Simple Analytic Expressions for the Magnetic Field of a Circular Current Loop

NASA Technical Reports Server (NTRS)

Simpson, James C.; Lane, John E.; Immer, Christopher D.; Youngquist, Robert C.

2001-01-01

Analytic expressions for the magnetic induction (magnetic flux density, B) of a simple planar circular current loop have been published in Cartesian and cylindrical coordinates [1,2], and are also known implicitly in spherical coordinates [3]. In this paper, we present explicit analytic expressions for B and its spatial derivatives in Cartesian, cylindrical, and spherical coordinates for a filamentary current loop. These results were obtained with extensive use of Mathematica "TM" and are exact throughout all space outside of the conductor. The field expressions reduce to the well-known limiting cases and satisfy V · B = 0 and V x B = 0 outside the conductor. These results are general and applicable to any model using filamentary circular current loops. Solenoids of arbitrary size may be easily modeled by approximating the total magnetic induction as the sum of those for the individual loops. The inclusion of the spatial derivatives expands their utility to magnetohydrodynamics where the derivatives are required. The equations can be coded into any high-level programming language. It is necessary to numerically evaluate complete elliptic integrals of the first and second kind, but this capability is now available with most programming packages.

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.

A Molecular Titration System Coordinates Ribosomal Protein Gene Transcription with Ribosomal RNA Synthesis.

PubMed

Albert, Benjamin; Knight, Britta; Merwin, Jason; Martin, Victoria; Ottoz, Diana; Gloor, Yvonne; Bruzzone, Maria Jessica; Rudner, Adam; Shore, David

2016-11-17

Cell growth potential is determined by the rate of ribosome biogenesis, a complex process that requires massive and coordinated transcriptional output. In the yeast Saccharomyces cerevisiae, ribosome biogenesis is highly regulated at the transcriptional level. Although evidence for a system that coordinates ribosomal RNA (rRNA) and ribosomal protein gene (RPG) transcription has been described, the molecular mechanisms remain poorly understood. Here we show that an interaction between the RPG transcriptional activator Ifh1 and the rRNA processing factor Utp22 serves to coordinate RPG transcription with that of rRNA. We demonstrate that Ifh1 is rapidly released from RPG promoters by a Utp22-independent mechanism following growth inhibition, but that its long-term dissociation requires Utp22. We present evidence that RNA polymerase I activity inhibits the ability of Utp22 to titrate Ifh1 from RPG promoters and propose that a dynamic Ifh1-Utp22 interaction fine-tunes RPG expression to coordinate RPG and rRNA transcription. Copyright © 2016 Elsevier Inc. All rights reserved.

Arabidopsis AIP1-2 restricted by WER-mediated patterning modulates planar polarity.

PubMed

Kiefer, Christian S; Claes, Andrea R; Nzayisenga, Jean-Claude; Pietra, Stefano; Stanislas, Thomas; Hüser, Anke; Ikeda, Yoshihisa; Grebe, Markus

2015-01-01

The coordination of cell polarity within the plane of the tissue layer (planar polarity) is crucial for the development of diverse multicellular organisms. Small Rac/Rho-family GTPases and the actin cytoskeleton contribute to planar polarity formation at sites of polarity establishment in animals and plants. Yet, upstream pathways coordinating planar polarity differ strikingly between kingdoms. In the root of Arabidopsis thaliana, a concentration gradient of the phytohormone auxin coordinates polar recruitment of Rho-of-plant (ROP) to sites of polar epidermal hair initiation. However, little is known about cytoskeletal components and interactions that contribute to this planar polarity or about their relation to the patterning machinery. Here, we show that ACTIN7 (ACT7) represents a main actin isoform required for planar polarity of root hair positioning, interacting with the negative modulator ACTIN-INTERACTING PROTEIN1-2 (AIP1-2). ACT7, AIP1-2 and their genetic interaction are required for coordinated planar polarity of ROP downstream of ethylene signalling. Strikingly, AIP1-2 displays hair cell file-enriched expression, restricted by WEREWOLF (WER)-dependent patterning and modified by ethylene and auxin action. Hence, our findings reveal AIP1-2, expressed under control of the WER-dependent patterning machinery and the ethylene signalling pathway, as a modulator of actin-mediated planar polarity. © 2015. Published by The Company of Biologists Ltd.

Vibrational self-consistent field theory using optimized curvilinear coordinates.

PubMed

Bulik, Ireneusz W; Frisch, Michael J; Vaccaro, Patrick H

2017-07-28

A vibrational SCF model is presented in which the functions forming the single-mode functions in the product wavefunction are expressed in terms of internal coordinates and the coordinates used for each mode are optimized variationally. This model involves no approximations to the kinetic energy operator and does not require a Taylor-series expansion of the potential. The non-linear optimization of coordinates is found to give much better product wavefunctions than the limited variations considered in most previous applications of SCF methods to vibrational problems. The approach is tested using published potential energy surfaces for water, ammonia, and formaldehyde. Variational flexibility allowed in the current ansätze results in excellent zero-point energies expressed through single-product states and accurate fundamental transition frequencies realized by short configuration-interaction expansions. Fully variational optimization of single-product states for excited vibrational levels also is discussed. The highlighted methodology constitutes an excellent starting point for more sophisticated treatments, as the bulk characteristics of many-mode coupling are accounted for efficiently in terms of compact wavefunctions (as evident from the accurate prediction of transition frequencies).

Cell Alignment Required in Differentiation of Myxococcus xanthus

NASA Astrophysics Data System (ADS)

Kim, Seung K.; Kaiser, Dale

1990-08-01

During fruiting body morphogenesis of Myxococcus xanthus, cell movement is required for transmission of C-factor, a short range intercellular signaling protein necessary for sporulation and developmental gene expression. Nonmotile cells fail to sporulate and to express C-factor-dependent genes, but both defects were rescued by a simple manipulation of cell position that oriented the cells in aligned, parallel groups. A similar pattern of aligned cells normally results from coordinated recruitment of wild-type cells into multicellular aggregates, which later form mature fruiting bodies. It is proposed that directed cell movement establishes critical contacts between adjacent cells, which are required for efficient intercellular C-factor transmission.

Conserved Non-Coding Regulatory Signatures in Arabidopsis Co-Expressed Gene Modules

PubMed Central

Spangler, Jacob B.; Ficklin, Stephen P.; Luo, Feng; Freeling, Michael; Feltus, F. Alex

2012-01-01

Complex traits and other polygenic processes require coordinated gene expression. Co-expression networks model mRNA co-expression: the product of gene regulatory networks. To identify regulatory mechanisms underlying coordinated gene expression in a tissue-enriched context, ten Arabidopsis thaliana co-expression networks were constructed after manually sorting 4,566 RNA profiling datasets into aerial, flower, leaf, root, rosette, seedling, seed, shoot, whole plant, and global (all samples combined) groups. Collectively, the ten networks contained 30% of the measurable genes of Arabidopsis and were circumscribed into 5,491 modules. Modules were scrutinized for cis regulatory mechanisms putatively encoded in conserved non-coding sequences (CNSs) previously identified as remnants of a whole genome duplication event. We determined the non-random association of 1,361 unique CNSs to 1,904 co-expression network gene modules. Furthermore, the CNS elements were placed in the context of known gene regulatory networks (GRNs) by connecting 250 CNS motifs with known GRN cis elements. Our results provide support for a regulatory role of some CNS elements and suggest the functional consequences of CNS activation of co-expression in specific gene sets dispersed throughout the genome. PMID:23024789

Conserved non-coding regulatory signatures in Arabidopsis co-expressed gene modules.

PubMed

Spangler, Jacob B; Ficklin, Stephen P; Luo, Feng; Freeling, Michael; Feltus, F Alex

2012-01-01

Complex traits and other polygenic processes require coordinated gene expression. Co-expression networks model mRNA co-expression: the product of gene regulatory networks. To identify regulatory mechanisms underlying coordinated gene expression in a tissue-enriched context, ten Arabidopsis thaliana co-expression networks were constructed after manually sorting 4,566 RNA profiling datasets into aerial, flower, leaf, root, rosette, seedling, seed, shoot, whole plant, and global (all samples combined) groups. Collectively, the ten networks contained 30% of the measurable genes of Arabidopsis and were circumscribed into 5,491 modules. Modules were scrutinized for cis regulatory mechanisms putatively encoded in conserved non-coding sequences (CNSs) previously identified as remnants of a whole genome duplication event. We determined the non-random association of 1,361 unique CNSs to 1,904 co-expression network gene modules. Furthermore, the CNS elements were placed in the context of known gene regulatory networks (GRNs) by connecting 250 CNS motifs with known GRN cis elements. Our results provide support for a regulatory role of some CNS elements and suggest the functional consequences of CNS activation of co-expression in specific gene sets dispersed throughout the genome.

Cellular and oscillatory substrates of fear extinction learning.

PubMed

Davis, Patrick; Zaki, Yosif; Maguire, Jamie; Reijmers, Leon G

2017-11-01

The mammalian brain contains dedicated circuits for both the learned expression and suppression of fear. These circuits require precise coordination to facilitate the appropriate expression of fear behavior, but the mechanisms underlying this coordination remain unclear. Using a combination of chemogenetics, activity-based neuronal-ensemble labeling and in vivo electrophysiology, we found that fear extinction learning confers on parvalbumin-expressing (PV) interneurons in the basolateral amygdala (BLA) a dedicated role in the selective suppression of a previously encoded fear memory and BLA fear-encoding neurons. In addition, following extinction learning, PV interneurons enable a competing interaction between a 6-12 Hz oscillation and a fear-associated 3-6 Hz oscillation within the BLA. Loss of this competition increases a 3-6 Hz oscillatory signature, with BLA→medial prefrontal cortex directionality signaling the recurrence of fear expression. The discovery of cellular and oscillatory substrates of fear extinction learning that critically depend on BLA PV interneurons could inform therapies aimed at preventing the pathological recurrence of fear following extinction learning.

Cellular and Oscillatory Substrates of Fear Extinction Learning

PubMed Central

Davis, Patrick; Zaki, Yosif; Maguire, Jamie; Reijmers, Leon G.

2018-01-01

The mammalian brain contains dedicated circuits for both the learned expression and suppression of fear. These circuits require precise coordination to facilitate the appropriate expression of fear behavior, but the mechanisms underlying this coordination remain unclear. Using a novel combination of chemogenetics, activity-based neuronal-ensemble labeling, and in vivo electrophysiology, we found that fear extinction learning confers parvalbumin-expressing (PV) interneurons in the basolateral amygdala (BLA) with a dedicated role in the selective suppression of a previously encoded fear memory and BLA fear-encoding neurons. In addition, following extinction learning, PV interneurons enable a competing interaction between a 6–12 Hz oscillation and a fear-associated 3–6 Hz oscillation within the BLA. Loss of this competition increases a 3–6 Hz oscillatory signature, with BLA→mPFC directionality signaling the recurrence of fear expression. The discovery of cellular and oscillatory substrates of fear extinction learning that critically depend on BLA PV-interneurons could inform therapies aimed at preventing the pathological recurrence of fear following extinction learning. PMID:28967909

Distinct regulation of Snail in two muscle lineages of the ascidian embryo achieves temporal coordination of muscle development.

PubMed

Tokuoka, Miki; Kobayashi, Kenji; Satou, Yutaka

2018-06-06

The transcriptional repressor Snail is required for proper differentiation of the tail muscle of ascidian tadpole larvae. Two muscle lineages (B5.1 and B6.4) contribute to the anterior tail muscle cells, and are consecutively separated from a transcriptionally quiescent germ cell lineage at the 16- and 32-cell stages. Concomitantly, cells of these lineages begin to express Tbx6.b ( Tbx6-r.b ) at the 16- and 32-cell stages, respectively. Meanwhile, Snail expression begins in these two lineages simultaneously at the 32-cell stage. Here, we show that Snail expression is regulated differently between these two lineages. In the B5.1 lineage, Snail was activated through Tbx6.b , which is activated by maternal factors, including Zic-r.a. In the B6.4 lineage, the MAPK pathway was cell-autonomously activated by a constitutively active form of Raf, enabling Zic-r.a to activate Snail independently of Tbx6.b As a result, Snail begins to be expressed at the 32-cell stage simultaneously in these two lineages. Such shortcuts might be required for coordinating developmental programs in embryos in which cells become separated progressively from stem cells, including germline cells. © 2018. Published by The Company of Biologists Ltd.

Hypersonic three-dimensional nonequilibrium boundary-layer equations in generalized curvilinear coordinates

NASA Technical Reports Server (NTRS)

Lee, Jong-Hun

1993-01-01

The basic governing equations for the second-order three-dimensional hypersonic thermal and chemical nonequilibrium boundary layer are derived by means of an order-of-magnitude analysis. A two-temperature concept is implemented into the system of boundary-layer equations by simplifying the rather complicated general three-temperature thermal gas model. The equations are written in a surface-oriented non-orthogonal curvilinear coordinate system, where two curvilinear coordinates are non-orthogonial and a third coordinate is normal to the surface. The equations are described with minimum use of tensor expressions arising from the coordinate transformation, to avoid unnecessary confusion for readers. The set of equations obtained will be suitable for the development of a three-dimensional nonequilibrium boundary-layer code. Such a code could be used to determine economically the aerodynamic/aerothermodynamic loads to the surfaces of hypersonic vehicles with general configurations. In addition, the basic equations for three-dimensional stagnation flow, of which solution is required as an initial value for space-marching integration of the boundary-layer equations, are given along with the boundary conditions, the boundary-layer parameters, and the inner-outer layer matching procedure. Expressions for the chemical reaction rates and the thermodynamic and transport properties in the thermal nonequilibrium environment are explicitly given.

Biological Networks Underlying Soybean Seed Oil Composition and Content

USDA-ARS?s Scientific Manuscript database

Soybean is the most important oil crop in the United States. Production of soybean seed oil requires coordinated expression of many biological components and pathways, which is further regulated by seed development and phyto-hormones. A new research project is initiated in my laboratory to delineat...

Regulation of Root Greening by Light and Auxin/Cytokinin Signaling in Arabidopsis[W

PubMed Central

Kobayashi, Koichi; Baba, Shinsuke; Obayashi, Takeshi; Sato, Mayuko; Toyooka, Kiminori; Keränen, Mika; Aro, Eva-Mari; Fukaki, Hidehiro; Ohta, Hiroyuki; Sugimoto, Keiko; Masuda, Tatsuru

2012-01-01

Tight coordination between plastid differentiation and plant development is best evidenced by the synchronized development of photosynthetic tissues and the biogenesis of chloroplasts. Here, we show that Arabidopsis thaliana roots demonstrate accelerated chlorophyll accumulation and chloroplast development when they are detached from shoots. However, this phenomenon is repressed by auxin treatment. Mutant analyses suggest that auxin transported from the shoot represses root greening via the function of INDOLE-3-ACETIC ACID14, AUXIN RESPONSE FACTOR7 (ARF7), and ARF19. Cytokinin signaling, on the contrary, is required for chlorophyll biosynthesis in roots. The regulation by auxin/cytokinin is dependent on the transcription factor LONG HYPOCOTYL5 (HY5), which is required for the expression of key chlorophyll biosynthesis genes in roots. The expression of yet another root greening transcription factor, GOLDEN2-LIKE2 (GLK2), was found to be regulated in opposing directions by auxin and cytokinin. Furthermore, both the hormone signaling and the GLK transcription factors modified the accumulation of HY5 in roots. Overexpression of GLKs in the hy5 mutant provided evidence that GLKs require HY5 to maximize their activities in root greening. We conclude that the combination of HY5 and GLKs, functioning downstream of light and auxin/cytokinin signaling pathways, is responsible for coordinated expression of the key genes in chloroplast biogenesis. PMID:22415275

Transcriptome analysis of ectopic chloroplast development in green curd cauliflower (Brassica oleracea L. var. botrytis)

USDA-ARS?s Scientific Manuscript database

Chloroplasts are the green plastids where photosynthesis takes place. The biogenesis of chloroplasts requires the coordinate expression of both nuclear and chloroplast genes and is regulated by developmental and environmental signals. Despite extensive studies of this process, the genetic basis and ...

Differential gene expression during conidiation in the grape powdery mildew fungus, Erysiphe necator

USDA-ARS?s Scientific Manuscript database

Asexual sporulation (conidiation) is coordinately regulated in the grape powdery mildew fungus Erysiphe necator, but nothing is known about its genetic regulation. We hypothesized that genes required for conidiation in other fungi would be up-regulated at conidiophore initiation and/or full conidia...

7 CFR 22.305 - Conformance with OMB Circular No. A-95.

Code of Federal Regulations, 2010 CFR

2010-01-01

... jurisdictional rural development planning process must conform to the review requirements expressed in OMB... 7 Agriculture 1 2010-01-01 2010-01-01 false Conformance with OMB Circular No. A-95. 22.305 Section 22.305 Agriculture Office of the Secretary of Agriculture RURAL DEVELOPMENT COORDINATION Roles and...

A transformation method for deriving from a photograph, position and heading of a vehicle in a plane

NASA Technical Reports Server (NTRS)

Sleeper, R. K.; Smith, E. G.

1976-01-01

Equations have been derived that transform perspectively viewed planar surface coordinates, as seen in a photograph, into coordinates of the original plane surface. These transformation equations are developed in terms of nine geometric variables that define the photographic setup and are redefined in terms of eight parameters. The parameters are then treated as independent quantities that fully characterize the transformation and are expressed directly in terms of the four corner coordinates of a reference rectangle in the object plane and their coordinates as seen in a photograph. Vehicle position is determined by transforming the perspectively viewed coordinate position of a representative vehicle target into runway coordinates. Vehicle heading is determined from the runway coordinates of two vehicle target points. When the targets are elevated above the plane of the reference grid, the computation of the heading angle is unaffected; however, the computation of the target position may require adjustment of two parameters. Methods are given for adjusting the parameters for elevation and an example is included for both nonelevated and elevated target conditions.

Silencing of Essential Genes within a Highly Coordinated Operon in Escherichia coli.

PubMed

Goh, Shan; Hohmeier, Angela; Stone, Timothy C; Offord, Victoria; Sarabia, Francisco; Garcia-Ruiz, Cristina; Good, Liam

2015-08-15

Essential bacterial genes located within operons are particularly challenging to study independently because of coordinated gene expression and the nonviability of knockout mutants. Essentiality scores for many operon genes remain uncertain. Antisense RNA (asRNA) silencing or in-frame gene disruption of genes may help establish essentiality but can lead to polar effects on genes downstream or upstream of the target gene. Here, the Escherichia coli ribF-ileS-lspA-fkpB-ispH operon was used to evaluate the possibility of independently studying an essential gene using expressed asRNA and target gene overexpression to deregulate coupled expression. The gene requirement for growth in conditional silencing strains was determined by the relationship of target mRNA reduction with growth inhibition as the minimum transcript level required for 50% growth (MTL50). Mupirocin and globomycin, the protein inhibitors of IleS and LspA, respectively, were used in sensitization assays of strains containing both asRNA-expressing and open reading frame-expressing plasmids to examine deregulation of the overlapping ileS-lspA genes. We found upstream and downstream polar silencing effects when either ileS or lspA was silenced, indicating coupled expression. Weighted MTL50 values (means and standard deviations) of ribF, ileS, and lspA were 0.65 ± 0.18, 0.64 ± 0.06, and 0.76 ± 0.10, respectively. However, they were not significantly different (P = 0.71 by weighted one-way analysis of variance). The gene requirement for ispH could not be determined due to insufficient growth reduction. Mupirocin and globomycin sensitization experiments indicated that ileS-lspA expression could not be decoupled. The results highlight the inherent challenges associated with genetic analyses of operons; however, coupling of essential genes may provide opportunities to improve RNA-silencing antimicrobials. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Silencing of Essential Genes within a Highly Coordinated Operon in Escherichia coli

PubMed Central

Hohmeier, Angela; Stone, Timothy C.; Offord, Victoria; Sarabia, Francisco; Garcia-Ruiz, Cristina; Good, Liam

2015-01-01

Essential bacterial genes located within operons are particularly challenging to study independently because of coordinated gene expression and the nonviability of knockout mutants. Essentiality scores for many operon genes remain uncertain. Antisense RNA (asRNA) silencing or in-frame gene disruption of genes may help establish essentiality but can lead to polar effects on genes downstream or upstream of the target gene. Here, the Escherichia coli ribF-ileS-lspA-fkpB-ispH operon was used to evaluate the possibility of independently studying an essential gene using expressed asRNA and target gene overexpression to deregulate coupled expression. The gene requirement for growth in conditional silencing strains was determined by the relationship of target mRNA reduction with growth inhibition as the minimum transcript level required for 50% growth (MTL50). Mupirocin and globomycin, the protein inhibitors of IleS and LspA, respectively, were used in sensitization assays of strains containing both asRNA-expressing and open reading frame-expressing plasmids to examine deregulation of the overlapping ileS-lspA genes. We found upstream and downstream polar silencing effects when either ileS or lspA was silenced, indicating coupled expression. Weighted MTL50 values (means and standard deviations) of ribF, ileS, and lspA were 0.65 ± 0.18, 0.64 ± 0.06, and 0.76 ± 0.10, respectively. However, they were not significantly different (P = 0.71 by weighted one-way analysis of variance). The gene requirement for ispH could not be determined due to insufficient growth reduction. Mupirocin and globomycin sensitization experiments indicated that ileS-lspA expression could not be decoupled. The results highlight the inherent challenges associated with genetic analyses of operons; however, coupling of essential genes may provide opportunities to improve RNA-silencing antimicrobials. PMID:26070674

Cloning and functional analysis of the promoters that upregulate carotenogenic gene expression during flower development in Gentiana lutea.

PubMed

Zhu, Changfu; Yang, Qingjie; Ni, Xiuzhen; Bai, Chao; Sheng, Yanmin; Shi, Lianxuan; Capell, Teresa; Sandmann, Gerhard; Christou, Paul

2014-04-01

Over the last two decades, many carotenogenic genes have been cloned and used to generate metabolically engineered plants producing higher levels of carotenoids. However, comparatively little is known about the regulation of endogenous carotenogenic genes in higher plants, and this restricts our ability to predict how engineered plants will perform in terms of carotenoid content and composition. During petal development in the Great Yellow Gentian (Gentiana lutea), carotenoid accumulation, the formation of chromoplasts and the upregulation of several carotenogenic genes are temporally coordinated. We investigated the regulatory mechanisms responsible for this coordinated expression by isolating five G. lutea carotenogenic gene (GlPDS, GlZDS, GlLYCB, GlBCH and GlLYCE) promoters by inverse polymerase chain reaction (PCR). Each promoter was sufficient for developmentally regulated expression of the gusA reporter gene following transient expression in tomato (Solanum lycopersicum cv. Micro-Tom). Interestingly, the GlLYCB and GlBCH promoters drove high levels of gusA expression in chromoplast-containing mature green fruits, but low levels in chloroplast-containing immature green fruits, indicating a strict correlation between promoter activity, tomato fruit development and chromoplast differentiation. As well as core promoter elements such as TATA and CAAT boxes, all five promoters together with previously characterized GlZEP promoter contained three common cis-regulatory motifs involved in the response to methyl jasmonate (CGTCA) and ethylene (ATCTA), and required for endosperm expression (Skn-1_motif, GTCAT). These shared common cis-acting elements may represent binding sites for transcription factors responsible for co-regulation. Our data provide insight into the regulatory basis of the coordinated upregulation of carotenogenic gene expression during flower development in G. lutea. © 2013 Scandinavian Plant Physiology Society.

Cdk1 activity acts as a quantitative platform for coordinating cell cycle progression with periodic transcription

PubMed Central

Banyai, Gabor; Baïdi, Feriel; Coudreuse, Damien; Szilagyi, Zsolt

2016-01-01

Cell proliferation is regulated by cyclin-dependent kinases (Cdks) and requires the periodic expression of particular gene clusters in different cell cycle phases. However, the interplay between the networks that generate these transcriptional oscillations and the core cell cycle machinery remains largely unexplored. In this work, we use a synthetic regulable Cdk1 module to demonstrate that periodic expression is governed by quantitative changes in Cdk1 activity, with different clusters directly responding to specific activity levels. We further establish that cell cycle events neither participate in nor interfere with the Cdk1-driven transcriptional program, provided that cells are exposed to the appropriate Cdk1 activities. These findings contrast with current models that propose self-sustained and Cdk1-independent transcriptional oscillations. Our work therefore supports a model in which Cdk1 activity serves as a quantitative platform for coordinating cell cycle transitions with the expression of critical genes to bring about proper cell cycle progression. PMID:27045731

The C. elegans SoxC protein SEM-2 opposes differentiation factors to promote a proliferative blast cell fate in the postembryonic mesoderm

PubMed Central

Tian, Chenxi; Shi, Herong; Colledge, Clark; Stern, Michael; Waterston, Robert; Liu, Jun

2011-01-01

The proper development of multicellular organisms requires precise regulation and coordination of cell fate specification, cell proliferation and differentiation. Abnormal regulation and coordination of these processes could lead to disease, including cancer. We have examined the function of the sole C. elegans SoxC protein, SEM-2, in the M lineage, which produces the postembryonic mesoderm. We found that SEM-2/SoxC is both necessary and sufficient to promote a proliferating blast cell fate, the sex myoblast fate, over a differentiated striated bodywall muscle fate. A number of factors control the specific expression of sem-2 in the sex myoblast precursors and their descendants. This includes direct control of sem-2 expression by a Hox-PBC complex. The crucial nature of the HOX/PBC factors in directly enhancing expression of this proliferative factor in the C. elegans M lineage suggests a possible more general link between Hox-PBC factors and SoxC proteins in regulating cell proliferation. PMID:21307099

Calcineurin/NFAT signaling in osteoblasts regulates bone mass.

PubMed

Winslow, Monte M; Pan, Minggui; Starbuck, Michael; Gallo, Elena M; Deng, Lei; Karsenty, Gerard; Crabtree, Gerald R

2006-06-01

Development and repair of the vertebrate skeleton requires the precise coordination of bone-forming osteoblasts and bone-resorbing osteoclasts. In diseases such as osteoporosis, bone resorption dominates over bone formation, suggesting a failure to harmonize osteoclast and osteoblast function. Here, we show that mice expressing a constitutively nuclear NFATc1 variant (NFATc1(nuc)) in osteoblasts develop high bone mass. NFATc1(nuc) mice have massive osteoblast overgrowth, enhanced osteoblast proliferation, and coordinated changes in the expression of Wnt signaling components. In contrast, viable NFATc1-deficient mice have defects in skull bone formation in addition to impaired osteoclast development. NFATc1(nuc) mice have increased osteoclastogenesis despite normal levels of RANKL and OPG, indicating that an additional NFAT-regulated mechanism influences osteoclastogenesis in vivo. Calcineurin/NFATc signaling in osteoblasts controls the expression of chemoattractants that attract monocytic osteoclast precursors, thereby coupling bone formation and bone resorption. Our results indicate that NFATc1 regulates bone mass by functioning in both osteoblasts and osteoclasts.

Graded levels of FGF protein span the midbrain and can instruct graded induction and repression of neural mapping labels

PubMed Central

Chen, Yao; Mohammadi, Moosa; Flanagan, John G.

2009-01-01

Summary Graded guidance labels are widely used in neural map formation, but it is not well understood which potential strategy leads to their graded expression. In midbrain tectal map development, FGFs can induce an entire midbrain, but their protein distribution is unclear, nor is it known whether they may act instructively to produce graded gene expression. Using a receptor-alkaline phosphatase fusion probe, we find a long-range posterior>anterior FGF protein gradient spanning the midbrain. Heparan sulfate proteoglycan (HSPG) is required for this gradient. To test whether graded FGF concentrations can instruct graded gene expression, a quantitative tectal explant assay was developed. Engrailed-2 and ephrin-As, normally in posterior>anterior tectal gradients, showed graded upregulation. Moreover, EphAs, normally in anterior>posterior countergradients, showed coordinately graded downregulation. These results provide a mechanism to establish graded mapping labels, and more generally provide a developmental strategy to coordinately induce a structure and pattern its cell properties in gradients. PMID:19555646

SOX1 links the function of neural patterning and Notch signalling in the ventral spinal cord during the neuron-glial fate switch

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

Genethliou, Nicholas; Panayiotou, Elena; Department of Biological Sciences, University of Cyprus, P.O. Box 20537, 1678 Nicosia

2009-12-25

During neural development the transition from neurogenesis to gliogenesis, known as the neuron-glial ({Nu}/G) fate switch, requires the coordinated function of patterning factors, pro-glial factors and Notch signalling. How this process is coordinated in the embryonic spinal cord is poorly understood. Here, we demonstrate that during the N/G fate switch in the ventral spinal cord (vSC) SOX1 links the function of neural patterning and Notch signalling. We show that, SOX1 expression in the vSC is regulated by PAX6, NKX2.2 and Notch signalling in a domain-specific manner. We further show that SOX1 regulates the expression of Hes1 and that loss ofmore » Sox1 leads to enhanced production of oligodendrocyte precursors from the pMN. Finally, we show that Notch signalling functions upstream of SOX1 during this fate switch and is independently required for the acquisition of the glial fate perse by regulating Nuclear Factor I A expression in a PAX6/SOX1/HES1/HES5-independent manner. These data integrate functional roles of neural patterning factors, Notch signalling and SOX1 during gliogenesis.« less

Bending wavefunctions for linear molecules

NASA Astrophysics Data System (ADS)

Hirano, Tsuneo; Nagashima, Umpei; Jensen, Per

2018-01-01

The bending motion of a linear triatomic molecule has two unique characteristics: the bending mode is doubly degenerate and only positive values of the bending angle, expressed by the bond angle supplement ρ bar , can be observed. The double degeneracy requires the wavefunction to be described as a two-dimensional oscillator. In the present work, we first review the conventional expressions based on two, symmetrically equivalent normal coordinates. Then we discuss an alternative expression for the bending wavefunction in terms of two geometrical coordinates, the bond angle supplement ρ bar (= π - τ ⩾ 0 , where τ is the bond angle) and the rotation angle χ (0 ⩽ χ < 2 π) describing rotation of the molecule around the molecular axis. In this formalism, defined for the (ρ bar , χ) polar-coordinate space with volume element ρ bar d ρ bar dχ , the one-dimensional wavefunction resulted through re-normalization for χ has zero amplitude at ρ bar = 0 , and the ro-vibrational average of the bending angle, i.e., the expectation value 〈 ρ bar 〉 , attains a non-zero, positive value for any ro-vibrational state including the vibrational ground state. This conclusion appears to cause some controversy since much conventional spectroscopic wisdom insists on 〈 ρ bar 〉 having the value zero.

Integrin-α5 Coordinates Assembly of Posterior Cranial Placodes in Zebrafish and Enhances Fgf-Dependent Regulation of Otic/Epibranchial Cells

PubMed Central

Bhat, Neha; Riley, Bruce B.

2011-01-01

Vertebrate sensory organs develop in part from cranial placodes, a series of ectodermal thickenings that coalesce from a common domain of preplacodal ectoderm. Mechanisms coordinating morphogenesis and differentiation of discrete placodes are still poorly understood. We have investigated whether placodal assembly in zebrafish requires Integrin- α5 (itga5), an extracellular matrix receptor initially expressed throughout the preplacodal ectoderm. Morpholino knockdown of itga5 had no detectable effect on anterior placodes (pituitary, nasal and lens), but posterior placodes developed abnormally, resulting in disorganization of trigeminal and epibranchial ganglia and reduction of the otic vesicle. Cell motion analysis in GFP-transgenic embryos showed that cell migration in itga5 morphants was highly erratic and unfocused, impairing convergence and blocking successive recruitment of new cells into these placodes. Further studies revealed genetic interactions between itga5 and Fgf signaling. First, itga5 morphants showed changes in gene expression mimicking modest reduction in Fgf signaling. Second, itga5 morphants showed elevated apoptosis in the otic/epibranchial domain, which was rescued by misexpression of Fgf8. Third, knockdown of the Fgf effector erm had no effect by itself but strongly enhanced defects in itga5 morphants. Finally, proper regulation of itga5 requires dlx3b/4b and pax8, which are themselves regulated by Fgf. These findings support a model in which itga5 coordinates cell migration into posterior placodes and augments Fgf signaling required for patterning of these tissues and cell survival in otic/epibranchial placodes. PMID:22164214

Representation of viruses in the remediated PDB archive

PubMed Central

Lawson, Catherine L.; Dutta, Shuchismita; Westbrook, John D.; Henrick, Kim; Berman, Helen M.

2008-01-01

A new scheme has been devised to represent viruses and other biological assemblies with regular noncrystallographic symmetry in the Protein Data Bank (PDB). The scheme describes existing and anticipated PDB entries of this type using generalized descriptions of deposited and experimental coordinate frames, symmetry and frame transformations. A simplified notation has been adopted to express the symmetry generation of assemblies from deposited coordinates and matrix operations describing the required point, helical or crystallographic symmetry. Complete correct information for building full assemblies, subassemblies and crystal asymmetric units of all virus entries is now available in the remediated PDB archive. PMID:18645236

A predictive biophysical model of translational coupling to coordinate and control protein expression in bacterial operons

PubMed Central

Tian, Tian; Salis, Howard M.

2015-01-01

Natural and engineered genetic systems require the coordinated expression of proteins. In bacteria, translational coupling provides a genetically encoded mechanism to control expression level ratios within multi-cistronic operons. We have developed a sequence-to-function biophysical model of translational coupling to predict expression level ratios in natural operons and to design synthetic operons with desired expression level ratios. To quantitatively measure ribosome re-initiation rates, we designed and characterized 22 bi-cistronic operon variants with systematically modified intergenic distances and upstream translation rates. We then derived a thermodynamic free energy model to calculate de novo initiation rates as a result of ribosome-assisted unfolding of intergenic RNA structures. The complete biophysical model has only five free parameters, but was able to accurately predict downstream translation rates for 120 synthetic bi-cistronic and tri-cistronic operons with rationally designed intergenic regions and systematically increased upstream translation rates. The biophysical model also accurately predicted the translation rates of the nine protein atp operon, compared to ribosome profiling measurements. Altogether, the biophysical model quantitatively predicts how translational coupling controls protein expression levels in synthetic and natural bacterial operons, providing a deeper understanding of an important post-transcriptional regulatory mechanism and offering the ability to rationally engineer operons with desired behaviors. PMID:26117546

MK-801 Impairs Cognitive Coordination on a Rotating Arena (Carousel) and Contextual Specificity of Hippocampal Immediate-Early Gene Expression in a Rat Model of Psychosis

PubMed Central

Kubík, Štěpán; Buchtová, Helena; Valeš, Karel; Stuchlík, Aleš

2014-01-01

Flexible behavior in dynamic, real-world environments requires more than static spatial learning and memory. Discordant and unstable cues must be organized in coherent subsets to give rise to meaningful spatial representations. We model this form of cognitive coordination on a rotating arena – Carousel where arena- and room-bound spatial cues are dissociated. Hippocampal neuronal ensemble activity can repeatedly switch between multiple representations of such an environment. Injection of tetrodotoxin into one hippocampus prevents cognitive coordination during avoidance of a stationary room-defined place on the Carousel and increases coactivity of previously unrelated neurons in the uninjected hippocampus. Place avoidance on the Carousel is impaired after systemic administration of non-competitive NMDAr blockers (MK-801) used to model schizophrenia in animals and people. We tested if this effect is due to cognitive disorganization or other effect of NMDAr antagonism such as hyperlocomotion, spatial memory impairment, or general learning deficit. We also examined if the same dose of MK-801 alters patterns of immediate-early gene (IEG) expression in the hippocampus. IEG expression is triggered in neuronal nuclei in a context-specific manner after behavioral exploration and it is used to map activity in neuronal populations. IEG expression is critical for maintenance of synaptic plasticity and memory consolidation. We show that the same dose of MK-801 that impairs spatial coordination of rats on the Carousel also eliminates contextual specificity of IEG expression in hippocampal CA1 ensembles. This effect is due to increased similarity between ensembles activated in different environments, consistent with the idea that it is caused by increased coactivity between neurons, which did not previously fire together. Our data support the proposition of the Hypersynchrony theory that cognitive disorganization in psychosis is due to increased coactivity between unrelated neurons. PMID:24659959

Multi-particle three-dimensional coordinate estimation in real-time optical manipulation

NASA Astrophysics Data System (ADS)

Dam, J. S.; Perch-Nielsen, I.; Palima, D.; Gluckstad, J.

2009-11-01

We have previously shown how stereoscopic images can be obtained in our three-dimensional optical micromanipulation system [J. S. Dam et al, Opt. Express 16, 7244 (2008)]. Here, we present an extension and application of this principle to automatically gather the three-dimensional coordinates for all trapped particles with high tracking range and high reliability without requiring user calibration. Through deconvolving of the red, green, and blue colour planes to correct for bleeding between colour planes, we show that we can extend the system to also utilize green illumination, in addition to the blue and red. Applying the green colour as on-axis illumination yields redundant information for enhanced error correction, which is used to verify the gathered data, resulting in reliable coordinates as well as producing visually attractive images.

Tumor targeting of gene expression through metal-coordinated conjugation with dextran.

PubMed

Hosseinkhani, Hossein; Aoyama, Teruyoshi; Ogawa, Osamu; Tabata, Yasuhiko

2003-03-07

Tumor targeting of plasmid DNA was achieved through the conjugation of dextran derivatives with chelate residues based on metal coordination. Diethylenetriamine pentaacetic acid (DTPA), spermidine (Sd), and spermine (Sm) were chemically introduced to the hydroxyl groups of dextran to obtain dextran-DTPA, dextran-Sd and dextran-Sm derivatives. Conjugation of the dextran derivative by Zn(2+) coordination decreased the apparent size of the plasmid DNA, depending on the derivative type. The negative zeta potential of plasmid DNA became almost 0 mV after Zn(2+)-coordinated conjugation with dextran-Sm. When the dextran derivative-plasmid DNA conjugates with Zn(2+) coordination were intravenously injected subcutaneously into mice bearing Meth-AR-1 fibrosarcoma, the dextran-Sm-plasmid DNA conjugate significantly enhanced the level of gene expression in the tumor, in contrast to the conjugate of other dextran derivatives and free plasmid DNA. The enhanced gene expression produced by the Zn(2+)-coordinated dextran-Sm-plasmid DNA conjugate was specific to the tumor, whereas a simple mixture of dextran-Sm and plasmid DNA was not effective. The level of gene expression depended on the percentage of chelate residues introduced, the mixing weight ratio of the plasmid DNA/Sm residue used for conjugate preparation, and the plasmid DNA dose. A fluorescent microscopic study revealed that localization of plasmid DNA in the tumor tissue was observed only after injection of the dextran-Sm-plasmid DNA conjugate with Zn(2+) coordination. In addition, the gene expression induced by the conjugate lasted for more than 10 days after the injection. We conclude that Zn(2+)-coordinated dextran-Sm conjugation is a promising way to enable plasmid DNA to target the tumor in gene expression as well as to prolong the duration of gene expression.

Computer Solution of the Two-Dimensional Tether Ball: Problem to Illustrate Newton's Second Law.

ERIC Educational Resources Information Center

Zimmerman, W. Bruce

Force diagrams involving angular velocity, linear velocity, centripetal force, work, and kinetic energy are given with related equations of motion expressed in polar coordinates. The computer is used to solve differential equations, thus reducing the mathematical requirements of the students. An experiment is conducted using an air table to check…

Generalized Squashing Factors for Covariant Description of Magnetic Connectivity in the Solar Corona

NASA Technical Reports Server (NTRS)

Titov, V. S.

2007-01-01

The study of magnetic connectivity in the solar corona reveals a need to generalize the field line mapping technique to arbitrary geometry of the boundaries and systems of coordinates. Indeed, the global description of the connectivity in the corona requires the use of the photospheric and solar wind boundaries. Both are closed surfaces and therefore do not admit a global regular system of coordinates. At least two overlapping regular systems of coordinates for each of the boundaries are necessary in this case to avoid spherical-pole-like singularities in the coordinates of the footpoints. This implies that the basic characteristic of magnetic connectivity-the squashing degree or factor Q of elemental flux tubes, according to Titov and coworkers-must be rewritten in covariant form. Such a covariant expression of Q is derived in this work. The derived expression is very flexible and highly efficient for describing the global magnetic connectivity in the solar corona. In addition, a general expression for a new characteristic Q1, which defines a squashing of the flux tubes in the directions perpendicular to the field lines, is determined. This new quantity makes it possible to filter out the quasi-separatrix layers whose large values of Q are caused by a projection effect at the field lines nearly touching the photosphere. Thus, the value Q1 provides a much more precise description of the volumetric properties of the magnetic field structure. The difference between Q and Q1 is illustrated by comparing their distributions for two configurations, one of which is the Titov-Demoulin model of a twisted magnetic field.

A molecular sensor that allows a gut commensal to control its nutrient foundation in a competitive ecosystem

PubMed Central

Hooper, Lora V.; Xu, Jian; Falk, Per G.; Midtvedt, Tore; Gordon, Jeffrey I.

1999-01-01

Little is known about how members of the indigenous microflora interact with their mammalian hosts to establish mutually beneficial relationships. We have used a gnotobiotic mouse model to show that Bacteroides thetaiotaomicron, a component of the intestinal microflora of mice and humans, uses a repressor, FucR, as a molecular sensor of l-fucose availability. FucR coordinates expression of an operon encoding enzymes in the l-fucose metabolic pathway with expression of another locus that regulates production of fucosylated glycans in intestinal enterocytes. Genetic and biochemical studies indicate that FucR does this by using fucose as an inducer at one locus and as a corepressor at the other locus. Coordinating this commensal’s immediate nutritional requirements with production of a host-derived energy source is consistent with its need to enter and persist within a competitive ecosystem. PMID:10449780

RNA-binding proteins ZFP36L1 and ZFP36L2 promote cell quiescence.

PubMed

Galloway, Alison; Saveliev, Alexander; Łukasiak, Sebastian; Hodson, Daniel J; Bolland, Daniel; Balmanno, Kathryn; Ahlfors, Helena; Monzón-Casanova, Elisa; Mannurita, Sara Ciullini; Bell, Lewis S; Andrews, Simon; Díaz-Muñoz, Manuel D; Cook, Simon J; Corcoran, Anne; Turner, Martin

2016-04-22

Progression through the stages of lymphocyte development requires coordination of the cell cycle. Such coordination ensures genomic integrity while cells somatically rearrange their antigen receptor genes [in a process called variable-diversity-joining (VDJ) recombination] and, upon successful rearrangement, expands the pools of progenitor lymphocytes. Here we show that in developing B lymphocytes, the RNA-binding proteins (RBPs) ZFP36L1 and ZFP36L2 are critical for maintaining quiescence before precursor B cell receptor (pre-BCR) expression and for reestablishing quiescence after pre-BCR-induced expansion. These RBPs suppress an evolutionarily conserved posttranscriptional regulon consisting of messenger RNAs whose protein products cooperatively promote transition into the S phase of the cell cycle. This mechanism promotes VDJ recombination and effective selection of cells expressing immunoglobulin-μ at the pre-BCR checkpoint. Copyright © 2016, American Association for the Advancement of Science.

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

Coordinated Regulation of Niche and Stem Cell Precursors by Hormonal Signaling

PubMed Central

Gancz, Dana; Lengil, Tamar; Gilboa, Lilach

2011-01-01

Stem cells and their niches constitute units that act cooperatively to achieve adult body homeostasis. How such units form and whether stem cell and niche precursors might be coordinated already during organogenesis are unknown. In fruit flies, primordial germ cells (PGCs), the precursors of germ line stem cells (GSCs), and somatic niche precursors develop within the larval ovary. Together they form the 16–20 GSC units of the adult ovary. We show that ecdysone receptors are required to coordinate the development of niche and GSC precursors. At early third instar, ecdysone receptors repress precocious differentiation of both niches and PGCs. Early repression is required for correct morphogenesis of the ovary and for protecting future GSCs from differentiation. At mid-third instar, ecdysone signaling is required for niche formation. Finally, and concurrent with the initiation of wandering behavior, ecdysone signaling initiates PGC differentiation by allowing the expression of the differentiation gene bag of marbles in PGCs that are not protected by the newly formed niches. All the ovarian functions of ecdysone receptors are mediated through early repression, and late activation, of the ecdysone target gene broad. These results show that, similar to mammals, a brain-gland-gonad axis controls the initiation of oogenesis in insects. They further exemplify how a physiological cue coordinates the formation of a stem cell unit within an organ: it is required for niche establishment and to ensure that precursor cells to adult stem cells remain undifferentiated until the niches can accommodate them. Similar principles might govern the formation of additional stem cell units during organogenesis. PMID:22131903

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

Calculating Free Energies Using Average Force

NASA Technical Reports Server (NTRS)

Darve, Eric; Pohorille, Andrew; DeVincenzi, Donald L. (Technical Monitor)

2001-01-01

A new, general formula that connects the derivatives of the free energy along the selected, generalized coordinates of the system with the instantaneous force acting on these coordinates is derived. The instantaneous force is defined as the force acting on the coordinate of interest so that when it is subtracted from the equations of motion the acceleration along this coordinate is zero. The formula applies to simulations in which the selected coordinates are either unconstrained or constrained to fixed values. It is shown that in the latter case the formula reduces to the expression previously derived by den Otter and Briels. If simulations are carried out without constraining the coordinates of interest, the formula leads to a new method for calculating the free energy changes along these coordinates. This method is tested in two examples - rotation around the C-C bond of 1,2-dichloroethane immersed in water and transfer of fluoromethane across the water-hexane interface. The calculated free energies are compared with those obtained by two commonly used methods. One of them relies on determining the probability density function of finding the system at different values of the selected coordinate and the other requires calculating the average force at discrete locations along this coordinate in a series of constrained simulations. The free energies calculated by these three methods are in excellent agreement. The relative advantages of each method are discussed.

SELF-GRAVITATIONAL FORCE CALCULATION OF SECOND-ORDER ACCURACY FOR INFINITESIMALLY THIN GASEOUS DISKS IN POLAR COORDINATES

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

Wang, Hsiang-Hsu; Taam, Ronald E.; Yen, David C. C., E-mail: yen@math.fju.edu.tw

Investigating the evolution of disk galaxies and the dynamics of proto-stellar disks can involve the use of both a hydrodynamical and a Poisson solver. These systems are usually approximated as infinitesimally thin disks using two-dimensional Cartesian or polar coordinates. In Cartesian coordinates, the calculations of the hydrodynamics and self-gravitational forces are relatively straightforward for attaining second-order accuracy. However, in polar coordinates, a second-order calculation of self-gravitational forces is required for matching the second-order accuracy of hydrodynamical schemes. We present a direct algorithm for calculating self-gravitational forces with second-order accuracy without artificial boundary conditions. The Poisson integral in polar coordinates ismore » expressed in a convolution form and the corresponding numerical complexity is nearly linear using a fast Fourier transform. Examples with analytic solutions are used to verify that the truncated error of this algorithm is of second order. The kernel integral around the singularity is applied to modify the particle method. The use of a softening length is avoided and the accuracy of the particle method is significantly improved.« less

Equidistant map projections of a triaxial ellipsoid with the use of reduced coordinates

NASA Astrophysics Data System (ADS)

Pędzich, Paweł

2017-12-01

The paper presents a new method of constructing equidistant map projections of a triaxial ellipsoid as a function of reduced coordinates. Equations for x and y coordinates are expressed with the use of the normal elliptic integral of the second kind and Jacobian elliptic functions. This solution allows to use common known and widely described in literature methods of solving such integrals and functions. The main advantage of this method is the fact that the calculations of x and y coordinates are practically based on a single algorithm that is required to solve the elliptic integral of the second kind. Equations are provided for three types of map projections: cylindrical, azimuthal and pseudocylindrical. These types of projections are often used in planetary cartography for presentation of entire and polar regions of extraterrestrial objects. The paper also contains equations for the calculation of the length of a meridian and a parallel of a triaxial ellipsoid in reduced coordinates. Moreover, graticules of three coordinates systems (planetographic, planetocentric and reduced) in developed map projections are presented. The basic properties of developed map projections are also described. The obtained map projections may be applied in planetary cartography in order to create maps of extraterrestrial objects.

ROLES OF CELL-INTRINSIC AND MICROENVIRONMENTAL FACTORS IN PHOTORECEPTOR CELL DIFFERENTIATION

PubMed Central

Bradford, Rebecca L.; Wang, Chenwei; Zack, Donald J.; Adler, Ruben

2005-01-01

Photoreceptor differentiation requires the coordinated expression of numerous genes. It is unknown whether those genes share common regulatory mechanisms or are independently regulated by distinct mechanisms. To distinguish between these scenarios, we have used in situ hybridization, RT-PCR and real time PCR to analyze the expression of visual pigments and other photoreceptor-specific genes during chick embryo retinal development in ovo, as well as in retinal cell cultures treated with molecules that regulate the expression of particular visual pigments. In ovo, onset of gene expression was asynchronous, becoming detectable at the time of photoreceptor generation (ED 5–8) for some photoreceptor genes, but only around the time of outer segment formation (ED 14–16) for others. Treatment of retinal cell cultures with activin, staurosporine or CNTF selectively induced or down-regulated specific visual pigment genes, but many cognate rod- or cone-specific genes were not affected by the treatments. These results indicate that many photoreceptor genes are independently regulated during development, are consistent with the existence of at least two distinct stages of gene expression during photoreceptor differentiation, suggest that intrinsic, coordinated regulation of a cascade of gene expression triggered by a commitment to the photoreceptor fate is not a general mechanism of photoreceptor differentiation, and imply that using a single photoreceptor-specific “marker” as a proxy to identify photoreceptor cell fate is problematic. PMID:16120439

Vascular Procr+ stem cells: Finding new branches while looking for the roots.

PubMed

Gur-Cohen, Shiri; Lapidot, Tsvee

2016-10-01

Generation and growth of the blood vasculature network is a highly synchronized process, requiring coordinated efforts of endothelial cells and pericytes to maintain blood vessel integrity and regeneration. In a recent paper published in Cell Research, Yu et al. identified and characterized bipotent Procr-expressing vascular endothelial stem cells, which give rise to both endothelial cells and pericytes.

Identification of conserved drought stress responsive gene-network across tissues and developmental stages in rice.

PubMed

Smita, Shuchi; Katiyar, Amit; Pandey, Dev Mani; Chinnusamy, Viswanathan; Archak, Sunil; Bansal, Kailash Chander

2013-01-01

Identification of genes that are coexpressed across various tissues and environmental stresses is biologically interesting, since they may play coordinated role in similar biological processes. Genes with correlated expression patterns can be best identified by using coexpression network analysis of transcriptome data. In the present study, we analyzed the temporal-spatial coordination of gene expression in root, leaf and panicle of rice under drought stress and constructed network using WGCNA and Cytoscape. Total of 2199 differentially expressed genes (DEGs) were identified in at least three or more tissues, wherein 88 genes have coordinated expression profile among all the six tissues under drought stress. These 88 highly coordinated genes were further subjected to module identification in the coexpression network. Based on chief topological properties we identified 18 hub genes such as ABC transporter, ATP-binding protein, dehydrin, protein phosphatase 2C, LTPL153 - Protease inhibitor, phosphatidylethanolaminebinding protein, lactose permease-related, NADP-dependent malic enzyme, etc. Motif enrichment analysis showed the presence of ABRE cis-elements in the promoters of > 62% of the coordinately expressed genes. Our results suggest that drought stress mediated upregulated gene expression was coordinated through an ABA-dependent signaling pathway across tissues, at least for the subset of genes identified in this study, while down regulation appears to be regulated by tissue specific pathways in rice.

Brg1 coordinates multiple processes during retinogenesis and is a tumor suppressor in retinoblastoma

DOE PAGES

Aldiri, Issam; Ajioka, Itsuki; Xu, Beisi; ...

2015-12-01

Retinal development requires precise temporal and spatial coordination of cell cycle exit, cell fate specification, cell migration and differentiation. When this process is disrupted, retinoblastoma, a developmental tumor of the retina, can form. Epigenetic modulators are central to precisely coordinating developmental events, and many epigenetic processes have been implicated in cancer. Studying epigenetic mechanisms in development is challenging because they often regulate multiple cellular processes; therefore, elucidating the primary molecular mechanisms involved can be difficult. Here we explore the role of Brg1 (Smarca4) in retinal development and retinoblastoma in mice using molecular and cellular approaches. Brg1 was found to regulatemore » retinal size by controlling cell cycle length, cell cycle exit and cell survival during development. Brg1 was not required for cell fate specification but was required for photoreceptor differentiation and cell adhesion/polarity programs that contribute to proper retinal lamination during development. The combination of defective cell differentiation and lamination led to retinal degeneration in Brg1-deficient retinae. Despite the hypocellularity, premature cell cycle exit, increased cell death and extended cell cycle length, retinal progenitor cells persisted in Brg1-deficient retinae, making them more susceptible to retinoblastoma. In conclusion, ChIP-Seq analysis suggests that Brg1 might regulate gene expression through multiple mechanisms.« less

Brg1 coordinates multiple processes during retinogenesis and is a tumor suppressor in retinoblastoma

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

Aldiri, Issam; Ajioka, Itsuki; Xu, Beisi

Retinal development requires precise temporal and spatial coordination of cell cycle exit, cell fate specification, cell migration and differentiation. When this process is disrupted, retinoblastoma, a developmental tumor of the retina, can form. Epigenetic modulators are central to precisely coordinating developmental events, and many epigenetic processes have been implicated in cancer. Studying epigenetic mechanisms in development is challenging because they often regulate multiple cellular processes; therefore, elucidating the primary molecular mechanisms involved can be difficult. Here we explore the role of Brg1 (Smarca4) in retinal development and retinoblastoma in mice using molecular and cellular approaches. Brg1 was found to regulatemore » retinal size by controlling cell cycle length, cell cycle exit and cell survival during development. Brg1 was not required for cell fate specification but was required for photoreceptor differentiation and cell adhesion/polarity programs that contribute to proper retinal lamination during development. The combination of defective cell differentiation and lamination led to retinal degeneration in Brg1-deficient retinae. Despite the hypocellularity, premature cell cycle exit, increased cell death and extended cell cycle length, retinal progenitor cells persisted in Brg1-deficient retinae, making them more susceptible to retinoblastoma. In conclusion, ChIP-Seq analysis suggests that Brg1 might regulate gene expression through multiple mechanisms.« less

Rhizobial infection does not require cortical expression of upstream common symbiosis genes responsible for the induction of Ca(2+) spiking.

PubMed

Hayashi, Teruyuki; Shimoda, Yoshikazu; Sato, Shusei; Tabata, Satoshi; Imaizumi-Anraku, Haruko; Hayashi, Makoto

2014-01-01

For the establishment of an effective root nodule symbiosis, a coordinated regulation of the infection processes between the epidermis and cortex is required. However, it remains unclear whether the symbiotic genes identified so far are involved in epidermal and/or cortical infection, e.g. epidermal and cortical infection thread formation or cortical cell division. To analyze the symbiotic gene requirements of the infection process, we have developed an epidermis-specific expression system (pEpi expression system) and examined the symbiotic genes NFR1, NFR5, NUP85, NUP133, CASTOR, POLLUX, CCaMK, CYCLOPS, NSP1 and NSP2 for involvement in the infection process in the epidermis and cortex. Our study shows that expression of the upstream common symbiosis genes CASTOR, POLLUX, NUP85 and NUP133 in the epidermis is sufficient to induce formation of infection threads and cortical cell division, leading to the development of fully effective nodules. Our system also shows a requirement of CCaMK, CYCLOPS, NSP1 and NSP2 for the entire nodulation process, and the different contributions of NFR1 and NFR5 to cortical infection thread formation. Based on these analyses using the pEpi expression system, we propose a functional model of symbiotic genes for epidermal and cortical infection. © 2013 The Authors The Plant Journal © 2013 John Wiley & Sons Ltd.

Developmental regulation of CYCA2s contributes to tissue-specific proliferation in Arabidopsis

PubMed Central

Vanneste, Steffen; Coppens, Frederik; Lee, EunKyoung; Donner, Tyler J; Xie, Zidian; Van Isterdael, Gert; Dhondt, Stijn; De Winter, Freya; De Rybel, Bert; Vuylsteke, Marnik; De Veylder, Lieven; Friml, Jiří; Inzé, Dirk; Grotewold, Erich; Scarpella, Enrico; Sack, Fred; Beemster, Gerrit T S; Beeckman, Tom

2011-01-01

In multicellular organisms, morphogenesis relies on a strict coordination in time and space of cell proliferation and differentiation. In contrast to animals, plant development displays continuous organ formation and adaptive growth responses during their lifespan relying on a tight coordination of cell proliferation. How developmental signals interact with the plant cell-cycle machinery is largely unknown. Here, we characterize plant A2-type cyclins, a small gene family of mitotic cyclins, and show how they contribute to the fine-tuning of local proliferation during plant development. Moreover, the timely repression of CYCA2;3 expression in newly formed guard cells is shown to require the stomatal transcription factors FOUR LIPS/MYB124 and MYB88, providing a direct link between developmental programming and cell-cycle exit in plants. Thus, transcriptional downregulation of CYCA2s represents a critical mechanism to coordinate proliferation during plant development. PMID:21772250

Numb deficiency in cerebellar Purkinje cells impairs synaptic expression of metabotropic glutamate receptor and motor coordination.

PubMed

Zhou, Liang; Yang, Dong; Wang, De-Juan; Xie, Ya-Jun; Zhou, Jia-Huan; Zhou, Lin; Huang, Hao; Han, Shuo; Shao, Chong-Yu; Li, Hua-Shun; Zhu, J Julius; Qiu, Meng-Sheng; De Zeeuw, Chris I; Shen, Ying

2015-12-15

Protein Numb, first identified as a cell-fate determinant in Drosophila, has been shown to promote the development of neurites in mammals and to be cotransported with endocytic receptors in clathrin-coated vesicles in vitro. Nevertheless, its function in mature neurons has not yet been elucidated. Here we show that cerebellar Purkinje cells (PCs) express high levels of Numb during adulthood and that conditional deletion of Numb in PCs is sufficient to impair motor coordination despite maintenance of a normal cerebellar cyto-architecture. Numb proved to be critical for internalization and recycling of metabotropic glutamate 1 receptor (mGlu1) in PCs. A significant decrease of mGlu1 and an inhibition of long-term depression at the parallel fiber-PC synapse were observed in conditional Numb knockout mice. Indeed, the trafficking of mGlu1 induced by agonists was inhibited significantly in these mutants, but the expression of ionotropic glutamate receptor subunits and of mGlu1-associated proteins was not affected by the loss of Numb. Moreover, transient and persistent forms of mGlu1 plasticity were robustly induced in mutant PCs, suggesting that they do not require mGlu1 trafficking. Together, our data demonstrate that Numb is a regulator for constitutive expression and dynamic transport of mGlu1.

ERECTA signaling controls Arabidopsis inflorescence architecture through chromatin-mediated activation of PRE1 expression.

PubMed

Cai, Hanyang; Zhao, Lihua; Wang, Lulu; Zhang, Man; Su, Zhenxia; Cheng, Yan; Zhao, Heming; Qin, Yuan

2017-06-01

Flowering plants display a remarkable diversity in inflorescence architecture, and pedicel length is one of the key contributors to this diversity. In Arabidopsis thaliana, the receptor-like kinase ERECTA (ER) mediated signaling pathway plays important roles in regulating inflorescence architecture by promoting cell proliferation. However, the regulating mechanism remains elusive in the pedicel. Genetic interactions between ERECTA signaling and the chromatin remodeling complex SWR1 in the control of inflorescence architecture were studied. Comparative transcriptome analysis was applied to identify downstream components. Chromatin immunoprecipitation and nucleosome occupancy was further investigated. The results indicated that the chromatin remodeler SWR1 coordinates with ERECTA signaling in regulating inflorescence architecture by activating the expression of PRE1 family genes and promoting pedicel elongation. It was found that SWR1 is required for the incorporation of the H2A.Z histone variant into nucleosomes of the whole PRE1 gene family and the ERECTA controlled expression of PRE1 gene family through regulating nucleosome dynamics. We propose that utilization of a chromatin remodeling complex to regulate gene expression is a common theme in developmental control across kingdoms. These findings shed light on the mechanisms through which chromatin remodelers orchestrate complex transcriptional regulation of gene expression in coordination with a developmental cue. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

Insights into the Regulation of DMSP Synthesis in the Diatom Thalassiosira pseudonana through APR Activity, Proteomics and Gene Expression Analyses on Cells Acclimating to Changes in Salinity, Light and Nitrogen

PubMed Central

Kettles, Nicola Louise; Kopriva, Stanislav; Malin, Gill

2014-01-01

Despite the importance of dimethylsulphoniopropionate (DMSP) in the global sulphur cycle and climate regulation, the biological pathways underpinning its synthesis in marine phytoplankton remain poorly understood. The intracellular concentration of DMSP increases with increased salinity, increased light intensity and nitrogen starvation in the diatom Thalassiosira pseudonana. We used these conditions to investigate DMSP synthesis at the cellular level via analysis of enzyme activity, gene expression and proteome comparison. The activity of the key sulphur assimilatory enzyme, adenosine 5′-phosphosulphate reductase was not coordinated with increasing intracellular DMSP concentration. Under all three treatments coordination in the expression of sulphur assimilation genes was limited to increases in sulphite reductase transcripts. Similarly, proteomic 2D gel analysis only revealed an increase in phosphoenolpyruvate carboxylase following increases in DMSP concentration. Our findings suggest that increased sulphur assimilation might not be required for increased DMSP synthesis, instead the availability of carbon and nitrogen substrates may be important in the regulation of this pathway. This contrasts with the regulation of sulphur metabolism in higher plants, which generally involves up-regulation of several sulphur assimilatory enzymes. In T. pseudonana changes relating to sulphur metabolism were specific to the individual treatments and, given that little coordination was seen in transcript and protein responses across the three growth conditions, different patterns of regulation might be responsible for the increase in DMSP concentration seen under each treatment. PMID:24733415

Cellular reprogramming dynamics follow a simple 1D reaction coordinate

NASA Astrophysics Data System (ADS)

Teja Pusuluri, Sai; Lang, Alex H.; Mehta, Pankaj; Castillo, Horacio E.

2018-01-01

Cellular reprogramming, the conversion of one cell type to another, induces global changes in gene expression involving thousands of genes, and understanding how cells globally alter their gene expression profile during reprogramming is an ongoing problem. Here we reanalyze time-course data on cellular reprogramming from differentiated cell types to induced pluripotent stem cells (iPSCs) and show that gene expression dynamics during reprogramming follow a simple 1D reaction coordinate. This reaction coordinate is independent of both the time it takes to reach the iPSC state as well as the details of the experimental protocol used. Using Monte-Carlo simulations, we show that such a reaction coordinate emerges from epigenetic landscape models where cellular reprogramming is viewed as a ‘barrier-crossing’ process between cell fates. Overall, our analysis and model suggest that gene expression dynamics during reprogramming follow a canonical trajectory consistent with the idea of an ‘optimal path’ in gene expression space for reprogramming.

Computer transformation of partial differential equations into any coordinate system

NASA Technical Reports Server (NTRS)

Sullivan, R. D.

1977-01-01

The use of tensors to provide a compact way of writing partial differential equations in a form valid in all coordinate systems is discussed. In order to find solutions to the equations with their boundary conditions they must be expressed in terms of the coordinate system under consideration. The process of arriving at these expressions from the tensor formulation was automated by a software system, TENSR. An allied system that analyzes the resulting expressions term by term and drops those that are negligible is also described.

Folded gastrulation and T48 drive the evolution of coordinated mesoderm internalization in flies

PubMed Central

Urbansky, Silvia; González Avalos, Paula; Wosch, Maike; Lemke, Steffen

2016-01-01

Gastrulation constitutes a fundamental yet diverse morphogenetic process of metazoan development. Modes of gastrulation range from stochastic translocation of individual cells to coordinated infolding of an epithelial sheet. How such morphogenetic differences are genetically encoded and whether they have provided specific developmental advantages is unclear. Here we identify two genes, folded gastrulation and t48, which in the evolution of fly gastrulation acted as a likely switch from an ingression of individual cells to the invagination of the blastoderm epithelium. Both genes are expressed and required for mesoderm invagination in the fruit fly Drosophila melanogaster but do not appear during mesoderm ingression of the midge Chironomus riparius. We demonstrate that early expression of either or both of these genes in C.riparius is sufficient to invoke mesoderm invagination similar to D.melanogaster. The possible genetic simplicity and a measurable increase in developmental robustness might explain repeated evolution of similar transitions in animal gastrulation. DOI: http://dx.doi.org/10.7554/eLife.18318.001 PMID:27685537

Single master regulatory gene coordinates the evolution and development of butterfly color and iridescence

PubMed Central

Zhang, Linlin

2017-01-01

The optix gene has been implicated in butterfly wing pattern adaptation by genetic association, mapping, and expression studies. The actual developmental function of this gene has remained unclear, however. Here we used CRISPR/Cas9 genome editing to show that optix plays a fundamental role in nymphalid butterfly wing pattern development, where it is required for determination of all chromatic coloration. optix knockouts in four species show complete replacement of color pigments with melanins, with corresponding changes in pigment-related gene expression, resulting in black and gray butterflies. We also show that optix simultaneously acts as a switch gene for blue structural iridescence in some butterflies, demonstrating simple regulatory coordination of structural and pigmentary coloration. Remarkably, these optix knockouts phenocopy the recurring “black and blue” wing pattern archetype that has arisen on many independent occasions in butterflies. Here we demonstrate a simple genetic basis for structural coloration, and show that optix plays a deeply conserved role in butterfly wing pattern development. PMID:28923944

Single master regulatory gene coordinates the evolution and development of butterfly color and iridescence.

PubMed

Zhang, Linlin; Mazo-Vargas, Anyi; Reed, Robert D

2017-10-03

The optix gene has been implicated in butterfly wing pattern adaptation by genetic association, mapping, and expression studies. The actual developmental function of this gene has remained unclear, however. Here we used CRISPR/Cas9 genome editing to show that optix plays a fundamental role in nymphalid butterfly wing pattern development, where it is required for determination of all chromatic coloration. optix knockouts in four species show complete replacement of color pigments with melanins, with corresponding changes in pigment-related gene expression, resulting in black and gray butterflies. We also show that optix simultaneously acts as a switch gene for blue structural iridescence in some butterflies, demonstrating simple regulatory coordination of structural and pigmentary coloration. Remarkably, these optix knockouts phenocopy the recurring "black and blue" wing pattern archetype that has arisen on many independent occasions in butterflies. Here we demonstrate a simple genetic basis for structural coloration, and show that optix plays a deeply conserved role in butterfly wing pattern development.

DIDO as a Switchboard that Regulates Self-Renewal and Differentiation in Embryonic Stem Cells.

PubMed

Fütterer, Agnes; de Celis, Jésus; Navajas, Rosana; Almonacid, Luis; Gutiérrez, Julio; Talavera-Gutiérrez, Amaia; Pacios-Bras, Cristina; Bernascone, Ilenia; Martin-Belmonte, Fernando; Martinéz-A, Carlos

2017-04-11

Transition from symmetric to asymmetric cell division requires precise coordination of differential gene expression. We show that embryonic stem cells (ESCs) mainly express DIDO3 and that their differentiation after leukemia inhibitory factor withdrawal requires DIDO1 expression. C-terminal truncation of DIDO3 (Dido3ΔCT) impedes ESC differentiation while retaining self-renewal; small hairpin RNA-Dido1 ESCs have the same phenotype. Dido3ΔCT ESC differentiation is rescued by ectopic expression of DIDO3, which binds the Dido locus via H3K4me3 and RNA POL II and induces DIDO1 expression. DIDO1, which is exported to cytoplasm, associates with, and is N-terminally phosphorylated by PKCiota. It binds the E3 ubiquitin ligase WWP2, which contributes to cell fate by OCT4 degradation, to allow expression of primitive endoderm (PE) markers. PE formation also depends on phosphorylated DIDO3 localization to centrosomes, which ensures their correct positioning for PE cell polarization. We propose that DIDO isoforms act as a switchboard that regulates genetic programs for ESC transition from pluripotency maintenance to promotion of differentiation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Inverse regulatory coordination of motility and curli-mediated adhesion in Escherichia coli.

PubMed

Pesavento, Christina; Becker, Gisela; Sommerfeldt, Nicole; Possling, Alexandra; Tschowri, Natalia; Mehlis, Anika; Hengge, Regine

2008-09-01

During the transition from post-exponential to stationary phase, Escherichia coli changes from the motile-planktonic to the adhesive-sedentary "lifestyle." We demonstrate this transition to be controlled by mutual inhibition of the FlhDC/motility and sigma(S)/adhesion control cascades at two distinct hierarchical levels. At the top level, motility gene expression and the general stress response are inversely coordinated by sigma(70)/sigma(FliA)/sigma(S) competition for core RNA polymerase and the FlhDC-controlled FliZ protein acting as a sigma(S) inhibitor. At a lower level, the signaling molecule bis-(3'-5')-cyclic-diguanosine monophosphate (c-di-GMP) reduces flagellar activity and stimulates transcription of csgD, which encodes an essential activator of adhesive curli fimbriae expression. This c-di-GMP is antagonistically controlled by sigma(S)-regulated GGDEF proteins (mainly YegE) and YhjH, an EAL protein and c-di-GMP phosphodiesterase under FlhDC/FliA control. The switch from motility-based foraging to the general stress response and curli expression requires sigma(S)-modulated down-regulation of expression of the flagellar regulatory cascade as well as proteolysis of the flagellar master regulator FlhDC. Control of YhjH by FlhDC and of YegE by sigma(S) produces a fine-tuned checkpoint system that "unlocks" curli expression only after down-regulation of flagellar gene expression. In summary, these data reveal the logic and sequence of molecular events underlying the motile-to-adhesive "lifestyle" switch in E. coli.

Coordinate regulation of the Suf and Isc Fe-S cluster biogenesis pathways by IscR is essential for viability of Escherichia coli.

PubMed

Mettert, Erin L; Kiley, Patricia J

2014-12-01

Fe-S cluster biogenesis is essential for the viability of most organisms. In Escherichia coli, this process requires either the housekeeping Isc or the stress-induced Suf pathway. The global regulator IscR coordinates cluster synthesis by repressing transcription of the isc operon by [2Fe-2S]-IscR and activating expression of the suf operon. We show that either [2Fe-2S]-IscR or apo-IscR can activate suf, making expression sensitive to mainly IscR levels and not the cluster state, unlike isc expression. We also demonstrate that in the absence of isc, IscR-dependent suf activation is essential since strains lacking both the Isc pathway and IscR were not viable unless Suf was expressed ectopically. Similarly, removal of the IscR binding site in the sufA promoter also led to a requirement for isc. Furthermore, suf expression was increased in a Δisc mutant, presumably due to increased IscR levels in this mutant. This was surprising because the iron-dependent repressor Fur, whose higher-affinity binding at the sufA promoter should occlude IscR binding, showed only partial repression. In addition, Fur derepression was not sufficient for viability in the absence of IscR and the Isc pathway, highlighting the importance of direct IscR activation. Finally, a mutant lacking Fur and the Isc pathway increased suf expression to the highest observed levels and nearly restored [2Fe-2S]-IscR activity, providing a mechanism for regulating IscR activity under stress conditions. Together, these findings have enhanced our understanding of the homeostatic mechanism by which cells use one regulator, IscR, to differentially control Fe-S cluster biogenesis pathways to ensure viability. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Growth Coordination During Drosophila melanogaster Imaginal Disc Regeneration Is Mediated by Signaling Through the Relaxin Receptor Lgr3 in the Prothoracic Gland.

PubMed

Jaszczak, Jacob S; Wolpe, Jacob B; Bhandari, Rajan; Jaszczak, Rebecca G; Halme, Adrian

2016-10-01

Damage to Drosophila melanogaster imaginal discs activates a regeneration checkpoint that (1) extends larval development and (2) coordinates the regeneration of the damaged disc with the growth of undamaged discs. These two systemic responses to damage are both mediated by Dilp8, a member of the insulin/insulin-like growth factor/relaxin family of peptide hormones, which is released by regenerating imaginal discs. Growth coordination between regenerating and undamaged imaginal discs is dependent on Dilp8 activation of nitric oxide synthase (NOS) in the prothoracic gland (PG), which slows the growth of undamaged discs by limiting ecdysone synthesis. Here we demonstrate that the Drosophila relaxin receptor homolog Lgr3, a leucine-rich repeat-containing G-protein-coupled receptor, is required for Dilp8-dependent growth coordination and developmental delay during the regeneration checkpoint. Lgr3 regulates these responses to damage via distinct mechanisms in different tissues. Using tissue-specific RNA-interference disruption of Lgr3 expression, we show that Lgr3 functions in the PG upstream of NOS, and is necessary for NOS activation and growth coordination during the regeneration checkpoint. When Lgr3 is depleted from neurons, imaginal disc damage no longer produces either developmental delay or growth inhibition. To reconcile these discrete tissue requirements for Lgr3 during regenerative growth coordination, we demonstrate that Lgr3 activity in both the CNS and PG is necessary for NOS activation in the PG following damage. Together, these results identify new roles for a relaxin receptor in mediating damage signaling to regulate growth and developmental timing. Copyright © 2016 by the Genetics Society of America.

New insights into Blimp-1 in T lymphocytes: a divergent regulator of cell destiny and effector function.

PubMed

Fu, Shin-Huei; Yeh, Li-Tzu; Chu, Chin-Chen; Yen, B Lin-Ju; Sytwu, Huey-Kang

2017-07-21

B lymphocyte-induced maturation protein-1 (Blimp-1) serves as a master regulator of the development and function of antibody-producing B cells. Given that its function in T lymphocytes has been identified within the past decade, we review recent findings with emphasis on its role in coordinated control of gene expression during the development, differentiation, and function of T cells. Expression of Blimp-1 is mainly confined to activated T cells and is essential for the production of interleukin (IL)-10 by a subset of forkhead box (Fox)p3 + regulatory T cells with an effector phenotype. Blimp-1 is also required to induce cell elimination in the thymus and critically modulates peripheral T cell activation and proliferation. In addition, Blimp-1 promotes T helper (Th) 2 lineage commitment and limits Th1, Th17 and follicular helper T cell differentiation. Furthermore, Blimp-1 coordinates with other transcription factors to regulate expression of IL-2, IL-21 and IL-10 in effector T lymphocytes. In CD8 + T cells, Blimp-1 expression is distinct in heterogeneous populations at the stages of clonal expansion, differentiation, contraction and memory formation when they encounter antigens. Moreover, Blimp-1 plays a fundamental role in coordinating cytokine receptor signaling networks and transcriptional programs to regulate diverse aspects of the formation and function of effector and memory CD8 + T cells and their exhaustion. Blimp-1 also functions as a gatekeeper of T cell activation and suppression to prevent or dampen autoimmune disease, antiviral responses and antitumor immunity. In this review, we discuss the emerging roles of Blimp-1 in the complex regulation of gene networks that regulate the destiny and effector function of T cells and provide a Blimp-1-dominated transcriptional framework for T lymphocyte homeostasis.

Coordinated regulation of neuronal mRNA steady-state levels through developmentally controlled intron retention

PubMed Central

Yap, Karen; Lim, Zhao Qin; Khandelia, Piyush; Friedman, Brad; Makeyev, Eugene V.

2012-01-01

Differentiated cells acquire unique structural and functional traits through coordinated expression of lineage-specific genes. An extensive battery of genes encoding components of the synaptic transmission machinery and specialized cytoskeletal proteins is activated during neurogenesis, but the underlying regulation is not well understood. Here we show that genes encoding critical presynaptic proteins are transcribed at a detectable level in both neurons and nonneuronal cells. However, in nonneuronal cells, the splicing of 3′-terminal introns within these genes is repressed by the polypyrimidine tract-binding protein (Ptbp1). This inhibits the export of incompletely spliced mRNAs to the cytoplasm and triggers their nuclear degradation. Clearance of these intron-containing transcripts occurs independently of the nonsense-mediated decay (NMD) pathway but requires components of the nuclear RNA surveillance machinery, including the nuclear pore-associated protein Tpr and the exosome complex. When Ptbp1 expression decreases during neuronal differentiation, the regulated introns are spliced out, thus allowing the accumulation of translation-competent mRNAs in the cytoplasm. We propose that this mechanism counters ectopic and precocious expression of functionally linked neuron-specific genes and ensures their coherent activation in the appropriate developmental context. PMID:22661231

Coordinated regulation of neuronal mRNA steady-state levels through developmentally controlled intron retention.

PubMed

Yap, Karen; Lim, Zhao Qin; Khandelia, Piyush; Friedman, Brad; Makeyev, Eugene V

2012-06-01

Differentiated cells acquire unique structural and functional traits through coordinated expression of lineage-specific genes. An extensive battery of genes encoding components of the synaptic transmission machinery and specialized cytoskeletal proteins is activated during neurogenesis, but the underlying regulation is not well understood. Here we show that genes encoding critical presynaptic proteins are transcribed at a detectable level in both neurons and nonneuronal cells. However, in nonneuronal cells, the splicing of 3'-terminal introns within these genes is repressed by the polypyrimidine tract-binding protein (Ptbp1). This inhibits the export of incompletely spliced mRNAs to the cytoplasm and triggers their nuclear degradation. Clearance of these intron-containing transcripts occurs independently of the nonsense-mediated decay (NMD) pathway but requires components of the nuclear RNA surveillance machinery, including the nuclear pore-associated protein Tpr and the exosome complex. When Ptbp1 expression decreases during neuronal differentiation, the regulated introns are spliced out, thus allowing the accumulation of translation-competent mRNAs in the cytoplasm. We propose that this mechanism counters ectopic and precocious expression of functionally linked neuron-specific genes and ensures their coherent activation in the appropriate developmental context.

Removal of S6K1 and S6K2 Leads to Divergent Alterations in Learning, Memory, and Synaptic Plasticity

ERIC Educational Resources Information Center

Antion, Marcia D.; Merhav, Maayan; Hoeffer, Charles A.; Reis, Gerald; Kozma, Sara C.; Thomas, George; Schuman Erin M.; Rosenblum, Kobi; Klann, Eric

2008-01-01

Protein synthesis is required for the expression of enduring memories and long-lasting synaptic plasticity. During cellular proliferation and growth, S6 kinases (S6Ks) are activated and coordinate the synthesis of de novo proteins. We hypothesized that protein synthesis mediated by S6Ks is critical for the manifestation of learning, memory, and…

Motion of the angular momentum vector in body coordinates for torque-free dual-spin spacecraft

NASA Technical Reports Server (NTRS)

Fedor, J. V.

1981-01-01

The motion of the angular momentum vector in body coordinates for torque free, asymmetric dual spin spacecraft without and, for a special case, with energy dissipation on the main spacecraft is investigated. Without energy dissipation, two integrals can be obtained from the Euler equations of motion. Using the classical method of elimination of variable, the motion about the equilibrium points (six for the general case) are derived with these integrals. For small nutation angle, theta, the trajectories about the theta = 0 deg and theta = 180 deg points readily show the requirements for stable motion about these points. Also the conditions needed to eliminate stable motion about the theta = 180 deg point as well as the other undesireable equilibrium points follow directly from these equations. For the special case where the angular momentum vector moves about the principal axis which contains the momentum wheel, the notion of 'free variable' azimuth angle is used. Physically this angle must vary from 0 to 2 pi in a circular periodic fashion. Expressions are thus obtained for the nutation angle in terms of the free variable and other spacecraft parameters. Results show that in general there are two separate trajectory expressions that govern the motion of the angular momentum vector in body coordinates.

Representation of viruses in the remediated PDB archive

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

Lawson, Catherine L., E-mail: cathy.lawson@rutgers.edu; Dutta, Shuchismita; Westbrook, John D.

2008-08-01

A new data model for PDB entries of viruses and other biological assemblies with regular noncrystallographic symmetry is described. A new scheme has been devised to represent viruses and other biological assemblies with regular noncrystallographic symmetry in the Protein Data Bank (PDB). The scheme describes existing and anticipated PDB entries of this type using generalized descriptions of deposited and experimental coordinate frames, symmetry and frame transformations. A simplified notation has been adopted to express the symmetry generation of assemblies from deposited coordinates and matrix operations describing the required point, helical or crystallographic symmetry. Complete correct information for building full assemblies,more » subassemblies and crystal asymmetric units of all virus entries is now available in the remediated PDB archive.« less

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.

Effector Regulatory T Cell Differentiation and Immune Homeostasis Depend on the Transcription Factor Myb.

PubMed

Dias, Sheila; D'Amico, Angela; Cretney, Erika; Liao, Yang; Tellier, Julie; Bruggeman, Christine; Almeida, Francisca F; Leahy, Jamie; Belz, Gabrielle T; Smyth, Gordon K; Shi, Wei; Nutt, Stephen L

2017-01-17

FoxP3-expressing regulatory T (Treg) cells are essential for maintaining immune homeostasis. Activated Treg cells undergo further differentiation into an effector state that highly expresses genes critical for Treg cell function, although how this process is coordinated on a transcriptional level is poorly understood. Here, we demonstrate that mice lacking the transcription factor Myb in Treg cells succumbed to a multi-organ inflammatory disease. Myb was specifically expressed in, and required for the differentiation of, thymus-derived effector Treg cells. The combination of transcriptome and genomic footprint analyses revealed that Myb directly regulated a large proportion of the gene expression specific to effector Treg cells, identifying Myb as a critical component of the gene regulatory network controlling effector Treg cell differentiation and function. Copyright © 2017 Elsevier Inc. All rights reserved.

Sequences required for induction of neurotensin receptor gene expression during neuronal differentiation of N1E-115 neuroblastoma cells.

PubMed

Tavares, D; Tully, K; Dobner, P R

1999-10-15

The promoter region of the mouse high affinity neurotensin receptor (Ntr-1) gene was characterized, and sequences required for expression in neuroblastoma cell lines that express high affinity NT-binding sites were characterized. Me(2)SO-induced neuronal differentiation of N1E-115 neuroblastoma cells increased both the expression of the endogenous Ntr-1 gene and reporter genes driven by NTR-1 promoter sequences by 3-4-fold. Deletion analysis revealed that an 83-base pair promoter region containing the transcriptional start site is required for Me(2)SO activation. Detailed mutational analysis of this region revealed that a CACCC box and the central region of a large GC-rich palindrome are the crucial cis-regulatory elements required for Me(2)SO induction. The CACCC box is bound by at least one factor that is induced upon Me(2)SO treatment of N1E-115 cells. The Me(2)SO effect was found to be both selective and cell type-restricted. Basal expression in the neuroblastoma cell lines required a distinct set of sequences, including an Sp1-like sequence, and a sequence resembling an NGFI-A-binding site; however, a more distal 5' sequence was found to repress basal activity in N1E-115 cells. These results provide evidence that Ntr-1 gene regulation involves both positive and negative regulatory elements located in the 5'-flanking region and that Ntr-1 gene activation involves the coordinate activation or induction of several factors, including a CACCC box binding complex.

Lrp5/6 are required for cerebellar development and for suppressing TH expression in Purkinje cells via β-catenin.

PubMed

Huang, Ying; Zhang, Qiong; Song, Ning-Ning; Zhang, Lei; Sun, Yu-Ling; Hu, Ling; Chen, Jia-Ying; Zhu, Weidong; Li, Jue; Ding, Yu-Qiang

2016-01-15

The cerebellum is responsible for coordinating motor functions and has a unique laminated architecture. Purkinje cells are inhibitory neurons and represent the only output from the cerebellar cortex. Tyrosine hydroxylase (TH) is the key enzyme for the synthesis of catecholamines, including dopamine and noradrenaline, and it is normally not expressed in cerebellar neurons. We report here that the low-density lipoprotein receptors (Lrp) 5 and 6, Wnt co-receptors, are required for the development of the cerebellum and for suppressing ectopic TH expression in Purkinje cells. Simultaneous inactivation of Lrp 5 and 6 by Nestin-Cre results in defective lamination and foliation of the cerebellum during postnatal development. Surprisingly, TH is ectopically expressed by Purkinje cells, although they still keep its other neurochemical characteristics. These phenotypes are also observed in the cerebellum of GFAP-Cre;β-catenin(flox/flox) mice, and AAV2-Cre-mediated gene deletion leads to ectopic TH expression in Purkinje cells of β-catenin(flox/flox) mice as well. Our results revealed a new role of the canonical Lrp5/6-β-catenin pathway in regulating the morphogenesis of the cerebellum during postnatal development.

Transcription factors lhx1/5-1 and pitx are required for the maintenance and regeneration of serotonergic neurons in planarians.

PubMed

Currie, Ko W; Pearson, Bret J

2013-09-01

In contrast to most adult organisms, freshwater planarians can regenerate any injured body part, including their entire nervous system. This allows for the analysis of genes required for both the maintenance and regeneration of specific neural subtypes. In addition, the loss of specific neural subtypes may uncover previously unknown behavioral roles for that neural population in the context of the adult animal. Here we show that two homeodomain transcription factor homologs, Smed-lhx1/5-1 and Smed-pitx, are required for the maintenance and regeneration of serotonergic neurons in planarians. When either lhx1/5-1 or pitx was knocked down by RNA interference, the expression of multiple canonical markers for serotonergic neurons was lost. Surprisingly, the loss of serotonergic function uncovered a role for these neurons in the coordination of motile cilia on the ventral epidermis of planarians that are required for their nonmuscular gliding locomotion. Finally, we show that in addition to its requirement in serotonergic neurons, Smed-pitx is required for proper midline patterning during regeneration, when it is required for the expression of the midline-organizing molecules Smed-slit in the anterior and Smed-wnt1 in the posterior.

A multicopper oxidase-related protein is essential for insect viability, longevity and ovary development.

PubMed

Peng, Zeyu; Green, Peter G; Arakane, Yasuyuki; Kanost, Michael R; Gorman, Maureen J

2014-01-01

Typical multicopper oxidases (MCOs) have ten conserved histidines and one conserved cysteine that coordinate four copper atoms. These copper ions are required for oxidase activity. During our studies of insect MCOs, we discovered a gene that we named multicopper oxidase-related protein (MCORP). MCORPs share sequence similarity with MCOs, but lack many of the copper-coordinating residues. We identified MCORP orthologs in many insect species, but not in other invertebrates or vertebrates. We predicted that MCORPs would lack oxidase activity due to the absence of copper-coordinating residues. To test this prediction, we purified recombinant Tribolium castaneum (red flour beetle) MCORP and analyzed its enzymatic activity using a variety of substrates. As expected, no oxidase activity was detected. To study MCORP function in vivo, we analyzed expression profiles of TcMCORP and Anopheles gambiae (African malaria mosquito) MCORP, and assessed RNAi-mediated knockdown phenotypes. We found that both MCORPs are constitutively expressed at a low level in all of the tissues we analyzed. Injection of TcMCORP dsRNA into larvae resulted in 100% mortality prior to adult eclosion, with death occurring mainly during the pharate pupal stage or late pharate adult stage. Injection of TcMCORP dsRNA into pharate pupae resulted in the death of approximately 20% of the treated insects during the pupal to adult transition and a greatly shortened life span for the remaining insects. In addition, knockdown of TcMCORP in females prevented oocyte maturation and, thus, greatly decreased the number of eggs laid. These results indicate that TcMCORP is an essential gene and that its function is required for reproduction. An understanding of the role MCORP plays in insect physiology may help to develop new strategies for controlling insect pests.

Coordination of Actin- and Microtubule-Based Cytoskeletons Supports Transport of Spermatids and Residual Bodies/Phagosomes During Spermatogenesis in the Rat Testis

PubMed Central

Tang, Elizabeth I.; Lee, Will M.

2016-01-01

Germ cell transport across the seminiferous epithelium during spermatogenesis requires the intricate coordination of cell junctions, signaling proteins, and both actin- and microtubule (MT)-based cytoskeletons. Although the involvement of cytoskeletons in germ cell transport has been suggested, the precise mechanism(s) remains elusive. Based on growing evidence that actin and MT interactions underlie fundamental cellular processes, such as cell motility, it is unlikely that actin- and MT-based cytoskeletons work independently to regulate germ cell transport in the testis. Using rats treated with adjudin, a potential male contraceptive that disrupts spermatid adhesion and transport in the testis, as a study model, we show herein that actin- and MT-based cytoskeletons are both necessary for transport of spermatids and residual bodies/phagosomes across the seminiferous epithelium in adult rat testes. Analysis of intratubular expression of F-actin and tubulin revealed disruption of both actin and MT networks, concomitant with misdirected spermatids and phagosomes in rats treated with adjudin. Actin regulatory proteins, epidermal growth factor receptor pathway substrate 8 and actin-related protein 3, were mislocalized and down-regulated at the actin-rich anchoring junction between germ and Sertoli cells (apical ectoplasmic specialization) after adjudin treatment. Nonreceptor tyrosine kinase p-FAK-Tyr407, known to regulate F-actin nucleation via actin-related protein 3, was also mislocalized and down-regulated at the apical ectoplasmic specialization, corroborating the observation of actin cytoskeleton disruption. Additionally, spatiotemporal expression of MT regulatory protein end-binding protein 1, shown to be involved in MT-actin cross talk herein, was also disrupted after adjudin treatment. In summary, spermatid/phagosome transport across the epithelium during spermatogenesis requires the coordination between actin- and MT-based cytoskeletons. PMID:26894662

Cyberinfrastructure for the digital brain: spatial standards for integrating rodent brain atlases

PubMed Central

Zaslavsky, Ilya; Baldock, Richard A.; Boline, Jyl

2014-01-01

Biomedical research entails capture and analysis of massive data volumes and new discoveries arise from data-integration and mining. This is only possible if data can be mapped onto a common framework such as the genome for genomic data. In neuroscience, the framework is intrinsically spatial and based on a number of paper atlases. This cannot meet today's data-intensive analysis and integration challenges. A scalable and extensible software infrastructure that is standards based but open for novel data and resources, is required for integrating information such as signal distributions, gene-expression, neuronal connectivity, electrophysiology, anatomy, and developmental processes. Therefore, the International Neuroinformatics Coordinating Facility (INCF) initiated the development of a spatial framework for neuroscience data integration with an associated Digital Atlasing Infrastructure (DAI). A prototype implementation of this infrastructure for the rodent brain is reported here. The infrastructure is based on a collection of reference spaces to which data is mapped at the required resolution, such as the Waxholm Space (WHS), a 3D reconstruction of the brain generated using high-resolution, multi-channel microMRI. The core standards of the digital atlasing service-oriented infrastructure include Waxholm Markup Language (WaxML): XML schema expressing a uniform information model for key elements such as coordinate systems, transformations, points of interest (POI)s, labels, and annotations; and Atlas Web Services: interfaces for querying and updating atlas data. The services return WaxML-encoded documents with information about capabilities, spatial reference systems (SRSs) and structures, and execute coordinate transformations and POI-based requests. Key elements of INCF-DAI cyberinfrastructure have been prototyped for both mouse and rat brain atlas sources, including the Allen Mouse Brain Atlas, UCSD Cell-Centered Database, and Edinburgh Mouse Atlas Project. PMID:25309417

Cyberinfrastructure for the digital brain: spatial standards for integrating rodent brain atlases.

PubMed

Zaslavsky, Ilya; Baldock, Richard A; Boline, Jyl

2014-01-01

Biomedical research entails capture and analysis of massive data volumes and new discoveries arise from data-integration and mining. This is only possible if data can be mapped onto a common framework such as the genome for genomic data. In neuroscience, the framework is intrinsically spatial and based on a number of paper atlases. This cannot meet today's data-intensive analysis and integration challenges. A scalable and extensible software infrastructure that is standards based but open for novel data and resources, is required for integrating information such as signal distributions, gene-expression, neuronal connectivity, electrophysiology, anatomy, and developmental processes. Therefore, the International Neuroinformatics Coordinating Facility (INCF) initiated the development of a spatial framework for neuroscience data integration with an associated Digital Atlasing Infrastructure (DAI). A prototype implementation of this infrastructure for the rodent brain is reported here. The infrastructure is based on a collection of reference spaces to which data is mapped at the required resolution, such as the Waxholm Space (WHS), a 3D reconstruction of the brain generated using high-resolution, multi-channel microMRI. The core standards of the digital atlasing service-oriented infrastructure include Waxholm Markup Language (WaxML): XML schema expressing a uniform information model for key elements such as coordinate systems, transformations, points of interest (POI)s, labels, and annotations; and Atlas Web Services: interfaces for querying and updating atlas data. The services return WaxML-encoded documents with information about capabilities, spatial reference systems (SRSs) and structures, and execute coordinate transformations and POI-based requests. Key elements of INCF-DAI cyberinfrastructure have been prototyped for both mouse and rat brain atlas sources, including the Allen Mouse Brain Atlas, UCSD Cell-Centered Database, and Edinburgh Mouse Atlas Project.

45 CFR 162.1801 - Coordination of benefits transaction.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Coordination of benefits transaction. 162.1801... RELATED REQUIREMENTS ADMINISTRATIVE REQUIREMENTS Coordination of Benefits § 162.1801 Coordination of benefits transaction. The coordination of benefits transaction is the transmission from any entity to a...

Meaningful use care coordination criteria: Perceived barriers and benefits among primary care providers.

PubMed

Cohen, Genna R; Adler-Milstein, Julia

2016-04-01

Stage 2 and proposed Stage 3 meaningful use criteria ask providers to support patient care coordination by electronically generating, exchanging, and reconciling key information during patient care transitions. A stratified random sample of primary care practices in Michigan (n = 328) that had already met Stage 1 meaningful use criteria was surveyed, in order to identify the anticipated barriers to meeting these criteria as well as the expected impact on patient care coordination from doing so. The top three barriers, as identified by >65% of the primary care providers surveyed, were difficulty sending and receiving patient information electronically, a lack of provider and practice staff time, and the complex workflow changes required. Despite these barriers, primary care providers expressed strong agreement that meeting the proposed Stage 3 care coordination criteria would improve their patients' treatment and ensure they know about their patients' visits to other providers. The survey results suggest the need to enhance policy approaches and organizational strategies to address the key barriers identified by providers and practices in order to realize important care coordination benefits. © 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.

Identification and characterization of polyclonal αβ T cells with dendritic cell properties

PubMed Central

Kuka, Mirela; Munitic, Ivana; Ashwell, Jonathan D.

2012-01-01

An efficient immune response requires coordination between innate and adaptive immunity, which act through cells different in origin and function. Here we report the identification of thymus-derived αβ TCR+ cells that express CD11c and MHC class II, and require FLT3L for development (TDC). TDC express genes heretofore found uniquely in T cells or DC, as well as a distinctive signature of cytotoxicity-related genes. Unlike other innate T cell subsets, TDC have a polyclonal TCR repertoire andrespond to cognate antigens. However, they differ from conventional T cells in that they do not require help from antigen-presenting cells, respond to TLR-mediated stimulation by producing IL-12 and process and present antigen. The physiologic relevance of TDC, found in mice and humans, is still under investigation, but the fact that they combine key features of T and DC cells suggests that they provide a bridge between the innate and adaptive immune systems. PMID:23187623

Differentially phased leaf growth and movements in Arabidopsis depend on coordinated circadian and light regulation.

PubMed

Dornbusch, Tino; Michaud, Olivier; Xenarios, Ioannis; Fankhauser, Christian

2014-10-01

In contrast to vastly studied hypocotyl growth, little is known about diel regulation of leaf growth and its coordination with movements such as changes in leaf elevation angle (hyponasty). We developed a 3D live-leaf growth analysis system enabling simultaneous monitoring of growth and movements. Leaf growth is maximal several hours after dawn, requires light, and is regulated by daylength, suggesting coupling between growth and metabolism. We identify both blade and petiole positioning as important components of leaf movements in Arabidopsis thaliana and reveal a temporal delay between growth and movements. In hypocotyls, the combination of circadian expression of PHYTOCHROME INTERACTING FACTOR4 (PIF4) and PIF5 and their light-regulated protein stability drives rhythmic hypocotyl elongation with peak growth at dawn. We find that PIF4 and PIF5 are not essential to sustain rhythmic leaf growth but influence their amplitude. Furthermore, EARLY FLOWERING3, a member of the evening complex (EC), is required to maintain the correct phase between growth and movement. Our study shows that the mechanisms underlying rhythmic hypocotyl and leaf growth differ. Moreover, we reveal the temporal relationship between leaf elongation and movements and demonstrate the importance of the EC for the coordination of these phenotypic traits. © 2014 American Society of Plant Biologists. All rights reserved.

Robust 3D face landmark localization based on local coordinate coding.

PubMed

Song, Mingli; Tao, Dacheng; Sun, Shengpeng; Chen, Chun; Maybank, Stephen J

2014-12-01

In the 3D facial animation and synthesis community, input faces are usually required to be labeled by a set of landmarks for parameterization. Because of the variations in pose, expression and resolution, automatic 3D face landmark localization remains a challenge. In this paper, a novel landmark localization approach is presented. The approach is based on local coordinate coding (LCC) and consists of two stages. In the first stage, we perform nose detection, relying on the fact that the nose shape is usually invariant under the variations in the pose, expression, and resolution. Then, we use the iterative closest points algorithm to find a 3D affine transformation that aligns the input face to a reference face. In the second stage, we perform resampling to build correspondences between the input 3D face and the training faces. Then, an LCC-based localization algorithm is proposed to obtain the positions of the landmarks in the input face. Experimental results show that the proposed method is comparable to state of the art methods in terms of its robustness, flexibility, and accuracy.

Sumoylation Dynamics During Keratinocyte Differentiation

PubMed Central

Deyrieux, Adeline F.; Rosas-Acosta, Germán; Ozbun, Michelle A.; Wilson, Van G.

2012-01-01

Summary SUMO modification regulates the activity of numerous transcription factors that have a direct role in cell cycle progression, apoptosis, cellular proliferation, and development, but its role in differentiation processes is less clear. Keratinocyte differentiation requires the coordinated activation of a series of transcription factors, and as several critical keratinocyte transcription factors are known to be SUMO substrates, we investigated the role of sumoylation in keratinocyte differentiation. In a human keratinocyte cell line model (HaCaT cells), calcium-induced differentiation led to the transient and coordinated transcriptional activation of the genes encoding critical sumoylation system components, including SAE1, SAE2, Ubc9, SENP1, Miz-1 (PIASxβ), SUMO2, and SUMO3. The increased gene expression resulted in higher levels of the respective proteins and changes in the pattern of sumoylated substrate proteins during the differentiation process. Similar to the HaCaT results, stratified human foreskin keratinocytes showed an upregulation of Ubc9 in the suprabasal layers. Lastly, abrogation of sumoylation by Gam1 expression severely disrupted normal HaCaT differentiation, consistent with an important role for sumoylation in the proper progression of this biological process. PMID:17164289

TRIC: Capturing the direct cellular targets of promoter‐bound transcriptional activators

PubMed Central

Dugan, Amanda; Pricer, Rachel; Katz, Micah

2016-01-01

Abstract Transcriptional activators coordinate the dynamic assembly of multiprotein coactivator complexes required for gene expression to occur. Here we combine the power of in vivo covalent chemical capture with p‐benzoyl‐L‐phenylalanine (Bpa), a genetically incorporated photo‐crosslinking amino acid, and chromatin immunoprecipitation (ChIP) to capture the direct protein interactions of the transcriptional activator VP16 with the general transcription factor TBP at the GAL1 promoter in live yeast. PMID:27213278

Post-transcriptional regulation of myotube elongation and myogenesis by Hoi Polloi

PubMed Central

Johnson, Aaron N.; Mokalled, Mayssa H.; Valera, Juliana M.; Poss, Kenneth D.; Olson, Eric N.

2013-01-01

Striated muscle development requires the coordinated expression of genes involved in sarcomere formation and contractility, as well as genes that determine muscle morphology. However, relatively little is known about the molecular mechanisms that control the early stages of muscle morphogenesis. To explore this facet of myogenesis, we performed a genetic screen for regulators of somatic muscle morphology in Drosophila, and identified the putative RNA-binding protein (RBP) Hoi Polloi (Hoip). Hoip is expressed in striated muscle precursors within the muscle lineage and controls two genetically separable events: myotube elongation and sarcomeric protein expression. Myotubes fail to elongate in hoip mutant embryos, even though the known regulators of somatic muscle elongation, target recognition and muscle attachment are expressed normally. In addition, a majority of sarcomeric proteins, including Myosin Heavy Chain (MHC) and Tropomyosin, require Hoip for their expression. A transgenic MHC construct that contains the endogenous MHC promoter and a spliced open reading frame rescues MHC protein expression in hoip embryos, demonstrating the involvement of Hoip in pre-mRNA splicing, but not in transcription, of muscle structural genes. In addition, the human Hoip ortholog NHP2L1 rescues muscle defects in hoip embryos, and knockdown of endogenous nhp2l1 in zebrafish disrupts skeletal muscle development. We conclude that Hoip is a conserved, post-transcriptional regulator of muscle morphogenesis and structural gene expression. PMID:23942517

47 CFR 27.903 - Coordination requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 2 2010-10-01 2010-10-01 false Coordination requirements. 27.903 Section 27.903 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES 1670-1675 MHz Band § 27.903 Coordination requirements. (a) The...

47 CFR 27.903 - Coordination requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 2 2011-10-01 2011-10-01 false Coordination requirements. 27.903 Section 27.903 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES 1670-1675 MHz Band § 27.903 Coordination requirements. (a) The...

APSR1, a novel gene required for meristem maintenance, is negatively regulated by low phosphate availability.

PubMed

González-Mendoza, Víctor; Zurita-Silva, Andrés; Sánchez-Calderón, Lenin; Sánchez-Sandoval, María Eugenia; Oropeza-Aburto, Araceli; Gutiérrez-Alanís, Dolores; Alatorre-Cobos, Fulgencio; Herrera-Estrella, Luis

2013-05-01

Proper root growth is crucial for anchorage, exploration, and exploitation of the soil substrate. Root growth is highly sensitive to a variety of environmental cues, among them water and nutrient availability have a great impact on root development. Phosphorus (P) availability is one of the most limiting nutrients that affect plant growth and development under natural and agricultural environments. Root growth in the direction of the long axis proceeds from the root tip and requires the coordinated activities of cell proliferation, cell elongation and cell differentiation. Here we report a novel gene, APSR1 (Altered Phosphate Starvation Response1), involved in root meristem maintenance. The loss of function mutant apsr1-1 showed a reduction in primary root length and root apical meristem size, short differentiated epidermal cells and long root hairs. Expression of APSR1 gene decreases in response to phosphate starvation and apsr1-1 did not show the typical progressive decrease of undifferentiated cells at root tip when grown under P limiting conditions. Interestingly, APSR1 expression pattern overlaps with root zones of auxin accumulation. Furthermore, apsr1-1 showed a clear decrease in the level of the auxin transporter PIN7. These data suggest that APSR1 is required for the coordination of cell processes necessary for correct root growth in response to phosphate starvation conceivably by direct or indirect modulation of PIN7. We also propose, based on its nuclear localization and structure, that APSR1 may potentially be a member of a novel group of transcription factors. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Knowing too little or too much: the effects of familiarity with a co-performer's part on interpersonal coordination in musical ensembles

PubMed Central

Ragert, Marie; Schroeder, Tim; Keller, Peter E.

2013-01-01

Expert ensemble musicians produce exquisitely coordinated sounds, but rehearsal is typically required to do so. Ensemble coordination may thus be influenced by the degree to which individuals are familiar with each other's parts. Such familiarity may affect the ability to predict and synchronize with co-performers' actions. Internal models related to action simulation and anticipatory musical imagery may be affected by knowledge of (1) the musical structure of a co-performer's part (e.g., in terms of its rhythm and phrase structure) and/or (2) the co-performer's idiosyncratic playing style (e.g., expressive micro-timing variations). The current study investigated the effects of familiarity on interpersonal coordination in piano duos. Skilled pianists were required to play several duets with different partners. One condition included duets for which co-performers had previously practiced both parts, while another condition included duets for which each performer had practiced only their own part. Each piece was recorded six times without joint rehearsal or visual contact to examine the effects of increasing familiarity. Interpersonal coordination was quantified by measuring asynchronies between pianists' keystroke timing and the correlation of their body (head and torso) movements, which were recorded with a motion capture system. The results suggest that familiarity with a co-performer's part, in the absence of familiarity with their playing style, engenders predictions about micro-timing variations that are based instead upon one's own playing style, leading to a mismatch between predictions and actual events at short timescales. Predictions at longer timescales—that is, those related to musical measures and phrases, and reflected in head movements and body sway—are, however, facilitated by familiarity with the structure of a co-performer's part. These findings point to a dissociation between interpersonal coordination at the level of keystrokes and body movements. PMID:23805116

ULTRAPETALA1 encodes a SAND domain putative transcriptional regulator that controls shoot and floral meristem activity in Arabidopsis.

PubMed

Carles, Cristel C; Choffnes-Inada, Dan; Reville, Keira; Lertpiriyapong, Kvin; Fletcher, Jennifer C

2005-03-01

The higher-plant shoot apical meristem is a dynamic structure continuously producing cells that become incorporated into new leaves, stems and flowers. The maintenance of a constant flow of cells through the meristem depends on coordination of two antagonistic processes: self-renewal of the stem cell population and initiation of the lateral organs. This coordination is stringently controlled by gene networks that contain both positive and negative components. We have previously defined the ULTRAPETALA1 (ULT1) gene as a key negative regulator of cell accumulation in Arabidopsis shoot and floral meristems, because mutations in ULT1 cause the enlargement of inflorescence and floral meristems, the production of supernumerary flowers and floral organs, and a delay in floral meristem termination. Here, we show that ULT1 negatively regulates the size of the WUSCHEL (WUS)-expressing organizing center in inflorescence meristems. We have cloned the ULT1 gene and find that it encodes a small protein containing a B-box-like motif and a SAND domain, a DNA-binding motif previously reported only in animal transcription factors. ULT1 and its Arabidopsis paralog ULT2 define a novel small gene family in plants. ULT1 and ULT2 are expressed coordinately in embryonic shoot apical meristems, in inflorescence and floral meristems, and in developing stamens, carpels and ovules. Additionally, ULT1 is expressed in vegetative meristems and leaf primordia. ULT2 protein can compensate for mutant ULT1 protein when overexpressed in an ult1 background, indicating that the two genes may regulate a common set of targets during plant development. Downregulation of both ULT genes can lead to shoot apical meristem arrest shortly after germination, revealing a requirement for ULT activity in early development.

c-Myb Coordinates Survival and the Expression of Genes That Are Critical for the Pre-BCR Checkpoint.

PubMed

Fahl, Shawn P; Daamen, Andrea R; Crittenden, Rowena B; Bender, Timothy P

2018-05-15

The c-Myb transcription factor is required for adult hematopoiesis, yet little is known about c-Myb function during lineage-specific differentiation due to the embryonic lethality of Myb -null mutations. We previously used tissue-specific inactivation of the murine Myb locus to demonstrate that c-Myb is required for differentiation to the pro-B cell stage, survival during the pro-B cell stage, and the pro-B to pre-B cell transition during B lymphopoiesis. However, few downstream mediators of c-Myb-regulated function have been identified. We demonstrate that c-Myb regulates the intrinsic survival of CD19 + pro-B cells in the absence of IL-7 by repressing expression of the proapoptotic proteins Bmf and Bim and that levels of Bmf and Bim mRNA are further repressed by IL-7 signaling in pro-B cells. c-Myb regulates two crucial components of the IL-7 signaling pathway: the IL-7Rα-chain and the negative regulator SOCS3 in CD19 + pro-B cells. Bypassing IL-7R signaling through constitutive activation of Stat5b largely rescues survival of c-Myb-deficient pro-B cells, whereas constitutively active Akt is much less effective. However, rescue of pro-B cell survival is not sufficient to rescue proliferation of pro-B cells or the pro-B to small pre-B cell transition, and we further demonstrate that c-Myb-deficient large pre-B cells are hypoproliferative. Analysis of genes crucial for the pre-BCR checkpoint demonstrates that, in addition to IL-7Rα, the genes encoding λ5, cyclin D3, and CXCR4 are downregulated in the absence of c-Myb, and λ5 is a direct c-Myb target. Thus, c-Myb coordinates survival with the expression of genes that are required during the pre-BCR checkpoint. Copyright © 2018 by The American Association of Immunologists, Inc.

EGO-1, a C. elegans RdRP, Modulates Gene Expression via Production of mRNA-Templated Short Antisense RNAs

PubMed Central

Maniar, Jay M.; Fire, Andrew Z.

2011-01-01

SUMMARY Background The development of the germline in Caenorhabditis elegans is a complex process involving the regulation of thousands of genes in a coordinated manner. Several genes required for small RNA biogenesis and function are among those required for the proper organization of the germline. EGO-1 is a putative RNA-directed RNA polymerase (RdRP) that is required for multiple aspects of C. elegans germline development and efficient RNAi of germline-expressed genes. RdRPs have been proposed to act through a variety of mechanisms including the post-transcriptional targeting of specific mRNAs as well as through a direct interaction with chromatin. Despite extensive investigation, the molecular role of EGO-1 has remained enigmatic. Results Here we use high-throughput small RNA and messenger RNA sequencing to investigate EGO-1 function. We found that EGO-1 is required to produce a distinct pool of small RNAs antisense to a number of germline-expressed mRNAs through several developmental stages. These potential mRNA targets fall into distinct classes, including genes required for kinetochore and nuclear pore assembly, histone-modifying activities and centromeric proteins. We also found several RNAi-related genes to be targets of EGO-1. Finally, we show a strong association between the loss of small RNAs and the rise of mRNA levels in ego-1(−) animals. Conclusions Our data support the conclusion that EGO-1 produces triphosphorylated small RNAs derived from mRNA templates and that these small RNAs modulate gene expression through the targeting of their cognate mRNAs. PMID:21396820

Hormone-dependent control of developmental timing through regulation of chromatin accessibility

PubMed Central

Uyehara, Christopher M.; Nystrom, Spencer L.; Niederhuber, Matthew J.; Leatham-Jensen, Mary; Ma, Yiqin; Buttitta, Laura A.

2017-01-01

Specification of tissue identity during development requires precise coordination of gene expression in both space and time. Spatially, master regulatory transcription factors are required to control tissue-specific gene expression programs. However, the mechanisms controlling how tissue-specific gene expression changes over time are less well understood. Here, we show that hormone-induced transcription factors control temporal gene expression by regulating the accessibility of DNA regulatory elements. Using the Drosophila wing, we demonstrate that temporal changes in gene expression are accompanied by genome-wide changes in chromatin accessibility at temporal-specific enhancers. We also uncover a temporal cascade of transcription factors following a pulse of the steroid hormone ecdysone such that different times in wing development can be defined by distinct combinations of hormone-induced transcription factors. Finally, we show that the ecdysone-induced transcription factor E93 controls temporal identity by directly regulating chromatin accessibility across the genome. Notably, we found that E93 controls enhancer activity through three different modalities, including promoting accessibility of late-acting enhancers and decreasing accessibility of early-acting enhancers. Together, this work supports a model in which an extrinsic signal triggers an intrinsic transcription factor cascade that drives development forward in time through regulation of chromatin accessibility. PMID:28536147

Applications of Differential Operators in Geodetic Coordinates

NASA Astrophysics Data System (ADS)

Hallam, K. A. T.; Oliveira, V. C., Jr.

2016-12-01

The definition of coordinate systems and frames is an essential step to even start a problem in physical geodesy and geophysics. The commonly used coordinate systems when dealing with problems on (or close to) the surface of the Earth are the geocentric Cartesian coordinates, geocentric spherical coordinates and geodetic coordinates. Transformations between Cartesian and spherical coordinates are widely known and used for several problems. More complex, but not less important, are the transformations between Cartesian and geodetic coordinates. Although most of them utilize an ellipsoidal frame in which the three coordinates are geodetic longitude (λ), geodetic latitude (φ) and the scale factor (u), the latter being a combination of X and Y, not the geometric height (h), the data sets measured on (or close to) the surface of the Earth are given in geodetic coordinates which are usually transformed into Cartesian or spherical coordinates for mathematical developments. It would be useful, however, to preclude coordinate transformations for the subsequent operations. Thus, we derived expressions for the gradient and Laplacian operators in geodetic coordinates in order to make further use on mathematical developments. Results obtained analitically and from numerical simulations validate our expressions. We applied our operators to derive the gravitational field produced by a point mass and used it for representing the regional gravity field in geodetic coordinates. The results obtained with the numerical simulations show that our approach is potentially useful in solving a wide range of problems in physical geodesy and geophysics.

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.

Coordinated gene expression for pheromone biosynthesis in the pine engraver beetle, Ips pini (Coleoptera: Scolytidae)

NASA Astrophysics Data System (ADS)

Keeling, Christopher I.; Blomquist, Gary J.; Tittiger, Claus

In several pine bark beetle species, phloem feeding induces aggregation pheromone production to coordinate a mass attack on the host tree. Male pine engraver beetles, Ips pini (Say) (Coleoptera: Scolytidae), produce the monoterpenoid pheromone component ipsdienol de novo via the mevalonate pathway in the anterior midgut upon feeding. To understand how pheromone production is regulated in this tissue, we used quantitative real-time PCR to examine feeding-induced changes in gene expression of seven mevalonate pathway genes: acetoacetyl-coenzyme A thiolase, 3-hydroxy-3-methylglutaryl coenzyme A synthase, 3-hydroxy-3-methylglutaryl coenzyme A reductase, mevalonate 5-diphosphate decarboxylase, isopentenyl-diphosphate isomerase, geranyl-diphosphate synthase (GPPS), and farnesyl-diphosphate synthase (FPPS). In males, expression of all these genes significantly increased upon feeding. In females, the expression of the early mevalonate pathway genes (up to and including the isomerase) increased significantly, but the expression of the later genes (GPPS and FPPS) was unaffected or decreased upon feeding. Thus, feeding coordinately regulates expression of the mevalonate pathway genes necessary for pheromone biosynthesis in male, but not female, midguts. Furthermore, basal mRNA levels were 5- to 41-fold more abundant in male midguts compared to female midguts. This is the first report of coordinated regulation of mevalonate pathway genes in an invertebrate model consistent with their sex-specific role in de novo pheromone biosynthesis.

Co-stimulatory function in primary germinal center responses: CD40 and B7 are required on distinct antigen-presenting cells.

PubMed

Watanabe, Masashi; Fujihara, Chiharu; Radtke, Andrea J; Chiang, Y Jeffrey; Bhatia, Sumeena; Germain, Ronald N; Hodes, Richard J

2017-09-04

T cell-dependent germinal center (GC) responses require coordinated interactions of T cells with two antigen-presenting cell (APC) populations, B cells and dendritic cells (DCs), in the presence of B7- and CD40-dependent co-stimulatory pathways. Contrary to the prevailing paradigm, we found unique cellular requirements for B7 and CD40 expression in primary GC responses to vaccine immunization with protein antigen and adjuvant: B7 was required on DCs but was not required on B cells, whereas CD40 was required on B cells but not on DCs in the generation of antigen-specific follicular helper T cells, antigen-specific GC B cells, and high-affinity class-switched antibody production. There was, in fact, no requirement for coexpression of B7 and CD40 on the same cell in these responses. Our findings support a substantially revised model for co-stimulatory function in the primary GC response, with crucial and distinct contributions of B7- and CD40-dependent pathways expressed by different APC populations and with important implications for understanding how to optimize vaccine responses or limit autoimmunity. This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.

Intra- and interregional coregulation of opioid genes: broken symmetry in spinal circuits

PubMed Central

Kononenko, Olga; Galatenko, Vladimir; Andersson, Malin; Bazov, Igor; Watanabe, Hiroyuki; Zhou, Xing Wu; Iatsyshyna, Anna; Mityakina, Irina; Yakovleva, Tatiana; Sarkisyan, Daniil; Ponomarev, Igor; Krishtal, Oleg; Marklund, Niklas; Tonevitsky, Alex; Adkins, DeAnna L.; Bakalkin, Georgy

2017-01-01

Regulation of the formation and rewiring of neural circuits by neuropeptides may require coordinated production of these signaling molecules and their receptors that may be established at the transcriptional level. Here, we address this hypothesis by comparing absolute expression levels of opioid peptides with their receptors, the largest neuropeptide family, and by characterizing coexpression (transcriptionally coordinated) patterns of these genes. We demonstrated that expression patterns of opioid genes highly correlate within and across functionally and anatomically different areas. Opioid peptide genes, compared with their receptor genes, are transcribed at much greater absolute levels, which suggests formation of a neuropeptide cloud that covers the receptor-expressed circuits. Surprisingly, we found that both expression levels and the proportion of opioid receptors are strongly lateralized in the spinal cord, interregional coexpression patterns are side specific, and intraregional coexpression profiles are affected differently by left- and right-side unilateral body injury. We propose that opioid genes are regulated as interconnected components of the same molecular system distributed between distinct anatomic regions. The striking feature of this system is its asymmetric coexpression patterns, which suggest side-specific regulation of selective neural circuits by opioid neurohormones.—Kononenko, O., Galatenko, V., Andersson, M., Bazov, I., Watanabe, H., Zhou, X. W., Iatsyshyna, A., Mityakina, I., Yakovleva, T., Sarkisyan, D., Ponomarev, I., Krishtal, O., Marklund, N., Tonevitsky, A., Adkins, D. L., Bakalkin, G. Intra- and interregional coregulation of opioid genes: broken symmetry in spinal circuits. PMID:28122917

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.

Temporally distinct transcriptional regulation of myocyte dedifferentiation and Myofiber growth during muscle regeneration.

PubMed

Louie, Ke'ale W; Saera-Vila, Alfonso; Kish, Phillip E; Colacino, Justin A; Kahana, Alon

2017-11-09

Tissue regeneration requires a series of steps, beginning with generation of the necessary cell mass, followed by cell migration into damaged area, and ending with differentiation and integration with surrounding tissues. Temporal regulation of these steps lies at the heart of the regenerative process, yet its basis is not well understood. The ability of zebrafish to dedifferentiate mature "post-mitotic" myocytes into proliferating myoblasts that in turn regenerate lost muscle tissue provides an opportunity to probe the molecular mechanisms of regeneration. Following subtotal excision of adult zebrafish lateral rectus muscle, dedifferentiating residual myocytes were collected at two time points prior to cell cycle reentry and compared to uninjured muscles using RNA-seq. Functional annotation (GAGE or K-means clustering followed by GO enrichment) revealed a coordinated response encompassing epigenetic regulation of transcription, RNA processing, and DNA replication and repair, along with protein degradation and translation that would rewire the cellular proteome and metabolome. Selected candidate genes were phenotypically validated in vivo by morpholino knockdown. Rapidly induced gene products, such as the Polycomb group factors Ezh2 and Suz12a, were necessary for both efficient dedifferentiation (i.e. cell reprogramming leading to cell cycle reentry) and complete anatomic regeneration. In contrast, the late activated gene fibronectin was important for efficient anatomic muscle regeneration but not for the early step of myocyte cell cycle reentry. Reprogramming of a "post-mitotic" myocyte into a dedifferentiated myoblast requires a complex coordinated effort that reshapes the cellular proteome and rewires metabolic pathways mediated by heritable yet nuanced epigenetic alterations and molecular switches, including transcription factors and non-coding RNAs. Our studies show that temporal regulation of gene expression is programmatically linked to distinct steps in the regeneration process, with immediate early expression driving dedifferentiation and reprogramming, and later expression facilitating anatomical regeneration.

InvS Coordinates Expression of PrgH and FimZ and Is Required for Invasion of Epithelial Cells by Salmonella enterica serovar Typhimurium

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

Wang, Lu; Cai, Xia; Wu, Shuyan

ABSTRACT Deep sequencing has revolutionized our understanding of the bacterial RNA world and has facilitated the identification of 280 small RNAs (sRNAs) inSalmonella. Despite the suspicions that sRNAs may play important roles inSalmonellapathogenesis, the functions of most sRNAs remain unknown. To advance our understanding of RNA biology inSalmonellavirulence, we searched for sRNAs required for bacterial invasion into nonphagocytic cells. After screening 75 sRNAs, we discovered that the ablation of InvS caused a significant decrease ofSalmonellainvasion into epithelial cells. A proteomic analysis showed that InvS modulated the levels of several type III secretedSalmonellaproteins. The level of PrgH, a type III secretionmore » apparatus protein, was significantly lower in the absence of InvS, consistent with the known roles of PrgH in effector secretion and bacterial invasion. We discovered that InvS modulatesfimZexpression and hence flagellar gene expression and motility. We propose that InvS coordinates the increase of PrgH and decrease in FimZ that promote efficientSalmonellainvasion into nonphagocytic cells. IMPORTANCESalmonellosis continues to be the most common foodborne infection reported by the CDC in the United States. Central toSalmonellapathogenesis is the ability to invade nonphagocytic cells and to replicate inside host cells. Invasion genes are known to be regulated by protein transcriptional networks, but little is known about the role played by small RNAs (sRNAs) in this process. We have identified a novel sRNA, InvS, that is involved inSalmonellainvasion. Our result will likely provide an opportunity to better understand the fundamental question of howSalmonellaregulates invasion gene expression and may inform strategies for therapeutic intervention.« less

An essential role for the RNA-binding protein Smaug during the Drosophila maternal-to-zygotic transition.

PubMed

Benoit, Beatrice; He, Chun Hua; Zhang, Fan; Votruba, Sarah M; Tadros, Wael; Westwood, J Timothy; Smibert, Craig A; Lipshitz, Howard D; Theurkauf, William E

2009-03-01

Genetic control of embryogenesis switches from the maternal to the zygotic genome during the maternal-to-zygotic transition (MZT), when maternal mRNAs are destroyed, high-level zygotic transcription is initiated, the replication checkpoint is activated and the cell cycle slows. The midblastula transition (MBT) is the first morphological event that requires zygotic gene expression. The Drosophila MBT is marked by blastoderm cellularization and follows 13 cleavage-stage divisions. The RNA-binding protein Smaug is required for cleavage-independent maternal transcript destruction during the Drosophila MZT. Here, we show that smaug mutants also disrupt syncytial blastoderm stage cell-cycle delays, DNA replication checkpoint activation, cellularization, and high-level zygotic expression of protein coding and micro RNA genes. We also show that Smaug protein levels increase through the cleavage divisions and peak when the checkpoint is activated and zygotic transcription initiates, and that transgenic expression of Smaug in an anterior-to-posterior gradient produces a concomitant gradient in the timing of maternal transcript destruction, cleavage cell cycle delays, zygotic gene transcription, cellularization and gastrulation. Smaug accumulation thus coordinates progression through the MZT.

JNK Controls the Onset of Mitosis in Planarian Stem Cells and Triggers Apoptotic Cell Death Required for Regeneration and Remodeling

PubMed Central

Almuedo-Castillo, María; Crespo, Xenia; Seebeck, Florian; Bartscherer, Kerstin; Salò, Emili; Adell, Teresa

2014-01-01

Regeneration of lost tissues depends on the precise interpretation of molecular signals that control and coordinate the onset of proliferation, cellular differentiation and cell death. However, the nature of those molecular signals and the mechanisms that integrate the cellular responses remain largely unknown. The planarian flatworm is a unique model in which regeneration and tissue renewal can be comprehensively studied in vivo. The presence of a population of adult pluripotent stem cells combined with the ability to decode signaling after wounding enable planarians to regenerate a complete, correctly proportioned animal within a few days after any kind of amputation, and to adapt their size to nutritional changes without compromising functionality. Here, we demonstrate that the stress-activated c-jun–NH2–kinase (JNK) links wound-induced apoptosis to the stem cell response during planarian regeneration. We show that JNK modulates the expression of wound-related genes, triggers apoptosis and attenuates the onset of mitosis in stem cells specifically after tissue loss. Furthermore, in pre-existing body regions, JNK activity is required to establish a positive balance between cell death and stem cell proliferation to enable tissue renewal, remodeling and the maintenance of proportionality. During homeostatic degrowth, JNK RNAi blocks apoptosis, resulting in impaired organ remodeling and rescaling. Our findings indicate that JNK-dependent apoptotic cell death is crucial to coordinate tissue renewal and remodeling required to regenerate and to maintain a correctly proportioned animal. Hence, JNK might act as a hub, translating wound signals into apoptotic cell death, controlled stem cell proliferation and differentiation, all of which are required to coordinate regeneration and tissue renewal. PMID:24922054

Fungus-Specific Sirtuin HstD Coordinates Secondary Metabolism and Development through Control of LaeA

PubMed Central

Kawauchi, Moriyuki; Nishiura, Mika

2013-01-01

The sirtuins are members of the NAD+-dependent histone deacetylase family that contribute to various cellular functions that affect aging, disease, and cancer development in metazoans. However, the physiological roles of the fungus-specific sirtuin family are still poorly understood. Here, we determined a novel function of the fungus-specific sirtuin HstD/Aspergillus oryzae Hst4 (AoHst4), which is a homolog of Hst4 in A. oryzae yeast. The deletion of all histone deacetylases in A. oryzae demonstrated that the fungus-specific sirtuin HstD/AoHst4 is required for the coordination of fungal development and secondary metabolite production. We also show that the expression of the laeA gene, which is the most studied fungus-specific coordinator for the regulation of secondary metabolism and fungal development, was induced in a ΔhstD strain. Genetic interaction analysis of hstD/Aohst4 and laeA clearly indicated that HstD/AoHst4 works upstream of LaeA to coordinate secondary metabolism and fungal development. The hstD/Aohst4 and laeA genes are fungus specific but conserved in the vast family of filamentous fungi. Thus, we conclude that the fungus-specific sirtuin HstD/AoHst4 coordinates fungal development and secondary metabolism via the regulation of LaeA in filamentous fungi. PMID:23729383

Optimized formulas for the gravitational field of a tesseroid

NASA Astrophysics Data System (ADS)

Grombein, Thomas; Seitz, Kurt; Heck, Bernhard

2013-07-01

Various tasks in geodesy, geophysics, and related geosciences require precise information on the impact of mass distributions on gravity field-related quantities, such as the gravitational potential and its partial derivatives. Using forward modeling based on Newton's integral, mass distributions are generally decomposed into regular elementary bodies. In classical approaches, prisms or point mass approximations are mostly utilized. Considering the effect of the sphericity of the Earth, alternative mass modeling methods based on tesseroid bodies (spherical prisms) should be taken into account, particularly in regional and global applications. Expressions for the gravitational field of a point mass are relatively simple when formulated in Cartesian coordinates. In the case of integrating over a tesseroid volume bounded by geocentric spherical coordinates, it will be shown that it is also beneficial to represent the integral kernel in terms of Cartesian coordinates. This considerably simplifies the determination of the tesseroid's potential derivatives in comparison with previously published methodologies that make use of integral kernels expressed in spherical coordinates. Based on this idea, optimized formulas for the gravitational potential of a homogeneous tesseroid and its derivatives up to second-order are elaborated in this paper. These new formulas do not suffer from the polar singularity of the spherical coordinate system and can, therefore, be evaluated for any position on the globe. Since integrals over tesseroid volumes cannot be solved analytically, the numerical evaluation is achieved by means of expanding the integral kernel in a Taylor series with fourth-order error in the spatial coordinates of the integration point. As the structure of the Cartesian integral kernel is substantially simplified, Taylor coefficients can be represented in a compact and computationally attractive form. Thus, the use of the optimized tesseroid formulas particularly benefits from a significant decrease in computation time by about 45 % compared to previously used algorithms. In order to show the computational efficiency and to validate the mathematical derivations, the new tesseroid formulas are applied to two realistic numerical experiments and are compared to previously published tesseroid methods and the conventional prism approach.

Reticulon 4B (Nogo-B) is necessary for macrophage infiltration and tissue repair.

PubMed

Yu, Jun; Fernández-Hernando, Carlos; Suarez, Yajaira; Schleicher, Michael; Hao, Zhengrong; Wright, Paulette L; DiLorenzo, Annarita; Kyriakides, Themis R; Sessa, William C

2009-10-13

Blood vessel formation during ischemia and wound healing requires coordination of the inflammatory response with genes that regulate blood vessel assembly. Here we show that the reticulon family member 4B, aka Nogo-B, is upregulated in response to ischemia and is necessary for blood flow recovery secondary to ischemia and wound healing. Mice lacking Nogo-B exhibit reduced arteriogenesis and angiogenesis that are linked to a decrease in macrophage infiltration and inflammatory gene expression in vivo. Bone marrow-derived macrophages isolated from Nogo knock-out mice have reduced spreading and chemotaxis due to impaired Rac activation. Bone marrow reconstitution experiments show that Nogo in myeloid cells is necessary to promote macrophage homing and functional recovery after limb ischemia. Thus, endogenous Nogo coordinates macrophage-mediated inflammation with arteriogenesis, wound healing, and blood flow control.

A contribution to the calculation of measurement uncertainty and optimization of measuring strategies in coordinate measurement

NASA Astrophysics Data System (ADS)

Waeldele, F.

1983-01-01

The influence of sample shape deviations on the measurement uncertainties and the optimization of computer aided coordinate measurement were investigated for a circle and a cylinder. Using the complete error propagation law in matrix form the parameter uncertainties are calculated, taking the correlation between the measurement points into account. Theoretical investigations show that the measuring points have to be equidistantly distributed and that for a cylindrical body a measuring point distribution along a cross section is better than along a helical line. The theoretically obtained expressions to calculate the uncertainties prove to be a good estimation basis. The simple error theory is not satisfactory for estimation. The complete statistical data analysis theory helps to avoid aggravating measurement errors and to adjust the number of measuring points to the required measuring uncertainty.

Deflection of light to second order: A tool for illustrating principles of general relativity

NASA Astrophysics Data System (ADS)

Bodenner, Jeremiah; Will, Clifford M.

2003-08-01

We calculate the deflection of light by a spherically symmetric body in general relativity, to second order in the quantity GM/dc2, where M is the mass of the body and d is a measure of the distance of closest approach of the ray. Using three different coordinate systems for the Schwarzschild metric we show that the answers for the deflection, while the same at order GM/dc2, differ at order (GM/dc2)2. We demonstrate that all three expressions are really the same by expressing them in terms of measurable, coordinate-independent quantities. These results provide concrete illustrations of the meaning of coordinates and coordinate invariance, which may be useful in teaching general relativity.

Schwarzschild-de Sitter spacetimes, McVittie coordinates, and trumpet geometries

NASA Astrophysics Data System (ADS)

Dennison, Kenneth A.; Baumgarte, Thomas W.

2017-12-01

Trumpet geometries play an important role in numerical simulations of black hole spacetimes, which are usually performed under the assumption of asymptotic flatness. Our Universe is not asymptotically flat, however, which has motivated numerical studies of black holes in asymptotically de Sitter spacetimes. We derive analytical expressions for trumpet geometries in Schwarzschild-de Sitter spacetimes by first generalizing the static maximal trumpet slicing of the Schwarzschild spacetime to static constant mean curvature trumpet slicings of Schwarzschild-de Sitter spacetimes. We then switch to a comoving isotropic radial coordinate which results in a coordinate system analogous to McVittie coordinates. At large distances from the black hole the resulting metric asymptotes to a Friedmann-Lemaître-Robertson-Walker metric with an exponentially-expanding scale factor. While McVittie coordinates have another asymptotically de Sitter end as the radial coordinate goes to zero, so that they generalize the notion of a "wormhole" geometry, our new coordinates approach a horizon-penetrating trumpet geometry in the same limit. Our analytical expressions clarify the role of time-dependence, boundary conditions and coordinate conditions for trumpet slices in a cosmological context, and provide a useful test for black hole simulations in asymptotically de Sitter spacetimes.

EXEL; Experience for Children in Learning. Parent-Directed Activities to Develop: Oral Expression, Visual Discrimination, Auditory Discrimination, Motor Coordination.

ERIC Educational Resources Information Center

Behrmann, Polly; Millman, Joan

The activities collected in this handbook are planned for parents to use with their children in a learning experience. They can also be used in the classroom. Sections contain games designed to develop visual discrimination, auditory discrimination, motor coordination and oral expression. An objective is given for each game, and directions for…

Atoh1-dependent rhombic lip neurons are required for temporal delay between independent respiratory oscillators in embryonic mice

PubMed Central

Tupal, Srinivasan; Huang, Wei-Hsiang; Picardo, Maria Cristina D; Ling, Guang-Yi; Del Negro, Christopher A; Zoghbi, Huda Y; Gray, Paul A

2014-01-01

All motor behaviors require precise temporal coordination of different muscle groups. Breathing, for example, involves the sequential activation of numerous muscles hypothesized to be driven by a primary respiratory oscillator, the preBötzinger Complex, and at least one other as-yet unidentified rhythmogenic population. We tested the roles of Atoh1-, Phox2b-, and Dbx1-derived neurons (three groups that have known roles in respiration) in the generation and coordination of respiratory output. We found that Dbx1-derived neurons are necessary for all respiratory behaviors, whereas independent but coupled respiratory rhythms persist from at least three different motor pools after eliminating or silencing Phox2b- or Atoh1-expressing hindbrain neurons. Without Atoh1 neurons, however, the motor pools become temporally disorganized and coupling between independent respiratory oscillators decreases. We propose Atoh1 neurons tune the sequential activation of independent oscillators essential for the fine control of different muscles during breathing. DOI: http://dx.doi.org/10.7554/eLife.02265.001 PMID:24842997

Distinct mechanisms coordinate transcription and translation under carbon and nitrogen starvation in Escherichia coli.

PubMed

Iyer, Sukanya; Le, Dai; Park, Bo Ryoung; Kim, Minsu

2018-05-14

Bacteria adapt to environmental stress by producing proteins that provide stress protection. However, stress can severely perturb the kinetics of gene expression, disrupting protein production. Here, we characterized how Escherichia coli mitigates such perturbations under nutrient stress through the kinetic coordination of transcription and translation. We observed that, when translation became limiting under nitrogen starvation, transcription elongation slowed accordingly. This slowdown was mediated by (p)ppGpp, the alarmone whose primary role is thought to be promoter regulation. This kinetic coordination by (p)ppGpp was critical for the robust synthesis of gene products. Surprisingly, under carbon starvation, (p)ppGpp was dispensable for robust synthesis. Characterization of the underlying kinetics revealed that under carbon starvation, transcription became limiting, and translation aided transcription elongation. This mechanism naturally coordinated transcription with translation, alleviating the need for (p)ppGpp as a mediator. These contrasting mechanisms for coordination resulted in the condition-dependent effects of (p)ppGpp on global protein synthesis and starvation survival. Our findings reveal a kinetic aspect of gene expression plasticity, establishing (p)ppGpp as a condition-dependent global effector of gene expression.

Single-cell analysis of peptide expression and electrophysiology of right parietal neurons involved in male copulation behavior of a simultaneous hermaphrodite.

PubMed

El Filali, Z; de Boer, P A C M; Pieneman, A W; de Lange, R P J; Jansen, R F; Ter Maat, A; van der Schors, R C; Li, K W; van Straalen, N M; Koene, J M

2015-12-01

Male copulation is a complex behavior that requires coordinated communication between the nervous system and the peripheral reproductive organs involved in mating. In hermaphroditic animals, such as the freshwater snail Lymnaea stagnalis, this complexity increases since the animal can behave both as male and female. The performance of the sexual role as a male is coordinated via a neuronal communication regulated by many peptidergic neurons, clustered in the cerebral and pedal ganglia and dispersed in the pleural and parietal ganglia. By combining single-cell matrix-assisted laser mass spectrometry with retrograde staining and electrophysiology, we analyzed neuropeptide expression of single neurons of the right parietal ganglion and their axonal projections into the penial nerve. Based on the neuropeptide profile of these neurons, we were able to reconstruct a chemical map of the right parietal ganglion revealing a striking correlation with the earlier electrophysiological and neuroanatomical studies. Neurons can be divided into two main groups: (i) neurons that express heptapeptides and (ii) neurons that do not. The neuronal projection of the different neurons into the penial nerve reveals a pattern where (spontaneous) activity is related to branching pattern. This heterogeneity in both neurochemical anatomy and branching pattern of the parietal neurons reflects the complexity of the peptidergic neurotransmission involved in the regulation of male mating behavior in this simultaneous hermaphrodite.

26 CFR 1.411(d)-1 - Coordination of vesting and discrimination requirements. [Reserved

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 5 2010-04-01 2010-04-01 false Coordination of vesting and discrimination requirements. [Reserved] 1.411(d)-1 Section 1.411(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF... Plans, Etc. § 1.411(d)-1 Coordination of vesting and discrimination requirements. [Reserved] ...

Genetic analysis of a region of the Bordetella pertussis chromosome encoding filamentous hemagglutinin and the pleiotropic regulatory locus vir.

PubMed Central

Stibitz, S; Weiss, A A; Falkow, S

1988-01-01

The vir locus of Bordetella pertussis apparently encodes a trans-acting positive regulator that is required for the coordinate expression of genes associated with virulence: pertussis toxin, filamentous hemagglutinin (FHA), hemolysin, and adenylate cyclase toxin. DNA clones of vir and of genes required for the synthesis of some of the factors under vir control were obtained with DNA probes from the chromosomal DNA surrounding sites of Tn5 insertion mutations that inactivated those genes. Two vir clones were found which also contained genes required for the proper expression of FHA in B. pertussis. The plasmids which contained both the fha and vir genes expressed immunologically reactive FHA in Escherichia coli, as detected by colony blots, whereas plasmids which contained only fha or vir were negative in this assay. The regulation of FHA production in E. coli, as in B. pertussis, was temperature dependent and inhibited by high concentrations of either magnesium ions or nicotinic acid, indicating that the sequences cloned in E. coli contained the information required to preserve the physiological responses seen in B. pertussis. Further characterization of the vir-fha clones by Tn5 mutagenesis in E. coli and by the return of cloned sequences to B. pertussis in trans and to the B. pertussis chromosome led to the localization of the vir locus, the structural gene for FHA, and genes that are possibly required for the synthesis and export of FHA. Images PMID:2898470

Coordination success and interpersonal perceptions: matching versus mismatching.

PubMed

Abele, Susanne; Stasser, Garold

2008-09-01

Coordination is an essential part of social functioning. The authors distinguish 2 types of coordination: matching and mismatching. In matching, coordination is successful if parties choose the same action. In mismatching, coordination is successful if people choose different actions. In 3 studies, the authors investigated the downstream social consequences of tacit coordination for interpersonal perceptions. In all studies, participants repeatedly choose between 2 bets with equivalent expected values, and payoffs increased either when they choose the same bet or when they choose different bets. In the 1st 2 studies, coordination success increased the perceptions of interpersonal similarity and liking when matching was required but not when mismatching was required. The authors' interpretation is that matching responses and coordination success had countervailing effects in the mismatching task. Also, percentage of matched responses did not affect perceptions when coordination was not required (Experiment 2). In 4 person teams, a frequently matching partner was viewed more favorably (smarter, more similar to self, and more liked) than were other teammates, even when mismatching increased payoffs (Experiment 3).

Direct solution for thermal stresses in a nose cap under an arbitrary axisymmetric temperature distribution

NASA Technical Reports Server (NTRS)

Davis, Randall C.

1988-01-01

The design of a nose cap for a hypersonic vehicle is an iterative process requiring a rapid, easy to use and accurate stress analysis. The objective of this paper is to develop such a stress analysis technique from a direct solution of the thermal stress equations for a spherical shell. The nose cap structure is treated as a thin spherical shell with an axisymmetric temperature distribution. The governing differential equations are solved by expressing the stress solution to the thermoelastic equations in terms of a series of derivatives of the Legendre polynomials. The process of finding the coefficients for the series solution in terms of the temperature distribution is generalized by expressing the temperature along the shell and through the thickness as a polynomial in the spherical angle coordinate. Under this generalization the orthogonality property of the Legendre polynomials leads to a sequence of integrals involving powers of the spherical shell coordinate times the derivative of the Legendre polynomials. The coefficients of the temperature polynomial appear outside of these integrals. Thus, the integrals are evaluated only once and their values tabulated for use with any arbitrary polynomial temperature distribution.

Periodic expression of nuclear and mitochondrial DNA replication genes during the trypanosomatid cell cycle.

PubMed

Pasion, S G; Brown, G W; Brown, L M; Ray, D S

1994-12-01

In trypanosomatids, DNA replication in the nucleus and in the single mitochondrion (or kinetoplast) initiates nearly simultaneously, suggesting that the DNA synthesis (S) phases of the nucleus and the mitochondrion are coordinately regulated. To investigate the basis for the temporal link between nuclear and mitochondrial DNA synthesis phases the expression of the genes encoding DNA ligase I, the 51 and 28 kDa subunits of replication protein A, dihydrofolate reductase and the mitochondrial type II topoisomerase were analyzed during the cell cycle progression of synchronous cultures of Crithidia fasciculata. These DNA replication genes were all expressed periodically, with peak mRNA levels occurring just prior to or at the peak of DNA synthesis in the synchronized cultures. A plasmid clone (pdN-1) in which TOP2, the gene encoding the mitochondrial topoisomerase, was disrupted by the insertion of a NEO drug-resistance cassette was found to express both a truncated TOP2 mRNA and a truncated topoisomerase polypeptide. The truncated mRNA was also expressed periodically coordinate with the expression of the endogenous TOP2 mRNA indicating that cis elements necessary for periodic expression are contained within cloned sequences. The expression of both TOP2 and nuclear DNA replication genes at the G1/S boundary suggests that regulated expression of these genes may play a role in coordinating nuclear and mitochondrial S phases in trypanosomatids.

20 CFR 30.627 - Under what circumstances will OWCP waive the statutory requirement to coordinate these benefits?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Under what circumstances will OWCP waive the statutory requirement to coordinate these benefits? 30.627 Section 30.627 Employees' Benefits OFFICE OF...' Compensation Benefits § 30.627 Under what circumstances will OWCP waive the statutory requirement to coordinate...

Control of early seed development.

PubMed

Chaudhury, A M; Koltunow, A; Payne, T; Luo, M; Tucker, M R; Dennis, E S; Peacock, W J

2001-01-01

Seed development requires coordinated expression of embryo and endosperm and has contributions from both sporophytic and male and female gametophytic genes. Genetic and molecular analyses in recent years have started to illuminate how products of these multiple genes interact to initiate seed development. Imprinting or differential expression of paternal and maternal genes seems to be involved in controlling seed development, presumably by controlling gene expression in developing endosperm. Epigenetic processes such as chromatin remodeling and DNA methylation affect imprinting of key seed-specific genes; however, the identity of many of these genes remains unknown. The discovery of FIS genes has illuminated control of autonomous endosperm development, a component of apomixis, which is an important developmental and agronomic trait. FIS genes are targets of imprinting, and the genes they control in developing endosperm are also regulated by DNA methylation and chromatin remodeling genes. These results define some exciting future areas of research in seed development.

AP-1/σ1B-adaptin mediates endosomal synaptic vesicle recycling, learning and memory

PubMed Central

Glyvuk, Nataliya; Tsytsyura, Yaroslav; Geumann, Constanze; D'Hooge, Rudi; Hüve, Jana; Kratzke, Manuel; Baltes, Jennifer; Böning, Daniel; Klingauf, Jürgen; Schu, Peter

2010-01-01

Synaptic vesicle recycling involves AP-2/clathrin-mediated endocytosis, but it is not known whether the endosomal pathway is also required. Mice deficient in the tissue-specific AP-1–σ1B complex have impaired synaptic vesicle recycling in hippocampal synapses. The ubiquitously expressed AP-1–σ1A complex mediates protein sorting between the trans-Golgi network and early endosomes. Vertebrates express three σ1 subunit isoforms: A, B and C. The expressions of σ1A and σ1B are highest in the brain. Synaptic vesicle reformation in cultured neurons from σ1B-deficient mice is reduced upon stimulation, and large endosomal intermediates accumulate. The σ1B-deficient mice have reduced motor coordination and severely impaired long-term spatial memory. These data reveal a molecular mechanism for a severe human X-chromosome-linked mental retardation. PMID:20203623

48 CFR 970.5223-7 - Sustainable acquisition program.

Code of Federal Regulations, 2010 CFR

2010-10-01

... coordinate its activities with and submit required reports through the Environmental Sustainability... clause, the Contractor shall coordinate its activities with and submit required reports through the Environmental Sustainability Coordinator or equivalent position. (g) The Contractor shall prepare and submit...

The DREAM complex: Master coordinator of cell cycle dependent gene expression

PubMed Central

Sadasivam, Subhashini; DeCaprio, James A.

2014-01-01

Preface The dimerization partner (DP), retinoblastoma (RB)-like, E2F and MuvB (DREAM) complex provides a previously unsuspected unifying role in the cell cycle by directly linking p130, p107, E2F, BMYB and FOXM1. DREAM mediates gene repression during G0 and coordinates periodic gene expression with peaks during G1/S and G2/M. Perturbations in DREAM regulation shift the balance from quiescence towards proliferation and contribute to increased mitotic gene expression levels frequently observed in cancers with poor prognosis. PMID:23842645

Over-expression, purification, and confirmation of Bacillus anthracis transcriptional regulator NprR

PubMed Central

Rice, Amy J.; Woo, Jerry K.; Khan, Attiya; Szypulinski, Michael Z.; Johnson, Michael E.; Lee, Hyunwoo; Lee, Hyun

2016-01-01

Quorum sensing (QS) has been recognized as an important biological phenomenon in which bacterial cells communicate and coordinate their gene expression and cellular processes with respect to population density. Bacillus anthracis is the etiological agent of fatal pulmonary anthrax infections, and the NprR/NprX QS system may be involved in its pathogenesis. NprR, renamed as aqsR for anthrax quorum sensing Regulator, is a transcriptional regulator that may control the expression of genes required for proliferation and survival. Currently, there is no protocol reported to over-express and purify B. anthracis AqsR. In this study, we describe cloning, purification, and confirmation of functional full-length B. anthracis AqsR protein. The AqsR gene was cloned into the pQE-30 vector with an HRV 3C protease recognition site between AqsR and the N-terminal His6-tag in order to yield near native AqsR after the His-tag cleavage, leaving only two additional amino acid residues at the N-terminus. PMID:26344899

Intersection of FOXO- and RUNX1-mediated gene expression programs in single breast epithelial cells during morphogenesis and tumor progression.

PubMed

Wang, Lixin; Brugge, Joan S; Janes, Kevin A

2011-10-04

Gene expression networks are complicated by the assortment of regulatory factors that bind DNA and modulate transcription combinatorially. Single-cell measurements can reveal biological mechanisms hidden by population averages, but their value has not been fully explored in the context of mRNA regulation. Here, we adapted a single-cell expression profiling technique to examine the gene expression program downstream of Forkhead box O (FOXO) transcription factors during 3D breast epithelial acinar morphogenesis. By analyzing patterns of mRNA fluctuations among individual matrix-attached epithelial cells, we found that a subset of FOXO target genes was jointly regulated by the transcription factor Runt-related transcription factor 1 (RUNX1). Knockdown of RUNX1 causes hyperproliferation and abnormal morphogenesis, both of which require normal FOXO function. Down-regulating RUNX1 and FOXOs simultaneously causes widespread oxidative stress, which arrests proliferation and restores normal acinar morphology. In hormone-negative breast cancers lacking human epidermal growth factor receptor 2 (HER2) amplification, we find that RUNX1 down-regulation is strongly associated with up-regulation of FOXO1, which may be required to support growth of RUNX1-negative tumors. The coordinate function of these two tumor suppressors may provide a failsafe mechanism that inhibits cancer progression.

Dynamic Changes in Nucleosome Occupancy Are Not Predictive of Gene Expression Dynamics but Are Linked to Transcription and Chromatin Regulators

PubMed Central

Huebert, Dana J.; Kuan, Pei-Fen; Keleş, Sündüz

2012-01-01

The response to stressful stimuli requires rapid, precise, and dynamic gene expression changes that must be coordinated across the genome. To gain insight into the temporal ordering of genome reorganization, we investigated dynamic relationships between changing nucleosome occupancy, transcription factor binding, and gene expression in Saccharomyces cerevisiae yeast responding to oxidative stress. We applied deep sequencing to nucleosomal DNA at six time points before and after hydrogen peroxide treatment and revealed many distinct dynamic patterns of nucleosome gain and loss. The timing of nucleosome repositioning was not predictive of the dynamics of downstream gene expression change but instead was linked to nucleosome position relative to transcription start sites and specific cis-regulatory elements. We measured genome-wide binding of the stress-activated transcription factor Msn2p over time and found that Msn2p binds different loci with different dynamics. Nucleosome eviction from Msn2p binding sites was common across the genome; however, we show that, contrary to expectation, nucleosome loss occurred after Msn2p binding and in fact required Msn2p. This negates the prevailing model that nucleosomes obscuring Msn2p sites regulate DNA access and must be lost before Msn2p can bind DNA. Together, these results highlight the complexities of stress-dependent chromatin changes and their effects on gene expression. PMID:22354995

Hindsight regulates photoreceptor axon targeting through transcriptional control of jitterbug/Filamin and multiple genes involved in axon guidance in Drosophila.

PubMed

Oliva, Carlos; Molina-Fernandez, Claudia; Maureira, Miguel; Candia, Noemi; López, Estefanía; Hassan, Bassem; Aerts, Stein; Cánovas, José; Olguín, Patricio; Sierralta, Jimena

2015-09-01

During axon targeting, a stereotyped pattern of connectivity is achieved by the integration of intrinsic genetic programs and the response to extrinsic long and short-range directional cues. How this coordination occurs is the subject of intense study. Transcription factors play a central role due to their ability to regulate the expression of multiple genes required to sense and respond to these cues during development. Here we show that the transcription factor HNT regulates layer-specific photoreceptor axon targeting in Drosophila through transcriptional control of jbug/Filamin and multiple genes involved in axon guidance and cytoskeleton organization.Using a microarray analysis we identified 235 genes whose expression levels were changed by HNT overexpression in the eye primordia. We analyzed nine candidate genes involved in cytoskeleton regulation and axon guidance, six of which displayed significantly altered gene expression levels in hnt mutant retinas. Functional analysis confirmed the role of OTK/PTK7 in photoreceptor axon targeting and uncovered Tiggrin, an integrin ligand, and Jbug/Filamin, a conserved actin- binding protein, as new factors that participate of photoreceptor axon targeting. Moreover, we provided in silico and molecular evidence that supports jbug/Filamin as a direct transcriptional target of HNT and that HNT acts partially through Jbug/Filamin in vivo to regulate axon guidance. Our work broadens the understanding of how HNT regulates the coordinated expression of a group of genes to achieve the correct connectivity pattern in the Drosophila visual system. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 75: 1018-1032, 2015. © 2015 Wiley Periodicals, Inc.

Coordination of gene expression of arachidonic and docosahexaenoic acid cascade enzymes during human brain development and aging.

PubMed

Ryan, Veronica H; Primiani, Christopher T; Rao, Jagadeesh S; Ahn, Kwangmi; Rapoport, Stanley I; Blanchard, Helene

2014-01-01

The polyunsaturated arachidonic and docosahexaenoic acids (AA and DHA) participate in cell membrane synthesis during neurodevelopment, neuroplasticity, and neurotransmission throughout life. Each is metabolized via coupled enzymatic reactions within separate but interacting metabolic cascades. AA and DHA pathway genes are coordinately expressed and underlie cascade interactions during human brain development and aging. The BrainCloud database for human non-pathological prefrontal cortex gene expression was used to quantify postnatal age changes in mRNA expression of 34 genes involved in AA and DHA metabolism. Expression patterns were split into Development (0 to 20 years) and Aging (21 to 78 years) intervals. Expression of genes for cytosolic phospholipases A2 (cPLA2), cyclooxygenases (COX)-1 and -2, and other AA cascade enzymes, correlated closely with age during Development, less so during Aging. Expression of DHA cascade enzymes was less inter-correlated in each period, but often changed in the opposite direction to expression of AA cascade genes. Except for the PLA2G4A (cPLA2 IVA) and PTGS2 (COX-2) genes at 1q25, highly inter-correlated genes were at distant chromosomal loci. Coordinated age-related gene expression during the brain Development and Aging intervals likely underlies coupled changes in enzymes of the AA and DHA cascades and largely occur through distant transcriptional regulation. Healthy brain aging does not show upregulation of PLA2G4 or PTGS2 expression, which was found in Alzheimer's disease.

Planar cell polarity controls directional Notch signaling in the Drosophila leg

PubMed Central

Capilla, Amalia; Johnson, Ruth; Daniels, Maki; Benavente, María; Bray, Sarah J.; Galindo, Máximo Ibo

2012-01-01

The generation of functional structures during development requires tight spatial regulation of signaling pathways. Thus, in Drosophila legs, in which Notch pathway activity is required to specify joints, only cells distal to ligand-producing cells are capable of responding. Here, we show that the asymmetric distribution of planar cell polarity (PCP) proteins correlates with this spatial restriction of Notch activation. Frizzled and Dishevelled are enriched at distal sides of each cell and hence localize at the interface with ligand-expressing cells in the non-responding cells. Elimination of PCP gene function in cells proximal to ligand-expressing cells is sufficient to alleviate the repression, resulting in ectopic Notch activity and ectopic joint formation. Mutations that compromise a direct interaction between Dishevelled and Notch reduce the efficacy of repression. Likewise, increased Rab5 levels or dominant-negative Deltex can suppress the ectopic joints. Together, these results suggest that PCP coordinates the spatial activity of the Notch pathway by regulating endocytic trafficking of the receptor. PMID:22736244

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

Gauge Theories of Vector Particles

DOE R&D Accomplishments Database

Glashow, S. L.; Gell-Mann, M.

1961-04-24

The possibility of generalizing the Yang-Mills trick is examined. Thus we seek theories of vector bosons invariant under continuous groups of coordinate-dependent linear transformations. All such theories may be expressed as superpositions of certain "simple" theories; we show that each "simple theory is associated with a simple Lie algebra. We may introduce mass terms for the vector bosons at the price of destroying the gauge-invariance for coordinate-dependent gauge functions. The theories corresponding to three particular simple Lie algebras - those which admit precisely two commuting quantum numbers - are examined in some detail as examples. One of them might play a role in the physics of the strong interactions if there is an underlying super-symmetry, transcending charge independence, that is badly broken. The intermediate vector boson theory of weak interactions is discussed also. The so-called "schizon" model cannot be made to conform to the requirements of partial gauge-invariance.

A Conserved Nuclear Cyclophilin Is Required for Both RNA Polymerase II Elongation and Co-transcriptional Splicing in Caenorhabditis elegans

PubMed Central

Ahn, Jeong H.; Rechsteiner, Andreas; Strome, Susan; Kelly, William G.

2016-01-01

The elongation phase of transcription by RNA Polymerase II (Pol II) involves numerous events that are tightly coordinated, including RNA processing, histone modification, and chromatin remodeling. RNA splicing factors are associated with elongating Pol II, and the interdependent coupling of splicing and elongation has been documented in several systems. Here we identify a conserved, multi-domain cyclophilin family member, SIG-7, as an essential factor for both normal transcription elongation and co-transcriptional splicing. In embryos depleted for SIG-7, RNA levels for over a thousand zygotically expressed genes are substantially reduced, Pol II becomes significantly reduced at the 3’ end of genes, marks of transcription elongation are reduced, and unspliced mRNAs accumulate. Our findings suggest that SIG-7 plays a central role in both Pol II elongation and co-transcriptional splicing and may provide an important link for their coordination and regulation. PMID:27541139

Equations of motion for the variable mass flow-variable exhaust velocity rocket

NASA Technical Reports Server (NTRS)

Tempelman, W. H.

1972-01-01

An equation of motion for a one dimensional rocket is derived as a function of the mass flow rate into the acceleration chamber and the velocity distribution along the chamber, thereby including the transient flow changes in the chamber. The derivation of the mass density requires the introduction of the special time coordinate. The equation of motion is derived from both classical force and momentum approaches and is shown to be consistent with the standard equation expressed in terms of flow parameters at the exit to the acceleration chamber.

Vascular gene expression: a hypothesis

PubMed Central

Martínez-Navarro, Angélica C.; Galván-Gordillo, Santiago V.; Xoconostle-Cázares, Beatriz; Ruiz-Medrano, Roberto

2013-01-01

The phloem is the conduit through which photoassimilates are distributed from autotrophic to heterotrophic tissues and is involved in the distribution of signaling molecules that coordinate plant growth and responses to the environment. Phloem function depends on the coordinate expression of a large array of genes. We have previously identified conserved motifs in upstream regions of the Arabidopsis genes, encoding the homologs of pumpkin phloem sap mRNAs, displaying expression in vascular tissues. This tissue-specific expression in Arabidopsis is predicted by the overrepresentation of GA/CT-rich motifs in gene promoters. In this work we have searched for common motifs in upstream regions of the homologous genes from plants considered to possess a “primitive” vascular tissue (a lycophyte), as well as from others that lack a true vascular tissue (a bryophyte), and finally from chlorophytes. Both lycophyte and bryophyte display motifs similar to those found in Arabidopsis with a significantly low E-value, while the chlorophytes showed either a different conserved motif or no conserved motif at all. These results suggest that these same genes are expressed coordinately in non-vascular plants; this coordinate expression may have been one of the prerequisites for the development of conducting tissues in plants. We have also analyzed the phylogeny of conserved proteins that may be involved in phloem function and development. The presence of CmPP16, APL, FT, and YDA in chlorophytes suggests the recruitment of ancient regulatory networks for the development of the vascular tissue during evolution while OPS is a novel protein specific to vascular plants. PMID:23882276

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.

Numerical Simulation of Subsonic and Transonic Propeller Flow. Ph.D. Thesis

NASA Technical Reports Server (NTRS)

Snyder, Aaron

1988-01-01

The numerical simulation of 3-D transonic flow about a system of propeller blades is investigated. In particular, it is shown that the use of helical coordinates significantly simplifies the form of the governing equation when the propeller system is assumed to be surrounded by an irrotational flow field of an inviscid fluid. The unsteady small disturbance equation, valid for lightly loaded blades and expressed in helical coordinates, is derived from the general blade-fixed potential equation, given for an arbitrary coordinate system. The use of a coordinate system which inherently adapts to the mean flow results in a disturbance equation requiring relatively few terms to accurately model the physics of the flow. Furthermore, the helical coordinate system presented here is novel in that it is periodic in the circumferential direction while, simultaneously, maintaining orthogonal properties at the mean blade locations. The periodic characteristic allows a complete cascade of blades to be treated, and the orthogonality property affords straightforward treatment of blade boundary conditions. An ADI numerical scheme is used to compute the solution of the steady flow as an asymptotic limit of an unsteady flow. As an example of the method, solutions are presented for subsonic and transonic flow about a 5 percent thick bicircular arc blade of an 8-bladed cascade. Both high and low advance ratio cases are computed and include a lifting as well as nonlifting cases. The nonlifting solutions obtained are compared to solutions from a Euler code.

Object-Place Recognition Learning Triggers Rapid Induction of Plasticity-Related Immediate Early Genes and Synaptic Proteins in the Rat Dentate Gyrus

PubMed Central

Soulé, Jonathan; Penke, Zsuzsa; Kanhema, Tambudzai; Alme, Maria Nordheim; Laroche, Serge; Bramham, Clive R.

2008-01-01

Long-term recognition memory requires protein synthesis, but little is known about the coordinate regulation of specific genes. Here, we examined expression of the plasticity-associated immediate early genes (Arc, Zif268, and Narp) in the dentate gyrus following long-term object-place recognition learning in rats. RT-PCR analysis from dentate gyrus tissue collected shortly after training did not reveal learning-specific changes in Arc mRNA expression. In situ hybridization and immunohistochemistry were therefore used to assess possible sparse effects on gene expression. Learning about objects increased the density of granule cells expressing Arc, and to a lesser extent Narp, specifically in the dorsal blade of the dentate gyrus, while Zif268 expression was elevated across both blades. Thus, object-place recognition triggers rapid, blade-specific upregulation of plasticity-associated immediate early genes. Furthermore, Western blot analysis of dentate gyrus homogenates demonstrated concomitant upregulation of three postsynaptic density proteins (Arc, PSD-95, and α-CaMKII) with key roles in long-term synaptic plasticity and long-term memory. PMID:19190776

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.

Toll-Like Receptor 4 Deficiency Impairs Motor Coordination

PubMed Central

Zhu, Jian-Wei; Li, Yi-Fei; Wang, Zhao-Tao; Jia, Wei-Qiang; Xu, Ru-Xiang

2016-01-01

The cerebellum plays an essential role in balance and motor coordination. Purkinje cells (PCs) are the sole output neurons of the cerebellar cortex and are critical for the execution of its functions, including motor coordination. Toll-like receptor (TLR) 4 is involved in the innate immune response and is abundantly expressed in the central nervous system; however, little is known about its role in cerebellum-related motor functions. To address this question, we evaluated motor behavior in TLR4 deficient mice. We found that TLR4−∕− mice showed impaired motor coordination. Morphological analyses revealed that TLR4 deficiency was associated with a reduction in the thickness of the molecular layer of the cerebellum. TLR4 was highly expressed in PCs but not in Bergmann glia or cerebellar granule cells; however, loss of TLR4 decreased the number of PCs. These findings suggest a novel role for TLR4 in cerebellum-related motor coordination through maintenance of the PC population. PMID:26909014

bicaudal-C is required for the formation of anterior neurogenic ectoderm in the sea urchin embryo.

PubMed

Yaguchi, Shunsuke; Yaguchi, Junko; Inaba, Kazuo

2014-10-31

bicaudal-C (bicC) mRNA encodes a protein containing RNA-binding domains that is reported to be maternally present with deflection in the oocytes/eggs of some species. The translated protein plays a critical role in the regulation of cell fate specification along the body axis during early embryogenesis in flies and frogs. However, it is unclear how it functions in eggs in which bicC mRNA is uniformly distributed, for instance, sea urchin eggs. Here, we show the function of BicC in the formation of neurogenic ectoderm of the sea urchin embryo. Loss-of-function experiments reveal that BicC is required for serotonergic neurogenesis and for expression of ankAT-1 gene, which is essential for the formation of apical tuft cilia in the neurogenic ectoderm of the sea urchin embryo. In contrast, the expression of FoxQ2, the neurogenic ectoderm specification transcription factor, is invariant in BicC morphants. Because FoxQ2 is an upstream factor of serotonergic neurogenesis and ankAT-1 expression, these data indicate that BicC functions in regulating the events that are coordinated by FoxQ2 during sea urchin embryogenesis.

TGF-β induction of FGF-2 expression in stromal cells requires integrated smad3 and MAPK pathways.

PubMed

Strand, Douglas W; Liang, Yao-Yun; Yang, Feng; Barron, David A; Ressler, Steven J; Schauer, Isaiah G; Feng, Xin-Hua; Rowley, David R

2014-01-01

Transforming Growth Factor-β (TGF-β) regulates the reactive stroma microenvironment associated with most carcinomas and mediates expression of many stromal derived factors important for tumor progression, including FGF-2 and CTGF. TGF-β is over-expressed in most carcinomas, and FGF-2 action is important in tumor-induced angiogenesis. The signaling mechanisms of how TGF-β regulates FGF-2 expression in the reactive stroma microenvironment are not understood. Accordingly, we have assessed key signaling pathways that mediate TGF-β1-induced FGF-2 expression in prostate stromal fibroblasts and mouse embryo fibroblasts (MEFs) null for Smad2 and Smad3. TGF-β1 induced phosphorylation of Smad2, Smad3, p38 and ERK1/2 proteins in both control MEFs and prostate fibroblasts. Of these, Smad3, but not Smad2 was found to be required for TGF-β1 induction of FGF-2 expression in stromal cells. ChIP analysis revealed a Smad3/Smad4 complex was associated with the -1.9 to -2.3 kb upstream proximal promoter of the FGF-2 gene, further suggesting a Smad3-specific regulation. In addition, chemical inhibition of p38 or ERK1/2 MAPK activity also blocked TGF-β1-induced FGF-2 expression in a Smad3-independent manner. Conversely, inhibition of JNK signaling enhanced FGF-2 expression. Together, these data indicate that expression of FGF-2 in fibroblasts in the tumor stromal cell microenvironment is coordinately dependent on both intact Smad3 and MAP kinase signaling pathways. These pathways and key downstream mediators of TGF-β action in the tumor reactive stroma microenvironment, may evolve as putative targets for therapeutic intervention.

Inflammation-induced formation of fat-associated lymphoid clusters

PubMed Central

Bénézech, Cécile; Kruglov, Andrei A.; Loo, Yunhua; Nakamura, Kyoko; Zhang, Yang; Nayar, Saba; Jones, Lucy H.; Flores-Langarica, Adriana; McIntosh, Alistair; Marshall, Jennifer; Barone, Francesca; Besra, Gurdyal; Miles, Katherine; Allen, Judith E.; Gray, Mohini; Kollias, George; Cunningham, Adam F.; Withers, David R.; Toellner, Kai Michael; Jones, Nick D.; Veldhoen, Marc; Nedospasov, Sergei A.; McKenzie, Andrew N.J.; Caamaño, Jorge H.

2015-01-01

Fat-associated lymphoid clusters (FALCs) are a recently discovered type of lymphoid tissue associated with visceral fat. Here we show that distribution of FALCs was heterogeneous with the pericardium containing large numbers of these clusters. FALCs contributed to the retention of B-1 B cells in the peritoneal cavity through high expression of the chemokine CXCL13 and supported B cell proliferation and germinal center differentiation during peritoneal immune challenges. FALC formation was induced by inflammation, which triggered recruitment of myeloid cells that express tumor necrosis factor (TNF) necessary for TNF receptor-signaling in stromal cells. CD1d-restricted Natural killer T (NKT) cells were likewise required for inducible formation of FALCs. Thus, FALCs support and coordinate innate B and T cell activation during serosal immune responses. PMID:26147686

Expressions to Rayleigh circumferential phase velocity and dispersion relation for a cylindrical surface under mechanical pressure

NASA Astrophysics Data System (ADS)

Sebold, Jean Eduardo; de Lacerda, Luiz Alkimin

2018-04-01

This paper describes a substantiated mathematical theory for Rayleigh waves propagated on some types of metal cylinders. More specifically, it presents not only a new way to express the dispersion relation of Rayleigh waves propagated on the cylindrical surface, but also how it can be used to construct a mathematical equation showing that the applied static mechanical pressure affects the shear modulus of the metal cylinder. All steps, required to conclude the process, consider the equation of motion as a function of radial and circumferential coordinates only, while the axial component can be overlooked without causing any problems. Some numerical experiments are done to illustrate the changes in the Rayleigh circumferential phase velocity in a metal cylindrical section due to static mechanical pressure around its external surface.

How Moving Together Brings Us Together: When Coordinated Rhythmic Movement Affects Cooperation

PubMed Central

Cross, Liam; Wilson, Andrew D.; Golonka, Sabrina

2016-01-01

Although it is well established that rhythmically coordinating with a social partner can increase cooperation, it is as yet unclear when and why intentional coordination has such effects. We distinguish three dimensions along which explanations might vary. First, pro-social effects might require in-phase synchrony or simply coordination. Second, the effects of rhythmic movements on cooperation might be direct or mediated by an intervening variable. Third, the pro-social effects might occur in proportion to the quality of the coordination, or occur once some threshold amount of coordination has occurred. We report an experiment and two follow-ups which sought to identify which classes of models are required to account for the positive effects of coordinated rhythmic movement on cooperation. Across the studies, we found evidence (1) that coordination, and not just synchrony, can have pro-social consequences (so long as the social nature of the task is perceived), (2) that the effects of intentional coordination are direct, not mediated, and (3) that the degree of the coordination did not predict the degree of cooperation. The fact of inter-personal coordination (moving together in time and in a social context) is all that's required for pro-social effects. We suggest that future research should use the kind of carefully controllable experimental task used here to continue to develop explanations for when and why coordination affects pro-social behaviors. PMID:28066301

Intracellular coordination of potyviral RNA functions in infection

PubMed Central

Mäkinen, Kristiina; Hafrén, Anders

2014-01-01

Establishment of an infection cycle requires mechanisms to allocate the genomes of (+)-stranded RNA viruses in a balanced ratio to translation, replication, encapsidation, and movement, as well as mechanisms to prevent translocation of viral RNA (vRNA) to cellular RNA degradation pathways. The ratio of vRNA allocated to various functions is likely balanced by the availability of regulatory proteins or competition of the interaction sites within regulatory ribonucleoprotein complexes. Due to the transient nature of viral processes and the interdependency between vRNA pathways, it is technically demanding to work out the exact molecular mechanisms underlying vRNA regulation. A substantial number of viral and host proteins have been identified that facilitate the steps that lead to the assembly of a functional potyviral RNA replication complex and their fusion with chloroplasts. Simultaneously with on-going viral replication, part of the replicated potyviral RNA enters movement pathways. Although not much is known about the processes of potyviral RNA release from viral replication complexes, the molecular interactions involved in these processes determine the fate of the replicated vRNA. Some viral and host cell proteins have been described that direct replicated potyviral RNA to translation to enable potyviral gene expression and productive infection. The antiviral defense of the cell causes vRNA degradation by RNA silencing. We hypothesize that also plant pathways involved in mRNA decay may have a role in the coordination of potyviral RNA expression. In this review, we discuss the roles of different potyviral and host proteins in the coordination of various potyviral RNA functions. PMID:24723931

Intracellular coordination of potyviral RNA functions in infection.

PubMed

Mäkinen, Kristiina; Hafrén, Anders

2014-01-01

Establishment of an infection cycle requires mechanisms to allocate the genomes of (+)-stranded RNA viruses in a balanced ratio to translation, replication, encapsidation, and movement, as well as mechanisms to prevent translocation of viral RNA (vRNA) to cellular RNA degradation pathways. The ratio of vRNA allocated to various functions is likely balanced by the availability of regulatory proteins or competition of the interaction sites within regulatory ribonucleoprotein complexes. Due to the transient nature of viral processes and the interdependency between vRNA pathways, it is technically demanding to work out the exact molecular mechanisms underlying vRNA regulation. A substantial number of viral and host proteins have been identified that facilitate the steps that lead to the assembly of a functional potyviral RNA replication complex and their fusion with chloroplasts. Simultaneously with on-going viral replication, part of the replicated potyviral RNA enters movement pathways. Although not much is known about the processes of potyviral RNA release from viral replication complexes, the molecular interactions involved in these processes determine the fate of the replicated vRNA. Some viral and host cell proteins have been described that direct replicated potyviral RNA to translation to enable potyviral gene expression and productive infection. The antiviral defense of the cell causes vRNA degradation by RNA silencing. We hypothesize that also plant pathways involved in mRNA decay may have a role in the coordination of potyviral RNA expression. In this review, we discuss the roles of different potyviral and host proteins in the coordination of various potyviral RNA functions.

Dysgraphia

MedlinePlus

Written expression disorder; Specific learning disorder with impairment in written expression ... can have dysgraphia only or along with other learning disabilities, such as: Developmental coordination disorder (includes poor handwriting) ...

Coordination of Gene Expression of Arachidonic and Docosahexaenoic Acid Cascade Enzymes during Human Brain Development and Aging

PubMed Central

Ryan, Veronica H.; Primiani, Christopher T.; Rao, Jagadeesh S.; Ahn, Kwangmi; Rapoport, Stanley I.; Blanchard, Helene

2014-01-01

Background The polyunsaturated arachidonic and docosahexaenoic acids (AA and DHA) participate in cell membrane synthesis during neurodevelopment, neuroplasticity, and neurotransmission throughout life. Each is metabolized via coupled enzymatic reactions within separate but interacting metabolic cascades. Hypothesis AA and DHA pathway genes are coordinately expressed and underlie cascade interactions during human brain development and aging. Methods The BrainCloud database for human non-pathological prefrontal cortex gene expression was used to quantify postnatal age changes in mRNA expression of 34 genes involved in AA and DHA metabolism. Results Expression patterns were split into Development (0 to 20 years) and Aging (21 to 78 years) intervals. Expression of genes for cytosolic phospholipases A2 (cPLA2), cyclooxygenases (COX)-1 and -2, and other AA cascade enzymes, correlated closely with age during Development, less so during Aging. Expression of DHA cascade enzymes was less inter-correlated in each period, but often changed in the opposite direction to expression of AA cascade genes. Except for the PLA2G4A (cPLA2 IVA) and PTGS2 (COX-2) genes at 1q25, highly inter-correlated genes were at distant chromosomal loci. Conclusions Coordinated age-related gene expression during the brain Development and Aging intervals likely underlies coupled changes in enzymes of the AA and DHA cascades and largely occur through distant transcriptional regulation. Healthy brain aging does not show upregulation of PLA2G4 or PTGS2 expression, which was found in Alzheimer's disease. PMID:24963629

Coordinate late expression of trefoil peptide genes (pS2/TFF1 and ITF/TFF3) in human breast, colon, and gastric tumor cells exposed to X-rays

NASA Technical Reports Server (NTRS)

Balcer-Kubiczek, Elizabeth K.; Harrison, George H.; Xu, Jing-Fan; Gutierrez, Peter L.

2002-01-01

The trefoil factors (TFFs) are pleiotropic factors involved in organization and homeostasis of the gastrointestinal tract, estrogen responsiveness, inflammatory disorders, and carcinogenesis. In an earlier study using cDNA array technologies to identify new genes expressed in irradiated cell survivors, we isolated a cDNA clone corresponding to the reported human TFF1 gene (E. K. Balcer-Kubiczek et al., Int. J. Radiat. Biol., 75: 529-541, 1999). To determine whether expression of other TFFs is altered by ionizing radiation, we quantified changes in expression of TFF3 as well as TFF1 in RNA samples obtained from irradiated and control human tumor breast, colon, and gastric tumor cells and examined expression kinetics up to 2 weeks after irradiation. X-ray-induced TFF1 and TFF3 expression profiles were compared with those induced by hydrogen peroxide (H2O2) or 17beta-estradiol (ES). The results revealed that TFF1 and TFF3 mRNA are coinduced by X-irradiation in a subset of the lines, but substantial heterogeneity in their responses was observed in cells derived from a single cell type. TFF1 and TFF3 transcriptional response to X-irradiation differed from that to H2O2 or ES in the timing of their induction as well as tissue-type dependence, i.e., their induction pattern after X-irradiation was late and sustained, whereas their induction by H2O2 or ES was early and transient. TFF1 mRNA, protein production in the cytoplasm, and secretion in the culture supernatant were coordinately regulated after X-irradiation. There was no requirement for TP53 in this induction. These results demonstrate the existence of a novel class of radiation-responsive genes that might be involved in bystander effects.

Alternative Polyadenylation and Nonsense-Mediated Decay Coordinately Regulate the Human HFE mRNA Levels

PubMed Central

Martins, Rute; Proença, Daniela; Silva, Bruno; Barbosa, Cristina; Silva, Ana Luísa; Faustino, Paula; Romão, Luísa

2012-01-01

Nonsense-mediated decay (NMD) is an mRNA surveillance pathway that selectively recognizes and degrades defective mRNAs carrying premature translation-termination codons. However, several studies have shown that NMD also targets physiological transcripts that encode full-length proteins, modulating their expression. Indeed, some features of physiological mRNAs can render them NMD-sensitive. Human HFE is a MHC class I protein mainly expressed in the liver that, when mutated, can cause hereditary hemochromatosis, a common genetic disorder of iron metabolism. The HFE gene structure comprises seven exons; although the sixth exon is 1056 base pairs (bp) long, only the first 41 bp encode for amino acids. Thus, the remaining downstream 1015 bp sequence corresponds to the HFE 3′ untranslated region (UTR), along with exon seven. Therefore, this 3′ UTR encompasses an exon/exon junction, a feature that can make the corresponding physiological transcript NMD-sensitive. Here, we demonstrate that in UPF1-depleted or in cycloheximide-treated HeLa and HepG2 cells the HFE transcripts are clearly upregulated, meaning that the physiological HFE mRNA is in fact an NMD-target. This role of NMD in controlling the HFE expression levels was further confirmed in HeLa cells transiently expressing the HFE human gene. Besides, we show, by 3′-RACE analysis in several human tissues that HFE mRNA expression results from alternative cleavage and polyadenylation at four different sites – two were previously described and two are novel polyadenylation sites: one located at exon six, which confers NMD-resistance to the corresponding transcripts, and another located at exon seven. In addition, we show that the amount of HFE mRNA isoforms resulting from cleavage and polyadenylation at exon seven, although present in both cell lines, is higher in HepG2 cells. These results reveal that NMD and alternative polyadenylation may act coordinately to control HFE mRNA levels, possibly varying its protein expression according to the physiological cellular requirements. PMID:22530027

Post-transcriptional regulation mediated by specific neurofilament introns in vivo.

PubMed

Wang, Chen; Szaro, Ben G

2016-04-01

Neurons regulate genes post-transcriptionally to coordinate the supply of cytoskeletal proteins, such as the medium neurofilament (NEFM), with demand for structural materials in response to extracellular cues encountered by developing axons. By using a method for evaluating functionality of cis-regulatory gene elements in vivo through plasmid injection into Xenopus embryos, we discovered that splicing of a specific nefm intron was required for robust transgene expression, regardless of promoter or cell type. Transgenes utilizing the nefm 3'-UTR but substituting other nefm introns expressed little or no protein owing to defects in handling of the messenger (m)RNA as opposed to transcription or splicing. Post-transcriptional events at multiple steps, but mainly during nucleocytoplasmic export, contributed to these varied levels of protein expression. An intron of the β-globin gene was also able to promote expression in a manner identical to that of the nefm intron, implying a more general preference for certain introns in controlling nefm expression. These results expand our knowledge of intron-mediated gene expression to encompass neurofilaments, indicating an additional layer of complexity in the control of a cytoskeletal gene needed for developing and maintaining healthy axons. © 2016. Published by The Company of Biologists Ltd.

Defects in Mitochondrial Fatty Acid Synthesis Result in Failure of Multiple Aspects of Mitochondrial Biogenesis in Saccharomyces cerevisiae

PubMed Central

Kursu, V. A. Samuli; Pietikäinen, Laura P.; Fontanesi, Flavia; Aaltonen, Mari J.; Suomi, Fumi; Nair, Remya Raghavan; Schonauer, Melissa S.; Dieckmann, Carol L.; Barrientos, Antoni; Hiltunen, J. Kalervo; Kastaniotis, Alexander J.

2014-01-01

Summary Mitochondrial fatty acid synthesis (mtFAS) shares acetyl-CoA with the Krebs cycle as a common substrate and is required for the production of octanoic acid (C8) precursors of lipoic acid (LA) in mitochondria. MtFAS is a conserved pathway essential for respiration. In a genetic screen in Saccharomyces cerevisiae designed to further elucidate the physiological role of mtFAS, we isolated mutants with defects in mitochondrial post-translational gene expression processes, indicating a novel link to mitochondrial gene expression and respiratory chain biogenesis. In our ensuing analysis, we show that mtFAS, but not lipoylation per se, is required for respiratory competence. We demonstrate that mtFAS is required for mRNA splicing, mitochondrial translation and respiratory complex assembly, and provide evidence that not LA per se, but fatty acids longer than C8 play a role in these processes. We also show that mtFAS- and LA-deficient strains suffer from a mild heme deficiency that may contribute to the respiratory complex assembly defect. Based on our data and previously published information, we propose a model implicating mtFAS as a sensor for mitochondrial acetyl-CoA availability and a coordinator of nuclear and mitochondrial gene expression by adapting the mitochondrial compartment to changes in the metabolic status of the cell. PMID:24102902

Defects in mitochondrial fatty acid synthesis result in failure of multiple aspects of mitochondrial biogenesis in Saccharomyces cerevisiae.

PubMed

Kursu, V A Samuli; Pietikäinen, Laura P; Fontanesi, Flavia; Aaltonen, Mari J; Suomi, Fumi; Raghavan Nair, Remya; Schonauer, Melissa S; Dieckmann, Carol L; Barrientos, Antoni; Hiltunen, J Kalervo; Kastaniotis, Alexander J

2013-11-01

Mitochondrial fatty acid synthesis (mtFAS) shares acetyl-CoA with the Krebs cycle as a common substrate and is required for the production of octanoic acid (C8) precursors of lipoic acid (LA) in mitochondria. MtFAS is a conserved pathway essential for respiration. In a genetic screen in Saccharomyces cerevisiae designed to further elucidate the physiological role of mtFAS, we isolated mutants with defects in mitochondrial post-translational gene expression processes, indicating a novel link to mitochondrial gene expression and respiratory chain biogenesis. In our ensuing analysis, we show that mtFAS, but not lipoylation per se, is required for respiratory competence. We demonstrate that mtFAS is required for mRNA splicing, mitochondrial translation and respiratory complex assembly, and provide evidence that not LA per se, but fatty acids longer than C8 play a role in these processes. We also show that mtFAS- and LA-deficient strains suffer from a mild haem deficiency that may contribute to the respiratory complex assembly defect. Based on our data and previously published information, we propose a model implicating mtFAS as a sensor for mitochondrial acetyl-CoA availability and a co-ordinator of nuclear and mitochondrial gene expression by adapting the mitochondrial compartment to changes in the metabolic status of the cell. © 2013 John Wiley & Sons Ltd.

α7 Nicotinic Acetylcholine Receptor (α7nAChR) Expression in Bone Marrow–Derived Non–T Cells Is Required for the Inflammatory Reflex

PubMed Central

Olofsson, Peder S; Katz, David A; Rosas-Ballina, Mauricio; Levine, Yaakov A; Ochani, Mahendar; Valdés-Ferrer, Sergio I; Pavlov, Valentin A; Tracey, Kevin J; Chavan, Sangeeta S

2012-01-01

The immune response to infection or injury coordinates host defense and tissue repair, but also has the capacity to damage host tissues. Recent advances in understanding protective mechanisms have found neural circuits that suppress release of damaging cytokines. Stimulation of the vagus nerve protects from excessive cytokine production and ameliorates experimental inflammatory disease. This mechanism, the inflammatory reflex, requires the α7 nicotinic acetylcholine receptor (α7nAChR), a ligand-gated ion channel expressed on macrophages, lymphocytes, neurons and other cells. To investigate cell-specific function of α7nAChR in the inflammatory reflex, we created chimeric mice by cross-transferring bone marrow between wild-type (WT) and α7nAChR-deficient mice. Deficiency of α7nAChR in bone marrow–derived cells significantly impaired vagus nerve–mediated regulation of tumor necrosis factor (TNF), whereas α7nAChR deficiency in neurons and other cells had no significant effect. In agreement with recent work, the inflammatory reflex was not functional in nude mice, because functional T cells are required for the integrity of the pathway. To investigate the role of T-cell α7nAChR, we adoptively transferred α7nAChR-deficient or WT T cells to nude mice. Transfer of WT and α7nAChR-deficient T cells restored function, indicating that α7nAChR expression on T cells is not necessary for this pathway. Together, these results indicate that α7nAChR expression in bone marrow–derived non–T cells is required for the integrity of the inflammatory reflex. PMID:22183893

Selective role for RGS12 as a Ras/Raf/MEK scaffold in nerve growth factor-mediated differentiation

PubMed Central

Willard, Melinda D; Willard, Francis S; Li, Xiaoyan; Cappell, Steven D; Snider, William D; Siderovski, David P

2007-01-01

Regulator of G-protein signaling (RGS) proteins accelerate GTP hydrolysis by heterotrimeric G-protein α subunits and thus inhibit signaling by many G protein-coupled receptors. Several RGS proteins have a multidomain architecture that adds further complexity to their roles in cell signaling in addition to their GTPase-accelerating activity. RGS12 contains a tandem repeat of Ras-binding domains but, to date, the role of this protein in Ras-mediated signal transduction has not been reported. Here, we show that RGS12 associates with the nerve growth factor (NGF) receptor tyrosine kinase TrkA, activated H-Ras, B-Raf, and MEK2 and facilitates their coordinated signaling to prolonged ERK activation. RGS12 is required for NGF-mediated neurite outgrowth of PC12 cells, but not outgrowth stimulated by basic fibroblast growth factor. siRNA-mediated knockdown of RGS12 expression also inhibits NGF-induced axonal growth in dissociated cultures of primary dorsal root ganglia neurons. These data suggest that RGS12 may play a critical, and receptor-selective, role in coordinating Ras-dependent signals that are required for promoting and/or maintaining neuronal differentiation. PMID:17380122

RhoA GTPase inhibition organizes contraction during epithelial morphogenesis

PubMed Central

Mason, Frank M.; Xie, Shicong; Vasquez, Claudia G.; Tworoger, Michael

2016-01-01

During morphogenesis, contraction of the actomyosin cytoskeleton within individual cells drives cell shape changes that fold tissues. Coordination of cytoskeletal contractility is mediated by regulating RhoA GTPase activity. Guanine nucleotide exchange factors (GEFs) activate and GTPase-activating proteins (GAPs) inhibit RhoA activity. Most studies of tissue folding, including apical constriction, have focused on how RhoA is activated by GEFs to promote cell contractility, with little investigation as to how GAPs may be important. Here, we identify a critical role for a RhoA GAP, Cumberland GAP (C-GAP), which coordinates with a RhoA GEF, RhoGEF2, to organize spatiotemporal contractility during Drosophila melanogaster apical constriction. C-GAP spatially restricts RhoA pathway activity to a central position in the apical cortex. RhoGEF2 pulses precede myosin, and C-GAP is required for pulsation, suggesting that contractile pulses result from RhoA activity cycling. Finally, C-GAP expression level influences the transition from reversible to irreversible cell shape change, which defines the onset of tissue shape change. Our data demonstrate that RhoA activity cycling and modulating the ratio of RhoGEF2 to C-GAP are required for tissue folding. PMID:27551058

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.

Anaerobic Cysteine Degradation and Potential Metabolic Coordination in Salmonella enterica and Escherichia coli

PubMed Central

Loddeke, Melissa; Schneider, Barbara; Oguri, Tamiko; Mehta, Iti; Xuan, Zhenyu

2017-01-01

ABSTRACT Salmonella enterica has two CyuR-activated enzymes that degrade cysteine, i.e., the aerobic CdsH and an unidentified anaerobic enzyme; Escherichia coli has only the latter. To identify the anaerobic enzyme, transcript profiling was performed for E. coli without cyuR and with overexpressed cyuR. Thirty-seven genes showed at least 5-fold changes in expression, and the cyuPA (formerly yhaOM) operon showed the greatest difference. Homology suggested that CyuP and CyuA represent a cysteine transporter and an iron-sulfur-containing cysteine desulfidase, respectively. E. coli and S. enterica ΔcyuA mutants grown with cysteine generated substantially less sulfide and had lower growth yields. Oxygen affected the CyuR-dependent genes reciprocally; cyuP-lacZ expression was greater anaerobically, whereas cdsH-lacZ expression was greater aerobically. In E. coli and S. enterica, anaerobic cyuP expression required cyuR and cysteine and was induced by l-cysteine, d-cysteine, and a few sulfur-containing compounds. Loss of either CyuA or RidA, both of which contribute to cysteine degradation to pyruvate, increased cyuP-lacZ expression, which suggests that CyuA modulates intracellular cysteine concentrations. Phylogenetic analysis showed that CyuA homologs are present in obligate and facultative anaerobes, confirming an anaerobic function, and in archaeal methanogens and bacterial acetogens, suggesting an ancient origin. Our results show that CyuA is the major anaerobic cysteine-catabolizing enzyme in both E. coli and S. enterica, and it is proposed that anaerobic cysteine catabolism can contribute to coordination of sulfur assimilation and amino acid synthesis. IMPORTANCE Sulfur-containing compounds such as cysteine and sulfide are essential and reactive metabolites. Exogenous sulfur-containing compounds can alter the thiol landscape and intracellular redox reactions and are known to affect several cellular processes, including swarming motility, antibiotic sensitivity, and biofilm formation. Cysteine inhibits several enzymes of amino acid synthesis; therefore, increasing cysteine concentrations could increase the levels of the inhibited enzymes. This inhibition implies that control of intracellular cysteine levels, which is the immediate product of sulfide assimilation, can affect several pathways and coordinate metabolism. For these and other reasons, cysteine and sulfide concentrations must be controlled, and this work shows that cysteine catabolism contributes to this control. PMID:28607157

The quantum chemical causality of pMHC-TCR biological avidity: Peptide atomic coordination data and the electronic state of agonist N termini.

PubMed

Antipas, Georgios S E; Germenis, Anastasios E

2015-06-01

The quantum state of functional avidity of the synapse formed between a peptide-Major Histocompatibility Complex (pMHC) and a T cell receptor (TCR) is a subject not previously touched upon. Here we present atomic pair correlation meta-data based on crystalized tertiary structures of the Tax (HTLV-1) peptide along with three artificially altered variants, all of which were presented by the (Class I) HLA-A201 protein in complexation with the human (CD8(+)) A6TCR. The meta-data reveal the existence of a direct relationship between pMHC-TCR functional avidity (agonist/antagonist) and peptide pair distribution function (PDF). In this context, antagonist peptides are consistently under-coordinated in respect to Tax. Moreover, Density Functional Theory (DFT) datasets in the BLYP/TZ2P level of theory resulting from relaxation of the H species on peptide tertiary structures reveal that the coordination requirement of agonist peptides is also expressed as a physical observable of the protonation state of their N termini: agonistic peptides are always found to retain a stable ammonium (NH3 (+)) terminal group while antagonist peptides are not.

Convergent microRNA actions coordinate neocortical development.

PubMed

Barca-Mayo, Olga; De Pietri Tonelli, Davide

2014-08-01

Neocortical development is a complex process that, at the cellular level, involves tight control of self-renewal, cell fate commitment, survival, differentiation and delamination/migration. These processes require, at the molecular level, the precise regulation of intrinsic signaling pathways and extrinsic factors with coordinated action in a spatially and temporally specific manner. Transcriptional regulation plays an important role during corticogenesis; however, microRNAs (miRNAs) are emerging as important post-transcriptional regulators of various aspects of central nervous system development. miRNAs are a class of small, single-stranded noncoding RNA molecules that control the expression of the majority of protein coding genes (i.e., targets). How do different miRNAs achieve precise control of gene networks during neocortical development? Here, we critically review all the miRNA-target interactions validated in vivo, with relevance to the generation and migration of pyramidal-projection glutamatergic neurons, and for the initial formation of cortical layers in the embryonic development of rodent neocortex. In particular, we focus on convergent miRNA actions, which are still a poorly understood layer of complexity in miRNA signaling, but potentially one of the keys to disclosing how miRNAs achieve the precise coordination of complex biological processes such as neocortical development.

Generalization of the Activated Complex Theory of Reaction Rates. I. Quantum Mechanical Treatment

DOE R&D Accomplishments Database

Marcus, R. A.

1964-01-01

In its usual form activated complex theory assumes a quasi-equilibrium between reactants and activated complex, a separable reaction coordinate, a Cartesian reaction coordinate, and an absence of interaction of rotation with internal motion in the complex. In the present paper a rate expression is derived without introducing the Cartesian assumption. The expression bears a formal resemblance to the usual one and reduces to it when the added assumptions of the latter are introduced.

Natural transformation occurs independently of the essential actin-like MreB cytoskeleton in Legionella pneumophila

PubMed Central

Juan, Pierre-Alexandre; Attaiech, Laetitia; Charpentier, Xavier

2015-01-01

Natural transformation is the process by which bacteria can actively take up and integrate exogenous DNA thereby providing a source of genetic diversity. Under specific growth conditions the coordinated expression of several genes – a situation referred to as “competence” – allows bacteria to assemble a highly processive and dedicated system that can import high molecular weight DNA. Within the cell these large imported DNA molecules are protected from degradation and brought to the chromosome for recombination. Here, we report elevated expression of mreB during competence in the Gram-negative pathogen Legionella pneumophila. Interestingly a similar observation had previously been reported in the distantly-related Gram-positive organism Bacillus subtilis. MreB is often viewed as the bacterial actin homolog contributing to bacterial morphogenesis by coordinating peptidoglycan-synthesising complexes. In addition MreB is increasingly found to be involved in a growing number of processes including chromosome segregation and motor-driven motility. Using genetic and pharmacological approaches, we examined the possible role of MreB during natural transformation in L. pneumophila. Our data show that natural transformation does not require MreB dynamics and exclude a direct role of MreB filaments in the transport of foreign DNA and its recombination in the chromosome. PMID:26526572

Natural transformation occurs independently of the essential actin-like MreB cytoskeleton in Legionella pneumophila.

PubMed

Juan, Pierre-Alexandre; Attaiech, Laetitia; Charpentier, Xavier

2015-11-03

Natural transformation is the process by which bacteria can actively take up and integrate exogenous DNA thereby providing a source of genetic diversity. Under specific growth conditions the coordinated expression of several genes--a situation referred to as "competence"--allows bacteria to assemble a highly processive and dedicated system that can import high molecular weight DNA. Within the cell these large imported DNA molecules are protected from degradation and brought to the chromosome for recombination. Here, we report elevated expression of mreB during competence in the Gram-negative pathogen Legionella pneumophila. Interestingly a similar observation had previously been reported in the distantly-related Gram-positive organism Bacillus subtilis. MreB is often viewed as the bacterial actin homolog contributing to bacterial morphogenesis by coordinating peptidoglycan-synthesising complexes. In addition MreB is increasingly found to be involved in a growing number of processes including chromosome segregation and motor-driven motility. Using genetic and pharmacological approaches, we examined the possible role of MreB during natural transformation in L. pneumophila. Our data show that natural transformation does not require MreB dynamics and exclude a direct role of MreB filaments in the transport of foreign DNA and its recombination in the chromosome.

Local requirement of the Drosophila insulin binding protein imp-L2 in coordinating developmental progression with nutritional conditions.

PubMed

Sarraf-Zadeh, Ladan; Christen, Stefan; Sauer, Uwe; Cognigni, Paola; Miguel-Aliaga, Irene; Stocker, Hugo; Köhler, Katja; Hafen, Ernst

2013-09-01

In Drosophila, growth takes place during the larval stages until the formation of the pupa. Starvation delays pupariation to allow prolonged feeding, ensuring that the animal reaches an appropriate size to form a fertile adult. Pupariation is induced by a peak of the steroid hormone ecdysone produced by the prothoracic gland (PG) after larvae have reached a certain body mass. Local downregulation of the insulin/insulin-like growth factor signaling (IIS) activity in the PG interferes with ecdysone production, indicating that IIS activity in the PG couples the nutritional state to development. However, the underlying mechanism is not well understood. In this study we show that the secreted Imaginal morphogenesis protein-Late 2 (Imp-L2), a growth inhibitor in Drosophila, is involved in this process. Imp-L2 inhibits the activity of the Drosophila insulin-like peptides by direct binding and is expressed by specific cells in the brain, the ring gland, the gut and the fat body. We demonstrate that Imp-L2 is required to regulate and adapt developmental timing to nutritional conditions by regulating IIS activity in the PG. Increasing Imp-L2 expression at its endogenous sites using an Imp-L2-Gal4 driver delays pupariation, while Imp-L2 mutants exhibit a slight acceleration of development. These effects are strongly enhanced by starvation and are accompanied by massive alterations of ecdysone production resulting most likely from increased Imp-L2 production by neurons directly contacting the PG and not from elevated Imp-L2 levels in the hemolymph. Taken together our results suggest that Imp-L2-expressing neurons sense the nutritional state of Drosophila larvae and coordinate dietary information and ecdysone production to adjust developmental timing under starvation conditions. Copyright © 2013 Elsevier Inc. All rights reserved.

NDH expression marks major transitions in plant evolution and reveals coordinate intracellular gene loss.

PubMed

Ruhlman, Tracey A; Chang, Wan-Jung; Chen, Jeremy J W; Huang, Yao-Ting; Chan, Ming-Tsair; Zhang, Jin; Liao, De-Chih; Blazier, John C; Jin, Xiaohua; Shih, Ming-Che; Jansen, Robert K; Lin, Choun-Sea

2015-04-11

Key innovations have facilitated novel niche utilization, such as the movement of the algal predecessors of land plants into terrestrial habitats where drastic fluctuations in light intensity, ultraviolet radiation and water limitation required a number of adaptations. The NDH (NADH dehydrogenase-like) complex of Viridiplantae plastids participates in adapting the photosynthetic response to environmental stress, suggesting its involvement in the transition to terrestrial habitats. Although relatively rare, the loss or pseudogenization of plastid NDH genes is widely distributed across diverse lineages of photoautotrophic seed plants and mutants/transgenics lacking NDH function demonstrate little difference from wild type under non-stressed conditions. This study analyzes large transcriptomic and genomic datasets to evaluate the persistence and loss of NDH expression across plants. Nuclear expression profiles showed accretion of the NDH gene complement at key transitions in land plant evolution, such as the transition to land and at the base of the angiosperm lineage. While detection of transcripts for a selection of non-NDH, photosynthesis related proteins was independent of the state of NDH, coordinate, lineage-specific loss of plastid NDH genes and expression of nuclear-encoded NDH subunits was documented in Pinaceae, gnetophytes, Orchidaceae and Geraniales confirming the independent and complete loss of NDH in these diverse seed plant taxa. The broad phylogenetic distribution of NDH loss and the subtle phenotypes of mutants suggest that the NDH complex is of limited biological significance in contemporary plants. While NDH activity appears dispensable under favorable conditions, there were likely sufficiently frequent episodes of abiotic stress affecting terrestrial habitats to allow the retention of NDH activity. These findings reveal genetic factors influencing plant/environment interactions in a changing climate through 450 million years of land plant evolution.

Plastid RNA polymerases: orchestration of enzymes with different evolutionary origins controls chloroplast biogenesis during the plant life cycle.

PubMed

Pfannschmidt, Thomas; Blanvillain, Robert; Merendino, Livia; Courtois, Florence; Chevalier, Fabien; Liebers, Monique; Grübler, Björn; Hommel, Elisabeth; Lerbs-Mache, Silva

2015-12-01

Chloroplasts are the sunlight-collecting organelles of photosynthetic eukaryotes that energetically drive the biosphere of our planet. They are the base for all major food webs by providing essential photosynthates to all heterotrophic organisms including humans. Recent research has focused largely on an understanding of the function of these organelles, but knowledge about the biogenesis of chloroplasts is rather limited. It is known that chloroplasts develop from undifferentiated precursor plastids, the proplastids, in meristematic cells. This review focuses on the activation and action of plastid RNA polymerases, which play a key role in the development of new chloroplasts from proplastids. Evolutionarily, plastids emerged from the endosymbiosis of a cyanobacterium-like ancestor into a heterotrophic eukaryote. As an evolutionary remnant of this process, they possess their own genome, which is expressed by two types of plastid RNA polymerase, phage-type and prokaryotic-type RNA polymerase. The protein subunits of these polymerases are encoded in both the nuclear and plastid genomes. Their activation and action therefore require a highly sophisticated regulation that controls and coordinates the expression of the components encoded in the plastid and nucleus. Stoichiometric expression and correct assembly of RNA polymerase complexes is achieved by a combination of developmental and environmentally induced programmes. This review highlights the current knowledge about the functional coordination between the different types of plastid RNA polymerases and provides working models of their sequential expression and function for future investigations. © 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.

Dendritic cell expression of the signaling molecule TRAF6 is required for immune tolerance in the lung

PubMed Central

Han, Daehee; Walsh, Matthew C; Kim, Kwang Soon; Hong, Sung-Wook; Lee, Junyoung; Yi, Jaeu; Rivas, Gloriany; Choi, Yongwon; Surh, Charles D

2017-01-01

Abstract Immune tolerance in the lung is important for preventing hypersensitivity, such as allergic asthma. Maintenance of tolerance in the lung is established by coordinated activities of poorly understood cellular and molecular mechanisms, including participation of dendritic cells (DCs). We have previously identified DC expression of the signaling molecule TRAF6 as a non-redundant requirement for the maintenance of immune tolerance in the small intestine of mice. Because mucosal tissues share similarities in how they interact with exogenous antigens, we examined the role of DC-expressed TRAF6 in the lung. As with the intestine, we found that the absence TRAF6 expression by DCs led to spontaneous generation of Th2-associated immune responses and increased susceptibility to model antigen-induced asthma. To examine the role of commensal microbiota, mice deficient in TRAF6 in DCs were treated with broad-spectrum antibiotics and/or re-derived on a germ-free (GF) background. Interestingly, we found that antibiotics-treated specific pathogen-free, but not GF, mice showed restored immune tolerance in the absence of DC-expressed TRAF6. We further found that antibiotics mediate microbiota-independent effects on lung T cells to promote immune tolerance in the lung. This work provides both a novel tool for studying immune tolerance in the lung and an advance in our conceptual understanding of potentially common molecular mechanisms of immune tolerance in both the intestine and the lung. PMID:28338920

HIF-1α coordinates lymphangiogenesis during wound healing and in response to inflammation

PubMed Central

Zampell, Jamie C.; Yan, Alan; Avraham, Tomer; Daluvoy, Sanjay; Weitman, Evan S.; Mehrara, Babak J.

2012-01-01

This study aimed to investigate the mechanisms that coordinate lymphangiogenesis. Using mouse models of lymphatic regeneration and inflammatory lymphangiogenesis, we explored the hypothesis that hypoxia inducible factor-α (HIF-1α) is a central regulator of lymphangiogenesis. We show that HIF-1α inhibition by small molecule inhibitors (YC-1 and 2-methyoxyestradiol) results in delayed lymphatic repair, decreased local vascular endothelial growth factor-C (VEGF-C) expression, reduced numbers of VEGF-C+ cells, and reductions in inflammatory lymphangiogenesis. Using transgenic HIF-1α/luciferase mice to image HIF-1α expression in real time in addition to Western blot analysis and pimonidazole staining for cellular hypoxia, we demonstrate that hypoxia stabilizes HIF-1α during initial stages of wound repair (1–2 wk); whereas inflammation secondary to gradients of lymphatic fluid stasis stabilizes HIF-1α thereafter (3–6 wk). In addition, we show that CD4+ cell-mediated inflammation is necessary for this response and regulates HIF-1α expression by macrophages, as CD4-deficient or CD4-depleted mice demonstrate 2-fold reductions in HIF-1α expression as compared to wild-types. In summary, we show that HIF-1α is a critical coordinator of lymphangiogenesis by regulating the expression of lymphangiogenic cytokines as part of an early response mechanism to hypoxia, inflammation, and lymphatic fluid stasis.—Zampell, J. C., Yan, A., Avraham, T., Daluvoy, S., Weitman, E. S., Mehrara, B. J. HIF-1α coordinates lymphangiogenesis during wound healing and in response to inflammation. PMID:22067482

The PHD Finger Protein MMD1/DUET Ensures the Progression of Male Meiotic Chromosome Condensation and Directly Regulates the Expression of the Condensin Gene CAP-D3.

PubMed

Wang, Jun; Niu, Baixiao; Huang, Jiyue; Wang, Hongkuan; Yang, Xiaohui; Dong, Aiwu; Makaroff, Christopher; Ma, Hong; Wang, Yingxiang

2016-08-01

Chromosome condensation, a process mediated by the condensin complex, is essential for proper chromosome segregation during cell division. Unlike rapid mitotic chromosome condensation, meiotic chromosome condensation occurs over a relatively long prophase I and is unusually complex due to the coordination with chromosome axis formation and homolog interaction. The molecular mechanisms that regulate meiotic chromosome condensation progression from prophase I to metaphase I are unclear. Here, we show that the Arabidopsis thaliana meiotic PHD-finger protein MMD1/DUET is required for progressive compaction of prophase I chromosomes to metaphase I bivalents. The MMD1 PHD domain is required for its function in chromosome condensation and binds to methylated histone tails. Transcriptome analysis and qRT-PCR showed that several condensin genes exhibit significantly reduced expression in mmd1 meiocytes. Furthermore, MMD1 specifically binds to the promoter region of the condensin subunit gene CAP-D3 to enhance its expression. Moreover, cap-d3 mutants exhibit similar chromosome condensation defects, revealing an MMD1-dependent mechanism for regulating meiotic chromosome condensation, which functions in part by promoting condensin gene expression. Together, these discoveries provide strong evidence that the histone reader MMD1/DUET defines an important step for regulating the progression of meiotic prophase I chromosome condensation. © 2016 American Society of Plant Biologists. All rights reserved.

The PHD Finger Protein MMD1/DUET Ensures the Progression of Male Meiotic Chromosome Condensation and Directly Regulates the Expression of the Condensin Gene CAP-D3[OPEN

PubMed Central

Wang, Jun; Niu, Baixiao; Huang, Jiyue; Wang, Hongkuan; Yang, Xiaohui; Dong, Aiwu

2016-01-01

Chromosome condensation, a process mediated by the condensin complex, is essential for proper chromosome segregation during cell division. Unlike rapid mitotic chromosome condensation, meiotic chromosome condensation occurs over a relatively long prophase I and is unusually complex due to the coordination with chromosome axis formation and homolog interaction. The molecular mechanisms that regulate meiotic chromosome condensation progression from prophase I to metaphase I are unclear. Here, we show that the Arabidopsis thaliana meiotic PHD-finger protein MMD1/DUET is required for progressive compaction of prophase I chromosomes to metaphase I bivalents. The MMD1 PHD domain is required for its function in chromosome condensation and binds to methylated histone tails. Transcriptome analysis and qRT-PCR showed that several condensin genes exhibit significantly reduced expression in mmd1 meiocytes. Furthermore, MMD1 specifically binds to the promoter region of the condensin subunit gene CAP-D3 to enhance its expression. Moreover, cap-d3 mutants exhibit similar chromosome condensation defects, revealing an MMD1-dependent mechanism for regulating meiotic chromosome condensation, which functions in part by promoting condensin gene expression. Together, these discoveries provide strong evidence that the histone reader MMD1/DUET defines an important step for regulating the progression of meiotic prophase I chromosome condensation. PMID:27385818

The mRNA cap-binding protein Cbc1 is required for high and timely expression of genes by promoting the accumulation of gene-specific activators at promoters.

PubMed

Li, Tianlu; De Clercq, Nikki; Medina, Daniel A; Garre, Elena; Sunnerhagen, Per; Pérez-Ortín, José E; Alepuz, Paula

2016-02-01

The highly conserved Saccharomyces cerevisiae cap-binding protein Cbc1/Sto1 binds mRNA co-transcriptionally and acts as a key coordinator of mRNA fate. Recently, Cbc1 has also been implicated in transcription elongation and pre-initiation complex (PIC) formation. Previously, we described Cbc1 to be required for cell growth under osmotic stress and to mediate osmostress-induced translation reprogramming. Here, we observe delayed global transcription kinetics in cbc1Δ during osmotic stress that correlates with delayed recruitment of TBP and RNA polymerase II to osmo-induced promoters. Interestingly, we detect an interaction between Cbc1 and the MAPK Hog1, which controls most gene expression changes during osmostress, and observe that deletion of CBC1 delays the accumulation of the activator complex Hot1-Hog1 at osmostress promoters. Additionally, CBC1 deletion specifically reduces transcription rates of highly transcribed genes under non-stress conditions, such as ribosomal protein (RP) genes, while having low impact on transcription of weakly expressed genes. For RP genes, we show that recruitment of the specific activator Rap1, and subsequently TBP, to promoters is Cbc1-dependent. Altogether, our results indicate that binding of Cbc1 to the capped mRNAs is necessary for the accumulation of specific activators as well as PIC components at the promoters of genes whose expression requires high and rapid transcription. Copyright © 2016 Elsevier B.V. All rights reserved.

Co-ordinated stage-dependent enhancement of Plasmodium falciparum antioxidant enzymes and heat shock protein expression in parasites growing in oxidatively stressed or G6PD-deficient red blood cells.

PubMed

Akide-Ndunge, Oscar Bate; Tambini, Elisa; Giribaldi, Giuliana; McMillan, Paul J; Müller, Sylke; Arese, Paolo; Turrini, Francesco

2009-05-29

Plasmodium falciparum-parasitized red blood cells (RBCs) are equipped with protective antioxidant enzymes and heat shock proteins (HSPs). The latter are only considered to protect against thermal stress. Important issues are poorly explored: first, it is insufficiently known how both systems are expressed in relation to the parasite developmental stage; secondly, it is unknown whether P. falciparum HSPs are redox-responsive, in view of redox sensitivity of HSP in eukaryotic cells; thirdly, it is poorly known how the antioxidant defense machinery would respond to increased oxidative stress or inhibited antioxidant defense. Those issues are interesting as several antimalarials increase the oxidative stress or block antioxidant defense in the parasitized RBC. In addition, numerous inhibitors of HSPs are currently developed for cancer therapy and might be tested as anti-malarials. Thus, the joint disruption of the parasite antioxidant enzymes/HSP system would interfere with parasite growth and open new perspectives for anti-malaria therapy. Stage-dependent mRNA expression of ten representative P. falciparum antioxidant enzymes and hsp60/70-2/70-3/75/90 was studied by quantitative real-time RT-PCR in parasites growing in normal RBCs, in RBCs oxidatively-stressed by moderate H2O2 generation and in G6PD-deficient RBCs. Protein expression of antioxidant enzymes was assayed by Western blotting. The pentosephosphate-pathway flux was measured in isolated parasites after Sendai-virus lysis of RBC membrane. In parasites growing in normal RBCs, mRNA expression of antioxidant enzymes and HSPs displayed co-ordinated stage-dependent modulation, being low at ring, highest at early trophozoite and again very low at schizont stage. Additional exogenous oxidative stress or growth in antioxidant blunted G6PD-deficient RBCs indicated remarkable flexibility of both systems, manifested by enhanced, co-ordinated mRNA expression of antioxidant enzymes and HSPs. Protein expression of antioxidant enzymes was also increased in oxidatively-stressed trophozoites. Results indicated that mRNA expression of parasite antioxidant enzymes and HSPs was co-ordinated and stage-dependent. Secondly, both systems were redox-responsive and showed remarkably increased and co-ordinated expression in oxidatively-stressed parasites and in parasites growing in antioxidant blunted G6PD-deficient RBCs. Lastly, as important anti-malarials either increase oxidant stress or impair antioxidant defense, results may encourage the inclusion of anti-HSP molecules in anti-malarial combined drugs.

Wounding coordinately induces cell wall protein, cell cycle and pectin methyl esterase genes involved in tuber closing layer and wound periderm development.

PubMed

Neubauer, Jonathan D; Lulai, Edward C; Thompson, Asunta L; Suttle, Jeffrey C; Bolton, Melvin D

2012-04-15

Little is known about the coordinate induction of genes that may be involved in agriculturally important wound-healing events. In this study, wound-healing events were determined together with wound-induced expression profiles of selected cell cycle, cell wall protein, and pectin methyl esterase genes using two diverse potato genotypes and two harvests (NDTX4271-5R and Russet Burbank tubers; 2008 and 2009 harvests). By 5 d after wounding, the closing layer and a nascent phellogen had formed. Phellogen cell divisions generated phellem layers until cessation of cell division at 28 d after wounding for both genotypes and harvests. Cell cycle genes encoding epidermal growth factor binding protein (StEBP), cyclin-dependent kinase B (StCDKB) and cyclin-dependent kinase regulatory subunit (StCKS1At) were induced by 1 d after wounding; these expressions coordinated with related phellogen formation and the induction and cessation of phellem cell formation. Genes encoding the structural cell wall proteins extensin (StExt1) and extensin-like (StExtlk) were dramatically up-regulated by 1-5 d after wounding, suggesting involvement with closing layer and later phellem cell layer formation. Wounding up-regulated pectin methyl esterase genes (StPME and StPrePME); StPME expression increased during closing layer and phellem cell formation, whereas maximum expression of StPrePME occurred at 5-14 d after wounding, implicating involvement in later modifications for closing layer and phellem cell formation. The coordinate induction and expression profile of StTLRP, a gene encoding a cell wall strengthening "tyrosine-and lysine-rich protein," suggested a role in the formation of the closing layer followed by phellem cell generation and maturation. Collectively, the genes monitored were wound-inducible and their expression profiles markedly coordinated with closing layer formation and the index for phellogen layer meristematic activity during wound periderm development; results were more influenced by harvest than genotype. Importantly, StTLRP was the only gene examined that may be involved in phellogen cell wall thickening after cessation of phellogen cell division. Published by Elsevier GmbH.

Weakener of White (Wow), a Gene That Modifies the Expression of the White Eye Color Locus and That Suppresses Position Effect Variegation in Drosophila Melanogaster

PubMed Central

Birchler, J. A.; Bhadra, U.; Rabinow, L.; Linsk, R.; Nguyen-Huynh, A. T.

1994-01-01

A locus is described in Drosophila melanogaster that modifies the expression of the white eye color gene. This trans-acting modifier reduces the expression of the white gene in the eye, but elevates the expression in other adult tissues. Because of the eye phenotype in which the expression of white is lessened but not eliminated, the newly described locus is called the Weakener of white (Wow). Northern analysis reveals that Wow can exert an inverse or direct modifying effect depending upon the developmental stage. Two related genes, brown and scarlet, that are coordinately expressed with white, are also affected by Wow. In addition, Wow modulates the steady state RNA level of the retrotransposon, copia. When tested with a white promoter-Alcohol dehydrogenase reporter, Wow confers the modifying effect to the reporter, suggesting a requirement of the white regulatory sequences for mediating the response. In addition to being a dosage sensitive regulator of white, brown, scarlet and copia, Wow acts as a suppressor of position effect variegation. There are many dosage sensitive suppressors of position effect variegation and many dosage-sensitive modifiers of gene expression. The Wow mutations provide evidence for an overlap between the two types of modifiers. PMID:7982560

Modulation of yeast genome expression in response to defective RNA polymerase III-dependent transcription.

PubMed

Conesa, Christine; Ruotolo, Roberta; Soularue, Pascal; Simms, Tiffany A; Donze, David; Sentenac, André; Dieci, Giorgio

2005-10-01

We used genome-wide expression analysis in Saccharomyces cerevisiae to explore whether and how the expression of protein-coding, RNA polymerase (Pol) II-transcribed genes is influenced by a decrease in RNA Pol III-dependent transcription. The Pol II transcriptome was characterized in four thermosensitive, slow-growth mutants affected in different components of the RNA Pol III transcription machinery. Unexpectedly, we found only a modest correlation between altered expression of Pol II-transcribed genes and their proximity to class III genes, a result also confirmed by the analysis of single tRNA gene deletants. Instead, the transcriptome of all of the four mutants was characterized by increased expression of genes known to be under the control of the Gcn4p transcriptional activator. Indeed, GCN4 was found to be translationally induced in the mutants, and deleting the GCN4 gene eliminated the response. The Gcn4p-dependent expression changes did not require the Gcn2 protein kinase and could be specifically counteracted by an increased gene dosage of initiator tRNA(Met). Initiator tRNA(Met) depletion thus triggers a GCN4-dependent reprogramming of genome expression in response to decreased Pol III transcription. Such an effect might represent a key element in the coordinated transcriptional response of yeast cells to environmental changes.

The research of statistical properties of colorimetric features of screens with a three-component color formation principle

NASA Astrophysics Data System (ADS)

Zharinov, I. O.; Zharinov, O. O.

2017-12-01

The problem of the research is concerned with quantitative analysis of influence of technological variation of the screen color profile parameters on chromaticity coordinates of the displayed image. Some mathematical expressions which approximate the two-dimensional distribution of chromaticity coordinates of an image, which is displayed on the screen with a three-component color formation principle were proposed. Proposed mathematical expressions show the way to development of correction techniques to improve reproducibility of the colorimetric features of displays.

Establishing bacterial communities by 'word of mouth': LuxS and autoinducer 2 in biofilm development.

PubMed

Hardie, Kim Rachael; Heurlier, Karin

2008-08-01

Multicellular bacterial communities (biofilms) abound in nature, and their successful formation and survival is likely to require cell-cell communication--including quorum sensing--to co-ordinate appropriate gene expression. The only mode of quorum sensing that is shared by both Gram-positive and Gram-negative bacteria involves the production of the signalling molecule autoinducer 2 by LuxS. A survey of the current literature reveals that luxS contributes to biofilm development in some bacteria. However, inconsistencies prevent biofilm development being attributed to the production of AI2 in all cases.

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

Machine Learning-Assisted Network Inference Approach to Identify a New Class of Genes that Coordinate the Functionality of Cancer Networks.

PubMed

Ghanat Bari, Mehrab; Ung, Choong Yong; Zhang, Cheng; Zhu, Shizhen; Li, Hu

2017-08-01

Emerging evidence indicates the existence of a new class of cancer genes that act as "signal linkers" coordinating oncogenic signals between mutated and differentially expressed genes. While frequently mutated oncogenes and differentially expressed genes, which we term Class I cancer genes, are readily detected by most analytical tools, the new class of cancer-related genes, i.e., Class II, escape detection because they are neither mutated nor differentially expressed. Given this hypothesis, we developed a Machine Learning-Assisted Network Inference (MALANI) algorithm, which assesses all genes regardless of expression or mutational status in the context of cancer etiology. We used 8807 expression arrays, corresponding to 9 cancer types, to build more than 2 × 10 8 Support Vector Machine (SVM) models for reconstructing a cancer network. We found that ~3% of ~19,000 not differentially expressed genes are Class II cancer gene candidates. Some Class II genes that we found, such as SLC19A1 and ATAD3B, have been recently reported to associate with cancer outcomes. To our knowledge, this is the first study that utilizes both machine learning and network biology approaches to uncover Class II cancer genes in coordinating functionality in cancer networks and will illuminate our understanding of how genes are modulated in a tissue-specific network contribute to tumorigenesis and therapy development.

Loss and Rebirth of the Animal Microtubule Organizing Center: How Maternal Expression of Centrosomal Proteins Cooperates with the Sperm Centriole in Zygotic Centrosome Reformation.

PubMed

Inoue, Daigo; Wittbrodt, Joachim; Gruss, Oliver J

2018-04-01

Centrosomes are the main microtubule organizing centers in animal cells. In particular during embryogenesis, they ensure faithful spindle formation and proper cell divisions. As metazoan centrosomes are eliminated during oogenesis, they have to be reassembled upon fertilization. Most metazoans use the sperm centrioles as templates for new centrosome biogenesis while the egg's cytoplasm re-prepares all components for on-going centrosome duplication in rapidly dividing embryonic cells. We discuss our knowledge and the experimental challenges to analyze zygotic centrosome reformation, which requires genetic experiments to enable scrutinizing respective male and female contributions. Male and female knockout animals and mRNA injection to mimic maternal expression of centrosomal proteins could point a way to the systematic molecular dissection of the process. The most recent data suggest that timely expression of centrosome components in oocytes is the key to zygotic centrosome reformation that uses male sperm as coordinators for de novo centrosome production. © 2018 WILEY Periodicals, Inc.

Metabolic reprogramming during TGFβ1-induced epithelial-to-mesenchymal transition

PubMed Central

Jiang, Lei; Xiao, Ling; Sugiura, Hidekazu; Huang, Xiumei; Ali, Aktar; Kuro-o, Makoto; Deberardinis, Ralph J.; Boothman, David A.

2014-01-01

Metastatic progression, including extravasation and micro-metastatic outgrowth, is the main cause of cancer patient death. Recent studies suggest that cancer cells reprogram their metabolism to support increased proliferation through increased glycolysis and biosynthetic activities, including lipogenesis pathways. However, metabolic changes during metastatic progression, including alterations in regulatory gene expression, remain undefined. We show that transforming growth factor beta 1 (TGFβ1) induced Epithelial-to-Mesenchymal Transition (EMT) is accompanied by coordinately reduced enzyme expression required to convert glucose into fatty acids, and concomitant enhanced respiration. Over-expressed Snail1, a transcription factor mediating TGFβ1-induced EMT, was sufficient to suppress carbohydrate-responsive-element-binding protein (ChREBP, a master lipogenic regulator), and fatty acid synthase (FASN), its effector lipogenic gene. Stable FASN knock-down was sufficient to induce EMT, stimulate migration and extravasation in vitro. FASN silencing enhanced lung metastasis and death in vivo. These data suggest that a metabolic transition that suppresses lipogenesis and favors energy production is an essential component of TGFβ1-induced EMT and metastasis. PMID:25284588

Daily rhythms in antennal protein and olfactory sensitivity in the malaria mosquito Anopheles gambiae

PubMed Central

Rund, Samuel S. C.; Bonar, Nicolle A.; Champion, Matthew M.; Ghazi, John P.; Houk, Cameron M.; Leming, Matthew T.; Syed, Zainulabeuddin; Duffield, Giles E.

2013-01-01

We recently characterized 24-hr daily rhythmic patterns of gene expression in Anopheles gambiae mosquitoes. These include numerous odorant binding proteins (OBPs), soluble odorant carrying proteins enriched in olfactory organs. Here we demonstrate that multiple rhythmically expressed genes including OBPs and takeout proteins, involved in regulating blood feeding behavior, have corresponding rhythmic protein levels as measured by quantitative proteomics. This includes AgamOBP1, previously shown as important to An. gambiae odorant sensing. Further, electrophysiological investigations demonstrate time-of-day specific differences in olfactory sensitivity of antennae to major host-derived odorants. The pre-dusk/dusk peaks in OBPs and takeout gene expression correspond with peak protein abundance at night, and in turn coincide with the time of increased olfactory sensitivity to odorants requiring OBPs and times of increased blood-feeding behavior. This suggests an important role for OBPs in modulating temporal changes in odorant sensitivity, enabling the olfactory system to coordinate with the circadian niche of An. gambiae. PMID:23986098

Emerin and histone deacetylase 3 (HDAC3) cooperatively regulate expression and nuclear positions of MyoD, Myf5, and Pax7 genes during myogenesis

PubMed Central

Demmerle, Justin; Koch, Adam J.; Holaska, James M.

2016-01-01

The spatial organization of chromatin is critical in establishing cell-type dependent gene expression programs. The inner nuclear membrane protein emerin has been implicated in regulating global chromatin architecture. We show emerin associates with genomic loci of muscle differentiation promoting factors in murine myogenic progenitors, including Myf5 and MyoD. Prior to their transcriptional activation Myf5 and MyoD loci localized to the nuclear lamina in proliferating progenitors and moved to the nucleoplasm upon transcriptional activation during differentiation. The Pax7 locus, which is transcribed in proliferating progenitors, localized to the nucleoplasm and Pax7 moved to the nuclear lamina upon repression during differentiation. Localization of Myf5, MyoD, and Pax7 to the nuclear lamina and proper temporal expression of these genes required emerin and HDAC3. Interestingly, activation of HDAC3 catalytic activity rescued both Myf5 localization to the nuclear lamina and its expression. Collectively, these data support a model whereby emerin facilitates repressive chromatin formation at the nuclear lamina by activating the catalytic activity of HDAC3 to regulate the coordinated spatiotemporal expression of myogenic differentiation genes. PMID:24062260

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

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.

Functional requirements of cellular differentiation: lessons from Bacillus subtilis.

PubMed

Narula, Jatin; Fujita, Masaya; Igoshin, Oleg A

2016-12-01

Successful execution of differentiation programs requires cells to assess multitudes of internal and external cues and respond with appropriate gene expression programs. Here, we review how Bacillus subtilis sporulation network deals with these tasks focusing on the lessons generalizable to other systems. With feedforward loops controlling both production and activation of downstream transcriptional regulators, cells achieve ultrasensitive threshold-like responses. The arrangement of sporulation network genes on the chromosome and transcriptional feedback loops allow coordination of sporulation decision with DNA-replication. Furthermore, to assess the starvation conditions without sensing specific metabolites, cells respond to changes in their growth rates with increased activity of sporulation master regulator. These design features of the sporulation network enable cells to robustly decide between vegetative growth and sporulation. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Minkowski metric in non-inertial observer radar coordinates

NASA Astrophysics Data System (ADS)

Minguzzi, E.

2005-12-01

We give a closed expression for the Minkowski (1+1)-dimensional metric in the radar coordinates of an arbitrary non-inertial observer O in terms of O's proper acceleration. Knowledge of the metric allows the non-inertial observer to perform experiments in spacetime without making reference to inertial frames. To clarify the relation between inertial and non-inertial observers the coordinate transformation between radar and inertial coordinates also is given. We show that every conformally flat coordinate system can be regarded as the radar coordinate system of a suitable observer for a suitable parametrization of the observer worldline. Therefore, the coordinate transformation between arbitrarily moving observers is a conformal transformation and conformally invariant (1+1)-dimensional theories lead to the same physics for all observers, independently of their relative motion.

Generalized and efficient algorithm for computing multipole energies and gradients based on Cartesian tensors

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

Lin, Dejun, E-mail: dejun.lin@gmail.com

2015-09-21

Accurate representation of intermolecular forces has been the central task of classical atomic simulations, known as molecular mechanics. Recent advancements in molecular mechanics models have put forward the explicit representation of permanent and/or induced electric multipole (EMP) moments. The formulas developed so far to calculate EMP interactions tend to have complicated expressions, especially in Cartesian coordinates, which can only be applied to a specific kernel potential function. For example, one needs to develop a new formula each time a new kernel function is encountered. The complication of these formalisms arises from an intriguing and yet obscured mathematical relation between themore » kernel functions and the gradient operators. Here, I uncover this relation via rigorous derivation and find that the formula to calculate EMP interactions is basically invariant to the potential kernel functions as long as they are of the form f(r), i.e., any Green’s function that depends on inter-particle distance. I provide an algorithm for efficient evaluation of EMP interaction energies, forces, and torques for any kernel f(r) up to any arbitrary rank of EMP moments in Cartesian coordinates. The working equations of this algorithm are essentially the same for any kernel f(r). Recently, a few recursive algorithms were proposed to calculate EMP interactions. Depending on the kernel functions, the algorithm here is about 4–16 times faster than these algorithms in terms of the required number of floating point operations and is much more memory efficient. I show that it is even faster than a theoretically ideal recursion scheme, i.e., one that requires 1 floating point multiplication and 1 addition per recursion step. This algorithm has a compact vector-based expression that is optimal for computer programming. The Cartesian nature of this algorithm makes it fit easily into modern molecular simulation packages as compared with spherical coordinate-based algorithms. A software library based on this algorithm has been implemented in C++11 and has been released.« less

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.

Over-expression and purification strategies for recombinant multi-protein oligomers: a case study of Mycobacterium tuberculosis σ/anti-σ factor protein complexes.

PubMed

Thakur, Krishan Gopal; Jaiswal, Ravi Kumar; Shukla, Jinal K; Praveena, T; Gopal, B

2010-12-01

The function of a protein in a cell often involves coordinated interactions with one or several regulatory partners. It is thus imperative to characterize a protein both in isolation as well as in the context of its complex with an interacting partner. High resolution structural information determined by X-ray crystallography and Nuclear Magnetic Resonance offer the best route to characterize protein complexes. These techniques, however, require highly purified and homogenous protein samples at high concentration. This requirement often presents a major hurdle for structural studies. Here we present a strategy based on co-expression and co-purification to obtain recombinant multi-protein complexes in the quantity and concentration range that can enable hitherto intractable structural projects. The feasibility of this strategy was examined using the σ factor/anti-σ factor protein complexes from Mycobacterium tuberculosis. The approach was successful across a wide range of σ factors and their cognate interacting partners. It thus appears likely that the analysis of these complexes based on variations in expression constructs and procedures for the purification and characterization of these recombinant protein samples would be widely applicable for other multi-protein systems. Copyright © 2010 Elsevier Inc. All rights reserved.

BRIEF COMMUNICATION: A note on the Coulomb collision operator in curvilinear coordinates

NASA Astrophysics Data System (ADS)

Goncharov, P. R.

2010-10-01

The dynamic friction force, diffusion tensor, flux density in velocity space and Coulomb collision term are expressed in curvilinear coordinates via Trubnikov potential functions corresponding to each species of a background plasma. For comparison, explicit formulae are given for the dynamic friction force, diffusion tensor and collisional flux density in velocity space in curvilinear coordinates via Rosenbluth potential functions summed over all species of the background plasma.

Embryo arrest and reactivation: potential candidates controlling embryonic diapause in the tammar wallaby and mink†.

PubMed

Fenelon, Jane C; Shaw, Geoffrey; Frankenberg, Stephen R; Murphy, Bruce D; Renfree, Marilyn B

2017-04-01

Embryonic diapause is a period of developmental arrest which requires coordination of a molecular cross-talk between the endometrium and blastocyst to ensure a successful reactivation, but the exact mechanisms are undefined. The objectives of this study were to screen the tammar blastocyst for potential diapause control factors and to investigate the potential for members of the epidermal growth factor (EGF) family to coordinate reactivation. A select number of factors were also examined in the mink to determine whether their expression patterns were conserved across diapause species. The full-length sequences of the tammar genes of interest were first cloned to establish their level of sequence conservation with other mammals. The uterine expression of EGF family members EGF and heparin-binding EGF (HBEGF) and their receptors (EGFR and erb-b2 receptor tyrosine kinase 4 (ERBB4)) was determined by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. Both HBEGF and EGF were significantly upregulated at reactivation compared to diapause. In the blastocyst, the expression of the potential diapause factors Forkhead box class O family members (FOXO1, FOXO3, and FOXO4), tumor protein 53 (TP53), cyclin-dependent kinase inhibitor 1A (CDKN1A), and the EGF family were examined by RT-PCR and immunofluorescence. Nuclear (and hence active) FOXO expression was confirmed for the first time in a mammalian diapause blastocyst in both the tammar and the mink-CDKN1A was also expressed, but TP53 is not involved and EGFR was not detected in the blastocyst. These results indicate that the EGF family, FOXOs, and CDKN1A are promising candidates for the molecular control of embryonic diapause in mammals. © The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Genetic Dissection of Nutrition-Induced Plasticity in Insulin/Insulin-Like Growth Factor Signaling and Median Life Span in a Drosophila Multiparent Population

PubMed Central

Stanley, Patrick D.; Ng’oma, Enoch; O’Day, Siri; King, Elizabeth G.

2017-01-01

The nutritional environments that organisms experience are inherently variable, requiring tight coordination of how resources are allocated to different functions relative to the total amount of resources available. A growing body of evidence supports the hypothesis that key endocrine pathways play a fundamental role in this coordination. In particular, the insulin/insulin-like growth factor signaling (IIS) and target of rapamycin (TOR) pathways have been implicated in nutrition-dependent changes in metabolism and nutrient allocation. However, little is known about the genetic basis of standing variation in IIS/TOR or how diet-dependent changes in expression in this pathway influence phenotypes related to resource allocation. To characterize natural genetic variation in the IIS/TOR pathway, we used >250 recombinant inbred lines (RILs) derived from a multiparental mapping population, the Drosophila Synthetic Population Resource, to map transcript-level QTL of genes encoding 52 core IIS/TOR components in three different nutritional environments [dietary restriction (DR), control (C), and high sugar (HS)]. Nearly all genes, 87%, were significantly differentially expressed between diets, though not always in ways predicted by loss-of-function mutants. We identified cis (i.e., local) expression QTL (eQTL) for six genes, all of which are significant in multiple nutrient environments. Further, we identified trans (i.e., distant) eQTL for two genes, specific to a single nutrient environment. Our results are consistent with many small changes in the IIS/TOR pathways. A discriminant function analysis for the C and DR treatments identified a pattern of gene expression associated with the diet treatment. Mapping the composite discriminant function scores revealed a significant global eQTL within the DR diet. A correlation between the discriminant function scores and the median life span (r = 0.46) provides evidence that gene expression changes in response to diet are associated with longevity in these RILs. PMID:28592498

On differential transformations between Cartesian and curvilinear (geodetic) coordinates

NASA Technical Reports Server (NTRS)

Soler, T.

1976-01-01

Differential transformations are developed between Cartesian and curvilinear orthogonal coordinates. Only matrix algebra is used for the presentation of the basic concepts. After defining the reference systems used the rotation (R), metric (H), and Jacobian (J) matrices of the transformations between cartesian and curvilinear coordinate systems are introduced. A value of R as a function of H and J is presented. Likewise an analytical expression for J(-1) as a function of H(-2) and R is obtained. Emphasis is placed on showing that differential equations are equivalent to conventional similarity transformations. Scaling methods are discussed along with ellipsoidal coordinates. Differential transformations between elipsoidal and geodetic coordinates are established.

45 CFR 1310.23 - Coordinated transportation.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 4 2012-10-01 2012-10-01 false Coordinated transportation. 1310.23 Section 1310... START PROGRAM HEAD START TRANSPORTATION Special Requirements § 1310.23 Coordinated transportation. (a) Each agency providing transportation services must make reasonable efforts to coordinate transportation...

45 CFR 1310.23 - Coordinated transportation.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 4 2013-10-01 2013-10-01 false Coordinated transportation. 1310.23 Section 1310... START PROGRAM HEAD START TRANSPORTATION Special Requirements § 1310.23 Coordinated transportation. (a) Each agency providing transportation services must make reasonable efforts to coordinate transportation...

45 CFR 1310.23 - Coordinated transportation.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 4 2014-10-01 2014-10-01 false Coordinated transportation. 1310.23 Section 1310... START PROGRAM HEAD START TRANSPORTATION Special Requirements § 1310.23 Coordinated transportation. (a) Each agency providing transportation services must make reasonable efforts to coordinate transportation...

78 FR 73819 - Forest Resource Coordinating Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-09

... DEPARTMENT OF AGRICULTURE Forest Service Forest Resource Coordinating Committee AGENCY: Forest... was required to cancel the October 17-18, 2013 meeting of the Forest Resource Coordinating Committee..., September 17, 2013, Page 57128. FOR FURTHER INFORMATION CONTACT: Maya Solomon, Forest Resource Coordinating...

Fusagene vectors: a novel strategy for the expression of multiple genes from a single cistron.

PubMed

Gäken, J; Jiang, J; Daniel, K; van Berkel, E; Hughes, C; Kuiper, M; Darling, D; Tavassoli, M; Galea-Lauri, J; Ford, K; Kemeny, M; Russell, S; Farzaneh, F

2000-12-01

Transduction of cells with multiple genes, allowing their stable and co-ordinated expression, is difficult with the available methodologies. A method has been developed for expression of multiple gene products, as fusion proteins, from a single cistron. The encoded proteins are post-synthetically cleaved and processed into each of their constituent proteins as individual, biologically active factors. Specifically, linkers encoding cleavage sites for the Golgi expressed endoprotease, furin, have been incorporated between in-frame cDNA sequences encoding different secreted or membrane bound proteins. With this strategy we have developed expression vectors encoding multiple proteins (IL-2 and B7.1, IL-4 and B7.1, IL-4 and IL-2, IL-12 p40 and p35, and IL-12 p40, p35 and IL-2 ). Transduction and analysis of over 100 individual clones, derived from murine and human tumour cell lines, demonstrate the efficient expression and biological activity of each of the encoded proteins. Fusagene vectors enable the co-ordinated expression of multiple gene products from a single, monocistronic, expression cassette.

Collective decision-making in microbes

PubMed Central

Ross-Gillespie, Adin; Kümmerli, Rolf

2014-01-01

Microbes are intensely social organisms that routinely cooperate and coordinate their activities to express elaborate population level phenotypes. Such coordination requires a process of collective decision-making, in which individuals detect and collate information not only from their physical environment, but also from their social environment, in order to arrive at an appropriately calibrated response. Here, we present a conceptual overview of collective decision-making as it applies to all group-living organisms; we introduce key concepts and principles developed in the context of animal and human group decisions; and we discuss, with appropriate examples, the applicability of each of these concepts in microbial contexts. In particular, we discuss the roles of information pooling, control skew, speed vs. accuracy trade-offs, local feedbacks, quorum thresholds, conflicts of interest, and the reliability of social information. We conclude that collective decision-making in microbes shares many features with collective decision-making in higher taxa, and we call for greater integration between this fledgling field and other allied areas of research, including in the humanities and the physical sciences. PMID:24624121

Uncoupling apical constriction from tissue invagination

PubMed Central

Chung, SeYeon; Kim, Sangjoon; Andrew, Deborah J

2017-01-01

Apical constriction is a widely utilized cell shape change linked to folding, bending and invagination of polarized epithelia. It remains unclear how apical constriction is regulated spatiotemporally during tissue invagination and how this cellular process contributes to tube formation in different developmental contexts. Using Drosophila salivary gland (SG) invagination as a model, we show that regulation of folded gastrulation expression by the Fork head transcription factor is required for apicomedial accumulation of Rho kinase and non-muscle myosin II, which coordinate apical constriction. We demonstrate that neither loss of spatially coordinated apical constriction nor its complete blockage prevent internalization and tube formation, although such manipulations affect the geometry of invagination. When apical constriction is disrupted, compressing force generated by a tissue-level myosin cable contributes to SG invagination. We demonstrate that fully elongated polarized SGs can form outside the embryo, suggesting that tube formation and elongation are intrinsic properties of the SG. DOI: http://dx.doi.org/10.7554/eLife.22235.001 PMID:28263180

A Method for Optimal Load Dispatch of a Multi-zone Power System with Zonal Exchange Constraints

NASA Astrophysics Data System (ADS)

Hazarika, Durlav; Das, Ranjay

2018-04-01

This paper presented a method for economic generation scheduling of a multi-zone power system having inter zonal operational constraints. For this purpose, the generator rescheduling for a multi area power system having inter zonal operational constraints has been represented as a two step optimal generation scheduling problem. At first, the optimal generation scheduling has been carried out for the zone having surplus or deficient generation with proper spinning reserve using co-ordination equation. The power exchange required for the deficit zones and zones having no generation are estimated based on load demand and generation for the zone. The incremental transmission loss formulas for the transmission lines participating in the power transfer process among the zones are formulated. Using these, incremental transmission loss expression in co-ordination equation, the optimal generation scheduling for the zonal exchange has been determined. Simulation is carried out on IEEE 118 bus test system to examine the applicability and validity of the method.

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

Transcription Factors of Lotus: Regulation of Isoflavonoid Biosynthesis Requires Coordinated Changes in Transcription Factor Activity1[W][OA

PubMed Central

Shelton, Dale; Stranne, Maria; Mikkelsen, Lisbeth; Pakseresht, Nima; Welham, Tracey; Hiraka, Hideki; Tabata, Satoshi; Sato, Shusei; Paquette, Suzanne; Wang, Trevor L.; Martin, Cathie; Bailey, Paul

2012-01-01

Isoflavonoids are a class of phenylpropanoids made by legumes, and consumption of dietary isoflavonoids confers benefits to human health. Our aim is to understand the regulation of isoflavonoid biosynthesis. Many studies have shown the importance of transcription factors in regulating the transcription of one or more genes encoding enzymes in phenylpropanoid metabolism. In this study, we coupled bioinformatics and coexpression analysis to identify candidate genes encoding transcription factors involved in regulating isoflavonoid biosynthesis in Lotus (Lotus japonicus). Genes encoding proteins belonging to 39 of the main transcription factor families were examined by microarray analysis of RNA from leaf tissue that had been elicited with glutathione. Phylogenetic analyses of each transcription factor family were used to identify subgroups of proteins that were specific to L. japonicus or closely related to known regulators of the phenylpropanoid pathway in other species. R2R3MYB subgroup 2 genes showed increased expression after treatment with glutathione. One member of this subgroup, LjMYB14, was constitutively overexpressed in L. japonicus and induced the expression of at least 12 genes that encoded enzymes in the general phenylpropanoid and isoflavonoid pathways. A distinct set of six R2R3MYB subgroup 2-like genes was identified. We suggest that these subgroup 2 sister group proteins and those belonging to the main subgroup 2 have roles in inducing isoflavonoid biosynthesis. The induction of isoflavonoid production in L. japonicus also involves the coordinated down-regulation of competing biosynthetic pathways by changing the expression of other transcription factors. PMID:22529285

Computational design of a Zn2+ receptor that controls bacterial gene expression

NASA Astrophysics Data System (ADS)

Dwyer, M. A.; Looger, L. L.; Hellinga, H. W.

2003-09-01

The control of cellular physiology and gene expression in response to extracellular signals is a basic property of living systems. We have constructed a synthetic bacterial signal transduction pathway in which gene expression is controlled by extracellular Zn2+. In this system a computationally designed Zn2+-binding periplasmic receptor senses the extracellular solute and triggers a two-component signal transduction pathway via a chimeric transmembrane protein, resulting in transcriptional up-regulation of a -galactosidase reporter gene. The Zn2+-binding site in the designed receptor is based on a four-coordinate, tetrahedral primary coordination sphere consisting of histidines and glutamates. In addition, mutations were introduced in a secondary coordination sphere to satisfy the residual hydrogen-bonding potential of the histidines coordinated to the metal. The importance of the secondary shell interactions is demonstrated by their effect on metal affinity and selectivity, as well as protein stability. Three designed protein sequences, comprising two distinct metal-binding positions, were all shown to bind Zn2+ and to function in the cell-based assay, indicating the generality of the design methodology. These experiments demonstrate that biological systems can be manipulated with computationally designed proteins that have drastically altered ligand-binding specificities, thereby extending the repertoire of genetic control by extracellular signals.

PGC-1α dictates endothelial function through regulation of eNOS expression

PubMed Central

Craige, Siobhan M.; Kröller-Schön, Swenja; Li, Chunying; Kant, Shashi; Cai, Shenghe; Chen, Kai; Contractor, Mayur M.; Pei, Yongmei; Schulz, Eberhard; Keaney, John F.

2016-01-01

Endothelial dysfunction is a characteristic of many vascular related diseases such as hypertension. Peroxisome proliferator activated receptor gamma, coactivator 1α (PGC-1α) is a unique stress sensor that largely acts to promote adaptive responses. Therefore, we sought to define the role of endothelial PGC-1α in vascular function using mice with endothelial specific loss of function (PGC-1α EC KO) and endothelial specific gain of function (PGC-1α EC TG). Here we report that endothelial PGC-1α is suppressed in angiotensin-II (ATII)-induced hypertension. Deletion of endothelial PGC-1α sensitized mice to endothelial dysfunction and hypertension in response to ATII, whereas PGC-1α EC TG mice were protected. Mechanistically, PGC-1α promotes eNOS expression and activity, which is necessary for protection from ATII-induced dysfunction as mice either treated with an eNOS inhibitor (LNAME) or lacking eNOS were no longer responsive to transgenic endothelial PGC-1α expression. Finally, we determined that the orphan nuclear receptor, estrogen related receptor α (ERRα) is required to coordinate the PGC-1α -induced eNOS expression. In conclusion, endothelial PGC-1α expression protects from vascular dysfunction by promoting NO• bioactivity through ERRα induced expression of eNOS. PMID:27910955

Recommended coordinate systems for thin spherocylindrical lenses.

PubMed

Deal, F C; Toop, J

1993-05-01

Because the set of thin spherocylindrical lenses forms a vector space, any such lens can be expressed in terms of its cartesian coordinates with respect to whatever set of basis lenses we may choose. Two types of cartesian coordinate systems have become prominent, those having coordinates associated with the lens power matrix and those having coordinates associated with the Humphrey Vision Analyzer. This paper emphasizes the value of a particular cartesian coordinate system of the latter type, and the cylindrical coordinate system related to it, by showing how it can simplify the trigonometry of adding lenses and how it preserves symmetry in depicting the sets of all spherical lenses, all Jackson crossed-cylinders, and all cylindrical lenses. It also discusses appropriate coordinates for keeping statistics on lenses and shows that an easy extension of the lens vector space to include general optical systems is not possible.

Elementary Green function as an integral superposition of Gaussian beams in inhomogeneous anisotropic layered structures in Cartesian coordinates

NASA Astrophysics Data System (ADS)

Červený, Vlastislav; Pšenčík, Ivan

2017-08-01

Integral superposition of Gaussian beams is a useful generalization of the standard ray theory. It removes some of the deficiencies of the ray theory like its failure to describe properly behaviour of waves in caustic regions. It also leads to a more efficient computation of seismic wavefields since it does not require the time-consuming two-point ray tracing. We present the formula for a high-frequency elementary Green function expressed in terms of the integral superposition of Gaussian beams for inhomogeneous, isotropic or anisotropic, layered structures, based on the dynamic ray tracing (DRT) in Cartesian coordinates. For the evaluation of the superposition formula, it is sufficient to solve the DRT in Cartesian coordinates just for the point-source initial conditions. Moreover, instead of seeking 3 × 3 paraxial matrices in Cartesian coordinates, it is sufficient to seek just 3 × 2 parts of these matrices. The presented formulae can be used for the computation of the elementary Green function corresponding to an arbitrary direct, multiply reflected/transmitted, unconverted or converted, independently propagating elementary wave of any of the three modes, P, S1 and S2. Receivers distributed along or in a vicinity of a target surface may be situated at an arbitrary part of the medium, including ray-theory shadow regions. The elementary Green function formula can be used as a basis for the computation of wavefields generated by various types of point sources (explosive, moment tensor).

Design of a Two-Step Calibration Method of Kinematic Parameters for Serial Robots

NASA Astrophysics Data System (ADS)

WANG, Wei; WANG, Lei; YUN, Chao

2017-03-01

Serial robots are used to handle workpieces with large dimensions, and calibrating kinematic parameters is one of the most efficient ways to upgrade their accuracy. Many models are set up to investigate how many kinematic parameters can be identified to meet the minimal principle, but the base frame and the kinematic parameter are indistinctly calibrated in a one-step way. A two-step method of calibrating kinematic parameters is proposed to improve the accuracy of the robot's base frame and kinematic parameters. The forward kinematics described with respect to the measuring coordinate frame are established based on the product-of-exponential (POE) formula. In the first step the robot's base coordinate frame is calibrated by the unit quaternion form. The errors of both the robot's reference configuration and the base coordinate frame's pose are equivalently transformed to the zero-position errors of the robot's joints. The simplified model of the robot's positioning error is established in second-power explicit expressions. Then the identification model is finished by the least square method, requiring measuring position coordinates only. The complete subtasks of calibrating the robot's 39 kinematic parameters are finished in the second step. It's proved by a group of calibration experiments that by the proposed two-step calibration method the average absolute accuracy of industrial robots is updated to 0.23 mm. This paper presents that the robot's base frame should be calibrated before its kinematic parameters in order to upgrade its absolute positioning accuracy.

A qualitative analysis of success stories from Michiana Coordinated School Health Leadership institute participants.

PubMed

Dewitt, Natalie; Lohrmann, David K; O'Neill, James; Clark, Jeffrey K

2011-12-01

The purpose of this study was to detect and document common themes among success stories, along with challenges, as related by participants in the Michiana Coordinated School Health Leadership Institute. Four-member teams from 18 Michigan and Indiana school districts participated in semiannual Institute workshops over a 3-year period and were tasked with implementing Coordinated School Health Programs (CSHPs). Qualitative methods were used to generate themes from interviews. Data were gathered through a combined survey/interview process related to programmatic successes, evidence of success, and implementation challenges. One participant from 11 of 18 participating school districts completed the survey/interview. Each participant reported at least 1 success that had a positive effect on students and/or staff, many of which were related to the federally mandated wellness policy. With some notable exceptions, success was based on subjective judgments rather than systematically collected data. Unanimous expression of time constraints and being overworked in their current positions constituted major challenges. Although the Institute required only process evaluation, some participants collected outcome data, a task that is important in validating the benefits of CSHPs. Most districts were not able to hire the recommended coordinator to ensure implementation of health program planning initially developed during the institute. Encouragingly, at the time of data collection many teams were still acting to ensure health programming remained a priority. Nevertheless, without the network of social support provided by the Institute, some respondents struggled to maintain momentum. © 2011, American School Health Association.

33 CFR 334.6 - Datum.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 3 2013-07-01 2013-07-01 false Datum. 334.6 Section 334.6... AND RESTRICTED AREA REGULATIONS § 334.6 Datum. (a) Geographic coordinates expressed in terms of... datum is the North American Datum of 1983 (NAD 83), unless such geographic coordinates are expressly...

33 CFR 334.6 - Datum.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 3 2012-07-01 2012-07-01 false Datum. 334.6 Section 334.6... AND RESTRICTED AREA REGULATIONS § 334.6 Datum. (a) Geographic coordinates expressed in terms of... datum is the North American Datum of 1983 (NAD 83), unless such geographic coordinates are expressly...

33 CFR 334.6 - Datum.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 3 2014-07-01 2014-07-01 false Datum. 334.6 Section 334.6... AND RESTRICTED AREA REGULATIONS § 334.6 Datum. (a) Geographic coordinates expressed in terms of... datum is the North American Datum of 1983 (NAD 83), unless such geographic coordinates are expressly...

33 CFR 334.6 - Datum.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 3 2011-07-01 2011-07-01 false Datum. 334.6 Section 334.6... AND RESTRICTED AREA REGULATIONS § 334.6 Datum. (a) Geographic coordinates expressed in terms of... datum is the North American Datum of 1983 (NAD 83), unless such geographic coordinates are expressly...

Guide to Understanding Facial Palsy

MedlinePlus

... to many different facial muscles. These muscles control facial expression. The coordinated activity of this nerve and these ... involves a weakness of the muscles responsible for facial expression and side-to-side eye movement. Moebius syndrome ...

Coordinate Intracellular Expression of Salmonella Genes Induced during Infection

PubMed Central

Heithoff, Douglas M.; Conner, Christopher P.; Hentschel, Ute; Govantes, Fernando; Hanna, Philip C.; Mahan, Michael J.

1999-01-01

Salmonella typhimurium in vivo-induced (ivi) genes were grouped by their coordinate behavior in response to a wide variety of environmental and genetic signals, including pH, Mg2+, Fe2+, and PhoPQ. All of the seven ivi fusions that are induced by both low pH and low Mg2+ (e.g., iviVI-A) are activated by the PhoPQ regulatory system. Iron-responsive ivi fusions include those induced under iron limitation (e.g., entF) as well as one induced by iron excess but only in the absence of PhoP (pdu). Intracellular expression studies showed that each of the pH- and Mg2+-responsive fusions is induced upon entry into and growth within three distinct mammalian cell lines: RAW 264.7 murine macrophages and two cultured human epithelial cell lines: HEp-2 and Henle-407. Each ivi fusion has a characteristic level of induction consistent within all three cell types, suggesting that this class of coordinately expressed ivi genes responds to general intracellular signals that are present both in initial and in progressive stages of infection and may reflect their responses to similar vacuolar microenvironments in these cell types. Investigation of ivi expression patterns reveals not only the inherent versatility of pathogens to express a given gene(s) at various host sites but also the ability to modify their expression within the context of different animal hosts, tissues, cell types, or subcellular compartments. PMID:9922242

Coordinated Changes in Xenobiotic Metabolizing Enzyme Gene Expression in Aging Male Rats

EPA Science Inventory

In order to gain better insight on aging and susceptibility, we characterized the expression of xenobiotic metabolizing enzymes (XMEs) from the livers of rats to evaluate the change in capacity to respond to xenobiotics across the adult lifespan. Gene expression profiles for XMEs...

Dynamic HypA zinc site is essential for acid viability and proper urease maturation in Helicobacter pylori.

PubMed

Johnson, Ryan C; Hu, Heidi Q; Merrell, D Scott; Maroney, Michael J

2015-04-01

Helicobacter pylori requires urease activity in order to survive in the acid environment of the human stomach. Urease is regulated in part by nickelation, a process that requires the HypA protein, which is a putative nickel metallochaperone that is generally associated with hydrogenase maturation. However, in H. pylori, HypA plays a dual role. In addition to an N-terminal nickel binding site, HypA proteins also contain a structural zinc site that is coordinated by two rigorously conserved CXXC sequences, which in H. pylori are flanked by His residues. These structural Zn sites are known to be dynamic, converting from Zn(Cys)4 centers at pH 7.2 to Zn(Cys)2(His)2 centers at pH 6.3 in the presence of Ni(ii) ions. In this study, mutant strains of H. pylori that express zinc site variants of the HypA protein are used to show that the structural changes in the zinc site are important for the acid viability of the bacterium, and that a reduction in acid viability in these variants can be traced in large measure to deficient urease activity. This in turn leads to a model that connects the Zn(Cys)4 coordination to urease maturation.

An approximate solution for interlaminar stresses in laminated composites: Applied mechanics program

NASA Technical Reports Server (NTRS)

Rose, Cheryl A.; Herakovich, Carl T.

1992-01-01

An approximate solution for interlaminar stresses in finite width, laminated composites subjected to uniform extensional, and bending loads is presented. The solution is based upon the principle of minimum complementary energy and an assumed, statically admissible stress state, derived by considering local material mismatch effects and global equilibrium requirements. The stresses in each layer are approximated by polynomial functions of the thickness coordinate, multiplied by combinations of exponential functions of the in-plane coordinate, expressed in terms of fourteen unknown decay parameters. Imposing the stationary condition of the laminate complementary energy with respect to the unknown variables yields a system of fourteen non-linear algebraic equations for the parameters. Newton's method is implemented to solve this system. Once the parameters are known, the stresses can be easily determined at any point in the laminate. Results are presented for through-thickness and interlaminar stress distributions for angle-ply, cross-ply (symmetric and unsymmetric laminates), and quasi-isotropic laminates subjected to uniform extension and bending. It is shown that the solution compares well with existing finite element solutions and represents an improved approximate solution for interlaminar stresses, primarily at interfaces where global equilibrium is satisfied by the in-plane stresses, but large local mismatch in properties requires the presence of interlaminar stresses.

DREAM mediates cAMP-dependent, Ca2+-induced stimulation of GFAP gene expression and regulates cortical astrogliogenesis.

PubMed

Cebolla, Beatriz; Fernández-Pérez, Antonio; Perea, Gertrudis; Araque, Alfonso; Vallejo, Mario

2008-06-25

In the developing mouse brain, once the generation of neurons is mostly completed during the prenatal period, precisely coordinated signals act on competent neural precursors to direct their differentiation into astrocytes, which occurs mostly after birth. Among these signals, those provided by neurotrophic cytokines and bone morphogenetic proteins appear to have a key role in triggering the neurogenic to gliogenic switch and in regulating astrocyte numbers. In addition, we have reported previously that the neurotrophic peptide pituitary adenylate cyclase-activating polypeptide (PACAP) is able to promote astrocyte differentiation of cortical precursors via activation of a cAMP-dependent pathway. Signals acting on progenitor cells of the developing cortex to generate astrocytes activate glial fibrillary acidic protein (GFAP) gene expression, but the transcriptional mechanisms that regulate this activation are unclear. Here, we identify the previously known transcriptional repressor downstream regulatory element antagonist modulator (DREAM) as an activator of GFAP gene expression. We found that DREAM occupies specific sites on the GFAP promoter before and after differentiation is initiated by exposure of cortical progenitor cells to PACAP. PACAP raises intracellular calcium concentration via a mechanism that requires cAMP, and DREAM-mediated transactivation of the GFAP gene requires the integrity of calcium-binding domains. Cortical progenitor cells from dream(-/-) mice fail to express GFAP in response to PACAP. Moreover, the neonatal cortex of dream(-/-) mice exhibits a reduced number of astrocytes and increased number of neurons. These results identify the PACAP-cAMP-Ca(2+)-DREAM cascade as a new pathway to activate GFAP gene expression during astrocyte differentiation.

Definition of DLPFC and M1 according to anatomical landmarks for navigated brain stimulation: inter-rater reliability, accuracy, and influence of gender and age.

PubMed

Mylius, V; Ayache, S S; Ahdab, R; Farhat, W H; Zouari, H G; Belke, M; Brugières, P; Wehrmann, E; Krakow, K; Timmesfeld, N; Schmidt, S; Oertel, W H; Knake, S; Lefaucheur, J P

2013-09-01

The optimization of the targeting of a defined cortical region is a challenge in the current practice of transcranial magnetic stimulation (TMS). The dorsolateral prefrontal cortex (DLPFC) and the primary motor cortex (M1) are among the most usual TMS targets, particularly in its "therapeutic" application. This study describes a practical algorithm to determine the anatomical location of the DLPFC and M1 using a three-dimensional (3D) brain reconstruction provided by a TMS-dedicated navigation system from individual magnetic resonance imaging (MRI) data. The coordinates of the right and left DLPFC and M1 were determined in 50 normal brains (100 hemispheres) by five different investigators using a standardized procedure. Inter-rater reliability was good, with 95% limits of agreement ranging between 7 and 16 mm for the different coordinates. As expressed in the Talairach space and compared with anatomical or imaging data from the literature, the coordinates of the DLPFC defined by our algorithm corresponded to the junction between BA9 and BA46, while M1 coordinates corresponded to the posterior border of hand representation. Finally, we found an influence of gender and possibly of age on some coordinates on both rostrocaudal and dorsoventral axes. Our algorithm only requires a short training and can be used to provide a reliable targeting of DLPFC and M1 between various TMS investigators. This method, based on an image-guided navigation system using individual MRI data, should be helpful to a variety of TMS studies, especially to standardize the procedure of stimulation in multicenter "therapeutic" studies. Copyright © 2013 Elsevier Inc. All rights reserved.

Coordinated Hard Sphere Mixture (CHaSM): A simplified model for oxide and silicate melts at mantle pressures and temperatures

NASA Astrophysics Data System (ADS)

Wolf, Aaron S.; Asimow, Paul D.; Stevenson, David J.

2015-08-01

We develop a new model to understand and predict the behavior of oxide and silicate melts at extreme temperatures and pressures, including deep mantle conditions like those in the early Earth magma ocean. The Coordinated Hard Sphere Mixture (CHaSM) is based on an extension of the hard sphere mixture model, accounting for the range of coordination states available to each cation in the liquid. By utilizing approximate analytic expressions for the hard sphere model, this method is capable of predicting complex liquid structure and thermodynamics while remaining computationally efficient, requiring only minutes of calculation time on standard desktop computers. This modeling framework is applied to the MgO system, where model parameters are trained on a collection of crystal polymorphs, producing realistic predictions of coordination evolution and the equation of state of MgO melt over a wide range of pressures and temperatures. We find that the typical coordination number of the Mg cation evolves continuously upward from 5.25 at 0 GPa to 8.5 at 250 GPa. The results produced by CHaSM are evaluated by comparison with predictions from published first-principles molecular dynamics calculations, indicating that CHaSM is accurately capturing the dominant physics controlling the behavior of oxide melts at high pressure. Finally, we present a simple quantitative model to explain the universality of the increasing Grüneisen parameter trend for liquids, which directly reflects their progressive evolution toward more compact solid-like structures upon compression. This general behavior is opposite that of solid materials, and produces steep adiabatic thermal profiles for silicate melts, thus playing a crucial role in magma ocean evolution.

Personal therapy for undergraduate music therapy students: a survey of AMTA program coordinators.

PubMed

Gardstrom, Susan C; Jackson, Nancy A

2011-01-01

The primary purpose of this study was to gather information in order to understand if and how various modalities of personal therapy are employed with undergraduate music therapy students in the United States. AMTA degree program coordinators were asked about 3 therapy modalities, in particular: verbal therapy, music therapy, and expressive arts therapy (excluding music therapy). It was predicted that less than a quarter of the respondents would indicate that personal therapy of any modality was required in their undergraduate curricula, but that a larger percentage would indicate that it was encouraged. Both hypotheses were supported, with just over 14% of the respondents indicating that they require some form of personal therapy and 32% indicating that they encourage it, with 73% of this latter subgroup encouraging verbal therapy and 46% encouraging music therapy. It was further predicted that, when therapy was required or encouraged, it was most often provided by an individual who was associated with the college/university and that therapy was usually provided in a group format. Respondent comments related to these 2 questions revealed considerable confusion between experiential exercises and personal therapy, leading to dubious validity of some of the numerical data. Qualitative treatment of narrative responses illuminated 4 salient issues regarding personal therapy for undergraduate music therapy students, as follows: (a) the legal and ethical feasibility of making personal therapy a requirement; (b) the cost and availability of qualified professionals; (c) the benefits of personal therapy as an integral facet of undergraduate music therapy training and education; and (d) the appropriateness of personal therapy at the undergraduate level of training.

Hierarchical cortical transcriptome disorganization in autism.

PubMed

Lombardo, Michael V; Courchesne, Eric; Lewis, Nathan E; Pramparo, Tiziano

2017-01-01

Autism spectrum disorders (ASD) are etiologically heterogeneous and complex. Functional genomics work has begun to identify a diverse array of dysregulated transcriptomic programs (e.g., synaptic, immune, cell cycle, DNA damage, WNT signaling, cortical patterning and differentiation) potentially involved in ASD brain abnormalities during childhood and adulthood. However, it remains unclear whether such diverse dysregulated pathways are independent of each other or instead reflect coordinated hierarchical systems-level pathology. Two ASD cortical transcriptome datasets were re-analyzed using consensus weighted gene co-expression network analysis (WGCNA) to identify common co-expression modules across datasets. Linear mixed-effect models and Bayesian replication statistics were used to identify replicable differentially expressed modules. Eigengene network analysis was then utilized to identify between-group differences in how co-expression modules interact and cluster into hierarchical meta-modular organization. Protein-protein interaction analyses were also used to determine whether dysregulated co-expression modules show enhanced interactions. We find replicable evidence for 10 gene co-expression modules that are differentially expressed in ASD cortex. Rather than being independent non-interacting sources of pathology, these dysregulated co-expression modules work in synergy and physically interact at the protein level. These systems-level transcriptional signals are characterized by downregulation of synaptic processes coordinated with upregulation of immune/inflammation, response to other organism, catabolism, viral processes, translation, protein targeting and localization, cell proliferation, and vasculature development. Hierarchical organization of meta-modules (clusters of highly correlated modules) is also highly affected in ASD. These findings highlight that dysregulation of the ASD cortical transcriptome is characterized by the dysregulation of multiple coordinated transcriptional programs producing synergistic systems-level effects that cannot be fully appreciated by studying the individual component biological processes in isolation.

Coordinate expression of cytokeratins 7 and 14, vimentin, and Bcl-2 in canine cutaneous epithelial tumors and cysts.

PubMed

Pieper, Jason B; Stern, Adam W; LeClerc, Suzette M; Campbell, Karen L

2015-07-01

Forty-seven canine cutaneous epithelial tumors and cysts were examined to determine coordinate expression of cytokeratins 7 (CK7) and 14 (CK14), vimentin, and Bcl-2 using commercially available antibodies. Within non-affected normal skin adjacent to tumors or cysts, CK7 expression was observed in luminal cells in apocrine glands; CK14 expression was observed in the stratum basale, stratum spinosum, stratum granulosum, basal layer of outer root sheath, sebaceous glands, and myoepithelial cells of apocrine glands; vimentin expression was observed in dermal papilla and scattered non-epithelial cells within the epidermis; and Bcl-2 expression was observed in scattered non-epithelial cells in the epidermis and some apocrine glands. The pattern of expression of CK7 and CK14 in cases of adenocarcinoma of the apocrine gland of the anal sac (CK7+/CK14-) and hepatoid gland tumors (CK7-/CK14+) may prove useful for diagnostic purposes. Loss of expression of CK14 and vimentin, identifying myoepithelial cells, was observed in apocrine and ceruminous adenocarcinomas. Differences in patterns of expression of Bcl-2 were observed between infundibular keratinizing acanthomas compared to trichoepitheliomas. © 2015 The Author(s).

National Coordinating Committee for Technology in Education and Training (NCC-TET) Requirements for the National Information Infrastructure (NII).

ERIC Educational Resources Information Center

Yrchik, John; Cradler, John

1994-01-01

Discusses guidelines that were developed to ensure that the National Information Infrastructure provides expanded opportunities for education and training. Topics include access requirements for homes and work places as well as schools; education and training application requirements, including coordination by federal departments and agencies; and…

Role of Metal Ions on the Activity of Mycobacterium tuberculosis Pyrazinamidase

PubMed Central

Sheen, Patricia; Ferrer, Patricia; Gilman, Robert H.; Christiansen, Gina; Moreno-Román, Paola; Gutiérrez, Andrés H.; Sotelo, Jun; Evangelista, Wilfredo; Fuentes, Patricia; Rueda, Daniel; Flores, Myra; Olivera, Paula; Solis, José; Pesaresi, Alessandro; Lamba, Doriano; Zimic, Mirko

2012-01-01

Pyrazinamidase of Mycobacterium tuberculosis catalyzes the conversion of pyrazinamide to the active molecule pyrazinoic acid. Reduction of pyrazinamidase activity results in a level of pyrazinamide resistance. Previous studies have suggested that pyrazinamidase has a metal-binding site and that a divalent metal cofactor is required for activity. To determine the effect of divalent metals on the pyrazinamidase, the recombinant wild-type pyrazinamidase corresponding to the H37Rv pyrazinamide-susceptible reference strain was expressed in Escherichia coli with and without a carboxy terminal. His-tagged pyrazinamidase was inactivated by metal depletion and reactivated by titration with divalent metals. Although Co2+, Mn2+, and Zn2+ restored pyrazinamidase activity, only Co2+ enhanced the enzymatic activity to levels higher than the wild-type pyrazinamidase. Cu2+, Fe2+, Fe3+, and Mg2+ did not restore the activity under the conditions tested. Various recombinant mutated pyrazinamidases with appropriate folding but different enzymatic activities showed a differential pattern of recovered activity. X-ray fluorescence and atomic absorbance spectroscopy showed that recombinant wild-type pyrazinamidase expressed in E. coli most likely contained Zn. In conclusion, this study suggests that M. tuberculosis pyrazinamidase is a metalloenzyme that is able to coordinate several ions, but in vivo, it is more likely to coordinate Zn2+. However, in vitro, the metal-depleted enzyme could be reactivated by several divalent metals with higher efficiency than Zn. PMID:22764307

Recombination and the evolution of coordinated phenotypic expression in a frequency-dependent game

PubMed Central

Arbilly, Michal; Motro, Uzi; Feldman, Marcus W.; Lotem, Arnon

2011-01-01

A long standing question in evolutionary biology concerns the maintenance of adaptive combinations of traits in the presence of recombination. This problem may be solved if positive epistasis selects for reducing the rate of recombination between such traits, but this requires sufficiently strong epistasis. Here we use a model that we developed previously to analyze a frequency-dependent strategy game in asexual populations, to study how adaptive combinations of traits may be maintained in the presence of recombination when epistasis is too weak to select for genetic linkage. Previously, in the asexual case, our model demonstrated the evolution of adaptive associations between social foraging strategies and learning rules. We verify that these adaptive associations, which are represented by different two-locus haplotypes, can easily be broken by genetic recombination. We also confirm that a modifier allele that reduces the rate of recombination fails to evolve (due to weak epistasis). However, we find that under the same conditions of weak epistasis, there is an alternative mechanism that allows association between traits to evolve. This is based on a genetic switch that responds to the presence of one social foraging allele by activating one of two alternative learning alleles that are carried by all individuals. We suggest that such coordinated phenotypic expression by genetic switches offers a general and robust mechanism for the evolution of adaptive combinations of traits in the presence of recombination. PMID:21945887

Estrogen-Related Receptor-α Coordinates Transcriptional Programs Essential for Exercise Tolerance and Muscle Fitness

PubMed Central

Perry, Marie-Claude; Dufour, Catherine R.; Tam, Ingrid S.; B'chir, Wafa

2014-01-01

Muscle fitness is an important determinant of health and disease. However, the molecular mechanisms involved in the coordinate regulation of the metabolic and structural determinants of muscle endurance are still poorly characterized. Herein, we demonstrate that estrogen-related receptor α (ERRα, NR3B1) is essential for skeletal muscle fitness. Notably, we show that ERRα-null animals are hypoactive and that genetic or therapeutic disruption of ERRα in mice results in reduced exercise tolerance. Mice lacking ERRα also exhibited lactatemia at exhaustion. Gene expression profiling demonstrates that ERRα plays a key role in various metabolic processes important for muscle function including energy substrate transport and use (Ldhd, Slc16a1, Hk2, and Glul), the tricarboxylic acid cycle (Cycs, and Idh3g), and oxidative metabolism (Pdha1, and Uqcrq). Metabolomics studies revealed impairment in replenishment of several amino acids (eg, glutamine) during recovery to exercise. Moreover, loss of ERRα was found to alter the expression of genes involved in oxidative stress response (Hmox1), maintenance of muscle fiber integrity (Trim63, and Hspa1b), and muscle plasticity and neovascularization (Vegfa). Taken together, our study shows that ERRα plays a key role in directing transcriptional programs required for optimal mitochondrial oxidative potential and muscle fitness, suggesting that modulation of ERRα activity could be used to manage metabolic myopathies and/or promote the adaptive response to physical exercise. PMID:25361393

Expression of DNAJB12 or DNAJB14 Causes Coordinate Invasion of the Nucleus by Membranes Associated with a Novel Nuclear Pore Structure

PubMed Central

Goodwin, Edward C.; Motamedi, Nasim; Lipovsky, Alex; Fernández-Busnadiego, Rubén; DiMaio, Daniel

2014-01-01

DNAJB12 and DNAJB14 are transmembrane proteins in the endoplasmic reticulum (ER) that serve as co-chaperones for Hsc70/Hsp70 heat shock proteins. We demonstrate that over-expression of DNAJB12 or DNAJB14 causes the formation of elaborate membranous structures within cell nuclei, which we designate DJANGOS for DNAJ-associated nuclear globular structures. DJANGOS contain DNAJB12, DNAJB14, Hsc70 and markers of the ER lumen and ER and nuclear membranes. Strikingly, they are evenly distributed underneath the nuclear envelope and are of uniform size in any one nucleus. DJANGOS are composed primarily of single-walled membrane tubes and sheets that connect to the nuclear envelope via a unique configuration of membranes, in which the nuclear pore complex appears anchored exclusively to the outer nuclear membrane, allowing both the inner and outer nuclear membranes to flow past the circumference of the nuclear pore complex into the nucleus. DJANGOS break down rapidly during cell division and reform synchronously in the daughter cell nuclei, demonstrating that they are dynamic structures that undergo coordinate formation and dissolution. Genetic studies showed that the chaperone activity of DNAJ/Hsc70 is required for the formation of DJANGOS. Further analysis of these structures will provide insight into nuclear pore formation and function, activities of molecular chaperones, and mechanisms that maintain membrane identity. PMID:24732912

Relaxation of structural parameters and potential coefficients of nonrigid molecules. General symmetry properties and application to ab initio study of 1,2-difluoroethane

NASA Astrophysics Data System (ADS)

Ha, T.-K.; Günthard, H. H.

1989-07-01

Structural parameters like bond length, bond angles, etc. and harmonic and anharmonic potential coefficients of molecules with internal rotation, inversion or puckering modes are generally assumed to vary with the large amplitude internal coordinates in a concerted manner (relaxation). Taking the coordinate vectors of the nuclear configuration of semirigid molecules with relaxation (SRMRs) as functions of relaxing structural parameters and finite amplitude internal coordinate, the isometric group of SRMRs is discussed and the irreducible representations of the latter are shown to classify into engendered and nonengendered ones. On this basis a concept of equivalent sets of nuclei SRMRs is introduced and an analytical expression is derived which defines the most general functional form of relaxation increments of all common types of structural parameters compatible with isometric symmetry. This formula is shown to be a close analog of an analytical expression defining the transformations induced by the isometric group of infinitesimal internal coordinates associated with typical structural parameters. Furthermore analogous formulae are given for the most general form of the relaxation of harmonic potential coefficients as a function of finite internal coordinates. The general relations are illustrated by ab initio calculations for 1,2-difluoroethane at the MP4/DZP//HF/4-31G* level for twelve values of the dihedral angle including complete structure optimization. The potential to internal rotation is found to be in essential agreement with experimentally derived data. For a complete set of ab initio structural parameters the associated relaxation increments are represented as Fourier series, which are shown to confirm the form predicted by the general formula and the isometric group of 1,2-difluoroethane. Depending on type of the structural parameters (bond length, bond angles, etc.), the associated relaxation increments appear to follow some simple rules. Similarly a complete set of harmonic potential coefficients derived from the ab initio calculations will be analyzed in terms of Fourier series and shown to conform to the symmetry requirements of the symmetry group. Relaxation of potential coefficients is found to amount to up to ≈5% for some types of diagonal and nondiagonal terms and to reflect certain "topological" rules similar to regularities of harmonic potential constants of quasi-rigid molecules found in empirical determinations of valence force fields.

Neuronal Correlates of Functional Coupling between Reach- and Grasp-Related Components of Muscle Activity

PubMed Central

Geed, Shashwati; McCurdy, Martha L.; van Kan, Peter L. E.

2017-01-01

Coordinated reach-to-grasp movements require precise spatiotemporal synchrony between proximal forelimb muscles (shoulder, elbow) that transport the hand toward a target during reach, and distal muscles (wrist, digit) that simultaneously preshape and orient the hand for grasp. The precise mechanisms through which the redundant neuromuscular circuitry coordinates reach with grasp, however, remain unclear. Recently, Geed and Van Kan (2016) demonstrated, using exploratory factor analysis (EFA), that limited numbers of global, template-like transport/preshape- and grasp-related muscle components underlie the complexity and variability of intramuscular electromyograms (EMGs) of up to 21 distal and proximal muscles recorded while monkeys performed reach-to-grasp tasks. Importantly, transport/preshape- and grasp-related muscle components showed invariant spatiotemporal coupling, which provides a potential mechanism for coordinating forelimb muscles during reach-to-grasp movements. In the present study, we tested whether ensemble discharges of forelimb neurons in the cerebellar nucleus interpositus (NI) and its target, the magnocellular red nucleus (RNm), a source of rubrospinal fibers, function as neuronal correlates of the transport/preshape- and grasp-related muscle components we identified. EFA applied to single-unit discharges of populations of NI and RNm neurons recorded while the same monkeys that were used previously performed the same reach-to-grasp tasks, revealed neuronal components in the ensemble discharges of both NI and RNm neuronal populations with characteristics broadly similar to muscle components. Subsets of NI and RNm neuronal components were strongly and significantly crosscorrelated with subsets of muscle components, suggesting that similar functional units of reach-to-grasp behavior are expressed by NI and RNm neuronal populations and forelimb muscles. Importantly, like transport/preshape- and grasp-related muscle components, their NI and RNm neuronal correlates showed invariant spatiotemporal coupling. Clinical and lesion studies have reported disruption of coupling between reach and grasp following cerebellar damage; the present results expand on those studies by identifying a neuronal mechanism that may underlie cerebellar contributions to spatiotemporal coordination of distal and proximal limb muscles during reaching to grasp. We conclude that finding similar functional units of behavior expressed at multiple levels of information processing along interposito-rubrospinal pathways and forelimb muscles supports the hypothesis that functionally related populations of NI and RNm neurons act synergistically in the control of complex coordinated motor behaviors. PMID:28270752

Digital Citizenship Instruction in Pennsylvania Public Schools: School Leaders Expressed Beliefs and Current Practices

ERIC Educational Resources Information Center

Suppo, Chris A.

2013-01-01

The purpose of this study was to investigate digital citizenship in Pennsylvania public schools based on the responses of school leaders including superintendents, curriculum coordinators, and technology coordinators. This study examined the relationship between Pennsylvania school leader's beliefs and the implementation of digital citizenship…

75 FR 78198 - Proposed Final Policy on Consultation and Coordination With Indian Tribes

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-15

... promote consistency in, and coordination of, the consultation process; and establish a management... found in Executive Order 13175. The Policy reflects the principles expressed in the 1984 EPA Policy for.... Definitions IV. Guiding Principles V. Consultation A. The Consultation Process B. What Activities May Involve...

Wing Defects in Drosophila xenicid Mutant Clones Are Caused by C-Terminal Deletion of Additional Sex Combs (Asx)

PubMed Central

Bischoff, Kara; Ballew, Anna C.; Simon, Michael A.; O'Reilly, Alana M.

2009-01-01

Background The coordinated action of genes that control patterning, cell fate determination, cell size, and cell adhesion is required for proper wing formation in Drosophila. Defects in any of these basic processes can lead to wing aberrations, including blisters. The xenicid mutation was originally identified in a screen designed to uncover regulators of adhesion between wing surfaces [1]. Principal Findings Here, we demonstrate that expression of the βPS integrin or the patterning protein Engrailed are not affected in developing wing imaginal discs in xenicid mutants. Instead, expression of the homeotic protein Ultrabithorax (Ubx) is strongly increased in xenicid mutant cells. Conclusion Our results suggest that upregulation of Ubx transforms cells from a wing blade fate to a haltere fate, and that the presence of haltere cells within the wing blade is the primary defect leading to the adult wing phenotypes observed. PMID:19956620

Electron dynamics inside a vacuum tube diode through linear differential equations

NASA Astrophysics Data System (ADS)

González, Gabriel; Orozco, Fco. Javier González; Orozco

2014-04-01

In this paper we analyze the motion of charged particles in a vacuum tube diode by solving linear differential equations. Our analysis is based on expressing the volume charge density as a function of the current density and coordinates only, i.e. ρ=ρ(J,z), while in the usual scheme the volume charge density is expressed as a function of the current density and electrostatic potential, i.e. ρ=ρ(J,V). We show that, in the case of slow varying charge density, the space-charge-limited current is reduced up to 50%. Our approach gives the well-known behavior of the classical current density proportional to the three-halves power of the bias potential and inversely proportional to the square of the gap distance between electrodes, and does not require the solution of the nonlinear differential equation normally associated with the Child-Langmuir formulation.

The pepper cysteine/histidine-rich DC1 domain protein CaDC1 binds both RNA and DNA and is required for plant cell death and defense response.

PubMed

Hwang, In Sun; Choi, Du Seok; Kim, Nak Hyun; Kim, Dae Sung; Hwang, Byung Kook

2014-01-01

Plant defense against microbial pathogens is coordinated by a complex regulatory network. Cysteine/histidine-rich DC1 domain proteins mediate a variety of cellular processes involved in plant growth, development and stress responses. We identified a pepper (Capsicum annuum) cysteine/histidine-rich DC1 domain protein gene, CaDC1, which positively regulates plant defense during microbial infection, based on gene silencing and transient expression in pepper, as well as ectopic expression in Arabidopsis. Induction of CaDC1 by avirulent Xanthomonas campestris pv vesicatoria (Xcv) infection was pronounced at both transcriptional and translational levels in pepper leaves. Purified CaDC1 protein bound to both DNA and RNA in vitro, especially in the presence of Zn(2+). CaDC1 was localized to both the nucleus and the cytoplasm, which was required for plant cell death signaling. The nuclear localization of CaDC1 was dependent on the divergent C1 (DC1) domain. CaDC1 silencing in pepper conferred increased susceptibility to Xcv infection, which was accompanied by reduced salicylic acid accumulation and defense-related gene expression. Ectopic expression of CaDC1 in Arabidopsis enhanced resistance to Hyaloperonospora arabidopsidis. CaDC1 binds both RNA and DNA and functions as a positive regulator of plant cell death and SA-dependent defense responses. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

Mechanisms of pathogenesis of emerging adenoviruses.

PubMed

Cook, James; Radke, Jay

2017-01-01

Periodic outbreaks of human adenovirus infections can cause severe illness in people with no known predisposing conditions. The reasons for this increased viral pathogenicity are uncertain. Adenoviruses are constantly undergoing mutation during circulation in the human population, but related phenotypic changes of the viruses are rarely detected because of the infrequency of such outbreaks and the limited biological studies of the emergent strains. Mutations and genetic recombinations have been identified in these new strains. However, the linkage between these genetic changes and increased pathogenicity is poorly understood. It has been observed recently that differences in virus-induced immunopathogenesis can be associated with altered expression of non-mutant viral genes associated with changes in viral modulation of the host innate immune response. Initial small animal studies indicate that these changes in viral gene expression can be associated with enhanced immunopathogenesis in vivo . Available evidence suggests the hypothesis that there is a critical threshold of expression of certain viral genes that determines both the sustainability of viral transmission in the human population and the enhancement of immunopathogenesis. Studies of this possibility will require extension of the analysis of outbreak viral strains from a sequencing-based focus to biological studies of relationships between viral gene expression and pathogenic responses. Advances in this area will require increased coordination among public health organizations, diagnostic microbiology laboratories, and research laboratories to identify, catalog, and systematically study differences between prototype and emergent viral strains that explain the increased pathogenicity that can occur during clinical outbreaks.

Revisiting and Computing Reaction Coordinates with Directional Milestoning

PubMed Central

Kirmizialtin, Serdal; Elber, Ron

2011-01-01

The method of Directional Milestoning is revisited. We start from an exact and more general expression and state the conditions and validity of the memory-loss approximation. An algorithm to compute a reaction coordinate from Directional Milestoning data is presented. The reaction coordinate is calculated as a set of discrete jumps between Milestones that maximizes the flux between two stable states. As an application we consider a conformational transition in solvated Adenosine. We compare a long molecular dynamic trajectory with Directional Milestoning and discuss the differences between the maximum flux path and minimum energy coordinates. PMID:21500798

CD146 coordinates brain endothelial cell–pericyte communication for blood–brain barrier development

PubMed Central

Chen, Jianan; Luo, Yongting; Hui, Hui; Cai, Tanxi; Huang, Hongxin; Yang, Fuquan; Feng, Jing; Zhang, Jingjing; Yan, Xiyun

2017-01-01

The blood–brain barrier (BBB) establishes a protective interface between the central neuronal system and peripheral blood circulation and is crucial for homeostasis of the CNS. BBB formation starts when the endothelial cells (ECs) invade the CNS and pericytes are recruited to the nascent vessels during embryogenesis. Despite the essential function of pericyte–EC interaction during BBB development, the molecular mechanisms coordinating the pericyte–EC behavior and communication remain incompletely understood. Here, we report a single cell receptor, CD146, that presents dynamic expression patterns in the cerebrovasculature at the stages of BBB induction and maturation, coordinates the interplay of ECs and pericytes, and orchestrates BBB development spatiotemporally. In mouse brain, CD146 is first expressed in the cerebrovascular ECs of immature capillaries without pericyte coverage; with increased coverage of pericytes, CD146 could only be detected in pericytes, but not in cerebrovascular ECs. Specific deletion of Cd146 in mice ECs resulted in reduced brain endothelial claudin-5 expression and BBB breakdown. By analyzing mice with specific deletion of Cd146 in pericytes, which have defects in pericyte coverage and BBB integrity, we demonstrate that CD146 functions as a coreceptor of PDGF receptor-β to mediate pericyte recruitment to cerebrovascular ECs. Moreover, we found that the attached pericytes in turn down-regulate endothelial CD146 by secreting TGF-β1 to promote further BBB maturation. These results reveal that the dynamic expression of CD146 controls the behavior of ECs and pericytes, thereby coordinating the formation of a mature and stable BBB. PMID:28827364

Zygotic Genome Activation in Vertebrates.

PubMed

Jukam, David; Shariati, S Ali M; Skotheim, Jan M

2017-08-21

The first major developmental transition in vertebrate embryos is the maternal-to-zygotic transition (MZT) when maternal mRNAs are degraded and zygotic transcription begins. During the MZT, the embryo takes charge of gene expression to control cell differentiation and further development. This spectacular organismal transition requires nuclear reprogramming and the initiation of RNAPII at thousands of promoters. Zygotic genome activation (ZGA) is mechanistically coordinated with other embryonic events, including changes in the cell cycle, chromatin state, and nuclear-to-cytoplasmic component ratios. Here, we review progress in understanding vertebrate ZGA dynamics in frogs, fish, mice, and humans to explore differences and emphasize common features. Copyright © 2017 Elsevier Inc. All rights reserved.

Researcher perspectives on competencies of return-to-work coordinators.

PubMed

Gardner, Bethany T; Pransky, Glenn; Shaw, William S; Hong, Qua Nha; Loisel, Patrick

2010-01-01

Return-to-work (RTW) coordination programs are successful in reducing long-term work disability, but research reports have not adequately described the role and competencies of the RTW coordinator. This study was conducted to clarify the impact of RTW coordinators, and competencies (knowledge, skills, and attitudes) required to achieve optimal RTW outcomes in injured workers. Studies involving RTW coordination for injured workers were identified through literature review. Semi-structured interviews were conducted with 12 principal investigators to obtain detailed information about the RTW coordinator role and competencies not included in published articles. Interview results were synthesized into principal conceptual groups by affinity mapping. All investigators strongly endorsed the role of RTW coordinator as key to the program's success. Affinity mapping identified 10 groups of essential competencies: (1) individual traits/qualities, (2) relevant knowledge base, (3) RTW focus and attitude, (4) organizational/administrative skills, (5) assessment skills, (6) communication skills, (7) interpersonal relationship skills, (8) conflict resolution skills, (9) problem-solving skills, and (10) RTW facilitation skills. Specific consensus competencies were identified within each affinity group. Most investigators endorsed similar competencies, although there was some variation by setting or scope of RTW intervention. RTW coordinators are essential contributors in RTW facilitation programs. This study identified specific competencies required to achieve success. More emphasis on mentorship and observation will be required to develop and evaluate necessary skills in this area.

MYC/MIZ1-dependent gene repression inversely coordinates the circadian clock with cell cycle and proliferation.

PubMed

Shostak, Anton; Ruppert, Bianca; Ha, Nati; Bruns, Philipp; Toprak, Umut H; Eils, Roland; Schlesner, Matthias; Diernfellner, Axel; Brunner, Michael

2016-06-24

The circadian clock and the cell cycle are major cellular systems that organize global physiology in temporal fashion. It seems conceivable that the potentially conflicting programs are coordinated. We show here that overexpression of MYC in U2OS cells attenuates the clock and conversely promotes cell proliferation while downregulation of MYC strengthens the clock and reduces proliferation. Inhibition of the circadian clock is crucially dependent on the formation of repressive complexes of MYC with MIZ1 and subsequent downregulation of the core clock genes BMAL1 (ARNTL), CLOCK and NPAS2. We show furthermore that BMAL1 expression levels correlate inversely with MYC levels in 102 human lymphomas. Our data suggest that MYC acts as a master coordinator that inversely modulates the impact of cell cycle and circadian clock on gene expression.

Functional Connectivity of Multiple Brain Regions Required for the Consolidation of Social Recognition Memory.

PubMed

Tanimizu, Toshiyuki; Kenney, Justin W; Okano, Emiko; Kadoma, Kazune; Frankland, Paul W; Kida, Satoshi

2017-04-12

Social recognition memory is an essential and basic component of social behavior that is used to discriminate familiar and novel animals/humans. Previous studies have shown the importance of several brain regions for social recognition memories; however, the mechanisms underlying the consolidation of social recognition memory at the molecular and anatomic levels remain unknown. Here, we show a brain network necessary for the generation of social recognition memory in mice. A mouse genetic study showed that cAMP-responsive element-binding protein (CREB)-mediated transcription is required for the formation of social recognition memory. Importantly, significant inductions of the CREB target immediate-early genes c-fos and Arc were observed in the hippocampus (CA1 and CA3 regions), medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), and amygdala (basolateral region) when social recognition memory was generated. Pharmacological experiments using a microinfusion of the protein synthesis inhibitor anisomycin showed that protein synthesis in these brain regions is required for the consolidation of social recognition memory. These findings suggested that social recognition memory is consolidated through the activation of CREB-mediated gene expression in the hippocampus/mPFC/ACC/amygdala. Network analyses suggested that these four brain regions show functional connectivity with other brain regions and, more importantly, that the hippocampus functions as a hub to integrate brain networks and generate social recognition memory, whereas the ACC and amygdala are important for coordinating brain activity when social interaction is initiated by connecting with other brain regions. We have found that a brain network composed of the hippocampus/mPFC/ACC/amygdala is required for the consolidation of social recognition memory. SIGNIFICANCE STATEMENT Here, we identify brain networks composed of multiple brain regions for the consolidation of social recognition memory. We found that social recognition memory is consolidated through CREB-meditated gene expression in the hippocampus, medial prefrontal cortex, anterior cingulate cortex (ACC), and amygdala. Importantly, network analyses based on c-fos expression suggest that functional connectivity of these four brain regions with other brain regions is increased with time spent in social investigation toward the generation of brain networks to consolidate social recognition memory. Furthermore, our findings suggest that hippocampus functions as a hub to integrate brain networks and generate social recognition memory, whereas ACC and amygdala are important for coordinating brain activity when social interaction is initiated by connecting with other brain regions. Copyright © 2017 the authors 0270-6474/17/374103-14$15.00/0.

48 CFR 952.223-78 - Sustainable acquisition program.

Code of Federal Regulations, 2010 CFR

2010-10-01

... activities with and submit required reports through the Environmental Sustainability Coordinator or... reports through the Environmental Sustainability Coordinator or equivalent position. Reporting under this... prepare and submit performance reports, if required, using prescribed DOE formats, at the end of the...

Continuously differentiable PIC shape functions for triangular meshes

DOE PAGES

Barnes, D. C.

2018-03-21

In this study, a new class of continuously-differentiable shape functions is developed and applied to two-dimensional electrostatic PIC simulation on an unstructured simplex (triangle) mesh. It is shown that troublesome aliasing instabilities are avoided for cold plasma simulation in which the Debye length is as small as 0.01 cell sizes. These new shape functions satisfy all requirements for PIC particle shape. They are non-negative, have compact support, and partition unity. They are given explicitly by cubic expressions in the usual triangle logical (areal) coordinates. The shape functions are not finite elements because their structure depends on the topology of themore » mesh, in particular, the number of triangles neighboring each mesh vertex. Nevertheless, they may be useful as approximations to solution of other problems in which continuity of derivatives is required or desired.« less

Continuously differentiable PIC shape functions for triangular meshes

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

Barnes, D. C.

In this study, a new class of continuously-differentiable shape functions is developed and applied to two-dimensional electrostatic PIC simulation on an unstructured simplex (triangle) mesh. It is shown that troublesome aliasing instabilities are avoided for cold plasma simulation in which the Debye length is as small as 0.01 cell sizes. These new shape functions satisfy all requirements for PIC particle shape. They are non-negative, have compact support, and partition unity. They are given explicitly by cubic expressions in the usual triangle logical (areal) coordinates. The shape functions are not finite elements because their structure depends on the topology of themore » mesh, in particular, the number of triangles neighboring each mesh vertex. Nevertheless, they may be useful as approximations to solution of other problems in which continuity of derivatives is required or desired.« less

47 CFR 25.262 - Licensing and domestic coordination requirements for 17/24 GHz BSS space stations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... requirements for 17/24 GHz BSS space stations. 25.262 Section 25.262 Telecommunication FEDERAL COMMUNICATIONS... Licensing and domestic coordination requirements for 17/24 GHz BSS space stations. (a) Except as described in paragraphs (b), (c) or (e) of this section, applicants seeking to operate a space station in the...

47 CFR 25.262 - Licensing and domestic coordination requirements for 17/24 GHz BSS space stations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... requirements for 17/24 GHz BSS space stations. 25.262 Section 25.262 Telecommunication FEDERAL COMMUNICATIONS... Licensing and domestic coordination requirements for 17/24 GHz BSS space stations. (a) Except as described in paragraphs (b), (c) or (e) of this section, applicants seeking to operate a space station in the...

47 CFR 25.262 - Licensing and domestic coordination requirements for 17/24 GHz BSS space stations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... requirements for 17/24 GHz BSS space stations. 25.262 Section 25.262 Telecommunication FEDERAL COMMUNICATIONS... Licensing and domestic coordination requirements for 17/24 GHz BSS space stations. (a) Except as described in paragraphs (b), (c) or (e) of this section, applicants seeking to operate a space station in the...

47 CFR 25.262 - Licensing and domestic coordination requirements for 17/24 GHz BSS space stations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... requirements for 17/24 GHz BSS space stations. 25.262 Section 25.262 Telecommunication FEDERAL COMMUNICATIONS... Licensing and domestic coordination requirements for 17/24 GHz BSS space stations. (a) Except as described in paragraphs (b), (c) or (e) of this section, applicants seeking to operate a space station in the...

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...

48 CFR 952.223-78 - Sustainable acquisition program.

Code of Federal Regulations, 2014 CFR

2014-10-01

... activities with and submit required reports through the Environmental Sustainability Coordinator or... Prime Contractor's Environmental Sustainability Coordinator at the supported facility. The Subcontractor... reports through the Environmental Sustainability Coordinator or equivalent position. Reporting under this...

48 CFR 952.223-78 - Sustainable acquisition program.

Code of Federal Regulations, 2012 CFR

2012-10-01

... activities with and submit required reports through the Environmental Sustainability Coordinator or... Prime Contractor's Environmental Sustainability Coordinator at the supported facility. The Subcontractor... reports through the Environmental Sustainability Coordinator or equivalent position. Reporting under this...

48 CFR 952.223-78 - Sustainable acquisition program.

Code of Federal Regulations, 2011 CFR

2011-10-01

... activities with and submit required reports through the Environmental Sustainability Coordinator or... Prime Contractor's Environmental Sustainability Coordinator at the supported facility. The Subcontractor... reports through the Environmental Sustainability Coordinator or equivalent position. Reporting under this...

48 CFR 952.223-78 - Sustainable acquisition program.

Code of Federal Regulations, 2013 CFR

2013-10-01

... activities with and submit required reports through the Environmental Sustainability Coordinator or... Prime Contractor's Environmental Sustainability Coordinator at the supported facility. The Subcontractor... reports through the Environmental Sustainability Coordinator or equivalent position. Reporting under this...

Deception Detection in Multicultural Coalitions: Foundations for a Cognitive Model

DTIC Science & Technology

2011-06-01

and spontaneous vs. deliberate and contrived facial expression of emotions , symmetry, leakage through microexpressions, hand postures, dynamic...sequences of visually detectable cues , such as facial muscle-group coordination and correlations expressed as changes in facial expressions and face...concert, whereas facial expressions of deceivers emphasize a few cues that arise more randomly and chaotically [15]. A smile without the use of

Inactivation of Pde8b enhances memory, motor performance, and protects against age-induced motor coordination decay

PubMed Central

Tsai, Li-Chun Lisa; Chan, Guy Chiu-Kai; Nangle, Shannon N.; Shimizu-Albergine, Masami; Jones, Graham; Storm, Daniel R.; Beavo, Joseph A.; Zweifel, Larry S.

2012-01-01

Phosphodiesterases (PDEs) are critical regulatory enzymes in cyclic nucleotide signaling. PDEs have diverse expression patterns within the central nervous system (CNS), show differing affinities for cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), and regulate a vast array of behaviors. Here, we investigated the expression profile of the PDE8 gene family members Pde8a and Pde8b in the mouse brain. We find that Pde8a expression is largely absent in the CNS; by contrast, Pde8b is expressed in select regions of the hippocampus, ventral striatum, and cerebellum. Behavioral analysis of mice with Pde8b gene inactivation (PDE8B KO) demonstrate an enhancement in contextual fear, spatial memory, performance in an appetitive instrumental conditioning task, motor-coordination, and have an attenuation of age-induced motor coordination decline. In addition to improvements observed in select behaviors, we find basal anxiety levels to be increased in PDE8B KO mice. These findings indicate that selective antagonism of PDE8B may be an attractive target for enhancement of cognitive and motor functions; however, possible alterations in affective state will need to be weighed against potential therapeutic value. PMID:22925203

Spatially coordinated dynamic gene transcription in living pituitary tissue

PubMed Central

Featherstone, Karen; Hey, Kirsty; Momiji, Hiroshi; McNamara, Anne V; Patist, Amanda L; Woodburn, Joanna; Spiller, David G; Christian, Helen C; McNeilly, Alan S; Mullins, John J; Finkenstädt, Bärbel F; Rand, David A; White, Michael RH; Davis, Julian RE

2016-01-01

Transcription at individual genes in single cells is often pulsatile and stochastic. A key question emerges regarding how this behaviour contributes to tissue phenotype, but it has been a challenge to quantitatively analyse this in living cells over time, as opposed to studying snap-shots of gene expression state. We have used imaging of reporter gene expression to track transcription in living pituitary tissue. We integrated live-cell imaging data with statistical modelling for quantitative real-time estimation of the timing of switching between transcriptional states across a whole tissue. Multiple levels of transcription rate were identified, indicating that gene expression is not a simple binary ‘on-off’ process. Immature tissue displayed shorter durations of high-expressing states than the adult. In adult pituitary tissue, direct cell contacts involving gap junctions allowed local spatial coordination of prolactin gene expression. Our findings identify how heterogeneous transcriptional dynamics of single cells may contribute to overall tissue behaviour. DOI: http://dx.doi.org/10.7554/eLife.08494.001 PMID:26828110

Activin receptor inhibition by Smad2 regulates Drosophila wing disc patterning through BMP-response elements

PubMed Central

Peterson, Aidan J.; O'Connor, Michael B.

2013-01-01

Imaginal disc development in Drosophila requires coordinated cellular proliferation and tissue patterning. In our studies of TGFβ superfamily signaling components, we found that a protein null mutation of Smad2, the only Activin subfamily R-Smad in the fruit fly, produces overgrown wing discs that resemble gain of function for BMP subfamily signaling. The wing discs are expanded specifically along the anterior-posterior axis, with increased proliferation in lateral regions. The morphological defect is not observed in mutants for the TGFβ receptor baboon, and epistasis tests showed that baboon is epistatic to Smad2 for disc overgrowth. Rescue experiments indicate that Baboon binding, but not canonical transcription factor activity, of Smad2 is required for normal disc growth. Smad2 mutant discs generate a P-Mad stripe that is narrower and sharper than the normal gradient, and activation targets are correspondingly expressed in narrowed domains. Repression targets of P-Mad are profoundly mis-regulated, with brinker and pentagone reporter expression eliminated in Smad2 mutants. Loss of expression requires a silencer element previously shown to be controlled by BMP signaling. Epistasis experiments show that Baboon, Mad and Schnurri are required to mediate the ectopic silencer output in the absence of Smad2. Taken together, our results show that loss of Smad2 permits promiscuous Baboon activity, which represses genes subject to control by Mad-dependent silencer elements. The absence of Brinker and Pentagone in Smad2 mutants explains the compound wing disc phenotype. Our results highlight the physiological relevance of substrate inhibition of a kinase, and reveal a novel interplay between the Activin and BMP pathways. PMID:23293296

Does stress remove the HDAC brakes for the formation and persistence of long-term memory?

PubMed

White, André O; Wood, Marcelo A

2014-07-01

It has been known for numerous decades that gene expression is required for long-lasting forms of memory. In the past decade, the study of epigenetic mechanisms in memory processes has revealed yet another layer of complexity in the regulation of gene expression. Epigenetic mechanisms do not only provide complexity in the protein regulatory complexes that control coordinate transcription for specific cell function, but the epigenome encodes critical information that integrates experience and cellular history for specific cell functions as well. Thus, epigenetic mechanisms provide a unique mechanism of gene expression regulation for memory processes. This may be why critical negative regulators of gene expression, such as histone deacetylases (HDACs), have powerful effects on the formation and persistence of memory. For example, HDAC inhibition has been shown to transform a subthreshold learning event into robust long-term memory and also generate a form of long-term memory that persists beyond the point at which normal long-term memory fails. A key question that is explored in this review, from a learning and memory perspective, is whether stress-dependent signaling drives the formation and persistence of long-term memory via HDAC-dependent mechanisms. Copyright © 2013 Elsevier Inc. All rights reserved.

Does stress remove the HDAC brakes for the formation and persistence of long-term memory?

PubMed Central

White, André O.; Wood, Marcelo A.

2013-01-01

It has been known for numerous decades that gene expression is required for long-lasting forms of memory. In the past decade, the study of epigenetic mechanisms in memory processes has revealed yet another layer of complexity in the regulation of gene expression. Epigenetic mechanisms do not only provide complexity in the protein regulatory complexes that control coordinate transcription for specific cell function, but the epigenome encodes critical information that integrates experience and cellular history for specific cell functions as well. Thus, epigenetic mechanisms provide a unique mechanism of gene expression regulation for memory processes. This may be why critical negative regulators of gene expression, such as histone deacetylases (HDACs), have powerful effects on the formation and persistence of memory. For example, HDAC inhibition has been shown to transform a subthreshold learning event into robust long-term memory and also generate a form of long-term memory that persists beyond the point at which normal long-term memory fails. A key question that is explored in this review, from a learning and memory perspective, is whether stress-dependent signaling drives the formation and persistence of long-term memory via HDAC-dependent mechanisms. PMID:24149059

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

Focal shift and the axial optical coordinate for high-aperture systems of finite Fresnel number.

PubMed

Sheppard, Colin J R; Török, Peter

2003-11-01

Analytic expressions are given for the on-axis intensity predicted by the Rayleigh-Sommerfeld and Kirchhoff diffraction integrals for a scalar optical system of high numerical aperture and finite value of Fresnel number. A definition of the axial optical coordinate is introduced that is valid for finite values of Fresnel number, for high-aperture systems, and for observation points distant from the focus. The focal shift effect is reexamined. For the case when the focal shift is small, explicit expressions are given for the focal shift and the axial peak in intensity.

Structural and Functional Coordination of DNA and Histone Methylation

PubMed Central

Cheng, Xiaodong

2014-01-01

One of the most fundamental questions in the control of gene expression in mammals is how epigenetic methylation patterns of DNA and histones are established, erased, and recognized. This central process in controlling gene expression includes coordinated covalent modifications of DNA and its associated histones. This article focuses on structural aspects of enzymatic activities of histone (arginine and lysine) methylation and demethylation and functional links between the methylation status of the DNA and histones. An interconnected network of methyltransferases, demethylases, and accessory proteins is responsible for changing or maintaining the modification status of specific regions of chromatin. PMID:25085914

Streamlining Collaborative Planning in Spacecraft Mission Architectures

NASA Technical Reports Server (NTRS)

Misra, Dhariti; Bopf, Michel; Fishman, Mark; Jones, Jeremy; Kerbel, Uri; Pell, Vince

2000-01-01

During the past two decades, the planning and scheduling community has substantially increased the capability and efficiency of individual planning and scheduling systems. Relatively recently, research work to streamline collaboration between planning systems is gaining attention. Spacecraft missions stand to benefit substantially from this work as they require the coordination of multiple planning organizations and planning systems. Up to the present time this coordination has demanded a great deal of human intervention and/or extensive custom software development efforts. This problem will become acute with increased requirements for cross-mission plan coordination and multi -spacecraft mission planning. The Advanced Architectures and Automation Branch of NASA's Goddard Space Flight Center is taking innovative steps to define collaborative planning architectures, and to identify coordinated planning tools for Cross-Mission Campaigns. Prototypes are being developed to validate these architectures and assess the usefulness of the coordination tools by the planning community. This presentation will focus on one such planning coordination too], named Visual Observation Layout Tool (VOLT), which is currently being developed to streamline the coordination between astronomical missions

45 CFR 1340.4 - Coordination requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND FAMILIES, CHILD ABUSE AND NEGLECT PREVENTION AND TREATMENT PROGRAM CHILD ABUSE AND NEGLECT PREVENTION AND TREATMENT General Provisions § 1340.4 Coordination requirements. All Federal agencies responsible for programs related to child...

47 CFR 25.111 - Additional information.

Code of Federal Regulations, 2010 CFR

2010-10-01

... information it requires for the Advance Publication, Coordination and Notification of frequency assignments... information required by the ITU Radiocommunication Bureau to advance publish, coordinate and notify the frequencies to be used for tracking, telemetry and control functions of DBS systems. [56 FR 24016, May 28...

45 CFR 1340.4 - Coordination requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

..., DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND FAMILIES, CHILD ABUSE AND NEGLECT PREVENTION AND TREATMENT PROGRAM CHILD ABUSE AND NEGLECT PREVENTION AND TREATMENT General Provisions § 1340.4 Coordination requirements. All Federal agencies responsible for programs related to child...

45 CFR 1340.4 - Coordination requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

..., DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND FAMILIES, CHILD ABUSE AND NEGLECT PREVENTION AND TREATMENT PROGRAM CHILD ABUSE AND NEGLECT PREVENTION AND TREATMENT General Provisions § 1340.4 Coordination requirements. All Federal agencies responsible for programs related to child...

45 CFR 1340.4 - Coordination requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

..., DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND FAMILIES, CHILD ABUSE AND NEGLECT PREVENTION AND TREATMENT PROGRAM CHILD ABUSE AND NEGLECT PREVENTION AND TREATMENT General Provisions § 1340.4 Coordination requirements. All Federal agencies responsible for programs related to child...

45 CFR 1340.4 - Coordination requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

..., DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND FAMILIES, CHILD ABUSE AND NEGLECT PREVENTION AND TREATMENT PROGRAM CHILD ABUSE AND NEGLECT PREVENTION AND TREATMENT General Provisions § 1340.4 Coordination requirements. All Federal agencies responsible for programs related to child...

Seeing red; the development of pON.mCherry, a broad-host range constitutive expression plasmid for Gram-negative bacteria.

PubMed

Gebhardt, Michael J; Jacobson, Rachael K; Shuman, Howard A

2017-01-01

The development of plasmid-mediated gene expression control in bacteria revolutionized the field of bacteriology. Many of these expression control systems rely on the addition of small molecules, generally metabolites or non-metabolized analogs thereof, to the growth medium to induce expression of the genes of interest. The paradigmatic example of an expression control system is the lac system from Escherichia coli, which typically relies on the Ptac promoter and the Lac repressor, LacI. In many cases, however, constitutive gene expression is desired, and other experimental approaches require the coordinated control of multiple genes. While multiple systems have been developed for use in E. coli and its close relatives, the utility and/or functionality of these tools does not always translate to other species. For example, for the Gram-negative pathogen, Legionella pneumophila, a causative agent of Legionnaires' Disease, the aforementioned Ptac system represents the only well-established expression control system. In order to enhance the tools available to study bacterial gene expression in L. pneumophila, we developed a plasmid, pON.mCherry, which confers constitutive gene expression from a mutagenized LacI binding site. We demonstrate that pON.mCherry neither interferes with other plasmids harboring an intact LacI-Ptac expression system nor alters the growth of Legionella species during intracellular growth. Furthermore, the broad-host range plasmid backbone of pON.mCherry allows constitutive gene expression in a wide variety of Gram-negative bacterial species, making pON.mCherry a useful tool for the greater research community.

Global analysis of epigenetic regulation of gene expression in response to drought stress in Sorghum.

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

Reddy, Anireddy; Ben-Hur, Asa

Abiotic stresses including drought are major limiting factors of crop yields and cause significant crop losses. Acquisition of stress tolerance to abiotic stresses requires coordinated regulation of a multitude of biochemical and physiological changes, and most of these changes depend on alterations in gene expression. The goal of this work is to perform global analysis of differential regulation of gene expression and alternative splicing, and their relationship with chromatin landscape in drought sensitive and tolerant cultivars. our Iso-Seq study revealed transcriptome-wide full-length isoforms at an unprecedented scale with over 11000 novel splice isoforms. Additionally, we uncovered alternative polyadenylation sites ofmore » ~11000 expressed genes and many novel genes. Overall, Iso-Seq results greatly enhanced sorghum gene annotations that are not only useful in analyzing all our RNA-seq, ChIP-seq and ATAC-seq data but also serve as a great resource to the plant biology community. Our studies identified differentially expressed genes and splicing events that are correlated with the drought-resistant phenotype. An association between alternative splicing and chromatin accessibility was also revealed. Several computational tools developed here (TAPIS and iDiffIR) have been made freely available to the research community in analyzing alternative splicing and differential alternative splicing.« less

Effects of relational coordination among colleagues and span of control on work engagement among home-visiting nurses.

PubMed

Naruse, Takashi; Sakai, Mahiro; Nagata, Satoko

2016-04-01

Home-visiting nursing agencies are required to foster staff nurse's work engagement; thus, the factors related to work engagement require identification. This study examined relational coordination among colleagues and agency span of control on the work engagement of home-visiting nurses. Cross-sectional data from 93 staff nurses in 31 home-visiting nursing agencies were collected via a survey and analyzed using mixed linear regression. There was no significant main effect of relational coordination among nurse colleagues on work engagement. In large agencies with a large span of control, relational coordination among nursing colleagues predicted work engagement. Nursing managers' relational coordination was found to be positively associated with staff nurse work engagement. Agency span of control is a moderating factor on the positive effect of relational coordination with nursing colleagues on staff nurse work engagement. © 2016 Japan Academy of Nursing Science.

Archimedes' Principle in General Coordinates

ERIC Educational Resources Information Center

Ridgely, Charles T.

2010-01-01

Archimedes' principle is well known to state that a body submerged in a fluid is buoyed up by a force equal to the weight of the fluid displaced by the body. Herein, Archimedes' principle is derived from first principles by using conservation of the stress-energy-momentum tensor in general coordinates. The resulting expression for the force is…

Generalization of the Activated Complex Theory of Reaction Rates. II. Classical Mechanical Treatment

DOE R&D Accomplishments Database

Marcus, R. A.

1964-01-01

In its usual classical form activated complex theory assumes a particular expression for the kinetic energy of the reacting system -- one associated with a rectilinear motion along the reaction coordinate. The derivation of the rate expression given in the present paper is based on the general kinetic energy expression.

The influence of asymmetric force requirements on a multi-frequency bimanual coordination task.

PubMed

Kennedy, Deanna M; Rhee, Joohyun; Jimenez, Judith; Shea, Charles H

2017-01-01

An experiment was designed to determine the impact of the force requirements on the production of bimanual 1:2 coordination patterns requiring the same (symmetric) or different (asymmetric) forces when Lissajous displays and goal templates are provided. The Lissajous displays have been shown to minimize the influence of attentional and perceptual constraints allowing constraints related to neural crosstalk to be more clearly observed. Participants (N=20) were randomly assigned to a force condition in which the left or right limb was required to produce more force than the contralateral limb. In each condition participants were required to rhythmically coordinate the pattern of isometric forces in a 1:2 coordination pattern. Participant performed 13 practice trials and 1 test trial per force level. The results indicated that participants were able to effectively coordinate the 1:2 multi-frequency goal patterns under both symmetric and asymmetric force requirements. However, consistent distortions in the force and force velocity time series were observed for one limb that appeared to be associated with the production of force in the contralateral limb. Distortions in the force produced by the left limb occurred regardless of the force requirements of the task (symmetric, asymmetric) or whether the left or right limb had to produce more force than the contralateral limb. However, distinct distortions in the right limb occurred only when the left limb was required to produce 5 times more force than the right limb. These results are consistent with the notion that neural crosstalk can influence both limbs, but may manifest differently for each limb depending on the force requirements of the task. Copyright © 2016 Elsevier B.V. All rights reserved.

Easing The Calculation Of Bolt-Circle Coordinates

NASA Technical Reports Server (NTRS)

Burley, Richard K.

1995-01-01

Bolt Circle Calculation (BOLT-CALC) computer program used to reduce significant time consumed in manually computing trigonometry of rectangular Cartesian coordinates of holes in bolt circle as shown on blueprint or drawing. Eliminates risk of computational errors, particularly in cases involving many holes or in cases in which coordinates expressed to many significant digits. Program assists in many practical situations arising in machine shops. Written in BASIC. Also successfully compiled and implemented by use of Microsoft's QuickBasic v4.0.

A space-time tensor formulation for continuum mechanics in general curvilinear, moving, and deforming coordinate systems

NASA Technical Reports Server (NTRS)

Avis, L. M.

1976-01-01

Tensor methods are used to express the continuum equations of motion in general curvilinear, moving, and deforming coordinate systems. The space-time tensor formulation is applicable to situations in which, for example, the boundaries move and deform. Placing a coordinate surface on such a boundary simplifies the boundary condition treatment. The space-time tensor formulation is also applicable to coordinate systems with coordinate surfaces defined as surfaces of constant pressure, density, temperature, or any other scalar continuum field function. The vanishing of the function gradient components along the coordinate surfaces may simplify the set of governing equations. In numerical integration of the equations of motion, the freedom of motion of the coordinate surfaces provides a potential for enhanced resolution of the continuum field function. An example problem of an incompressible, inviscid fluid with a top free surface is considered, where the surfaces of constant pressure (including the top free surface) are coordinate surfaces.

High level continuity for coordinate generation with precise controls

NASA Technical Reports Server (NTRS)

Eiseman, P. R.

1982-01-01

Coordinate generation techniques with precise local controls have been derived and analyzed for continuity requirements up to both the first and second derivatives, and have been projected to higher level continuity requirements from the established pattern. The desired local control precision was obtained when a family of coordinate surfaces could be uniformly distributed without a consequent creation of flat spots on the coordinate curves transverse to the family. Relative to the uniform distribution, the family could be redistributed from an a priori distribution function or from a solution adaptive approach, both without distortion from the underlying transformation which may be independently chosen to fit a nontrivial geometry and topology.

Brain coordination dynamics: True and false faces of phase synchrony and metastability

PubMed Central

Tognoli, Emmanuelle; Kelso, J.A. Scott

2009-01-01

Understanding the coordination of multiple parts in a complex system such as the brain is a fundamental challenge. We present a theoretical model of cortical coordination dynamics that shows how brain areas may cooperate (integration) and at the same time retain their functional specificity (segregation). This model expresses a range of desirable properties that the brain is known to exhibit, including self-organization, multi-functionality, metastability and switching. Empirically, the model motivates a thorough investigation of collective phase relationships among brain oscillations in neurophysiological data. The most serious obstacle to interpreting coupled oscillations as genuine evidence of inter-areal coordination in the brain stems from volume conduction of electrical fields. Spurious coupling due to volume conduction gives rise to zero-lag (inphase) and antiphase synchronization whose magnitude and persistence obscure the subtle expression of real synchrony. Through forward modeling and the help of a novel colorimetric method, we show how true synchronization can be deciphered from continuous EEG patterns. Developing empirical efforts along the lines of continuous EEG analysis constitutes a major response to the challenge of understanding how different brain areas work together. Key predictions of cortical coordination dynamics can now be tested thereby revealing the essential modus operandi of the intact living brain. PMID:18938209

From Adult Finger Tapping to Fetal Heart Beating: Retracing the Role of Coordination in Constituting Agency.

PubMed

Solfo, Alessandro; van Leeuwen, Cees

2018-01-01

Sense of agency can be defined as the self-awareness of bodily movement, whereas extended agency as the self-awareness of affecting, through movement, events concomitant with movement. As a distinctive manifestation of agency, we review Spizzo's effect. This effect arises when agents coordinate their rhythmic movements with visual pulses. Once coordination is established, agents feel controlling the onset or the offset of the pulses through their movements. Spizzo's effect, therefore, constitutes a manifest case of extended agency, in which agents are aware of controlling, through movement, the pulses temporally concomitant with movement. We propose that sense of agency requires continuity of kinesthesia, which in turn requires the continuity of selfhood. The continuity of kinesthesia is necessarily deduced from the consistent kinematics observed in movements, whereas the continuity of selfhood may stem from the patterns of rhythmic coordination that humans encounter ever since intrauterine life. The primacy of these patterns in adults is in accordance with phenomena such as Spizzo's effect, which require coordination to be induced. We, therefore, propose coordination as the fundamental interaction from which selfhood, kinesthesia, and agency arise. Copyright © 2017 Cognitive Science Society, Inc.

IL-1 receptor antagonist-deficient mice develop autoimmune arthritis due to intrinsic activation of IL-17-producing CCR2+Vγ6+γδ T cells

PubMed Central

Akitsu, Aoi; Ishigame, Harumichi; Kakuta, Shigeru; Chung, Soo-hyun; Ikeda, Satoshi; Shimizu, Kenji; Kubo, Sachiko; Liu, Yang; Umemura, Masayuki; Matsuzaki, Goro; Yoshikai, Yasunobu; Saijo, Shinobu; Iwakura, Yoichiro

2015-01-01

Interleukin-17 (IL-17)-producing γδ T (γδ17) cells have been implicated in inflammatory diseases, but the underlying pathogenic mechanisms remain unclear. Here, we show that both CD4+ and γδ17 cells are required for the development of autoimmune arthritis in IL-1 receptor antagonist (IL-1Ra)-deficient mice. Specifically, activated CD4+ T cells direct γδ T-cell infiltration by inducing CCL2 expression in joints. Furthermore, IL-17 reporter mice reveal that the Vγ6+ subset of CCR2+ γδ T cells preferentially produces IL-17 in inflamed joints. Importantly, because IL-1Ra normally suppresses IL-1R expression on γδ T cells, IL-1Ra-deficient mice exhibit elevated IL-1R expression on Vγ6+ cells, which play a critical role in inducing them to produce IL-17. Our findings demonstrate a pathogenic mechanism in which adaptive and innate immunity induce an autoimmune disease in a coordinated manner. PMID:26108163

Linking clinician interaction and coordination to clinical performance in Patient-Aligned Care Teams.

PubMed

Hysong, Sylvia J; Thomas, Candice L; Spitzmüller, Christiane; Amspoker, Amber B; Woodard, LeChauncy; Modi, Varsha; Naik, Aanand D

2016-01-15

Team coordination within clinical care settings is a critical component of effective patient care. Less is known about the extent, effectiveness, and impact of coordination activities among professionals within VA Patient-Aligned Care Teams (PACTs). This study will address these gaps by describing the specific, fundamental tasks and practices involved in PACT coordination, their impact on performance measures, and the role of coordination task complexity. First, we will use a web-based survey of coordination practices among 1600 PACTs in the national VHA. Survey findings will characterize PACT coordination practices and assess their association with clinical performance measures. Functional job analysis, using 6-8 subject matter experts who are 3rd and 4th year residents in VA Primary Care rotations, will be utilized to identify the tasks involved in completing clinical performance measures to standard. From this, expert ratings of coordination complexity will be used to determine the level of coordinative complexity required for each of the clinical performance measures drawn from the VA External Peer Review Program (EPRP). For objective 3, data collected from the first two methods will evaluate the effect of clinical complexity on the relationships between measures of PACT coordination and their ratings on the clinical performance measures. Results from this study will support successful implementation of coordinated team-based work in clinical settings by providing knowledge regarding which aspects of care require the most complex levels of coordination and how specific coordination practices impact clinical performance.

Antagonistic interactions in the zebrafish midline prior to the emergence of asymmetric gene expression are important for left–right patterning

PubMed Central

Grimes, Daniel T.

2016-01-01

Left–right (L-R) asymmetry of the internal organs of vertebrates is presaged by domains of asymmetric gene expression in the lateral plate mesoderm (LPM) during somitogenesis. Ciliated L-R coordinators (LRCs) are critical for biasing the initiation of asymmetrically expressed genes, such as nodal and pitx2, to the left LPM. Other midline structures, including the notochord and floorplate, are then required to maintain these asymmetries. Here we report an unexpected role for the zebrafish EGF-CFC gene one-eyed pinhead (oep) in the midline to promote pitx2 expression in the LPM. Late zygotic oep (LZoep) mutants have strongly reduced or absent pitx2 expression in the LPM, but this expression can be rescued to strong levels by restoring oep in midline structures only. Furthermore, removing midline structures from LZoep embryos can rescue pitx2 expression in the LPM, suggesting the midline is a source of an LPM pitx2 repressor that is itself inhibited by oep. Reducing lefty1 activity in LZoep embryos mimics removal of the midline, implicating lefty1 in the midline-derived repression. Together, this suggests a model where Oep in the midline functions to overcome a midline-derived repressor, involving lefty1, to allow for the expression of left side-specific genes in the LPM. This article is part of the themed issue ‘Provocative questions in left–right asymmetry’. PMID:27821532

The chloroplast division mutant caa33 of Arabidopsis thaliana reveals a crucial impact of chloroplast homeostasis on stress acclimation and retrograde plastid-to-nucleus signaling

PubMed Central

Šimková, Klára; Kim, Chanhong; Gacek, Katarzyna; Baruah, Aiswarya; Laloi, Christophe; Apel, Klaus

2011-01-01

SUMMARY Retrograde plastid-to-nucleus signaling tightly controls and coordinates nuclear and plastid gene expression that is required for plastid biogenesis and chloroplast activities. As chloroplasts act as sensors of environmental changes, plastid-derived signaling also modulates stress responses of plants by transferring stress-related signals and altering nuclear gene expression. Various mutant screens have been undertaken to identify constituents of plastid signaling pathways. Almost all mutations identified in these screens have in common that they target plastid-specific but not extra-plastidic functions. They have been suggested to define either genuine constituents of retrograde signaling pathways or components required for the synthesis of plastid signals. Here we report the characterization of the caa33 (constitutive activator of AAA-ATPase) mutant, which reveals another way of how mutations that affect plastid functions may modulate retrograde plastid signaling. caa33 disturbs a plastid-specific function by impeding plastid division thereby perturbing plastid homeostasis. This results in pre-conditioning plants by activating the expression of stress genes, enhancing pathogen resistance and attenuating the plant’s capacity to respond to plastid signals. Our study reveals an intimate link between chloroplast activity and the plant’s susceptibility to stress and emphasizes the need to consider the possible impact of pre-conditioning on retrograde plastid-to-nucleus signaling. PMID:22014227

Microconnectomics of the pretectum and ventral thalamus in the chicken (Gallus gallus).

PubMed

Vega-Zuniga, Tomas; Marín, Gonzalo; González-Cabrera, Cristian; Planitscher, Eva; Hartmann, Anja; Marks, Vanessa; Mpodozis, Jorge; Luksch, Harald

2016-08-01

The avian pretectal and ventrothalamic nuclei, encompassing the griseum tectale (GT), n. lentiformis mesencephali (LM), and n. geniculatus lateralis pars ventralis (GLv), are prominent retinorecipient structures related to optic flow operations and visuomotor control. Hence, a close coordination of these neural circuits is to be expected. Yet the connectivity among these nuclei is poorly known. Here, using intracellular labeling and in situ hybridization, we investigated the detailed morphology, connectivity, and neurochemical identity of neurons in these nuclei. Two different cell types exist in the GT: one that generates an axonal projection to the optic tectum (TeO), LM, GLv, and n. intercalatus thalami (ICT), and a second population that only projects to the LM and GLv. In situ hybridization revealed that most neurons in the GT express the vesicular glutamate transporter (VGluT2) mRNA, indicating a glutamatergic identity. In the LM, three morphological cell types were defined, two of which project axons towards dorsal targets. The LM neurons showed strong VGluT2 expression. Finally, the cells located in the GLv project to the TeO, LM, GT, n. principalis precommisuralis (PPC), and ICT. All neurons in the GLv showed strong expression of the vesicular inhibitory amino acid transporter (VIAAT) mRNA, suggesting a GABAergic identity. Our results show that the pretectal and ventrothalamic nuclei are highly interconnected, especially by glutamatergic and GABAergic neurons from the GT and GLv, respectively. This complex morphology and connectivity might be required to organize orienting visuomotor behaviors and coordinate the specific optic flow patterns that they induce. J. Comp. Neurol. 524:2208-2229, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Stability of the line preserving flows

NASA Astrophysics Data System (ADS)

Figura, Przemysław

2017-11-01

We examine the equations that are used to describe flows which preserve field lines. We study what happens if we introduce perturbations to the governing equations. The stability of the line preserving flows in the case of the magneto-fluids permeated by magnetic fields is strictly connected to the non-null magnetic reconnection processes. In most of our study we use the Euler potential representation of the external magnetic field. We provide general expressions for the perturbations of the Euler potentials that describe the magnetic field. Similarly, we provide expressions for the case of steady flow as well as we obtain certain conditions required for the stability of the flow. In addition, for steady flows we formulate conditions under which the perturbations of the external field are negligible and the field may be described by its initial unperturbed form. Then we consider the flow equation that transforms quantities from the laboratory coordinate system to the related external field coordinate system. We introduce perturbations to the equation and obtain its simplified versions for the case of a steady flow. For a given system, use of this method allows us to simplify the considerations provided that some part of the system may be described as a perturbation. Next, to study regions favourable for the magnetic reconnection to occur we introduce a deviation vector to the basic line preserving flows condition equation. We provide expressions of the vector for some simplifying cases. This method allows us to examine if given perturbations either stabilise the system or induce magnetic reconnection. To illustrate some of our results we study two examples, namely a simple laboratory plasma flow and a simple planetary magnetosphere model.

N-methylpurine DNA glycosylase inhibits p53-mediated cell cycle arrest and coordinates with p53 to determine sensitivity to alkylating agents

PubMed Central

Song, Shanshan; Xing, Guichun; Yuan, Lin; Wang, Jian; Wang, Shan; Yin, Yuxin; Tian, Chunyan; He, Fuchu; Zhang, Lingqiang

2012-01-01

Alkylating agents induce genome-wide base damage, which is repaired mainly by N-methylpurine DNA glycosylase (MPG). An elevated expression of MPG in certain types of tumor cells confers higher sensitivity to alkylation agents because MPG-induced apurinic/apyrimidic (AP) sites trigger more strand breaks. However, the determinant of drug sensitivity or insensitivity still remains unclear. Here, we report that the p53 status coordinates with MPG to play a pivotal role in such process. MPG expression is positive in breast, lung and colon cancers (38.7%, 43.4% and 25.3%, respectively) but negative in all adjacent normal tissues. MPG directly binds to the tumor suppressor p53 and represses p53 activity in unstressed cells. The overexpression of MPG reduced, whereas depletion of MPG increased, the expression levels of pro-arrest gene downstream of p53 including p21, 14-3-3σ and Gadd45 but not proapoptotic ones. The N-terminal region of MPG was specifically required for the interaction with the DNA binding domain of p53. Upon DNA alkylation stress, in p53 wild-type tumor cells, p53 dissociated from MPG and induced cell growth arrest. Then, AP sites were repaired efficiently, which led to insensitivity to alkylating agents. By contrast, in p53-mutated cells, the AP sites were repaired with low efficacy. To our knowledge, this is the first direct evidence to show that a DNA repair enzyme functions as a selective regulator of p53, and these findings provide new insights into the functional linkage between MPG and p53 in cancer therapy. PMID:22801474

N-methylpurine DNA glycosylase inhibits p53-mediated cell cycle arrest and coordinates with p53 to determine sensitivity to alkylating agents.

PubMed

Song, Shanshan; Xing, Guichun; Yuan, Lin; Wang, Jian; Wang, Shan; Yin, Yuxin; Tian, Chunyan; He, Fuchu; Zhang, Lingqiang

2012-08-01

Alkylating agents induce genome-wide base damage, which is repaired mainly by N-methylpurine DNA glycosylase (MPG). An elevated expression of MPG in certain types of tumor cells confers higher sensitivity to alkylation agents because MPG-induced apurinic/apyrimidic (AP) sites trigger more strand breaks. However, the determinant of drug sensitivity or insensitivity still remains unclear. Here, we report that the p53 status coordinates with MPG to play a pivotal role in such process. MPG expression is positive in breast, lung and colon cancers (38.7%, 43.4% and 25.3%, respectively) but negative in all adjacent normal tissues. MPG directly binds to the tumor suppressor p53 and represses p53 activity in unstressed cells. The overexpression of MPG reduced, whereas depletion of MPG increased, the expression levels of pro-arrest gene downstream of p53 including p21, 14-3-3σ and Gadd45 but not proapoptotic ones. The N-terminal region of MPG was specifically required for the interaction with the DNA binding domain of p53. Upon DNA alkylation stress, in p53 wild-type tumor cells, p53 dissociated from MPG and induced cell growth arrest. Then, AP sites were repaired efficiently, which led to insensitivity to alkylating agents. By contrast, in p53-mutated cells, the AP sites were repaired with low efficacy. To our knowledge, this is the first direct evidence to show that a DNA repair enzyme functions as a selective regulator of p53, and these findings provide new insights into the functional linkage between MPG and p53 in cancer therapy.

A Direct Method for Mapping the Center of Pressure Measured by an Insole Pressure Sensor System to the Shoe's Local Coordinate System.

PubMed

Weaver, Brian T; Braman, Jerrod E; Haut, Roger C

2016-06-01

A direct method to express the center of pressure (CoP) measured by an insole pressure sensor system (IPSS) into a known coordinate system measured by motion tracking equipment is presented. A custom probe was constructed with reflective markers to allow its tip to be precisely tracked with motion tracking equipment. This probe was utilized to activate individual sensors on an IPSS that was placed in a shoe fitted with reflective markers used to establish a local shoe coordinate system. When pressed onto the IPSS the location of the probe's tip was coincident with the CoP measured by the IPSS (IPSS-CoP). Two separate pushes (i.e., data points) were used to develop vectors in each respective coordinate system. Simple vector mathematics determined the rotational and translational components of the transformation matrix needed to express the IPSS-CoP into the local shoe coordinate system. Validation was performed by comparing IPSS-CoP with an embedded force plate measured CoP (FP-CoP) from data gathered during kinematic trials. Six male subjects stood on an embedded FP and performed anterior/posterior (AP) sway, internal rotation, and external rotation of the body relative to a firmly planted foot. The IPSS-CoP was highly correlated with the FP-CoP for all motions, root mean square errors (RMSRRs) were comparable to other research, and there were no statistical differences between the displacement of the IPSS-CoP and FP-CoP for both the AP and medial/lateral (ML) axes, respectively. The results demonstrated that this methodology could be utilized to determine the transformation variables need to express IPSS-CoP into a known coordinate system measured by motion tracking equipment and that these variables can be determined outside the laboratory anywhere motion tracking equipment is available.

Efficient biosynthesis of L-phenylglycine by an engineered Escherichia coli with a tunable multi-enzyme-coordinate expression system.

PubMed

Liu, Qiaoli; Zhou, Junping; Yang, Taowei; Zhang, Xian; Xu, Meijuan; Rao, Zhiming

2018-03-01

Whole-cell catalysis with co-expression of two or more enzymes in a single host as a simple low-cost biosynthesis method has been widely studied and applied but hardly with regulation of multi-enzyme expression. Here we developed an efficient whole-cell catalyst for biosynthesis of L-phenylglycine (L-Phg) from benzoylformic acid through co-expression of leucine dehydrogenase from Bacillus cereus (BcLeuDH) and NAD + -dependent mutant formate dehydrogenase from Candida boidinii (CbFDH A10C ) in Escherichia coli with tunable multi-enzyme-coordinate expression system. By co-expressing one to four copies of CbFDH A10C and optimization of the RBS sequence of BcLeuDH in the expression system, the ratio of BcLeuDH to CbFDH in E. coli BL21/pETDuet-rbs 4 leudh-3fdh A10C was finally regulated to 2:1, which was the optimal one determined by enzyme-catalyzed synthesis. The catalyst activity of E. coli BL21/pETDuet-rbs 4 leudh-3fdh A10C was 28.4 mg L -1  min -1  g -1 dry cell weight for L-Phg production using whole-cell transformation, it's was 3.7 times higher than that of engineered E. coli without enzyme expression regulation. Under optimum conditions (pH 8.0 and 35 °C), 60 g L -1 benzoylformic acid was completely converted to pure chiral L-Phg in 4.5 h with 10 g L -1 dry cells and 50.4 g L -1 ammonium formate, and with enantiomeric excess > 99.9%. This multi-enzyme-coordinate expression system strategy significantly improved L-Phg productivity and demonstrated a novel low-cost method for enantiopure L-Phg production.

Understanding nuclear motions in molecules: Derivation of Eckart frame ro-vibrational Hamiltonian operators via a gateway Hamiltonian operator

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

Szalay, Viktor, E-mail: szalay.viktor@wigner.mta.hu

A new ro-vibrational Hamiltonian operator, named gateway Hamiltonian operator, with exact kinetic energy term, T-hat, is presented. It is in the Eckart frame and it is of the same form as Watson’s normal coordinate Hamiltonian. However, the vibrational coordinates employed are not normal coordinates. The new Hamiltonian is shown to provide easy access to Eckart frame ro-vibrational Hamiltonians with exact T-hat given in terms of any desired set of vibrational coordinates. A general expression of the Eckart frame ro-vibrational Hamiltonian operator is given and some of its properties are discussed.

Light-cone observables and gauge-invariance in the geodesic light-cone formalism

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

Scaccabarozzi, Fulvio; Yoo, Jaiyul, E-mail: fulvio@physik.uzh.ch, E-mail: jyoo@physik.uzh.ch

The remarkable properties of the geodesic light-cone (GLC) coordinates allow analytic expressions for the light-cone observables, providing a new non-perturbative way for calculating the effects of inhomogeneities in our Universe. However, the gauge-invariance of these expressions in the GLC formalism has not been shown explicitly. Here we provide this missing part of the GLC formalism by proving the gauge-invariance of the GLC expressions for the light-cone observables, such as the observed redshift, the luminosity distance, and the physical area and volume of the observed sources. Our study provides a new insight on the properties of the GLC coordinates and itmore » complements the previous work by the GLC collaboration, leading to a comprehensive description of light propagation in the GLC representation.« less

The Ethylene Responsive Factor Required for Nodulation 1 (ERN1) Transcription Factor Is Required for Infection-Thread Formation in Lotus japonicus.

PubMed

Kawaharada, Yasuyuki; James, Euan K; Kelly, Simon; Sandal, Niels; Stougaard, Jens

2017-03-01

Several hundred genes are transcriptionally regulated during infection-thread formation and development of nitrogen-fixing root nodules. We have characterized a set of Lotus japonicus mutants impaired in root-nodule formation and found that the causative gene, Ern1, encodes a protein with a characteristic APETALA2/Ethylene Responsive Factor (AP2/ERF) transcription-factor domain. Phenotypic characterization of four ern1 alleles shows that infection pockets are formed but root-hair infection threads are absent. Formation of root-nodule primordia is delayed and no normal transcellular infection threads are found in the infected nodules. Corroborating the role of ERN1 (ERF Required for Nodulation1) in nodule organogenesis, spontaneous nodulation induced by an autoactive CCaMK and cytokinin-induced nodule primordia were not observed in ern1 mutants. Expression of Ern1 is induced in the susceptible zone by Nod factor treatment or rhizobial inoculation. At the cellular level, the pErn1:GUS reporter is highly expressed in root epidermal cells of the susceptible zone and in the cortical cells that form nodule primordia. The genetic regulation of this cellular expression pattern was further investigated in symbiotic mutants. Nod factor induction of Ern1 in epidermal cells was found to depend on Nfr1, Cyclops, and Nsp2 but was independent of Nin and Nf-ya1. These results suggest that ERN1 functions as a transcriptional regulator involved in the formation of infection threads and development of nodule primordia and may coordinate these two processes.

"The Doctor Needs to Know": Acceptability of Smartphone Location Tracking for Care Coordination.

PubMed

Liss, David T; Serrano, Eloisa; Wakeman, Julie; Nowicki, Christine; Buchanan, David R; Cesan, Ana; Brown, Tiffany

2018-05-04

Care coordination can be highly challenging to carry out. When care is fragmented across health systems and providers, there is an increased likelihood of hospital readmissions and wasteful health care spending. During and after care transitions, smartphones have the potential to bolster information transfer and care coordination. However, little research has examined patients' perceptions of using smartphones to coordinate care. This study's primary objective was to explore patient acceptability of a smartphone app that could facilitate care coordination in a safety net setting. Our secondary objective was to identify how clinicians and other members of primary care teams could use this app to coordinate care. This qualitative study was conducted at a federally qualified health center in metropolitan Chicago, IL. We conducted four focus groups (two in English, two in Spanish) with high-risk adults who owned a smartphone and received services from an organizational care management program. We also conducted structured interviews with clinicians and a group interview with care managers. Focus groups elicited patients' perceptions of a smartphone app designed to: (1) identify emergency department (ED) visits and inpatient stays using real-time location data; (2) send automated notifications (ie, alerts) to users' phones, asking whether they were a patient in the hospital; and (3) send automated messages to primary care teams to notify them about patients' confirmed ED visits and inpatient stays. Focus group transcripts were coded based on emergent themes. Clinicians and care managers were asked about messages they would like to receive from the app. Five main themes emerged in patient focus group discussions. First, participants expressed a high degree of willingness to use the proposed app during inpatient stays. Second, participants expressed varying degrees of willingness to use the app during ED visits, particularly for low acuity ED visits. Third, participants stated their willingness to have their location tracked by the proposed app due to its perceived benefits. Fourth, the most frequently mentioned barriers to acceptability were inconveniences such as "false alarm" notifications and smartphone battery drainage. Finally, there was some tension between how to maximize usability without unnecessarily increasing user burden. Both clinicians and care managers expressed interest in receiving messages from the app at the time of hospital arrival and at discharge. Clinicians were particularly interested in conducting outreach during ED visits and inpatient stays, while care managers expressed more interest in coordinating postdischarge care. High-risk primary care patients in a safety net setting reported a willingness to utilize smartphone location tracking technology to facilitate care coordination. Further research is needed on the development and implementation of new smartphone-based approaches to care coordination. ©David T Liss, Eloisa Serrano, Julie Wakeman, Christine Nowicki, David R Buchanan, Ana Cesan, Tiffany Brown. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 04.05.2018.

STAT4 and T-bet control follicular helper T cell development in viral infections.

PubMed

Weinstein, Jason S; Laidlaw, Brian J; Lu, Yisi; Wang, Jessica K; Schulz, Vincent P; Li, Ningcheng; Herman, Edward I; Kaech, Susan M; Gallagher, Patrick G; Craft, Joe

2018-01-02

Follicular helper T (Tfh) cells promote germinal center (GC) B cell survival and proliferation and guide their differentiation and immunoglobulin isotype switching by delivering contact-dependent and soluble factors, including IL-21, IL-4, IL-9, and IFN-γ. IL-21 and IFN-γ are coexpressed by Tfh cells during viral infections, but transcriptional regulation of these cytokines is not completely understood. In this study, we show that the T helper type 1 cell (Th1 cell) transcriptional regulators T-bet and STAT4 are coexpressed with Bcl6 in Tfh cells after acute viral infection, with a temporal decline in T-bet in the waning response. T-bet is important for Tfh cell production of IFN-γ, but not IL-21, and for a robust GC reaction. STAT4, phosphorylated in Tfh cells upon infection, is required for expression of T-bet and Bcl6 and for IFN-γ and IL-21. These data indicate that T-bet is expressed with Bcl6 in Tfh cells and is required alongside STAT4 to coordinate Tfh cell IL-21 and IFN-γ production and for promotion of the GC response after acute viral challenge. © 2018 Weinstein et al.

Towards Using Reo for Compliance-Aware Business Process Modeling

NASA Astrophysics Data System (ADS)

Arbab, Farhad; Kokash, Natallia; Meng, Sun

Business process modeling and implementation of process supporting infrastructures are two challenging tasks that are not fully aligned. On the one hand, languages such as Business Process Modeling Notation (BPMN) exist to capture business processes at the level of domain analysis. On the other hand, programming paradigms and technologies such as Service-Oriented Computing (SOC) and web services have emerged to simplify the development of distributed web systems that underly business processes. BPMN is the most recognized language for specifying process workflows at the early design steps. However, it is rather declarative and may lead to the executable models which are incomplete or semantically erroneous. Therefore, an approach for expressing and analyzing BPMN models in a formal setting is required. In this paper we describe how BPMN diagrams can be represented by means of a semantically precise channel-based coordination language called Reo which admits formal analysis using model checking and bisimulation techniques. Moreover, since additional requirements may come from various regulatory/legislative documents, we discuss the opportunities offered by Reo and its mathematical abstractions for expressing process-related constraints such as Quality of Service (QoS) or time-aware conditions on process states.

Algebra of constraints for a string in curved background

NASA Astrophysics Data System (ADS)

Wess, Julius

1990-06-01

A string field theory with curved background develops anomalies and Schwinger terms in the conformal algebra. It is generally believed that these Schwinger terms and anomalies are expressible in terms of the curvature tensor of the background metric 1 and that, therefore, they are covariant under a change of coordinates in the target space. As far as I know, all the relevant computations have been done in special gauges, i.e. in Riemann normal coordinates. The question remains whether this is true in any gauge. We have tried to investigate this problem in a Hamiltonian formulation of the model. A classical Lagrangian serves to define the canonical variables and the classical constraints. They are expressed in terms of the canonical variables and, classically, they are first class. When quantized, an ordering prescription has to be imposed which leads to anomalies and Schwinger terms. We then try to redefine the constraints in such a way that the Schwinger terms depend on the curvature tensor only. The redefinition of the constraints is limited by the requirement that it should be local and that the energy momentum tensor should be conserved. In our approach, it is natural that the constraints are improved, order by order, in the number of derivatives: we find that, up to third order in the derivatives, Schwinger terms and anomalies are expressible in terms of the curvature tensor. In the fourth order of the derivaties however, we find a contribution to the Schwinger terms that cannot be removed by a redefinition and that cannot be cast in a covariant form. The anomaly on the other hand is fully expressible in terms of the curvature scalar. The energy momentum tensor ceases to be symmetric which indicates a Lorentz anomaly as well. The question remains if the Schwinger terms take a covariant form if we allow Einstein anomalies as well 2.

Biphasic regulation of the transcription factor ABORTED MICROSPORES (AMS) is essential for tapetum and pollen development in Arabidopsis.

PubMed

Ferguson, Alison C; Pearce, Simon; Band, Leah R; Yang, Caiyun; Ferjentsikova, Ivana; King, John; Yuan, Zheng; Zhang, Dabing; Wilson, Zoe A

2017-01-01

Viable pollen is essential for plant reproduction and crop yield. Its production requires coordinated expression at specific stages during anther development, involving early meiosis-associated events and late pollen wall formation. The ABORTED MICROSPORES (AMS) transcription factor is a master regulator of sporopollenin biosynthesis, secretion and pollen wall formation in Arabidopsis. Here we show that it has complex regulation and additional essential roles earlier in pollen formation. An inducible-AMS reporter was created for functional rescue, protein expression pattern analysis, and to distinguish between direct and indirect targets. Mathematical modelling was used to create regulatory networks based on wild-type RNA and protein expression. Dual activity of AMS was defined by biphasic protein expression in anther tapetal cells, with an initial peak around pollen meiosis and then later during pollen wall development. Direct AMS-regulated targets exhibit temporal regulation, indicating that additional factors are associated with their regulation. We demonstrate that AMS biphasic expression is essential for pollen development, and defines distinct functional activities during early and late pollen development. Mathematical modelling suggests that AMS may competitively form a protein complex with other tapetum-expressed transcription factors, and that biphasic regulation is due to repression of upstream regulators and promotion of AMS protein degradation. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

MicroRNA-Mediated Down-Regulation of M-CSF Receptor Contributes to Maturation of Mouse Monocyte-Derived Dendritic Cells

PubMed Central

Riepsaame, Joey; van Oudenaren, Adri; den Broeder, Berlinda J. H.; van IJcken, Wilfred F. J.; Pothof, Joris; Leenen, Pieter J. M.

2013-01-01

Dendritic cell (DC) maturation is a tightly regulated process that requires coordinated and timed developmental cues. Here we investigate whether microRNAs are involved in this process. We identify microRNAs in mouse GM-CSF-generated, monocyte-related DC (GM-DC) that are differentially expressed during both spontaneous and LPS-induced maturation and characterize M-CSF receptor (M-CSFR), encoded by the Csf1r gene, as a key target for microRNA-mediated regulation in the final step toward mature DC. MicroRNA-22, -34a, and -155 are up-regulated in mature MHCIIhi CD86hi DC and mediate Csf1r mRNA and protein down-regulation. Experimental inhibition of Csf1r-targeting microRNAs in vitro results not only in sustained high level M-CSFR protein expression but also in impaired DC maturation upon stimulation by LPS. Accordingly, over-expression of Csf1r in GM-DC inhibits terminal differentiation. Taken together, these results show that developmentally regulated microRNAs control Csf1r expression, supplementing previously identified mechanisms that regulate its transcription and protein surface expression. Furthermore, our data indicate a novel function for Csf1r in mouse monocyte-derived DC, showing that down-regulation of M-CSFR expression is essential for final DC maturation. PMID:24198819

32 CFR 555.10 - Coordination requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 3 2013-07-01 2013-07-01 false Coordination requirements. 555.10 Section 555.10 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY MILITARY RESERVATIONS AND... be reported to the designated POC in the Principal Laboratory, with a copy of the notification to...

48 CFR 970.5223-7 - Sustainable acquisition program.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Environmental Sustainability Coordinator or equivalent position. (g) The Contractor shall prepare and submit... Sustainability Coordinator at the supported facility. The Subcontractor will advise the Contractor if it is... coordinate its activities with and submit required reports through the Environmental Sustainability...

48 CFR 970.5223-7 - Sustainable acquisition program.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Environmental Sustainability Coordinator or equivalent position. (g) The Contractor shall prepare and submit... Sustainability Coordinator at the supported facility. The Subcontractor will advise the Contractor if it is... coordinate its activities with and submit required reports through the Environmental Sustainability...

48 CFR 970.5223-7 - Sustainable acquisition program.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Environmental Sustainability Coordinator or equivalent position. (g) The Contractor shall prepare and submit... Sustainability Coordinator at the supported facility. The Subcontractor will advise the Contractor if it is... coordinate its activities with and submit required reports through the Environmental Sustainability...

48 CFR 970.5223-7 - Sustainable acquisition program.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Environmental Sustainability Coordinator or equivalent position. (g) The Contractor shall prepare and submit... Sustainability Coordinator at the supported facility. The Subcontractor will advise the Contractor if it is... coordinate its activities with and submit required reports through the Environmental Sustainability...

Candida albicans Swi/Snf and Mediator Complexes Differentially Regulate Mrr1-Induced MDR1 Expression and Fluconazole Resistance.

PubMed

Liu, Zhongle; Myers, Lawrence C

2017-11-01

Long-term azole treatment of patients with chronic Candida albicans infections can lead to drug resistance. Gain-of-function (GOF) mutations in the transcription factor Mrr1 and the consequent transcriptional activation of MDR1 , a drug efflux coding gene, is a common pathway by which this human fungal pathogen acquires fluconazole resistance. This work elucidates the previously unknown downstream transcription mechanisms utilized by hyperactive Mrr1. We identified the Swi/Snf chromatin remodeling complex as a key coactivator for Mrr1, which is required to maintain basal and induced open chromatin, and Mrr1 occupancy, at the MDR1 promoter. Deletion of snf2 , the catalytic subunit of Swi/Snf, largely abrogates the increases in MDR1 expression and fluconazole MIC observed in MRR1 GOF mutant strains. Mediator positively and negatively regulates key Mrr1 target promoters. Deletion of the Mediator tail module med3 subunit reduces, but does not eliminate, the increased MDR1 expression and fluconazole MIC conferred by MRR1 GOF mutations. Eliminating the kinase activity of the Mediator Ssn3 subunit suppresses the decreased MDR1 expression and fluconazole MIC of the snf2 null mutation in MRR1 GOF strains. Ssn3 deletion also suppresses MDR1 promoter histone displacement defects in snf2 null mutants. The combination of this work with studies on other hyperactive zinc cluster transcription factors that confer azole resistance in fungal pathogens reveals a complex picture where the induction of drug efflux pump expression requires the coordination of multiple coactivators. The observed variations in transcription factor and target promoter dependence of this process may make the search for azole sensitivity-restoring small molecules more complicated. Copyright © 2017 American Society for Microbiology.

Close the gap for vision: The key is to invest on coordination.

PubMed

Hsueh, Ya-seng Arthur; Dunt, David; Anjou, Mitchell D; Boudville, Andrea; Taylor, Hugh

2013-12-01

The study aims to estimate costs required for coordination and case management activities support access to treatment for the three most common eye conditions among Indigenous Australians, cataract, refractive error and diabetic retinopathy. Coordination activities were identified using in-depth interviews, focus groups and face-to-face consultations. Data were collected at 21 sites across Australia. The estimation of costs used salary data from relevant government websites and was organised by diagnosis and type of coordination activity. Urban and remote regions of Australia. Needs-based provision support services to facilitate access to eye care for cataract, refractive error and diabetic retinopathy to Indigenous Australians. Cost (AUD$ in 2011) of equivalent full time (EFT) coordination staff. The annual coordination workforce required for the three eye conditions was 8.3 EFT staff per 10 000 Indigenous Australians. The annual cost of eye care coordination workforce is estimated to be AUD$21 337 012 in 2011. This innovative, 'activity-based' model identified the workforce required to support the provision of eye care for Indigenous Australians and estimated their costs. The findings are of clear value to government funders and other decision makers. The model can potentially be used to estimate staffing and associated costs for other Indigenous and non-Indigenous health needs. © 2013 The Authors. Australian Journal of Rural Health © National Rural Health Alliance Inc.

36 CFR 801.6 - Coordination with requirements under the National Environmental Policy Act (42 U.S.C. 4321 et seq.).

Code of Federal Regulations, 2011 CFR

2011-07-01

... OF THE URBAN DEVELOPMENT ACTION GRANT PROGRAM § 801.6 Coordination with requirements under the... Policy Act apply to the effect that the project will have on the human environment. To the extent that... Environmental Impact Statement (EIS) subject to the time requirements for a draft and final EIS, in which case...

36 CFR 801.6 - Coordination with requirements under the National Environmental Policy Act (42 U.S.C. 4321 et seq.).

Code of Federal Regulations, 2014 CFR

2014-07-01

... OF THE URBAN DEVELOPMENT ACTION GRANT PROGRAM § 801.6 Coordination with requirements under the... Policy Act apply to the effect that the project will have on the human environment. To the extent that... Environmental Impact Statement (EIS) subject to the time requirements for a draft and final EIS, in which case...

36 CFR 801.6 - Coordination with requirements under the National Environmental Policy Act (42 U.S.C. 4321 et seq.).

Code of Federal Regulations, 2012 CFR

2012-07-01

... OF THE URBAN DEVELOPMENT ACTION GRANT PROGRAM § 801.6 Coordination with requirements under the... Policy Act apply to the effect that the project will have on the human environment. To the extent that... Environmental Impact Statement (EIS) subject to the time requirements for a draft and final EIS, in which case...

36 CFR 801.6 - Coordination with requirements under the National Environmental Policy Act (42 U.S.C. 4321 et seq.).

Code of Federal Regulations, 2010 CFR

2010-07-01

... OF THE URBAN DEVELOPMENT ACTION GRANT PROGRAM § 801.6 Coordination with requirements under the... Policy Act apply to the effect that the project will have on the human environment. To the extent that... Environmental Impact Statement (EIS) subject to the time requirements for a draft and final EIS, in which case...

36 CFR § 801.6 - Coordination with requirements under the National Environmental Policy Act (42 U.S.C. 4321 et seq.).

Code of Federal Regulations, 2013 CFR

2013-07-01

... OF THE URBAN DEVELOPMENT ACTION GRANT PROGRAM § 801.6 Coordination with requirements under the... Policy Act apply to the effect that the project will have on the human environment. To the extent that... Environmental Impact Statement (EIS) subject to the time requirements for a draft and final EIS, in which case...

U.S.-India Security Burden-Sharing? The Potential for Coordinated Capacity-Building in the Indian Ocean

DTIC Science & Technology

2013-04-01

their country’s eco - nomic image and prospects. Regardless of terminology, many Bang- ladeshi officers and experts express a desire to coordinate on...put on the back burner for short-term considerations. 2014 Indian central elections – A new Prime Minister in India could inject a very different tone

What to Do Regarding Coordinating Work and the Family.

ERIC Educational Resources Information Center

Ohio State Univ., Columbus. Instructional Materials Lab.

These materials for the curriculum area of coordinating work and family comprise one of six such packages that are part of the Ohio Vocational Consumer/Homemaking Curriculum Guide. The curriculum area or perennial problem, expressed in the title of this document, is divided into two practical problems, i.e., what to do (1) regarding provision of…

Statewide Coordinating Agencies and State Commissions for Federal Programs in Higher Education. A Directory of Professional Personnel. 1969.

ERIC Educational Resources Information Center

Winandy, Donald H.; Marsh, Robert

This is a comprehensive, up-dated directory of professional personnel of state higher education governing or coordinating agencies and state commissions for the administration of certain federal programs relating to higher education. The directory, compiled from questionnaires, originated from a need expressed by many persons in the field for…

Coordination and Human Resource Planning in the Hawaii Visitor Industry.

ERIC Educational Resources Information Center

Hawaii State Commission on Manpower and Full Employment, Honolulu.

This report was undertaken in response to a request by the Sixth Legislature, which expressed its concern with the lack of coordination and overall human resource planning in the visitor industry and that the findings of the January 6-7, 1970 Travel Industry Congress had not been fully implemented. The State Commission on Manpower and Full…

Valence, Covalence, Hypervalence, Oxidation State, and Coordination Number

ERIC Educational Resources Information Center

Smith, Derek W.

2005-01-01

Valence as a numerical measure of an atom's combining power, expressed by the number of bonds it forms in a molecular formulation of the compound in question, was unable to cope with coordination compounds. The covalence of an atom is the nearest model equivalent, but is subject to ambiguity since it often depends on which bonding model is being…

Dlx1/2 and Otp coordinate the production of hypothalamic GHRH- and AgRP-neurons.

PubMed

Lee, Bora; Kim, Janghyun; An, Taekyeong; Kim, Sangsoo; Patel, Esha M; Raber, Jacob; Lee, Soo-Kyung; Lee, Seunghee; Lee, Jae W

2018-05-23

Despite critical roles of the hypothalamic arcuate neurons in controlling the growth and energy homeostasis, the gene regulatory network directing their development remains unclear. Here we report that the transcription factors Dlx1/2 and Otp coordinate the balanced generation of the two functionally related neurons in the hypothalamic arcuate nucleus, GHRH-neurons promoting the growth and AgRP-neurons controlling the feeding and energy expenditure. Dlx1/2-deficient mice show a loss-of-GHRH-neurons and an increase of AgRP-neurons, and consistently develop dwarfism and consume less energy. These results indicate that Dlx1/2 are crucial for specifying the GHRH-neuronal identity and, simultaneously, for suppressing AgRP-neuronal fate. We further show that Otp is required for the generation of AgRP-neurons and that Dlx1/2 repress the expression of Otp by directly binding the Otp gene. Together, our study demonstrates that the identity of GHRH- and AgRP-neurons is synchronously specified and segregated by the Dlx1/2-Otp gene regulatory axis.

A proposed group management scheme for XTP multicast

NASA Technical Reports Server (NTRS)

Dempsey, Bert J.; Weaver, Alfred C.

1990-01-01

The purpose of a group management scheme is to enable its associated transfer layer protocol to be responsive to user determined reliability requirements for multicasting. Group management (GM) must assist the client process in coordinating multicast group membership, allow the user to express the subset of the multicast group that a particular multicast distribution must reach in order to be successful (reliable), and provide the transfer layer protocol with the group membership information necessary to guarantee delivery to this subset. GM provides services and mechanisms that respond to the need of the client process or process level management protocols to coordinate, modify, and determine attributes of the multicast group, especially membership. XTP GM provides a link between process groups and their multicast groups by maintaining a group membership database that identifies members in a name space understood by the underlying transfer layer protocol. Other attributes of the multicast group useful to both the client process and the data transfer protocol may be stored in the database. Examples include the relative dispersion, most recent update, and default delivery parameters of a group.

SIRT3 mediates multi-tissue coupling for metabolic fuel switching.

PubMed

Dittenhafer-Reed, Kristin E; Richards, Alicia L; Fan, Jing; Smallegan, Michael J; Fotuhi Siahpirani, Alireza; Kemmerer, Zachary A; Prolla, Tomas A; Roy, Sushmita; Coon, Joshua J; Denu, John M

2015-04-07

SIRT3 is a member of the Sirtuin family of NAD(+)-dependent deacylases and plays a critical role in metabolic regulation. Organism-wide SIRT3 loss manifests in metabolic alterations; however, the coordinating role of SIRT3 among metabolically distinct tissues is unknown. Using multi-tissue quantitative proteomics comparing fasted wild-type mice to mice lacking SIRT3, innovative bioinformatic analysis, and biochemical validation, we provide a comprehensive view of mitochondrial acetylation and SIRT3 function. We find SIRT3 regulates the acetyl-proteome in core mitochondrial processes common to brain, heart, kidney, liver, and skeletal muscle, but differentially regulates metabolic pathways in fuel-producing and fuel-utilizing tissues. We propose an additional maintenance function for SIRT3 in liver and kidney where SIRT3 expression is elevated to reduce the acetate load on mitochondrial proteins. We provide evidence that SIRT3 impacts ketone body utilization in the brain and reveal a pivotal role for SIRT3 in the coordination between tissues required for metabolic homeostasis. Copyright © 2015 Elsevier Inc. All rights reserved.

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

Role of the PDZ-scaffold protein NHERF1/EBP50 in cancer biology: from signaling regulation to clinical relevance.

PubMed

Vaquero, J; Nguyen Ho-Bouldoires, T H; Clapéron, A; Fouassier, L

2017-06-01

The transmission of cellular information requires fine and subtle regulation of proteins that need to interact in a coordinated and specific way to form efficient signaling networks. The spatial and temporal coordination relies on scaffold proteins. Thanks to protein interaction domains such as PDZ domains, scaffold proteins organize multiprotein complexes enabling the proper transmission of cellular information through intracellular networks. NHERF1/EBP50 is a PDZ-scaffold protein that was initially identified as an organizer and regulator of transporters and channels at the apical side of epithelia through actin-binding ezrin-moesin-radixin proteins. Since, NHERF1/EBP50 has emerged as a major regulator of cancer signaling network by assembling cancer-related proteins. The PDZ-scaffold EBP50 carries either anti-tumor or pro-tumor functions, two antinomic functions dictated by EBP50 expression or subcellular localization. The dual function of NHERF1/EBP50 encompasses the regulation of several major signaling pathways engaged in cancer, including the receptor tyrosine kinases PDGFR and EGFR, PI3K/PTEN/AKT and Wnt-β-catenin pathways.

Interactive and coordinated visualization approaches for biological data analysis.

PubMed

Cruz, António; Arrais, Joel P; Machado, Penousal

2018-03-26

The field of computational biology has become largely dependent on data visualization tools to analyze the increasing quantities of data gathered through the use of new and growing technologies. Aside from the volume, which often results in large amounts of noise and complex relationships with no clear structure, the visualization of biological data sets is hindered by their heterogeneity, as data are obtained from different sources and contain a wide variety of attributes, including spatial and temporal information. This requires visualization approaches that are able to not only represent various data structures simultaneously but also provide exploratory methods that allow the identification of meaningful relationships that would not be perceptible through data analysis algorithms alone. In this article, we present a survey of visualization approaches applied to the analysis of biological data. We focus on graph-based visualizations and tools that use coordinated multiple views to represent high-dimensional multivariate data, in particular time series gene expression, protein-protein interaction networks and biological pathways. We then discuss how these methods can be used to help solve the current challenges surrounding the visualization of complex biological data sets.

Enhancer and Transcription Factor Dynamics during Myeloid Differentiation Reveal an Early Differentiation Block in Cebpa null Progenitors.

PubMed

Pundhir, Sachin; Bratt Lauridsen, Felicia Kathrine; Schuster, Mikkel Bruhn; Jakobsen, Janus Schou; Ge, Ying; Schoof, Erwin Marten; Rapin, Nicolas; Waage, Johannes; Hasemann, Marie Sigurd; Porse, Bo Torben

2018-05-29

Transcription factors PU.1 and CEBPA are required for the proper coordination of enhancer activity during granulocytic-monocytic (GM) lineage differentiation to form myeloid cells. However, precisely how these factors control the chronology of enhancer establishment during differentiation is not known. Through integrated analyses of enhancer dynamics, transcription factor binding, and proximal gene expression during successive stages of murine GM-lineage differentiation, we unravel the distinct kinetics by which PU.1 and CEBPA coordinate GM enhancer activity. We find no evidence of a pioneering function of PU.1 during late GM-lineage differentiation. Instead, we delineate a set of enhancers that gain accessibility in a CEBPA-dependent manner, suggesting a pioneering function of CEBPA. Analyses of Cebpa null bone marrow demonstrate that CEBPA controls PU.1 levels and, unexpectedly, that the loss of CEBPA results in an early differentiation block. Taken together, our data provide insights into how PU.1 and CEBPA functionally interact to drive GM-lineage differentiation. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Tentonin 3/TMEM150c Confers Distinct Mechanosensitive Currents in Dorsal-Root Ganglion Neurons with Proprioceptive Function.

PubMed

Hong, Gyu-Sang; Lee, Byeongjun; Wee, Jungwon; Chun, Hyeyeon; Kim, Hyungsup; Jung, Jooyoung; Cha, Joo Young; Riew, Tae-Ryong; Kim, Gyu Hyun; Kim, In-Beom; Oh, Uhtaek

2016-07-06

Touch sensation or proprioception requires the transduction of mechanical stimuli into electrical signals by mechanoreceptors in the periphery. These mechanoreceptors are equipped with various transducer channels. Although Piezo1 and 2 are mechanically activated (MA) channels with rapid inactivation, MA molecules with other inactivation kinetics have not been identified. Here we report that heterologously expressed Tentonin3 (TTN3)/TMEM150C is activated by mechanical stimuli with distinctly slow inactivation kinetics. Genetic ablation of Ttn3/Tmem150c markedly reduced slowly adapting neurons in dorsal-root ganglion neurons. The MA TTN3 currents were inhibited by known blockers of mechanosensitive ion channels. Moreover, TTN3 was localized in muscle spindle afferents. Ttn3-deficient mice exhibited the loss of coordinated movements and abnormal gait. Thus, TTN3 appears to be a component of a mechanosensitive channel with a slow inactivation rate and contributes to motor coordination. Identification of this gene advances our understanding of the various types of mechanosensations, including proprioception. Copyright © 2016 Elsevier Inc. All rights reserved.

34 CFR 364.26 - What are the requirements for cooperation, coordination, and working relationships?

Code of Federal Regulations, 2010 CFR

2010-07-01

... EDUCATION STATE INDEPENDENT LIVING SERVICES PROGRAM AND CENTERS FOR INDEPENDENT LIVING PROGRAM: GENERAL... 34 Education 2 2010-07-01 2010-07-01 false What are the requirements for cooperation, coordination, and working relationships? 364.26 Section 364.26 Education Regulations of the Offices of the...

34 CFR 364.26 - What are the requirements for cooperation, coordination, and working relationships?

Code of Federal Regulations, 2011 CFR

2011-07-01

... EDUCATION STATE INDEPENDENT LIVING SERVICES PROGRAM AND CENTERS FOR INDEPENDENT LIVING PROGRAM: GENERAL... 34 Education 2 2011-07-01 2010-07-01 true What are the requirements for cooperation, coordination, and working relationships? 364.26 Section 364.26 Education Regulations of the Offices of the...

10 CFR 1021.341 - Coordination with other environmental review requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... environmental review requirements. (a) In accordance with 40 CFR 1500.4(k) and (o), 1502.25, and 1506.4, DOE shall integrate the NEPA process and coordinate NEPA compliance with other environmental review... agencies when necessary or appropriate, to ensure compliance and to avoid delays, and shall incorporate any...

Roadside Judgments in Children with Developmental Co-ordination Disorder

ERIC Educational Resources Information Center

Purcell, Catherine; Wann, John P.; Wilmut, Kate; Poulter, Damian

2011-01-01

As pedestrians, the perceptual ability to accurately judge the relative rate of approaching vehicles and select a suitable crossing gap requires sensitivity to looming. It also requires that crossing judgments are synchronized with motoric capabilities. Previous research has suggested that children with Developmental Co-ordination Disorder (DCD)…

47 CFR 27.73 - WCS, AMT, and Goldstone coordination requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... requirements. 27.73 Section 27.73 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON... must cooperate in good faith in the coordination and deployment of new facilities. WCS licensees must also cooperate in good faith in the selection and use of new station sites and new frequencies when...

47 CFR 27.73 - WCS, AMT, and Goldstone coordination requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... requirements. 27.73 Section 27.73 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON... must cooperate in good faith in the coordination and deployment of new facilities. WCS licensees must also cooperate in good faith in the selection and use of new station sites and new frequencies when...

(De)stabilization of Required and Spontaneous Postural Dynamics with Learning

ERIC Educational Resources Information Center

Faugloire, Elise; Bardy, Benoit G.; Stoffregen, Thomas A.

2009-01-01

The present research examined how learning a new ankle-hip coordination influenced the preexisting postural repertoire. Standing participants learned a new ankle-hip coordination mode (relative phase of 90[degrees]). Before and after practice, postural patterns were evaluated in two different tasks. In the required task, specific ankle-hip…

44 CFR 5.22 - Coordination of publication.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 44 Emergency Management and Assistance 1 2011-10-01 2011-10-01 false Coordination of publication..., DEPARTMENT OF HOMELAND SECURITY GENERAL PRODUCTION OR DISCLOSURE OF INFORMATION Publication of or... of publication. The Chief Counsel, FEMA, is responsible for coordination of FEMA materials required...

44 CFR 5.22 - Coordination of publication.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 44 Emergency Management and Assistance 1 2014-10-01 2014-10-01 false Coordination of publication..., DEPARTMENT OF HOMELAND SECURITY GENERAL PRODUCTION OR DISCLOSURE OF INFORMATION Publication of or... of publication. The Chief Counsel, FEMA, is responsible for coordination of FEMA materials required...

Expression of DISC1-interactome members correlates with cognitive phenotypes related to schizophrenia.

PubMed

Rampino, Antonio; Walker, Rosie May; Torrance, Helen Scott; Anderson, Susan Maguire; Fazio, Leonardo; Di Giorgio, Annabella; Taurisano, Paolo; Gelao, Barbara; Romano, Raffaella; Masellis, Rita; Ursini, Gianluca; Caforio, Grazia; Blasi, Giuseppe; Millar, J Kirsty; Porteous, David John; Thomson, Pippa Ann; Bertolino, Alessandro; Evans, Kathryn Louise

2014-01-01

Cognitive dysfunction is central to the schizophrenia phenotype. Genetic and functional studies have implicated Disrupted-in-Schizophrenia 1 (DISC1), a leading candidate gene for schizophrenia and related psychiatric conditions, in cognitive function. Altered expression of DISC1 and DISC1-interactors has been identified in schizophrenia. Dysregulated expression of DISC1-interactome genes might, therefore, contribute to schizophrenia susceptibility via disruption of molecular systems required for normal cognitive function. Here, the blood RNA expression levels of DISC1 and DISC1-interacting proteins were measured in 63 control subjects. Cognitive function was assessed using neuropsychiatric tests and functional magnetic resonance imaging was used to assess the activity of prefrontal cortical regions during the N-back working memory task, which is abnormal in schizophrenia. Pairwise correlations between gene expression levels and the relationship between gene expression levels and cognitive function and N-back-elicited brain activity were assessed. Finally, the expression levels of DISC1, AKAP9, FEZ1, NDEL1 and PCM1 were compared between 63 controls and 69 schizophrenic subjects. We found that DISC1-interactome genes showed correlated expression in the blood of healthy individuals. The expression levels of several interactome members were correlated with cognitive performance and N-back-elicited activity in the prefrontal cortex. In addition, DISC1 and NDEL1 showed decreased expression in schizophrenic subjects compared to healthy controls. Our findings highlight the importance of the coordinated expression of DISC1-interactome genes for normal cognitive function and suggest that dysregulated DISC1 and NDEL1 expression might, in part, contribute to susceptibility for schizophrenia via disruption of prefrontal cortex-dependent cognitive functions.

Expression of DISC1-Interactome Members Correlates with Cognitive Phenotypes Related to Schizophrenia

PubMed Central

Rampino, Antonio; Walker, Rosie May; Torrance, Helen Scott; Anderson, Susan Maguire; Fazio, Leonardo; Di Giorgio, Annabella; Taurisano, Paolo; Gelao, Barbara; Romano, Raffaella; Masellis, Rita; Ursini, Gianluca; Caforio, Grazia; Blasi, Giuseppe; Millar, J. Kirsty; Porteous, David John; Thomson, Pippa Ann; Bertolino, Alessandro; Evans, Kathryn Louise

2014-01-01

Cognitive dysfunction is central to the schizophrenia phenotype. Genetic and functional studies have implicated Disrupted-in-Schizophrenia 1 (DISC1), a leading candidate gene for schizophrenia and related psychiatric conditions, in cognitive function. Altered expression of DISC1 and DISC1-interactors has been identified in schizophrenia. Dysregulated expression of DISC1-interactome genes might, therefore, contribute to schizophrenia susceptibility via disruption of molecular systems required for normal cognitive function. Here, the blood RNA expression levels of DISC1 and DISC1-interacting proteins were measured in 63 control subjects. Cognitive function was assessed using neuropsychiatric tests and functional magnetic resonance imaging was used to assess the activity of prefrontal cortical regions during the N-back working memory task, which is abnormal in schizophrenia. Pairwise correlations between gene expression levels and the relationship between gene expression levels and cognitive function and N-back-elicited brain activity were assessed. Finally, the expression levels of DISC1, AKAP9, FEZ1, NDEL1 and PCM1 were compared between 63 controls and 69 schizophrenic subjects. We found that DISC1-interactome genes showed correlated expression in the blood of healthy individuals. The expression levels of several interactome members were correlated with cognitive performance and N-back-elicited activity in the prefrontal cortex. In addition, DISC1 and NDEL1 showed decreased expression in schizophrenic subjects compared to healthy controls. Our findings highlight the importance of the coordinated expression of DISC1-interactome genes for normal cognitive function and suggest that dysregulated DISC1 and NDEL1 expression might, in part, contribute to susceptibility for schizophrenia via disruption of prefrontal cortex-dependent cognitive functions. PMID:24940743

The putative hydrolase YycJ (WalJ) affects the coordination of cell division with DNA replication in Bacillus subtilis and may play a conserved role in cell wall metabolism.

PubMed

Biller, Steven J; Wayne, Kyle J; Winkler, Malcolm E; Burkholder, William F

2011-02-01

Bacteria must accurately replicate and segregate their genetic information to ensure the production of viable daughter cells. The high fidelity of chromosome partitioning is achieved through mechanisms that coordinate cell division with DNA replication. We report that YycJ (WalJ), a predicted member of the metallo-β-lactamase superfamily found in most low-G+C Gram-positive bacteria, contributes to the fidelity of cell division in Bacillus subtilis. B. subtilis ΔwalJ (ΔwalJ(Bsu)) mutants divide over unsegregated chromosomes more frequently than wild-type cells, and this phenotype is exacerbated when DNA replication is inhibited. Two lines of evidence suggest that WalJ(Bsu) and its ortholog in the Gram-positive pathogen Streptococcus pneumoniae, WalJ(Spn) (VicX), play a role in cell wall metabolism: (i) strains of B. subtilis and S. pneumoniae lacking walJ exhibit increased sensitivity to a narrow spectrum of cephalosporin antibiotics, and (ii) reducing the expression of a two-component system that regulates genes involved in cell wall metabolism, WalRK (YycFG), renders walJ essential for growth in B. subtilis, as observed previously with S. pneumoniae. Together, these results suggest that the enzymatic activity of WalJ directly or indirectly affects cell wall metabolism and is required for accurate coordination of cell division with DNA replication.

Coordinated Flexibility: How Initial Gaze Position Modulates Eye-Hand Coordination and Reaching

ERIC Educational Resources Information Center

Adam, Jos J.; Buetti, Simona; Kerzel, Dirk

2012-01-01

Reaching to targets in space requires the coordination of eye and hand movements. In two experiments, we recorded eye and hand kinematics to examine the role of gaze position at target onset on eye-hand coordination and reaching performance. Experiment 1 showed that with eyes and hand aligned on the same peripheral start location, time lags…

Mapping spontaneous facial expression in people with Parkinson's disease: A multiple case study design.

PubMed

Gunnery, Sarah D; Naumova, Elena N; Saint-Hilaire, Marie; Tickle-Degnen, Linda

2017-01-01

People with Parkinson's disease (PD) often experience a decrease in their facial expressivity, but little is known about how the coordinated movements across regions of the face are impaired in PD. The face has neurologically independent regions that coordinate to articulate distinct social meanings that others perceive as gestalt expressions, and so understanding how different regions of the face are affected is important. Using the Facial Action Coding System, this study comprehensively measured spontaneous facial expression across 600 frames for a multiple case study of people with PD who were rated as having varying degrees of facial expression deficits, and created correlation matrices for frequency and intensity of produced muscle activations across different areas of the face. Data visualization techniques were used to create temporal and correlational mappings of muscle action in the face at different degrees of facial expressivity. Results showed that as severity of facial expression deficit increased, there was a decrease in number, duration, intensity, and coactivation of facial muscle action. This understanding of how regions of the parkinsonian face move independently and in conjunction with other regions will provide a new focus for future research aiming to model how facial expression in PD relates to disease progression, stigma, and quality of life.

4 Hz oscillations synchronize prefrontal-amygdala circuits during fear behaviour

PubMed Central

Karalis, Nikolaos; Dejean, Cyril; Chaudun, Fabrice; Khoder, Suzana; Rozeske, Robert R.; Wurtz, Hélène; Bagur, Sophie; Benchenane, Karim; Sirota, Anton; Courtin, Julien; Herry, Cyril

2016-01-01

Fear expression relies on the coordinated activity of prefrontal and amygdala circuits, yet the mechanisms allowing long-range network synchronization during fear remain unknown. Using a combination of extracellular recordings, pharmacological, and optogenetic manipulations we report that freezing, a behavioural expression of fear, temporally coincides with the development of sustained, internally generated 4 Hz oscillations within prefrontal-amygdala circuits. 4 Hz oscillations predict freezing onset and offset and synchronize prefrontal-amygdala circuits. Optogenetic induction of prefrontal 4 Hz oscillations coordinates prefrontal-amygdala activity and elicits fear behaviour. These results unravel a novel sustained oscillatory mechanism mediating prefrontal-amygdala coupling during fear behaviour. PMID:26878674

beamter/deltaC and the role of Notch ligands in the zebrafish somite segmentation, hindbrain neurogenesis and hypochord differentiation.

PubMed

Jülich, Dörthe; Hwee Lim, Chiaw; Round, Jennifer; Nicolaije, Claudia; Schroeder, Joshua; Davies, Alexander; Geisler, Robert; Lewis, Julian; Jiang, Yun-Jin; Holley, Scott A

2005-10-15

The Tübingen large-scale zebrafish genetic screen completed in 1996 identified a set of five genes required for orderly somite segmentation. Four of them have been molecularly identified and three were found to code for components of the Notch pathway, which are required for the coordinated oscillation of gene expression, known as the segmentation clock, in the presomitic mesoderm (PSM). Here, we show that the final member of the group, beamter (bea), codes for the Notch ligand DeltaC, and we present and characterize two new alleles, including one allele encoding for a protein truncated in the 7th EGF repeat and an allele deleting only the DSL domain which was previously shown to be necessary for ligand function. Interestingly however, when we over-express any of the mutant deltaC mRNAs, we observe antimorphic effects on both hindbrain neurogenesis and hypochord formation. Expression of bea/deltaC oscillates in the PSM, and a triple fluorescent in situ analysis of its oscillation in relation to that of other oscillating genes in the PSM reveals differences in subcellular localization of the oscillating mRNAs in individual cells in different oscillation phases. Mutations in aei/deltaD and bea/deltaC differ in the way they disrupt the oscillating expression of her1 and deltaC. Furthermore, we find that the double mutants have significantly stronger defects in hypochord formation but not in somitogenesis or hindbrain neurogenesis, indicating genetically that the two delta's may function either semi-redundantly or distinctly, depending upon context.

Individual Differences in Algebraic Cognition: Relation to the Approximate Number and Sematic Memory Systems

PubMed Central

Geary, David C.; Hoard, Mary K.; Nugent, Lara; Rouder, Jeffrey N.

2015-01-01

The relation between performance on measures of algebraic cognition and acuity of the approximate number system (ANS) and memory for addition facts was assessed for 171 (92 girls) 9th graders, controlling parental education, sex, reading achievement, speed of numeral processing, fluency of symbolic number processing, intelligence, and the central executive component of working memory. The algebraic tasks assessed accuracy in placing x,y pairs in the coordinate plane, speed and accuracy of expression evaluation, and schema memory for algebra equations. ANS acuity was related to accuracy of placements in the coordinate plane and expression evaluation, but not schema memory. Frequency of fact-retrieval errors was related to schema memory but not coordinate plane or expression evaluation accuracy. The results suggest the ANS may contribute to or is influenced by spatial-numerical and numerical only quantity judgments in algebraic contexts, whereas difficulties in committing addition facts to long-term memory may presage slow formation of memories for the basic structure of algebra equations. More generally, the results suggest different brain and cognitive systems are engaged during the learning of different components of algebraic competence, controlling demographic and domain general abilities. PMID:26255604

Neuroinflammation increases GABAergic tone and impairs cognitive and motor function in hyperammonemia by increasing GAT-3 membrane expression. Reversal by sulforaphane by promoting M2 polarization of microglia.

PubMed

Hernandez-Rabaza, Vicente; Cabrera-Pastor, Andrea; Taoro-Gonzalez, Lucas; Gonzalez-Usano, Alba; Agusti, Ana; Balzano, Tiziano; Llansola, Marta; Felipo, Vicente

2016-04-18

Hyperammonemia induces neuroinflammation and increases GABAergic tone in the cerebellum which contributes to cognitive and motor impairment in hepatic encephalopathy (HE). The link between neuroinflammation and GABAergic tone remains unknown. New treatments reducing neuroinflammation and GABAergic tone could improve neurological impairment. The aims were, in hyperammonemic rats, to assess whether: (a) Enhancing endogenous anti-inflammatory mechanisms by sulforaphane treatment reduces neuroinflammation and restores learning and motor coordination. (b) Reduction of neuroinflammation by sulforaphane normalizes extracellular GABA and glutamate-NO-cGMP pathway and identify underlying mechanisms. (c) Identify steps by which hyperammonemia-induced microglial activation impairs cognitive and motor function and how sulforaphane restores them. We analyzed in control and hyperammonemic rats, treated or not with sulforaphane, (a) learning in the Y maze; (b) motor coordination in the beam walking; (c) glutamate-NO-cGMP pathway and extracellular GABA by microdialysis; (d) microglial activation, by analyzing by immunohistochemistry or Western blot markers of pro-inflammatory (M1) (IL-1b, Iba-1) and anti-inflammatory (M2) microglia (Iba1, IL-4, IL-10, Arg1, YM-1); and (e) membrane expression of the GABA transporter GAT-3. Hyperammonemia induces activation of astrocytes and microglia in the cerebellum as assessed by immunohistochemistry. Hyperammonemia-induced neuroinflammation is associated with increased membrane expression of the GABA transporter GAT-3, mainly in activated astrocytes. This is also associated with increased extracellular GABA in the cerebellum and with motor in-coordination and impaired learning ability in the Y maze. Sulforaphane promotes polarization of microglia from the M1 to the M2 phenotype, reducing IL-1b and increasing IL-4, IL-10, Arg1, and YM-1 in the cerebellum. This is associated with astrocytes deactivation and normalization of GAT-3 membrane expression, extracellular GABA, glutamate-nitric oxide-cGMP pathway, and learning and motor coordination. Neuroinflammation increases GABAergic tone in the cerebellum by increasing GAT-3 membrane expression. This impairs motor coordination and learning in the Y maze. Sulforaphane could be a new therapeutic approach to improve cognitive and motor function in hyperammonemia, hepatic encephalopathy, and other pathologies associated with neuroinflammation by promoting microglia differentiation from M1 to M2.

Epithelial cell integrin β1 is required for developmental angiogenesis in the pituitary gland

PubMed Central

Scully, Kathleen M.; Skowronska-Krawczyk, Dorota; Krawczyk, Michal; Merkurjev, Daria; Taylor, Havilah; Livolsi, Antonia; Tollkuhn, Jessica; Stan, Radu V.; Rosenfeld, Michael G.

2016-01-01

As a key component of the vertebrate neuroendocrine system, the pituitary gland relies on the progressive and coordinated development of distinct hormone-producing cell types and an invading vascular network. The molecular mechanisms that drive formation of the pituitary vasculature, which is necessary for regulated synthesis and secretion of hormones that maintain homeostasis, metabolism, and endocrine function, remain poorly understood. Here, we report that expression of integrin β1 in embryonic pituitary epithelial cells is required for angiogenesis in the developing mouse pituitary gland. Deletion of pituitary epithelial integrin β1 before the onset of angiogenesis resulted in failure of invading endothelial cells to recruit pericytes efficiently, whereas deletion later in embryogenesis led to decreased vascular density and lumen formation. In both cases, lack of epithelial integrin β1 was associated with a complete absence of vasculature in the pituitary gland at birth. Within pituitary epithelial cells, integrin β1 directs a large transcriptional program that includes components of the extracellular matrix and associated signaling factors that are linked to the observed non–cell-autonomous effects on angiogenesis. We conclude that epithelial integrin β1 functions as a critical and canonical regulator of developmental angiogenesis in the pituitary gland, thus providing insight into the long-standing systems biology conundrum of how vascular invasion is coordinated with tissue development. PMID:27810956

Development of an International Clinical Education Extracurricular Experience Through a Collaborative Partnership.

PubMed

Mandich, MaryBeth; Erickson, Mia; Nardella, Beth

2017-01-01

Participating in global health care through international clinical education may enhance the development of cultural competence and professionalism. Many logistical issues need to be resolved in the development of international clinical education experiences that meet program requirements. The purpose of this case report is to describe how a university developed such an experience for students by partnering with Amizade Global Service-Learning (Amizade), an organization that facilitates global learning experiences. Medical, nursing, and pharmacy students were already participating in a 4-week international health-related service learning rotation through Amizade. The preexisting relationship and contractual agreement with the university provided the necessary legal framework. Amizade staff assisted in finding a physical therapist qualified and willing to host a student. The academic coordinator for clinical education at the university and Amizade liaisons determined living arrangements, schedule, clinical settings, and patient population. The selected student had expressed interest and had met all clinical education placement requirements. The academic coordinator for clinical education had ongoing electronic communications with all parties. The student demonstrated predicted attributes of cultural competence and professionalism; through the partnership with Amizade, the student was exposed to several unique interprofessional experiences. The steps used by the university faculty in developing this interprofessional, international clinical education experience through a collaborative partnership may provide guidance for other institutions. © 2017 American Physical Therapy Association

Coordinated activation of the secretory pathway during notochord formation in the Xenopus embryo.

PubMed

Tanegashima, Kosuke; Zhao, Hui; Rebbert, Martha L; Dawid, Igor B

2009-11-01

We compared the transcriptome in the developing notochord of Xenopus laevis embryos with that of other embryonic regions. A coordinated and intense activation of a large set of secretory pathway genes was observed in the notochord, but not in notochord precursors in the axial mesoderm at early gastrula stage. The genes encoding Xbp1 and Creb3l2 were also activated in the notochord. These two transcription factors are implicated in the activation of secretory pathway genes during the unfolded protein response, where cells react to the stress of a build-up of unfolded proteins in their endoplasmic reticulum. Xbp1 and Creb3l2 are differentially expressed but not differentially activated in the notochord. Reduction of expression of Xbp1 or Creb3l2 by injection of antisense morpholinos led to strong deficits in notochord but not somitic muscle development. In addition, the expression of some, but not all, genes encoding secretory proteins was inhibited by injection of xbp1 morpholinos. Furthermore, expression of activated forms of Xbp1 or Creb3l2 in animal explants could activate a similar subset of secretory pathway genes. We conclude that coordinated activation of a battery of secretory pathway genes mediated by Xbp1 and Creb/ATF factors is a characteristic and necessary feature of notochord formation.

Jaw-phonatory coordination in chronic developmental stuttering.

PubMed

Loucks, Torrey M J; De Nil, Luc F; Sasisekaran, Jayanthi

2007-01-01

A deficiency in sensorimotor integration in a person who stutters may be a factor in the pathophysiology of developmental stuttering. To test oral sensorimotor function in adults who stutter, we used a task that requires the coordination of a jaw-opening movement with phonation onset. The task was adapted from previous limb coordination studies, which show that movement coordination depends on intact proprioception. We hypothesized that adult stutterers would show deficient jaw-phonatory coordination relative to control participants. The task required initiation of phonation as a jaw-opening movement passed through a narrow spatial target. Target amplitude and jaw movement speed were varied. The stuttering group showed significantly higher movement error and spatial variability in jaw-phonatory coordination compared to the control group, but group differences in movement velocity or duration were not found. The aberrant jaw-phonatory coordination of the stuttering participants suggests that stuttering is associated with an oral proprioceptive limitation, although, the findings are also consistent with a motor control deficit. As a result of this activity, reader will (1) learn about a hypothesis and evidence supporting the view that a sensorimotor deficit contributes to chronic developmental stuttering and (2) will obtain information about the role of proprioception in multi-articulatory coordination and how it can be tested using an oral-phonatory coordination task.

Boric acid inhibits human prostate cancer cell proliferation.

PubMed

Barranco, Wade T; Eckhert, Curtis D

2004-12-08

The role of boron in biology includes coordinated regulation of gene expression in mixed bacterial populations and the growth and proliferation of higher plants and lower animals. Here we report that boric acid, the dominant form of boron in plasma, inhibits the proliferation of prostate cancer cell lines, DU-145 and LNCaP, in a dose-dependent manner. Non-tumorigenic prostate cell lines, PWR-1E and RWPE-1, and the cancer line PC-3 were also inhibited, but required concentrations higher than observed human blood levels. Studies using DU-145 cells showed that boric acid induced a cell death-independent proliferative inhibition, with little effect on cell cycle stage distribution and mitochondrial function.

Optimal Interception of a Maneuvering Long-range Missile

NASA Astrophysics Data System (ADS)

X. Vinh, Nguyen; T. Kabamba, Pierre; Takehira, Tetsuya

2001-01-01

In a Newtonian central force field, the minimum-fuel interception of a satellite, or a ballistic missile, in elliptic trajectory can be obtained via Lawden's theory of primer vector. To secure interception when the target performs evasive maneuvers, a new control law, with explicit solutions, is implemented. It is shown that by a rotation of coordinate system, the problem of three-dimensional interception is reduced to a planar problem. The general case of planar interception of a long-range ballistic missile is then studied. Examples of interception at a specified time, head-on interception and minimum-fuel interception are presented. In each case, the requirement for the thrust acceleration is expressed explicitly as a function of time.

Enhancer competition between H19 and Igf2 does not mediate their imprinting

PubMed Central

Schmidt, Jennifer V.; Levorse, John M.; Tilghman, Shirley M.

1999-01-01

The linked H19 and Igf2 genes on mouse distal chromosome 7 are subject to genomic imprinting. Competition between the promoters of the genes for transcription from shared enhancers has been proposed as an explanation for the coordinate expression and reciprocal imprinting of these two genes. To test this model, we have used Cre-loxP technology to generate in mice a conditional deletion of the H19 promoter and structural gene that leaves no transcription unit in the locus. Contrary to the prediction of enhancer competition we find that transcriptional activity from the H19 promoter is not required for the imprinted silencing of the Igf2 gene. PMID:10449763

Expression of Tlx in both stem cells and transit amplifying progenitors regulates stem cell activation and differentiation in the neonatal lateral subependymal zone.

PubMed

Obernier, Kirsten; Simeonova, Ina; Fila, Tatiana; Mandl, Claudia; Hölzl-Wenig, Gabriele; Monaghan-Nichols, Paula; Ciccolini, Francesca

2011-09-01

Niche homeostasis in the postnatal subependymal zone of the lateral ventricle (lSEZ) requires coordinated proliferation and differentiation of neural progenitor cells. The mechanisms regulating this balance are scarcely known. Recent observations indicate that the orphan nuclear receptor Tlx is an intrinsic factor essential in maintaining this balance. However, the effect of Tlx on gene expression depends on age and cell-type cues. Therefore, it is essential to establish its expression pattern at different developmental ages. Here, we show for the first time that in the neonatal lSEZ activated neural stem cells (NSCs) and especially transit-amplifying progenitors (TAPs) express Tlx and that its expression may be regulated at the posttranscriptional level. We also provide evidence that in both cell types Tlx affects gene expression in a positive and negative manner. In activated NSCs, but not in TAPs, absence of Tlx leads to overexpression of negative cell cycle regulators and impairment of proliferation. Moreover, in both cell types, the homeobox transcription factor Dlx2 is downregulated in the absence of Tlx. This is paralleled by increased expression of Olig2 in activated NSCs and glial fibrillary acidic protein in TAPs, indicating that in both populations Tlx decreases gliogenesis. Consistent with this, we found a higher proportion of cells expressing glial makers in the neonatal lSEZ of mutant mice than in the wild type counterpart. Thus, Tlx playing a dual role affects the expression of distinct genes in these two lSEZ cell types. Copyright © 2011 AlphaMed Press.

Expression of Cancer/Testis Antigens in Prostate Cancer is Associated With Disease Progression

PubMed Central

Suyama, Takahito; Shiraishi, Takumi; Zeng, Yu; Yu, Wayne; Parekh, Nehal; Vessella, Robert L.; Luo, Jun; Getzenberg, Robert H.; Kulkarni, Prakash

2011-01-01

Background The cancer/testis antigens (CTAs) are a unique group of proteins normally expressed in germ cells but aberrantly expressed in several types of cancers including prostate cancer (PCa). However, their role in PCa has not been fully explored. Methods CTA expression profiling in PCa samples and cell lines was done utilizing a custom microarray that contained probes for two-thirds of all CTAs. The data were validated by quantitative PCR (Q-PCR). Functional studies were carried out by silencing gene expression with siRNA. DNA methylation was determined by methylation-specific PCR. Results A majority of CTAs expressed in PCa are located on the X chromosome (CT-X antigens). Several CT-X antigens from the MAGEA/CSAG subfamilies are coordinately upregulated in castrate-resistant prostate cancer (CRPC) but not in primary PCa. In contrast, PAGE4 is highly upregulated in primary PCa but is virtually silent in CRPC. Further, there was good correlation between the extent of promoter DNA methylation and CTA expression. Finally, silencing the expression of MAGEA2 the most highly upregulated member, significantly impaired proliferation of prostate cancer cells while increasing their chemosensitivity. Conclusions Considered together, the remarkable stage-specific expression patterns of the CT-X antigens strongly suggests that these CTAs may serve as unique biomarkers that could potentially be used to distinguish men with aggressive disease who need treatment from men with indolent disease not requiring immediate intervention. The data also suggest that the CT-X antigens may be novel therapeutic targets for CRPC for which there are currently no effective therapeutics. PMID:20583133

Coordinated Gene Expression of Neuroinflammatory and Cell Signaling Markers in Dorsolateral Prefrontal Cortex during Human Brain Development and Aging

PubMed Central

Primiani, Christopher T.; Ryan, Veronica H.; Rao, Jagadeesh S.; Cam, Margaret C.; Ahn, Kwangmi; Modi, Hiren R.; Rapoport, Stanley I.

2014-01-01

Background Age changes in expression of inflammatory, synaptic, and neurotrophic genes are not well characterized during human brain development and senescence. Knowing these changes may elucidate structural, metabolic, and functional brain processes over the lifespan, as well vulnerability to neurodevelopmental or neurodegenerative diseases. Hypothesis Expression levels of inflammatory, synaptic, and neurotrophic genes in the human brain are coordinated over the lifespan and underlie changes in phenotypic networks or cascades. Methods We used a large-scale microarray dataset from human prefrontal cortex, BrainCloud, to quantify age changes over the lifespan, divided into Development (0 to 21 years, 87 brains) and Aging (22 to 78 years, 144 brains) intervals, in transcription levels of 39 genes. Results Gene expression levels followed different trajectories over the lifespan. Many changes were intercorrelated within three similar groups or clusters of genes during both Development and Aging, despite different roles of the gene products in the two intervals. During Development, changes were related to reported neuronal loss, dendritic growth and pruning, and microglial events; TLR4, IL1R1, NFKB1, MOBP, PLA2G4A, and PTGS2 expression increased in the first years of life, while expression of synaptic genes GAP43 and DBN1 decreased, before reaching plateaus. During Aging, expression was upregulated for potentially pro-inflammatory genes such as NFKB1, TRAF6, TLR4, IL1R1, TSPO, and GFAP, but downregulated for neurotrophic and synaptic integrity genes such as BDNF, NGF, PDGFA, SYN, and DBN1. Conclusions Coordinated changes in gene transcription cascades underlie changes in synaptic, neurotrophic, and inflammatory phenotypic networks during brain Development and Aging. Early postnatal expression changes relate to neuronal, glial, and myelin growth and synaptic pruning events, while late Aging is associated with pro-inflammatory and synaptic loss changes. Thus, comparable transcriptional regulatory networks that operate throughout the lifespan underlie different phenotypic processes during Aging compared to Development. PMID:25329999

Coordinated gene expression of neuroinflammatory and cell signaling markers in dorsolateral prefrontal cortex during human brain development and aging.

PubMed

Primiani, Christopher T; Ryan, Veronica H; Rao, Jagadeesh S; Cam, Margaret C; Ahn, Kwangmi; Modi, Hiren R; Rapoport, Stanley I

2014-01-01

Age changes in expression of inflammatory, synaptic, and neurotrophic genes are not well characterized during human brain development and senescence. Knowing these changes may elucidate structural, metabolic, and functional brain processes over the lifespan, as well vulnerability to neurodevelopmental or neurodegenerative diseases. Expression levels of inflammatory, synaptic, and neurotrophic genes in the human brain are coordinated over the lifespan and underlie changes in phenotypic networks or cascades. We used a large-scale microarray dataset from human prefrontal cortex, BrainCloud, to quantify age changes over the lifespan, divided into Development (0 to 21 years, 87 brains) and Aging (22 to 78 years, 144 brains) intervals, in transcription levels of 39 genes. Gene expression levels followed different trajectories over the lifespan. Many changes were intercorrelated within three similar groups or clusters of genes during both Development and Aging, despite different roles of the gene products in the two intervals. During Development, changes were related to reported neuronal loss, dendritic growth and pruning, and microglial events; TLR4, IL1R1, NFKB1, MOBP, PLA2G4A, and PTGS2 expression increased in the first years of life, while expression of synaptic genes GAP43 and DBN1 decreased, before reaching plateaus. During Aging, expression was upregulated for potentially pro-inflammatory genes such as NFKB1, TRAF6, TLR4, IL1R1, TSPO, and GFAP, but downregulated for neurotrophic and synaptic integrity genes such as BDNF, NGF, PDGFA, SYN, and DBN1. Coordinated changes in gene transcription cascades underlie changes in synaptic, neurotrophic, and inflammatory phenotypic networks during brain Development and Aging. Early postnatal expression changes relate to neuronal, glial, and myelin growth and synaptic pruning events, while late Aging is associated with pro-inflammatory and synaptic loss changes. Thus, comparable transcriptional regulatory networks that operate throughout the lifespan underlie different phenotypic processes during Aging compared to Development.

RNA-seq Transcriptional Profiling of an Arbuscular Mycorrhiza Provides Insights into Regulated and Coordinated Gene Expression in Lotus japonicus and Rhizophagus irregularis.

PubMed

Handa, Yoshihiro; Nishide, Hiroyo; Takeda, Naoya; Suzuki, Yutaka; Kawaguchi, Masayoshi; Saito, Katsuharu

2015-08-01

Gene expression during arbuscular mycorrhizal development is highly orchestrated in both plants and arbuscular mycorrhizal fungi. To elucidate the gene expression profiles of the symbiotic association, we performed a digital gene expression analysis of Lotus japonicus and Rhizophagus irregularis using a HiSeq 2000 next-generation sequencer with a Cufflinks assembly and de novo transcriptome assembly. There were 3,641 genes differentially expressed during arbuscular mycorrhizal development in L. japonicus, approximately 80% of which were up-regulated. The up-regulated genes included secreted proteins, transporters, proteins involved in lipid and amino acid metabolism, ribosomes and histones. We also detected many genes that were differentially expressed in small-secreted peptides and transcription factors, which may be involved in signal transduction or transcription regulation during symbiosis. Co-regulated genes between arbuscular mycorrhizal and root nodule symbiosis were not particularly abundant, but transcripts encoding for membrane traffic-related proteins, transporters and iron transport-related proteins were found to be highly co-up-regulated. In transcripts of arbuscular mycorrhizal fungi, expansion of cytochrome P450 was observed, which may contribute to various metabolic pathways required to accommodate roots and soil. The comprehensive gene expression data of both plants and arbuscular mycorrhizal fungi provide a powerful platform for investigating the functional and molecular mechanisms underlying arbuscular mycorrhizal symbiosis. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Evaluation of potential mechanisms of atrazine-induced reproductive impairment in fathead minnow (Pimephales promelas) and Japanese medaka (Oryzias latipes)

USGS Publications Warehouse

Richter, Cathy; Papoulias, Diana M.; Whyte, Jeffrey J.; Tillitt, Donald E.

2016-01-01

Atrazine has been implicated in reproductive dysfunction of exposed organisms, and previous studies documented decreased egg production in Japanese medaka (Oryzias latipes) and fathead minnows (Pimephales promelas) during 30-d to 38-d exposures to 0.5 µg/L, 5 µg/L, and 50 µg/L atrazine. The authors evaluated possible mechanisms underlying the reduction in egg production. Gene expression in steroidogenesis pathways and the hypothalamus–pituitary–gonad axis of male and female fish was measured. Atrazine did not significantly induce gonad aromatase (cyp19a1a) expression. An atrazine-induced shift in the number of females in an active reproductive state was observed. Expression of the egg maturation genes vitellogenin 1 (vtg1) and zona pellucida glycoprotein 3.1 (zp3.1) in medaka females was correlated and had a bimodal distribution. In both species, females with low vtg1 or zp3.1 expression also had low expression of steroidogenesis genes in the gonad, estrogen receptor in the liver, and gonadotropins in the brain. In the medaka, the number of females per tank that had high expression of zp3.1 was significantly correlated with egg production per tank. The number of medaka females with low expression of zp3.1 increased significantly with atrazine exposure. Thus, the decline in egg production observed in response to atrazine exposure may be the result of a coordinated downregulation of genes required for reproduction in a subset of females.

Time-Varying Expression of the Formation Flying along Circular Trajectories

NASA Technical Reports Server (NTRS)

Kawaguchi, Jun'ichiro

2007-01-01

Usually, the formation flying associated with circular orbits is discussed through the well-known Hill s or C-W equations of motion. This paper dares to present and discuss the coordinates that may contain time-varying coefficients. The discussion presents how the controller s performance is affected by the selection of coordinates, and also looks at the special coordinate suitable for designating a target bin to which each spacecraft in the formation has only to be guided. It is revealed that the latter strategy may incorporate the J2 disturbance automatically.

Darboux coordinates and instanton corrections in projective superspace

NASA Astrophysics Data System (ADS)

Crichigno, P. Marcos; Jain, Dharmesh

2012-10-01

By demanding consistency of the Legendre transform construction of hyperkähler metrics in projective superspace, we derive the expression for the Darboux coordinates on the hyperkähler manifold. We apply these results to study the Coulomb branch moduli space of 4D, {N}=2 super-Yang-Mills theory (SYM) on {{{R}}^3}× {S^1} , recovering the results by GMN. We also apply this method to study the electric corrections to the moduli space of 5D, {N}=1 SYM on {{{R}}^3}× {T^2} and give the Darboux coordinates explicitly.

Interplay between ChREBP and SREBP-1c coordinates postprandial glycolysis and lipogenesis in livers of mice[S

PubMed Central

Li, Shili; Choi, Hwa Y.; Fang, Fei; Fukasawa, Masashi; Uyeda, Kosaku; Hammer, Robert E.; Horton, Jay D.; Engelking, Luke J.; Liang, Guosheng

2018-01-01

Lipogenesis in liver is highest in the postprandial state; insulin activates SREBP-1c, which transcriptionally activates genes involved in FA synthesis, whereas glucose activates carbohydrate-responsive element-binding protein (ChREBP), which activates both glycolysis and FA synthesis. Whether SREBP-1c and ChREBP act independently of one another is unknown. Here, we characterized mice with liver-specific deletion of ChREBP (L-Chrebp−/− mice). Hepatic ChREBP deficiency resulted in reduced mRNA levels of glycolytic and lipogenic enzymes, particularly in response to sucrose refeeding following fasting, a dietary regimen that elicits maximal lipogenesis. mRNA and protein levels of SREBP-1c, a master transcriptional regulator of lipogenesis, were also reduced in L-Chrebp−/− livers. Adeno-associated virus-mediated restoration of nuclear SREBP-1c in L-Chrebp−/− mice normalized expression of a subset of lipogenic genes, while not affecting glycolytic genes. Conversely, ChREBP overexpression alone failed to support expression of lipogenic genes in the livers of mice lacking active SREBPs as a result of Scap deficiency. Together, these data show that SREBP-1c and ChREBP are both required for coordinated induction of glycolytic and lipogenic mRNAs. Whereas SREBP-1c mediates insulin’s induction of lipogenic genes, ChREBP mediates glucose’s induction of both glycolytic and lipogenic genes. These overlapping, but distinct, actions ensure that the liver synthesizes FAs only when insulin and carbohydrates are both present. PMID:29335275

NADPH Oxidase 1 Modulates WNT and NOTCH1 Signaling To Control the Fate of Proliferative Progenitor Cells in the Colon▿

PubMed Central

Coant, Nicolas; Ben Mkaddem, Sanae; Pedruzzi, Eric; Guichard, Cécile; Tréton, Xavier; Ducroc, Robert; Freund, Jean-Noel; Cazals-Hatem, Dominique; Bouhnik, Yoram; Woerther, Paul-Louis; Skurnik, David; Grodet, Alain; Fay, Michèle; Biard, Denis; Lesuffleur, Thécla; Deffert, Christine; Moreau, Richard; Groyer, André; Krause, Karl-Heinz; Daniel, Fanny; Ogier-Denis, Eric

2010-01-01

The homeostatic self-renewal of the colonic epithelium requires coordinated regulation of the canonical Wnt/β-catenin and Notch signaling pathways to control proliferation and lineage commitment of multipotent stem cells. However, the molecular mechanisms by which the Wnt/β-catenin and Notch1 pathways interplay in controlling cell proliferation and fate in the colon are poorly understood. Here we show that NADPH oxidase 1 (NOX1), a reactive oxygen species (ROS)-producing oxidase that is highly expressed in colonic epithelial cells, is a pivotal determinant of cell proliferation and fate that integrates Wnt/β-catenin and Notch1 signals. NOX1-deficient mice reveal a massive conversion of progenitor cells into postmitotic goblet cells at the cost of colonocytes due to the concerted repression of phosphatidylinositol 3-kinase (PI3K)/AKT/Wnt/β-catenin and Notch1 signaling. This conversion correlates with the following: (i) the redox-dependent activation of the dual phosphatase PTEN, causing the inactivation of the Wnt pathway effector β-catenin, and (ii) the downregulation of Notch1 signaling that provokes derepression of mouse atonal homolog 1 (Math1) expression. We conclude that NOX1 controls the balance between goblet and absorptive cell types in the colon by coordinately modulating PI3K/AKT/Wnt/β-catenin and Notch1 signaling. This finding provides the molecular basis for the role of NOX1 in cell proliferation and postmitotic differentiation. PMID:20351171

40 CFR 123.3 - Coordination with other programs.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 21 2010-07-01 2010-07-01 false Coordination with other programs. 123.3 Section 123.3 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS STATE PROGRAM REQUIREMENTS General § 123.3 Coordination with other programs. Issuance of State permits...

40 CFR 123.3 - Coordination with other programs.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 22 2011-07-01 2011-07-01 false Coordination with other programs. 123.3 Section 123.3 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS STATE PROGRAM REQUIREMENTS General § 123.3 Coordination with other programs. Issuance of State permits...

40 CFR 123.3 - Coordination with other programs.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 23 2012-07-01 2012-07-01 false Coordination with other programs. 123.3 Section 123.3 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS STATE PROGRAM REQUIREMENTS General § 123.3 Coordination with other programs. Issuance of State permits...

Coordinate Regulation of Stem Cell Competition by Slit-Robo and JAK-STAT Signaling in the Drosophila Testis

PubMed Central

Stine, Rachel R.; Greenspan, Leah J.; Ramachandran, Kapil V.; Matunis, Erika L.

2014-01-01

Stem cells in tissues reside in and receive signals from local microenvironments called niches. Understanding how multiple signals within niches integrate to control stem cell function is challenging. The Drosophila testis stem cell niche consists of somatic hub cells that maintain both germline stem cells and somatic cyst stem cells (CySCs). Here, we show a role for the axon guidance pathway Slit-Roundabout (Robo) in the testis niche. The ligand Slit is expressed specifically in hub cells while its receptor, Roundabout 2 (Robo2), is required in CySCs in order for them to compete for occupancy in the niche. CySCs also require the Slit-Robo effector Abelson tyrosine kinase (Abl) to prevent over-adhesion of CySCs to the niche, and CySCs mutant for Abl outcompete wild type CySCs for niche occupancy. Both Robo2 and Abl phenotypes can be rescued through modulation of adherens junction components, suggesting that the two work together to balance CySC adhesion levels. Interestingly, expression of Robo2 requires JAK-STAT signaling, an important maintenance pathway for both germline and cyst stem cells in the testis. Our work indicates that Slit-Robo signaling affects stem cell function downstream of the JAK-STAT pathway by controlling the ability of stem cells to compete for occupancy in their niche. PMID:25375180

The roles of categorical and coordinate spatial relations in recognizing buildings.

PubMed

Palermo, Liana; Piccardi, Laura; Nori, Raffaella; Giusberti, Fiorella; Guariglia, Cecilia

2012-11-01

Categorical spatial information is considered more useful for recognizing objects, and coordinate spatial information for guiding actions--for example, during navigation or grasping. In contrast with this assumption, we hypothesized that buildings, unlike other categories of objects, require both categorical and coordinate spatial information in order to be recognized. This hypothesis arose from evidence that right-brain-damaged patients have deficits in both coordinate judgments and recognition of buildings and from the fact that buildings are very useful for guiding navigation in urban environments. To test this hypothesis, we assessed 210 healthy college students while they performed four different tasks that required categorical and coordinate judgments and the recognition of common objects and buildings. Our results showed that both categorical and coordinate spatial representations are necessary to recognize a building, whereas only categorical representations are necessary to recognize an object. We discuss our data in view of a recent neural framework for visuospatial processing, suggesting that recognizing buildings may specifically activate the parieto-medial-temporal pathway.

Long noncoding RNA HOTTIP cooperates with CCCTC-binding factor to coordinate HOXA gene expression.

PubMed

Wang, Feng; Tang, Zhongqiong; Shao, Honglian; Guo, Jun; Tan, Tao; Dong, Yang; Lin, Lianbing

2018-06-12

The spatiotemporal control of HOX gene expression is dependent on positional identity and often correlated to their genomic location within each loci. Maintenance of HOX expression patterns is under complex transcriptional and epigenetic regulation, which is not well understood. Here we demonstrate that HOTTIP, a lincRNA transcribed from the 5' edge of the HOXA locus, physically associates with the CCCTC-binding factor (CTCF) that serves as an insulator by organizing HOXA cluster into disjoint domains, to cooperatively maintain the chromatin modifications of HOXA genes and thus coordinate the transcriptional activation of distal HOXA genes in human foreskin fibroblasts. Our results reveal the functional connection of HOTTIP and CTCF, and shed light on lincRNAs in gene activation and CTCF mediated chromatin organization. Copyright © 2018 Elsevier Inc. All rights reserved.

A second cistron in the CACNA1A gene encodes a transcription factor that mediates cerebellar development and SCA6

PubMed Central

Du, Xiaofei; Wang, Jun; Zhu, Haipeng; Rinaldo, Lorenzo; Lamar, Kay-Marie; Palmenberg, Ann C.; Hansel, Christian; Gomez, Christopher M.

2014-01-01

SUMMARY The CACNA1A gene, encoding the voltage-gated calcium channel subunit α1A, is involved in pre- and postsynaptic Ca2+ signaling, gene expression, and several genetic neurological disorders. We found that CACNA1A employs a novel strategy to directly coordinate a gene expression program, using a bicistronic mRNA bearing a cryptic internal ribosomal entry site (IRES). The first cistron encodes the well-characterized α1A subunit. The second expresses a newly-recognized transcription factor, α1ACT, that coordinates expression of a program of genes involved in neural and Purkinje cell development. α1ACT also contains the polyglutamine (polyQ) tract that, when expanded, causes spinocerebellar ataxia type 6 (SCA6). When expressed as an independent polypeptide, α1ACT, bearing an expanded polyQ tract, lacks transcription factor function and neurite outgrowth properties, causes cell death in culture, and leads to ataxia and cerebellar atrophy in transgenic mice. Suppression of CACNA1A IRES function in SCA6 may be a potential therapeutic strategy. PMID:23827678

Multiphasic and tissue-specific roles of sonic hedgehog in cloacal septation and external genitalia development

PubMed Central

Seifert, Ashley W.; Bouldin, Cortney M.; Choi, Kyung-Suk; Harfe, Brian D.; Cohn, Martin J.

2009-01-01

Malformations of the external genitalia are among the most common congenital anomalies in humans. The urogenital and anorectal sinuses develop from the embryonic cloaca, and the penis and clitoris develop from the genital tubercle. Within the genital tubercle, the endodermally derived urethral epithelium functions as an organizer and expresses sonic hedgehog (Shh). Shh knockout mice lack external genitalia and have a persistent cloaca. This identified an early requirement for Shh, but precluded analysis of its later role in the genital tubercle. We conducted temporally controlled deletions of Shh and report that Shh is required continuously through the onset of sexual differentiation. Shh function is divisible into two temporal phases; an anogenital phase, during which Shh regulates outgrowth and patterning of the genital tubercle and septation of the cloaca, and a later external genital phase, during which Shh regulates urethral tube closure. Disruption of Shh function during the anogenital phase causes coordinated anorectal and genitourinary malformations, whereas inactivation during the external genital phase causes hypospadias. Shh directs cloacal septation by promoting cell proliferation in adjacent urorectal septum mesenchyme. Additionally, conditional inactivation of smoothened in the genital ectoderm and cloacal/urethral endoderm shows that the ectoderm is a direct target of Shh and is required for urethral tube closure, highlighting a novel role for genital ectoderm in urethragenesis. Identification of the stages during which disruption of Shh results in either isolated or coordinated malformations of anorectal and external genital organs provides a new tool for investigating the etiology of anogenital malformations in humans. PMID:19906862

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.

On the efficiency of treating singularities in triatomic variational vibrational computations. The vibrational states of H(+)3 up to dissociation.

PubMed

Szidarovszky, Tamás; Császár, Attila G; Czakó, Gábor

2010-08-01

Several techniques of varying efficiency are investigated, which treat all singularities present in the triatomic vibrational kinetic energy operator given in orthogonal internal coordinates of the two distances-one angle type. The strategies are based on the use of a direct-product basis built from one-dimensional discrete variable representation (DVR) bases corresponding to the two distances and orthogonal Legendre polynomials, or the corresponding Legendre-DVR basis, corresponding to the angle. The use of Legendre functions ensures the efficient treatment of the angular singularity. Matrix elements of the singular radial operators are calculated employing DVRs using the quadrature approximation as well as special DVRs satisfying the boundary conditions and thus allowing for the use of exact DVR expressions. Potential optimized (PO) radial DVRs, based on one-dimensional Hamiltonians with potentials obtained by fixing or relaxing the two non-active coordinates, are also studied. The numerical calculations employed Hermite-DVR, spherical-oscillator-DVR, and Bessel-DVR bases as the primitive radial functions. A new analytical formula is given for the determination of the matrix elements of the singular radial operator using the Bessel-DVR basis. The usually claimed failure of the quadrature approximation in certain singular integrals is revisited in one and three dimensions. It is shown that as long as no potential optimization is carried out the quadrature approximation works almost as well as the exact DVR expressions. If wave functions with finite amplitude at the boundary are to be computed, the basis sets need to meet the required boundary conditions. The present numerical results also confirm that PO-DVRs should be constructed employing relaxed potentials and PO-DVRs can be useful for optimizing quadrature points for calculations applying large coordinate intervals and describing large-amplitude motions. The utility and efficiency of the different algorithms is demonstrated by the computation of converged near-dissociation vibrational energy levels for the H molecular ion.

A Minimalistic Resource Allocation Model to Explain Ubiquitous Increase in Protein Expression with Growth Rate

PubMed Central

Keren, Leeat; Segal, Eran; Milo, Ron

2016-01-01

Most proteins show changes in level across growth conditions. Many of these changes seem to be coordinated with the specific growth rate rather than the growth environment or the protein function. Although cellular growth rates, gene expression levels and gene regulation have been at the center of biological research for decades, there are only a few models giving a base line prediction of the dependence of the proteome fraction occupied by a gene with the specific growth rate. We present a simple model that predicts a widely coordinated increase in the fraction of many proteins out of the proteome, proportionally with the growth rate. The model reveals how passive redistribution of resources, due to active regulation of only a few proteins, can have proteome wide effects that are quantitatively predictable. Our model provides a potential explanation for why and how such a coordinated response of a large fraction of the proteome to the specific growth rate arises under different environmental conditions. The simplicity of our model can also be useful by serving as a baseline null hypothesis in the search for active regulation. We exemplify the usage of the model by analyzing the relationship between growth rate and proteome composition for the model microorganism E.coli as reflected in recent proteomics data sets spanning various growth conditions. We find that the fraction out of the proteome of a large number of proteins, and from different cellular processes, increases proportionally with the growth rate. Notably, ribosomal proteins, which have been previously reported to increase in fraction with growth rate, are only a small part of this group of proteins. We suggest that, although the fractions of many proteins change with the growth rate, such changes may be partially driven by a global effect, not necessarily requiring specific cellular control mechanisms. PMID:27073913

45 CFR 162.1802 - Standards for coordination of benefits information transaction.

Code of Federal Regulations, 2012 CFR

2012-10-01

....) (ii) The ASC X12 Standards for Electronic Data Interchange Technical Report Type 3—Health Care Claim... DATA STANDARDS AND RELATED REQUIREMENTS ADMINISTRATIVE REQUIREMENTS Coordination of Benefits § 162.1802....1) for the NCPDP Data Record in the Detail Data Record. (Incorporated by reference in § 162.920). (2...

45 CFR 162.1802 - Standards for coordination of benefits information transaction.

Code of Federal Regulations, 2011 CFR

2011-10-01

....) (ii) The ASC X12 Standards for Electronic Data Interchange Technical Report Type 3—Health Care Claim... DATA STANDARDS AND RELATED REQUIREMENTS ADMINISTRATIVE REQUIREMENTS Coordination of Benefits § 162.1802....1) for the NCPDP Data Record in the Detail Data Record. (Incorporated by reference in § 162.920). (2...

45 CFR 162.1802 - Standards for coordination of benefits information transaction.

Code of Federal Regulations, 2013 CFR

2013-10-01

....) (ii) The ASC X12 Standards for Electronic Data Interchange Technical Report Type 3—Health Care Claim... DATA STANDARDS AND RELATED REQUIREMENTS ADMINISTRATIVE REQUIREMENTS Coordination of Benefits § 162.1802....1) for the NCPDP Data Record in the Detail Data Record. (Incorporated by reference in § 162.920). (2...

Cluster of Sound Speed Fields by an Integral Measure

DTIC Science & Technology

2010-06-01

the same cost in time. The increasing the number of sensor depths does not cause execution time to increase. And finally assume that the time required...to be P = Z − ∫ 0 b ∂C(ρ, θ, λ) ∂ρ ∂C(ρ, θ, λ) ∂ρ dρ (2) where (ρ,θ,λ) are the usual geocentric spherical coordinates, and the limits of integration...but using spherical coordinates requires that the horizontal (θ , λ) terms be normalized by the radius. In the case of geocentric coordinates this

Interpersonal Coordination of Head Motion in Distressed Couples

PubMed Central

Hammal, Zakia; Cohn, Jeffrey F.; George, David T.

2015-01-01

In automatic emotional expression analysis, head motion has been considered mostly a nuisance variable, something to control when extracting features for action unit or expression detection. As an initial step toward understanding the contribution of head motion to emotion communication, we investigated the interpersonal coordination of rigid head motion in intimate couples with a history of interpersonal violence. Episodes of conflict and non-conflict were elicited in dyadic interaction tasks and validated using linguistic criteria. Head motion parameters were analyzed using Student’s paired t-tests; actor-partner analyses to model mutual influence within couples; and windowed cross-correlation to reveal dynamics of change in direction of influence over time. Partners’ RMS angular displacement for yaw and RMS angular velocity for pitch and yaw each demonstrated strong mutual influence between partners. Partners’ RMS angular displacement for pitch was higher during conflict. In both conflict and non-conflict, head angular displacement and angular velocity for pitch and yaw were strongly correlated, with frequent shifts in lead-lag relationships. The overall amount of coordination between partners’ head movement was more highly correlated during non-conflict compared with conflict interaction. While conflict increased head motion, it served to attenuate interpersonal coordination. PMID:26167256

Status of research and development in coordinate-measurement technology

NASA Astrophysics Data System (ADS)

Dich, L. Z.; Latyev, S. M.

1994-09-01

This paper discusses problems involved in developing and operating coordinate-measuring machines. The status of this area of precision instrumentation is analyzed. These problems are made critical not only by the requirements of the machine-tool industry but also by those of the microelectronics industry, both of which use coordinate tables, step-up gears, and other equipment in which precise coordinate measurements are necessary.

48 CFR 970.5223-2 - Affirmative procurement program.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Contractor shall coordinate its activities with the DOE Recycling Coordinator. Reports required by paragraph (c) of this clause shall be submitted through the DOE Recycling Coordinator. (c) The Contractor shall... “subcontractor” and the term “DOE Recycling Coordinator” will be understood to mean “Contractor Recycling...

Local Working Agreements and the Tennessee SOPs

EPA Pesticide Factsheets

TN Interagency workgroup convened to improve communication and Coordination, identify permit requirements, implement concurrent reviews, reduce permit revisions; and develop coordinated JD/Pre-App process

ACHP | Handbook on Coordinating NEPA and Section 106

Science.gov Websites

Search skip specific nav links Home arrow Handbook on Coordinating NEPA and Section 106 Handbook on handbook designed to help coordinate required review processes under the National Historic Preservation Act and the National Environmental Policy Act. The handbook stands to significantly improve the

21 CFR 1311.20 - Coordinators for CSOS digital certificate holders.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Coordinators for CSOS digital certificate holders... REQUIREMENTS FOR ELECTRONIC ORDERS AND PRESCRIPTIONS (Eff. 6-1-10) Obtaining and Using Digital Certificates for Electronic Orders § 1311.20 Coordinators for CSOS digital certificate holders. (a) Each registrant...

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...

78 FR 53506 - Proposed Information Collection (Care Coordination Home Telehealth (CCHT) Patient Satisfaction...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-29

... Coordination Home Telehealth (CCHT) Patient Satisfaction Survey, VA Form 10-0481); Activity: Comment Request... required to obtain patient perspective on satisfaction with the CCHT program and messaging devices. DATES.... Titles: Care Coordination Home Telehealth (CCHT) Patient Satisfaction Survey, VA Form 10-0481. OMB...

Coordination for the Improvement of Basic Skills.

ERIC Educational Resources Information Center

Roberts, Jane M. E.

The Title II Basic Skills legislation, which is part of the Educational Amendments of 1978, requires coordination of basic skills improvement among related federally-supported programs. Coordination, while essential, is made difficult by the proliferation of agencies and bureaus concerned with basic skills and by the need for autonomy among…

Glucose Elevates NITRATE TRANSPORTER2.1 Protein Levels and Nitrate Transport Activity Independently of Its HEXOKINASE1-Mediated Stimulation of NITRATE TRANSPORTER2.1 Expression1[W][OPEN

PubMed Central

de Jong, Femke; Thodey, Kate; Lejay, Laurence V.; Bevan, Michael W.

2014-01-01

Mineral nutrient uptake and assimilation is closely coordinated with the production of photosynthate to supply nutrients for growth. In Arabidopsis (Arabidopsis thaliana), nitrate uptake from the soil is mediated by genes encoding high- and low-affinity transporters that are transcriptionally regulated by both nitrate and photosynthate availability. In this study, we have studied the interactions of nitrate and glucose (Glc) on gene expression, nitrate transport, and growth using glucose-insensitive2-1 (gin2-1), which is defective in sugar responses. We confirm and extend previous work by showing that HEXOKINASE1-mediated oxidative pentose phosphate pathway (OPPP) metabolism is required for Glc-mediated NITRATE TRANSPORTER2.1 (NRT2.1) expression. Treatment with pyruvate and shikimate, two products derived from intermediates of the OPPP that are destined for amino acid production, restores wild-type levels of NRT2.1 expression, suggesting that metabolites derived from OPPP metabolism can, together with Glc, directly stimulate high levels of NRT2.1 expression. Nitrate-mediated NRT2.1 expression is not influenced by gin2-1, showing that Glc does not influence NRT2.1 expression through nitrate-mediated mechanisms. We also show that Glc stimulates NRT2.1 protein levels and transport activity independently of its HEXOKINASE1-mediated stimulation of NRT2.1 expression, demonstrating another possible posttranscriptional mechanism influencing nitrate uptake. In gin2-1 plants, nitrate-responsive biomass growth was strongly reduced, showing that the supply of OPPP metabolites is essential for assimilating nitrate for growth. PMID:24272701

Lymphatic function is regulated by a coordinated expression of lymphangiogenic and anti-lymphangiogenic cytokines

PubMed Central

Zampell, Jamie C.; Avraham, Tomer; Yoder, Nicole; Fort, Nicholas; Yan, Alan; Weitman, Evan S.

2012-01-01

Lymphangiogenic cytokines such as vascular endothelial growth factor-C (VEGF-C) are critically required for lymphatic regeneration; however, in some circumstances, lymphatic function is impaired despite normal or elevated levels of these cytokines. The recent identification of anti-lymphangiogenic molecules such as interferon-γ (IFN-γ), transforming growth factor-β1, and endostatin has led us to hypothesize that impaired lymphatic function may represent a dysregulated balance in the expression of pro/anti-lymphangiogenic stimuli. We observed that nude mice have significantly improved lymphatic function compared with wild-type mice in a tail model of lymphedema. We show that gradients of lymphatic fluid stasis regulate the expression of lymphangiogenic cytokines (VEGF-A, VEGF-C, and hepatocyte growth factor) and that paradoxically the expression of these molecules is increased in wild-type mice. More importantly, we show that as a consequence of T-cell-mediated inflammation, these same gradients also regulate expression patterns of anti-lymphangiogenic molecules corresponding temporally and spatially with impaired lymphatic function in wild-type mice. We show that neutralization of IFN-γ significantly increases inflammatory lymph node lymphangiogenesis independently of changes in VEGF-A or VEGF-C expression, suggesting that alterations in the balance of pro- and anti-lymphangiogenic cytokine expression can regulate lymphatic vessel formation. In conclusion, we show that gradients of lymphatic fluid stasis regulate not only the expression of pro-lymphangiogenic cytokines but also potent suppressors of lymphangiogenesis as a consequence of T-cell inflammation and that modulation of the balance between these stimuli can regulate lymphatic function. PMID:21940662

A colitogenic memory CD4+ T cell population mediates gastrointestinal graft-versus-host disease

PubMed Central

Zhou, Vivian; Agle, Kimberle; Chen, Xiao; Beres, Amy; Komorowski, Richard; Belle, Ludovic; Taylor, Carolyn; Zhu, Fenlu; Haribhai, Dipica; Williams, Calvin B.; Verbsky, James; Blumenschein, Wendy; Sadekova, Svetlana; Bowman, Eddie; Ballantyne, Christie; Weaver, Casey; Serody, David A.; Vincent, Benjamin; Serody, Jonathan; Cua, Daniel J.; Drobyski, William R.

2016-01-01

Damage to the gastrointestinal tract is a major cause of morbidity and mortality in graft-versus-host disease (GVHD) and is attributable to T cell–mediated inflammation. In this work, we identified a unique CD4+ T cell population that constitutively expresses the β2 integrin CD11c and displays a biased central memory phenotype and memory T cell transcriptional profile, innate-like properties, and increased expression of the gut-homing molecules α4β7 and CCR9. Using several complementary murine GVHD models, we determined that adoptive transfer and early accumulation of β2 integrin–expressing CD4+ T cells in the gastrointestinal tract initiated Th1-mediated proinflammatory cytokine production, augmented pathological damage in the colon, and increased mortality. The pathogenic effect of this CD4+ T cell population critically depended on coexpression of the IL-23 receptor, which was required for maximal inflammatory effects. Non–Foxp3-expressing CD4+ T cells produced IL-10, which regulated colonic inflammation and attenuated lethality in the absence of functional CD4+Foxp3+ T cells. Thus, the coordinate expression of CD11c and the IL-23 receptor defines an IL-10–regulated, colitogenic memory CD4+ T cell subset that is poised to initiate inflammation when there is loss of tolerance and breakdown of mucosal barriers. PMID:27500496

The transcription factor c-Fos coordinates with histone lysine-specific demethylase 2A to activate the expression of cyclooxygenase-2

PubMed Central

Du, Yipeng; Cao, Lin-lin; Li, Meiting; Shen, Changchun; Hou, Tianyun; Zhao, Ying; Wang, Haiying; Deng, Dajun; Wang, Lina; He, Qihua; Zhu, Wei-Guo

2015-01-01

Cyclooxygenase-2 (COX-2) is overexpressed in a variety of human epithelial cancers, including lung cancer, and is highly associated with a poor prognosis and a low survival rate. Understanding how COX-2 is regulated in response to carcinogens will offer insight into designing anti-cancer strategies and preventing cancer development. Here, we analyzed COX-2 expression in several human lung cancer cell lines and found that COX-2 expression was absent in the H719 and H460 cell lines by a DNA methylation-independent mechanism. The re-expression of COX-2 was observed after 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment in both cell lines. Further investigation found that H3K36 dimethylation was significantly reduced near the COX-2 promoter because histone demethylase 2A (KDM2A) was recruited to the COX-2 promoter after TPA treatment. In addition, the transcription factor c-Fos was found to be required to recruit KDM2A to the COX-2 promoter for reactivation of COX-2 in response to TPA treatment in both the H719 and H460 cell lines. Together, our data reveal a novel mechanism by which the carcinogen TPA activates COX-2 expression by regulating H3K36 dimethylation near the COX-2 promoter. PMID:26430963

Interleukin 18 function requires both interleukin 18 receptor and Na-Cl co-transporter

PubMed Central

Wang, Jing; Sun, Chongxiu; Gerdes, Norbert; Liu, Conglin; Liao, Mengyang; Liu, Jian; Shi, Michael A.; He, Aina; Zhou, Yi; Sukhova, Galina K.; Chen, Huimei; Cheng, Xianwu; Kuzuya, Masafumi; Murohara, Toyoaki; Zhang, Jie; Cheng, Xiang; Jiang, Mengmeng; Shull, Gary E.; Rogers, Shaunessy; Yang, Chao-Ling; Ke, Qiang; Jelen, Sabina; Bindels, René; Ellison, David H.; Jarolim, Petr; Libby, Peter; Shi, Guo-Ping

2015-01-01

Interleukin-18 (IL18) participates in atherogenesis through several putative mechanisms1,2. Interruption of IL18 action reduces atherosclerosis in mice3,4. This study shows that the absence of IL18 receptor (IL18r) does not affect atherosclerosis in apolipoprotein E-deficient (Apoe−/−) mice, nor does it affect IL18 cell surface binding or signaling. IL18 antibody-mediated immunoprecipitation identified an interaction between IL18 and Na-Cl co-transporter (NCC), a 12-transmembrane-domain ion transporter protein preferentially expressed in the kidney5. Yet, we find NCC expression and colocalization with IL18r in atherosclerotic lesions and both molecules form a complex. IL18 also binds to the cell surface and induces cell signaling and down-stream cytokine expression in NCC-transfected COS-7 cells that do not express IL18r. In Apoe−/− mice, combined deficiency of IL18r and NCC, but not single deficiency, protects mice from atherosclerosis. Peritoneal macrophages from Apoe−/− mice or those lacking IL18r or NCC respond to IL18 binding or IL18 induction of cell signaling and cytokine and chemokine production, but those with combined deficiency of IL18r and NCC do not. This study identifies NCC as an IL18-binding protein that coordinates with IL18r in cell signaling, inflammatory molecule expression, and experimental atherogenesis. PMID:26099046

Scientific basis for learning transfer from movements to urinary bladder functions for bladder repair in human patients with CNS injury.

PubMed

Schalow, G

2010-01-01

Coordination Dynamics Therapy (CDT) has been shown to be able to partly repair CNS injury. The repair is based on a movement-based re-learning theory which requires at least three levels of description: the movement or pattern (and anamnesis) level, the collective variable level, and the neuron level. Upon CDT not only the actually performed movement pattern itself is repaired, but the entire dynamics of CNS organization is improved, which is the theoretical basis for (re-) learning transfer. The transfer of learning for repair from jumping on springboard and exercising on a special CDT and recording device to urinary bladder functions is investigated at the neuron level. At the movement or pattern level, the improvement of central nervous system (CNS) functioning in human patients can be seen (or partly measured) by the improvement of the performance of the pattern. At the collective variable level, coordination tendencies can be measured by the so-called 'coordination dynamics' before, during and after treatment. At the neuron level, re-learning can additionally be assessed by surface electromyography (sEMG) as alterations of single motor unit firings and motor programs. But to express the ongoing interaction between the numerous neural, muscular, and metabolic elements involved in perception and action, it is relevant to inquire how the individual afferent and efferent neurons adjust their phase and frequency coordination to other neurons to satisfy learning task requirements. With the single-nerve fibre action potential recording method it was possible to measure that distributed single neurons communicate by phase and frequency coordination. It is shown that this timed firing of neurons is getting impaired upon injury and has to be improved by learning The stability of phase and frequency coordination among afferent and efferent neuron firings can be related to pattern stability. The stability of phase and frequency coordination at the neuron level can therefore be assessed integratively at the (non-invasive) collective variable level by the arrhythmicity of turning (coordination dynamics) when a patient is exercising on a special CDT device. Upon jumping on springboard and exercising on the special CDT device, the intertwined neuronal networks, subserving movements (somatic) and urinary bladder functions (autonomic and somatic) in the sacral spinal cord, are synchronously activated and entrained to give rise to learning transfer from movements to bladder functions. Jumping on springboard and other movements primarily repair the pattern dynamics, whereas the exactly coordinated performed movements, performed on the special CDT device for turning, primarily improve the preciseness of the timed firing of neurons. The synchronous learning of perceptuomotor and perceptuobladder functioning from a dynamical perspective (giving rise to learning transfer) can be understood at the neuron level. Especially the activated phase and frequency coordination upon natural stimulation under physiologic and pathophysiologic conditions among a and gamma-motoneurons, muscle spindle afferents, touch and pain afferents, and urinary bladder stretch and tension receptor afferents in the human sacral spinal cord make understandable that somatic and parasympathetic functions are integrated in their functioning and give rise to learning transfer from movements to bladder functions. The power of this human treatment research project lies in the unit of theory, diagnostic/measurement, and praxis, namely that CNS injury can partly be repaired, including urinary bladder functions, and the repair can partly be understood even at the neuron level of description in human.

Widespread receptivity to neuropeptide PDF throughout the neuronal circadian clock network of Drosophila revealed by real-time cyclic AMP imaging.

PubMed

Shafer, Orie T; Kim, Dong Jo; Dunbar-Yaffe, Richard; Nikolaev, Viacheslav O; Lohse, Martin J; Taghert, Paul H

2008-04-24

The neuropeptide PDF is released by sixteen clock neurons in Drosophila and helps maintain circadian activity rhythms by coordinating a network of approximately 150 neuronal clocks. Whether PDF acts directly on elements of this neural network remains unknown. We address this question by adapting Epac1-camps, a genetically encoded cAMP FRET sensor, for use in the living brain. We find that a subset of the PDF-expressing neurons respond to PDF with long-lasting cAMP increases and confirm that such responses require the PDF receptor. In contrast, an unrelated Drosophila neuropeptide, DH31, stimulates large cAMP increases in all PDF-expressing clock neurons. Thus, the network of approximately 150 clock neurons displays widespread, though not uniform, PDF receptivity. This work introduces a sensitive means of measuring cAMP changes in a living brain with subcellular resolution. Specifically, it experimentally confirms the longstanding hypothesis that PDF is a direct modulator of most neurons in the Drosophila clock network.

Notch regulates BMP responsiveness and lateral branching in vessel networks via SMAD6

PubMed Central

Mouillesseaux, Kevin P.; Wiley, David S.; Saunders, Lauren M.; Wylie, Lyndsay A.; Kushner, Erich J.; Chong, Diana C.; Citrin, Kathryn M.; Barber, Andrew T.; Park, Youngsook; Kim, Jun-Dae; Samsa, Leigh Ann; Kim, Jongmin; Liu, Jiandong; Jin, Suk-Won; Bautch, Victoria L.

2016-01-01

Functional blood vessel growth depends on generation of distinct but coordinated responses from endothelial cells. Bone morphogenetic proteins (BMP), part of the TGFβ superfamily, bind receptors to induce phosphorylation and nuclear translocation of SMAD transcription factors (R-SMAD1/5/8) and regulate vessel growth. However, SMAD1/5/8 signalling results in both pro- and anti-angiogenic outputs, highlighting a poor understanding of the complexities of BMP signalling in the vasculature. Here we show that BMP6 and BMP2 ligands are pro-angiogenic in vitro and in vivo, and that lateral vessel branching requires threshold levels of R-SMAD phosphorylation. Endothelial cell responsiveness to these pro-angiogenic BMP ligands is regulated by Notch status and Notch sets responsiveness by regulating a cell-intrinsic BMP inhibitor, SMAD6, which affects BMP responses upstream of target gene expression. Thus, we reveal a paradigm for Notch-dependent regulation of angiogenesis: Notch regulates SMAD6 expression to affect BMP responsiveness of endothelial cells and new vessel branch formation. PMID:27834400

The Transcription Factor Rbf1 Is the Master Regulator for b-Mating Type Controlled Pathogenic Development in Ustilago maydis

PubMed Central

Vranes, Miroslav; Wahl, Ramon; Pothiratana, Chetsada; Schuler, David; Vincon, Volker; Finkernagel, Florian; Flor-Parra, Ignacio; Kämper, Jörg

2010-01-01

In the phytopathogenic basidiomycete Ustilago maydis, sexual and pathogenic development are tightly connected and controlled by the heterodimeric bE/bW transcription factor complex encoded by the b-mating type locus. The formation of the active bE/bW heterodimer leads to the formation of filaments, induces a G2 cell cycle arrest, and triggers pathogenicity. Here, we identify a set of 345 bE/bW responsive genes which show altered expression during these developmental changes; several of these genes are associated with cell cycle coordination, morphogenesis and pathogenicity. 90% of the genes that show altered expression upon bE/bW-activation require the zinc finger transcription factor Rbf1, one of the few factors directly regulated by the bE/bW heterodimer. Rbf1 is a novel master regulator in a multilayered network of transcription factors that facilitates the complex regulatory traits of sexual and pathogenic development. PMID:20700446

The tyrosine kinase Stitcher activates Grainy head and epidermal wound healing in Drosophila.

PubMed

Wang, Shenqiu; Tsarouhas, Vasilios; Xylourgidis, Nikos; Sabri, Nafiseh; Tiklová, Katarína; Nautiyal, Naumi; Gallio, Marco; Samakovlis, Christos

2009-07-01

Epidermal injury initiates a cascade of inflammation, epithelial remodelling and integument repair at wound sites. The regeneration of the extracellular barrier and damaged tissue repair rely on the precise orchestration of epithelial responses triggered by the injury. Grainy head (Grh) transcription factors induce gene expression to crosslink the extracellular barrier in wounded flies and mice. However, the activation mechanisms and functions of Grh factors in re-epithelialization remain unknown. Here we identify stitcher (stit), a new Grh target in Drosophila melanogaster. stit encodes a Ret-family receptor tyrosine kinase required for efficient epidermal wound healing. Live imaging analysis reveals that Stit promotes actin cable assembly during wound re-epithelialization. Stit activation also induces extracellular signal-regulated kinase (ERK) phosphorylation along with the Grh-dependent expression of stit and barrier repair genes at the wound sites. The transcriptional stimulation of stit on injury triggers a positive feedback loop increasing the magnitude of epithelial responses. Thus, Stit activation upon wounding coordinates cytoskeletal rearrangements and the level of Grh-mediated transcriptional wound responses.

Epidermal wound repair is regulated by the planar cell polarity signaling pathway.

PubMed

Caddy, Jacinta; Wilanowski, Tomasz; Darido, Charbel; Dworkin, Sebastian; Ting, Stephen B; Zhao, Quan; Rank, Gerhard; Auden, Alana; Srivastava, Seema; Papenfuss, Tony A; Murdoch, Jennifer N; Humbert, Patrick O; Parekh, Vishwas; Boulos, Nidal; Weber, Thomas; Zuo, Jian; Cunningham, John M; Jane, Stephen M

2010-07-20

The mammalian PCP pathway regulates diverse developmental processes requiring coordinated cellular movement, including neural tube closure and cochlear stereociliary orientation. Here, we show that epidermal wound repair is regulated by PCP signaling. Mice carrying mutant alleles of PCP genes Vangl2, Celsr1, PTK7, and Scrb1, and the transcription factor Grhl3, interact genetically, exhibiting failed wound healing, neural tube defects, and disordered cochlear polarity. Using phylogenetic analysis, ChIP, and gene expression in Grhl3(-)(/-) mice, we identified RhoGEF19, a homolog of a RhoA activator involved in PCP signaling in Xenopus, as a direct target of GRHL3. Knockdown of Grhl3 or RhoGEF19 in keratinocytes induced defects in actin polymerization, cellular polarity, and wound healing, and re-expression of RhoGEF19 rescued these defects in Grhl3-kd cells. These results define a role for Grhl3 in PCP signaling and broadly implicate this pathway in epidermal repair. (c) 2010 Elsevier Inc. All rights reserved.

Epidermal wound repair is regulated by the planar cell polarity signaling pathway

PubMed Central

Caddy, Jacinta; Wilanowski, Tomasz; Darido, Charbel; Dworkin, Sebastian; Ting, Stephen B.; Zhao, Quan; Rank, Gerhard; Auden, Alana; Srivastava, Seema; Papenfuss, Tony A.; Murdoch, Jennifer N.; Humbert, Patrick O.; Boulos, Nidal; Weber, Thomas; Zuo, Jian; Cunningham, John M.; Jane, Stephen M.

2010-01-01

SUMMARY The mammalian PCP pathway regulates diverse developmental processes requiring coordinated cellular movement, including neural tube closure and cochlear stereociliary orientation. Here, we show that epidermal wound repair is regulated by PCP signaling. Mice carrying mutant alleles of PCP genes Vangl2, Celsr1, PTK7, and Scrb1, and the transcription factor Grhl3, interact genetically, exhibiting failed wound healing, neural tube defects and disordered cochlear polarity. Using phylogenetic analysis, ChIP, and gene expression in Grhl3−/− mice, we identified RhoGEF19, a homologue of a RhoA activator involved in PCP signaling in Xenopus, as a direct target of GRHL3. Knockdown of Grhl3 or RhoGEF19 in keratinocytes induced defects in actin polymerisation, cellular polarity and wound healing, and re-expression of RhoGEF19 rescued these defects in Grhl3-kd cells. These results define a role for Grhl3 in PCP signaling, and broadly implicate this pathway in epidermal repair. PMID:20643356

Sleep and Movement Differentiates Actions of Two Types of Somatostatin-Expressing GABAergic Interneuron in Rat Hippocampus

PubMed Central

Katona, Linda; Lapray, Damien; Viney, Tim J.; Oulhaj, Abderrahim; Borhegyi, Zsolt; Micklem, Benjamin R.; Klausberger, Thomas; Somogyi, Peter

2014-01-01

Summary Neuropeptides acting on pre- and postsynaptic receptors are coreleased with GABA by interneurons including bistratified and O-LM cells, both expressing somatostatin but innervating segregated dendritic domains of pyramidal cells. Neuropeptide release requires high-frequency action potentials, but the firing patterns of most peptide/GABA-releasing interneurons during behavior are unknown. We show that behavioral and network states differentiate the activities of bistratified and O-LM cells in freely moving rats. Bistratified cells fire at higher rates during sleep than O-LM cells and, unlike O-LM cells, strongly increase spiking during sharp wave-associated ripples (SWRs). In contrast, O-LM interneurons decrease firing during sleep relative to awake states and are mostly inhibited during SWRs. During movement, both cell types fire cooperatively at the troughs of theta oscillations but with different frequencies. Somatostatin and GABA are differentially released to distinct dendritic zones of CA1 pyramidal cells during sleep and wakefulness to coordinate segregated glutamatergic inputs from entorhinal cortex and CA3. PMID:24794095

ZBTB20 is required for anterior pituitary development and lactotrope specification.

PubMed

Cao, Dongmei; Ma, Xianhua; Cai, Jiao; Luan, Jing; Liu, An-Jun; Yang, Rui; Cao, Yi; Zhu, Xiaotong; Zhang, Hai; Chen, Yu-Xia; Shi, Yuguang; Shi, Guang-Xia; Zou, Dajin; Cao, Xuetao; Grusby, Michael J; Xie, Zhifang; Zhang, Weiping J

2016-04-15

The anterior pituitary harbours five distinct hormone-producing cell types, and their cellular differentiation is a highly regulated and coordinated process. Here we show that ZBTB20 is essential for anterior pituitary development and lactotrope specification in mice. In anterior pituitary, ZBTB20 is highly expressed by all the mature endocrine cell types, and to some less extent by somatolactotropes, the precursors of prolactin (PRL)-producing lactotropes. Disruption of Zbtb20 leads to anterior pituitary hypoplasia, hypopituitary dwarfism and a complete loss of mature lactotropes. In ZBTB20-null mice, although lactotrope lineage commitment is normally initiated, somatolactotropes exhibit profound defects in lineage specification and expansion. Furthermore, endogenous ZBTB20 protein binds to Prl promoter, and its knockdown decreases PRL expression and secretion in a lactotrope cell line MMQ. In addition, ZBTB20 overexpression enhances the transcriptional activity of Prl promoter in vitro. In conclusion, our findings point to ZBTB20 as a critical regulator of anterior pituitary development and lactotrope specification.

ZBTB20 is required for anterior pituitary development and lactotrope specification

PubMed Central

Cao, Dongmei; Ma, Xianhua; Cai, Jiao; Luan, Jing; Liu, An-Jun; Yang, Rui; Cao, Yi; Zhu, Xiaotong; Zhang, Hai; Chen, Yu-Xia; Shi, Yuguang; Shi, Guang-Xia; Zou, Dajin; Cao, Xuetao; Grusby, Michael J.; Xie, Zhifang; Zhang, Weiping J.

2016-01-01

The anterior pituitary harbours five distinct hormone-producing cell types, and their cellular differentiation is a highly regulated and coordinated process. Here we show that ZBTB20 is essential for anterior pituitary development and lactotrope specification in mice. In anterior pituitary, ZBTB20 is highly expressed by all the mature endocrine cell types, and to some less extent by somatolactotropes, the precursors of prolactin (PRL)-producing lactotropes. Disruption of Zbtb20 leads to anterior pituitary hypoplasia, hypopituitary dwarfism and a complete loss of mature lactotropes. In ZBTB20-null mice, although lactotrope lineage commitment is normally initiated, somatolactotropes exhibit profound defects in lineage specification and expansion. Furthermore, endogenous ZBTB20 protein binds to Prl promoter, and its knockdown decreases PRL expression and secretion in a lactotrope cell line MMQ. In addition, ZBTB20 overexpression enhances the transcriptional activity of Prl promoter in vitro. In conclusion, our findings point to ZBTB20 as a critical regulator of anterior pituitary development and lactotrope specification. PMID:27079169

Snapin-regulated late endosomal transport is critical for efficient autophagy-lysosomal function in neurons.

PubMed

Cai, Qian; Lu, Li; Tian, Jin-Hua; Zhu, Yi-Bing; Qiao, Haifa; Sheng, Zu-Hang

2010-10-06

Neuron maintenance and survival require late endocytic transport from distal processes to the soma where lysosomes are predominantly localized. Here, we report a role for Snapin in attaching dynein to late endosomes through its intermediate chain (DIC). snapin(-/-) neurons exhibit aberrant accumulation of immature lysosomes, clustering and impaired retrograde transport of late endosomes along processes, reduced lysosomal proteolysis due to impaired delivery of internalized proteins and hydrolase precursors from late endosomes to lysosomes, and impaired clearance of autolysosomes, combined with reduced neuron viability and neurodegeneration. The phenotypes are rescued by expressing the snapin transgene, but not the DIC-binding-defective Snapin-L99K mutant. Snapin overexpression in wild-type neurons enhances late endocytic transport and lysosomal function, whereas expressing the mutant defective in Snapin-DIC coupling shows a dominant-negative effect. Altogether, our study highlights new mechanistic insights into how Snapin-DIC coordinates retrograde transport and late endosomal-lysosomal trafficking critical for autophagy-lysosomal function, and thus neuronal homeostasis. Copyright © 2010 Elsevier Inc. All rights reserved.

Parvalbumin-expressing interneurons coordinate hippocampal network dynamics required for memory consolidation

NASA Astrophysics Data System (ADS)

Ognjanovski, Nicolette; Schaeffer, Samantha; Wu, Jiaxing; Mofakham, Sima; Maruyama, Daniel; Zochowski, Michal; Aton, Sara J.

2017-04-01

Activity in hippocampal area CA1 is essential for consolidating episodic memories, but it is unclear how CA1 activity patterns drive memory formation. We find that in the hours following single-trial contextual fear conditioning (CFC), fast-spiking interneurons (which typically express parvalbumin (PV)) show greater firing coherence with CA1 network oscillations. Post-CFC inhibition of PV+ interneurons blocks fear memory consolidation. This effect is associated with loss of two network changes associated with normal consolidation: (1) augmented sleep-associated delta (0.5-4 Hz), theta (4-12 Hz) and ripple (150-250 Hz) oscillations; and (2) stabilization of CA1 neurons' functional connectivity patterns. Rhythmic activation of PV+ interneurons increases CA1 network coherence and leads to a sustained increase in the strength and stability of functional connections between neurons. Our results suggest that immediately following learning, PV+ interneurons drive CA1 oscillations and reactivation of CA1 ensembles, which directly promotes network plasticity and long-term memory formation.

An Analysis of the Accessibility of Earth-Approaching Asteroids.

DTIC Science & Technology

1985-12-01

coordinate system. Outputs are the X,Y,Z coordinates of the sun in the geocentric-equatorial coordinate system. The obliquity of the ecliptic is a variable...All positions and velocities are calculated in heliocentric- ecliptic coordinates thus requiring no transformations into unusual frames of reference...tion vectors of the departure and arrival planets in the heliocentric- ecliptic reference frame. ,\\. , V I(W() - / n (16) %: ~22% .b The angle between

Adaptation of multijoint coordination during standing balance in healthy young and healthy old individuals

PubMed Central

Pasma, J. H.; Schouten, A. C.; Aarts, R. G. K. M.; Meskers, C. G. M.; Maier, A. B.; van der Kooij, H.

2015-01-01

Standing balance requires multijoint coordination between the ankles and hips. We investigated how humans adapt their multijoint coordination to adjust to various conditions and whether the adaptation differed between healthy young participants and healthy elderly. Balance was disturbed by push/pull rods, applying two continuous and independent force disturbances at the level of the hip and between the shoulder blades. In addition, external force fields were applied, represented by an external stiffness at the hip, either stabilizing or destabilizing the participants' balance. Multivariate closed-loop system-identification techniques were used to describe the neuromuscular control mechanisms by quantifying the corrective joint torques as a response to body sway, represented by frequency response functions (FRFs). Model fits on the FRFs resulted in an estimation of time delays, intrinsic stiffness, reflexive stiffness, and reflexive damping of both the ankle and hip joint. The elderly generated similar corrective joint torques but had reduced body sway compared with the young participants, corresponding to the increased FRF magnitude with age. When a stabilizing or destabilizing external force field was applied at the hip, both young and elderly participants adapted their multijoint coordination by lowering or respectively increasing their neuromuscular control actions around the ankles, expressed in a change of FRF magnitude. However, the elderly adapted less compared with the young participants. Model fits on the FRFs showed that elderly had higher intrinsic and reflexive stiffness of the ankle, together with higher time delays of the hip. Furthermore, the elderly adapted their reflexive stiffness around the ankle joint less compared with young participants. These results imply that elderly were stiffer and were less able to adapt to external force fields. PMID:26719084

Analysis on influence of installation error of off-axis three-mirror optical system on imaging line-of-sight

NASA Astrophysics Data System (ADS)

Gao, Lingyu; Li, Xinghua; Guo, Qianrui; Quan, Jing; Hu, Zhengyue; Su, Zhikun; Zhang, Dong; Liu, Peilu; Li, Haopeng

2018-01-01

The internal structure of off-axis three-mirror system is commonly complex. The mirror installation error in assembly always affects the imaging line-of-sight and further degrades the image quality. Due to the complexity of the optical path in off-axis three-mirror optical system, the straightforward theoretical analysis on the variations of imaging line-of-sight is extremely difficult. In order to simplify the theoretical analysis, an equivalent single-mirror system is proposed and presented in this paper. In addition, the mathematical model of single-mirror system is established and the accurate expressions of imaging coordinate are derived. Utilizing the simulation software ZEMAX, off-axis three-mirror model and single-mirror model are both established. By adjusting the position of mirror and simulating the line-of-sight rotation of optical system, the variations of imaging coordinates are clearly observed. The final simulation results include: in off-axis three-mirror system, the varying sensitivity of the imaging coordinate to the rotation of line-of-sight is approximately 30 um/″; in single-mirror system, the varying sensitivity of the imaging coordinate to the rotation of line-of-sight is 31.5 um/″. Compared to the simulation results of the off-axis three-mirror model, the 5% relative error of single-mirror model analysis highly satisfies the requirement of equivalent analysis and also verifies its validity. This paper presents a new method to analyze the installation error of the mirror in the off-axis three-mirror system influencing on the imaging line-of-sight. Moreover, the off-axis three-mirror model is totally equivalent to the single-mirror model in theoretical analysis.

34 CFR 364.29 - What are the requirements for coordinating Federal and State sources of funding?

Code of Federal Regulations, 2011 CFR

2011-07-01

... EDUCATION STATE INDEPENDENT LIVING SERVICES PROGRAM AND CENTERS FOR INDEPENDENT LIVING PROGRAM: GENERAL... 34 Education 2 2011-07-01 2010-07-01 true What are the requirements for coordinating Federal and State sources of funding? 364.29 Section 364.29 Education Regulations of the Offices of the Department...

34 CFR 364.29 - What are the requirements for coordinating Federal and State sources of funding?

Code of Federal Regulations, 2010 CFR

2010-07-01

... EDUCATION STATE INDEPENDENT LIVING SERVICES PROGRAM AND CENTERS FOR INDEPENDENT LIVING PROGRAM: GENERAL... 34 Education 2 2010-07-01 2010-07-01 false What are the requirements for coordinating Federal and State sources of funding? 364.29 Section 364.29 Education Regulations of the Offices of the Department...

34 CFR 403.15 - What are the personnel requirements regarding coordination with services under chapter 1 of title...

Code of Federal Regulations, 2010 CFR

2010-07-01

... VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION STATE VOCATIONAL AND APPLIED TECHNOLOGY EDUCATION... 34 Education 3 2010-07-01 2010-07-01 false What are the personnel requirements regarding coordination with services under chapter 1 of title I of the Elementary and Secondary Education Act? 403.15...

Raising the Bar: Challenging Students in a Capstone Project Course with an Android and Mobile Web Parallel Development Team Project

ERIC Educational Resources Information Center

Wong, Wilson; Pepe, James; Englander, Irv

2017-01-01

Information systems capstone projects aim to prepare students for what they will encounter in the industry after graduation. Corporate application development is often a complex endeavor that requires coordination between related products. For example, software development in the mobile application sector may require a coordinated parallel…

Stakeholder perceptions of aid coordination implementation in the Zambian health sector.

PubMed

Sundewall, Jesper; Jönsson, Kristina; Cheelo, Caesar; Tomson, Göran

2010-05-01

In this study, we analysed stakeholder perceptions of the process of implementing the coordination of health-sector aid in Zambia, Africa. The aim of coordination of health aid is to increase the effectiveness of health systems and to ensure that donors comply with national priorities. With increases in the number of donors involved and resources available for health aid globally, the attention devoted to coordination worldwide has risen. While the theoretical basis of coordination has been relatively well-explored, less research has been carried out on the practicalities of how such coordination is to be implemented. In our study, we focused on potential differences between the views of the stakeholders, both government and donors, on the systems by which health aid is coordinated. A qualitative case study was conducted comprising interviews with government and donor stakeholders in the health sector, as well as document review and observations of meetings. Results suggested that stakeholders are generally satisfied with the implementation of health-sector aid coordination in Zambia. However, there were differences in perceptions of the level of coordination of plans and agreements, which can be attributed to difficulties in harmonizing and aligning organizational requirements with the Zambian health-sector plans. In order to achieve the aims of the Paris Declaration; to increase harmonization, alignment and ownership--resources from donors must be better coordinated in the health sector planning process. This requires careful consideration of contextual constraints surrounding each donor. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

Interventions for coordination of walking following stroke: systematic review.

PubMed

Hollands, Kristen L; Pelton, Trudy A; Tyson, Sarah F; Hollands, Mark A; van Vliet, Paulette M

2012-03-01

Impairments in gait coordination may be a factor in falls and mobility limitations after stroke. Therefore, rehabilitation targeting gait coordination may be an effective way to improve walking post-stroke. This review sought to examine current treatments that target impairments of gait coordination, the theoretical basis on which they are derived and the effects of such interventions. Few high quality RCTs with a low risk of bias specifically targeting and measuring restoration of coordinated gait were found. Consequently, we took a pragmatic approach to describing and quantifying the available evidence and included non-randomised study designs and limited the influence of heterogeneity in experimental design and control comparators by restricting meta-analyses to pre- and post-test comparisons of experimental interventions only. Results show that physiotherapy interventions significantly improved gait function and coordination. Interventions involving repetitive task-specific practice and/or auditory cueing appeared to be the most promising approaches to restore gait coordination. The fact that overall improvements in gait coordination coincided with increased walking speed lends support to the hypothesis that targeting gait coordination gait may be a way of improving overall walking ability post-stroke. However, establishing the mechanism for improved locomotor control requires a better understanding of the nature of both neuroplasticity and coordination deficits in functional tasks after stroke. Future research requires the measurement of impairment, activity and cortical activation in an effort to establish the mechanism by which functional gains are achieved. Copyright © 2011 Elsevier B.V. All rights reserved.

Complex regulation of AprA metalloprotease in Pseudomonas fluorescens M114: evidence for the involvement of iron, the ECF sigma factor, PbrA and pseudobactin M114 siderophore.

PubMed

Maunsell, Bláithín; Adams, Claire; O'Gara, Fergal

2006-01-01

In the soil bacterium Pseudomonas fluorescens M114, extracellular proteolytic activity and fluorescent siderophore (pseudobactin M114) production were previously shown to be co-ordinately negatively regulated in response to environmental iron levels. An iron-starvation extracytoplasmic function sigma factor, PbrA, required for the transcription of siderophore biosynthetic genes, was also implicated in M114 protease regulation. The current study centred on the characterization and genetic regulation of the gene(s) responsible for protease production in M114. A serralysin-type metalloprotease gene, aprA, was identified and found to encode the major, if not only, extracellular protease produced by this strain. The expression of aprA and its protein product were found to be subject to complex regulation. Transcription analysis confirmed that PbrA was required for full aprA transcription under low iron conditions, while the ferric uptake regulator, Fur, was implicated in aprA repression under high iron conditions. Interestingly, the iron regulation of AprA was dependent on culture conditions, with PbrA-independent AprA-mediated proteolytic activity observed on skim milk agar supplemented with yeast extract, when supplied with iron or purified pseudobactin M114. These effects were not observed on skim milk agar without yeast extract. PbrA-independent aprA expression was also observed from a truncated transcriptional fusion when grown in sucrose asparagine tryptone broth supplied with iron or purified pseudobactin M114. Thus, experimental evidence suggested that iron mediated its effects via transcriptional activation by PbrA under low iron conditions, while an as-yet-unidentified sigma factor(s) may be required for the PbrA-independent aprA expression and AprA proteolytic activity induced by siderophore and iron.

The elastic theory of shells using geometric algebra

PubMed Central

Lasenby, J.; Agarwal, A.

2017-01-01

We present a novel derivation of the elastic theory of shells. We use the language of geometric algebra, which allows us to express the fundamental laws in component-free form, thus aiding physical interpretation. It also provides the tools to express equations in an arbitrary coordinate system, which enhances their usefulness. The role of moments and angular velocity, and the apparent use by previous authors of an unphysical angular velocity, has been clarified through the use of a bivector representation. In the linearized theory, clarification of previous coordinate conventions which have been the cause of confusion is provided, and the introduction of prior strain into the linearized theory of shells is made possible. PMID:28405404

The elastic theory of shells using geometric algebra.

PubMed

Gregory, A L; Lasenby, J; Agarwal, A

2017-03-01

We present a novel derivation of the elastic theory of shells. We use the language of geometric algebra, which allows us to express the fundamental laws in component-free form, thus aiding physical interpretation. It also provides the tools to express equations in an arbitrary coordinate system, which enhances their usefulness. The role of moments and angular velocity, and the apparent use by previous authors of an unphysical angular velocity, has been clarified through the use of a bivector representation. In the linearized theory, clarification of previous coordinate conventions which have been the cause of confusion is provided, and the introduction of prior strain into the linearized theory of shells is made possible.

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

His86 from the N-terminus of frataxin coordinates iron and is required for Fe-S cluster synthesis.

PubMed

Gentry, Leslie E; Thacker, Matthew A; Doughty, Reece; Timkovich, Russell; Busenlehner, Laura S

2013-09-03

Human frataxin has a vital role in the biosynthesis of iron-sulfur (Fe-S) clusters in mitochondria, and its deficiency causes the neurodegenerative disease Friedreich's ataxia. Proposed functions for frataxin in the Fe-S pathway include iron donation to the Fe-S cluster machinery and regulation of cysteine desulfurase activity to control the rate of Fe-S production, although further molecular detail is required to distinguish these two possibilities. It is well established that frataxin can coordinate iron using glutamate and aspartate side chains on the protein surface; however, in this work we identify a new iron coordinating residue in the N-terminus of human frataxin using complementary spectroscopic and structural approaches. Further, we demonstrate that His86 in this N-terminal region is required for high affinity iron coordination and iron assembly of Fe-S clusters by ISCU as part of the Fe-S cluster biosynthetic complex. If a binding site that includes His86 is important for Fe-S cluster synthesis as part of its chaperone function, this raises the possibility that either iron binding at the acidic surface of frataxin may be spurious or that it is required for protein-protein interactions with the Fe-S biosynthetic quaternary complex. Our data suggest that iron coordination to frataxin may be significant to the Fe-S cluster biosynthesis pathway in mitochondria.

Environmental Compliance Issue Coordination

EPA Pesticide Factsheets

An order to establish the Department of Energy (DOE) requirements for coordination of significant environmental compliance issues to ensure timely development and consistent application of Departmental environmental policy and guidance

WRKY6 Transcription Factor Restricts Arsenate Uptake and Transposon Activation in Arabidopsis[W

PubMed Central

Castrillo, Gabriel; Sánchez-Bermejo, Eduardo; de Lorenzo, Laura; Crevillén, Pedro; Fraile-Escanciano, Ana; TC, Mohan; Mouriz, Alfonso; Catarecha, Pablo; Sobrino-Plata, Juan; Olsson, Sanna; Leo del Puerto, Yolanda; Mateos, Isabel; Rojo, Enrique; Hernández, Luis E.; Jarillo, Jose A.; Piñeiro, Manuel; Paz-Ares, Javier; Leyva, Antonio

2013-01-01

Stress constantly challenges plant adaptation to the environment. Of all stress types, arsenic was a major threat during the early evolution of plants. The most prevalent chemical form of arsenic is arsenate, whose similarity to phosphate renders it easily incorporated into cells via the phosphate transporters. Here, we found that arsenate stress provokes a notable transposon burst in plants, in coordination with arsenate/phosphate transporter repression, which immediately restricts arsenate uptake. This repression was accompanied by delocalization of the phosphate transporter from the plasma membrane. When arsenate was removed, the system rapidly restored transcriptional expression and membrane localization of the transporter. We identify WRKY6 as an arsenate-responsive transcription factor that mediates arsenate/phosphate transporter gene expression and restricts arsenate-induced transposon activation. Plants therefore have a dual WRKY-dependent signaling mechanism that modulates arsenate uptake and transposon expression, providing a coordinated strategy for arsenate tolerance and transposon gene silencing. PMID:23922208

An alternative Biot's displacement formulation for porous materials.

PubMed

Dazel, Olivier; Brouard, Bruno; Depollier, Claude; Griffiths, Stéphane

2007-06-01

This paper proposes an alternative displacement formulation of Biot's linear model for poroelastic materials. Its advantage is a simplification of the formalism without making any additional assumptions. The main difference between the method proposed in this paper and the original one is the choice of the generalized coordinates. In the present approach, the generalized coordinates are chosen in order to simplify the expression of the strain energy, which is expressed as the sum of two decoupled terms. Hence, new equations of motion are obtained whose elastic forces are decoupled. The simplification of the formalism is extended to Biot and Willis thought experiments, and simpler expressions of the parameters of the three Biot waves are also provided. A rigorous derivation of equivalent and limp models is then proposed. It is finally shown that, for the particular case of sound-absorbing materials, additional simplifications of the formalism can be obtained.

Roles for the Histone Modifying and Exchange Complex NuA4 in Cell Cycle Progression in Drosophila melanogaster.

PubMed

Flegel, Kerry; Grushko, Olga; Bolin, Kelsey; Griggs, Ellen; Buttitta, Laura

2016-07-01

Robust and synchronous repression of E2F-dependent gene expression is critical to the proper timing of cell cycle exit when cells transition to a postmitotic state. Previously NuA4 was suggested to act as a barrier to proliferation in Drosophila by repressing E2F-dependent gene expression. Here we show that NuA4 activity is required for proper cell cycle exit and the repression of cell cycle genes during the transition to a postmitotic state in vivo However, the delay of cell cycle exit caused by compromising NuA4 is not due to additional proliferation or effects on E2F activity. Instead NuA4 inhibition results in slowed cell cycle progression through late S and G2 phases due to aberrant activation of an intrinsic p53-independent DNA damage response. A reduction in NuA4 function ultimately produces a paradoxical cell cycle gene expression program, where certain cell cycle genes become derepressed in cells that are delayed during the G2 phase of the final cell cycle. Bypassing the G2 delay when NuA4 is inhibited leads to abnormal mitoses and results in severe tissue defects. NuA4 physically and genetically interacts with components of the E2F complex termed D: rosophila, R: bf, E: 2F A: nd M: yb/ M: ulti-vulva class B: (DREAM/MMB), and modulates a DREAM/MMB-dependent ectopic neuron phenotype in the posterior wing margin. However, this effect is also likely due to the cell cycle delay, as simply reducing Cdk1 is sufficient to generate a similar phenotype. Our work reveals that the major requirement for NuA4 in the cell cycle in vivo is to suppress an endogenous DNA damage response, which is required to coordinate proper S and G2 cell cycle progression with differentiation and cell cycle gene expression. Copyright © 2016 by the Genetics Society of America.

Roles for the Histone Modifying and Exchange Complex NuA4 in Cell Cycle Progression in Drosophila melanogaster

PubMed Central

Flegel, Kerry; Grushko, Olga; Bolin, Kelsey; Griggs, Ellen; Buttitta, Laura

2016-01-01

Robust and synchronous repression of E2F-dependent gene expression is critical to the proper timing of cell cycle exit when cells transition to a postmitotic state. Previously NuA4 was suggested to act as a barrier to proliferation in Drosophila by repressing E2F-dependent gene expression. Here we show that NuA4 activity is required for proper cell cycle exit and the repression of cell cycle genes during the transition to a postmitotic state in vivo. However, the delay of cell cycle exit caused by compromising NuA4 is not due to additional proliferation or effects on E2F activity. Instead NuA4 inhibition results in slowed cell cycle progression through late S and G2 phases due to aberrant activation of an intrinsic p53-independent DNA damage response. A reduction in NuA4 function ultimately produces a paradoxical cell cycle gene expression program, where certain cell cycle genes become derepressed in cells that are delayed during the G2 phase of the final cell cycle. Bypassing the G2 delay when NuA4 is inhibited leads to abnormal mitoses and results in severe tissue defects. NuA4 physically and genetically interacts with components of the E2F complex termed Drosophila, Rbf, E2F and Myb/Multi-vulva class B (DREAM/MMB), and modulates a DREAM/MMB-dependent ectopic neuron phenotype in the posterior wing margin. However, this effect is also likely due to the cell cycle delay, as simply reducing Cdk1 is sufficient to generate a similar phenotype. Our work reveals that the major requirement for NuA4 in the cell cycle in vivo is to suppress an endogenous DNA damage response, which is required to coordinate proper S and G2 cell cycle progression with differentiation and cell cycle gene expression. PMID:27184390

Coordinating the Chain of Utterances: An Analysis of Communicative Flow and Turn Taking in an Interpreted Group Dialogue for Deaf-Blind Persons

ERIC Educational Resources Information Center

Berge, Sigrid Slettebakk; Raanes, Eli

2013-01-01

This article explains how interpreters for deaf-blind people coordinate and express turn-taking signals in an interpreted dialogue. Empirical materials are derived from a video-ethnographic study of an interpreted-mediated board meeting with five deaf-blind participants. The results show that the interpreters provide access to visual and auditory…

Lorentz-covariant coordinate-space representation of the leading hadronic contribution to the anomalous magnetic moment of the muon

NASA Astrophysics Data System (ADS)

Meyer, Harvey B.

2017-09-01

We present a Lorentz-covariant, Euclidean coordinate-space expression for the hadronic vacuum polarisation, the Adler function and the leading hadronic contribution to the anomalous magnetic moment of the muon. The representation offers a high degree of flexibility for an implementation in lattice QCD. We expect it to be particularly helpful for the quark-line disconnected contributions.

Transcript Profile Analyses of Maize Silks Reveal Effective Activation of Genes Involved in Microtubule-Based Movement, Ubiquitin-Dependent Protein Degradation, and Transport in the Pollination Process

PubMed Central

Chen, Hao; Sun, Wei; Zhang, Xian Sheng

2013-01-01

Pollination is the first crucial step of sexual reproduction in flowering plants, and it requires communication and coordination between the pollen and the stigma. Maize (Zea mays) is a model monocot with extraordinarily long silks, and a fully sequenced genome, but little is known about the mechanism of its pollen–stigma interactions. In this study, the dynamic gene expression of silks at four different stages before and after pollination was analyzed. The expression profiles of immature silks (IMS), mature silks (MS), and silks at 20 minutes and 3 hours after pollination (20MAP and 3HAP, respectively) were compared. In total, we identified 6,337 differentially expressed genes in silks (SDEG) at the four stages. Among them, the expression of 172 genes were induced upon pollination, most of which participated in RNA binding, processing and transcription, signal transduction, and lipid metabolism processes. Genes in the SDEG dataset could be divided into 12 time-course clusters according to their expression patterns. Gene Ontology (GO) enrichment analysis revealed that many genes involved in microtubule-based movement, ubiquitin-mediated protein degradation, and transport were predominantly expressed at specific stages, indicating that they might play important roles in the pollination process of maize. These results add to current knowledge about the pollination process of grasses and provide a foundation for future studies on key genes involved in the pollen–silk interaction in maize. PMID:23301084

Comprehensive analysis of CLE polypeptide signaling gene expression and over-expression activity in Arabidopsis

USDA-ARS?s Scientific Manuscript database

Intercellular signaling is essential for the coordination of growth and development in higher plants. Although hundreds of putative receptors have been identified in Arabidopsis thaliana, only a few families of extracellular signaling molecules have been discovered and their biological roles are lar...

Topographic Information Requirements and Computer-Graphic Display Techniques for Nap-of-the-Earth Flight.

DTIC Science & Technology

1979-12-01

required of the Army aviator. The successful accomplishment of many of these activities depends upon the aviator’s ability to extract information from maps...Cruise NOE VBI Determine Position VB2 Crew Coordination (Topographic) VB3 Radio Communication VI . TERM4INATION C. Post-Flight VIC1 Debriefing 11LA 1I...NOE FUNCTION: VBI DETERMINE POSITION INFORMATION REQUIREMENT SPECIFICS SOURCE COMMENTS See Function IIIAl ! FUNCTION: VB2 CREW COORDINATION

40 CFR 233.31 - Coordination requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... discharge may affect the biological, chemical, or physical integrity of the waters of any State(s) other... coordinated with Federal and Federal-State water related planning and review processes. ...

Path description of coordinate-space amplitudes

NASA Astrophysics Data System (ADS)

Erdoǧan, Ozan; Sterman, George

2017-06-01

We develop a coordinate version of light-cone-ordered perturbation theory, for general time-ordered products of fields, by carrying out integrals over one light-cone coordinate for each interaction vertex. The resulting expressions depend on the lengths of paths, measured in the same light-cone coordinate. Each path is associated with a denominator equal to a "light-cone deficit," analogous to the "energy deficits" of momentum-space time- or light-cone-ordered perturbation theory. In effect, the role played by intermediate states in momentum space is played by paths between external fields in coordinate space. We derive a class of identities satisfied by coordinate diagrams, from which their imaginary parts can be derived. Using scalar QED as an example, we show how the eikonal approximation arises naturally when the external points in a Green function approach the light cone, and we give applications to products of Wilson lines. Although much of our discussion is directed at massless fields in four dimensions, we extend the formalism to massive fields and dimensional regularization.

The Role and Load of the Athletic Training Clinical Education Coordinator

ERIC Educational Resources Information Center

Radtke, Sarah

2017-01-01

Context: The position of clinical education coordinator has been identified as a required one in athletic training education. However, the literature has yet to address the job responsibilities of clinical education coordinators and the commensurate work load/release time needed to accomplish these responsibilities in athletic training education.…

The Developmental Effect of Concurrent Cognitive and Locomotor Skills: Time-Sharing from a Dynamical Perspective.

ERIC Educational Resources Information Center

Whitall, Jill

1991-01-01

Presents research on the effects of concurrent verbal cognition on locomotor skills. Results revealed no interference with coordination variables across age, but some interference with control variables, particularly in younger subjects. Coordination of gait required less attention than setting of control parameters. This coordination was in place…

Jaw-Phonatory Coordination in Chronic Developmental Stuttering

ERIC Educational Resources Information Center

Loucks, Torrey M. J.; De Nil, Luc F.; Sasisekaran, Jayanthi

2007-01-01

A deficiency in sensorimotor integration in a person who stutters may be a factor in the pathophysiology of developmental stuttering. To test oral sensorimotor function in adults who stutter, we used a task that requires the coordination of a jaw-opening movement with phonation onset. The task was adapted from previous limb coordination studies,…

Nonlinear finite element formulation for the large displacement analysis in multibody system dynamics

NASA Technical Reports Server (NTRS)

Rismantab-Sany, J.; Chang, B.; Shabana, A. A.

1989-01-01

A total Lagrangian finite element formulation for the deformable bodies in multibody mechanical systems that undergo finite relative rotations is developed. The deformable bodies are discretized using finite element methods. The shape functions that are used to describe the displacement field are required to include the rigid body modes that describe only large translational displacements. This does not impose any limitations on the technique because most commonly used shape functions satisfy this requirement. The configuration of an element is defined using four sets of coordinate systems: Body, Element, Intermediate element, Global. The body coordinate system serves as a unique standard for the assembly of the elements forming the deformable body. The element coordinate system is rigidly attached to the element and therefore it translates and rotates with the element. The intermediate element coordinate system, whose axes are initially parallel to the element axes, has an origin which is rigidly attached to the origin of the body coordinate system and is used to conveniently describe the configuration of the element in undeformed state with respect to the body coordinate system.

Implementation of system dynamic simulation method to optimize profit in supply chain network of vegetable product

NASA Astrophysics Data System (ADS)

Tama, I. P.; Akbar, Z.; Eunike, A.

2018-04-01

Vegetables are categorized as a perishable product, which is a product with short lifespan thus requires proper handling and planning to reduce losses caused by the short lifespan. In order to reduce the losses, coordination among the players in the supply chain is required. On the other hand, the decision in the supply chain of vegetables and other farming products in the traditional market of developing country is independent among the players. This research is conducted by using System Dynamic Simulation method to develop model and scenario by coordinating the supply quantity amongst players in the supply chain. The scenarios are developed based on newsboy inventory model. This study aims to compare scenarios combining tiers involved in coordination program. The result shows that coordination in supply chain increases total supply chain profit, although there will always be players who experienced decrements in profit. The scenario of coordination among the farmer, the distributor, and the wholesaler resulted in the highest increase in total supply chain profit compared to other coordination scenarios, with an increased value of 10.49%.

PecS and PecT coregulate the synthesis of HrpN and pectate lyases, two virulence determinants in Erwinia chrysanthemi 3937.

PubMed

Nasser, William; Reverchon, Sylvie; Vedel, Regine; Boccara, Martine

2005-11-01

Erwinia chrysanthemi strain 3937 is a necrotrophic bacterial plant pathogen. Pectinolytic enzymes and, in particular, pectate lyases play a key role in soft rot symptoms; however, the efficient colonization of plants by E. chrysanthemi requires additional factors. These factors include HrpN (harpin), a heat-stable, glycine-rich hydrophilic protein, which is secreted by the type III secretion system. We investigated the expression of hrpN in E. chrysanthemi 3937 in various environmental conditions and different regulatory backgrounds. Using lacZ fusions, hrpN expression was markedly influenced by the carbon source, osmolarity, growth phase, and growth substrate. hrpN was repressed when pectinolysis started and negatively regulated by the repressors of pectate lyase synthesis, PecS and PecT. Primer extension data and in vitro DNA-protein interaction experiments support a model whereby PecS represses hrpN expression by binding to the hrpN regulatory region and inhibiting transcript elongation. The results suggest coordinated regulation of HrpN and pectate lyases by PecS and PecT. A putative model of the synthesis of these two virulence factors in E. chrysanthemi during pathogenesis is presented.

The PARP1-Siah1 Axis Controls HIV-1 Transcription and Expression of Siah1 Substrates.

PubMed

Yu, Dan; Liu, Rongdiao; Yang, Geng; Zhou, Qiang

2018-06-26

Recent studies have revealed a key role of PARP1 that catalyzes the poly-ADP-ribosylation (PARylation) of substrates in regulating gene transcription. We show here that HIV-1 transcriptional activation also requires PARP1 activity. Because efficient HIV-1 transactivation is known to depend on the ELL2-containing super elongation complex (SEC), we investigated the functional relationship between PARP1 and ELL2-SEC in HIV-1 transcriptional control. We show that PARP1 elevates ELL2 protein levels to form more ELL2-SEC in cells. This effect is caused by PARP1's suppression of expression of Siah1, an E3 ubiquitin ligase for ELL2, at both mRNA and protein levels. At the mRNA level, PARP1 coordinates with the co-repressor NCoR to suppress Siah1 transcription. At the protein level, PARP1 promotes Siah1 proteolysis, likely through inducing PARylation-dependent ubiquitination (PARdU) of Siah1. Thus, a PARP1-Siah1 axis activates HIV-1 transcription and controls the expression of ELL2 and other Siah1 substrates. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

The chemokine receptor CXCR6 controls the functional topography of interleukin-22 producing intestinal innate lymphoid cells.

PubMed

Satoh-Takayama, Naoko; Serafini, Nicolas; Verrier, Thomas; Rekiki, Abdessalem; Renauld, Jean-Christophe; Frankel, Gad; Di Santo, James P

2014-11-20

Interleukin-22 (IL-22) plays a critical role in mucosal defense, although the molecular mechanisms that ensure IL-22 tissue distribution remain poorly understood. We show that the CXCL16-CXCR6 chemokine-chemokine receptor axis regulated group 3 innate lymphoid cell (ILC3) diversity and function. CXCL16 was constitutively expressed by CX3CR1(+) intestinal dendritic cells (DCs) and coexpressed with IL-23 after Citrobacter rodentium infection. Intestinal ILC3s expressed CXCR6 and its ablation generated a selective loss of the NKp46(+) ILC3 subset, a depletion of intestinal IL-22, and the inability to control C. rodentium infection. CD4(+) ILC3s were unaffected by CXCR6 deficiency and remained clustered within lymphoid follicles. In contrast, the lamina propria of Cxcr6(-/-) mice was devoid of ILC3s. The loss of ILC3-dependent IL-22 epithelial stimulation reduced antimicrobial peptide expression that explained the sensitivity of Cxcr6(-/-) mice to C. rodentium. Our results delineate a critical CXCL16-CXCR6 crosstalk that coordinates the intestinal topography of IL-22 secretion required for mucosal defense. Copyright © 2014 Elsevier Inc. All rights reserved.

MondoA Is an Essential Glucose-Responsive Transcription Factor in Human Pancreatic β-Cells.

PubMed

Richards, Paul; Rachdi, Latif; Oshima, Masaya; Marchetti, Piero; Bugliani, Marco; Armanet, Mathieu; Postic, Catherine; Guilmeau, Sandra; Scharfmann, Raphael

2018-03-01

Although the mechanisms by which glucose regulates insulin secretion from pancreatic β-cells are now well described, the way glucose modulates gene expression in such cells needs more understanding. Here, we demonstrate that MondoA, but not its paralog carbohydrate-responsive element-binding protein, is the predominant glucose-responsive transcription factor in human pancreatic β-EndoC-βH1 cells and in human islets. In high-glucose conditions, MondoA shuttles to the nucleus where it is required for the induction of the glucose-responsive genes arrestin domain-containing protein 4 (ARRDC4) and thioredoxin interacting protein (TXNIP), the latter being a protein strongly linked to β-cell dysfunction and diabetes. Importantly, increasing cAMP signaling in human β-cells, using forskolin or the glucagon-like peptide 1 mimetic Exendin-4, inhibits the shuttling of MondoA and potently inhibits TXNIP and ARRDC4 expression. Furthermore, we demonstrate that silencing MondoA expression improves glucose uptake in EndoC-βH1 cells. These results highlight MondoA as a novel target in β-cells that coordinates transcriptional response to elevated glucose levels. © 2017 by the American Diabetes Association.

Individual differences in algebraic cognition: Relation to the approximate number and semantic memory systems.

PubMed

Geary, David C; Hoard, Mary K; Nugent, Lara; Rouder, Jeffrey N

2015-12-01

The relation between performance on measures of algebraic cognition and acuity of the approximate number system (ANS) and memory for addition facts was assessed for 171 ninth graders (92 girls) while controlling for parental education, sex, reading achievement, speed of numeral processing, fluency of symbolic number processing, intelligence, and the central executive component of working memory. The algebraic tasks assessed accuracy in placing x,y pairs in the coordinate plane, speed and accuracy of expression evaluation, and schema memory for algebra equations. ANS acuity was related to accuracy of placements in the coordinate plane and expression evaluation but not to schema memory. Frequency of fact retrieval errors was related to schema memory but not to coordinate plane or expression evaluation accuracy. The results suggest that the ANS may contribute to or be influenced by spatial-numerical and numerical-only quantity judgments in algebraic contexts, whereas difficulties in committing addition facts to long-term memory may presage slow formation of memories for the basic structure of algebra equations. More generally, the results suggest that different brain and cognitive systems are engaged during the learning of different components of algebraic competence while controlling for demographic and domain general abilities. Copyright © 2015 Elsevier Inc. All rights reserved.

Reference coordinate systems: An update. Supplement 11

NASA Technical Reports Server (NTRS)

Mueller, Ivan I.

1988-01-01

A common requirement for all geodetic investigations is a well-defined coordinate system attached to the earth in some prescribed way, as well as a well-defined inertial coordinate system in which the motions of the terrestrial frame can be monitored. The paper deals with the problems encountered when establishing such coordinate systems and the transformations between them. In addition, problems related to the modeling of the deformable earth are discussed. This paper is an updated version of the earlier work, Reference Coordinate Systems for Earth Dynamics: A Preview, by the author.

Determining coordinates of the rotational pole using satellite data from four sites

NASA Astrophysics Data System (ADS)

Pisacane, V. L.; Dillon, S. C.

1981-02-01

The precision of the terrestrial coordinates of the rotational pole was determined from the satellite data using the Navy Navigation Satellite System (TRANSIT). Observations were made in Maine, Minnesota, California, and Hawaii; the data agreed with extrapolated and final coordinates from the Bureau International de l'Heure and final coordinates from the Doppler Polar Motion Service. The investigation indicates that low-cost and near-real-time estimates of the terrestrial coordinates of the pole are available as a by-product of the routine support required for the TRANSIT.

Patient- and family-centered care coordination: a framework for integrating care for children and youth across multiple systems.

PubMed

2014-05-01

Understanding a care coordination framework, its functions, and its effects on children and families is critical for patients and families themselves, as well as for pediatricians, pediatric medical subspecialists/surgical specialists, and anyone providing services to children and families. Care coordination is an essential element of a transformed American health care delivery system that emphasizes optimal quality and cost outcomes, addresses family-centered care, and calls for partnership across various settings and communities. High-quality, cost-effective health care requires that the delivery system include elements for the provision of services supporting the coordination of care across settings and professionals. This requirement of supporting coordination of care is generally true for health systems providing care for all children and youth but especially for those with special health care needs. At the foundation of an efficient and effective system of care delivery is the patient-/family-centered medical home. From its inception, the medical home has had care coordination as a core element. In general, optimal outcomes for children and youth, especially those with special health care needs, require interfacing among multiple care systems and individuals, including the following: medical, social, and behavioral professionals; the educational system; payers; medical equipment providers; home care agencies; advocacy groups; needed supportive therapies/services; and families. Coordination of care across settings permits an integration of services that is centered on the comprehensive needs of the patient and family, leading to decreased health care costs, reduction in fragmented care, and improvement in the patient/family experience of care. Copyright © 2014 by the American Academy of Pediatrics.

Expression of hLAMP-1-Positive Particles During Early Heart Development in the Chick.

PubMed

Abd-Elhamid, T H; Conway, M L; Sinning, A R

2017-10-01

Heart development requires coordinated activity of various factors, the disturbance of which can lead to congenital heart defects. Heart lectin-associated matrix protein-1 (hLAMP-1) is a matrix protein expressed within Hensen's node at Hamburger-Hamilton (HH) stage 4, in the lateral mesoderm by HH stages 5-6 and enhanced within the left pre-cardiac field at HH stage 7. At HH stages 15-16, hLAMP-1 expression is observed in the atrioventricular canal and the outflow tract. Also, the role of hLAMP-1 in induction of mesenchyme formation in chick heart has been well documented. To further elucidate the role of this molecule in heart development, we examined its expression patterns during HH stages 8-14 in the chick. In this regard, we immunostained sections of the heart during HH stages 8-14 with antibodies specific to hLAMP-1. Our results showed prominent expression of hLAMP-1-positive particles in the extracellular matrix associated with the pre-cardiac mesoderm, the endoderm, ectoderm as well as neuroectoderm at HH stages 8-9. After formation of the linear heart tube at HH stage 10, the expression of hLAMP-1-stained particles disappears in those regions of original contact between the endoderm and heart forming fields due to rupture of the dorsal mesocardium while their expression becomes confined to the arterial and venous poles of the heart tube. This expression pattern is maintained until HH stage 14. This expression pattern suggests that hLAMP-1 may be involved in the formation of the endocardial tube. © 2017 Blackwell Verlag GmbH.

Sequential induction of three recombination directionality factors directs assembly of tripartite integrative and conjugative elements.

PubMed

Haskett, Timothy L; Terpolilli, Jason J; Ramachandran, Vinoy K; Verdonk, Callum J; Poole, Phillip S; O'Hara, Graham W; Ramsay, Joshua P

2018-03-01

Tripartite integrative and conjugative elements (ICE3) are a novel form of ICE that exist as three separate DNA regions integrated within the genomes of Mesorhizobium spp. Prior to conjugative transfer the three ICE3 regions of M. ciceri WSM1271 ICEMcSym1271 combine and excise to form a single circular element. This assembly requires three coordinated recombination events involving three site-specific recombinases IntS, IntG and IntM. Here, we demonstrate that three excisionases-or recombination directionality factors-RdfS, RdfG and RdfM are required for ICE3 excision. Transcriptome sequencing revealed that expression of ICE3 transfer and conjugation genes was induced by quorum sensing. Quorum sensing activated expression of rdfS, and in turn RdfS stimulated transcription of both rdfG and rdfM. Therefore, RdfS acts as a "master controller" of ICE3 assembly and excision. The dependence of all three excisive reactions on RdfS ensures that ICE3 excision occurs via a stepwise sequence of recombination events that avoids splitting the chromosome into a non-viable configuration. These discoveries expose a surprisingly simple control system guiding molecular assembly of these novel and complex mobile genetic elements and highlight the diverse and critical functions of excisionase proteins in control of horizontal gene transfer.

Nitric oxide regulation of calcitonin gene-related peptide gene expression in rat trigeminal ganglia neurons

PubMed Central

Bellamy, Jamie; Bowen, Elizabeth J.; Russo, Andrew F.; Durham, Paul L.

2006-01-01

Calcitonin gene-related peptide (CGRP) and nitric oxide are involved in the underlying pathophysiology of migraine and other diseases involving neurogenic inflammation. We have tested the hypothesis that nitric oxide might trigger signaling mechanisms within the trigeminal ganglia neurons that would coordinately stimulate CGRP synthesis and release. Treatment of primary trigeminal ganglia cultures with nitric oxide donors caused a greater than four-fold increase in CGRP release compared with unstimulated cultures. Similarly, CGRP promoter activity was also stimulated by nitric oxide donors and overexpression of inducible nitric oxide synthase (iNOS). Cotreatment with the antimigraine drug sumatriptan greatly repressed nitric oxide stimulation of CGRP promoter activity and secretion. Somewhat surprisingly, the mechanisms of nitric oxide stimulation of CGRP secretion did not require cGMP or PI3-kinase signaling pathways, but rather, nitric oxide action required extracellular calcium and likely involves T-type calcium channels. Furthermore, nitric oxide was shown to increase expression of the active forms of the mitogen-activated protein kinases Jun amino-terminal kinase and p38 but not extracellular signal-related kinase in trigeminal neurons. In summary, our results provide new insight into the cellular mechanisms by which nitric oxide induces CGRP synthesis and secretion from trigeminal neurons. PMID:16630053

30 CFR 773.5 - Regulatory coordination with requirements under other laws.

Code of Federal Regulations, 2013 CFR

2013-07-01

... operations with applicable requirements of the Endangered Species Act of 1973, as amended (16 U.S.C. 1531 et seq.); the Fish and Wildlife Coordination Act, as amended (16 U.S.C. 661 et seq.); the Migratory Bird Treaty Act of 1918, as amended (16 U.S.C. 703 et seq.); The National Historic Preservation Act of 1966...

30 CFR 773.5 - Regulatory coordination with requirements under other laws.

Code of Federal Regulations, 2011 CFR

2011-07-01

... operations with applicable requirements of the Endangered Species Act of 1973, as amended (16 U.S.C. 1531 et seq.); the Fish and Wildlife Coordination Act, as amended (16 U.S.C. 661 et seq.); the Migratory Bird Treaty Act of 1918, as amended (16 U.S.C. 703 et seq.); The National Historic Preservation Act of 1966...

30 CFR 773.5 - Regulatory coordination with requirements under other laws.

Code of Federal Regulations, 2014 CFR

2014-07-01

... operations with applicable requirements of the Endangered Species Act of 1973, as amended (16 U.S.C. 1531 et seq.); the Fish and Wildlife Coordination Act, as amended (16 U.S.C. 661 et seq.); the Migratory Bird Treaty Act of 1918, as amended (16 U.S.C. 703 et seq.); The National Historic Preservation Act of 1966...

30 CFR 773.5 - Regulatory coordination with requirements under other laws.

Code of Federal Regulations, 2012 CFR

2012-07-01

... operations with applicable requirements of the Endangered Species Act of 1973, as amended (16 U.S.C. 1531 et seq.); the Fish and Wildlife Coordination Act, as amended (16 U.S.C. 661 et seq.); the Migratory Bird Treaty Act of 1918, as amended (16 U.S.C. 703 et seq.); The National Historic Preservation Act of 1966...

30 CFR 773.5 - Regulatory coordination with requirements under other laws.

Code of Federal Regulations, 2010 CFR

2010-07-01

... operations with applicable requirements of the Endangered Species Act of 1973, as amended (16 U.S.C. 1531 et seq.); the Fish and Wildlife Coordination Act, as amended (16 U.S.C. 661 et seq.); the Migratory Bird Treaty Act of 1918, as amended (16 U.S.C. 703 et seq.); The National Historic Preservation Act of 1966...

34 CFR 403.15 - What are the personnel requirements regarding coordination with services under chapter 1 of title...

Code of Federal Regulations, 2011 CFR

2011-07-01

... 34 Education 3 2011-07-01 2011-07-01 false What are the personnel requirements regarding coordination with services under chapter 1 of title I of the Elementary and Secondary Education Act? 403.15 Section 403.15 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF...

20 CFR 663.320 - What are the requirements for coordination of WIA training funds and other grant assistance?

Code of Federal Regulations, 2010 CFR

2010-04-01

... coordination of WIA training funds and other grant assistance? (a) WIA funding for training is limited to participants who: (1) Are unable to obtain grant assistance from other sources to pay the costs of their training; or (2) Require assistance beyond that available under grant assistance from other sources to pay...

Proline Coordination with Fatty Acid Synthesis and Redox Metabolism of Chloroplast and Mitochondria.

PubMed

Shinde, Suhas; Villamor, Joji Grace; Lin, Wendar; Sharma, Sandeep; Verslues, Paul E

2016-10-01

Proline (Pro) accumulation is one of the most prominent changes in plant metabolism during drought and low water potential; however, the regulation and function of Pro metabolism remain unclear. We used a combination of forward genetic screening based on a Proline Dehydrogenase1 (PDH1) promoter-luciferase reporter (PDH1 pro :LUC2) and RNA sequencing of the Pro synthesis mutant p5cs1-4 to identify multiple loci affecting Pro accumulation in Arabidopsis (Arabidopsis thaliana). Two mutants having high PDH1 pro :LUC2 expression and increased Pro accumulation at low water potential were found to be alleles of Cytochrome P450, Family 86, Subfamily A, Polypeptide2 (CYP86A2) and Long Chain Acyl Synthetase2 (LACS2), which catalyze two successive steps in very-long-chain fatty acid (VLCFA) synthesis. Reverse genetic experiments found additional VLCFA and lipid metabolism-related mutants with increased Pro accumulation. Altered cellular redox status is a key factor in the coordination of Pro and VLCFA metabolism. The NADPH oxidase inhibitor diphenyleneiodonium (DPI) induced high levels of Pro accumulation and strongly repressed PDH1 pro :LUC2 expression. cyp86a2 and lacs2 mutants were hypersensitive to diphenyleneiodonium but could be reverted to wild-type Pro and PDH1 pro :LUC2 expression by reactive oxygen species scavengers. The coordination of Pro and redox metabolism also was indicated by the altered expression of chloroplast and mitochondria electron transport genes in p5cs1-4 These results show that Pro metabolism is both influenced by and influences cellular redox status via previously unknown coordination with several metabolic pathways. In particular, Pro and VLCFA synthesis share dual roles to help buffer cellular redox status while producing products useful for stress resistance, namely the compatible solute Pro and cuticle lipids. © 2016 American Society of Plant Biologists. All Rights Reserved.

Proline Coordination with Fatty Acid Synthesis and Redox Metabolism of Chloroplast and Mitochondria1[OPEN

PubMed Central

Shinde, Suhas; Villamor, Joji Grace; Lin, Wendar; Verslues, Paul E.

2016-01-01

Proline (Pro) accumulation is one of the most prominent changes in plant metabolism during drought and low water potential; however, the regulation and function of Pro metabolism remain unclear. We used a combination of forward genetic screening based on a Proline Dehydrogenase1 (PDH1) promoter-luciferase reporter (PDH1pro:LUC2) and RNA sequencing of the Pro synthesis mutant p5cs1-4 to identify multiple loci affecting Pro accumulation in Arabidopsis (Arabidopsis thaliana). Two mutants having high PDH1pro:LUC2 expression and increased Pro accumulation at low water potential were found to be alleles of Cytochrome P450, Family 86, Subfamily A, Polypeptide2 (CYP86A2) and Long Chain Acyl Synthetase2 (LACS2), which catalyze two successive steps in very-long-chain fatty acid (VLCFA) synthesis. Reverse genetic experiments found additional VLCFA and lipid metabolism-related mutants with increased Pro accumulation. Altered cellular redox status is a key factor in the coordination of Pro and VLCFA metabolism. The NADPH oxidase inhibitor diphenyleneiodonium (DPI) induced high levels of Pro accumulation and strongly repressed PDH1pro:LUC2 expression. cyp86a2 and lacs2 mutants were hypersensitive to diphenyleneiodonium but could be reverted to wild-type Pro and PDH1pro:LUC2 expression by reactive oxygen species scavengers. The coordination of Pro and redox metabolism also was indicated by the altered expression of chloroplast and mitochondria electron transport genes in p5cs1-4. These results show that Pro metabolism is both influenced by and influences cellular redox status via previously unknown coordination with several metabolic pathways. In particular, Pro and VLCFA synthesis share dual roles to help buffer cellular redox status while producing products useful for stress resistance, namely the compatible solute Pro and cuticle lipids. PMID:27512016

Are electronic medical records helpful for care coordination? Experiences of physician practices.

PubMed

O'Malley, Ann S; Grossman, Joy M; Cohen, Genna R; Kemper, Nicole M; Pham, Hoangmai H

2010-03-01

Policies promoting widespread adoption of electronic medical records (EMRs) are premised on the hope that they can improve the coordination of care. Yet little is known about whether and how physician practices use current EMRs to facilitate coordination. We examine whether and how practices use commercial EMRs to support coordination tasks and identify work-around practices have created to address new coordination challenges. Semi-structured telephone interviews in 12 randomly selected communities. Sixty respondents, including 52 physicians or staff from 26 practices with commercial ambulatory care EMRs in place for at least 2 years, chief medical officers at four EMR vendors, and four national thought leaders. Six major themes emerged: (1) EMRs facilitate within-office care coordination, chiefly by providing access to data during patient encounters and through electronic messaging; (2) EMRs are less able to support coordination between clinicians and settings, in part due to their design and a lack of standardization of key data elements required for information exchange; (3) managing information overflow from EMRs is a challenge for clinicians; (4) clinicians believe current EMRs cannot adequately capture the medical decision-making process and future care plans to support coordination; (5) realizing EMRs' potential for facilitating coordination requires evolution of practice operational processes; (6) current fee-for-service reimbursement encourages EMR use for documentation of billable events (office visits, procedures) and not of care coordination (which is not a billable activity). There is a gap between policy-makers' expectation of, and clinical practitioners' experience with, current electronic medical records' ability to support coordination of care. Policymakers could expand current health information technology policies to support assessment of how well the technology facilitates tasks necessary for coordination. By reforming payment policy to include care coordination, policymakers could encourage the evolution of EMR technology to include capabilities that support coordination, for example, allowing for inter-practice data exchange and multi-provider clinical decision support.

47 CFR 15.525 - Coordination requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... FCC Office of Engineering and Technology, which shall coordinate this information with the Federal... the UWB device. If the imaging device is intended to be used for mobile applications, the geographical...

The POU Factor Ventral Veins Lacking/Drifter Directs the Timing of Metamorphosis through Ecdysteroid and Juvenile Hormone Signaling

PubMed Central

Chaieb, Leila; Koyama, Takashi; Sarwar, Prioty; Mirth, Christen K.; Smith, Wendy A.; Suzuki, Yuichiro

2014-01-01

Although endocrine changes are known to modulate the timing of major developmental transitions, the genetic mechanisms underlying these changes remain poorly understood. In insects, two developmental hormones, juvenile hormone (JH) and ecdysteroids, are coordinated with each other to induce developmental changes associated with metamorphosis. However, the regulation underlying the coordination of JH and ecdysteroid synthesis remains elusive. Here, we examined the function of a homolog of the vertebrate POU domain protein, Ventral veins lacking (Vvl)/Drifter, in regulating both of these hormonal pathways in the red flour beetle, Tribolium castaneum (Tenebrionidae). RNA interference-mediated silencing of vvl expression led to both precocious metamorphosis and inhibition of molting in the larva. Ectopic application of a JH analog on vvl knockdown larvae delayed the onset of metamorphosis and led to a prolonged larval stage, indicating that Vvl acts upstream of JH signaling. Accordingly, vvl knockdown also reduced the expression of a JH biosynthesis gene, JH acid methyltransferase 3 (jhamt3). In addition, ecdysone titer and the expression of the ecdysone response gene, hormone receptor 3 (HR3), were reduced in vvl knockdown larvae. The expression of the ecdysone biosynthesis gene phantom (phm) and spook (spo) were reduced in vvl knockdown larvae in the anterior and posterior halves, respectively, indicating that Vvl might influence ecdysone biosynthesis in both the prothoracic gland and additional endocrine sources. Injection of 20-hydroxyecdysone (20E) into vvl knockdown larvae could restore the expression of HR3 although molting was never restored. These findings suggest that Vvl coordinates both JH and ecdysteroid biosynthesis as well as molting behavior to influence molting and the timing of metamorphosis. Thus, in both vertebrates and insects, POU factors modulate the production of major neuroendocrine regulators during sexual maturation. PMID:24945490

A Regulatory Network for Coordinated Flower Maturation

PubMed Central

Ploense, Sara E.; Wu, Miin-Feng; Yadav, Vandana; Tholl, Dorothea; Chételat, Aurore; Haupt, Ina; Kennerley, Brian J.; Hodgens, Charles; Farmer, Edward E.; Nagpal, Punita; Reed, Jason W.

2012-01-01

For self-pollinating plants to reproduce, male and female organ development must be coordinated as flowers mature. The Arabidopsis transcription factors AUXIN RESPONSE FACTOR 6 (ARF6) and ARF8 regulate this complex process by promoting petal expansion, stamen filament elongation, anther dehiscence, and gynoecium maturation, thereby ensuring that pollen released from the anthers is deposited on the stigma of a receptive gynoecium. ARF6 and ARF8 induce jasmonate production, which in turn triggers expression of MYB21 and MYB24, encoding R2R3 MYB transcription factors that promote petal and stamen growth. To understand the dynamics of this flower maturation regulatory network, we have characterized morphological, chemical, and global gene expression phenotypes of arf, myb, and jasmonate pathway mutant flowers. We found that MYB21 and MYB24 promoted not only petal and stamen development but also gynoecium growth. As well as regulating reproductive competence, both the ARF and MYB factors promoted nectary development or function and volatile sesquiterpene production, which may attract insect pollinators and/or repel pathogens. Mutants lacking jasmonate synthesis or response had decreased MYB21 expression and stamen and petal growth at the stage when flowers normally open, but had increased MYB21 expression in petals of older flowers, resulting in renewed and persistent petal expansion at later stages. Both auxin response and jasmonate synthesis promoted positive feedbacks that may ensure rapid petal and stamen growth as flowers open. MYB21 also fed back negatively on expression of jasmonate biosynthesis pathway genes to decrease flower jasmonate level, which correlated with termination of growth after flowers have opened. These dynamic feedbacks may promote timely, coordinated, and transient growth of flower organs. PMID:22346763

Transcriptomic basis of functional difference and coordination between seeds and the silique wall of Brassica napus during the seed-filling stage.

PubMed

Liu, Han; Yang, Qingyong; Fan, Chuchuan; Zhao, Xiaoqin; Wang, Xuemin; Zhou, Yongming

2015-04-01

The silique of oilseed rape (Brassica napus) is a composite organ including seeds and the silique wall (SW) that possesses distinctly physiological, biochemical and functional differentiations. Yet, the molecular events controlling such differences between the SW and seeds, as well as their coordination during silique development at transcriptional level are largely unknown. Here, we identified large sets of differentially expressed genes in the SW and seeds of siliques at 21-22 days after flowering with a Brassica 95K EST microarray. At this particular stage, there were 3278 SW preferentially expressed genes and 2425 seed preferentially expressed genes. Using the MapMan visualization software, genes differentially regulated in various metabolic pathways and sub-pathways between the SW and seeds were revealed. Photosynthesis and transport-related genes were more actively transcripted in the SW, while those involved in lipid metabolism were more active in seeds during the seed filling stage. On the other hand, genes involved in secondary metabolisms were selectively regulated in the SW and seeds. Large numbers of transcription factors were identified to be differentially expressed between the SW and seeds, suggesting a complex pattern of transcriptional control in these two organs. Furthermore, most genes discussed in categories or pathways showed a similar expression pattern through 21 DAF to 42 DAF. Our results thus provide insights into the coordination of seeds and the SW in the developing silique at the transcriptional levels, which will facilitate the functional studies of important genes for improving B. napus seed productivity and quality. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Structural and functional studies of a family of Dictyostelium discoideum developmentally regulated, prestalk genes coding for small proteins.

PubMed

Vicente, Juan J; Galardi-Castilla, María; Escalante, Ricardo; Sastre, Leandro

2008-01-03

The social amoeba Dictyostelium discoideum executes a multicellular development program upon starvation. This morphogenetic process requires the differential regulation of a large number of genes and is coordinated by extracellular signals. The MADS-box transcription factor SrfA is required for several stages of development, including slug migration and spore terminal differentiation. Subtractive hybridization allowed the isolation of a gene, sigN (SrfA-induced gene N), that was dependent on the transcription factor SrfA for expression at the slug stage of development. Homology searches detected the existence of a large family of sigN-related genes in the Dictyostelium discoideum genome. The 13 most similar genes are grouped in two regions of chromosome 2 and have been named Group1 and Group2 sigN genes. The putative encoded proteins are 87-89 amino acids long. All these genes have a similar structure, composed of a first exon containing a 13 nucleotides long open reading frame and a second exon comprising the remaining of the putative coding region. The expression of these genes is induced at10 hours of development. Analyses of their promoter regions indicate that these genes are expressed in the prestalk region of developing structures. The addition of antibodies raised against SigN Group 2 proteins induced disintegration of multi-cellular structures at the mound stage of development. A large family of genes coding for small proteins has been identified in D. discoideum. Two groups of very similar genes from this family have been shown to be specifically expressed in prestalk cells during development. Functional studies using antibodies raised against Group 2 SigN proteins indicate that these genes could play a role during multicellular development.

How precise can atoms of a nanocluster be located in 3D using a tilt series of scanning transmission electron microscopy images?

PubMed

Alania, M; De Backer, A; Lobato, I; Krause, F F; Van Dyck, D; Rosenauer, A; Van Aert, S

2017-10-01

In this paper, we investigate how precise atoms of a small nanocluster can ultimately be located in three dimensions (3D) from a tilt series of images acquired using annular dark field (ADF) scanning transmission electron microscopy (STEM). Therefore, we derive an expression for the statistical precision with which the 3D atomic position coordinates can be estimated in a quantitative analysis. Evaluating this statistical precision as a function of the microscope settings also allows us to derive the optimal experimental design. In this manner, the optimal angular tilt range, required electron dose, optimal detector angles, and number of projection images can be determined. Copyright © 2016 Elsevier B.V. All rights reserved.

Technology-dependent children and the demand for pharmaceutical care.

PubMed

Okido, Aline Cristiane Cavicchioli; Cunha, Suelen Teles da; Neves, Eliane Tatsch; Dupas, Giselle; Lima, Regina Aparecida Garcia de

2016-01-01

to understand the experience of mothers of technology-dependent children as regards pharmaceutical care. this was a qualitative, descriptive-exploratory study developed based on open interviews using a structured characterization tool, and applied during home visits to 12 mothers caring for technology-dependent children. The data was submitted to inductive content analysis. this study is split into two themes: (i) maternal overload during pharmaceutical care, demonstrating the need to administer drugs continuously and the repercussions of this exhaustive care on the caregivers; (ii) the ease or difficulty of access to the medicines required, showing informal strategies and support networks. pharmaceutical care is a daily challenge expressed in maternal overload and difficulty accessing the drugs, made worse by failures in the care network and coordinated care.

Direct reactivation of a coherent neocortical memory of context

PubMed Central

Cowansage, Kiriana Kater; Shuman, Tristan; Dillingham, Blythe Christine; Chang, Allene; Golshani, Peyman; Mayford, Mark

2014-01-01

Summary Declarative memories are thought to be stored within anatomically distributed neuronal networks requiring the hippocampus; however, it is unclear how neocortical areas participate in memory at the time of encoding. Here, we use a c-fos-based genetic tagging system to selectively express the channelrhodopsin variant, ChEF, and optogenetically reactivate a specific neural ensemble in retrosplenial cortex (RSC) engaged by context fear conditioning. Artificial stimulation of RSC was sufficient to produce both context-specific behavior and downstream cellular activity commensurate with natural experience. Moreover, optogenetically, but not contextually-elicited responses were insensitive to hippocampal inactivation, suggesting that although the hippocampus is needed to coordinate activation by sensory cues, a higher-order cortical framework can independently subserve learned behavior, even shortly after learning. PMID:25308330

Temporal expression of IL-1β and IL-10 in rat skin, muscle, small bowel, and colon wounds: a correlative study.

PubMed

Alzoghaibi, Mohammed A; Al-Oraini, Abdullah I; Al-Sagheir, Ali I; Zubaidi, Ahmad M

2014-05-01

Cytokines play a major role in coordinated wound healing events. We hypothesized that rapid intestinal healing is due to an early upregulation of the pro-inflammatory cytokine interleukin-1β (IL-1β), followed by increases in the expression of the anti-inflammatory cytokine IL-10. We characterized the time course of IL-1β and IL-10 release at four wounds (skin, muscle, small bowel, and colonic anastomosis) after surgery on 38 juvenile male Sprague-Dawley rats. The tissue samples of each site were harvested at 0 (control), 1, 3, 5, 7, and 14 days postoperatively (n=6-8 per group) and analyzed by enzyme-linked immunosorbent assay kits for IL-1β and IL-10. IL-1β expression peaked at days 5 and 7 in small bowel and colonic wounds when compared to skin or muscle. Similarly, IL-10 showed high expression in these time points in small bowel and colonic wounds. However, IL-10 showed the same expression in all time points in muscle and skin tissues except at day 1. The high expression in IL-1β and IL-10 levels in small bowel and colon might explain the accelerated healing process in these wounds in comparison to skin and muscle tissues. Additional studies are required to determine whether IL-1β and IL-10 expression is the major factor defining site-specific differences in healing rates in different tissues. Understanding cytokine action in the wound healing process could lead to novel and effective therapeutic strategies.

A distinct regulatory region of the Bmp5 locus activates gene expression following adult bone fracture or soft tissue injury.

PubMed

Guenther, Catherine A; Wang, Zhen; Li, Emma; Tran, Misha C; Logan, Catriona Y; Nusse, Roel; Pantalena-Filho, Luiz; Yang, George P; Kingsley, David M

2015-08-01

Bone morphogenetic proteins (BMPs) are key signaling molecules required for normal development of bones and other tissues. Previous studies have shown that null mutations in the mouse Bmp5 gene alter the size, shape and number of multiple bone and cartilage structures during development. Bmp5 mutations also delay healing of rib fractures in adult mutants, suggesting that the same signals used to pattern embryonic bone and cartilage are also reused during skeletal regeneration and repair. Despite intense interest in BMPs as agents for stimulating bone formation in clinical applications, little is known about the regulatory elements that control developmental or injury-induced BMP expression. To compare the DNA sequences that activate gene expression during embryonic bone formation and following acute injuries in adult animals, we assayed regions surrounding the Bmp5 gene for their ability to stimulate lacZ reporter gene expression in transgenic mice. Multiple genomic fragments, distributed across the Bmp5 locus, collectively coordinate expression in discrete anatomic domains during normal development, including in embryonic ribs. In contrast, a distinct regulatory region activated expression following rib fracture in adult animals. The same injury control region triggered gene expression in mesenchymal cells following tibia fracture, in migrating keratinocytes following dorsal skin wounding, and in regenerating epithelial cells following lung injury. The Bmp5 gene thus contains an "injury response" control region that is distinct from embryonic enhancers, and that is activated by multiple types of injury in adult animals. Copyright © 2015 Elsevier Inc. All rights reserved.

Superbranes, D = 11 CJS Supergravity and Enlarged Superspace Coordinates/Fields Correspondence

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

Azcarraga, J.A. de; IFIC - CSIC-UVEG, Facultad de Fisica, 46100-Burjassot, Valencia

2005-04-25

We discuss the role of enlarged superspaces in two seemingly different contexts, the structure of the p-brane actions and that of the Cremmer-Julia-Scherk eleven-dimensional supergravity. Both provide examples of a common principle: the existence of an enlarged superspaces coordinates/fields correspondence by which all the (worldvolume or spacetime) fields of the theory are associated to coordinates of enlarged superspaces. In the context of p-branes, enlarged superspaces may be used to construct manifestly supersymmetry-invariant Wess-Zumino terms and as a way of expressing the Born-Infeld worldvolume fields of D-branes and the worldvolume M5-brane two-form in terms of fields associated to the coordinates ofmore » these enlarged superspaces. This is tantamount to saying that the Born-Infeld fields have a superspace origin, as do the other worldvolume fields, and that they have a composite structure. In D=11 supergravity theory enlarged superspaces arise when its underlying gauge structure is investigated and, as a result, the composite nature of the A3 field is revealed: there is a full one-parametric family of enlarged superspace groups that solve the problem of expressing A3 in terms of spacetime fields associated to their coordinates. The corresponding enlarged supersymmetry algebras turn out to be deformations of an expansion of the osp(1 vertical bar 32) algebra. The unifying mathematical structure underlying all these facts is the cohomology of the supersymmetry algebras involved.« less

Effect of task-oriented activities on hand functions, cognitive functions and self-expression of elderly patients with dementia.

PubMed

Son, Bo-Young; Bang, Yo-Soon; Hwang, Min-Ji; Oh, Eun-Ju

2017-08-01

[Purpose] This study investigates the effects of task-oriented activities on hand function, cognitive function, and self-expression of the elderly with dementia, and then identify the influencing factors on self-expression in sub-factors of dependent variables. [Subjects and Methods] Forty elderly persons were divided into two groups: intervention group (n=20) and control group (n=20). The interventions were applied to the subjects 3 times a week, 50 minutes per each time, for a total of five weeks. We measured the jamar hand dynamometer test for grip strength, the jamar hydraulic pinch gauge test for prehension test, nine-hole pegboard test for coordination test, and Loewenstein Occupational Therapy Cognitive Assessment-Geriatric Population for cognitive function, and self-expression rating scale for self-expression test. [Results] The task-oriented activities promoted hand function, cognitive function (visual perception, spatial perception, visuomotor organization, attention & concentration) and self-expression of the elderly with early dementia, and the factors influencing the self-expression were cognitive function (visual perception) and hand function (coordination). The study showed that the task-oriented program enabled self-expression by improving hand function and cognitive function. [Conclusion] This study suggested that there should be provided the task-oriented program for prevention and treatment of the elderly with early dementia in the clinical settings and it was considered that results have a value as basic data that can be verified relationship of hand function, cognitive function, and self-expression.

The host-pathogen interaction between wheat and yellow rust induces temporally coordinated waves of gene expression.

PubMed

Dobon, Albor; Bunting, Daniel C E; Cabrera-Quio, Luis Enrique; Uauy, Cristobal; Saunders, Diane G O

2016-05-20

Understanding how plants and pathogens modulate gene expression during the host-pathogen interaction is key to uncovering the molecular mechanisms that regulate disease progression. Recent advances in sequencing technologies have provided new opportunities to decode the complexity of such interactions. In this study, we used an RNA-based sequencing approach (RNA-seq) to assess the global expression profiles of the wheat yellow rust pathogen Puccinia striiformis f. sp. tritici (PST) and its host during infection. We performed a detailed RNA-seq time-course for a susceptible and a resistant wheat host infected with PST. This study (i) defined the global gene expression profiles for PST and its wheat host, (ii) substantially improved the gene models for PST, (iii) evaluated the utility of several programmes for quantification of global gene expression for PST and wheat, and (iv) identified clusters of differentially expressed genes in the host and pathogen. By focusing on components of the defence response in susceptible and resistant hosts, we were able to visualise the effect of PST infection on the expression of various defence components and host immune receptors. Our data showed sequential, temporally coordinated activation and suppression of expression of a suite of immune-response regulators that varied between compatible and incompatible interactions. These findings provide the framework for a better understanding of how PST causes disease and support the idea that PST can suppress the expression of defence components in wheat to successfully colonize a susceptible host.

Effect of task-oriented activities on hand functions, cognitive functions and self-expression of elderly patients with dementia

PubMed Central

Son, Bo-Young; Bang, Yo-Soon; Hwang, Min-Ji; Oh, Eun-Ju

2017-01-01

[Purpose] This study investigates the effects of task-oriented activities on hand function, cognitive function, and self-expression of the elderly with dementia, and then identify the influencing factors on self-expression in sub-factors of dependent variables. [Subjects and Methods] Forty elderly persons were divided into two groups: intervention group (n=20) and control group (n=20). The interventions were applied to the subjects 3 times a week, 50 minutes per each time, for a total of five weeks. We measured the jamar hand dynamometer test for grip strength, the jamar hydraulic pinch gauge test for prehension test, nine-hole pegboard test for coordination test, and Loewenstein Occupational Therapy Cognitive Assessment-Geriatric Population for cognitive function, and self-expression rating scale for self-expression test. [Results] The task-oriented activities promoted hand function, cognitive function (visual perception, spatial perception, visuomotor organization, attention & concentration) and self-expression of the elderly with early dementia, and the factors influencing the self-expression were cognitive function (visual perception) and hand function (coordination). The study showed that the task-oriented program enabled self-expression by improving hand function and cognitive function. [Conclusion] This study suggested that there should be provided the task-oriented program for prevention and treatment of the elderly with early dementia in the clinical settings and it was considered that results have a value as basic data that can be verified relationship of hand function, cognitive function, and self-expression. PMID:28878462

Regulation of notochord-specific expression of Ci-Bra downstream genes in Ciona intestinalis embryos.

PubMed

Takahashi, Hiroki; Hotta, Kohji; Takagi, Chiyo; Ueno, Naoto; Satoh, Nori; Shoguchi, Eiichi

2010-02-01

Brachyury, a T-box transcription factor, is expressed in ascidian embryos exclusively in primordial notochord cells and plays a pivotal role in differentiation of notochord cells. Previously, we identified approximately 450 genes downstream of Ciona intestinalis Brachyury (Ci-Bra), and characterized the expression profiles of 45 of these in differentiating notochord cells. In this study, we looked for cisregulatory sequences in minimal enhancers of 20 Ci-Bra downstream genes by electroporating region within approximately 3 kb upstream of each gene fused with lacZ. Eight of the 20 reporters were expressed in notochord cells. The minimal enchancer for each of these eight genes was narrowed to a region approximately 0.5-1.0-kb long. We also explored the genome-wide and coordinate regulation of 43 Ci-Bra-downstream genes. When we determined their chromosomal localization, it became evident that they are not clustered in a given region of the genome, but rather distributed evenly over 13 of the 14 pairs of chromosomes, suggesting that gene clustering does not contribute to coordinate control of the Ci-Bra downstream gene expression. Our results might provide Insights Into the molecular mechanisms underlying notochord formation in chordates.

Expression of Arabidopsis Hexokinase in Citrus Guard Cells Controls Stomatal Aperture and Reduces Transpiration.

PubMed

Lugassi, Nitsan; Kelly, Gilor; Fidel, Lena; Yaniv, Yossi; Attia, Ziv; Levi, Asher; Alchanatis, Victor; Moshelion, Menachem; Raveh, Eran; Carmi, Nir; Granot, David

2015-01-01

Hexokinase (HXK) is a sugar-phosphorylating enzyme involved in sugar-sensing. It has recently been shown that HXK in guard cells mediates stomatal closure and coordinates photosynthesis with transpiration in the annual species tomato and Arabidopsis. To examine the role of HXK in the control of the stomatal movement of perennial plants, we generated citrus plants that express Arabidopsis HXK1 (AtHXK1) under KST1, a guard cell-specific promoter. The expression of KST1 in the guard cells of citrus plants has been verified using GFP as a reporter gene. The expression of AtHXK1 in the guard cells of citrus reduced stomatal conductance and transpiration with no negative effect on the rate of photosynthesis, leading to increased water-use efficiency. The effects of light intensity and humidity on stomatal behavior were examined in rooted leaves of the citrus plants. The optimal intensity of photosynthetically active radiation and lower humidity enhanced stomatal closure of AtHXK1-expressing leaves, supporting the role of sugar in the regulation of citrus stomata. These results suggest that HXK coordinates photosynthesis and transpiration and stimulates stomatal closure not only in annual species, but also in perennial species.

Expression of Arabidopsis Hexokinase in Citrus Guard Cells Controls Stomatal Aperture and Reduces Transpiration

PubMed Central

Lugassi, Nitsan; Kelly, Gilor; Fidel, Lena; Yaniv, Yossi; Attia, Ziv; Levi, Asher; Alchanatis, Victor; Moshelion, Menachem; Raveh, Eran; Carmi, Nir; Granot, David

2015-01-01

Hexokinase (HXK) is a sugar-phosphorylating enzyme involved in sugar-sensing. It has recently been shown that HXK in guard cells mediates stomatal closure and coordinates photosynthesis with transpiration in the annual species tomato and Arabidopsis. To examine the role of HXK in the control of the stomatal movement of perennial plants, we generated citrus plants that express Arabidopsis HXK1 (AtHXK1) under KST1, a guard cell-specific promoter. The expression of KST1 in the guard cells of citrus plants has been verified using GFP as a reporter gene. The expression of AtHXK1 in the guard cells of citrus reduced stomatal conductance and transpiration with no negative effect on the rate of photosynthesis, leading to increased water-use efficiency. The effects of light intensity and humidity on stomatal behavior were examined in rooted leaves of the citrus plants. The optimal intensity of photosynthetically active radiation and lower humidity enhanced stomatal closure of AtHXK1-expressing leaves, supporting the role of sugar in the regulation of citrus stomata. These results suggest that HXK coordinates photosynthesis and transpiration and stimulates stomatal closure not only in annual species, but also in perennial species. PMID:26734024

Genetic background modulates lncRNA-coordinated tissue response to low dose ionizing radiation

DOE PAGES

Tang, Jonathan; Huang, Yurong; Nguyen, David H.; ...

2015-02-04

Long noncoding RNAs (lncRNAs) are emerging as key regulators of diverse cell functions and processes. However, the relevance of lncRNAs in the cell and tissue response to ionizing radiation has not yet been characterized. Here we used microarray profiling to determine lncRNA and mRNA expression in mammary glands of BALB/c and SPRET/EiJ mice after low-dose ionizing radiation (LDIR) exposure. We found that unirradiated mammary tissues of these strains differed significantly in baseline expressions of 290 lncRNAs. LDIR exposure (10 cGy) induced a significant change in the expression of many lncRNAs. The vast majority of lncRNAs identified to be differentially expressed aftermore » LDIR in either BALB/c or SPRET/EiJ had a significantly correlated expression pattern with at least one LDIR responsive mRNA. Functional analysis revealed that the response to LDIR in BALB/c mice is highly dynamic with enrichment for genes involved in tissue injury, inflammatory responses, and mammary gland development at 2, 4, and 8 weeks after LDIR, respectively. Our study demonstrates that genetic background strongly influences the expression of lncRNAs and their response to radiation and that lncRNAs may coordinate the tissue response to LDIR exposure via regulation of coding mRNAs.« less

Genetic background modulates lncRNA-coordinated tissue response to low dose ionizing radiation

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

Tang, Jonathan; Huang, Yurong; Nguyen, David H.

Long noncoding RNAs (lncRNAs) are emerging as key regulators of diverse cell functions and processes. However, the relevance of lncRNAs in the cell and tissue response to ionizing radiation has not yet been characterized. Here we used microarray profiling to determine lncRNA and mRNA expression in mammary glands of BALB/c and SPRET/EiJ mice after low-dose ionizing radiation (LDIR) exposure. We found that unirradiated mammary tissues of these strains differed significantly in baseline expressions of 290 lncRNAs. LDIR exposure (10 cGy) induced a significant change in the expression of many lncRNAs. The vast majority of lncRNAs identified to be differentially expressed aftermore » LDIR in either BALB/c or SPRET/EiJ had a significantly correlated expression pattern with at least one LDIR responsive mRNA. Functional analysis revealed that the response to LDIR in BALB/c mice is highly dynamic with enrichment for genes involved in tissue injury, inflammatory responses, and mammary gland development at 2, 4, and 8 weeks after LDIR, respectively. Our study demonstrates that genetic background strongly influences the expression of lncRNAs and their response to radiation and that lncRNAs may coordinate the tissue response to LDIR exposure via regulation of coding mRNAs.« less

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

CLOCK expression identifies developing circadian oscillator neurons in the brains of Drosophila embryos.

PubMed

Houl, Jerry H; Ng, Fanny; Taylor, Pete; Hardin, Paul E

2008-12-18

The Drosophila circadian oscillator is composed of transcriptional feedback loops in which CLOCK-CYCLE (CLK-CYC) heterodimers activate their feedback regulators period (per) and timeless (tim) via E-box mediated transcription. These feedback loop oscillators are present in distinct clusters of dorsal and lateral neurons in the adult brain, but how this pattern of expression is established during development is not known. Since CLK is required to initiate feedback loop function, defining the pattern of CLK expression in embryos and larvae will shed light on oscillator neuron development. A novel CLK antiserum is used to show that CLK expression in the larval CNS and adult brain is limited to circadian oscillator cells. CLK is initially expressed in presumptive small ventral lateral neurons (s-LNvs), dorsal neurons 2 s (DN2s), and dorsal neuron 1 s (DN1s) at embryonic stage (ES) 16, and this CLK expression pattern persists through larval development. PER then accumulates in all CLK-expressing cells except presumptive DN2s during late ES 16 and ES 17, consistent with the delayed accumulation of PER in adult oscillator neurons and antiphase cycling of PER in larval DN2s. PER is also expressed in non-CLK-expressing cells in the embryonic CNS starting at ES 12. Although PER expression in CLK-negative cells continues in ClkJrk embryos, PER expression in cells that co-express PER and CLK is eliminated. These data demonstrate that brain oscillator neurons begin development during embryogenesis, that PER expression in non-oscillator cells is CLK-independent, and that oscillator phase is an intrinsic characteristic of brain oscillator neurons. These results define the temporal and spatial coordinates of factors that initiate Clk expression, imply that circadian photoreceptors are not activated until the end of embryogenesis, and suggest that PER functions in a different capacity before oscillator cell development is initiated.

Protease-activated receptor-4 and purinergic receptor P2Y12 dimerize, co-internalize, and activate Akt signaling via endosomal recruitment of β-arrestin.

PubMed

Smith, Thomas H; Li, Julia G; Dores, Michael R; Trejo, JoAnn

2017-08-18

Vascular inflammation and thrombosis require the concerted actions of several different agonists, many of which act on G protein-coupled receptors (GPCRs). GPCR dimerization is a well-established phenomenon that can alter protomer function. In platelets and other cell types, protease-activated receptor-4 (PAR4) has been shown to dimerize with the purinergic receptor P2Y12 to coordinate β-arrestin-mediated Akt signaling, an important mediator of integrin activation. However, the mechanism by which the PAR4-P2Y12 dimer controls β-arrestin-dependent Akt signaling is not known. We now report that PAR4 and P2Y12 heterodimer internalization is required for β-arrestin recruitment to endosomes and Akt signaling. Using bioluminescence resonance energy transfer, immunofluorescence microscopy, and co-immunoprecipitation in cells expressing receptors exogenously and endogenously, we demonstrate that PAR4 and P2Y12 specifically interact and form dimers expressed at the cell surface. We also found that activation of PAR4 but not of P2Y12 drives internalization of the PAR4-P2Y12 heterodimer. Remarkably, activated PAR4 internalization was required for recruitment of β-arrestin to endocytic vesicles, which was dependent on co-expression of P2Y12. Interestingly, stimulation of the PAR4-P2Y12 heterodimer promotes β-arrestin and Akt co-localization to intracellular vesicles. Moreover, activated PAR4-P2Y12 internalization is required for sustained Akt activation. Thus, internalization of the PAR4-P2Y12 heterodimer is necessary for β-arrestin recruitment to endosomes and Akt signaling and lays the foundation for examining whether blockade of PAR4 internalization reduces integrin and platelet activation. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.