulator is completely informed and the crowd recommendation wherein the regulator collects the crowd’s average and recommends that value. We show by analysis and simulations that soft regulation with crowd recommendation performs well. It converges to optimum, and is as good as the best recommendation for a wide range of confidence levels. This work sheds a new theoretical perspective on the concept of the wisdom of crowds. PMID:26977699

Dynamics of DNA methylation and Histone H4 acetylation during floral bud differentiation in azalea

PubMed Central

2010-01-01

Background The ability to control the timing of flowering is a key strategy for planning production in ornamental species such as azalea, however it requires a thorough understanding of floral transition. Floral transition is achieved through a complex genetic network and regulated by multiple environmental and endogenous cues. Dynamic changes between chromatin states facilitating or inhibiting DNA transcription regulate the expression of floral induction pathways in response to environmental and developmental signals. DNA methylation and histone modifications are involved in controlling the functional state of chromatin and gene expression. Results The results of this work indicate that epigenetic mechanisms such as DNA methylation and histone H4 acetylation have opposite and particular dynamics during the transition from vegetative to reproductive development in the apical shoots of azalea. Global levels of DNA methylation and histone H4 acetylation as well as immunodetection of 5-mdC and acetylated H4, in addition to a morphological study have permitted the delimitation of four basic phases in the development of the azalea bud and allowed the identification of a stage of epigenetic reprogramming which showed a sharp decrease of whole DNA methylation similar to that is defined in other developmental processes in plants and in mammals. Conclusion The epigenetic control and reorganization of chromatin seem to be decisive for coordinating floral development in azalea. DNA methylation and H4 deacetylation act simultaneously and co-ordinately, restructuring the chromatin and regulating the gene expression during soot apical meristem development and floral differentiation. PMID:20067625

Multi-objective decoupling algorithm for active distance control of intelligent hybrid electric vehicle

NASA Astrophysics Data System (ADS)

Luo, Yugong; Chen, Tao; Li, Keqiang

2015-12-01

The paper presents a novel active distance control strategy for intelligent hybrid electric vehicles (IHEV) with the purpose of guaranteeing an optimal performance in view of the driving functions, optimum safety, fuel economy and ride comfort. Considering the complexity of driving situations, the objects of safety and ride comfort are decoupled from that of fuel economy, and a hierarchical control architecture is adopted to improve the real-time performance and the adaptability. The hierarchical control structure consists of four layers: active distance control object determination, comprehensive driving and braking torque calculation, comprehensive torque distribution and torque coordination. The safety distance control and the emergency stop algorithms are designed to achieve the safety and ride comfort goals. The optimal rule-based energy management algorithm of the hybrid electric system is developed to improve the fuel economy. The torque coordination control strategy is proposed to regulate engine torque, motor torque and hydraulic braking torque to improve the ride comfort. This strategy is verified by simulation and experiment using a forward simulation platform and a prototype vehicle. The results show that the novel control strategy can achieve the integrated and coordinated control of its multiple subsystems, which guarantees top performance of the driving functions and optimum safety, fuel economy and ride comfort.

Multiple Sensory-Motor Pathways Lead to Coordinated Visual Attention

PubMed Central

Yu, Chen; Smith, Linda B.

2016-01-01

Joint attention has been extensively studied in the developmental literature because of overwhelming evidence that the ability to socially coordinate visual attention to an object is essential to healthy developmental outcomes, including language learning. The goal of the present study is to understand the complex system of sensory-motor behaviors that may underlie the establishment of joint attention between parents and toddlers. In an experimental task, parents and toddlers played together with multiple toys. We objectively measured joint attention – and the sensory-motor behaviors that underlie it – using a dual head-mounted eye-tracking system and frame-by-frame coding of manual actions. By tracking the momentary visual fixations and hand actions of each participant, we precisely determined just how often they fixated on the same object at the same time, the visual behaviors that preceded joint attention, and manual behaviors that preceded and co-occurred with joint attention. We found that multiple sequential sensory-motor patterns lead to joint attention. In addition, there are developmental changes in this multi-pathway system evidenced as variations in strength among multiple routes. We propose that coordinated visual attention between parents and toddlers is primarily a sensory-motor behavior. Skill in achieving coordinated visual attention in social settings – like skills in other sensory-motor domains – emerges from multiple pathways to the same functional end. PMID:27016038

Multiple Sensory-Motor Pathways Lead to Coordinated Visual Attention.

PubMed

Yu, Chen; Smith, Linda B

2017-02-01

Joint attention has been extensively studied in the developmental literature because of overwhelming evidence that the ability to socially coordinate visual attention to an object is essential to healthy developmental outcomes, including language learning. The goal of this study was to understand the complex system of sensory-motor behaviors that may underlie the establishment of joint attention between parents and toddlers. In an experimental task, parents and toddlers played together with multiple toys. We objectively measured joint attention-and the sensory-motor behaviors that underlie it-using a dual head-mounted eye-tracking system and frame-by-frame coding of manual actions. By tracking the momentary visual fixations and hand actions of each participant, we precisely determined just how often they fixated on the same object at the same time, the visual behaviors that preceded joint attention and manual behaviors that preceded and co-occurred with joint attention. We found that multiple sequential sensory-motor patterns lead to joint attention. In addition, there are developmental changes in this multi-pathway system evidenced as variations in strength among multiple routes. We propose that coordinated visual attention between parents and toddlers is primarily a sensory-motor behavior. Skill in achieving coordinated visual attention in social settings-like skills in other sensory-motor domains-emerges from multiple pathways to the same functional end. Copyright © 2016 Cognitive Science Society, Inc.

Coordinate Regulation of Yeast Sterol Regulatory Element-binding Protein (SREBP) and Mga2 Transcription Factors.

PubMed

Burr, Risa; Stewart, Emerson V; Espenshade, Peter J

2017-03-31

The Mga2 and Sre1 transcription factors regulate oxygen-responsive lipid homeostasis in the fission yeast Schizosaccharomyces pombe in a manner analogous to the mammalian sterol regulatory element-binding protein (SREBP)-1 and SREBP-2 transcription factors. Mga2 and SREBP-1 regulate triacylglycerol and glycerophospholipid synthesis, whereas Sre1 and SREBP-2 regulate sterol synthesis. In mammals, a shared activation mechanism allows for coordinate regulation of SREBP-1 and SREBP-2. In contrast, distinct pathways activate fission yeast Mga2 and Sre1. Therefore, it is unclear whether and how these two related pathways are coordinated to maintain lipid balance in fission yeast. Previously, we showed that Sre1 cleavage is defective in the absence of mga2 Here, we report that this defect is due to deficient unsaturated fatty acid synthesis, resulting in aberrant membrane transport. This defect is recapitulated by treatment with the fatty acid synthase inhibitor cerulenin and is rescued by addition of exogenous unsaturated fatty acids. Furthermore, sterol synthesis inhibition blocks Mga2 pathway activation. Together, these data demonstrate that Sre1 and Mga2 are each regulated by the lipid product of the other transcription factor pathway, providing a source of coordination for these two branches of lipid synthesis. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Mediator independently orchestrates multiple steps of preinitiation complex assembly in vivo.

PubMed

Eyboulet, Fanny; Wydau-Dematteis, Sandra; Eychenne, Thomas; Alibert, Olivier; Neil, Helen; Boschiero, Claire; Nevers, Marie-Claire; Volland, Hervé; Cornu, David; Redeker, Virginie; Werner, Michel; Soutourina, Julie

2015-10-30

Mediator is a large multiprotein complex conserved in all eukaryotes, which has a crucial coregulator function in transcription by RNA polymerase II (Pol II). However, the molecular mechanisms of its action in vivo remain to be understood. Med17 is an essential and central component of the Mediator head module. In this work, we utilised our large collection of conditional temperature-sensitive med17 mutants to investigate Mediator's role in coordinating preinitiation complex (PIC) formation in vivo at the genome level after a transfer to a non-permissive temperature for 45 minutes. The effect of a yeast mutation proposed to be equivalent to the human Med17-L371P responsible for infantile cerebral atrophy was also analyzed. The ChIP-seq results demonstrate that med17 mutations differentially affected the global presence of several PIC components including Mediator, TBP, TFIIH modules and Pol II. Our data show that Mediator stabilizes TFIIK kinase and TFIIH core modules independently, suggesting that the recruitment or the stability of TFIIH modules is regulated independently on yeast genome. We demonstrate that Mediator selectively contributes to TBP recruitment or stabilization to chromatin. This study provides an extensive genome-wide view of Mediator's role in PIC formation, suggesting that Mediator coordinates multiple steps of a PIC assembly pathway. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

78 FR 3827 - Golden Nematode; Removal of Regulated Areas in Livingston and Steuben Counties, NY

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-17

... to coordinates 42[deg]87'35'', -77[deg]66'51''; then west along a farm road to coordinates 42[deg]87'35'', -77[deg]66'84''; then south along Little Conesus Creek to coordinates 42[deg]87'12.56'', - 77... coordinates 42[deg]87'12.60'', - 77[deg]67'05.50''; then south to coordinates 42[deg]87'11.19'', - 77[deg]67...

15 CFR Appendix A to Subpart G of... - Channel Islands National Marine Sanctuary Boundary Coordinates

Code of Federal Regulations, 2010 CFR

2010-01-01

... Sanctuary Boundary Coordinates A Appendix A to Subpart G of Part 922 Commerce and Foreign Trade Regulations..., DEPARTMENT OF COMMERCE OCEAN AND COASTAL RESOURCE MANAGEMENT NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Channel Islands National Marine Sanctuary Pt. 922, Subpt. G, App. A Appendix A to Subpart G of Part 922...

15 CFR Appendix A to Subpart O of... - Olympic Coast National Marine Sanctuary Boundary Coordinates

Code of Federal Regulations, 2010 CFR

2010-01-01

... Sanctuary Boundary Coordinates A Appendix A to Subpart O of Part 922 Commerce and Foreign Trade Regulations..., DEPARTMENT OF COMMERCE OCEAN AND COASTAL RESOURCE MANAGEMENT NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Olympic Coast National Marine Sanctuary Pt. 922, Subpt. O, App. A Appendix A to Subpart O of Part 922...

Coordination of flower development by homeotic master regulators.

PubMed

Ito, Toshiro

2011-02-01

Floral homeotic genes encode transcription factors and act as master regulators of flower development. The homeotic protein complex is expressed in a specific whorl of the floral primordium and determines floral organ identity by the combinatorial action. Homeotic proteins continue to be expressed until late in flower development to coordinate growth and organogenesis. Recent genomic studies have shown that homeotic proteins bind thousands of target sites in the genome and regulate the expression of transcription factors, chromatin components and various proteins involved in hormone biosynthesis and signaling and other physiological activities. Further, homeotic proteins program chromatin to direct the developmental coordination of stem cell maintenance and differentiation in shaping floral organs. Copyright © 2010 Elsevier Ltd. All rights reserved.

7 CFR 1944.257 - Service coordinator.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 13 2011-01-01 2009-01-01 true Service coordinator. 1944.257 Section 1944.257 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS... disability, using a commonly accepted assessment tool. The service coordinator then will refer to the...

7 CFR 1944.257 - Service coordinator.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 13 2010-01-01 2009-01-01 true Service coordinator. 1944.257 Section 1944.257 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS... disability, using a commonly accepted assessment tool. The service coordinator then will refer to the...

Hydrogen sulfide induces systemic tolerance to salinity and non-ionic osmotic stress in strawberry plants through modification of reactive species biosynthesis and transcriptional regulation of multiple defence pathways

PubMed Central

Christou, Anastasis; Manganaris, George A.; Papadopoulos, Ioannis; Fotopoulos, Vasileios

2013-01-01

Hydrogen sulfide (H2S) has been recently found to act as a potent priming agent. This study explored the hypothesis that hydroponic pretreatment of strawberry (Fragaria × ananassa cv. Camarosa) roots with a H2S donor, sodium hydrosulfide (NaHS; 100 μM for 48h), could induce long-lasting priming effects and tolerance to subsequent exposure to 100mM NaCI or 10% (w/v) PEG-6000 for 7 d. Hydrogen sulfide pretreatment of roots resulted in increased leaf chlorophyll fluorescence, stomatal conductance and leaf relative water content as well as lower lipid peroxidation levels in comparison with plants directly subjected to salt and non-ionic osmotic stress, thus suggesting a systemic mitigating effect of H2S pretreatment to cellular damage derived from abiotic stress factors. In addition, root pretreatment with NaHS resulted in the minimization of oxidative and nitrosative stress in strawberry plants, manifested via lower levels of synthesis of NO and H2O2 in leaves and the maintenance of high ascorbate and glutathione redox states, following subsequent salt and non-ionic osmotic stresses. Quantitative real-time RT-PCR gene expression analysis of key antioxidant (cAPX, CAT, MnSOD, GR), ascorbate and glutathione biosynthesis (GCS, GDH, GS), transcription factor (DREB), and salt overly sensitive (SOS) pathway (SOS2-like, SOS3-like, SOS4) genes suggests that H2S plays a pivotal role in the coordinated regulation of multiple transcriptional pathways. The ameliorative effects of H2S were more pronounced in strawberry plants subjected to both stress conditions immediately after NaHS root pretreatment, rather than in plants subjected to stress conditions 3 d after root pretreatment. Overall, H2S-pretreated plants managed to overcome the deleterious effects of salt and non-ionic osmotic stress by controlling oxidative and nitrosative cellular damage through increased performance of antioxidant mechanisms and the coordinated regulation of the SOS pathway, thus proposing a novel role for H2S in plant priming, and in particular in a fruit crop such as strawberry. PMID:23567865

Hunger and thirst interact to regulate ingestive behavior in flies and mammals.

PubMed

Jourjine, Nicholas

2017-05-01

In animals, nervous systems regulate the ingestion of food and water in a manner that reflects internal metabolic need. While the coordination of these two ingestive behaviors is essential for homeostasis, it has been unclear how internal signals of hunger and thirst interact to effectively coordinate food and water ingestion. In the last year, work in insects and mammals has begun to elucidate some of these interactions. As reviewed here, these studies have identified novel molecular and neural mechanisms that coordinate the regulation of food and water ingestion behaviors. These mechanisms include peptide signals that modulate neural circuits for both thirst and hunger, neurons that regulate both food and water ingestion, and neurons that integrate sensory information about both food and water in the external world. These studies argue that a deeper understanding of hunger and thirst will require closer examination of how these two biological drives interact. © 2017 WILEY Periodicals, Inc.

Deadlines in space: Selective effects of coordinate spatial processing in multitasking.

PubMed

Todorov, Ivo; Del Missier, Fabio; Konke, Linn Andersson; Mäntylä, Timo

2015-11-01

Many everyday activities require coordination and monitoring of multiple deadlines. One way to handle these temporal demands might be to represent future goals and deadlines as a pattern of spatial relations. We examined the hypothesis that spatial ability, in addition to executive functioning, contributes to individual differences in multitasking. In two studies, participants completed a multitasking session in which they monitored four digital clocks running at different rates. In Study 1, we found that individual differences in spatial ability and executive functions were independent predictors of multiple-task performance. In Study 2, we found that individual differences in specific spatial abilities were selectively related to multiple-task performance, as only coordinate spatial processing, but not categorical, predicted multitasking, even beyond executive functioning and numeracy. In both studies, males outperformed females in spatial ability and multitasking and in Study 2 these sex differences generalized to a simulation of everyday multitasking. Menstrual changes moderated the effects on multitasking, in that sex differences in coordinate spatial processing and multitasking were observed between males and females in the luteal phase of the menstrual cycle, but not between males and females at menses. Overall, these findings suggest that multiple-task performance reflects independent contributions of spatial ability and executive functioning. Furthermore, our results support the distinction of categorical versus coordinate spatial processing, and suggest that these two basic relational processes are selectively affected by female sex hormones and differentially effective in transforming and handling temporal patterns as spatial relations in the context of multitasking.

Calcium as a signal integrator in developing epithelial tissues.

PubMed

Brodskiy, Pavel A; Zartman, Jeremiah J

2018-05-16

Decoding how tissue properties emerge across multiple spatial and temporal scales from the integration of local signals is a grand challenge in quantitative biology. For example, the collective behavior of epithelial cells is critical for shaping developing embryos. Understanding how epithelial cells interpret a diverse range of local signals to coordinate tissue-level processes requires a systems-level understanding of development. Integration of multiple signaling pathways that specify cell signaling information requires second messengers such as calcium ions. Increasingly, specific roles have been uncovered for calcium signaling throughout development. Calcium signaling regulates many processes including division, migration, death, and differentiation. However, the pleiotropic and ubiquitous nature of calcium signaling implies that many additional functions remain to be discovered. Here we review a selection of recent studies to highlight important insights into how multiple signals are transduced by calcium transients in developing epithelial tissues. Quantitative imaging and computational modeling have provided important insights into how calcium signaling integration occurs. Reverse-engineering the conserved features of signal integration mediated by calcium signaling will enable novel approaches in regenerative medicine and synthetic control of morphogenesis.

Concurrent negotiation and coordination for grid resource coallocation.

PubMed

Sim, Kwang Mong; Shi, Benyun

2010-06-01

Bolstering resource coallocation is essential for realizing the Grid vision, because computationally intensive applications often require multiple computing resources from different administrative domains. Given that resource providers and consumers may have different requirements, successfully obtaining commitments through concurrent negotiations with multiple resource providers to simultaneously access several resources is a very challenging task for consumers. The impetus of this paper is that it is one of the earliest works that consider a concurrent negotiation mechanism for Grid resource coallocation. The concurrent negotiation mechanism is designed for 1) managing (de)commitment of contracts through one-to-many negotiations and 2) coordination of multiple concurrent one-to-many negotiations between a consumer and multiple resource providers. The novel contributions of this paper are devising 1) a utility-oriented coordination (UOC) strategy, 2) three classes of commitment management strategies (CMSs) for concurrent negotiation, and 3) the negotiation protocols of consumers and providers. Implementing these ideas in a testbed, three series of experiments were carried out in a variety of settings to compare the following: 1) the CMSs in this paper with the work of others in a single one-to-many negotiation environment for one resource where decommitment is allowed for both provider and consumer agents; 2) the performance of the three classes of CMSs in different resource market types; and 3) the UOC strategy with the work of others [e.g., the patient coordination strategy (PCS )] for coordinating multiple concurrent negotiations. Empirical results show the following: 1) the UOC strategy achieved higher utility, faster negotiation speed, and higher success rates than PCS for different resource market types; and 2) the CMS in this paper achieved higher final utility than the CMS in other works. Additionally, the properties of the three classes of CMSs in different kinds of resource markets are also verified.

Middle age onset short-term intermittent fasting dietary restriction prevents brain function impairments in male Wistar rats.

PubMed

Singh, Rumani; Manchanda, Shaffi; Kaur, Taranjeet; Kumar, Sushil; Lakhanpal, Dinesh; Lakhman, Sukhwinder S; Kaur, Gurcharan

2015-12-01

Intermittent fasting dietary restriction (IF-DR) is recently reported to be an effective intervention to retard age associated disease load and to promote healthy aging. Since sustaining long term caloric restriction regimen is not practically feasible in humans, so use of alternate approach such as late onset short term IF-DR regimen which is reported to trigger similar biological pathways is gaining scientific interest. The current study was designed to investigate the effect of IF-DR regimen implemented for 12 weeks in middle age rats on their motor coordination skills and protein and DNA damage in different brain regions. Further, the effect of IF-DR regimen was also studied on expression of energy regulators, cell survival pathways and synaptic plasticity marker proteins. Our data demonstrate that there was an improvement in motor coordination and learning response with decline in protein oxidative damage and recovery in expression of energy regulating neuropeptides. We further observed significant downregulation in nuclear factor kappa B (NF-κB) and cytochrome c (Cyt c) levels and moderate upregulation of mortalin and synaptophysin expression. The present data may provide an insight on how a modest level of short term IF-DR, imposed in middle age, can slow down or prevent the age-associated impairment of brain functions and promote healthy aging by involving multiple regulatory pathways aimed at maintaining energy homeostasis.

Disruption of stomatal lineage signaling or transcriptional regulators has differential effects on mesophyll development, but maintains coordination of gas exchange.

PubMed

Dow, Graham J; Berry, Joseph A; Bergmann, Dominique C

2017-10-01

Stomata are simultaneously tasked with permitting the uptake of carbon dioxide for photosynthesis while limiting water loss from the plant. This process is mainly regulated by guard cell control of the stomatal aperture, but recent advancements have highlighted the importance of several genes that control stomatal development. Using targeted genetic manipulations of the stomatal lineage and a combination of gas exchange and microscopy techniques, we show that changes in stomatal development of the epidermal layer lead to coupled changes in the underlying mesophyll tissues. This coordinated response tends to match leaf photosynthetic potential (V cmax ) with gas-exchange capacity (g smax ), and hence the uptake of carbon dioxide for water lost. We found that different genetic regulators systematically altered tissue coordination in separate ways: the transcription factor SPEECHLESS (SPCH) primarily affected leaf size and thickness, whereas peptides in the EPIDERMAL PATTERNING FACTOR (EPF) family altered cell density in the mesophyll. It was also determined that interlayer coordination required the cell-surface receptor TOO MANY MOUTHS (TMM). These results demonstrate that stomata-specific regulators can alter mesophyll properties, which provides insight into how molecular pathways can organize leaf tissues to coordinate gas exchange and suggests new strategies for improving plant water-use efficiency. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

The Regulation of Filamentous Growth in Yeast

PubMed Central

Cullen, Paul J.; Sprague, George F.

2012-01-01

Filamentous growth is a nutrient-regulated growth response that occurs in many fungal species. In pathogens, filamentous growth is critical for host–cell attachment, invasion into tissues, and virulence. The budding yeast Saccharomyces cerevisiae undergoes filamentous growth, which provides a genetically tractable system to study the molecular basis of the response. Filamentous growth is regulated by evolutionarily conserved signaling pathways. One of these pathways is a mitogen activated protein kinase (MAPK) pathway. A remarkable feature of the filamentous growth MAPK pathway is that it is composed of factors that also function in other pathways. An intriguing challenge therefore has been to understand how pathways that share components establish and maintain their identity. Other canonical signaling pathways—rat sarcoma/protein kinase A (RAS/PKA), sucrose nonfermentable (SNF), and target of rapamycin (TOR)—also regulate filamentous growth, which raises the question of how signals from multiple pathways become integrated into a coordinated response. Together, these pathways regulate cell differentiation to the filamentous type, which is characterized by changes in cell adhesion, cell polarity, and cell shape. How these changes are accomplished is also discussed. High-throughput genomics approaches have recently uncovered new connections to filamentous growth regulation. These connections suggest that filamentous growth is a more complex and globally regulated behavior than is currently appreciated, which may help to pave the way for future investigations into this eukaryotic cell differentiation behavior. PMID:22219507

Coordinated action of histone modification and microRNA regulations in human genome.

PubMed

Wang, Xuan; Zheng, Guantao; Dong, Dong

2015-10-10

Both histone modifications and microRNAs (miRNAs) play pivotal role in gene expression regulation. Although numerous studies have been devoted to explore the gene regulation by miRNA and epigenetic regulations, their coordinated actions have not been comprehensively examined. In this work, we systematically investigated the combinatorial relationship between miRNA and epigenetic regulation by taking advantage of recently published whole genome-wide histone modification data and high quality miRNA targeting data. The results showed that miRNA targets have distinct histone modification patterns compared with non-targets in their promoter regions. Based on this finding, we proposed a machine learning approach to fit predictive models on the task to discern whether a gene is targeted by a specific miRNA. We found a considerable advantage in both sensitivity and specificity in diverse human cell lines. Finally, we found that our predicted miRNA targets are consistently annotated with Gene Ontology terms. Our work is the first genome-wide investigation of the coordinated action of miRNA and histone modification regulations, which provide a guide to deeply understand the complexity of transcriptional regulation. Copyright © 2015 Elsevier B.V. All rights reserved.

Coordination of NF-kappaB and NFAT antagonism by the forkhead transcription factor Foxd1.

PubMed

Lin, Ling; Peng, Stanford L

2006-04-15

Forkhead transcription factors play critical roles in the maintenance of immune homeostasis. In this study, we demonstrate that this regulation most likely involves intricate interactions between the forkhead family members and inflammatory transcription factors: the forkhead member Foxd1 coordinates the regulation of the activity of two key inflammatory transcription factors, NF-AT and NF-kappaB, with Foxd1 deficiency resulting in multiorgan, systemic inflammation, exaggerated Th cell-derived cytokine production, and T cell proliferation in autologous MLRs. Foxd1-deficient T cells possess increased activity of both NF-AT and NF-kappaB: the former correlates with the ability of Foxd1 to regulate casein kinase 1, an NF-AT inhibitory kinase; the latter with the ability of Foxd1 to regulate Foxj1, which regulates the NF-kappaB inhibitory subunit IkappaB beta. Thus, Foxd1 modulates inflammatory reactions and prevents autoimmunity by directly regulating anti-inflammatory regulators of the NF-AT pathway, and by coordinating the suppression of the NF-kappaB pathway via Foxj1. These findings indicate the presence of a general network of forkhead proteins that enforce T cell quiescence.

MarA, SoxS and Rob of Escherichia coli - Global regulators of multidrug resistance, virulence and stress response.

PubMed

Duval, Valérie; Lister, Ida M

2013-01-01

Bacteria have a great capacity for adjusting their metabolism in response to environmental changes by linking extracellular stimuli to the regulation of genes by transcription factors. By working in a co-operative manner, transcription factors provide a rapid response to external threats, allowing the bacteria to survive. This review will focus on transcription factors MarA, SoxS and Rob in Escherichia coli , three members of the AraC family of proteins. These homologous proteins exemplify the ability to respond to multiple threats such as oxidative stress, drugs and toxic compounds, acidic pH, and host antimicrobial peptides. MarA, SoxS and Rob recognize similar DNA sequences in the promoter region of more than 40 regulatory target genes. As their regulons overlap, a finely tuned adaptive response allows E. coli to survive in the presence of different assaults in a co-ordinated manner. These regulators are well conserved amongst Enterobacteriaceae and due to their broad involvement in bacterial adaptation in the host, have recently been explored as targets to develop new anti-virulence agents. The regulators are also being examined for their roles in novel technologies such as biofuel production.

Voluntary coordination as a strategy of plan implementation for health systems agencies.

PubMed

Berry, D E; Candia, G R

1979-10-01

Health planning agencies are faced with the difficult mission of guiding change within a large complex social system whose power is dispersed. Initial short- and long-range plans have been established as frameworks, and now the major focus is implementation. Regulation (non-voluntary coordination) and voluntary coordination are the major means of implementation. Voluntary coordination is a significant strategy for consideration by Health Systems Agencies (HSAs). It may interact with regulation as a competitor, substitute, or complement. Because of limited regulatory powers, HSAs are dependent upon voluntary coordination as a major means of influencing behavior. Conflict, a major feature of voluntary coordination, has the potential of being used as a constructive means for dialogue; negotiation and bargaining may become positive approaches to arriving at decisions. Legitimized community authority is the primary source of authority in a strategy dominated by voluntary coordination as contrasted to state or federal mandates in a regulatory strategy. Knowledge of the environment within which the HSA operates will assist HSA staff and board to arrive at rational and realistic decisions.

7 CFR 227.35 - Responsibilities of State coordinator.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 227.35 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS NUTRITION EDUCATION AND TRAINING PROGRAM State Coordinator... implementation of the State Plan, (f) Coordination of the Program with the Child Nutrition Programs at the State...

7 CFR 227.35 - Responsibilities of State coordinator.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 227.35 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS NUTRITION EDUCATION AND TRAINING PROGRAM State Coordinator... implementation of the State Plan, (f) Coordination of the Program with the Child Nutrition Programs at the State...

7 CFR 227.35 - Responsibilities of State coordinator.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 227.35 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS NUTRITION EDUCATION AND TRAINING PROGRAM State Coordinator... implementation of the State Plan, (f) Coordination of the Program with the Child Nutrition Programs at the State...

7 CFR 227.35 - Responsibilities of State coordinator.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 227.35 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS NUTRITION EDUCATION AND TRAINING PROGRAM State Coordinator... implementation of the State Plan, (f) Coordination of the Program with the Child Nutrition Programs at the State...

7 CFR 227.35 - Responsibilities of State coordinator.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 227.35 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS NUTRITION EDUCATION AND TRAINING PROGRAM State Coordinator... implementation of the State Plan, (f) Coordination of the Program with the Child Nutrition Programs at the State...

YY1 as a controlling factor for the Peg3 and Gnas imprinted domains

PubMed Central

Kim, Jeong Do; Hinz, Angela K.; Choo, Jung Ha; Stubbs, Lisa; Kim, Joomyeong

2007-01-01

Imprinting Control Regions (ICRs) often harbor tandem arrays of transcription factor binding sites, as demonstrated by the identification of multiple YY1 binding sites within the ICRs of Peg3, Nespas, and Xist/Tsix domains. In the current study, we have sought to characterize possible roles of YY1 in transcriptional control and epigenetic modification of these imprinted domains. RNA interference-based knockdown experiments in Neuro2A cells resulted in overall transcriptional up-regulation of most of the imprinted genes within the Peg3 domain and also, concomitantly, caused significant loss in the DNA methylation of Peg3-DMR (Differentially Methylated Regions). A similar overall and coordinated expression change was also observed for the imprinted genes of the Gnas domain: up-regulation of Nespas and down-regulation of Nesp and Gnasxl. YY1 knockdown also resulted in changes in the expression levels of Xist and Snrpn. These results support the idea that YY1 plays a major role, as a trans factor, for the control of these imprinted domains. PMID:17067777

Dual role for argonautes in microRNA processing and posttranscriptional regulation of microRNA expression.

PubMed

Diederichs, Sven; Haber, Daniel A

2007-12-14

MicroRNAs are small endogenous noncoding RNAs involved in posttranscriptional gene regulation. During microRNA biogenesis, Drosha and Dicer process the primary transcript (pri-miRNA) through a precursor hairpin (pre-miRNA) to the mature miRNA. The miRNA is incorporated into the RNA-Induced Silencing Complex (RISC) with Argonaute proteins, the effector molecules in RNA interference (RNAi). Here, we show that all Argonautes elevate mature miRNA expression posttranscriptionally, independent of RNase activity. Also, we identify a role for the RISC slicer Argonaute2 (Ago2) in cleaving the pre-miRNA to an additional processing intermediate, termed Ago2-cleaved precursor miRNA or ac-pre-miRNA. This endogenous, on-pathway intermediate results from cleavage of the pre-miRNA hairpin 12 nucleotides from its 3'-end. By analogy to siRNA processing, Ago2 cleavage may facilitate removal of the nicked passenger strand from RISC after maturation. The multiple roles of Argonautes in the RNAi effector phase and miRNA biogenesis and maturation suggest coordinate regulation of microRNA expression and function.

Cdc13 N-Terminal Dimerization DNA Binding and Telomere Length Regulation

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

M Mitchell; J Smith; M Mason

The essential yeast protein Cdc13 facilitates chromosome end replication by recruiting telomerase to telomeres, and together with its interacting partners Stn1 and Ten1, it protects chromosome ends from nucleolytic attack, thus contributing to genome integrity. Although Cdc13 has been studied extensively, the precise role of its N-terminal domain (Cdc13N) in telomere length regulation remains unclear. Here we present a structural, biochemical, and functional characterization of Cdc13N. The structure reveals that this domain comprises an oligonucleotide/oligosaccharide binding (OB) fold and is involved in Cdc13 dimerization. Biochemical data show that Cdc13N weakly binds long, single-stranded, telomeric DNA in a fashion that ismore » directly dependent on domain oligomerization. When introduced into full-length Cdc13 in vivo, point mutations that prevented Cdc13N dimerization or DNA binding caused telomere shortening or lengthening, respectively. The multiple DNA binding domains and dimeric nature of Cdc13 offer unique insights into how it coordinates the recruitment and regulation of telomerase access to the telomeres.« less

Improvisation and the self-organization of multiple musical bodies.

PubMed

Walton, Ashley E; Richardson, Michael J; Langland-Hassan, Peter; Chemero, Anthony

2015-01-01

Understanding everyday behavior relies heavily upon understanding our ability to improvise, how we are able to continuously anticipate and adapt in order to coordinate with our environment and others. Here we consider the ability of musicians to improvise, where they must spontaneously coordinate their actions with co-performers in order to produce novel musical expressions. Investigations of this behavior have traditionally focused on describing the organization of cognitive structures. The focus, here, however, is on the ability of the time-evolving patterns of inter-musician movement coordination as revealed by the mathematical tools of complex dynamical systems to provide a new understanding of what potentiates the novelty of spontaneous musical action. We demonstrate this approach through the application of cross wavelet spectral analysis, which isolates the strength and patterning of the behavioral coordination that occurs between improvising musicians across a range of nested time-scales. Revealing the sophistication of the previously unexplored dynamics of movement coordination between improvising musicians is an important step toward understanding how creative musical expressions emerge from the spontaneous coordination of multiple musical bodies.

Improvisation and the self-organization of multiple musical bodies

PubMed Central

Walton, Ashley E.; Richardson, Michael J.; Langland-Hassan, Peter; Chemero, Anthony

2015-01-01

Understanding everyday behavior relies heavily upon understanding our ability to improvise, how we are able to continuously anticipate and adapt in order to coordinate with our environment and others. Here we consider the ability of musicians to improvise, where they must spontaneously coordinate their actions with co-performers in order to produce novel musical expressions. Investigations of this behavior have traditionally focused on describing the organization of cognitive structures. The focus, here, however, is on the ability of the time-evolving patterns of inter-musician movement coordination as revealed by the mathematical tools of complex dynamical systems to provide a new understanding of what potentiates the novelty of spontaneous musical action. We demonstrate this approach through the application of cross wavelet spectral analysis, which isolates the strength and patterning of the behavioral coordination that occurs between improvising musicians across a range of nested time-scales. Revealing the sophistication of the previously unexplored dynamics of movement coordination between improvising musicians is an important step toward understanding how creative musical expressions emerge from the spontaneous coordination of multiple musical bodies. PMID:25941499

Mutations in chromatin regulators functionally link Cornelia de Lange syndrome and clinically overlapping phenotypes.

PubMed

Parenti, Ilaria; Teresa-Rodrigo, María E; Pozojevic, Jelena; Ruiz Gil, Sara; Bader, Ingrid; Braunholz, Diana; Bramswig, Nuria C; Gervasini, Cristina; Larizza, Lidia; Pfeiffer, Lutz; Ozkinay, Ferda; Ramos, Feliciano; Reiz, Benedikt; Rittinger, Olaf; Strom, Tim M; Watrin, Erwan; Wendt, Kerstin; Wieczorek, Dagmar; Wollnik, Bernd; Baquero-Montoya, Carolina; Pié, Juan; Deardorff, Matthew A; Gillessen-Kaesbach, Gabriele; Kaiser, Frank J

2017-03-01

The coordinated tissue-specific regulation of gene expression is essential for the proper development of all organisms. Mutations in multiple transcriptional regulators cause a group of neurodevelopmental disorders termed "transcriptomopathies" that share core phenotypical features including growth retardation, developmental delay, intellectual disability and facial dysmorphism. Cornelia de Lange syndrome (CdLS) belongs to this class of disorders and is caused by mutations in different subunits or regulators of the cohesin complex. Herein, we report on the clinical and molecular characterization of seven patients with features overlapping with CdLS who were found to carry mutations in chromatin regulators previously associated to other neurodevelopmental disorders that are frequently considered in the differential diagnosis of CdLS. The identified mutations affect the methyltransferase-encoding genes KMT2A and SETD5 and different subunits of the SWI/SNF chromatin-remodeling complex. Complementary to this, a patient with Coffin-Siris syndrome was found to carry a missense substitution in NIPBL. Our findings indicate that mutations in a variety of chromatin-associated factors result in overlapping clinical phenotypes, underscoring the genetic heterogeneity that should be considered when assessing the clinical and molecular diagnosis of neurodevelopmental syndromes. It is clear that emerging molecular mechanisms of chromatin dysregulation are central to understanding the pathogenesis of these clinically overlapping genetic disorders.

Differential Roles of Postsynaptic Density-93 Isoforms in Regulating Synaptic Transmission

PubMed Central

Krüger, Juliane M.; Favaro, Plinio D.; Liu, Mingna; Kitlińska, Agata; Huang, Xiaojie; Raabe, Monika; Akad, Derya S.; Liu, Yanling; Urlaub, Henning; Dong, Yan; Xu, Weifeng

2013-01-01

In the postsynaptic density of glutamatergic synapses, the discs large (DLG)-membrane-associated guanylate kinase (MAGUK) family of scaffolding proteins coordinates a multiplicity of signaling pathways to maintain and regulate synaptic transmission. Postsynaptic density-93 (PSD-93) is the most variable paralog in this family; it exists in six different N-terminal isoforms. Probably because of the structural and functional variability of these isoforms, the synaptic role of PSD-93 remains controversial. To accurately characterize the synaptic role of PSD-93, we quantified the expression of all six isoforms in the mouse hippocampus and examined them individually in hippocampal synapses. Using molecular manipulations, including overexpression, gene knockdown, PSD-93 knock-out mice combined with biochemical assays, and slice electrophysiology both in rat and mice, we demonstrate that PSD-93 is required at different developmental synaptic states to maintain the strength of excitatory synaptic transmission. This strength is differentially regulated by the six isoforms of PSD-93, including regulations of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor-active and inactive synapses, and activity-dependent modulations. Collectively, these results demonstrate that alternative combinations of N-terminal PSD-93 isoforms and DLG-MAGUK paralogs can fine-tune signaling scaffolds to adjust synaptic needs to regulate synaptic transmission. PMID:24068818

Diversity and regulation of plant Ca2+ pumps: insights from expression in yeast

NASA Technical Reports Server (NTRS)

Sze, H.; Liang, F.; Hwang, I.; Curran, A. C.; Harper, J. F.; Evans, M. L. (Principal Investigator)

2000-01-01

The spatial and temporal regulation of calcium concentration in plant cells depends on the coordinate activities of channels and active transporters located on different organelles and membranes. Several Ca2+ pumps have been identified and characterized by functional expression of plant genes in a yeast mutant (K616). This expression system has opened the way to a genetic and biochemical characterization of the regulatory and catalytic features of diverse Ca2+ pumps. Plant Ca(2+)-ATPases fall into two major types: AtECA1 represents one of four or more members of the type IIA (ER-type) Ca(2+)-ATPases in Arabidopsis, and AtACA2 is one of seven or more members of the type IIB (PM-type) Ca(2+)-ATPases that are regulated by a novel amino terminal domain. Type IIB pumps are widely distributed on membranes, including the PM (plasma membrane), vacuole, and ER (endoplasmic reticulum). The regulatory domain serves multiple functions, including autoinhibition, calmodulin binding, and sites for modification by phosphorylation. This domain, however, is considerably diverse among several type IIB ATPases, suggesting that the pumps are differentially regulated. Understanding of Ca2+ transporters at the molecular level is providing insights into their roles in signaling networks and in regulating fundamental processes of cell biology.

48 CFR 836.574 - Subcontracts and work coordination.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Subcontracts and work... Subcontracts and work coordination. The contracting officer shall insert the clause at 852.236-80, Subcontracts and work coordination, in solicitations and contracts for construction expected to exceed the micro...

The interaction of DiaA and DnaA regulates the replication cycle in E. coli by directly promoting ATP–DnaA-specific initiation complexes

PubMed Central

Keyamura, Kenji; Fujikawa, Norie; Ishida, Takuma; Ozaki, Shogo; Su’etsugu, Masayuki; Fujimitsu, Kazuyuki; Kagawa, Wataru; Yokoyama, Shigeyuki; Kurumizaka, Hitoshi; Katayama, Tsutomu

2007-01-01

Escherichia coli DiaA is a DnaA-binding protein that is required for the timely initiation of chromosomal replication during the cell cycle. In this study, we determined the crystal structure of DiaA at 1.8 Å resolution. DiaA forms a homotetramer consisting of a symmetrical pair of homodimers. Mutational analysis revealed that the DnaA-binding activity and formation of homotetramers are required for the stimulation of initiation by DiaA. DiaA tetramers can bind multiple DnaA molecules simultaneously. DiaA stimulated the assembly of multiple DnaA molecules on oriC, conformational changes in ATP–DnaA-specific initiation complexes, and unwinding of oriC duplex DNA. The mutant DiaA proteins are defective in these stimulations. DiaA associated also with ADP–DnaA, and stimulated the assembly of inactive ADP–DnaA–oriC complexes. Specific residues in the putative phosphosugar-binding motif of DiaA were required for the stimulation of initiation and formation of ATP–DnaA-specific–oriC complexes. Our data indicate that DiaA regulates initiation by a novel mechanism, in which DiaA tetramers most likely bind to multiple DnaA molecules and stimulate the assembly of specific ATP–DnaA–oriC complexes. These results suggest an essential role for DiaA in the promotion of replication initiation in a cell cycle coordinated manner. PMID:17699754

Identifying and Coordinating Care for Complex Patients

PubMed Central

Rudin, Robert S.; Gidengil, Courtney A.; Predmore, Zachary; Schneider, Eric C.; Sorace, James; Hornstein, Rachel

2017-01-01

Abstract In the United States, a relatively small proportion of complex patients---defined as having multiple comorbidities, high risk for poor outcomes, and high cost---incur most of the nation's health care costs. Improved care coordination and management of complex patients could reduce costs while increasing quality of care. However, care coordination efforts face multiple challenges, such as segmenting populations of complex patients to better match their needs with the design of specific interventions, understanding how to reduce spending, and integrating care coordination programs into providers' care delivery processes. Innovative uses of analytics and health information technology (HIT) may address these challenges. Rudin and colleagues at RAND completed a literature review and held discussions with subject matter experts, reaching the conclusion that analytics and HIT are being used in innovative ways to coordinate care for complex patients but that the capabilities are limited, evidence of their effectiveness is lacking, and challenges are substantial, and important foundational work is still needed. PMID:28845354

45 CFR 708.9 - Coordinating offset with another Federal agency.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 3 2010-10-01 2010-10-01 false Coordinating offset with another Federal agency. 708.9 Section 708.9 Public Welfare Regulations Relating to Public Welfare (Continued) COMMISSION ON CIVIL RIGHTS COLLECTION BY SALARY OFFSET FROM INDEBTED CURRENT AND FORMER EMPLOYEES § 708.9 Coordinating...

48 CFR 536.570-9 - Shop drawings, coordination drawings, and schedules.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 4 2013-10-01 2013-10-01 false Shop drawings... CONTRACTS Contract Clauses 536.570-9 Shop drawings, coordination drawings, and schedules. Insert the clause at 552.236-78, Shop Drawings, Coordination Drawings, and Schedules, in solicitations and contracts if...

48 CFR 552.236-78 - Shop Drawings, Coordination Drawings, and Schedules.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 4 2013-10-01 2013-10-01 false Shop Drawings... Provisions and Clauses 552.236-78 Shop Drawings, Coordination Drawings, and Schedules. As prescribed in 536.570-9, insert the following clause: Shop Drawings, Coordination Drawings, and Schedules (SEP 1999) The...

48 CFR 536.570-9 - Shop drawings, coordination drawings, and schedules.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 4 2012-10-01 2012-10-01 false Shop drawings... CONTRACTS Contract Clauses 536.570-9 Shop drawings, coordination drawings, and schedules. Insert the clause at 552.236-78, Shop Drawings, Coordination Drawings, and Schedules, in solicitations and contracts if...

48 CFR 536.570-9 - Shop drawings, coordination drawings, and schedules.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Shop drawings... CONTRACTS Contract Clauses 536.570-9 Shop drawings, coordination drawings, and schedules. Insert the clause at 552.236-78, Shop Drawings, Coordination Drawings, and Schedules, in solicitations and contracts if...

48 CFR 536.570-9 - Shop drawings, coordination drawings, and schedules.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Shop drawings... CONTRACTS Contract Clauses 536.570-9 Shop drawings, coordination drawings, and schedules. Insert the clause at 552.236-78, Shop Drawings, Coordination Drawings, and Schedules, in solicitations and contracts if...

48 CFR 552.236-78 - Shop Drawings, Coordination Drawings, and Schedules.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Shop Drawings... Provisions and Clauses 552.236-78 Shop Drawings, Coordination Drawings, and Schedules. As prescribed in 536.570-9, insert the following clause: Shop Drawings, Coordination Drawings, and Schedules (SEP 1999) The...

48 CFR 536.570-9 - Shop drawings, coordination drawings, and schedules.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 4 2014-10-01 2014-10-01 false Shop drawings... CONTRACTS Contract Clauses 536.570-9 Shop drawings, coordination drawings, and schedules. Insert the clause at 552.236-78, Shop Drawings, Coordination Drawings, and Schedules, in solicitations and contracts if...

48 CFR 552.236-78 - Shop Drawings, Coordination Drawings, and Schedules.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Shop Drawings... Provisions and Clauses 552.236-78 Shop Drawings, Coordination Drawings, and Schedules. As prescribed in 536.570-9, insert the following clause: Shop Drawings, Coordination Drawings, and Schedules (SEP 1999) The...

48 CFR 552.236-78 - Shop Drawings, Coordination Drawings, and Schedules.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 4 2012-10-01 2012-10-01 false Shop Drawings... Provisions and Clauses 552.236-78 Shop Drawings, Coordination Drawings, and Schedules. As prescribed in 536.570-9, insert the following clause: Shop Drawings, Coordination Drawings, and Schedules (SEP 1999) The...

48 CFR 552.236-78 - Shop Drawings, Coordination Drawings, and Schedules.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 4 2014-10-01 2014-10-01 false Shop Drawings... Provisions and Clauses 552.236-78 Shop Drawings, Coordination Drawings, and Schedules. As prescribed in 536.570-9, insert the following clause: Shop Drawings, Coordination Drawings, and Schedules (SEP 1999) The...

77 FR 70526 - Shipping Coordinating Committee; Notice of Committee Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-26

... DEPARTMENT OF STATE [Public Notice 8093] Shipping Coordinating Committee; Notice of Committee Meeting The Shipping Coordinating Committee (SHC) will conduct an open meeting at 10 a.m. on Tuesday... amendments to the requirements for foam-type fire extinguishers in SOLAS regulation II-2/10.5 --Development...

Genetic dissection of sorghum grain quality traits using diverse and segregating populations.

PubMed

Boyles, Richard E; Pfeiffer, Brian K; Cooper, Elizabeth A; Rauh, Bradley L; Zielinski, Kelsey J; Myers, Matthew T; Brenton, Zachary; Rooney, William L; Kresovich, Stephen

2017-04-01

Coordinated association and linkage mapping identified 25 grain quality QTLs in multiple environments, and fine mapping of the Wx locus supports the use of high-density genetic markers in linkage mapping. There is a wide range of end-use products made from cereal grains, and these products often demand different grain characteristics. Fortunately, cereal crop species including sorghum [Sorghum bicolor (L.) Moench] contain high phenotypic variation for traits influencing grain quality. Identifying genetic variants underlying this phenotypic variation allows plant breeders to develop genotypes with grain attributes optimized for their intended usage. Multiple sorghum mapping populations were rigorously phenotyped across two environments (SC Coastal Plain and Central TX) in 2 years for five major grain quality traits: amylose, starch, crude protein, crude fat, and gross energy. Coordinated association and linkage mapping revealed several robust QTLs that make prime targets to improve grain quality for food, feed, and fuel products. Although the amylose QTL interval spanned many megabases, the marker with greatest significance was located just 12 kb from waxy (Wx), the primary gene regulating amylose production in cereal grains. This suggests higher resolution mapping in recombinant inbred line (RIL) populations can be obtained when genotyped at a high marker density. The major QTL for crude fat content, identified in both a RIL population and grain sorghum diversity panel, encompassed the DGAT1 locus, a critical gene involved in maize lipid biosynthesis. Another QTL on chromosome 1 was consistently mapped in both RIL populations for multiple grain quality traits including starch, crude protein, and gross energy. Collectively, these genetic regions offer excellent opportunities to manipulate grain composition and set up future studies for gene validation.

An Expanded Theoretical Framework of Care Coordination Across Transitions in Care Settings.

PubMed

Radwin, Laurel E; Castonguay, Denise; Keenan, Carolyn B; Hermann, Cherice

2016-01-01

For many patients, high-quality, patient-centered, and cost-effective health care requires coordination among multiple clinicians and settings. Ensuring optimal care coordination requires a clear understanding of how clinician activities and continuity during transitions affect patient-centeredness and quality outcomes. This article describes an expanded theoretical framework to better understand care coordination. The framework provides clear articulation of concepts. Examples are provided of ways to measure the concepts.

Better dual-task processing in simultaneous interpreters

PubMed Central

Strobach, Tilo; Becker, Maxi; Schubert, Torsten; Kühn, Simone

2015-01-01

Simultaneous interpreting (SI) is a highly complex activity and requires the performance and coordination of multiple, simultaneous tasks: analysis and understanding of the discourse in a first language, reformulating linguistic material, storing of intermediate processing steps, and language production in a second language among others. It is, however, an open issue whether persons with experience in SI possess superior skills in coordination of multiple tasks and whether they are able to transfer these skills to lab-based dual-task situations. Within the present study, we set out to explore whether interpreting experience is associated with related higher-order executive functioning in the context of dual-task situations of the Psychological Refractory Period (PRP) type. In this PRP situation, we found faster reactions times in participants with experience in simultaneous interpretation in contrast to control participants without such experience. Thus, simultaneous interpreters possess superior skills in coordination of multiple tasks in lab-based dual-task situations. PMID:26528232

New nonlinear control algorithms for multiple robot arms

NASA Technical Reports Server (NTRS)

Tarn, T. J.; Bejczy, A. K.; Yun, X.

1988-01-01

Multiple coordinated robot arms are modeled by considering the arms as closed kinematic chains and as a force-constrained mechanical system working on the same object simultaneously. In both formulations, a novel dynamic control method is discussed. It is based on feedback linearization and simultaneous output decoupling technique. By applying a nonlinear feedback and a nonlinear coordinate transformation, the complicated model of the multiple robot arms in either formulation is converted into a linear and output decoupled system. The linear system control theory and optimal control theory are used to design robust controllers in the task space. The first formulation has the advantage of automatically handling the coordination and load distribution among the robot arms. In the second formulation, it was found that by choosing a general output equation it became possible simultaneously to superimpose the position and velocity error feedback with the force-torque error feedback in the task space.

Neuropeptide action in insects and crustaceans.

PubMed

Mykles, Donald L; Adams, Michael E; Gäde, Gerd; Lange, Angela B; Marco, Heather G; Orchard, Ian

2010-01-01

Physiological processes are regulated by a diverse array of neuropeptides that coordinate organ systems. The neuropeptides, many of which act through G protein-coupled receptors, affect the levels of cyclic nucleotides (cAMP and cGMP) and Ca(2+) in target tissues. In this perspective, their roles in molting, osmoregulation, metabolite utilization, and cardiovascular function are highlighted. In decapod crustaceans, inhibitory neuropeptides (molt-inhibiting hormone and crustacean hyperglycemic hormone) suppress the molting gland through cAMP- and cGMP-mediated signaling. In insects, the complex movements during ecdysis are controlled by ecdysis-triggering hormone and a cascade of downstream neuropeptides. Adipokinetic/hypertrehalosemic/hyperprolinemic hormones mobilize energy stores in response to increased locomotory activity. Crustacean cardioacceleratory (cardioactive) peptide, proctolin, and FMRFamide-related peptides act on the heart, accessory pulsatile organs, and excurrent ostia to control hemolymph distribution to tissues. The osmoregulatory challenge of blood gorging in Rhodnius prolixus requires the coordinated release of serotonin and diuretic and antidiuretic hormones acting on the midgut and Malpighian tubules. These studies illustrate how multiple neuropeptides allow for flexibility in response to physiological challenges.

Network Analysis of Enzyme Activities and Metabolite Levels and Their Relationship to Biomass in a Large Panel of Arabidopsis Accessions[C][W][OA

PubMed Central

Sulpice, Ronan; Trenkamp, Sandra; Steinfath, Matthias; Usadel, Bjorn; Gibon, Yves; Witucka-Wall, Hanna; Pyl, Eva-Theresa; Tschoep, Hendrik; Steinhauser, Marie Caroline; Guenther, Manuela; Hoehne, Melanie; Rohwer, Johann M.; Altmann, Thomas; Fernie, Alisdair R.; Stitt, Mark

2010-01-01

Natural genetic diversity provides a powerful resource to investigate how networks respond to multiple simultaneous changes. In this work, we profile maximum catalytic activities of 37 enzymes from central metabolism and generate a matrix to investigate species-wide connectivity between metabolites, enzymes, and biomass. Most enzyme activities change in a highly coordinated manner, especially those in the Calvin-Benson cycle. Metabolites show coordinated changes in defined sectors of metabolism. Little connectivity was observed between maximum enzyme activities and metabolites, even after applying multivariate analysis methods. Measurements of posttranscriptional regulation will be required to relate these two functional levels. Individual enzyme activities correlate only weakly with biomass. However, when they are used to estimate protein abundances, and the latter are summed and expressed as a fraction of total protein, a significant positive correlation to biomass is observed. The correlation is additive to that obtained between starch and biomass. Thus, biomass is predicted by two independent integrative metabolic biomarkers: preferential investment in photosynthetic machinery and optimization of carbon use. PMID:20699391

The RNA polymerase II CTD coordinates transcription and RNA processing

PubMed Central

Hsin, Jing-Ping; Manley, James L.

2012-01-01

The C-terminal domain (CTD) of the RNA polymerase II largest subunit consists of multiple heptad repeats (consensus Tyr1–Ser2–Pro3–Thr4–Ser5–Pro6–Ser7), varying in number from 26 in yeast to 52 in vertebrates. The CTD functions to help couple transcription and processing of the nascent RNA and also plays roles in transcription elongation and termination. The CTD is subject to extensive post-translational modification, most notably phosphorylation, during the transcription cycle, which modulates its activities in the above processes. Therefore, understanding the nature of CTD modifications, including how they function and how they are regulated, is essential to understanding the mechanisms that control gene expression. While the significance of phosphorylation of Ser2 and Ser5 residues has been studied and appreciated for some time, several additional modifications have more recently been added to the CTD repertoire, and insight into their function has begun to emerge. Here, we review findings regarding modification and function of the CTD, highlighting the important role this unique domain plays in coordinating gene activity. PMID:23028141

Coordination of size-control, reproduction and generational memory in freshwater planarians

NASA Astrophysics Data System (ADS)

Yang, Xingbo; Kaj, Kelson; Schwab, David; Collins, Eva-Maria

Uncovering the mechanisms that control size, growth, and division rates of systems reproducing through binary division means understanding basic principles of their life cycle. Recent work has focused on how division rates are regulated in bacteria and yeast, but this question has not yet been addressed in more complex, multicellular organisms. We have acquired a unique large-scale data set on the growth and asexual reproduction of two freshwater planarian species, Dugesia japonica and Dugesia tigrina, which reproduce by transverse fission and succeeding regeneration of head and tail pieces into new worms. We developed a new additive theoretical model that mixes multiple size control strategies based on worm size, growth, and waiting time. Our model quantifies the proportions of each strategy in the mixed dynamics, revealing the ability of the two planarian species to utilize different strategies in a coordinated manner for size control. Additionally, we found that head and tail offspring of both species employ different mechanisms to monitor and trigger their reproduction cycles. Finally, we show that generation-dependent memory effects in planarians need to be taken into account to accurately capture the experimental data.

Exploring Mechanisms Underlying Impaired Brain Function in Gulf War Illness through Advanced Network Analysis

DTIC Science & Technology

2017-10-01

networks of the brain responsible for visual processing, mood regulation, motor coordination, sensory processing, and language command, but increased...4    For each subject, the rsFMRI voxel time-series were temporally shifted to account for differences in slice acquisition times...responsible for visual processing, mood regulation, motor coordination, sensory processing, and language command, but increased connectivity in

32 CFR 705.18 - Authority and coordination.

Code of Federal Regulations, 2010 CFR

2010-07-01

... naval command will coordinate its community relations program with the senior authority having... exceptions to policy or regulations. This authority may be delegated. (1) Policy, direction and guidance for...

A model for regulation of mammalian ribosomal DNA transcription. Co-ordination of initiation and termination.

PubMed Central

Nashimoto, M; Mishima, Y

1988-01-01

Based on recent experimental data about transcription initiation and termination, a model for regulation of mammalian ribosomal DNA transcription is developed using a simple kinetic scheme. In this model, the existence of the transition pathway from the terminator to the promoter increases the rate of ribosomal RNA precursor synthesis. In addition to this 'non-transcribed spacer' traverse of RNA polymerase I, the co-ordination of initiation and termination allows a rapid on/off switch transition from the minimum to the maximum rate of ribosomal RNA precursor synthesis. Furthermore, taking account of the participation of two factors in the termination event, we propose a plausible molecular mechanism for the co-ordination of initiation and termination. This co-ordination is emphasized by repetition of the terminator unit. PMID:3223915

The Perceived Impact of 42 CFR Part 2 on Coordination and Integration of Care: A Qualitative Analysis.

PubMed

McCarty, Dennis; Rieckmann, Traci; Baker, Robin L; McConnell, K John

2017-03-01

Title 42 of the Code of Federal Regulations Part 2 (42 CFR Part 2) controls the release of patient information about treatment for substance use disorders. In 2016, the Substance Abuse and Mental Health Services Administration (SAMHSA) released a proposed rule to update the regulations, reduce provider burdens, and facilitate information exchange. Oregon's Medicaid program (Oregon Health Plan) altered the financing and structure of medical, dental, and behavioral care to promote greater integration and coordination. A qualitative analysis examined the perceived impact of 42 CFR Part 2 on care coordination and integration. Interviews with 76 stakeholders (114 interviews) conducted in 2012-2015 probed the processes of integrating behavioral health into primary care settings in Oregon and assessed issues associated with adherence to 42 CFR Part 2. Respondents expressed concerns that the regulations caused legal confusion, inhibited communication and information sharing, and required updating. Addiction treatment directors noted the challenges of obtaining patient consent to share information with primary care providers. The confidentiality regulations were perceived as a barrier to care coordination and integration. The Oregon Health Authority, therefore, requested regulatory changes. SAMHSA's proposed revisions permit a general consent to an entire health care team and allow inclusion of substance use disorder information within health information exchanges, but they mandate data segmentation of diagnostic and procedure codes related to substance use disorders and restrict access only to parties with authorized consent, possibly adding barriers to the coordination and integration of addiction treatment with primary care.

Differential expression of immune-regulatory genes associated with PD-L1 display in melanoma: implications for PD-1 pathway blockade

PubMed Central

Taube, Janis M.; Young, Geoffrey D.; McMiller, Tracee L.; Chen, Shuming; Salas, January T.; Pritchard, Theresa S.; Xu, Haiying; Meeker, Alan K.; Fan, Jinshui; Cheadle, Chris; Berger, Alan E.; Pardoll, Drew M.; Topalian, Suzanne L.

2015-01-01

Purpose Blocking the immunosuppressive PD-1/PD-L1 pathway has anti-tumor activity in multiple cancer types, and PD-L1 expression on tumor cells and infiltrating myeloid cells correlates with the likelihood of response. We previously found that IFNG (interferon-gamma) was over-expressed by TILs in PD-L1+ vs. PD-L1(−) melanomas, creating adaptive immune resistance by promoting PD-L1 display. The current study was undertaken to identify additional factors in the PD-L1+ melanoma microenvironment coordinately contributing to immunosuppression. Experimental design Archived, formalin-fixed paraffin-embedded melanoma specimens were assessed for PD-L1 protein expression at the tumor cell surface with immunohistochemistry (IHC). Whole genome expression analysis, quantitative (q)RT-PCR, immunohistochemistry, and functional in vitro validation studies were employed to assess factors differentially expressed in PD-L1+ versus PD-L1(−) melanomas. Results Functional annotation clustering based on whole genome expression profiling revealed pathways up-regulated in PD-L1+ melanomas, involving immune cell activation, inflammation, and antigen processing and presentation. Analysis by qRT-PCR demonstrated over-expression of functionally related genes in PD-L1+ melanomas, involved in CD8+ T cell activation (CD8A, IFNG, PRF1, CCL5), antigen presentation (CD163, TLR3, CXCL1, LYZ), and immunosuppression [PDCD1 (PD-1), CD274(PD-L1), LAG3, IL10]. Functional studies demonstrated that some factors, including IL-10 and IL-32-gamma, induced PD-L1 expression on monocytes but not tumor cells. Conclusions These studies elucidate the complexity of immune checkpoint regulation in the tumor microenvironment, identifying multiple factors likely contributing to coordinated immunosuppression. These factors may provide tumor escape mechanisms from anti-PD-1/PD-L1 therapy, and should be considered for co-targeting in combinatorial immunomodulation treatment strategies. PMID:25944800

Coordinating cell proliferation and differentiation: Antagonism between cell cycle regulators and cell type-specific gene expression

PubMed Central

Ruijtenberg, Suzan; van den Heuvel, Sander

2016-01-01

ABSTRACT Cell proliferation and differentiation show a remarkable inverse relationship. Precursor cells continue division before acquiring a fully differentiated state, while terminal differentiation usually coincides with proliferation arrest and permanent exit from the division cycle. Mechanistic insight in the temporal coordination between cell cycle exit and differentiation has come from studies of cells in culture and genetic animal models. As initially described for skeletal muscle differentiation, temporal coordination involves mutual antagonism between cyclin-dependent kinases that promote cell cycle entry and transcription factors that induce tissue-specific gene expression. Recent insights highlight the contribution of chromatin-regulating complexes that act in conjunction with the transcription factors and determine their activity. In particular SWI/SNF chromatin remodelers contribute to dual regulation of cell cycle and tissue-specific gene expression during terminal differentiation. We review the concerted regulation of the cell cycle and cell type-specific transcription, and discuss common mutations in human cancer that emphasize the clinical importance of proliferation versus differentiation control. PMID:26825227

Thioredoxin and NADPH-Dependent Thioredoxin Reductase C Regulation of Tetrapyrrole Biosynthesis.

PubMed

Da, Qingen; Wang, Peng; Wang, Menglong; Sun, Ting; Jin, Honglei; Liu, Bing; Wang, Jinfa; Grimm, Bernhard; Wang, Hong-Bin

2017-10-01

In chloroplasts, thioredoxin (TRX) isoforms and NADPH-dependent thioredoxin reductase C (NTRC) act as redox regulatory factors involved in multiple plastid biogenesis and metabolic processes. To date, less is known about the functional coordination between TRXs and NTRC in chlorophyll biosynthesis. In this study, we aimed to explore the potential functions of TRX m and NTRC in the regulation of the tetrapyrrole biosynthesis (TBS) pathway. Silencing of three genes, TRX m1 , TRX m2 , and TRX m4 ( TRX ms ), led to pale-green leaves, a significantly reduced 5-aminolevulinic acid (ALA)-synthesizing capacity, and reduced accumulation of chlorophyll and its metabolic intermediates in Arabidopsis ( Arabidopsis thaliana ). The contents of ALA dehydratase, protoporphyrinogen IX oxidase, the I subunit of Mg-chelatase, Mg-protoporphyrin IX methyltransferase (CHLM), and NADPH-protochlorophyllide oxidoreductase were decreased in triple TRX m- silenced seedlings compared with the wild type, although the transcript levels of the corresponding genes were not altered significantly. Protein-protein interaction analyses revealed a physical interaction between the TRX m isoforms and CHLM. 4-Acetoamido-4-maleimidylstilbene-2,2-disulfonate labeling showed the regulatory impact of TRX ms on the CHLM redox status. Since CHLM also is regulated by NTRC (Richter et al., 2013), we assessed the concurrent functions of TRX m and NTRC in the control of CHLM. Combined deficiencies of three TRX m isoforms and NTRC led to a cumulative decrease in leaf pigmentation, TBS intermediate contents, ALA synthesis rate, and CHLM activity. We discuss the coordinated roles of TRX m and NTRC in the redox control of CHLM stability with its corollary activity in the TBS pathway. © 2017 American Society of Plant Biologists. All Rights Reserved.

Thioredoxin and NADPH-Dependent Thioredoxin Reductase C Regulation of Tetrapyrrole Biosynthesis1[OPEN

PubMed Central

Sun, Ting; Jin, Honglei; Wang, Jinfa

2017-01-01

In chloroplasts, thioredoxin (TRX) isoforms and NADPH-dependent thioredoxin reductase C (NTRC) act as redox regulatory factors involved in multiple plastid biogenesis and metabolic processes. To date, less is known about the functional coordination between TRXs and NTRC in chlorophyll biosynthesis. In this study, we aimed to explore the potential functions of TRX m and NTRC in the regulation of the tetrapyrrole biosynthesis (TBS) pathway. Silencing of three genes, TRX m1, TRX m2, and TRX m4 (TRX ms), led to pale-green leaves, a significantly reduced 5-aminolevulinic acid (ALA)-synthesizing capacity, and reduced accumulation of chlorophyll and its metabolic intermediates in Arabidopsis (Arabidopsis thaliana). The contents of ALA dehydratase, protoporphyrinogen IX oxidase, the I subunit of Mg-chelatase, Mg-protoporphyrin IX methyltransferase (CHLM), and NADPH-protochlorophyllide oxidoreductase were decreased in triple TRX m-silenced seedlings compared with the wild type, although the transcript levels of the corresponding genes were not altered significantly. Protein-protein interaction analyses revealed a physical interaction between the TRX m isoforms and CHLM. 4-Acetoamido-4-maleimidylstilbene-2,2-disulfonate labeling showed the regulatory impact of TRX ms on the CHLM redox status. Since CHLM also is regulated by NTRC (Richter et al., 2013), we assessed the concurrent functions of TRX m and NTRC in the control of CHLM. Combined deficiencies of three TRX m isoforms and NTRC led to a cumulative decrease in leaf pigmentation, TBS intermediate contents, ALA synthesis rate, and CHLM activity. We discuss the coordinated roles of TRX m and NTRC in the redox control of CHLM stability with its corollary activity in the TBS pathway. PMID:28827456

Hsp90 Orchestrates Transcriptional Regulation by Hsf1 and Cell Wall Remodelling by MAPK Signalling during Thermal Adaptation in a Pathogenic Yeast

PubMed Central

Leach, Michelle D.; Budge, Susan; Walker, Louise; Munro, Carol; Cowen, Leah E.; Brown, Alistair J. P.

2012-01-01

Thermal adaptation is essential in all organisms. In yeasts, the heat shock response is commanded by the heat shock transcription factor Hsf1. Here we have integrated unbiased genetic screens with directed molecular dissection to demonstrate that multiple signalling cascades contribute to thermal adaptation in the pathogenic yeast Candida albicans. We show that the molecular chaperone heat shock protein 90 (Hsp90) interacts with and down-regulates Hsf1 thereby modulating short term thermal adaptation. In the longer term, thermal adaptation depends on key MAP kinase signalling pathways that are associated with cell wall remodelling: the Hog1, Mkc1 and Cek1 pathways. We demonstrate that these pathways are differentially activated and display cross talk during heat shock. As a result ambient temperature significantly affects the resistance of C. albicans cells to cell wall stresses (Calcofluor White and Congo Red), but not osmotic stress (NaCl). We also show that the inactivation of MAP kinase signalling disrupts this cross talk between thermal and cell wall adaptation. Critically, Hsp90 coordinates this cross talk. Genetic and pharmacological inhibition of Hsp90 disrupts the Hsf1-Hsp90 regulatory circuit thereby disturbing HSP gene regulation and reducing the resistance of C. albicans to proteotoxic stresses. Hsp90 depletion also affects cell wall biogenesis by impairing the activation of its client proteins Mkc1 and Hog1, as well as Cek1, which we implicate as a new Hsp90 client in this study. Therefore Hsp90 modulates the short term Hsf1-mediated activation of the classic heat shock response, coordinating this response with long term thermal adaptation via Mkc1- Hog1- and Cek1-mediated cell wall remodelling. PMID:23300438

Use of motor abundance in old adults in the regulation of a narrow-based stance.

PubMed

Hsu, Wei-Li; Lin, Kwan-Hwa; Yang, Rong-Sen; Cheng, Chih-Hsiu

2014-02-01

The ability to maintain stable balance while standing decreases with age. The body must coordinate multiple joints using "freeze" or "free" strategy, or a combination of both to ensure balance stability. The purpose of this study was to examine age-related changes in the use of motor abundance during upright stance on a narrow base without visual input. Uncontrolled manifold (UCM) analysis was used to decompose the movement variability of joints into goal-equivalent variability (GEV) and non-goal-equivalent variability (NGEV). The ratio between GEV and NGEV (UCM(ratio)) quantifies the joint coordination related to postural stability, and a high UCM(ratio) value indicates flexible control of joints. To perform balance tests, participants in this study (healthy young and old adults, 20 each) were asked to stand on a flat platform and on narrow wooden blocks with their eyes open and then eyes closed. In upright balance tests, both old and young adults maintained postural stability. GEV was greater than NGEV across all participants and conditions. However, GEV was higher in the young adults than in the old adults, whereas NGEV was higher in the old adults than in the young adults. Therefore, the old adults exhibited a lower UCM(ratio) than the young adults. The old adults were unable to exploit motor abundance and used a less flexible multi-joint coordination pattern to achieve stable balance. The UCM(ratio) value reflects the quality of postural control and can be used for assessing joint coordination in balance disorders.

A novel method for improving the accuracy of coordinate transformation in multiple measurement systems

NASA Astrophysics Data System (ADS)

Liu, W. L.; Li, Y. W.

2017-09-01

Large-scale dimensional metrology usually requires a combination of multiple measurement systems, such as laser tracking, total station, laser scanning, coordinate measuring arm and video photogrammetry, etc. Often, the results from different measurement systems must be combined to provide useful results. The coordinate transformation is used to unify coordinate frames in combination; however, coordinate transformation uncertainties directly affect the accuracy of the final measurement results. In this paper, a novel method is proposed for improving the accuracy of coordinate transformation, combining the advantages of the best-fit least-square and radial basis function (RBF) neural networks. First of all, the configuration of coordinate transformation is introduced and a transformation matrix containing seven variables is obtained. Second, the 3D uncertainty of the transformation model and the residual error variable vector are established based on the best-fit least-square. Finally, in order to optimize the uncertainty of the developed seven-variable transformation model, we used the RBF neural network to identify the uncertainty of the dynamic, and unstructured, owing to its great ability to approximate any nonlinear function to the designed accuracy. Intensive experimental studies were conducted to check the validity of the theoretical results. The results show that the mean error of coordinate transformation decreased from 0.078 mm to 0.054 mm after using this method in contrast with the GUM method.

43 CFR 1610.3 - Coordination with other Federal agencies, State and local governments, and Indian tribes.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Coordination with other Federal agencies, State and local governments, and Indian tribes. 1610.3 Section 1610.3 Public Lands: Interior Regulations... MANAGEMENT (1000) PLANNING, PROGRAMMING, BUDGETING Resource Management Planning § 1610.3 Coordination with...

50 CFR Appendix C to Part 404 - Boundary Coordinated for Papaha

Code of Federal Regulations, 2013 CFR

2013-10-01

... 50 Wildlife and Fisheries 11 2013-10-01 2013-10-01 false Boundary Coordinated for Papaha C Appendix C to Part 404 Wildlife and Fisheries JOINT REGULATIONS (UNITED STATES FISH AND WILDLIFE SERVICE... HAWAIIAN ISLANDS MARINE NATIONAL MONUMENT Pt. 404, App. C Appendix C to Part 404—Boundary Coordinated for...

50 CFR Appendix C to Part 404 - Boundary Coordinated for Papaha

Code of Federal Regulations, 2011 CFR

2011-10-01

... 50 Wildlife and Fisheries 9 2011-10-01 2011-10-01 false Boundary Coordinated for Papaha C Appendix C to Part 404 Wildlife and Fisheries JOINT REGULATIONS (UNITED STATES FISH AND WILDLIFE SERVICE... HAWAIIAN ISLANDS MARINE NATIONAL MONUMENT Pt. 404, App. C Appendix C to Part 404—Boundary Coordinated for...

50 CFR Appendix D to Part 404 - Boundary Coordinates for Papaha

Code of Federal Regulations, 2010 CFR

2010-10-01

... 50 Wildlife and Fisheries 7 2010-10-01 2010-10-01 false Boundary Coordinates for Papaha D Appendix D to Part 404 Wildlife and Fisheries JOINT REGULATIONS (UNITED STATES FISH AND WILDLIFE SERVICE... HAWAIIAN ISLANDS MARINE NATIONAL MONUMENT Pt. 404, App. D Appendix D to Part 404—Boundary Coordinates for...

45 CFR 607.7 - Coordinating offset with another Federal agency.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 3 2013-10-01 2013-10-01 false Coordinating offset with another Federal agency. 607.7 Section 607.7 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION SALARY OFFSET § 607.7 Coordinating offset with another Federal agency. (a) When the NSF is the...

45 CFR 607.7 - Coordinating offset with another Federal agency.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 3 2014-10-01 2014-10-01 false Coordinating offset with another Federal agency. 607.7 Section 607.7 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION SALARY OFFSET § 607.7 Coordinating offset with another Federal agency. (a) When the NSF is the...

45 CFR 607.7 - Coordinating offset with another Federal agency.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 3 2012-10-01 2012-10-01 false Coordinating offset with another Federal agency. 607.7 Section 607.7 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION SALARY OFFSET § 607.7 Coordinating offset with another Federal agency. (a) When the NSF is the...

15 CFR 922.31 - Promotion and coordination of Sanctuary use.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Promotion and coordination of Sanctuary use. 922.31 Section 922.31 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign... Implementation § 922.31 Promotion and coordination of Sanctuary use. The Secretary shall take such action as is...

Coordination of peptidoglycan synthesis and outer membrane constriction during Escherichia coli cell division

PubMed Central

Gray, Andrew N; Egan, Alexander JF; van't Veer, Inge L; Verheul, Jolanda; Colavin, Alexandre; Koumoutsi, Alexandra; Biboy, Jacob; Altelaar, A F Maarten; Damen, Mirjam J; Huang, Kerwyn Casey; Simorre, Jean-Pierre; Breukink, Eefjan; den Blaauwen, Tanneke; Typas, Athanasios; Gross, Carol A; Vollmer, Waldemar

2015-01-01

To maintain cellular structure and integrity during division, Gram-negative bacteria must carefully coordinate constriction of a tripartite cell envelope of inner membrane, peptidoglycan (PG), and outer membrane (OM). It has remained enigmatic how this is accomplished. Here, we show that envelope machines facilitating septal PG synthesis (PBP1B-LpoB complex) and OM constriction (Tol system) are physically and functionally coordinated via YbgF, renamed CpoB (Coordinator of PG synthesis and OM constriction, associated with PBP1B). CpoB localizes to the septum concurrent with PBP1B-LpoB and Tol at the onset of constriction, interacts with both complexes, and regulates PBP1B activity in response to Tol energy state. This coordination links PG synthesis with OM invagination and imparts a unique mode of bifunctional PG synthase regulation by selectively modulating PBP1B cross-linking activity. Coordination of the PBP1B and Tol machines by CpoB contributes to effective PBP1B function in vivo and maintenance of cell envelope integrity during division. DOI: http://dx.doi.org/10.7554/eLife.07118.001 PMID:25951518

Sox21 deletion in mice causes postnatal growth deficiency without physiological disruption of hypothalamic-pituitary endocrine axes

PubMed Central

Cheung, Leonard Y. M.; Okano, Hideyuki

2016-01-01

The hypothalamic-pituitary axes are the coordinating centers for multiple endocrine gland functions and physiological processes. Defects in the hypothalamus or pituitary gland can cause reduced growth and severe short stature, affecting approximately 1 in 4000 children, and a large percentage of cases of pituitary hormone deficiencies do not have an identified genetic cause. SOX21 is a protein that regulates hair, neural, and trophoblast stem cell differentiation. Mice lacking Sox21 have reduced growth, but the etiology of this growth defect has not been described. We studied the expression of Sox21 in hypothalamic-pituitary development and examined multiple endocrine axes in these mice. We find no evidence of reduced intrauterine growth, food intake, or physical activity, but there is evidence for increased energy expenditure in mutants. In addition, despite changes in pituitary hormone expression, hypothalamic-pituitary axes appear to be functional. Therefore, SOX21 variants may be a cause of non-endocrine short stature in humans. PMID:27616671

Two FGFRL-Wnt circuits organize the planarian anteroposterior axis.

PubMed

Scimone, M Lucila; Cote, Lauren E; Rogers, Travis; Reddien, Peter W

2016-04-11

How positional information instructs adult tissue maintenance is poorly understood. Planarians undergo whole-body regeneration and tissue turnover, providing a model for adult positional information studies. Genes encoding secreted and transmembrane components of multiple developmental pathways are predominantly expressed in planarian muscle cells. Several of these genes regulate regional identity, consistent with muscle harboring positional information. Here, single-cell RNA-sequencing of 115 muscle cells from distinct anterior-posterior regions identified 44 regionally expressed genes, including multiple Wnt and ndk/FGF receptor-like (ndl/FGFRL) genes. Two distinct FGFRL-Wnt circuits, involving juxtaposed anterior FGFRL and posterior Wnt expression domains, controlled planarian head and trunk patterning. ndl-3 and wntP-2 inhibition expanded the trunk, forming ectopic mouths and secondary pharynges, which independently extended and ingested food. fz5/8-4 inhibition, like that of ndk and wntA, caused posterior brain expansion and ectopic eye formation. Our results suggest that FGFRL-Wnt circuits operate within a body-wide coordinate system to control adult axial positioning.

A recovery principle provides insight into auxin pattern control in the Arabidopsis root

PubMed Central

Moore, Simon; Liu, Junli; Zhang, Xiaoxian; Lindsey, Keith

2017-01-01

Regulated auxin patterning provides a key mechanism for controlling root growth and development. We have developed a data-driven mechanistic model using realistic root geometry and formulated a principle to theoretically investigate quantitative auxin pattern recovery following auxin transport perturbation. This principle reveals that auxin patterning is potentially controlled by multiple combinations of interlinked levels and localisation of influx and efflux carriers. We demonstrate that (1) when efflux carriers maintain polarity but change levels, maintaining the same auxin pattern requires non-uniform and polar distribution of influx carriers; (2) the emergence of the same auxin pattern, from different levels of influx carriers with the same nonpolar localisation, requires simultaneous modulation of efflux carrier level and polarity; and (3) multiple patterns of influx and efflux carriers for maintaining an auxin pattern do not have spatially proportional correlation. This reveals that auxin pattern formation requires coordination between influx and efflux carriers. We further show that the model makes various predictions that can be experimentally validated. PMID:28220889

A post-transcriptional mechanism pacing expression of neural genes with precursor cell differentiation status.

PubMed

Dai, Weijun; Li, Wencheng; Hoque, Mainul; Li, Zhuyun; Tian, Bin; Makeyev, Eugene V

2015-07-06

Nervous system (NS) development relies on coherent upregulation of extensive sets of genes in a precise spatiotemporal manner. How such transcriptome-wide effects are orchestrated at the molecular level remains an open question. Here we show that 3'-untranslated regions (3' UTRs) of multiple neural transcripts contain AU-rich cis-elements (AREs) recognized by tristetraprolin (TTP/Zfp36), an RNA-binding protein previously implicated in regulation of mRNA stability. We further demonstrate that the efficiency of ARE-dependent mRNA degradation declines in the neural lineage because of a decrease in the TTP protein expression mediated by the NS-enriched microRNA miR-9. Importantly, TTP downregulation in this context is essential for proper neuronal differentiation. On the other hand, inactivation of TTP in non-neuronal cells leads to dramatic upregulation of multiple NS-specific genes. We conclude that the newly identified miR-9/TTP circuitry limits unscheduled accumulation of neuronal mRNAs in non-neuronal cells and ensures coordinated upregulation of these transcripts in neurons.

Synaptic Plasticity and NO-cGMP-PKG Signaling Coordinately Regulate ERK-Driven Gene Expression in the Lateral Amygdala and in the Auditory Thalamus Following Pavlovian Fear Conditioning

ERIC Educational Resources Information Center

Ota, Kristie T.; Monsey, Melissa S.; Wu, Melissa S.; Young, Grace J.; Schafe, Glenn E.

2010-01-01

We have recently hypothesized that NO-cGMP-PKG signaling in the lateral nucleus of the amygdala (LA) during auditory fear conditioning coordinately regulates ERK-driven transcriptional changes in both auditory thalamic (MGm/PIN) and LA neurons that serve to promote pre- and postsynaptic alterations at thalamo-LA synapses, respectively. In the…

CTCF counter-regulates cardiomyocyte development and maturation programs in the embryonic heart.

PubMed

Gomez-Velazquez, Melisa; Badia-Careaga, Claudio; Lechuga-Vieco, Ana Victoria; Nieto-Arellano, Rocio; Tena, Juan J; Rollan, Isabel; Alvarez, Alba; Torroja, Carlos; Caceres, Eva F; Roy, Anna R; Galjart, Niels; Delgado-Olguin, Paul; Sanchez-Cabo, Fatima; Enriquez, Jose Antonio; Gomez-Skarmeta, Jose Luis; Manzanares, Miguel

2017-08-01

Cardiac progenitors are specified early in development and progressively differentiate and mature into fully functional cardiomyocytes. This process is controlled by an extensively studied transcriptional program. However, the regulatory events coordinating the progression of such program from development to maturation are largely unknown. Here, we show that the genome organizer CTCF is essential for cardiogenesis and that it mediates genomic interactions to coordinate cardiomyocyte differentiation and maturation in the developing heart. Inactivation of Ctcf in cardiac progenitor cells and their derivatives in vivo during development caused severe cardiac defects and death at embryonic day 12.5. Genome wide expression analysis in Ctcf mutant hearts revealed that genes controlling mitochondrial function and protein production, required for cardiomyocyte maturation, were upregulated. However, mitochondria from mutant cardiomyocytes do not mature properly. In contrast, multiple development regulatory genes near predicted heart enhancers, including genes in the IrxA cluster, were downregulated in Ctcf mutants, suggesting that CTCF promotes cardiomyocyte differentiation by facilitating enhancer-promoter interactions. Accordingly, loss of CTCF disrupts gene expression and chromatin interactions as shown by chromatin conformation capture followed by deep sequencing. Furthermore, CRISPR-mediated deletion of an intergenic CTCF site within the IrxA cluster alters gene expression in the developing heart. Thus, CTCF mediates local regulatory interactions to coordinate transcriptional programs controlling transitions in morphology and function during heart development.

CTCF counter-regulates cardiomyocyte development and maturation programs in the embryonic heart

PubMed Central

Gomez-Velazquez, Melisa; Badia-Careaga, Claudio; Lechuga-Vieco, Ana Victoria; Nieto-Arellano, Rocio; Rollan, Isabel; Alvarez, Alba; Torroja, Carlos; Caceres, Eva F.; Roy, Anna R.; Galjart, Niels; Sanchez-Cabo, Fatima; Enriquez, Jose Antonio; Gomez-Skarmeta, Jose Luis

2017-01-01

Cardiac progenitors are specified early in development and progressively differentiate and mature into fully functional cardiomyocytes. This process is controlled by an extensively studied transcriptional program. However, the regulatory events coordinating the progression of such program from development to maturation are largely unknown. Here, we show that the genome organizer CTCF is essential for cardiogenesis and that it mediates genomic interactions to coordinate cardiomyocyte differentiation and maturation in the developing heart. Inactivation of Ctcf in cardiac progenitor cells and their derivatives in vivo during development caused severe cardiac defects and death at embryonic day 12.5. Genome wide expression analysis in Ctcf mutant hearts revealed that genes controlling mitochondrial function and protein production, required for cardiomyocyte maturation, were upregulated. However, mitochondria from mutant cardiomyocytes do not mature properly. In contrast, multiple development regulatory genes near predicted heart enhancers, including genes in the IrxA cluster, were downregulated in Ctcf mutants, suggesting that CTCF promotes cardiomyocyte differentiation by facilitating enhancer-promoter interactions. Accordingly, loss of CTCF disrupts gene expression and chromatin interactions as shown by chromatin conformation capture followed by deep sequencing. Furthermore, CRISPR-mediated deletion of an intergenic CTCF site within the IrxA cluster alters gene expression in the developing heart. Thus, CTCF mediates local regulatory interactions to coordinate transcriptional programs controlling transitions in morphology and function during heart development. PMID:28846746

Co-regulation of Iron Metabolism and Virulence Associated Functions by Iron and XibR, a Novel Iron Binding Transcription Factor, in the Plant Pathogen Xanthomonas

PubMed Central

Pandey, Sheo Shankar; Patnana, Pradeep Kumar; Lomada, Santosh Kumar; Tomar, Archana; Chatterjee, Subhadeep

2016-01-01

Abilities of bacterial pathogens to adapt to the iron limitation present in hosts is critical to their virulence. Bacterial pathogens have evolved diverse strategies to coordinately regulate iron metabolism and virulence associated functions to maintain iron homeostasis in response to changing iron availability in the environment. In many bacteria the ferric uptake regulator (Fur) functions as transcription factor that utilize ferrous form of iron as cofactor to regulate transcription of iron metabolism and many cellular functions. However, mechanisms of fine-tuning and coordinated regulation of virulence associated function beyond iron and Fur-Fe2+ remain undefined. In this study, we show that a novel transcriptional regulator XibR (named X anthomonas iron binding regulator) of the NtrC family, is required for fine-tuning and co-coordinately regulating the expression of several iron regulated genes and virulence associated functions in phytopathogen Xanthomonas campestris pv. campestris (Xcc). Genome wide expression analysis of iron-starvation stimulon and XibR regulon, GUS assays, genetic and functional studies of xibR mutant revealed that XibR positively regulates functions involved in iron storage and uptake, chemotaxis, motility and negatively regulates siderophore production, in response to iron. Furthermore, chromatin immunoprecipitation followed by quantitative real-time PCR indicated that iron promoted binding of the XibR to the upstream regulatory sequence of operon’s involved in chemotaxis and motility. Circular dichroism spectroscopy showed that purified XibR bound ferric form of iron. Electrophoretic mobility shift assay revealed that iron positively affected the binding of XibR to the upstream regulatory sequences of the target virulence genes, an effect that was reversed by ferric iron chelator deferoxamine. Taken together, these data revealed that how XibR coordinately regulates virulence associated and iron metabolism functions in Xanthomonads in response to iron availability. Our results provide insight of the complex regulatory mechanism of fine-tuning of virulence associated functions with iron availability in this important group of phytopathogen. PMID:27902780

Multiple Genes Repress Motility in Uropathogenic Escherichia coli Constitutively Expressing Type 1 Fimbriae▿ †

PubMed Central

Simms, Amy N.; Mobley, Harry L. T.

2008-01-01

Two surface organelles of uropathogenic Escherichia coli (UPEC), flagella and type 1 fimbriae, are critical for colonization of the urinary tract but mediate opposite actions. Flagella propel bacteria through urine and along mucus layers, while type 1 fimbriae allow bacteria to adhere to specific receptors present on uroepithelial cells. Constitutive expression of type 1 fimbriae leads to repression of motility and chemotaxis in UPEC strain CFT073, suggesting that UPEC may coordinately regulate motility and adherence. To identify genes involved in this regulation of motility by type 1 fimbriae, transposon mutagenesis was performed on a phase-locked type 1 fimbrial ON variant of strain CFT073 (CFT073 fim L-ON), followed by a screen for restoration of motility in soft agar. Functions of the genes identified included attachment, metabolism, transport, DNA mismatch repair, and transcriptional regulation, and a number of genes had hypothetical function. Isogenic deletion mutants of these genes were also constructed in CFT073 fim L-ON. Motility was partially restored in six of these mutants, including complementable mutations in four genes encoding known transcriptional regulators, lrhA, lrp, slyA, and papX; a mismatch repair gene, mutS; and one hypothetical gene, ydiV. Type 1 fimbrial expression in these mutants was unaltered, and the majority of these mutants expressed larger amounts of flagellin than the fim L-ON parental strain. Our results indicate that repression of motility in CFT073 fim L-ON is not solely due to the constitutive expression of type 1 fimbriae on the surfaces of the bacteria and that multiple genes may contribute to this repression. PMID:18359812

The Arabidopsis phytohormone crosstalk network involves a consecutive metabolic route and circular control units of transcription factors that regulate enzyme-encoding genes.

PubMed

Yue, Xun; Li, Xing Guo; Gao, Xin-Qi; Zhao, Xiang Yu; Dong, Yu Xiu; Zhou, Chao

2016-09-02

Phytohormone synergies and signaling interdependency are important topics in plant developmental biology. Physiological and genetic experimental evidence for phytohormone crosstalk has been accumulating and a genome-scale enzyme correlation model representing the Arabidopsis metabolic pathway has been published. However, an integrated molecular characterization of phytohormone crosstalk is still not available. A novel modeling methodology and advanced computational approaches were used to construct an enzyme-based Arabidopsis phytohormone crosstalk network (EAPCN) at the biosynthesis level. The EAPCN provided the structural connectivity architecture of phytohormone biosynthesis pathways and revealed a surprising result; that enzymes localized at the highly connected nodes formed a consecutive metabolic route. Furthermore, our analysis revealed that the transcription factors (TFs) that regulate enzyme-encoding genes in the consecutive metabolic route formed structures, which we describe as circular control units operating at the transcriptional level. Furthermore, the downstream TFs in phytohormone signal transduction pathways were found to be involved in the circular control units that included the TFs regulating enzyme-encoding genes. In addition, multiple functional enzymes in the EAPCN were found to be involved in ion and pH homeostasis, environmental signal perception, cellular redox homeostasis, and circadian clocks. Last, publicly available transcriptional profiles and a protein expression map of the Arabidopsis root apical meristem were used as a case study to validate the proposed framework. Our results revealed multiple scales of coupled mechanisms in that hormonal crosstalk networks that play a central role in coordinating internal developmental processes with environmental signals, and give a broader view of Arabidopsis phytohormone crosstalk. We also uncovered potential key regulators that can be further analyzed in future studies.

The machinery at endoplasmic reticulum-plasma membrane contact sites contributes to spatial regulation of multiple Legionella effector proteins.

PubMed

Hubber, Andree; Arasaki, Kohei; Nakatsu, Fubito; Hardiman, Camille; Lambright, David; De Camilli, Pietro; Nagai, Hiroki; Roy, Craig R

2014-07-01

The Dot/Icm system of the intracellular pathogen Legionella pneumophila has the capacity to deliver over 270 effector proteins into host cells during infection. Important questions remain as to spatial and temporal mechanisms used to regulate such a large array of virulence determinants after they have been delivered into host cells. Here we investigated several L. pneumophila effector proteins that contain a conserved phosphatidylinositol-4-phosphate (PI4P)-binding domain first described in the effector DrrA (SidM). This PI4P binding domain was essential for the localization of effectors to the early L. pneumophila-containing vacuole (LCV), and DrrA-mediated recruitment of Rab1 to the LCV required PI4P-binding activity. It was found that the host cell machinery that regulates sites of contact between the plasma membrane (PM) and the endoplasmic reticulum (ER) modulates PI4P dynamics on the LCV to control localization of these effectors. Specifically, phosphatidylinositol-4-kinase IIIα (PI4KIIIα) was important for generating a PI4P signature that enabled L. pneumophila effectors to localize to the PM-derived vacuole, and the ER-associated phosphatase Sac1 was involved in metabolizing the PI4P on the vacuole to promote the dissociation of effectors. A defect in L. pneumophila replication in macrophages deficient in PI4KIIIα was observed, highlighting that a PM-derived PI4P signature is critical for biogenesis of a vacuole that supports intracellular multiplication of L. pneumophila. These data indicate that PI4P metabolism by enzymes controlling PM-ER contact sites regulate the association of L. pneumophila effectors to coordinate early stages of vacuole biogenesis.

Tick Tock: Circadian Regulation of Plant Innate Immunity.

PubMed

Lu, Hua; McClung, C Robertson; Zhang, Chong

2017-08-04

Many living organisms on Earth have evolved the ability to integrate environmental and internal signals to determine time and thereafter adjust appropriately their metabolism, physiology, and behavior. The circadian clock is the endogenous timekeeper critical for multiple biological processes in many organisms. A growing body of evidence supports the importance of the circadian clock for plant health. Plants activate timed defense with various strategies to anticipate daily attacks of pathogens and pests and to modulate responses to specific invaders in a time-of-day-dependent manner (gating). Pathogen infection is also known to reciprocally modulate clock activity. Such a cross talk likely reflects the adaptive nature of plants to coordinate limited resources for growth, development, and defense. This review summarizes recent progress in circadian regulation of plant innate immunity with a focus on the molecular events linking the circadian clock and defense. More and better knowledge of clock-defense cross talk could help to improve disease resistance and productivity in economically important crops.

Perspectives on the mechanism of transcriptional regulation by long non-coding RNAs.

PubMed

Roberts, Thomas C; Morris, Kevin V; Weinberg, Marc S

2014-01-01

Long non-coding RNAs (lncRNAs) are increasingly being recognized as epigenetic regulators of gene transcription. The diversity and complexity of lncRNA genes means that they exert their regulatory effects by a variety of mechanisms. Although there is still much to be learned about the mechanism of lncRNA function, general principles are starting to emerge. In particular, the application of high throughput (deep) sequencing methodologies has greatly advanced our understanding of lncRNA gene function. lncRNAs function as adaptors that link specific chromatin loci with chromatin-remodeling complexes and transcription factors. lncRNAs can act in cis or trans to guide epigenetic-modifier complexes to distinct genomic sites, or act as scaffolds which recruit multiple proteins simultaneously, thereby coordinating their activities. In this review we discuss the genomic organization of lncRNAs, the importance of RNA secondary structure to lncRNA functionality, the multitude of ways in which they interact with the genome, and what evolutionary conservation tells us about their function.

An Overview of Seafood Supply, Food Safety and Regulation in New South Wales, Australia

PubMed Central

Hussain, Malik A.; Saputra, Themy; Szabo, Elizabeth A.; Nelan, Bruce

2017-01-01

Seafood consumption is increasing in Australia, especially in New South Wales (NSW). Average per capita seafood consumption in NSW is higher than the national average. Seafood supply in NSW comes from domestic (wild catch and aquaculture) and overseas (seafood imports) sources. The contribution of wild catch and aquaculture in domestic seafood production (2012–2013) was 73.42% and 26.52%, respectively. Seafood-associated foodborne illness outbreaks are not common and on an average four outbreaks occur each year in NSW. Most of the outbreaks in 2015 and 2016 were related to ciguatera poisoning. The regulation of the seafood industry and the management of food safety is an example of the coordinated work of multiple government agencies and organizations in which NSW Food Authority is responsible for managing the overall risks through the Seafood Safety Scheme. Overall, seafood supply in NSW is of high quality and poses low food safety risk to consumers. PMID:28753923

Polo kinase Cdc5 is a central regulator of meiosis I

PubMed Central

Attner, Michelle A.; Miller, Matthew P.; Ee, Ly-sha; Elkin, Sheryl K.; Amon, Angelika

2013-01-01

During meiosis, two consecutive rounds of chromosome segregation yield four haploid gametes from one diploid cell. The Polo kinase Cdc5 is required for meiotic progression, but how Cdc5 coordinates multiple cell-cycle events during meiosis I is not understood. Here we show that CDC5-dependent phosphorylation of Rec8, a subunit of the cohesin complex that links sister chromatids, is required for efficient cohesin removal from chromosome arms, which is a prerequisite for meiosis I chromosome segregation. CDC5 also establishes conditions for centromeric cohesin removal during meiosis II by promoting the degradation of Spo13, a protein that protects centromeric cohesin during meiosis I. Despite CDC5’s central role in meiosis I, the protein kinase is dispensable during meiosis II and does not even phosphorylate its meiosis I targets during the second meiotic division. We conclude that Cdc5 has evolved into a master regulator of the unique meiosis I chromosome segregation pattern. PMID:23918381

CDK regulation of transcription by RNAP II: Not over 'til it's over?

PubMed

Fisher, Robert P

2017-03-15

Transcription by RNA polymerase (RNAP) II is regulated at multiple steps by phosphorylation, catalyzed mainly by members of the cyclin-dependent kinase (CDK) family. The CDKs involved in transcription have overlapping substrate specificities, but play largely non-redundant roles in coordinating gene expression. Novel functions and targets of CDKs have recently emerged at the end of the transcription cycle, when the primary transcript is cleaved, and in most cases polyadenylated, and transcription is terminated by the action of the "torpedo" exonuclease Xrn2, which is a CDK substrate. Collectively, various functions have been ascribed to CDKs or CDK-mediated phosphorylation: recruiting cleavage and polyadenylation factors, preventing premature termination within gene bodies while promoting efficient termination of full-length transcripts, and preventing extensive readthrough transcription into intergenic regions or neighboring genes. The assignment of precise functions to specific CDKs is still in progress, but recent advances suggest ways in which the CDK network and RNAP II machinery might cooperate to ensure timely exit from the transcription cycle.

CDK regulation of transcription by RNAP II: Not over ‘til it's over?

PubMed Central

Fisher, Robert P.

2017-01-01

ABSTRACT Transcription by RNA polymerase (RNAP) II is regulated at multiple steps by phosphorylation, catalyzed mainly by members of the cyclin-dependent kinase (CDK) family. The CDKs involved in transcription have overlapping substrate specificities, but play largely non-redundant roles in coordinating gene expression. Novel functions and targets of CDKs have recently emerged at the end of the transcription cycle, when the primary transcript is cleaved, and in most cases polyadenylated, and transcription is terminated by the action of the “torpedo” exonuclease Xrn2, which is a CDK substrate. Collectively, various functions have been ascribed to CDKs or CDK-mediated phosphorylation: recruiting cleavage and polyadenylation factors, preventing premature termination within gene bodies while promoting efficient termination of full-length transcripts, and preventing extensive readthrough transcription into intergenic regions or neighboring genes. The assignment of precise functions to specific CDKs is still in progress, but recent advances suggest ways in which the CDK network and RNAP II machinery might cooperate to ensure timely exit from the transcription cycle. PMID:28005463

Alternative Splicing of Four Trafficking Genes Regulates Myofiber Structure and Skeletal Muscle Physiology.

PubMed

Giudice, Jimena; Loehr, James A; Rodney, George G; Cooper, Thomas A

2016-11-15

During development, transcriptional and post-transcriptional networks are coordinately regulated to drive organ maturation. Alternative splicing contributes by producing temporal-specific protein isoforms. We previously found that genes undergoing splicing transitions during mouse postnatal heart development are enriched for vesicular trafficking and membrane dynamics functions. Here, we show that adult trafficking isoforms are also expressed in adult skeletal muscle and hypothesize that striated muscle utilizes alternative splicing to generate specific isoforms required for function of adult tissue. We deliver morpholinos into flexor digitorum brevis muscles in adult mice to redirect splicing of four trafficking genes to the fetal isoforms. The splicing switch results in multiple structural and functional defects, including transverse tubule (T-tubule) disruption and dihydropyridine receptor alpha (DHPR) and Ryr1 mislocalization, impairing excitation-contraction coupling, calcium handling, and force generation. The results demonstrate a previously unrecognized role for trafficking functions in adult muscle tissue homeostasis and a specific requirement for the adult splice variants. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

The role of the cerebellum in the regulation of language functions.

PubMed

Starowicz-Filip, Anna; Chrobak, Adrian Andrzej; Moskała, Marek; Krzyżewski, Roger M; Kwinta, Borys; Kwiatkowski, Stanisław; Milczarek, Olga; Rajtar-Zembaty, Anna; Przewoźnik, Dorota

2017-08-29

The present paper is a review of studies on the role of the cerebellum in the regulation of language functions. This brain structure until recently associated chiefly with motor skills, visual-motor coordination and balance, proves to be significant also for cognitive functioning. With regard to language functions, studies show that the cerebellum determines verbal fluency (both semantic and formal) expressive and receptive grammar processing, the ability to identify and correct language mistakes, and writing skills. Cerebellar damage is a possible cause of aphasia or the cerebellar mutism syndrome (CMS). Decreased cerebellocortical connectivity as well as anomalies in the structure of the cerebellum are emphasized in numerous developmental dyslexia theories. The cerebellum is characterized by linguistic lateralization. From the neuroanatomical perspective, its right hemisphere and dentate nucleus, having multiple cerebellocortical connections with the cerebral cortical language areas, are particularly important for language functions. Usually, language deficits developed as a result of a cerebellar damage have subclinical intensity and require applying sensitive neuropsychological diagnostic tools designed to assess higher verbal functions.

System-dependent regulations of colour-pattern development: a mutagenesis study of the pale grass blue butterfly

PubMed Central

Iwata, Masaki; Hiyama, Atsuki; Otaki, Joji M.

2013-01-01

Developmental studies on wing colour patterns have been performed in nymphalid butterflies, but efficient genetic manipulations, including mutagenesis, have not been well established. Here, we have performed mutagenesis experiments in a lycaenid butterfly, the pale grass blue Zizeeria maha, to produce colour-pattern mutants. We fed the P-generation larvae an artificial diet containing the mutagen ethyl methane sulfonate (EMS), and the F1- and F2-generation adults showed various aberrant colour patterns: dorsoventral transformation, anterioposterior background colouration gap, weak contrast, disarrangement of spots, reduction of the size of spots, loss of spots, fusion of spots, and ectopic spots. Among them, the disarrangement, reduction, and loss of spots were likely produced by the coordinated changes of many spots of a single wing around the discal spot in a system-dependent manner, demonstrating the existence of the central symmetry system. The present study revealed multiple genetic regulations for system-dependent and wing-wide colour-pattern determination in lycaenid butterflies. PMID:23917124

Genome-wide Analysis Reveals SR Protein Cooperation and Competition in Regulated Splicing

PubMed Central

Pandit, Shatakshi; Zhou, Yu; Shiue, Lily; Coutinho-Mansfield, Gabriela; Li, Hairi; Qiu, Jinsong; Huang, Jie; Yeo, Gene W.; Ares, Manuel; Fu, Xiang-Dong

2013-01-01

Summary SR proteins are well-characterized RNA binding proteins that promote exon inclusion by binding to exonic splicing enhancers (ESEs). However, it has been unclear whether regulatory rules deduced on model genes apply generally to activities of SR proteins in the cell. Here, we report global analyses of two prototypical SR proteins SRSF1 (SF2/ASF) and SRSF2 (SC35) using splicing-sensitive arrays and CLIP-seq on mouse embryo fibroblasts (MEFs). Unexpectedly, we find that these SR proteins promote both inclusion and skipping of exons in vivo, but their binding patterns do not explain such opposite responses. Further analyses reveal that loss of one SR protein is accompanied by coordinated loss or compensatory gain in the interaction of other SR proteins at the affected exons. Therefore, specific effects on regulated splicing by one SR protein actually depend on a complex set of relationships with multiple other SR proteins in mammalian genomes. PMID:23562324

A needs assessment of health information technology for improving care coordination in three leading patient-centered medical homes.

PubMed

Richardson, Joshua E; Vest, Joshua R; Green, Cori M; Kern, Lisa M; Kaushal, Rainu

2015-07-01

We investigated ways that patient-centered medical homes (PCMHs) are currently using health information technology (IT) for care coordination and what types of health IT are needed to improve care coordination. A multi-disciplinary team of researchers conducted semi-structured telephone interviews with 28 participants from 3 PCMHs in the United States. Participants included administrators and clinicians from PCMHs, electronic health record (EHR) and health information exchange (HIE) representatives, and policy makers. Participants identified multiple barriers to care coordination using current health IT tools. We identified five areas in which health IT can improve care coordination in PCMHs: 1) monitoring patient populations, 2) notifying clinicians and other staff when specific patients move across care settings, 3) collaborating around patients, 4) reporting activities, and 5) interoperability. To accomplish these tasks, many participants described using homegrown care coordination systems separate from EHRs. The participants in this study have resources, experience, and expertise with using health IT for care coordination, yet they still identified multiple areas for improvement. We hypothesize that focusing health IT development in the five areas we identified can enable more effective care coordination. Key findings from this work are that homegrown systems apart from EHRs are currently used to support care coordination and, also, that reporting tools are key components of care coordination. New health IT that enables monitoring, notifying, collaborating, reporting, and interoperability would enhance care coordination within PCMHs beyond what current health IT enables. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Regulating the Intersection of Metabolism and Pathogenesis in Gram-positive Bacteria

PubMed Central

RICHARDSON, ANTHONY R.; SOMERVILLE, GREG A.; SONENSHEIN, ABRAHAM L.

2015-01-01

Pathogenic bacteria must contend with immune systems that actively restrict the availability of nutrients and cofactors, and create a hostile growth environment. To deal with these hostile environments, pathogenic bacteria have evolved or acquired virulence determinants that aid in the acquisition of nutrients. This connection between pathogenesis and nutrition may explain why regulators of metabolism in nonpathogenic bacteria are used by pathogenic bacteria to regulate both metabolism and virulence. Such coordinated regulation is presumably advantageous because it conserves carbon and energy by aligning synthesis of virulence determinants with the nutritional environment. In Gram-positive bacterial pathogens, at least three metabolite-responsive global regulators, CcpA, CodY, and Rex, have been shown to coordinate the expression of metabolism and virulence genes. In this chapter, we discuss how environmental challenges alter metabolism, the regulators that respond to this altered metabolism, and how these regulators influence the host-pathogen interaction. PMID:26185086

A Global Protein Kinase and Phosphatase Interaction Network in Yeast

PubMed Central

Breitkreutz, Ashton; Choi, Hyungwon; Sharom, Jeffrey R.; Boucher, Lorrie; Neduva, Victor; Larsen, Brett; Lin, Zhen-Yuan; Breitkreutz, Bobby-Joe; Stark, Chris; Liu, Guomin; Ahn, Jessica; Dewar-Darch, Danielle; Reguly, Teresa; Tang, Xiaojing; Almeida, Ricardo; Qin, Zhaohui Steve; Pawson, Tony; Gingras, Anne-Claude; Nesvizhskii, Alexey I.; Tyers, Mike

2011-01-01

The interactions of protein kinases and phosphatases with their regulatory subunits and substrates underpin cellular regulation. We identified a kinase and phosphatase interaction (KPI) network of 1844 interactions in budding yeast by mass spectrometric analysis of protein complexes. The KPI network contained many dense local regions of interactions that suggested new functions. Notably, the cell cycle phosphatase Cdc14 associated with multiple kinases that revealed roles for Cdc14 in mitogen-activated protein kinase signaling, the DNA damage response, and metabolism, whereas interactions of the target of rapamycin complex 1 (TORC1) uncovered new effector kinases in nitrogen and carbon metabolism. An extensive backbone of kinase-kinase interactions cross-connects the proteome and may serve to coordinate diverse cellular responses. PMID:20489023

Diverse roles of ERECTA family genes in plant development.

PubMed

Shpak, Elena D

2013-12-01

Multiple receptor-like kinases (RLKs) enable intercellular communication that coordinates growth and development of plant tissues. ERECTA family receptors (ERfs) are an ancient family of leucine-rich repeat RLKs that in Arabidopsis consists of three genes: ERECTA, ERL1, and ERL2. ERfs sense secreted cysteine-rich peptides from the EPF/EPFL family and transmit the signal through a MAP kinase cascade. This review discusses the functions of ERfs in stomata development, in regulation of longitudinal growth of aboveground organs, during reproductive development, and in the shoot apical meristem. In addition the role of ERECTA in plant responses to biotic and abiotic factors is examined. Elena D. Shpak (Corresponding author). © 2013 Institute of Botany, Chinese Academy of Sciences.

18 CFR 1307.13 - Effect on other regulations; supervision and coordination.

Code of Federal Regulations, 2010 CFR

2010-04-01

... TENNESSEE VALLEY AUTHORITY NONDISCRIMINATION WITH RESPECT TO HANDICAP § 1307.13 Effect on other regulations... other regulations or instructions, insofar as they prohibit discrimination on the ground of handicap in...

18 CFR 1307.13 - Effect on other regulations; supervision and coordination.

Code of Federal Regulations, 2014 CFR

2014-04-01

... TENNESSEE VALLEY AUTHORITY NONDISCRIMINATION WITH RESPECT TO HANDICAP § 1307.13 Effect on other regulations... other regulations or instructions, insofar as they prohibit discrimination on the ground of handicap in...

18 CFR 1307.13 - Effect on other regulations; supervision and coordination.

Code of Federal Regulations, 2012 CFR

2012-04-01

... TENNESSEE VALLEY AUTHORITY NONDISCRIMINATION WITH RESPECT TO HANDICAP § 1307.13 Effect on other regulations... other regulations or instructions, insofar as they prohibit discrimination on the ground of handicap in...

18 CFR 1307.13 - Effect on other regulations; supervision and coordination.

Code of Federal Regulations, 2013 CFR

2013-04-01

... TENNESSEE VALLEY AUTHORITY NONDISCRIMINATION WITH RESPECT TO HANDICAP § 1307.13 Effect on other regulations... other regulations or instructions, insofar as they prohibit discrimination on the ground of handicap in...

18 CFR 1307.13 - Effect on other regulations; supervision and coordination.

Code of Federal Regulations, 2011 CFR

2011-04-01

... TENNESSEE VALLEY AUTHORITY NONDISCRIMINATION WITH RESPECT TO HANDICAP § 1307.13 Effect on other regulations... other regulations or instructions, insofar as they prohibit discrimination on the ground of handicap in...

A Lyapunov-based Approach for Time-Coordinated 3D Path-Following of Multiple Quadrotors in SO(3)

DTIC Science & Technology

2012-12-10

January 2006. [22] T. Lee, “ Robust adaptive geometric tracking controls on so(3) with an application to the attitude dynamicsof a quadrotor uav,” 2011...in the presence of time-varying communication networks and spatial and temporal constraints. The objective is to enable n Quadrotors to track prede?ned...developing control laws to solve the Time-Coordinated 3D Path-Following task for multiple Quadrotor UAVs in the presence of time-varying communication

75 FR 55947 - Coordinated Communications

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-15

...The Federal Election Commission is revising its regulations regarding coordinated communications. The Commission is issuing these rules and offering a more complete explanation and justification for parts of the existing rules to comply with the decision of the Court of Appeals for the District of Columbia Circuit in Shays v. FEC and to address other issues involving the coordinated communications rules.

33 CFR 100.717 - Annual Fort Myers Beach Offshore Grand Prix; Fort Myers, FL.

Code of Federal Regulations, 2011 CFR

2011-07-01

...°58.30′ W). All coordinates referenced use datum: NAD 83. (b) Special local regulations. (1) No vessel... coordinates referenced use datum: NAD 83. (3) All vessel traffic, not involved with the Fort Myers Beach... clear of the racecourse. All coordinates referenced use datum: NAD 83. (4) All vessel traffic, not...

45 CFR 607.7 - Coordinating offset with another Federal agency.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 3 2010-10-01 2010-10-01 false Coordinating offset with another Federal agency. 607.7 Section 607.7 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION SALARY OFFSET § 607.7 Coordinating offset with another Federal agency. (a) When the NSF is the creditor agency and the Chief Financial...

45 CFR 607.7 - Coordinating offset with another Federal agency.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 3 2011-10-01 2011-10-01 false Coordinating offset with another Federal agency. 607.7 Section 607.7 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION SALARY OFFSET § 607.7 Coordinating offset with another Federal agency. (a) When the NSF is the creditor agency and the Chief Financial...

33 CFR 100.717 - Annual Fort Myers Beach Offshore Grand Prix; Fort Myers, FL.

Code of Federal Regulations, 2010 CFR

2010-07-01

...°58.30′ W). All coordinates referenced use datum: NAD 83. (b) Special local regulations. (1) No vessel... coordinates referenced use datum: NAD 83. (3) All vessel traffic, not involved with the Fort Myers Beach... clear of the racecourse. All coordinates referenced use datum: NAD 83. (4) All vessel traffic, not...

33 CFR 100.717 - Annual Fort Myers Beach Offshore Grand Prix; Fort Myers, FL.

Code of Federal Regulations, 2013 CFR

2013-07-01

...°58.30′ W). All coordinates referenced use datum: NAD 83. (b) Special local regulations. (1) No vessel... coordinates referenced use datum: NAD 83. (3) All vessel traffic, not involved with the Fort Myers Beach... clear of the racecourse. All coordinates referenced use datum: NAD 83. (4) All vessel traffic, not...

33 CFR 100.717 - Annual Fort Myers Beach Offshore Grand Prix; Fort Myers, FL.

Code of Federal Regulations, 2014 CFR

2014-07-01

...°58.30′ W). All coordinates referenced use datum: NAD 83. (b) Special local regulations. (1) No vessel... coordinates referenced use datum: NAD 83. (3) All vessel traffic, not involved with the Fort Myers Beach... clear of the racecourse. All coordinates referenced use datum: NAD 83. (4) All vessel traffic, not...

33 CFR 100.717 - Annual Fort Myers Beach Offshore Grand Prix; Fort Myers, FL.

Code of Federal Regulations, 2012 CFR

2012-07-01

...°58.30′ W). All coordinates referenced use datum: NAD 83. (b) Special local regulations. (1) No vessel... coordinates referenced use datum: NAD 83. (3) All vessel traffic, not involved with the Fort Myers Beach... clear of the racecourse. All coordinates referenced use datum: NAD 83. (4) All vessel traffic, not...

Strike-parallel and strike-normal coordinate system around geometrically complicated rupture traces: use by NGA-West2 and further improvements

USGS Publications Warehouse

Spudich, Paul A.; Chiou, Brian

2015-01-01

We present a two-dimensional system of generalized coordinates for use with geometrically complex fault ruptures that are neither straight nor continuous. The coordinates are a generalization of the conventional strike-normal and strike-parallel coordinates of a single straight fault. The presented conventions and formulations are applicable to a single curved trace, as well as multiple traces representing the rupture of branching faults or noncontiguous faults. An early application of our generalized system is in the second round of the Next Generation of Ground-Motion Attenuation Model project for the Western United States (NGA-West2), where they were used in the characterization of the hanging-wall effects. We further improve the NGA-West2 strike-parallel formulation for multiple rupture traces with a more intuitive definition of the nominal strike direction. We also derive an analytical expression for the gradient of the generalized strike-normal coordinate. The direction of this gradient may be used as the strike-normal direction in the study of polarization effects on ground motions.

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 active site structure of tetanus neurotoxin resolved by multiple scattering analysis in X-Ray absorption spectroscopy.

PubMed Central

Meneghini, C; Morante, S

1998-01-01

A detailed study of the x-ray absorption spectrum of tetanus neurotoxin in the K-edge EXAFS region of the zinc absorber is presented that allows the complete identification of the amino acid residues coordinated to the zinc active site. A very satisfactory interpretation of the experimental data can be given if multiple scattering contributions are included in the analysis. Comparing the absorption spectrum of tetanus neurotoxin to that of two other structurally similar zinc-endopeptidases, thermolysin and astacin, in which the zinc coordination mode is known from crystallographic data, we conclude that in tetanus neurotoxin, besides a water molecule, zinc is coordinated to two histidines and a tyrosine. PMID:9746536

Neural-adaptive control of single-master-multiple-slaves teleoperation for coordinated multiple mobile manipulators with time-varying communication delays and input uncertainties.

PubMed

Li, Zhijun; Su, Chun-Yi

2013-09-01

In this paper, adaptive neural network control is investigated for single-master-multiple-slaves teleoperation in consideration of time delays and input dead-zone uncertainties for multiple mobile manipulators carrying a common object in a cooperative manner. Firstly, concise dynamics of teleoperation systems consisting of a single master robot, multiple coordinated slave robots, and the object are developed in the task space. To handle asymmetric time-varying delays in communication channels and unknown asymmetric input dead zones, the nonlinear dynamics of the teleoperation system are transformed into two subsystems through feedback linearization: local master or slave dynamics including the unknown input dead zones and delayed dynamics for the purpose of synchronization. Then, a model reference neural network control strategy based on linear matrix inequalities (LMI) and adaptive techniques is proposed. The developed control approach ensures that the defined tracking errors converge to zero whereas the coordination internal force errors remain bounded and can be made arbitrarily small. Throughout this paper, stability analysis is performed via explicit Lyapunov techniques under specific LMI conditions. The proposed adaptive neural network control scheme is robust against motion disturbances, parametric uncertainties, time-varying delays, and input dead zones, which is validated by simulation studies.

The multiple-function multi-input/multi-output digital controller system for the AFW wind-tunnel model

NASA Technical Reports Server (NTRS)

Hoadley, Sherwood T.; Mcgraw, Sandra M.

1992-01-01

A real time multiple-function digital controller system was developed for the Active Flexible Wing (AFW) Program. The digital controller system (DCS) allowed simultaneous execution of two control laws: flutter suppression and either roll trim or a rolling maneuver load control. The DCS operated within, but independently of, a slower host operating system environment, at regulated speeds up to 200 Hz. It also coordinated the acquisition, storage, and transfer of data for near real time controller performance evaluation and both open- and closed-loop plant estimation. It synchronized the operation of four different processing units, allowing flexibility in the number, form, functionality, and order of control laws, and variability in the selection of the sensors and actuators employed. Most importantly, the DCS allowed for the successful demonstration of active flutter suppression to conditions approximately 26 percent (in dynamic pressure) above the open-loop boundary in cases when the model was fixed in roll and up to 23 percent when it was free to roll. Aggressive roll maneuvers with load control were achieved above the flutter boundary. The purpose here is to present the development, validation, and wind tunnel testing of this multiple-function digital controller system.

Motion and force control of multiple robotic manipulators

NASA Technical Reports Server (NTRS)

Wen, John T.; Kreutz-Delgado, Kenneth

1992-01-01

This paper addresses the motion and force control problem of multiple robot arms manipulating a cooperatively held object. A general control paradigm is introduced which decouples the motion and force control problems. For motion control, different control strategies are constructed based on the variables used as the control input in the controller design. There are three natural choices; acceleration of a generalized coordinate, arm tip force vectors, and the joint torques. The first two choices require full model information but produce simple models for the control design problem. The last choice results in a class of relatively model independent control laws by exploiting the Hamiltonian structure of the open loop system. The motion control only determines the joint torque to within a manifold, due to the multiple-arm kinematic constraint. To resolve the nonuniqueness of the joint torques, two methods are introduced. If the arm and object models are available, an optimization can be performed to best allocate the desired and effector control force to the joint actuators. The other possibility is to control the internal force about some set point. It is shown that effective force regulation can be achieved even if little model information is available.

Multiple Sensor Platform Coordination Using Stigmergy

DTIC Science & Technology

1998-03-01

French biologist P.P. Grass`e in 1959 while studying nest building of termites . He observed that indirect coordination among termites was accomplished...through sensing and modification of their environment. The chemicals secreted by each termite during nest building affected the building actions of...neighboring termites , resulting in a coordinated building strategy. Stigmergy is not limited to termites . Some species of ants use stigmergy for trail

Dynamic infrared imaging analysis of apical hook development in Arabidopsis: the case of brassinosteroids.

PubMed

Smet, Dajo; Žádníková, Petra; Vandenbussche, Filip; Benková, Eva; Van Der Straeten, Dominique

2014-06-01

Germination of Arabidopsis seeds in darkness induces apical hook development, based on a tightly regulated differential growth coordinated by a multiple hormone cross-talk. Here, we endeavoured to clarify the function of brassinosteroids (BRs) and cross-talk with ethylene in hook development. An automated infrared imaging system was developed to study the kinetics of hook development in etiolated Arabidopsis seedlings. To ascertain the photomorphogenic control of hook opening, the system was equipped with an automatic light dimmer. We demonstrate that ethylene and BRs are indispensable for hook formation and maintenance. Ethylene regulation of hook formation functions partly through BRs, with BR feedback inhibition of ethylene action. Conversely, BR-mediated extension of hook maintenance functions partly through ethylene. Furthermore, we revealed that a short light pulse is sufficient to induce rapid hook opening. Our dynamic infrared imaging system allows high-resolution, kinetic imaging of up to 112 seedlings in a single experimental run. At this high throughput, it is ideally suited to rapidly gain insight in pathway networks. We demonstrate that BRs and ethylene cooperatively regulate apical hook development in a phase-dependent manner. Furthermore, we show that light is a predominant regulator of hook opening, inhibiting ethylene- and BR-mediated postponement of hook opening. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

The role of a vertical reference point in changing gait regulation in cricket run-ups.

PubMed

Greenwood, Daniel; Davids, Keith; Renshaw, Ian

2016-10-01

The need to identify information sources which facilitate a functional coupling of perception and action in representative practice contexts is an important challenge for sport scientists and coaches. The current study investigated the role of visual information in regulating athlete gait behaviours during a locomotor pointing task in cricket. Integration of experiential knowledge of elite coaches and theoretical understanding from previous empirical research led us to investigate whether the presence of an umpire would act as a vertical informational constraint that could constrain the emergent coordination tendencies of cricket bowlers' run-up patterns. To test this idea, umpire presence was manipulated during run-ups of 10 elite medium-fast bowlers. As hypothesised, removal of the umpire from the performance environment did not result in an inability to regulate gait to intercept a target, however, the absence of this informational constraint resulted in the emergence of different movement patterns in participant run-ups. Significantly lower standard deviation values of heel-to-crease distances were observed in the umpire condition at multiple steps, compared to performance in the no-umpire condition. Manipulation of this informational constraint altered gait regulation of participants, offering a mechanism to understand how perception-action couplings can be varied during performance in locomotor pointing tasks in sport.

The POU Transcription Factor Oct-1 Represses Virus-Induced Interferon A Gene Expression

PubMed Central

Mesplède, Thibault; Island, Marie-Laure; Christeff, Nicolas; Petek, Fahrettin; Doly, Janine; Navarro, Sébastien

2005-01-01

Alpha interferon (IFN-α) and IFN-β are able to interfere with viral infection. They exert a vast array of biologic functions, including growth arrest, cell differentiation, and immune system regulation. This regulation extends from innate immunity to cellular and humoral adaptive immune responses. A strict control of expression is needed to prevent detrimental effects of unregulated IFN. Multiple IFN-A subtypes are coordinately induced in human and mouse cells infected by virus and exhibit differences in expression of their individual mRNAs. We demonstrated that the weakly expressed IFN-A11 gene is negatively regulated after viral infection, due to a distal negative regulatory element, binding homeoprotein pituitary homeobox 1 (Pitx1). Here we show that the POU protein Oct-1 binds in vitro and in vivo to the IFN-A11 promoter and represses IFN-A expression upon interferon regulatory factor overexpression. Furthermore, we show that Oct-1-deficient MEFs exhibit increased in vivo IFN-A gene expression and increased antiviral activity. Finally, the IFN-A expression pattern is modified in Oct-1-deficient MEFs. The broad representation of effective and potent octamer-like sequences within IFN-A promoters suggests an important role for Oct-1 in IFN-A regulation. PMID:16166650

Effects of walking speed on asymmetry and bilateral coordination of gait

PubMed Central

Plotnik, Meir; Bartsch, Ronny P.; Zeev, Aviva; Giladi, Nir; Hausdorff, Jeffery M.

2013-01-01

The mechanisms regulating the bilateral coordination of gait in humans are largely unknown. Our objective was to study how bilateral coordination changes as a result of gait speed modifications during over ground walking. 15 young adults wore force sensitive insoles that measured vertical forces used to determine the timing of the gait cycle events under three walking conditions (i.e., usual-walking, fast and slow). Ground reaction force impact (GRFI) associated with heel-strikes was also quantified, representing the potential contribution of sensory feedback to the regulation of gait. Gait asymmetry (GA) was quantified based on the differences between right and left swing times and the bilateral coordination of gait was assessed using the phase coordination index (PCI), a metric that quantifies the consistency and accuracy of the anti-phase stepping pattern. GA was preserved in the three different gait speeds. PCI was higher (reduced coordination) in the slow gait condition, compared to usual-walking (3.51% vs. 2.47%, respectively, p=0.002), but was not significantly affected in the fast condition. GRFI values were lower in the slow walking as compared to usual-walking and higher in the fast walking condition (p<0.001). Stepwise regression revealed that slowed gait related changes in PCI were not associated with the slowed gait related changes in GRFI. The present findings suggest that left-right anti-phase stepping is similar in normal and fast walking, but altered during slowed walking. This behavior might reflect a relative increase in attention resources required to regulate a slow gait speed, consistent with the possibility that cortical function and supraspinal input influences the bilateral coordination of gait. PMID:23680424

Genomic Pangea: coordinate gene regulation and cell-specific chromosomal topologies.

PubMed

Laster, Kyle; Kosak, Steven T

2010-06-01

The eukaryotic nucleus is functionally organized. Gene loci, for example, often reveal altered localization patterns according to their developmental regulation. Whole chromosomes also demonstrate non-random nuclear positions, correlated with inherent characteristics such as gene density or size. Given that hundreds to thousands of genes are coordinately regulated in any given cell type, interest has grown in whether chromosomes may be specifically localized according to gene regulation. A synthesis of the evidence for preferential chromosomal organization suggests that, beyond basic characteristics, chromosomes can assume positions functionally related to gene expression. Moreover, analysis of total chromosome organization during cellular differentiation indicates that unique chromosome topologies, albeit probabilistic, in effect define a cell lineage. Future work with new techniques, including the advanced forms of the chromosome conformation capture (3C), and the development of next-generation whole-genome imaging approaches, will help to refine our view of chromosomal organization. We suggest that genomic organization during cellular differentiation should be viewed as a dynamic process, with gene expression patterns leading to chromosome associations that feed back on themselves, leading to the self-organization of the genome according to coordinate gene regulation. Copyright 2010 Elsevier Ltd. All rights reserved.

Coordinated Science Campaign Scheduling for Sensor Webs

NASA Technical Reports Server (NTRS)

Edgington, Will; Morris, Robert; Dungan, Jennifer; Williams, Jenny; Carlson, Jean; Fleming, Damian; Wood, Terri; Yorke-Smith, Neil

2005-01-01

Future Earth observing missions will study different aspects and interacting pieces of the Earth's eco-system. Scientists are designing increasingly complex, interdisciplinary campaigns to exploit the diverse capabilities of multiple Earth sensing assets. In addition, spacecraft platforms are being configured into clusters, trains, or other distributed organizations in order to improve either the quality or the coverage of observations. These simultaneous advances in the design of science campaigns and in the missions that will provide the sensing resources to support them offer new challenges in the coordination of data and operations that are not addressed by current practice. For example, the scheduling of scientific observations for satellites in low Earth orbit is currently conducted independently by each mission operations center. An absence of an information infrastructure to enable the scheduling of coordinated observations involving multiple sensors makes it difficult to execute campaigns involving multiple assets. This paper proposes a software architecture and describes a prototype system called DESOPS (Distributed Earth Science Observation Planning and Scheduling) that will address this deficiency.

Arabidopsis CRY2 and ZTL mediate blue-light regulation of the transcription factor CIB1 by distinct mechanisms

PubMed Central

Liu, Hongtao; Wang, Qin; Liu, Yawen; Zhao, Xiaoying; Imaizumi, Takato; Somers, David E.; Tobin, Elaine M.; Lin, Chentao

2013-01-01

Plants possess multiple photoreceptors to mediate light regulation of growth and development, but it is not well understood how different photoreceptors coordinate their actions to jointly regulate developmental responses, such as flowering time. In Arabidopsis, the photoexcited cryptochrome 2 interacts with the transcription factor CRYPTOCHROME-INTERACTING basic helix–loop–helix 1 (CIB1) to activate transcription and floral initiation. We show that the CIB1 protein expression is regulated by blue light; CIB1 is highly expressed in plants exposed to blue light, but levels of the CIB1 protein decreases in the absence of blue light. We demonstrate that CIB1 is degraded by the 26S proteasome and that blue light suppresses CIB1 degradation. Surprisingly, although cryptochrome 2 physically interacts with CIB1 in response to blue light, it is not the photoreceptor mediating blue-light suppression of CIB1 degradation. Instead, two of the three light–oxygen–voltage (LOV)-domain photoreceptors, ZEITLUPE and LOV KELCH PROTEIN 2, but not FLAVIN-BINDING KELCH REPEAT 1, are required for the function and blue-light suppression of degradation of CIB1. These results support the hypothesis that the evolutionarily unrelated blue-light receptors, cryptochrome and LOV-domain F-box proteins, mediate blue-light regulation of the same transcription factor by distinct mechanisms. PMID:24101505

Multiple roles for the actin cytoskeleton during regulated exocytosis

PubMed Central

Porat-Shliom, Natalie; Milberg, Oleg; Masedunskas, Andrius; Weigert, Roberto

2014-01-01

Regulated exocytosis is the main mechanism utilized by specialized secretory cells to deliver molecules to the cell surface by virtue of membranous containers (i.e. secretory vesicles). The process involves a series of highly coordinated and sequential steps, which include the biogenesis of the vesicles, their delivery to the cell periphery, their fusion with the plasma membrane and the release of their content into the extracellular space. Each of these steps is regulated by the actin cytoskeleton. In this review, we summarize the current knowledge regarding the involvement of actin and its associated molecules during each of the exocytic steps in vertebrates, and suggest that the overall role of the actin cytoskeleton during regulated exocytosis is linked to the architecture and the physiology of the secretory cells under examination. Specifically, in neurons, neuroendocrine, endocrine, and hematopoietic cells, which contain small secretory vesicles that undergo rapid exocytosis (on the order of milliseconds), the actin cytoskeleton plays a role in pre-fusion events, where it acts primarily as a functional barrier and facilitates docking. In exocrine and other secretory cells, which contain large secretory vesicles that undergo slow exocytosis (seconds to minutes), the actin cytoskeleton plays a role in post-fusion events, where it regulates the dynamics of the fusion pore, facilitates the integration of the vesicles into the plasma membrane, provides structural support, and promotes the expulsion of large cargo molecules. PMID:22986507

The ASYMMETRIC LEAVES Complex Employs Multiple Modes of Regulation to Affect Adaxial-Abaxial Patterning and Leaf Complexity[OPEN

PubMed Central

Husbands, Aman Y.; Benkovics, Anna H.; Nogueira, Fabio T.S.; Lodha, Mukesh; Timmermans, Marja C.P.

2015-01-01

Flattened leaf architecture is not a default state but depends on positional information to precisely coordinate patterns of cell division in the growing primordium. This information is provided, in part, by the boundary between the adaxial (top) and abaxial (bottom) domains of the leaf, which are specified via an intricate gene regulatory network whose precise circuitry remains poorly defined. Here, we examined the contribution of the ASYMMETRIC LEAVES (AS) pathway to adaxial-abaxial patterning in Arabidopsis thaliana and demonstrate that AS1-AS2 affects this process via multiple, distinct regulatory mechanisms. AS1-AS2 uses Polycomb-dependent and -independent mechanisms to directly repress the abaxial determinants MIR166A, YABBY5, and AUXIN RESPONSE FACTOR3 (ARF3), as well as a nonrepressive mechanism in the regulation of the adaxial determinant TAS3A. These regulatory interactions, together with data from prior studies, lead to a model in which the sequential polarization of determinants, including AS1-AS2, explains the establishment and maintenance of adaxial-abaxial leaf polarity. Moreover, our analyses show that the shared repression of ARF3 by the AS and trans-acting small interfering RNA (ta-siRNA) pathways intersects with additional AS1-AS2 targets to affect multiple nodes in leaf development, impacting polarity as well as leaf complexity. These data illustrate the surprisingly multifaceted contribution of AS1-AS2 to leaf development showing that, in conjunction with the ta-siRNA pathway, AS1-AS2 keeps the Arabidopsis leaf both flat and simple. PMID:26589551

Movement coordination patterns between the foot joints during walking.

PubMed

Arnold, John B; Caravaggi, Paolo; Fraysse, François; Thewlis, Dominic; Leardini, Alberto

2017-01-01

In 3D gait analysis, kinematics of the foot joints are usually reported via isolated time histories of joint rotations and no information is provided on the relationship between rotations at different joints. The aim of this study was to identify movement coordination patterns in the foot during walking by expanding an existing vector coding technique according to an established multi-segment foot and ankle model. A graphical representation is also described to summarise the coordination patterns of joint rotations across multiple patients. Three-dimensional multi-segment foot kinematics were recorded in 13 adults during walking. A modified vector coding technique was used to identify coordination patterns between foot joints involving calcaneus, midfoot, metatarsus and hallux segments. According to the type and direction of joints rotations, these were classified as in-phase (same direction), anti-phase (opposite directions), proximal or distal joint dominant. In early stance, 51 to 75% of walking trials showed proximal-phase coordination between foot joints comprising the calcaneus, midfoot and metatarsus. In-phase coordination was more prominent in late stance, reflecting synergy in the simultaneous inversion occurring at multiple foot joints. Conversely, a distal-phase coordination pattern was identified for sagittal plane motion of the ankle relative to the midtarsal joint, highlighting the critical role of arch shortening to locomotor function in push-off. This study has identified coordination patterns between movement of the calcaneus, midfoot, metatarsus and hallux by expanding an existing vector cording technique for assessing and classifying coordination patterns of foot joints rotations during walking. This approach provides a different perspective in the analysis of multi-segment foot kinematics, and may be used for the objective quantification of the alterations in foot joint coordination patterns due to lower limb pathologies or following injuries.

Tools for Coordinated Planning Between Observatories

NASA Technical Reports Server (NTRS)

Jones, Jeremy; Fishman, Mark; Grella, Vince; Kerbel, Uri; Maks, Lori; Misra, Dharitri; Pell, Vince; Powers, Edward I. (Technical Monitor)

2001-01-01

With the realization of NASA's era of great observatories, there are now more than three space-based telescopes operating in different wavebands. This situation provides astronomers with a unique opportunity to simultaneously observe with multiple observatories. Yet scheduling multiple observatories simultaneously is highly inefficient when compared to observations using only one single observatory. Thus, programs using multiple observatories are limited not due to scientific restrictions, but due to operational inefficiencies. At present, multi-observatory programs are conducted by submitting observing proposals separately to each concerned observatory. To assure that the proposed observations can be scheduled, each observatory's staff has to check that the observations are valid and meet all the constraints for their own observatory; in addition, they have to verify that the observations satisfy the constraints of the other observatories. Thus, coordinated observations require painstaking manual collaboration among the observatory staff at each observatory. Due to the lack of automated tools for coordinated observations, this process is time consuming, error-prone, and the outcome of the requests is not certain until the very end. To increase observatory operations efficiency, such manpower intensive processes need to undergo re-engineering. To overcome this critical deficiency, Goddard Space Flight Center's Advanced Architectures and Automation Branch is developing a prototype effort called the Visual Observation Layout Tool (VOLT). The main objective of the VOLT project is to provide visual tools to help automate the planning of coordinated observations by multiple astronomical observatories, as well as to increase the scheduling probability of all observations.

TEOSINTE BRANCHED1 Regulates Inflorescence Architecture and Development in Bread Wheat (Triticum aestivum)[OPEN

PubMed Central

Greenwood, Julian R.; Bencivenga, Stefano; Cockram, James; Cavanagh, Colin; Swain, Steve M.

2018-01-01

The flowers of major cereals are arranged on reproductive branches known as spikelets, which group together to form an inflorescence. Diversity for inflorescence architecture has been exploited during domestication to increase crop yields, and genetic variation for this trait has potential to further boost grain production. Multiple genes that regulate inflorescence architecture have been identified by studying alleles that modify gene activity or dosage; however, little is known in wheat. Here, we show TEOSINTE BRANCHED1 (TB1) regulates inflorescence architecture in bread wheat (Triticum aestivum) by investigating lines that display a form of inflorescence branching known as “paired spikelets.” We show that TB1 interacts with FLOWERING LOCUS T1 and that increased dosage of TB1 alters inflorescence architecture and growth rate in a process that includes reduced expression of meristem identity genes, with allelic diversity for TB1 found to associate genetically with paired spikelet development in modern cultivars. We propose TB1 coordinates formation of axillary spikelets during the vegetative to floral transition and that alleles known to modify dosage or function of TB1 could help increase wheat yields. PMID:29444813

GSK3-mediated raptor phosphorylation supports amino-acid-dependent mTORC1-directed signalling

PubMed Central

Stretton, Clare; Hoffmann, Thorsten M.; Munson, Michael J.; Prescott, Alan; Taylor, Peter M.; Ganley, Ian G.; Hundal, Harinder S.

2015-01-01

The mammalian or mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) is a ubiquitously expressed multimeric protein kinase complex that integrates nutrient and growth factor signals for the co-ordinated regulation of cellular metabolism and cell growth. Herein, we demonstrate that suppressing the cellular activity of glycogen synthase kinase-3 (GSK3), by use of pharmacological inhibitors or shRNA-mediated gene silencing, results in substantial reduction in amino acid (AA)-regulated mTORC1-directed signalling, as assessed by phosphorylation of multiple downstream mTORC1 targets. We show that GSK3 regulates mTORC1 activity through its ability to phosphorylate the mTOR-associated scaffold protein raptor (regulatory-associated protein of mTOR) on Ser859. We further demonstrate that either GSK3 inhibition or expression of a S859A mutated raptor leads to reduced interaction between mTOR and raptor and under these circumstances, irrespective of AA availability, there is a consequential loss in phosphorylation of mTOR substrates, such as p70S6K1 (ribosomal S6 kinase 1) and uncoordinated-51-like kinase (ULK1), which results in increased autophagic flux and reduced cellular proliferation. PMID:26348909

Cryptococcal titan cell formation is regulated by G-protein signaling in response to multiple stimuli.

PubMed

Okagaki, Laura H; Wang, Yina; Ballou, Elizabeth R; O'Meara, Teresa R; Bahn, Yong-Sun; Alspaugh, J Andrew; Xue, Chaoyang; Nielsen, Kirsten

2011-10-01

The titan cell is a recently described morphological form of the pathogenic fungus Cryptococcus neoformans. Occurring during the earliest stages of lung infection, titan cells are 5 to 10 times larger than the normal yeast-like cells, thereby resisting engulfment by lung phagocytes and favoring the persistence of infection. These enlarged cells exhibit an altered capsule structure, a thickened cell wall, increased ploidy, and resistance to nitrosative and oxidative stresses. We demonstrate that two G-protein-coupled receptors are important for induction of the titan cell phenotype: the Ste3a pheromone receptor (in mating type a cells) and the Gpr5 protein. Both receptors control titan cell formation through elements of the cyclic AMP (cAMP)/protein kinase A (PKA) pathway. This conserved signaling pathway, in turn, mediates its effect on titan cells through the PKA-regulated Rim101 transcription factor. Additional downstream effectors required for titan cell formation include the G(1) cyclin Pcl103, the Rho104 GTPase, and two GTPase-activating proteins, Gap1 and Cnc1560. These observations support developing models in which the PKA signaling pathway coordinately regulates many virulence-associated phenotypes in diverse human pathogens.

Cryptococcal Titan Cell Formation Is Regulated by G-Protein Signaling in Response to Multiple Stimuli▿†

PubMed Central

Okagaki, Laura H.; Wang, Yina; Ballou, Elizabeth R.; O'Meara, Teresa R.; Bahn, Yong-Sun; Alspaugh, J. Andrew; Xue, Chaoyang; Nielsen, Kirsten

2011-01-01

The titan cell is a recently described morphological form of the pathogenic fungus Cryptococcus neoformans. Occurring during the earliest stages of lung infection, titan cells are 5 to 10 times larger than the normal yeast-like cells, thereby resisting engulfment by lung phagocytes and favoring the persistence of infection. These enlarged cells exhibit an altered capsule structure, a thickened cell wall, increased ploidy, and resistance to nitrosative and oxidative stresses. We demonstrate that two G-protein-coupled receptors are important for induction of the titan cell phenotype: the Ste3a pheromone receptor (in mating type a cells) and the Gpr5 protein. Both receptors control titan cell formation through elements of the cyclic AMP (cAMP)/protein kinase A (PKA) pathway. This conserved signaling pathway, in turn, mediates its effect on titan cells through the PKA-regulated Rim101 transcription factor. Additional downstream effectors required for titan cell formation include the G1 cyclin Pcl103, the Rho104 GTPase, and two GTPase-activating proteins, Gap1 and Cnc1560. These observations support developing models in which the PKA signaling pathway coordinately regulates many virulence-associated phenotypes in diverse human pathogens. PMID:21821718

TEOSINTE BRANCHED1 Regulates Inflorescence Architecture and Development in Bread Wheat (Triticum aestivum).

PubMed

Dixon, Laura E; Greenwood, Julian R; Bencivenga, Stefano; Zhang, Peng; Cockram, James; Mellers, Gregory; Ramm, Kerrie; Cavanagh, Colin; Swain, Steve M; Boden, Scott A

2018-03-01

The flowers of major cereals are arranged on reproductive branches known as spikelets, which group together to form an inflorescence. Diversity for inflorescence architecture has been exploited during domestication to increase crop yields, and genetic variation for this trait has potential to further boost grain production. Multiple genes that regulate inflorescence architecture have been identified by studying alleles that modify gene activity or dosage; however, little is known in wheat. Here, we show TEOSINTE BRANCHED1 ( TB1 ) regulates inflorescence architecture in bread wheat ( Triticum aestivum ) by investigating lines that display a form of inflorescence branching known as "paired spikelets." We show that TB1 interacts with FLOWERING LOCUS T1 and that increased dosage of TB1 alters inflorescence architecture and growth rate in a process that includes reduced expression of meristem identity genes, with allelic diversity for TB1 found to associate genetically with paired spikelet development in modern cultivars. We propose TB1 coordinates formation of axillary spikelets during the vegetative to floral transition and that alleles known to modify dosage or function of TB1 could help increase wheat yields. © 2018 American Society of Plant Biologists. All rights reserved.

Motor Force Homeostasis in Skeletal Muscle Contraction

PubMed Central

Chen, Bin; Gao, Huajian

2011-01-01

In active biological contractile processes such as skeletal muscle contraction, cellular mitosis, and neuronal growth, an interesting common observation is that multiple motors can perform coordinated and synchronous actions, whereas individual myosin motors appear to randomly attach to and detach from actin filaments. Recent experiment has demonstrated that, during skeletal muscle shortening at a wide range of velocities, individual myosin motors maintain a force of ∼6 pN during a working stroke. To understand how such force-homeostasis can be so precisely regulated in an apparently chaotic system, here we develop a molecular model within a coupled stochastic-elastic theoretical framework. The model reveals that the unique force-stretch relation of myosin motor and the stochastic behavior of actin-myosin binding cause the average number of working motors to increase in linear proportion to the filament load, so that the force on each working motor is regulated at ∼6 pN, in excellent agreement with experiment. This study suggests that it might be a general principle to use catch bonds together with a force-stretch relation similar to that of myosin motors to regulate force homeostasis in many biological processes. PMID:21767492

Structural basis for regulation of rhizobial nodulation and symbiosis gene expression by the regulatory protein NolR.

PubMed

Lee, Soon Goo; Krishnan, Hari B; Jez, Joseph M

2014-04-29

The symbiosis between rhizobial microbes and host plants involves the coordinated expression of multiple genes, which leads to nodule formation and nitrogen fixation. As part of the transcriptional machinery for nodulation and symbiosis across a range of Rhizobium, NolR serves as a global regulatory protein. Here, we present the X-ray crystal structures of NolR in the unliganded form and complexed with two different 22-base pair (bp) double-stranded operator sequences (oligos AT and AA). Structural and biochemical analysis of NolR reveals protein-DNA interactions with an asymmetric operator site and defines a mechanism for conformational switching of a key residue (Gln56) to accommodate variation in target DNA sequences from diverse rhizobial genes for nodulation and symbiosis. This conformational switching alters the energetic contributions to DNA binding without changes in affinity for the target sequence. Two possible models for the role of NolR in the regulation of different nodulation and symbiosis genes are proposed. To our knowledge, these studies provide the first structural insight on the regulation of genes involved in the agriculturally and ecologically important symbiosis of microbes and plants that leads to nodule formation and nitrogen fixation.

Abscisic Acid–Responsive Guard Cell Metabolomes of Arabidopsis Wild-Type and gpa1 G-Protein Mutants[C][W

PubMed Central

Jin, Xiaofen; Wang, Rui-Sheng; Zhu, Mengmeng; Jeon, Byeong Wook; Albert, Reka; Chen, Sixue; Assmann, Sarah M.

2013-01-01

Individual metabolites have been implicated in abscisic acid (ABA) signaling in guard cells, but a metabolite profile of this specialized cell type is lacking. We used liquid chromatography–multiple reaction monitoring mass spectrometry for targeted analysis of 85 signaling-related metabolites in Arabidopsis thaliana guard cell protoplasts over a time course of ABA treatment. The analysis utilized ∼350 million guard cell protoplasts from ∼30,000 plants of the Arabidopsis Columbia accession (Col) wild type and the heterotrimeric G-protein α subunit mutant, gpa1, which has ABA-hyposensitive stomata. These metabolomes revealed coordinated regulation of signaling metabolites in unrelated biochemical pathways. Metabolites clustered into different temporal modules in Col versus gpa1, with fewer metabolites showing ABA-altered profiles in gpa1. Ca2+-mobilizing agents sphingosine-1-phosphate and cyclic adenosine diphosphate ribose exhibited weaker ABA-stimulated increases in gpa1. Hormone metabolites were responsive to ABA, with generally greater responsiveness in Col than in gpa1. Most hormones also showed different ABA responses in guard cell versus mesophyll cell metabolomes. These findings suggest that ABA functions upstream to regulate other hormones, and are also consistent with G proteins modulating multiple hormonal signaling pathways. In particular, indole-3-acetic acid levels declined after ABA treatment in Col but not gpa1 guard cells. Consistent with this observation, the auxin antagonist α-(phenyl ethyl-2-one)-indole-3-acetic acid enhanced ABA-regulated stomatal movement and restored partial ABA sensitivity to gpa1. PMID:24368793

Structural and Biochemical Insights into the Multiple Functions of Yeast Grx3.

PubMed

Chi, Chang-Biao; Tang, YaJun; Zhang, Jiahai; Dai, Ya-Nan; Abdalla, Mohnad; Chen, Yuxing; Zhou, Cong-Zhao

2018-04-13

The yeast Saccharomyces cerevisiae monothiol glutaredoxin Grx3 plays a key role in cellular defense against oxidative stress and more importantly, cooperates with BolA-like iron repressor of activation protein Fra2 to regulate the localization of the iron-sensing transcription factor Aft2. The interplay among Grx3, Fra2 and Aft2 responsible for the regulation of iron homeostasis has not been clearly described. Here we solved the crystal structures of the Trx domain (Grx3 Trx ) and Grx domain (Grx3 Grx ) of Grx3 in addition to the solution structure of Fra2. Structural analyses and activity assays indicated that the Trx domain also contributes to the glutathione S-transferase activity of Grx3, via an inter-domain disulfide bond between Cys37 and Cys176. NMR titration and pull-down assays combined with surface plasmon resonance experiments revealed that Fra2 could form a noncovalent heterodimer with Grx3 via an interface between the helix-turn-helix motif of Fra2 and the C-terminal segment of Grx3 Grx , different from the previously identified covalent heterodimer mediated by Fe-S cluster. Comparative affinity assays indicated that the interaction between Fra2 and Aft2 is much stronger than that between Grx3 and Aft2, or Aft2 toward its target DNA. These structural and biochemical analyses enabled us to propose a model how Grx3 executes multiple functions to coordinate the regulation of Aft2-controlled iron metabolism. Copyright © 2018 Elsevier Ltd. All rights reserved.

Introduction to special issue: Self-regulation of appetite-it's complicated.

PubMed

Young-Hyman, Deborah

2017-03-01

A meeting of multidisciplinary biobehavioral scientists and National Institutes of Health (NIH) program staff was convened by the Office of Behavioral and Social Sciences Research, Division of Program Coordination, Planning, and Strategic Initiatives, Office of the Director, NIH to examine mechanisms associated with humans' ability to self-regulate appetite and appetitive behavior. Based upon prior discussions of the NIH Obesity Research Task Force Behavioral Phenotyping Work Group, the premise was adopted that, in modern society, multiple factors on multiple levels interact to create circumstances wherein self-control of appetite is difficult, leading to overconsumption of unhealthy foods versus healthy eating patterns, contributing to our current levels of obesity. Through presentations and group discussions, the panel examined how foundational processes/mechanisms directly and indirectly affect appetitive behavior and how these processes can be manipulated to affect food intake and thereby weight. The meeting identified evidence-based mechanisms with the potential to impact self-regulation of appetite and appetitive states (hunger, satiety, food wanting, restraint, reward) and associated behaviors such as overconsumption, eating in the absence of hunger, food seeking, and decision-making that could inform novel weight intervention strategies in free-living, nonlaboratory settings. The three summary papers contained in this issue represent the synthesis of the material presented at the meeting and the panel's recommendations on how existing evidence regarding mechanisms and pathways to appetitive behavior can be used to inform future research and novel prevention and intervention strategies to impact prevalence of obesity. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

7 CFR Exhibit K to Subpart G of... - Locations and Telephone Numbers of U.S. Fish and Wildlife Service's Wetland Coordinators

Code of Federal Regulations, 2013 CFR

2013-01-01

... Wildlife Service's Wetland Coordinators K Exhibit K to Subpart G of Part 1940 Agriculture Regulations of... Part 1940—Locations and Telephone Numbers of U.S. Fish and Wildlife Service's Wetland Coordinators The U.S. Fish and Wildlife Service (FWS) is presently preparing the National Wetlands Inventory. Each...

7 CFR Exhibit K to Subpart G of... - Locations and Telephone Numbers of U.S. Fish and Wildlife Service's Wetland Coordinators

Code of Federal Regulations, 2010 CFR

2010-01-01

... Wildlife Service's Wetland Coordinators K Exhibit K to Subpart G of Part 1940 Agriculture Regulations of... Part 1940—Locations and Telephone Numbers of U.S. Fish and Wildlife Service's Wetland Coordinators The U.S. Fish and Wildlife Service (FWS) is presently preparing the National Wetlands Inventory. Each...

7 CFR Exhibit K to Subpart G of... - Locations and Telephone Numbers of U.S. Fish and Wildlife Service's Wetland Coordinators

Code of Federal Regulations, 2012 CFR

2012-01-01

... Wildlife Service's Wetland Coordinators K Exhibit K to Subpart G of Part 1940 Agriculture Regulations of... Part 1940—Locations and Telephone Numbers of U.S. Fish and Wildlife Service's Wetland Coordinators The U.S. Fish and Wildlife Service (FWS) is presently preparing the National Wetlands Inventory. Each...

7 CFR Exhibit K to Subpart G of... - Locations and Telephone Numbers of U.S. Fish and Wildlife Service's Wetland Coordinators

Code of Federal Regulations, 2011 CFR

2011-01-01

... Wildlife Service's Wetland Coordinators K Exhibit K to Subpart G of Part 1940 Agriculture Regulations of... Part 1940—Locations and Telephone Numbers of U.S. Fish and Wildlife Service's Wetland Coordinators The U.S. Fish and Wildlife Service (FWS) is presently preparing the National Wetlands Inventory. Each...

7 CFR Exhibit K to Subpart G of... - Locations and Telephone Numbers of U.S. Fish and Wildlife Service's Wetland Coordinators

Code of Federal Regulations, 2014 CFR

2014-01-01

... Wildlife Service's Wetland Coordinators K Exhibit K to Subpart G of Part 1940 Agriculture Regulations of... Part 1940—Locations and Telephone Numbers of U.S. Fish and Wildlife Service's Wetland Coordinators The U.S. Fish and Wildlife Service (FWS) is presently preparing the National Wetlands Inventory. Each...

48 CFR 25.801 - General.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false General. 25.801 Section 25.801 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION SOCIOECONOMIC PROGRAMS FOREIGN ACQUISITION Other International Agreements and Coordination 25.801 General. Treaties and...

Coordinated neuronal activity enhances corticocortical communication

PubMed Central

Zandvakili, Amin; Kohn, Adam

2015-01-01

Summary Relaying neural signals between cortical areas is central to cognition and sensory processing. The temporal coordination of activity in a source population has been suggested to determine corticocortical signaling efficacy, but others have argued that coordination is functionally irrelevant. We reasoned that if coordination significantly influenced signaling, spiking in downstream networks should be preceded by transiently elevated coordination in a source population. We developed a metric to quantify network coordination in brief epochs, and applied it to simultaneous recordings of neuronal populations in cortical areas V1 and V2 of the macaque monkey. Spiking in the input layers of V2 was preceded by brief epochs of elevated V1 coordination, but this was not the case in other layers of V2. Our results indicate that V1 coordination influences its signaling to direct downstream targets, but that coordinated V1 epochs do not propagate through multiple downstream networks as in some corticocortical signaling schemes. PMID:26291164

Cell cycle-regulated PLEIADE/AtMAP65-3 links membrane and microtubule dynamics during plant cytokinesis.

PubMed

Steiner, Alexander; Rybak, Katarzyna; Altmann, Melina; McFarlane, Heather E; Klaeger, Susan; Nguyen, Ngoc; Facher, Eva; Ivakov, Alexander; Wanner, Gerhard; Kuster, Bernhard; Persson, Staffan; Braun, Pascal; Hauser, Marie-Theres; Assaad, Farhah F

2016-11-01

Cytokinesis, the partitioning of the cytoplasm following nuclear division, requires extensive coordination between cell cycle cues, membrane trafficking and microtubule dynamics. Plant cytokinesis occurs within a transient membrane compartment known as the cell plate, to which vesicles are delivered by a plant-specific microtubule array, the phragmoplast. While membrane proteins required for cytokinesis are known, how these are coordinated with microtubule dynamics and regulated by cell cycle cues remains unclear. Here, we document physical and genetic interactions between Transport Protein Particle II (TRAPPII) tethering factors and microtubule-associated proteins of the PLEIADE/AtMAP65 family. These interactions do not specifically affect the recruitment of either TRAPPII or MAP65 proteins to the cell plate or midzone. Rather, and based on single versus double mutant phenotypes, it appears that they are required to coordinate cytokinesis with the nuclear division cycle. As MAP65 family members are known to be targets of cell cycle-regulated kinases, our results provide a conceptual framework for how membrane and microtubule dynamics may be coordinated with each other and with the nuclear cycle during plant cytokinesis. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

One ligand, two regulators and three binding sites: How KDPG controls primary carbon metabolism in Pseudomonas

PubMed Central

Fung, Rowena K. Y.; Grenga, Lucia; Trampari, Eleftheria; Pepe, Simona

2017-01-01

Effective regulation of primary carbon metabolism is critically important for bacteria to successfully adapt to different environments. We have identified an uncharacterised transcriptional regulator; RccR, that controls this process in response to carbon source availability. Disruption of rccR in the plant-associated microbe Pseudomonas fluorescens inhibits growth in defined media, and compromises its ability to colonise the wheat rhizosphere. Structurally, RccR is almost identical to the Entner-Doudoroff (ED) pathway regulator HexR, and both proteins are controlled by the same ED-intermediate; 2-keto-3-deoxy-6-phosphogluconate (KDPG). Despite these similarities, HexR and RccR control entirely different aspects of primary metabolism, with RccR regulating pyruvate metabolism (aceEF), the glyoxylate shunt (aceA, glcB, pntAA) and gluconeogenesis (pckA, gap). RccR displays complex and unusual regulatory behaviour; switching repression between the pyruvate metabolism and glyoxylate shunt/gluconeogenesis loci depending on the available carbon source. This regulatory complexity is enabled by two distinct pseudo-palindromic binding sites, differing only in the length of their linker regions, with KDPG binding increasing affinity for the 28 bp aceA binding site but decreasing affinity for the 15 bp aceE site. Thus, RccR is able to simultaneously suppress and activate gene expression in response to carbon source availability. Together, the RccR and HexR regulators enable the rapid coordination of multiple aspects of primary carbon metabolism, in response to levels of a single key intermediate. PMID:28658302

TCF7L2 is a master regulator of insulin production and processing.

PubMed

Zhou, Yuedan; Park, Soo-Young; Su, Jing; Bailey, Kathleen; Ottosson-Laakso, Emilia; Shcherbina, Liliya; Oskolkov, Nikolay; Zhang, Enming; Thevenin, Thomas; Fadista, João; Bennet, Hedvig; Vikman, Petter; Wierup, Nils; Fex, Malin; Rung, Johan; Wollheim, Claes; Nobrega, Marcelo; Renström, Erik; Groop, Leif; Hansson, Ola

2014-12-15

Genome-wide association studies have revealed >60 loci associated with type 2 diabetes (T2D), but the underlying causal variants and functional mechanisms remain largely elusive. Although variants in TCF7L2 confer the strongest risk of T2D among common variants by presumed effects on islet function, the molecular mechanisms are not yet well understood. Using RNA-sequencing, we have identified a TCF7L2-regulated transcriptional network responsible for its effect on insulin secretion in rodent and human pancreatic islets. ISL1 is a primary target of TCF7L2 and regulates proinsulin production and processing via MAFA, PDX1, NKX6.1, PCSK1, PCSK2 and SLC30A8, thereby providing evidence for a coordinated regulation of insulin production and processing. The risk T-allele of rs7903146 was associated with increased TCF7L2 expression, and decreased insulin content and secretion. Using gene expression profiles of 66 human pancreatic islets donors', we also show that the identified TCF7L2-ISL1 transcriptional network is regulated in a genotype-dependent manner. Taken together, these results demonstrate that not only synthesis of proinsulin is regulated by TCF7L2 but also processing and possibly clearance of proinsulin and insulin. These multiple targets in key pathways may explain why TCF7L2 has emerged as the gene showing one of the strongest associations with T2D. © The Author 2014. Published by Oxford University Press.

Calibration method for video and radiation imagers

DOEpatents

Cunningham, Mark F [Oak Ridge, TN; Fabris, Lorenzo [Knoxville, TN; Gee, Timothy F [Oak Ridge, TN; Goddard, Jr., James S.; Karnowski, Thomas P [Knoxville, TN; Ziock, Klaus-peter [Clinton, TN

2011-07-05

The relationship between the high energy radiation imager pixel (HERIP) coordinate and real-world x-coordinate is determined by a least square fit between the HERIP x-coordinate and the measured real-world x-coordinates of calibration markers that emit high energy radiation imager and reflect visible light. Upon calibration, a high energy radiation imager pixel position may be determined based on a real-world coordinate of a moving vehicle. Further, a scale parameter for said high energy radiation imager may be determined based on the real-world coordinate. The scale parameter depends on the y-coordinate of the moving vehicle as provided by a visible light camera. The high energy radiation imager may be employed to detect radiation from moving vehicles in multiple lanes, which correspondingly have different distances to the high energy radiation imager.

Enhancing healthcare sector coordination through infrastructure and logistics support.

PubMed

Zoraster, Richard M

2010-01-01

The International Response to the 2004 Southeast Asia Tsunami was noted to have multiple areas of poor coordination, and in 2005, the "Health Cluster"approach to coordination was formulated. However, the 2010 Haiti response suggests that many of the same problems continue and that there are significant limitations to the cluster meetings. These limitations include the inconsistent attendance, poor dissemination of information, and perceived lack of benefit to providers. This article proposes that healthcare coordination would be greatly improved with logistical support, leading to improved efficiency and outcomes for those affected by disasters.

Optimizing plasmonic nanoantennas via coordinated multiple coupling

NASA Astrophysics Data System (ADS)

Lin, Linhan; Zheng, Yuebing

2015-10-01

Plasmonic nanoantennas, which can efficiently convert light from free space into sub-wavelength scale with the local field enhancement, are fundamental building blocks for nanophotonic systems. Predominant design methods, which exploit a single type of near- or far-field coupling in pairs or arrays of plasmonic nanostructures, have limited the tunability of spectral response and the local field enhancement. To overcome this limit, we are developing a general strategy towards exploiting the coordinated effects of multiple coupling. Using Au bowtie nanoantenna arrays with metal-insulator-metal configuration as examples, we numerically demonstrate that coordinated design and implementation of various optical coupling effects leads to both the increased tunability in the spectral response and the significantly enhanced electromagnetic field. Furthermore, we design and analyze a refractive index sensor with an ultra-high figure-of-merit (254), a high signal-to-noise ratio and a wide working range of refractive indices, and a narrow-band near-infrared plasmonic absorber with 100% absorption efficiency, high quality factor of up to 114 and a wide range of tunable wavelength from 800 nm to 1,500 nm. The plasmonic nanoantennas that exploit coordinated multiple coupling will benefit a broad range of applications, including label-free bio-chemical detection, reflective filter, optical trapping, hot-electron generation, and heat-assisted magnetic recording.

49 CFR 1580.201 - Rail security coordinator.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 9 2013-10-01 2013-10-01 false Rail security coordinator. 1580.201 Section 1580.201 Transportation Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY MARITIME AND LAND TRANSPORTATION SECURITY RAIL TRANSPORTATION...

49 CFR 1544.215 - Security coordinators.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 9 2012-10-01 2012-10-01 false Security coordinators. 1544.215 Section 1544.215 Transportation Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY AIRCRAFT OPERATOR SECURITY: AIR CARRIERS AND...

49 CFR 1580.201 - Rail security coordinator.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 9 2011-10-01 2011-10-01 false Rail security coordinator. 1580.201 Section 1580.201 Transportation Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY MARITIME AND LAND TRANSPORTATION SECURITY RAIL TRANSPORTATION...

49 CFR 1544.215 - Security coordinators.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 9 2011-10-01 2011-10-01 false Security coordinators. 1544.215 Section 1544.215 Transportation Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY AIRCRAFT OPERATOR SECURITY: AIR CARRIERS AND...

49 CFR 1544.215 - Security coordinators.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 9 2013-10-01 2013-10-01 false Security coordinators. 1544.215 Section 1544.215 Transportation Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY AIRCRAFT OPERATOR SECURITY: AIR CARRIERS AND...

49 CFR 1544.215 - Security coordinators.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 9 2010-10-01 2010-10-01 false Security coordinators. 1544.215 Section 1544.215 Transportation Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY AIRCRAFT OPERATOR SECURITY: AIR CARRIERS AND...

49 CFR 1544.215 - Security coordinators.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 9 2014-10-01 2014-10-01 false Security coordinators. 1544.215 Section 1544.215 Transportation Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY AIRCRAFT OPERATOR SECURITY: AIR CARRIERS AND...

49 CFR 1580.111 - Harmonization of federal regulation of nuclear facilities.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 9 2014-10-01 2014-10-01 false Harmonization of federal regulation of nuclear facilities. 1580.111 Section 1580.111 Transportation Other Regulations Relating to Transportation (Continued... regulation of nuclear facilities. TSA will coordinate activities under this subpart with the Nuclear...

49 CFR 1580.111 - Harmonization of federal regulation of nuclear facilities.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 9 2011-10-01 2011-10-01 false Harmonization of federal regulation of nuclear facilities. 1580.111 Section 1580.111 Transportation Other Regulations Relating to Transportation (Continued... regulation of nuclear facilities. TSA will coordinate activities under this subpart with the Nuclear...

49 CFR 1580.111 - Harmonization of federal regulation of nuclear facilities.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 9 2013-10-01 2013-10-01 false Harmonization of federal regulation of nuclear facilities. 1580.111 Section 1580.111 Transportation Other Regulations Relating to Transportation (Continued... regulation of nuclear facilities. TSA will coordinate activities under this subpart with the Nuclear...

49 CFR 1580.111 - Harmonization of federal regulation of nuclear facilities.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 9 2010-10-01 2010-10-01 false Harmonization of federal regulation of nuclear facilities. 1580.111 Section 1580.111 Transportation Other Regulations Relating to Transportation (Continued... regulation of nuclear facilities. TSA will coordinate activities under this subpart with the Nuclear...

49 CFR 1580.111 - Harmonization of federal regulation of nuclear facilities.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 9 2012-10-01 2012-10-01 false Harmonization of federal regulation of nuclear facilities. 1580.111 Section 1580.111 Transportation Other Regulations Relating to Transportation (Continued... regulation of nuclear facilities. TSA will coordinate activities under this subpart with the Nuclear...

Multiple scaling power in liquid gallium under pressure conditions

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

Li, Renfeng; Wang, Luhong; Li, Liangliang

Generally, a single scaling exponent, Df, can characterize the fractal structures of metallic glasses according to the scaling power law. However, when the scaling power law is applied to liquid gallium upon compression, the results show multiple scaling exponents and the values are beyond 3 within the first four coordination spheres in real space, indicating that the power law fails to describe the fractal feature in liquid gallium. The increase in the first coordination number with pressure leads to the fact that first coordination spheres at different pressures are not similar to each other in a geometrical sense. This multiplemore » scaling power behavior is confined within a correlation length of ξ ≈ 14–15 Å at applied pressure according to decay of G(r) in liquid gallium. Beyond this length the liquid gallium system could roughly be viewed as homogeneous, as indicated by the scaling exponent, Ds, which is close to 3 beyond the first four coordination spheres.« less

Safety in the operating theatre--a transition to systems-based care.

PubMed

Weiser, Thomas G; Porter, Michael P; Maier, Ronald V

2013-03-01

All surgeons want the best, safest care for their patients, but providing this requires the complex coordination of multiple disciplines to ensure that all elements of care are timely, appropriate, and well organized. Quality-improvement initiatives are beginning to lead to improvements in the quality of care and coordination amongst teams in the operating room. As the population ages and patients present with more complex disease pathology, the demands for efficient systematization will increase. Although evidence suggests that postoperative mortality rates are declining, there is substantial room for improvement. Multiple quality metrics are used as surrogates for safe care, but surgical teams--including surgeons, anaesthetists, and nurses--must think beyond these simple interventions if they are to effectively communicate and coordinate in the face of increasing demands.

Calcium Dysregulation and Homeostasis of Neural Calcium in the Molecular Mechanisms of Neurodegenerative Diseases Provide Multiple Targets for Neuroprotection

PubMed Central

Zündorf, Gregor

2011-01-01

Abstract The intracellular free calcium concentration subserves complex signaling roles in brain. Calcium cations (Ca2+) regulate neuronal plasticity underlying learning and memory and neuronal survival. Homo- and heterocellular control of Ca2+ homeostasis supports brain physiology maintaining neural integrity. Ca2+ fluxes across the plasma membrane and between intracellular organelles and compartments integrate diverse cellular functions. A vast array of checkpoints controls Ca2+, like G protein-coupled receptors, ion channels, Ca2+ binding proteins, transcriptional networks, and ion exchangers, in both the plasma membrane and the membranes of mitochondria and endoplasmic reticulum. Interactions between Ca2+ and reactive oxygen species signaling coordinate signaling, which can be either beneficial or detrimental. In neurodegenerative disorders, cellular Ca2+-regulating systems are compromised. Oxidative stress, perturbed energy metabolism, and alterations of disease-related proteins result in Ca2+-dependent synaptic dysfunction, impaired plasticity, and neuronal demise. We review Ca2+ control processes relevant for physiological and pathophysiological conditions in brain tissue. Dysregulation of Ca2+ is decisive for brain cell death and degeneration after ischemic stroke, long-term neurodegeneration in Alzheimer's disease, Parkinson's disease, Huntington's disease, inflammatory processes, such as in multiple sclerosis, epileptic sclerosis, and leucodystrophies. Understanding the underlying molecular processes is of critical importance for the development of novel therapeutic strategies to prevent neurodegeneration and confer neuroprotection. Antioxid. Redox Signal. 14, 1275–1288. PMID:20615073

Myosin II Activity Softens Cells in Suspension.

PubMed

Chan, Chii J; Ekpenyong, Andrew E; Golfier, Stefan; Li, Wenhong; Chalut, Kevin J; Otto, Oliver; Elgeti, Jens; Guck, Jochen; Lautenschläger, Franziska

2015-04-21

The cellular cytoskeleton is crucial for many cellular functions such as cell motility and wound healing, as well as other processes that require shape change or force generation. Actin is one cytoskeleton component that regulates cell mechanics. Important properties driving this regulation include the amount of actin, its level of cross-linking, and its coordination with the activity of specific molecular motors like myosin. While studies investigating the contribution of myosin activity to cell mechanics have been performed on cells attached to a substrate, we investigated mechanical properties of cells in suspension. To do this, we used multiple probes for cell mechanics including a microfluidic optical stretcher, a microfluidic microcirculation mimetic, and real-time deformability cytometry. We found that nonadherent blood cells, cells arrested in mitosis, and naturally adherent cells brought into suspension, stiffen and become more solidlike upon myosin inhibition across multiple timescales (milliseconds to minutes). Our results hold across several pharmacological and genetic perturbations targeting myosin. Our findings suggest that myosin II activity contributes to increased whole-cell compliance and fluidity. This finding is contrary to what has been reported for cells attached to a substrate, which stiffen via active myosin driven prestress. Our results establish the importance of myosin II as an active component in modulating suspended cell mechanics, with a functional role distinctly different from that for substrate-adhered cells. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Genetics Home Reference: multiple system atrophy

MedlinePlus

... inability to hold the body upright and balanced (postural instability). The other type of multiple system atrophy , ... cells in parts of the nervous system that control movement, balance and coordination, and autonomic functioning. The ...

Economic evaluation of distribution system smart grid investments

DOE PAGES

Onen, Ahmet; Cheng, Danling; Broadwater, Robert P.; ...

2014-12-31

This paper investigates economic benefits of smart grid automation investments. A system consisting of 7 substations and 14 feeders is used in the evaluation. Here benefits that can be quantified in terms of dollar savings are considered, termed “hard dollar” benefits. Smart Grid investment evaluations to be considered include investments in improved efficiency, more cost effective use of existing system capacity with automated switches, and coordinated control of capacitor banks and voltage regulators. These Smart Grid evaluations are sequentially ordered, resulting in a series of incremental hard dollar benefits. Hard dollar benefits come from improved efficiency, delaying large capital equipmentmore » investments, shortened storm restoration times, and reduced customer energy use. Analyses used in the evaluation involve hourly power flow analysis over multiple years and Monte Carlo simulations of switching operations during storms using a reconfiguration for restoration algorithm. The economic analysis uses the time varying value of the Locational Marginal Price. Algorithms used include reconfiguration for restoration involving either manual or automated switches and coordinated control involving two modes of control. Field validations of phase balancing and capacitor design results are presented. The evaluation shows that investments in automation can improve performance while at the same time lowering costs.« less

Interplay between reactive oxygen species and hormones in the control of plant development and stress tolerance.

PubMed

Xia, Xiao-Jian; Zhou, Yan-Hong; Shi, Kai; Zhou, Jie; Foyer, Christine H; Yu, Jing-Quan

2015-05-01

As a consequence of a sessile lifestyle, plants are continuously exposed to changing environmental conditions and often life-threatening stresses caused by exposure to excessive light, extremes of temperature, limiting nutrient or water availability, and pathogen/insect attack. The flexible coordination of plant growth and development is necessary to optimize vigour and fitness in a changing environment through rapid and appropriate responses to such stresses. The concept that reactive oxygen species (ROS) are versatile signalling molecules in plants that contribute to stress acclimation is well established. This review provides an overview of our current knowledge of how ROS production and signalling are integrated with the action of auxin, brassinosteroids, gibberellins, abscisic acid, ethylene, strigolactones, salicylic acid, and jasmonic acid in the coordinate regulation of plant growth and stress tolerance. We consider the local and systemic crosstalk between ROS and hormonal signalling pathways and identify multiple points of reciprocal control, as well as providing insights into the integration nodes that involve Ca(2+)-dependent processes and mitogen-activated protein kinase phosphorylation cascades. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Assisting community management of groundwater: Irrigator attitudes in two watersheds in Rajasthan and Gujarat, India

NASA Astrophysics Data System (ADS)

Varua, M. E.; Ward, J.; Maheshwari, B.; Oza, S.; Purohit, R.; Hakimuddin; Chinnasamy, P.

2016-06-01

The absence of either state regulations or markets to coordinate the operation of individual wells has focussed attention on community level institutions as the primary loci for sustainable groundwater management in Rajasthan and Gujarat, India. The reported research relied on theoretical propositions that livelihood strategies, groundwater management and the propensity to cooperate are associated with the attitudinal orientations of well owners in the Meghraj and Dharta watersheds, located in Gujarat and Rajasthan respectively. The research tested the hypothesis that attitudes to groundwater management and farming practices, household income and trust levels of assisting agencies were not consistent across the watersheds, implying that a targeted approach, in contrast to default uniform programs, would assist communities craft rules to manage groundwater across multiple hydro-geological settings. Hierarchical cluster analysis of attitudes held by survey respondents revealed four statistically significant discrete clusters, supporting acceptance of the hypothesis. Further analyses revealed significant differences in farming practices, household wealth and willingness to adapt across the four groundwater management clusters. In conclusion, the need to account for attitudinal diversity is highlighted and a framework to guide the specific design of processes to assist communities craft coordinating instruments to sustainably manage local aquifers described.

Nutrient-sensing nuclear receptors PPARα and FXR control liver energy balance.

PubMed

Preidis, Geoffrey A; Kim, Kang Ho; Moore, David D

2017-04-03

The nuclear receptors PPARα (encoded by NR1C1) and farnesoid X receptor (FXR, encoded by NR1H4) are activated in the liver in the fasted and fed state, respectively. PPARα activation induces fatty acid oxidation, while FXR controls bile acid homeostasis, but both nuclear receptors also regulate numerous other metabolic pathways relevant to liver energy balance. Here we review evidence that they function coordinately to control key nutrient pathways, including fatty acid oxidation and gluconeogenesis in the fasted state and lipogenesis and glycolysis in the fed state. We have also recently reported that these receptors have mutually antagonistic impacts on autophagy, which is induced by PPARα but suppressed by FXR. Secretion of multiple blood proteins is a major drain on liver energy and nutrient resources, and we present preliminary evidence that the liver secretome may be directly suppressed by PPARα, but induced by FXR. Finally, previous studies demonstrated a striking deficiency in bile acid levels in malnourished mice that is consistent with results in malnourished children. We present evidence that hepatic targets of PPARα and FXR are dysregulated in chronic undernutrition. We conclude that PPARα and FXR function coordinately to integrate liver energy balance.

Circadian rhythms accelerate wound healing in female Siberian hamsters

PubMed Central

Cable, Erin J.; Onishi, Kenneth G.; Prendergast, Brian J.

2017-01-01

Circadian rhythms (CRs) provide temporal regulation and coordination of numerous physiological traits, including immune function. CRs in multiple aspects of immune function are absent in rodents that have been rendered circadian-arrhythmic through various methods. In Siberian hamsters, circadian arrhythmia can be induced by disruptive light treatments (DPS). Here we examined CRs in wound healing, and the effects of circadian disruption on wound healing in DPS-arrhythmic hamsters. Circadian entrained/rhythmic (RHYTH) and behaviorally-arrhythmic (ARR) female hamsters were administered a cutaneous wound either 3 h after light onset (ZT03) or 2 h after dark onset (ZT18); wound size was quantified daily using image analyses. Among RHYTH hamsters, ZT03 wounds healed faster than ZT18 wounds, whereas in ARR hamsters, circadian phase did not affect wound healing. In addition, wounds healed slower in ARR hamsters. The results document a clear CR in wound healing, and indicate that the mere presence of organismal circadian organization enhances this aspect of immune function. Faster wound healing in CR-competent hamsters may be mediated by CR-driven coordination of the temporal order of mechanisms (inflammation, leukocyte trafficking, tissue remodeling) underlying cutaneous wound healing. PMID:27998755

Pediatric Care Coordination: Lessons Learned and Future Priorities.

PubMed

Cady, Rhonda G; Looman, Wendy S; Lindeke, Linda L; LaPlante, Bonnie; Lundeen, Barbara; Seeley, Amanda; Kautto, Mary E

2015-09-30

A fundamental component of the medical home model is care coordination. In Minnesota, this model informed design and implementation of the state's health care home (HCH) model, a key element of statewide healthcare reform legislation. Children with medical complexity (CMC) often require care from multiple specialists and community resources. Coordinating this multi-faceted care within the HCH is challenging. This article describes the need for specialized models of care coordination for CMC. Two models of care coordination for CMC were developed to address this challenge. The TeleFamilies Model of Pediatric Care Coordination uses an advanced practice registered nurse care (APRN) coordinator embedded within an established HCH. The PRoSPer Model of Pediatric Care Coordination uses a registered nurse/social worker care coordinator team embedded within a specialty care system. We describe key findings from implementation of these models, and conclude with lessons learned. Replication of the models is encouraged to increase the evidence base for care coordination for the growing population of children with medical complexities.

49 CFR 1548.13 - Security coordinators.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 9 2012-10-01 2012-10-01 false Security coordinators. 1548.13 Section 1548.13 Transportation Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY INDIRECT AIR CARRIER SECURITY § 1548.13 Security...

49 CFR 1548.13 - Security coordinators.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 9 2011-10-01 2011-10-01 false Security coordinators. 1548.13 Section 1548.13 Transportation Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY INDIRECT AIR CARRIER SECURITY § 1548.13 Security...

49 CFR 1548.13 - Security coordinators.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 9 2010-10-01 2010-10-01 false Security coordinators. 1548.13 Section 1548.13 Transportation Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY INDIRECT AIR CARRIER SECURITY § 1548.13 Security...

49 CFR 1548.13 - Security coordinators.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 9 2014-10-01 2014-10-01 false Security coordinators. 1548.13 Section 1548.13 Transportation Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY INDIRECT AIR CARRIER SECURITY § 1548.13 Security...

49 CFR 1548.13 - Security coordinators.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 9 2013-10-01 2013-10-01 false Security coordinators. 1548.13 Section 1548.13 Transportation Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY INDIRECT AIR CARRIER SECURITY § 1548.13 Security...

Block coordination copolymers

DOEpatents

Koh, Kyoung Moo; Wong-Foy, Antek G; Matzger, Adam J; Benin, Annabelle I; Willis, Richard R

2014-11-11

The present invention provides compositions of crystalline coordination copolymers wherein multiple organic molecules are assembled to produce porous framework materials with layered or core-shell structures. These materials are synthesized by sequential growth techniques such as the seed growth technique. In addition, the invention provides a simple procedure for controlling functionality.

Block coordination copolymers

DOEpatents

Koh, Kyoung Moo; Wong-Foy, Antek G.; Matzger, Adam J.; Benin, Annabelle I.; Willis, Richard R.

2012-12-04

The present invention provides compositions of crystalline coordination copolymers wherein multiple organic molecules are assembled to produce porous framework materials with layered or core-shell structures. These materials are synthesized by sequential growth techniques such as the seed growth technique. In addition, the invention provides a simple procedure for controlling functionality.

Block coordination copolymers

DOEpatents

Koh, Kyoung Moo; Wong-Foy, Antek G; Matzger, Adam J; Benin, Annabelle I; Willis, Richard R

2012-11-13

The present invention provides compositions of crystalline coordination copolymers wherein multiple organic molecules are assembled to produce porous framework materials with layered or core-shell structures. These materials are synthesized by sequential growth techniques such as the seed growth technique. In addition, the invention provides a simple procedure for controlling functionality.

SMARCA4/Brg1 coordinates genetic and epigenetic networks underlying Shh-type medulloblastoma development.

PubMed

Shi, X; Wang, Q; Gu, J; Xuan, Z; Wu, J I

2016-11-03

Recent large-scale genomic studies have classified medulloblastoma into four subtypes: Wnt, Shh, Group 3 and Group 4. Each is characterized by specific mutations and distinct epigenetic states. Previously, we showed that a chromatin regulator SMARCA4/Brg1 is required for Gli-mediated transcription activation in Sonic hedgehog (Shh) signaling. We report here that Brg1 controls a transcriptional program that specifically regulates Shh-type medulloblastoma growth. Using a mouse model of Shh-type medulloblastoma, we deleted Brg1 in precancerous progenitors and primary or transplanted tumors. Brg1 deletion significantly inhibited tumor formation and progression. Genome-wide expression analyses and binding experiments indicate that Brg1 specifically coordinates with key transcription factors including Gli1, Atoh1 and REST to regulate the expression of both oncogenes and tumor suppressors that are required for medulloblastoma identity and proliferation. Shh-type medulloblastoma displays distinct H3K27me3 properties. We demonstrate that Brg1 modulates activities of H3K27me3 modifiers to regulate the expression of medulloblastoma genes. Brg1-regulated pathways are conserved in human Shh-type medulloblastoma, and Brg1 is important for the growth of a human medulloblastoma cell line. Thus, Brg1 coordinates a genetic and epigenetic network that regulates the transcriptional program underlying the Shh-type medulloblastoma development.

Network inference reveals novel connections in pathways regulating growth and defense in the yeast salt response.

PubMed

MacGilvray, Matthew E; Shishkova, Evgenia; Chasman, Deborah; Place, Michael; Gitter, Anthony; Coon, Joshua J; Gasch, Audrey P

2018-05-01

Cells respond to stressful conditions by coordinating a complex, multi-faceted response that spans many levels of physiology. Much of the response is coordinated by changes in protein phosphorylation. Although the regulators of transcriptome changes during stress are well characterized in Saccharomyces cerevisiae, the upstream regulatory network controlling protein phosphorylation is less well dissected. Here, we developed a computational approach to infer the signaling network that regulates phosphorylation changes in response to salt stress. We developed an approach to link predicted regulators to groups of likely co-regulated phospho-peptides responding to stress, thereby creating new edges in a background protein interaction network. We then use integer linear programming (ILP) to integrate wild type and mutant phospho-proteomic data and predict the network controlling stress-activated phospho-proteomic changes. The network we inferred predicted new regulatory connections between stress-activated and growth-regulating pathways and suggested mechanisms coordinating metabolism, cell-cycle progression, and growth during stress. We confirmed several network predictions with co-immunoprecipitations coupled with mass-spectrometry protein identification and mutant phospho-proteomic analysis. Results show that the cAMP-phosphodiesterase Pde2 physically interacts with many stress-regulated transcription factors targeted by PKA, and that reduced phosphorylation of those factors during stress requires the Rck2 kinase that we show physically interacts with Pde2. Together, our work shows how a high-quality computational network model can facilitate discovery of new pathway interactions during osmotic stress.

Intensive Care Research Coordinators in Australia and New Zealand: a cross-sectional survey of demographics, responsibilities, job satisfaction and importance.

PubMed

Roberts, Brigit; Eastwood, Glenn M; Raunow, Heike; Howe, Belinda; Rickard, Claire M

2011-11-01

The achievement of successful clinical research projects depends on multiple team members including Research Coordinators (RCs), who are the link between the researcher and the trial participants. The RCs main responsibility is to ensure that all research is conducted according to the appropriate protocols, regulations and guidelines. Description of demographics, the role and associated responsibilities and assessment of items of importance to, and satisfaction with, various job related items. An observational web-based cross-sectional study of RCs working in Intensive Care Units (ICU) across Australia and New Zealand. Fifty-six participants completed the survey. Forty percent had more than 6 years experience in ICU research and one-third held a Masters Degree. Most respondents performed research related tasks including ethics submission, patient screening, education and data collection. Autonomy and work hours were the most satisfying job characteristics reported and aspects relating to autonomy were most important for the RCs. Inadequate remuneration was of great concern to the participants. Research Coordinators in Australia and New Zealand have many and varied roles with a significant workload. Unfortunately, the RCs do not feel their employers are adequately remunerating the demand on their time and efforts. The results indicate that RCs enjoy high levels of satisfaction with general conditions and facets of their work and its environment and they remain passionate about their role in the ICU setting. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

Neuron-specific specificity protein 4 bigenomically regulates the transcription of all mitochondria- and nucleus-encoded cytochrome c oxidase subunit genes in neurons.

PubMed

Johar, Kaid; Priya, Anusha; Dhar, Shilpa; Liu, Qiuli; Wong-Riley, Margaret T T

2013-11-01

Neurons are highly dependent on oxidative metabolism for their energy supply, and cytochrome c oxidase (COX) is a key energy-generating enzyme in the mitochondria. A unique feature of COX is that it is one of only four proteins in mammalian cells that are bigenomically regulated. Of its thirteen subunits, three are encoded in the mitochondrial genome and ten are nuclear-encoded on nine different chromosomes. The mechanism of regulating this multisubunit, bigenomic enzyme poses a distinct challenge. In recent years, we found that nuclear respiratory factors 1 and 2 (NRF-1 and NRF-2) mediate such bigenomic coordination. The latest candidate is the specificity factor (Sp) family of proteins. In N2a cells, we found that Sp1 regulates all 13 COX subunits. However, we discovered recently that in primary neurons, it is Sp4 and not Sp1 that regulates some of the key glutamatergic receptor subunit genes. The question naturally arises as to the role of Sp4 in regulating COX in primary neurons. The present study utilized multiple approaches, including chromatin immunoprecipitation, promoter mutational analysis, knockdown and over-expression of Sp4, as well as functional assays to document that Sp4 indeed functionally regulate all 13 subunits of COX as well as mitochondrial transcription factors A and B. The present study discovered that among the specificity family of transcription factors, it is the less known neuron-specific Sp4 that regulates the expression of all 13 subunits of mitochondrial cytochrome c oxidase (COX) enzyme in primary neurons. Sp4 also regulates the three mitochondrial transcription factors (TFAM, TFB1M, and TFB2M) and a COX assembly protein SURF-1 in primary neurons. © 2013 International Society for Neurochemistry.

MicroRNA-132 dysregulation in schizophrenia has implications for both neurodevelopment and adult brain function

PubMed Central

Miller, Brooke H.; Zeier, Zane; Xi, Li; Lanz, Thomas A.; Deng, Shibing; Strathmann, Julia; Willoughby, David; Kenny, Paul J.; Elsworth, John D.; Lawrence, Matthew S.; Roth, Robert H.; Edbauer, Dieter; Kleiman, Robin J.; Wahlestedt, Claes

2012-01-01

Schizophrenia is characterized by affective, cognitive, neuromorphological, and molecular abnormalities that may have a neurodevelopmental origin. MicroRNAs (miRNAs) are small noncoding RNA sequences critical to neurodevelopment and adult neuronal processes by coordinating the activity of multiple genes within biological networks. We examined the expression of 854 miRNAs in prefrontal cortical tissue from 100 control, schizophrenic, and bipolar subjects. The cyclic AMP-responsive element binding- and NMDA-regulated microRNA miR-132 was significantly down-regulated in both the schizophrenic discovery cohort and a second, independent set of schizophrenic subjects. Analysis of miR-132 target gene expression in schizophrenia gene-expression microarrays identified 26 genes up-regulated in schizophrenia subjects. Consistent with NMDA-mediated hypofunction observed in schizophrenic subjects, administration of an NMDA antagonist to adult mice results in miR-132 down-regulation in the prefrontal cortex. Furthermore, miR-132 expression in the murine prefrontal cortex exhibits significant developmental regulation and overlaps with critical neurodevelopmental processes during adolescence. Adult prefrontal expression of miR-132 can be down-regulated by pharmacologic inhibition of NMDA receptor signaling during a brief postnatal period. Several key genes, including DNMT3A, GATA2, and DPYSL3, are regulated by miR-132 and exhibited altered expression either during normal neurodevelopment or in tissue from adult schizophrenic subjects. Our data suggest miR-132 dysregulation and subsequent abnormal expression of miR-132 target genes contribute to the neurodevelopmental and neuromorphological pathologies present in schizophrenia. PMID:22315408

Integrative analyses shed new light on human ribosomal protein gene regulation

PubMed Central

Li, Xin; Zheng, Yiyu; Hu, Haiyan; Li, Xiaoman

2016-01-01

Ribosomal protein genes (RPGs) are important house-keeping genes that are well-known for their coordinated expression. Previous studies on RPGs are largely limited to their promoter regions. Recent high-throughput studies provide an unprecedented opportunity to study how human RPGs are transcriptionally modulated and how such transcriptional regulation may contribute to the coordinate gene expression in various tissues and cell types. By analyzing the DNase I hypersensitive sites under 349 experimental conditions, we predicted 217 RPG regulatory regions in the human genome. More than 86.6% of these computationally predicted regulatory regions were partially corroborated by independent experimental measurements. Motif analyses on these predicted regulatory regions identified 31 DNA motifs, including 57.1% of experimentally validated motifs in literature that regulate RPGs. Interestingly, we observed that the majority of the predicted motifs were shared by the predicted distal and proximal regulatory regions of the same RPGs, a likely general mechanism for enhancer-promoter interactions. We also found that RPGs may be differently regulated in different cells, indicating that condition-specific RPG regulatory regions still need to be discovered and investigated. Our study advances the understanding of how RPGs are coordinately modulated, which sheds light to the general principles of gene transcriptional regulation in mammals. PMID:27346035

Integrative analyses shed new light on human ribosomal protein gene regulation.

PubMed

Li, Xin; Zheng, Yiyu; Hu, Haiyan; Li, Xiaoman

2016-06-27

Ribosomal protein genes (RPGs) are important house-keeping genes that are well-known for their coordinated expression. Previous studies on RPGs are largely limited to their promoter regions. Recent high-throughput studies provide an unprecedented opportunity to study how human RPGs are transcriptionally modulated and how such transcriptional regulation may contribute to the coordinate gene expression in various tissues and cell types. By analyzing the DNase I hypersensitive sites under 349 experimental conditions, we predicted 217 RPG regulatory regions in the human genome. More than 86.6% of these computationally predicted regulatory regions were partially corroborated by independent experimental measurements. Motif analyses on these predicted regulatory regions identified 31 DNA motifs, including 57.1% of experimentally validated motifs in literature that regulate RPGs. Interestingly, we observed that the majority of the predicted motifs were shared by the predicted distal and proximal regulatory regions of the same RPGs, a likely general mechanism for enhancer-promoter interactions. We also found that RPGs may be differently regulated in different cells, indicating that condition-specific RPG regulatory regions still need to be discovered and investigated. Our study advances the understanding of how RPGs are coordinately modulated, which sheds light to the general principles of gene transcriptional regulation in mammals.

An MRM-based workflow for absolute quantitation of lysine-acetylated metabolic enzymes in mouse liver.

PubMed

Xu, Leilei; Wang, Fang; Xu, Ying; Wang, Yi; Zhang, Cuiping; Qin, Xue; Yu, Hongxiu; Yang, Pengyuan

2015-12-07

As a key post-translational modification mechanism, protein acetylation plays critical roles in regulating and/or coordinating cell metabolism. Acetylation is a prevalent modification process in enzymes. Protein acetylation modification occurs in sub-stoichiometric amounts; therefore extracting biologically meaningful information from these acetylation sites requires an adaptable, sensitive, specific, and robust method for their quantification. In this work, we combine immunoassays and multiple reaction monitoring-mass spectrometry (MRM-MS) technology to develop an absolute quantification for acetylation modification. With this hybrid method, we quantified the acetylation level of metabolic enzymes, which could demonstrate the regulatory mechanisms of the studied enzymes. The development of this quantitative workflow is a pivotal step for advancing our knowledge and understanding of the regulatory effects of protein acetylation in physiology and pathophysiology.

Programmed Cell Death and Caspase Functions During Neural Development.

PubMed

Yamaguchi, Yoshifumi; Miura, Masayuki

2015-01-01

Programmed cell death (PCD) is a fundamental component of nervous system development. PCD serves as the mechanism for quantitative matching of the number of projecting neurons and their target cells through direct competition for neurotrophic factors in the vertebrate peripheral nervous system. In addition, PCD plays roles in regulating neural cell numbers, canceling developmental errors or noise, and tissue remodeling processes. These findings are mainly derived from genetic studies that prevent cells from dying by apoptosis, which is a major form of PCD and is executed by activation of evolutionarily conserved cysteine protease caspases. Recent studies suggest that caspase activation can be coordinated in time and space at multiple levels, which might underlie nonapoptotic roles of caspases in neural development in addition to apoptotic roles. © 2015 Elsevier Inc. All rights reserved.

Coordination of receptor signaling in multiple hematopoietic cell lineages by the adaptor protein SLP-76.

PubMed

Jordan, Martha S; Koretzky, Gary A

2010-04-01

The adaptor protein SLP-76 is expressed in multiple hematopoietic lineages including T cells, platelets, and neutrophils. SLP-76 mediated signaling is dependent on its multiple protein interaction domains, as it creates a scaffold on which key signaling complexes are built. SLP-76 is critical for supporting signaling downstream of both immunoreceptors and integrins. The signaling molecules used both upstream and downstream of SLP-76 are similar among these receptors and across cell types; however, important differences exist. Appreciating how SLP-76 coordinates signal transduction across different cell and receptor types provides insights into the complex interplay of pathways critical for activation of cells of the immune system that are essential for host defense.

Target-Derived Neurotrophins Coordinate Transcription and Transport of Bclw to Prevent Axonal Degeneration

PubMed Central

Cosker, Katharina E.; Pazyra-Murphy, Maria F.; Fenstermacher, Sara J.

2013-01-01

Establishment of neuronal circuitry depends on both formation and refinement of neural connections. During this process, target-derived neurotrophins regulate both transcription and translation to enable selective axon survival or elimination. However, it is not known whether retrograde signaling pathways that control transcription are coordinated with neurotrophin-regulated actions that transpire in the axon. Here we report that target-derived neurotrophins coordinate transcription of the antiapoptotic gene bclw with transport of bclw mRNA to the axon, and thereby prevent axonal degeneration in rat and mouse sensory neurons. We show that neurotrophin stimulation of nerve terminals elicits new bclw transcripts that are immediately transported to the axons and translated into protein. Bclw interacts with Bax and suppresses the caspase6 apoptotic cascade that fosters axonal degeneration. The scope of bclw regulation at the levels of transcription, transport, and translation provides a mechanism whereby sustained neurotrophin stimulation can be integrated over time, so that axonal survival is restricted to neurons connected within a stable circuit. PMID:23516285

The Circadian Clock Coordinates Ribosome Biogenesis

PubMed Central

Symul, Laura; Martin, Eva; Atger, Florian; Naef, Felix; Gachon, Frédéric

2013-01-01

Biological rhythms play a fundamental role in the physiology and behavior of most living organisms. Rhythmic circadian expression of clock-controlled genes is orchestrated by a molecular clock that relies on interconnected negative feedback loops of transcription regulators. Here we show that the circadian clock exerts its function also through the regulation of mRNA translation. Namely, the circadian clock influences the temporal translation of a subset of mRNAs involved in ribosome biogenesis by controlling the transcription of translation initiation factors as well as the clock-dependent rhythmic activation of signaling pathways involved in their regulation. Moreover, the circadian oscillator directly regulates the transcription of ribosomal protein mRNAs and ribosomal RNAs. Thus the circadian clock exerts a major role in coordinating transcription and translation steps underlying ribosome biogenesis. PMID:23300384

34 CFR 361.22 - Coordination with education officials.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 34 Education 2 2011-07-01 2010-07-01 true Coordination with education officials. 361.22 Section 361.22 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION STATE VOCATIONAL REHABILITATION...

15 CFR 923.56 - Plan coordination.

Code of Federal Regulations, 2014 CFR

2014-01-01

... OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE OCEAN AND COASTAL RESOURCE MANAGEMENT COASTAL ZONE MANAGEMENT PROGRAM REGULATIONS Coordination, Public Involvement and National Interest § 923... interstate plans applicable to areas within the coastal zone— (1) Existing on January 1 of the year in which...

15 CFR 923.56 - Plan coordination.

Code of Federal Regulations, 2012 CFR

2012-01-01

... OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE OCEAN AND COASTAL RESOURCE MANAGEMENT COASTAL ZONE MANAGEMENT PROGRAM REGULATIONS Coordination, Public Involvement and National Interest § 923... interstate plans applicable to areas within the coastal zone— (1) Existing on January 1 of the year in which...

15 CFR 923.56 - Plan coordination.

Code of Federal Regulations, 2010 CFR

2010-01-01

... OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE OCEAN AND COASTAL RESOURCE MANAGEMENT COASTAL ZONE MANAGEMENT PROGRAM REGULATIONS Coordination, Public Involvement and National Interest § 923... interstate plans applicable to areas within the coastal zone— (1) Existing on January 1 of the year in which...

15 CFR 923.56 - Plan coordination.

Code of Federal Regulations, 2013 CFR

2013-01-01

... OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE OCEAN AND COASTAL RESOURCE MANAGEMENT COASTAL ZONE MANAGEMENT PROGRAM REGULATIONS Coordination, Public Involvement and National Interest § 923... interstate plans applicable to areas within the coastal zone— (1) Existing on January 1 of the year in which...

15 CFR 923.56 - Plan coordination.

Code of Federal Regulations, 2011 CFR

2011-01-01

... OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE OCEAN AND COASTAL RESOURCE MANAGEMENT COASTAL ZONE MANAGEMENT PROGRAM REGULATIONS Coordination, Public Involvement and National Interest § 923... interstate plans applicable to areas within the coastal zone— (1) Existing on January 1 of the year in which...

22 CFR 9.11 - Systematic declassification review.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Section 9.11 Foreign Relations DEPARTMENT OF STATE GENERAL SECURITY INFORMATION REGULATIONS § 9.11 Systematic declassification review. The Information and Privacy Coordinator shall be responsible for... Information and Privacy Coordinator shall prioritize such review on the basis of researcher interest and the...

7 CFR 624.5 - Coordination.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Presidentially-declared natural disasters. (b) When an NRCS State Conservationist determines that a watershed... Regulations of the Department of Agriculture (Continued) NATURAL RESOURCES CONSERVATION SERVICE, DEPARTMENT OF... an area to be a major disaster area, NRCS will provide assistance which will be coordinated with the...

34 CFR 361.22 - Coordination with education officials.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 34 Education 2 2013-07-01 2013-07-01 false Coordination with education officials. 361.22 Section 361.22 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION STATE VOCATIONAL REHABILITATION...

34 CFR 361.22 - Coordination with education officials.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 34 Education 2 2014-07-01 2013-07-01 true Coordination with education officials. 361.22 Section 361.22 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION STATE VOCATIONAL REHABILITATION...

34 CFR 361.22 - Coordination with education officials.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 34 Education 2 2012-07-01 2012-07-01 false Coordination with education officials. 361.22 Section 361.22 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION STATE VOCATIONAL REHABILITATION...

34 CFR 361.22 - Coordination with education officials.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 2 2010-07-01 2010-07-01 false Coordination with education officials. 361.22 Section 361.22 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION STATE VOCATIONAL REHABILITATION...

36 CFR 13.1104 - Coordinates.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 36 Parks, Forests, and Public Property 1 2011-07-01 2011-07-01 false Coordinates. 13.1104 Section 13.1104 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK SYSTEM UNITS IN ALASKA Special Regulations-Glacier Bay National Park and Preserve...

36 CFR 13.1104 - Coordinates.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Coordinates. 13.1104 Section 13.1104 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK SYSTEM UNITS IN ALASKA Special Regulations-Glacier Bay National Park and Preserve...

36 CFR 13.1104 - Coordinates.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 36 Parks, Forests, and Public Property 1 2014-07-01 2014-07-01 false Coordinates. 13.1104 Section 13.1104 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK SYSTEM UNITS IN ALASKA Special Regulations-Glacier Bay National Park and Preserve...

15 CFR Appendix F to Subpart M of... - Davidson Seamount Management Zone

Code of Federal Regulations, 2013 CFR

2013-01-01

... Trade (Continued) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE OCEAN AND COASTAL RESOURCE MANAGEMENT NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Monterey Bay National Marine... [Coordinates in this appendix are unprojected (Geographic Coordinate System) and are calculated using the North...

15 CFR Appendix F to Subpart M of... - Davidson Seamount Management Zone

Code of Federal Regulations, 2012 CFR

2012-01-01

... Trade (Continued) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE OCEAN AND COASTAL RESOURCE MANAGEMENT NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Monterey Bay National Marine... [Coordinates in this appendix are unprojected (Geographic Coordinate System) and are calculated using the North...

15 CFR Appendix F to Subpart M of... - Davidson Seamount Management Zone

Code of Federal Regulations, 2014 CFR

2014-01-01

... Trade (Continued) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE OCEAN AND COASTAL RESOURCE MANAGEMENT NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Monterey Bay National Marine... [Coordinates in this appendix are unprojected (Geographic Coordinate System) and are calculated using the North...

36 CFR 1010.4 - NEPA Compliance Coordinator.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) Develop procedures within the Trust's planning and decision-making processes to ensure that environmental... and documentation of the environmental aspects of the Trust's planning and decision-making processes... decisions of the NEPA Compliance Coordinator in accordance with the Trust's regulations and procedures. (b...

36 CFR 13.1104 - Coordinates.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 36 Parks, Forests, and Public Property 1 2012-07-01 2012-07-01 false Coordinates. 13.1104 Section 13.1104 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK SYSTEM UNITS IN ALASKA Special Regulations-Glacier Bay National Park and Preserve...

36 CFR 13.1104 - Coordinates.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 36 Parks, Forests, and Public Property 1 2013-07-01 2013-07-01 false Coordinates. 13.1104 Section 13.1104 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK SYSTEM UNITS IN ALASKA Special Regulations-Glacier Bay National Park and Preserve...

29 CFR 1405.6 - Program coordination.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Regulations Relating to Labor (Continued) FEDERAL MEDIATION AND CONCILIATION SERVICE PART-TIME EMPLOYMENT Part... Part-time Employment Coordinator with responsibility for: (a) Consulting in the part-time employment...) Responding to requests for advice and assistance on part-time employment within the agency; (c) Maintaining...

Analyzing Group Coordination when Solving Geometry Problems with Dynamic Geometry Software

ERIC Educational Resources Information Center

Oner, Diler

2013-01-01

In CSCL research, collaborative activity is conceptualized along various yet intertwined dimensions. When functioning within these multiple dimensions, participants make use of several resources, which can be social or content-related (and sometimes temporal) in nature. It is the effective coordination of these resources that appears to…

Multiple Sensory-Motor Pathways Lead to Coordinated Visual Attention

ERIC Educational Resources Information Center

Yu, Chen; Smith, Linda B.

2017-01-01

Joint attention has been extensively studied in the developmental literature because of overwhelming evidence that the ability to socially coordinate visual attention to an object is essential to healthy developmental outcomes, including language learning. The goal of this study was to understand the complex system of sensory-motor behaviors that…

Market-Based Coordination and Auditing Mechanisms for Self-Interested Multi-Robot Systems

ERIC Educational Resources Information Center

Ham, MyungJoo

2009-01-01

We propose market-based coordinated task allocation mechanisms, which allocate complex tasks that require synchronized and collaborated services of multiple robot agents to robot agents, and an auditing mechanism, which ensures proper behaviors of robot agents by verifying inter-agent activities, for self-interested, fully-distributed, and…

Force-independent distribution of correlated neural inputs to hand muscles during three-digit grasping.

PubMed

Poston, Brach; Danna-Dos Santos, Alessander; Jesunathadas, Mark; Hamm, Thomas M; Santello, Marco

2010-08-01

The ability to modulate digit forces during grasping relies on the coordination of multiple hand muscles. Because many muscles innervate each digit, the CNS can potentially choose from a large number of muscle coordination patterns to generate a given digit force. Studies of single-digit force production tasks have revealed that the electromyographic (EMG) activity scales uniformly across all muscles as a function of digit force. However, the extent to which this finding applies to the coordination of forces across multiple digits is unknown. We addressed this question by asking subjects (n = 8) to exert isometric forces using a three-digit grip (thumb, index, and middle fingers) that allowed for the quantification of hand muscle coordination within and across digits as a function of grasp force (5, 20, 40, 60, and 80% maximal voluntary force). We recorded EMG from 12 muscles (6 extrinsic and 6 intrinsic) of the three digits. Hand muscle coordination patterns were quantified in the amplitude and frequency domains (EMG-EMG coherence). EMG amplitude scaled uniformly across all hand muscles as a function of grasp force (muscle x force interaction: P = 0.997; cosines of angle between muscle activation pattern vector pairs: 0.897-0.997). Similarly, EMG-EMG coherence was not significantly affected by force (P = 0.324). However, coherence was stronger across extrinsic than that across intrinsic muscle pairs (P = 0.0039). These findings indicate that the distribution of neural drive to multiple hand muscles is force independent and may reflect the anatomical properties or functional roles of hand muscle groups.

Deconvolution of subcellular protrusion heterogeneity and the underlying actin regulator dynamics from live cell imaging.

PubMed

Wang, Chuangqi; Choi, Hee June; Kim, Sung-Jin; Desai, Aesha; Lee, Namgyu; Kim, Dohoon; Bae, Yongho; Lee, Kwonmoo

2018-04-27

Cell protrusion is morphodynamically heterogeneous at the subcellular level. However, the mechanism of cell protrusion has been understood based on the ensemble average of actin regulator dynamics. Here, we establish a computational framework called HACKS (deconvolution of heterogeneous activity in coordination of cytoskeleton at the subcellular level) to deconvolve the subcellular heterogeneity of lamellipodial protrusion from live cell imaging. HACKS identifies distinct subcellular protrusion phenotypes based on machine-learning algorithms and reveals their underlying actin regulator dynamics at the leading edge. Using our method, we discover "accelerating protrusion", which is driven by the temporally ordered coordination of Arp2/3 and VASP activities. We validate our finding by pharmacological perturbations and further identify the fine regulation of Arp2/3 and VASP recruitment associated with accelerating protrusion. Our study suggests HACKS can identify specific subcellular protrusion phenotypes susceptible to pharmacological perturbation and reveal how actin regulator dynamics are changed by the perturbation.

An allosteric photoredox catalyst inspired by photosynthetic machinery

PubMed Central

Lifschitz, Alejo M.; Young, Ryan M.; Mendez-Arroyo, Jose; Stern, Charlotte L.; McGuirk, C. Michael; Wasielewski, Michael R.; Mirkin, Chad A.

2015-01-01

Biological photosynthetic machinery allosterically regulate light harvesting via conformational and electronic changes at the antenna protein complexes as a response to specific chemical inputs. Fundamental limitations in current approaches to regulating inorganic light-harvesting mimics prevent their use in catalysis. Here we show that a light-harvesting antenna/reaction centre mimic can be regulated by utilizing a coordination framework incorporating antenna hemilabile ligands and assembled via a high-yielding, modular approach. As in nature, allosteric regulation is afforded by coupling the conformational changes to the disruptions in the electrochemical landscape of the framework upon recognition of specific coordinating analytes. The hemilabile ligands enable switching using remarkably mild and redox-inactive inputs, allowing one to regulate the photoredox catalytic activity of the photosynthetic mimic reversibly and in situ. Thus, we demonstrate that bioinspired regulatory mechanisms can be applied to inorganic light-harvesting arrays displaying switchable catalytic properties and with potential uses in solar energy conversion and photonic devices. PMID:25817586

A complex regulatory network coordinating cell cycles during C. elegans development is revealed by a genome-wide RNAi screen.

PubMed

Roy, Sarah H; Tobin, David V; Memar, Nadin; Beltz, Eleanor; Holmen, Jenna; Clayton, Joseph E; Chiu, Daniel J; Young, Laura D; Green, Travis H; Lubin, Isabella; Liu, Yuying; Conradt, Barbara; Saito, R Mako

2014-02-28

The development and homeostasis of multicellular animals requires precise coordination of cell division and differentiation. We performed a genome-wide RNA interference screen in Caenorhabditis elegans to reveal the components of a regulatory network that promotes developmentally programmed cell-cycle quiescence. The 107 identified genes are predicted to constitute regulatory networks that are conserved among higher animals because almost half of the genes are represented by clear human orthologs. Using a series of mutant backgrounds to assess their genetic activities, the RNA interference clones displaying similar properties were clustered to establish potential regulatory relationships within the network. This approach uncovered four distinct genetic pathways controlling cell-cycle entry during intestinal organogenesis. The enhanced phenotypes observed for animals carrying compound mutations attest to the collaboration between distinct mechanisms to ensure strict developmental regulation of cell cycles. Moreover, we characterized ubc-25, a gene encoding an E2 ubiquitin-conjugating enzyme whose human ortholog, UBE2Q2, is deregulated in several cancers. Our genetic analyses suggested that ubc-25 acts in a linear pathway with cul-1/Cul1, in parallel to pathways employing cki-1/p27 and lin-35/pRb to promote cell-cycle quiescence. Further investigation of the potential regulatory mechanism demonstrated that ubc-25 activity negatively regulates CYE-1/cyclin E protein abundance in vivo. Together, our results show that the ubc-25-mediated pathway acts within a complex network that integrates the actions of multiple molecular mechanisms to control cell cycles during development. Copyright © 2014 Roy et al.

Diurnal Cycling Transcription Factors of Pineapple Revealed by Genome-Wide Annotation and Global Transcriptomic Analysis

PubMed Central

Sharma, Anupma; Wai, Ching Man; Ming, Ray

2017-01-01

Abstract Circadian clock provides fitness advantage by coordinating internal metabolic and physiological processes to external cyclic environments. Core clock components exhibit daily rhythmic changes in gene expression, and the majority of them are transcription factors (TFs) and transcription coregulators (TCs). We annotated 1,398 TFs from 67 TF families and 80 TCs from 20 TC families in pineapple, and analyzed their tissue-specific and diurnal expression patterns. Approximately 42% of TFs and 45% of TCs displayed diel rhythmic expression, including 177 TF/TCs cycling only in the nonphotosynthetic leaf tissue, 247 cycling only in the photosynthetic leaf tissue, and 201 cycling in both. We identified 68 TF/TCs whose cycling expression was tightly coupled between the photosynthetic and nonphotosynthetic leaf tissues. These TF/TCs likely coordinate key biological processes in pineapple as we demonstrated that this group is enriched in homologous genes that form the core circadian clock in Arabidopsis and includes a STOP1 homolog. Two lines of evidence support the important role of the STOP1 homolog in regulating CAM photosynthesis in pineapple. First, STOP1 responds to acidic pH and regulates a malate channel in multiple plant species. Second, the cycling expression pattern of the pineapple STOP1 and the diurnal pattern of malate accumulation in pineapple leaf are correlated. We further examined duplicate-gene retention and loss in major known circadian genes and refined their evolutionary relationships between pineapple and other plants. Significant variations in duplicate-gene retention and loss were observed for most clock genes in both monocots and dicots. PMID:28922793

Coordination of Myeloid Differentiation with Reduced Cell Cycle Progression by PU.1 Induction of MicroRNAs Targeting Cell Cycle Regulators and Lipid Anabolism.

PubMed

Solomon, Lauren A; Podder, Shreya; He, Jessica; Jackson-Chornenki, Nicholas L; Gibson, Kristen; Ziliotto, Rachel G; Rhee, Jess; DeKoter, Rodney P

2017-05-15

During macrophage development, myeloid progenitor cells undergo terminal differentiation coordinated with reduced cell cycle progression. Differentiation of macrophages from myeloid progenitors is accompanied by increased expression of the E26 transformation-specific transcription factor PU.1. Reduced PU.1 expression leads to increased proliferation and impaired differentiation of myeloid progenitor cells. It is not understood how PU.1 coordinates macrophage differentiation with reduced cell cycle progression. In this study, we utilized cultured PU.1-inducible myeloid cells to perform genome-wide chromatin immunoprecipitation sequencing (ChIP-seq) analysis coupled with gene expression analysis to determine targets of PU.1 that may be involved in regulating cell cycle progression. We found that genes encoding cell cycle regulators and enzymes involved in lipid anabolism were directly and inducibly bound by PU.1 although their steady-state mRNA transcript levels were reduced. Inhibition of lipid anabolism was sufficient to reduce cell cycle progression in these cells. Induction of PU.1 reduced expression of E2f1 , an important activator of genes involved in cell cycle and lipid anabolism, indirectly through microRNA 223. Next-generation sequencing identified microRNAs validated as targeting cell cycle and lipid anabolism for downregulation. These results suggest that PU.1 coordinates cell cycle progression with differentiation through induction of microRNAs targeting cell cycle regulators and lipid anabolism. Copyright © 2017 American Society for Microbiology.

Optimal Coordination of Building Loads and Energy Storage for Power Grid and End User Services

DOE PAGES

Hao, He; Wu, Di; Lian, Jianming; ...

2017-01-18

Demand response and energy storage play a profound role in the smart grid. The focus of this study is to evaluate benefits of coordinating flexible loads and energy storage to provide power grid and end user services. We present a Generalized Battery Model (GBM) to describe the flexibility of building loads and energy storage. An optimization-based approach is proposed to characterize the parameters (power and energy limits) of the GBM for flexible building loads. We then develop optimal coordination algorithms to provide power grid and end user services such as energy arbitrage, frequency regulation, spinning reserve, as well as energymore » cost and demand charge reduction. Several case studies have been performed to demonstrate the efficacy of the GBM and coordination algorithms, and evaluate the benefits of using their flexibility for power grid and end user services. We show that optimal coordination yields significant cost savings and revenue. Moreover, the best option for power grid services is to provide energy arbitrage and frequency regulation. Finally and furthermore, when coordinating flexible loads with energy storage to provide end user services, it is recommended to consider demand charge in addition to time-of-use price in order to flatten the aggregate power profile.« less

Target-based calibration method for multifields of view measurement using multiple stereo digital image correlation systems

NASA Astrophysics Data System (ADS)

Dong, Shuai; Yu, Shanshan; Huang, Zheng; Song, Shoutan; Shao, Xinxing; Kang, Xin; He, Xiaoyuan

2017-12-01

Multiple digital image correlation (DIC) systems can enlarge the measurement field without losing effective resolution in the area of interest (AOI). However, the results calculated in substereo DIC systems are located in its local coordinate system in most cases. To stitch the data obtained by each individual system, a data merging algorithm is presented in this paper for global measurement of multiple stereo DIC systems. A set of encoded targets is employed to assist the extrinsic calibration, of which the three-dimensional (3-D) coordinates are reconstructed via digital close range photogrammetry. Combining the 3-D targets with precalibrated intrinsic parameters of all cameras, the extrinsic calibration is significantly simplified. After calculating in substereo DIC systems, all data can be merged into a universal coordinate system based on the extrinsic calibration. Four stereo DIC systems are applied to a four point bending experiment of a steel reinforced concrete beam structure. Results demonstrate high accuracy for the displacement data merging in the overlapping field of views (FOVs) and show feasibility for the distributed FOVs measurement.

Lessons Learned from Coordinating Relay Activities at Mars

NASA Technical Reports Server (NTRS)

Gladden, Roy E.; Hwang, Pauline; Waggoner, Bruce; McLaughlin, Bruce; Fieseler, Paul; Thomas, Reid; Bigwood, Maria; Herrera, Paul

2005-01-01

The Mission Management Office at the Jet Propulsion Laboratory was tasked with coordinating the relay of data between multiple spacecraft at Mars in support of the Mars Exploration Rover Missions in early 2004. The confluence of three orbiters (Mars Global Surveyor, Mars Odyssey, and Mars Express), two rovers (Spirit and Opportunity), and one lander (Beagle 2) has provided a challenging operational scenario that required careful coordination between missions to provide the necessary support and to avoid potential interference during simultaneous relay sessions. As these coordination efforts progressed, several important lessons were learned that should be applied to future Mars relay activities.

Age-Related Differences in Multiple Task Monitoring

PubMed Central

Todorov, Ivo; Del Missier, Fabio; Mäntylä, Timo

2014-01-01

Coordinating multiple tasks with narrow deadlines is particularly challenging for older adults because of age related decline in cognitive control functions. We tested the hypothesis that multiple task performance reflects age- and gender-related differences in executive functioning and spatial ability. Young and older adults completed a multitasking session with four monitoring tasks as well as separate tasks measuring executive functioning and spatial ability. For both age groups, men exceeded women in multitasking, measured as monitoring accuracy. Individual differences in executive functioning and spatial ability were independent predictors of young adults' monitoring accuracy, but only spatial ability was related to sex differences. For older adults, age and executive functioning, but not spatial ability, predicted multitasking performance. These results suggest that executive functions contribute to multiple task performance across the adult life span and that reliance on spatial skills for coordinating deadlines is modulated by age. PMID:25215609

Price competition and equilibrium analysis in multiple hybrid channel supply chain

NASA Astrophysics Data System (ADS)

Kuang, Guihua; Wang, Aihu; Sha, Jin

2017-06-01

The amazing boom of Internet and logistics industry prompts more and more enterprises to sell commodity through multiple channels. Such market conditions make the participants of multiple hybrid channel supply chain compete each other in traditional and direct channel at the same time. This paper builds a two-echelon supply chain model with a single manufacturer and a single retailer who both can choose different channel or channel combination for their own sales, then, discusses the price competition and calculates the equilibrium price under different sales channel selection combinations. Our analysis shows that no matter the manufacturer and retailer choose same or different channel price to compete, the equilibrium price does not necessarily exist the equilibrium price in the multiple hybrid channel supply chain and wholesale price change is not always able to coordinate supply chain completely. We also present the sufficient and necessary conditions for the existence of equilibrium price and coordination wholesale price.

Age-related differences in multiple task monitoring.

PubMed

Todorov, Ivo; Del Missier, Fabio; Mäntylä, Timo

2014-01-01

Coordinating multiple tasks with narrow deadlines is particularly challenging for older adults because of age related decline in cognitive control functions. We tested the hypothesis that multiple task performance reflects age- and gender-related differences in executive functioning and spatial ability. Young and older adults completed a multitasking session with four monitoring tasks as well as separate tasks measuring executive functioning and spatial ability. For both age groups, men exceeded women in multitasking, measured as monitoring accuracy. Individual differences in executive functioning and spatial ability were independent predictors of young adults' monitoring accuracy, but only spatial ability was related to sex differences. For older adults, age and executive functioning, but not spatial ability, predicted multitasking performance. These results suggest that executive functions contribute to multiple task performance across the adult life span and that reliance on spatial skills for coordinating deadlines is modulated by age.

Babies' Self-Regulation: Taking a Broad Perspective

ERIC Educational Resources Information Center

Elliot, Enid; Gonzalez-Mena, Janet

2011-01-01

Self-regulation is a complex process that involves coordinating various systems of the body and mind, including feelings. It's not only about emotions but also about cognition. Self-regulation has an impact on social development, influencing how babies and toddlers get along with others. Through self-regulation, babies and toddlers learn to pay…

Time-Coordination Strategies and Control Laws for Multi-Agent Unmanned Systems

NASA Technical Reports Server (NTRS)

Puig-Navarro, Javier; Hovakimyan, Naira; Allen, B. Danette

2017-01-01

Time-critical coordination tools for unmanned systems can be employed to enforce the type of temporal constraints required in terminal control areas, ensure minimum distance requirements among vehicles are satisfied, and successfully perform coordinated missions. In comparison with previous literature, this paper presents an ampler spectrum of coordination and temporal specifications for unmanned systems, and proposes a general control law that can enforce this range of constraints. The constraint classification presented con- siders the nature of the desired arrival window and the permissible coordination errors to define six different types of time-coordination strategies. The resulting decentralized coordination control law allows the vehicles to negotiate their speeds along their paths in response to information exchanged over the communication network. This control law organizes the different members in the fleet hierarchically per their behavior and informational needs as reference agent, leaders, and followers. Examples and simulation results for all the coordination strategies presented demonstrate the applicability and efficacy of the coordination control law for multiple unmanned systems.

Regulation of a transcription factor network by Cdk1 coordinates late cell cycle gene expression

PubMed Central

Landry, Benjamin D; Mapa, Claudine E; Arsenault, Heather E; Poti, Kristin E; Benanti, Jennifer A

2014-01-01

To maintain genome stability, regulators of chromosome segregation must be expressed in coordination with mitotic events. Expression of these late cell cycle genes is regulated by cyclin-dependent kinase (Cdk1), which phosphorylates a network of conserved transcription factors (TFs). However, the effects of Cdk1 phosphorylation on many key TFs are not known. We find that elimination of Cdk1-mediated phosphorylation of four S-phase TFs decreases expression of many late cell cycle genes, delays mitotic progression, and reduces fitness in budding yeast. Blocking phosphorylation impairs degradation of all four TFs. Consequently, phosphorylation-deficient mutants of the repressors Yox1 and Yhp1 exhibit increased promoter occupancy and decreased expression of their target genes. Interestingly, although phosphorylation of the transcriptional activator Hcm1 on its N-terminus promotes its degradation, phosphorylation on its C-terminus is required for its activity, indicating that Cdk1 both activates and inhibits a single TF. We conclude that Cdk1 promotes gene expression by both activating transcriptional activators and inactivating transcriptional repressors. Furthermore, our data suggest that coordinated regulation of the TF network by Cdk1 is necessary for faithful cell division. PMID:24714560

Regulation of a transcription factor network by Cdk1 coordinates late cell cycle gene expression.

PubMed

Landry, Benjamin D; Mapa, Claudine E; Arsenault, Heather E; Poti, Kristin E; Benanti, Jennifer A

2014-05-02

To maintain genome stability, regulators of chromosome segregation must be expressed in coordination with mitotic events. Expression of these late cell cycle genes is regulated by cyclin-dependent kinase (Cdk1), which phosphorylates a network of conserved transcription factors (TFs). However, the effects of Cdk1 phosphorylation on many key TFs are not known. We find that elimination of Cdk1-mediated phosphorylation of four S-phase TFs decreases expression of many late cell cycle genes, delays mitotic progression, and reduces fitness in budding yeast. Blocking phosphorylation impairs degradation of all four TFs. Consequently, phosphorylation-deficient mutants of the repressors Yox1 and Yhp1 exhibit increased promoter occupancy and decreased expression of their target genes. Interestingly, although phosphorylation of the transcriptional activator Hcm1 on its N-terminus promotes its degradation, phosphorylation on its C-terminus is required for its activity, indicating that Cdk1 both activates and inhibits a single TF. We conclude that Cdk1 promotes gene expression by both activating transcriptional activators and inactivating transcriptional repressors. Furthermore, our data suggest that coordinated regulation of the TF network by Cdk1 is necessary for faithful cell division.

The cellular response to vascular endothelial growth factors requires co-ordinated signal transduction, trafficking and proteolysis

PubMed Central

Smith, Gina A.; Fearnley, Gareth W.; Tomlinson, Darren C.; Harrison, Michael A.; Ponnambalam, Sreenivasan

2015-01-01

VEGFs (vascular endothelial growth factors) are a family of conserved disulfide-linked soluble secretory glycoproteins found in higher eukaryotes. VEGFs mediate a wide range of responses in different tissues including metabolic homoeostasis, cell proliferation, migration and tubulogenesis. Such responses are initiated by VEGF binding to soluble and membrane-bound VEGFRs (VEGF receptor tyrosine kinases) and co-receptors. VEGF and receptor splice isoform diversity further enhances complexity of membrane protein assembly and function in signal transduction pathways that control multiple cellular responses. Different signal transduction pathways are simultaneously activated by VEGFR–VEGF complexes with membrane trafficking along the endosome–lysosome network further modulating signal output from multiple enzymatic events associated with such pathways. Balancing VEGFR–VEGF signal transduction with trafficking and proteolysis is essential in controlling the intensity and duration of different intracellular signalling events. Dysfunction in VEGF-regulated signal transduction is important in chronic disease states including cancer, atherosclerosis and blindness. This family of growth factors and receptors is an important model system for understanding human disease pathology and developing new therapeutics for treating such ailments. PMID:26285805

Hierarchical Feedback Modules and Reaction Hubs in Cell Signaling Networks

PubMed Central

Xu, Jianfeng; Lan, Yueheng

2015-01-01

Despite much effort, identification of modular structures and study of their organizing and functional roles remain a formidable challenge in molecular systems biology, which, however, is essential in reaching a systematic understanding of large-scale cell regulation networks and hence gaining capacity of exerting effective interference to cell activity. Combining graph theoretic methods with available dynamics information, we successfully retrieved multiple feedback modules of three important signaling networks. These feedbacks are structurally arranged in a hierarchical way and dynamically produce layered temporal profiles of output signals. We found that global and local feedbacks act in very different ways and on distinct features of the information flow conveyed by signal transduction but work highly coordinately to implement specific biological functions. The redundancy embodied with multiple signal-relaying channels and feedback controls bestow great robustness and the reaction hubs seated at junctions of different paths announce their paramount importance through exquisite parameter management. The current investigation reveals intriguing general features of the organization of cell signaling networks and their relevance to biological function, which may find interesting applications in analysis, design and control of bio-networks. PMID:25951347

Dynamic equilibrium strategy for drought emergency temporary water transfer and allocation management

NASA Astrophysics Data System (ADS)

Xu, Jiuping; Ma, Ning; Lv, Chengwei

2016-08-01

Efficient water transfer and allocation are critical for disaster mitigation in drought emergencies. This is especially important when the different interests of the multiple decision makers and the fluctuating water resource supply and demand simultaneously cause space and time conflicts. To achieve more effective and efficient water transfers and allocations, this paper proposes a novel optimization method with an integrated bi-level structure and a dynamic strategy, in which the bi-level structure works to deal with space dimension conflicts in drought emergencies, and the dynamic strategy is used to deal with time dimension conflicts. Combining these two optimization methods, however, makes calculation complex, so an integrated interactive fuzzy program and a PSO-POA are combined to develop a hybrid-heuristic algorithm. The successful application of the proposed model in a real world case region demonstrates its practicality and efficiency. Dynamic cooperation between multiple reservoirs under the coordination of a global regulator reflects the model's efficiency and effectiveness in drought emergency water transfer and allocation, especially in a fluctuating environment. On this basis, some corresponding management recommendations are proposed to improve practical operations.

Two FGFRL-Wnt circuits organize the planarian anteroposterior axis

PubMed Central

Scimone, M Lucila; Cote, Lauren E; Rogers, Travis; Reddien, Peter W

2016-01-01

How positional information instructs adult tissue maintenance is poorly understood. Planarians undergo whole-body regeneration and tissue turnover, providing a model for adult positional information studies. Genes encoding secreted and transmembrane components of multiple developmental pathways are predominantly expressed in planarian muscle cells. Several of these genes regulate regional identity, consistent with muscle harboring positional information. Here, single-cell RNA-sequencing of 115 muscle cells from distinct anterior-posterior regions identified 44 regionally expressed genes, including multiple Wnt and ndk/FGF receptor-like (ndl/FGFRL) genes. Two distinct FGFRL-Wnt circuits, involving juxtaposed anterior FGFRL and posterior Wnt expression domains, controlled planarian head and trunk patterning. ndl-3 and wntP-2 inhibition expanded the trunk, forming ectopic mouths and secondary pharynges, which independently extended and ingested food. fz5/8-4 inhibition, like that of ndk and wntA, caused posterior brain expansion and ectopic eye formation. Our results suggest that FGFRL-Wnt circuits operate within a body-wide coordinate system to control adult axial positioning. DOI: http://dx.doi.org/10.7554/eLife.12845.001 PMID:27063937

A post-transcriptional mechanism pacing expression of neural genes with precursor cell differentiation status

PubMed Central

Dai, Weijun; Li, Wencheng; Hoque, Mainul; Li, Zhuyun; Tian, Bin; Makeyev, Eugene V.

2015-01-01

Nervous system (NS) development relies on coherent upregulation of extensive sets of genes in a precise spatiotemporal manner. How such transcriptome-wide effects are orchestrated at the molecular level remains an open question. Here we show that 3′-untranslated regions (3′ UTRs) of multiple neural transcripts contain AU-rich cis-elements (AREs) recognized by tristetraprolin (TTP/Zfp36), an RNA-binding protein previously implicated in regulation of mRNA stability. We further demonstrate that the efficiency of ARE-dependent mRNA degradation declines in the neural lineage because of a decrease in the TTP protein expression mediated by the NS-enriched microRNA miR-9. Importantly, TTP downregulation in this context is essential for proper neuronal differentiation. On the other hand, inactivation of TTP in non-neuronal cells leads to dramatic upregulation of multiple NS-specific genes. We conclude that the newly identified miR-9/TTP circuitry limits unscheduled accumulation of neuronal mRNAs in non-neuronal cells and ensures coordinated upregulation of these transcripts in neurons. PMID:26144867

41 CFR 128-1.8004 - Seismic Safety Coordinators.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 41 Public Contracts and Property Management 3 2014-01-01 2014-01-01 false Seismic Safety... Management Regulations System (Continued) DEPARTMENT OF JUSTICE 1-INTRODUCTION 1.80-Seismic Safety Program § 128-1.8004 Seismic Safety Coordinators. (a) The Justice Management Division shall designate an...

41 CFR 128-1.8004 - Seismic Safety Coordinators.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 41 Public Contracts and Property Management 3 2012-01-01 2012-01-01 false Seismic Safety... Management Regulations System (Continued) DEPARTMENT OF JUSTICE 1-INTRODUCTION 1.80-Seismic Safety Program § 128-1.8004 Seismic Safety Coordinators. (a) The Justice Management Division shall designate an...

41 CFR 128-1.8004 - Seismic Safety Coordinators.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 41 Public Contracts and Property Management 3 2013-07-01 2013-07-01 false Seismic Safety... Management Regulations System (Continued) DEPARTMENT OF JUSTICE 1-INTRODUCTION 1.80-Seismic Safety Program § 128-1.8004 Seismic Safety Coordinators. (a) The Justice Management Division shall designate an...

41 CFR 128-1.8004 - Seismic Safety Coordinators.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 41 Public Contracts and Property Management 3 2011-01-01 2011-01-01 false Seismic Safety... Management Regulations System (Continued) DEPARTMENT OF JUSTICE 1-INTRODUCTION 1.80-Seismic Safety Program § 128-1.8004 Seismic Safety Coordinators. (a) The Justice Management Division shall designate an...

Legal Considerations in Cooperative Education Administration.

ERIC Educational Resources Information Center

Hunt, Donald C.

The laws, regulations, and rulings that are common to all cooperative education programs and that frequently present problems to coordinators, faculty, administrators, and employers are briefly explained. The objective is to provide coordinators of cooperative programs in education, business, industry, and government with a discussion of the…

40 CFR 501.3 - Coordination with other programs.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 31 2012-07-01 2012-07-01 false Coordination with other programs. 501.3 Section 501.3 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SEWAGE SLUDGE STATE SLUDGE MANAGEMENT PROGRAM REGULATIONS Purpose, Scope and General Program Requirements § 501.3...

40 CFR 501.3 - Coordination with other programs.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 29 2010-07-01 2010-07-01 false Coordination with other programs. 501.3 Section 501.3 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SEWAGE SLUDGE STATE SLUDGE MANAGEMENT PROGRAM REGULATIONS Purpose, Scope and General Program Requirements § 501.3...

40 CFR 501.3 - Coordination with other programs.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 31 2013-07-01 2013-07-01 false Coordination with other programs. 501.3 Section 501.3 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SEWAGE SLUDGE STATE SLUDGE MANAGEMENT PROGRAM REGULATIONS Purpose, Scope and General Program Requirements § 501.3...

40 CFR 501.3 - Coordination with other programs.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 30 2014-07-01 2014-07-01 false Coordination with other programs. 501.3 Section 501.3 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SEWAGE SLUDGE STATE SLUDGE MANAGEMENT PROGRAM REGULATIONS Purpose, Scope and General Program Requirements § 501.3...

40 CFR 501.3 - Coordination with other programs.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 30 2011-07-01 2011-07-01 false Coordination with other programs. 501.3 Section 501.3 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SEWAGE SLUDGE STATE SLUDGE MANAGEMENT PROGRAM REGULATIONS Purpose, Scope and General Program Requirements § 501.3...

48 CFR 225.872-4 - Individual determinations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Individual determinations. 225.872-4 Section 225.872-4 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS... and Coordination 225.872-4 Individual determinations. If the offer of an end product from a qualifying...

29 CFR 1690.104 - Authority.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Opportunity Programs) 43 FR 28967, July 5, 1978. (These regulations will also appear as EEOC Management... 29 Labor 4 2012-07-01 2012-07-01 false Authority. 1690.104 Section 1690.104 Labor Regulations... COORDINATION OF EQUAL EMPLOYMENT OPPORTUNITY ISSUANCES General § 1690.104 Authority. These regulations are...

29 CFR 1690.104 - Authority.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Opportunity Programs) 43 FR 28967, July 5, 1978. (These regulations will also appear as EEOC Management... 29 Labor 4 2010-07-01 2010-07-01 false Authority. 1690.104 Section 1690.104 Labor Regulations... COORDINATION OF EQUAL EMPLOYMENT OPPORTUNITY ISSUANCES General § 1690.104 Authority. These regulations are...

29 CFR 1690.104 - Authority.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Opportunity Programs) 43 FR 28967, July 5, 1978. (These regulations will also appear as EEOC Management... 29 Labor 4 2011-07-01 2011-07-01 false Authority. 1690.104 Section 1690.104 Labor Regulations... COORDINATION OF EQUAL EMPLOYMENT OPPORTUNITY ISSUANCES General § 1690.104 Authority. These regulations are...

29 CFR 1690.104 - Authority.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Opportunity Programs) 43 FR 28967, July 5, 1978. (These regulations will also appear as EEOC Management... 29 Labor 4 2013-07-01 2013-07-01 false Authority. 1690.104 Section 1690.104 Labor Regulations... COORDINATION OF EQUAL EMPLOYMENT OPPORTUNITY ISSUANCES General § 1690.104 Authority. These regulations are...

29 CFR 1690.104 - Authority.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Opportunity Programs) 43 FR 28967, July 5, 1978. (These regulations will also appear as EEOC Management... 29 Labor 4 2014-07-01 2014-07-01 false Authority. 1690.104 Section 1690.104 Labor Regulations... COORDINATION OF EQUAL EMPLOYMENT OPPORTUNITY ISSUANCES General § 1690.104 Authority. These regulations are...

Experience in connecting the power generating units of thermal power plants to automatic secondary frequency regulation within the united power system of Russia

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

Zhukov, A. V.; Komarov, A. N.; Safronov, A. N.

The principles of central control of the power generating units of thermal power plants by automatic secondary frequency and active power overcurrent regulation systems, and the algorithms for interactions between automatic power control systems for the power production units in thermal power plants and centralized systems for automatic frequency and power regulation, are discussed. The order of switching the power generating units of thermal power plants over to control by a centralized system for automatic frequency and power regulation and by the Central Coordinating System for automatic frequency and power regulation is presented. The results of full-scale system tests ofmore » the control of power generating units of the Kirishskaya, Stavropol, and Perm GRES (State Regional Electric Power Plants) by the Central Coordinating System for automatic frequency and power regulation at the United Power System of Russia on September 23-25, 2008, are reported.« less

Science Planning for Multi-Spacecraft Coordinated Observations

NASA Technical Reports Server (NTRS)

Maks, Lori; Fishman, Mark; Pell, Vince; Obenschain, Arthur F. (Technical Monitor)

2002-01-01

Fulfilling the promise of an era of great observatories, NASA now has more than three space-based astronomical telescopes operating in different wavebands. This situation provides astronomers with a unique opportunity to simultaneously observe with multiple observatories. Yet scheduling multiple observatories simultaneously is highly inefficient when compared to single observatory observations. Thus, programs using multiple observatories are limited not due to scientific restrictions, but due to operational inefficiencies. Each year, a number of proposals are accepted by a space-based observatory for conduction of astronomical observations and gathering of science data for the study of galactic events. Since each space-based observatory uses a set of instruments designed to operate in specific energy regions, most such studies are conducted by submitting observation proposals to multiple observatories, with requests to coordinate among themselves. To assure that the proposed observations can be scheduled, each observatory's staff has to check that the observations are valid and meet all the constraints for their own observatory; in addition, they have to verify that the observations satisfy the constraints of the other observatories. Thus, coordinated observations require painstaking manual collaboration among the observatory staff at each observatory. In order to exploit new paradigms for observatory operation, the Goddard Space Flight Center's Advanced Architectures and Automation Branch has developed a prototype tool called the Visual Observation Layout Tool (VOLT). The main objective of VOLT is to provide a visual tool to automate the science planning of coordinated observations for multiple spacecraft, as well as to increase the scheduling probability of observations. However, VOLT is also useful for single observatory planning to optimize observatory control. Three space-based missions are interested in using VOLT (the Hubble Space Telescope, the Chandra X-Ray Observatory, and the Far Ultraviolet Spectroscopic Explorer). The VOLT team members have collaborated with these missions to gather requirements and obtain feedback on their mission planning processes. VOLT has been developed as a cross-platform Java client application for use by scientists and observatory science planning staff to visualize scheduling options and constraints. It also supports a lightweight graphical user interface for remote viewing via a Web front end. Additionally, it uniquely supports the ability to interact with multiple, diverse scheduling packages in order to determine windows of opportunity for observations and visually portray the constraints of each observation request. VOLT enables science data capture scenarios which are currently either impossible, or which require extensive time and manpower to coordinate amongst multiple observatories. it supports early detection of planning conflicts by generating coordinated solutions based on observatory schedulability and constraints. The project development approach has included frequent prototype demonstrations to our interested missions to obtain feedback after each release of the software. We will present an overview of our lessons learned in infusing the VOLT tool into the operations of the missions we have collaborated with and a brief demonstration of the software.

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

Pachuilo, Andrew R; Ragan, Eric; Goodall, John R

Visualization tools can take advantage of multiple coordinated views to support analysis of large, multidimensional data sets. Effective design of such views and layouts can be challenging, but understanding users analysis strategies can inform design improvements. We outline an approach for intelligent design configuration of visualization tools with multiple coordinated views, and we discuss a proposed software framework to support the approach. The proposed software framework could capture and learn from user interaction data to automate new compositions of views and widgets. Such a framework could reduce the time needed for meta analysis of the visualization use and lead tomore » more effective visualization design.« less

The Arabidopsis endoplasmic reticulum associated degradation pathways are involved in the regulation of heat stress response

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

Li, Lin-Mao; University of Chinese Academy of Sciences, Beijing; Lü, Shi-You

Abstracts: The Cytosolic Protein Response (CPR) in the cytosol and the Unfolded Protein Response (UPR) and ER-associated degradation (ERAD) in the endoplasmic reticulum are major pathways of the cellular proteostasis network. However, despite years of effort, how these protein quality control systems coordinated in vivo remains largely unknown, particularly in plants. In this study, the roles of two evolutionarily conserved ERAD pathways (DOA10 and HRD1) in heat stress response were investigated through reverse genetic approaches in Arabidopsis. Phenotypic analysis of the mutants showed that the two ERAD pathways additively play negative roles in heat tolerance, which was demonstrated by higher survivalmore » rate and lower electrolyte leakage in the loss of function mutants compared to the wild type plants. Importantly, gene expression analysis revealed that the mutant plants showed elevated transcriptional regulation of several downstream genes, including those encoding CPR and UPR marker genes, under both basal and heat stress conditions. Finally, multiple components of ERAD genes exhibited rapid response to increasing temperature. Taken together, our data not only unravels key insights into the crosstalk between different protein quality control processes, but also provides candidate genes to genetically improve plant heat tolerance in the future. - Highlights: • ERAD pathways cooperatively regulate plant thermotolerance. • ERAD pathways cooperatively regulate UPR and CPR. • ERAD components gene expression are upregulated by heat stress.« less

C. elegans STRADalpha and SAD cooperatively regulate neuronal polarity and synaptic organization.

PubMed

Kim, Joanne S M; Hung, Wesley; Narbonne, Patrick; Roy, Richard; Zhen, Mei

2010-01-01

Neurons are polarized cells with morphologically and functionally distinct axons and dendrites. The SAD kinases are crucial for establishing the axon-dendrite identity across species. Previous studies suggest that a tumour suppressor kinase, LKB1, in the presence of a pseudokinase, STRADalpha, initiates axonal differentiation and growth through activating the SAD kinases in vertebrate neurons. STRADalpha was implicated in the localization, stabilization and activation of LKB1 in various cell culture studies. Its in vivo functions, however, have not been examined. In our present study, we analyzed the neuronal phenotypes of the first loss-of-function mutants for STRADalpha and examined their genetic interactions with LKB1 and SAD in C. elegans. Unexpectedly, only the C. elegans STRADalpha, STRD-1, functions exclusively through the SAD kinase, SAD-1, to regulate neuronal polarity and synaptic organization. Moreover, STRD-1 tightly associates with SAD-1 to coordinate its synaptic localizations. By contrast, the C. elegans LKB1, PAR-4, also functions in an additional genetic pathway independently of SAD-1 and STRD-1 to regulate neuronal polarity. We propose that STRD-1 establishes neuronal polarity and organizes synaptic proteins in a complex with the SAD-1 kinase. Our findings suggest that instead of a single, linear genetic pathway, STRADalpha and LKB1 regulate neuronal development through multiple effectors that are shared in some cellular contexts but distinct in others.

The ASYMMETRIC LEAVES Complex Employs Multiple Modes of Regulation to Affect Adaxial-Abaxial Patterning and Leaf Complexity.

PubMed

Husbands, Aman Y; Benkovics, Anna H; Nogueira, Fabio T S; Lodha, Mukesh; Timmermans, Marja C P

2015-12-01

Flattened leaf architecture is not a default state but depends on positional information to precisely coordinate patterns of cell division in the growing primordium. This information is provided, in part, by the boundary between the adaxial (top) and abaxial (bottom) domains of the leaf, which are specified via an intricate gene regulatory network whose precise circuitry remains poorly defined. Here, we examined the contribution of the ASYMMETRIC LEAVES (AS) pathway to adaxial-abaxial patterning in Arabidopsis thaliana and demonstrate that AS1-AS2 affects this process via multiple, distinct regulatory mechanisms. AS1-AS2 uses Polycomb-dependent and -independent mechanisms to directly repress the abaxial determinants MIR166A, YABBY5, and AUXIN RESPONSE FACTOR3 (ARF3), as well as a nonrepressive mechanism in the regulation of the adaxial determinant TAS3A. These regulatory interactions, together with data from prior studies, lead to a model in which the sequential polarization of determinants, including AS1-AS2, explains the establishment and maintenance of adaxial-abaxial leaf polarity. Moreover, our analyses show that the shared repression of ARF3 by the AS and trans-acting small interfering RNA (ta-siRNA) pathways intersects with additional AS1-AS2 targets to affect multiple nodes in leaf development, impacting polarity as well as leaf complexity. These data illustrate the surprisingly multifaceted contribution of AS1-AS2 to leaf development showing that, in conjunction with the ta-siRNA pathway, AS1-AS2 keeps the Arabidopsis leaf both flat and simple. © 2015 American Society of Plant Biologists. All rights reserved.

Endothelial Ca2+ oscillations reflect VEGFR signaling-regulated angiogenic capacity in vivo

PubMed Central

Yokota, Yasuhiro; Nakajima, Hiroyuki; Wakayama, Yuki; Muto, Akira; Kawakami, Koichi; Fukuhara, Shigetomo; Mochizuki, Naoki

2015-01-01

Sprouting angiogenesis is a well-coordinated process controlled by multiple extracellular inputs, including vascular endothelial growth factor (VEGF). However, little is known about when and how individual endothelial cell (EC) responds to angiogenic inputs in vivo. Here, we visualized endothelial Ca2+ dynamics in zebrafish and found that intracellular Ca2+ oscillations occurred in ECs exhibiting angiogenic behavior. Ca2+ oscillations depended upon VEGF receptor-2 (Vegfr2) and Vegfr3 in ECs budding from the dorsal aorta (DA) and posterior cardinal vein, respectively. Thus, visualizing Ca2+ oscillations allowed us to monitor EC responses to angiogenic cues. Vegfr-dependent Ca2+ oscillations occurred in migrating tip cells as well as stalk cells budding from the DA. We investigated how Dll4/Notch signaling regulates endothelial Ca2+ oscillations and found that it was required for the selection of single stalk cell as well as tip cell. Thus, we captured spatio-temporal Ca2+ dynamics during sprouting angiogenesis, as a result of cellular responses to angiogenic inputs. DOI: http://dx.doi.org/10.7554/eLife.08817.001 PMID:26588168

Nuclear receptor TLX prevents retinal dystrophy and recruits the corepressor atrophin1.

PubMed

Zhang, Chun-Li; Zou, Yuhua; Yu, Ruth T; Gage, Fred H; Evans, Ronald M

2006-05-15

During mammalian embryogenesis, precise coordination of progenitor cell proliferation and differentiation is essential for proper organ size and function. The involvement of TLX (NR2E1), an orphan nuclear receptor, has been implicated in ocular development, as Tlx-/- mice exhibit visual impairment. Using genetic and biochemical approaches, we show that TLX modulates retinal progenitor cell proliferation and cell cycle re-entry by directly regulating the expression of Pten and its target cyclin D1. Additionally, TLX finely tunes the progenitor differentiation program by modulating the phospholipase C and mitogen-activated protein kinase (MAPK) pathways and the expression of an array of cell type-specific transcriptional regulators. Consequently, Tlx-/- mice have a dramatic reduction in retina thickness and enhanced generation of S-cones, and develop severe early onset retinal dystrophy. Furthermore, TLX interacts with atrophin1 (Atn1), a corepressor that is involved in human neurodegenerative dentatorubral-pallidoluysian atrophy (DRPLA) and that is essential for development of multiple tissues. Together, these results reveal a molecular strategy by which an orphan nuclear receptor can precisely orchestrate tissue-specific proliferation and differentiation programs to prevent retinal malformation and degeneration.

Genetic and Cellular Mechanisms Regulating Anterior Foregut and Esophageal Development

PubMed Central

Jacobs, Ian J.; Ku, Wei-Yao; Que, Jianwen

2012-01-01

Separation of the single anterior foregut tube into the esophagus and trachea involves cell proliferation and differentiation, as well as dynamic changes in cell-cell adhesion and migration. These biological processes are regulated and coordinated at multiple levels through the interplay of the epithelium and mesenchyme. Genetic studies and in vitro modeling have shed light on relevant regulatory networks that include a number of transcription factors and signaling pathways. These signaling molecules exhibit unique expression patterns and play specific functions in their respective territories before the separation process occurs. Disruption of regulatory networks inevitably leads to defective separation and malformation of the trachea and esophagus and results in the formation of a relatively common birth defect, esophageal atresia with or without tracheoesophageal fistula (EA/TEF). Significantly, some of the signaling pathways and transcription factors involved in anterior foregut separation continue to play important roles in the morphogenesis of the individual organs. In this review, we will focus on new findings related to these different developmental processes and discuss them in the context of developmental disorders (or birth defects) commonly seen in clinics. PMID:22750256

ILK modulates epithelial polarity and matrix formation in hair follicles.

PubMed

Rudkouskaya, Alena; Welch, Ian; Dagnino, Lina

2014-03-01

Hair follicle morphogenesis requires coordination of multiple signals and communication between its epithelial and mesenchymal constituents. Cell adhesion protein platforms, which include integrins and integrin-linked kinase (ILK), are critical for hair follicle formation. However, their precise contribution to this process is poorly understood. We show that in the absence of ILK, the hair follicle matrix lineage fails to develop, likely due to abnormalities in development of apical-basal cell polarity, as well as in laminin-511 and basement membrane assembly at the tip of the hair bud. These defects also result in impaired specification of hair matrix and absence of precortex and inner sheath root cell lineages. The molecular pathways affected in ILK-deficient follicles are similar to those in the absence of epidermal integrin β1 and include Wnt, but not sonic hedgehog, signaling. ILK-deficient hair buds also show abnormalities in the dermal papilla. Addition of exogenous laminin-511 restores morphological and molecular markers associated with hair matrix formation, indicating that ILK regulates hair bud cell polarity and functions upstream from laminin-511 assembly to regulate the developmental progression of hair follicles beyond the germ stage.