Repressive coping and self-reports of parenting.

PubMed

Myers, L B; Brewin, C R; Winter, D A

1999-03-01

To investigate whether women who possess a repressive coping style (repressors) self-report more positive judgments of their childhood on questionnaire and repertory grid measures compared with non-repressors. Repressors (low anxiety-high defensiveness) were compared with a composite group of non-repressors, containing some low anxious (low anxiety-low defensiveness), some high anxious (high anxiety-low defensiveness), some defensive high anxious (high anxiety-high defensiveness) and some non-extreme scorers. Participants completed the Parental Bonding Instrument (PBI; Parker, Tupling & Brown, 1979) and a 10 x 10 repertory grid, Self-Identification Form. On the PBI, repressors scored significantly higher than non-repressors on paternal care and significantly lower on paternal overprotection. There were no group differences for maternal measures. On the repertory grid, repressors compared with non-repressors perceived (a) themselves as significantly closer to their father, a woman they like, and their ideal partner, and significantly further from a woman they dislike, and a man they dislike; and (b) their father as significantly closer to a woman they like, a partner/person they admire, and an ideal partner. In addition, repressors were significantly tighter on construing than non-repressors. The results supported the hypothesis that repressors would rate their interactions with their fathers more positively than non-repressors when allowed to do so on self-report measures.

REST Controls Self-Renewal and Tumorigenic Competence of Human Glioblastoma Cells

PubMed Central

Conti, Luciano; Crisafulli, Laura; Brilli, Elisa; Conforti, Paola; Zunino, Franco; Magrassi, Lorenzo; Schiffer, Davide; Cattaneo, Elena

2012-01-01

The Repressor Element 1 Silencing Transcription factor (REST/NRSF) is a master repressor of neuronal programs in non-neuronal lineages shown to function as a central regulator of developmental programs and stem cell physiology. Aberrant REST function has been associated with a number of pathological conditions. In cancer biology, REST has been shown to play a tumor suppressor activity in epithelial cancers but an oncogenic role in brain childhood malignancies such as neuroblastoma and medulloblastoma. Here we examined REST expression in human glioblastoma multiforme (GBM) specimens and its role in GBM cells carrying self-renewal and tumorigenic competence. We found REST to be expressed in GBM specimens, its presence being particularly enriched in tumor cells in the perivascular compartment. Significantly, REST is highly expressed in self-renewing tumorigenic-competent GBM cells and its knock down strongly reduces their self-renewal in vitro and tumor-initiating capacity in vivo and affects levels of miR-124 and its downstream targets. These results indicate that REST contributes to GBM maintenance by affecting its self-renewing and tumorigenic cellular component and that, hence, a better understanding of these circuitries in these cells might lead to new exploitable therapeutic targets. PMID:22701651

AmrZ Beta-Sheet Residues Are Essential for DNA Binding and Transcriptional Control of Pseudomonas aeruginosa Virulence Genes ▿ †

PubMed Central

Waligora, Elizabeth A.; Ramsey, Deborah M.; Pryor, Edward E.; Lu, Haiping; Hollis, Thomas; Sloan, Gina P.; Deora, Rajendar; Wozniak, Daniel J.

2010-01-01

AmrZ is a putative ribbon-helix-helix (RHH) transcriptional regulator. RHH proteins utilize residues within the β-sheet for DNA binding, while the α-helices promote oligomerization. AmrZ is of interest due to its dual roles as a transcriptional activator and as a repressor, regulating genes encoding virulence factors associated with both chronic and acute Pseudomonas aeruginosa infection. In this study, cross-linking revealed that AmrZ forms oligomers in solution but that the amino terminus, containing an unordered region and a β-sheet, were not required for oligomerization. The first 12 unordered residues (extended amino terminus) contributed minimally to DNA binding. Mutagenesis of the AmrZ β-sheet demonstrated that residues 18, 20, and 22 were essential for DNA binding at both activation and repressor sites, suggesting that AmrZ utilizes a similar mechanism for binding to these sites. Mice infected with amrZ mutants exhibited reduced bacterial burden, morbidity, and mortality. Direct in vivo competition assays showed a 5-fold competitive advantage for the wild type over an isogenic amrZ mutant. Finally, the reduced infection phenotype of the amrZ-null strain was similar to that of a strain expressing a DNA-binding-deficient AmrZ variant, indicating that DNA binding and transcriptional regulation by AmrZ is responsible for the in vivo virulence defect. These recent infection data, along with previously identified AmrZ-regulated virulence factors, suggest the necessity of AmrZ transcriptional regulation for optimal virulence during acute infection. PMID:20709902

High Performance Computing Innovation Service Portal Study (HPC-ISP)

DTIC Science & Technology

2009-04-01

threatened by global competition. It is essential that these suppliers remain competitive and maintain their technological advantage . In this increasingly...place themselves, as well as customers who rely on them, in competitive jeopardy. Despite the potential competitive advantage associated with adopting...computing users into the HPC fold and to enable more entry-level users to exploit HPC more fully for competitive advantage . About half of the surveyed

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

Principals of Design for High Performing Organizations: A Suggested Research Program. Appendixes

DTIC Science & Technology

1994-03-01

keiretsu are subjected to the measure of the market and the sting of competition . The Japanese model combines fierce internal competition with a...reasonable that such a quasi-market can exploit the benefits of competition and price signals to provide internal customers with better service at a...system. Would the restriction of market entry necessarily lead to monopolistic competition that ends up extracting unnecessary rents from captive

Rce1, a novel transcriptional repressor, regulates cellulase gene expression by antagonizing the transactivator Xyr1 in Trichoderma reesei.

PubMed

Cao, Yanli; Zheng, Fanglin; Wang, Lei; Zhao, Guolei; Chen, Guanjun; Zhang, Weixin; Liu, Weifeng

2017-07-01

Cellulase gene expression in the model cellulolytic fungus Trichoderma reesei is supposed to be controlled by an intricate regulatory network involving multiple transcription factors. Here, we identified a novel transcriptional repressor of cellulase gene expression, Rce1. Disruption of the rce1 gene not only facilitated the induced expression of cellulase genes but also led to a significant delay in terminating the induction process. However, Rce1 did not participate in Cre1-mediated catabolite repression. Electrophoretic mobility shift (EMSA) and DNase I footprinting assays in combination with chromatin immunoprecipitation (ChIP) demonstrated that Rce1 could bind directly to a cbh1 (cellobiohydrolase 1-encoding) gene promoter region containing a cluster of Xyr1 binding sites. Furthermore, competitive binding assays revealed that Rce1 antagonized Xyr1 from binding to the cbh1 promoter. These results indicate that intricate interactions exist between a variety of transcription factors to ensure tight and energy-efficient regulation of cellulase gene expression in T. reesei. This study also provides important clues regarding increased cellulase production in T. reesei. © 2017 John Wiley & Sons Ltd.

tif-dependent induction of colicin E1, prophage lambda, and filamentation in Escherichia coli K-12.

PubMed

Tessman, E S; Peterson, P K

1980-09-01

To help understand how the tif-1 mutation of the recA gene of Escherichia coli confers adenine activability on the recA protein, we used the fact that cytidine plus guanosine inhibits induction of prophage lambda and cell filamentation in a tif-1 mutant, and that adenine reverses this inhibition. We varied the amount of adenine in agar plates containing a fixed amount of cytidine and scored for survivors of three different tif-dependent lethal induction processes. Much more adenine was required for cell killing when cytidine was present than when it was absent. Therefore adenine does not override cytidine inhibition, but instead appears to compete with it for a site of action which may be on the recA protein. The competition is not at the cell transport level. Our results lead to a model in which the tif form of the recA protein is an allosteric enzyme that binds both negative and positive modulators. By varying the adenine-cytidine ratio of the medium it is possible to control the degree of induction in a tif-1 cell. For the three different tif-dependent inductions studied here, least adenine was required for lambda induction and most for lethal filamentation, presumably reflecting requirements for different amounts of activated recA protein in each process. Varying the adenine-cytidine ratio revealed two stable intermediate stages in lambda induction, as well as a stage of colicin E1 induction in which the cells produced colicin without cell death. The rate of filament formation could be similarly controlled. Experiments with tif (ColE1, lambda) gave evidence of a competition between colicin repressor and lambda repressor for activated recA protein.

Drought-Up-Regulated TaNAC69-1 is a Transcriptional Repressor of TaSHY2 and TaIAA7, and Enhances Root Length and Biomass in Wheat.

PubMed

Chen, Dandan; Richardson, Terese; Chai, Shoucheng; Lynne McIntyre, C; Rae, Anne L; Xue, Gang-Ping

2016-10-01

A well-known physiological adaptation process of plants encountering drying soil is to achieve water balance by reducing shoot growth and maintaining or promoting root elongation, but little is known about the molecular basis of this process. This study investigated the role of a drought-up-regulated Triticum aestivum NAC69-1 (TaNAC69-1) in the modulation of root growth in wheat. TaNAC69-1 was predominantly expressed in wheat roots at the early vegetative stage. Overexpression of TaNAC69-1 in wheat roots using OsRSP3 (essentially root-specific) and OsPIP2;3 (root-predominant) promoters resulted in enhanced primary seminal root length and a marked increase in maturity root biomass. Competitive growth analysis under water-limited conditions showed that OsRSP3 promoter-driven TaNAC69-1 transgenic lines produced 32% and 35% more above-ground biomass and grains than wild-type plants, respectively. TaNAC69-1 overexpression in the roots down-regulated the expression of TaSHY2 and TaIAA7, which are from the auxin/IAA (Aux/IAA) transcriptional repressor gene family and are the homologs of negative root growth regulators SHY2/IAA3 and IAA7 in Arabidopsis. The expression of TaSHY2 and TaIAA7 in roots was down-regulated by drought stress and up-regulated by cytokinin treatment, which inhibited root growth. DNA binding and transient expression analyses revealed that TaNAC69-1 bound to the promoters of TaSHY2 and TaIAA7, acted as a transcriptional repressor and repressed the expression of reporter genes driven by the TaSHY2 or TaIAA7 promoter. These data suggest that TaNAC69-1 is a transcriptional repressor of TaSHY2 and TaIAA7 homologous to Arabidopsis negative root growth regulators and is likely to be involved in promoting root elongation in drying soil. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Specific repression of β-globin promoter activity by nuclear ferritin

PubMed Central

Broyles, Robert H.; Belegu, Visar; DeWitt, Christina R.; Shah, Sandeep N.; Stewart, Charles A.; Pye, Quentin N.; Floyd, Robert A.

2001-01-01

Developmental hemoglobin switching involves sequential globin gene activations and repressions that are incompletely understood. Earlier observations, described herein, led us to hypothesize that nuclear ferritin is a repressor of the adult β-globin gene in embryonic erythroid cells. Our data show that a ferritin-family protein in K562 cell nuclear extracts binds specifically to a highly conserved CAGTGC motif in the β-globin promoter at −153 to −148 bp from the cap site, and mutation of the CAGTGC motif reduces binding 20-fold in competition gel-shift assays. Purified human ferritin that is enriched in ferritin-H chains also binds the CAGTGC promoter segment. Expression clones of ferritin-H markedly repress β-globin promoter-driven reporter gene expression in cotransfected CV-1 cells in which the β-promoter has been stimulated with the transcription activator erythroid Krüppel-like factor (EKLF). We have constructed chloramphenicol acetyltransferase reporter plasmids containing either a wild-type or mutant β-globin promoter for the −150 CAGTGC motif and have compared the constructs for susceptibility to repression by ferritin-H in cotransfection assays. We find that stimulation by cotransfected EKLF is retained with the mutant promoter, whereas repression by ferritin-H is lost. Thus, mutation of the −150 CAGTGC motif not only markedly reduces in vitro binding of nuclear ferritin but also abrogates the ability of expressed ferritin-H to repress this promoter in our cell transfection assay, providing a strong link between DNA binding and function, and strong support for our proposal that nuclear ferritin-H is a repressor of the human β-globin gene. Such a repressor could be helpful in treating sickle cell and other genetic diseases. PMID:11481480

Competitive interactions between walleye (Sander vitreus) and smallmouth bass (Micropterus dolomieu) under various controlled conditions

USGS Publications Warehouse

Wuellner, M.R.; Graeb, B.D.S.; Willis, D.W.; Galster, B.J.; Selch, T.M.; Chipps, S.R.

2011-01-01

The range of smallmouth bass (Micropterus dolomieu) is expanding northward, creating new interactions with native predators, including walleye (Sander vitreus). We used a series of experiments to investigate competition between walleye (WAE) and smallmouth bass (SMB) at different life stages and light conditions, identified behaviors that allowed one fish to outcompete another, and evaluated whether prey switching mitigated competitive interactions. Juvenile and adult SMB appeared to outcompete WAE when fed during the daytime; neither species dominated when fed near dusk. Attack rates and capture efficiencies of both species were similar with an intra- or interspecific competitor, but SMB often exploited prey before the competitor had a chance to feed (exploitative competition) or displayed agonistic behaviors toward a potential competitor (interference competition). Prey selectivity of WAE or SMB did not differ when by themselves or with a potential competitor. These results indicate that SMB could outcompete WAE under limiting prey conditions due to the aggressive nature of SMB, but resources may be partitioned at least along a temporal scale. ?? 2011 Taylor & Francis.

Desiring TESOL and International Education: Market Abuse and Exploitation

ERIC Educational Resources Information Center

Chowdhury, Raqib; Ha, Phan Le

2014-01-01

This book addresses how Western universities have constructed themselves as global providers of education, and are driven to be globally competitive. It examines how the term "international" has been exploited by the market in the form of government educational policies and agencies, host institutions, academia and the mass media. The…

Admission Policy Evolution in Emerging Professional Programs: A Case Study

ERIC Educational Resources Information Center

Holley, Paul W.

2006-01-01

Professional program admission at U.S. universities has become increasingly competitive in the last 20 years, due to enrollment caps, core class requirements, transfer course acceptance, industry draw, and the appeal of starting salaries. As the competition steadily increases, students often find methods to exploit traditional policy, resulting in…

How players exploit variability and regularity of game actions in female volleyball teams.

PubMed

Ramos, Ana; Coutinho, Patrícia; Silva, Pedro; Davids, Keith; Mesquita, Isabel

2017-05-01

Variability analysis has been used to understand how competitive constraints shape different behaviours in team sports. In this study, we analysed and compared variability of tactical performance indices in players within complex I at two different competitive levels in volleyball. We also examined whether variability was influenced by set type and period. Eight matches from the 2012 Olympics competition and from the Portuguese national league in the 2014-2015 season were analysed (1496 rallies). Variability of setting conditions, attack zone, attack tempo and block opposition was assessed using Shannon entropy measures. Magnitude-based inferences were used to analyse the practical significance of compared values of selected variables. Results showed differences between elite and national teams for all variables, which were co-adapted to the competitive constraints of set type and set periods. Elite teams exploited system stability in setting conditions and block opposition, but greater unpredictability in zone and tempo of attack. These findings suggest that uncertainty in attacking actions was a key factor that could only be achieved with greater performance stability in other game actions. Data suggested how coaches could help setters develop the capacity to play at faster tempos, diversifying attack zones, especially at critical moments in competition.

Radiation-induced tetramer-to-dimer transition of Escherichia coli lactose repressor

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

Goffinont, S.; Davidkova, M.; Spotheim-Maurizot, M., E-mail: spotheim@cnrs-orleans.fr

2009-08-21

The wild type lactose repressor of Escherichia coli is a tetrameric protein formed by two identical dimers. They are associated via a C-terminal 4-helix bundle (called tetramerization domain) whose stability is ensured by the interaction of leucine zipper motifs. Upon in vitro {gamma}-irradiation the repressor losses its ability to bind the operator DNA sequence due to damage of its DNA-binding domains. Using an engineered dimeric repressor for comparison, we show here that irradiation induces also the change of repressor oligomerisation state from tetramer to dimer. The splitting of the tetramer into dimers can result from the oxidation of the leucinemore » residues of the tetramerization domain.« less

A Small-Molecule Inducible Synthetic Circuit for Control of the SOS Gene Network without DNA Damage.

PubMed

Kubiak, Jeffrey M; Culyba, Matthew J; Liu, Monica Yun; Mo, Charlie Y; Goulian, Mark; Kohli, Rahul M

2017-11-17

The bacterial SOS stress-response pathway is a pro-mutagenic DNA repair system that mediates bacterial survival and adaptation to genotoxic stressors, including antibiotics and UV light. The SOS pathway is composed of a network of genes under the control of the transcriptional repressor, LexA. Activation of the pathway involves linked but distinct events: an initial DNA damage event leads to activation of RecA, which promotes autoproteolysis of LexA, abrogating its repressor function and leading to induction of the SOS gene network. These linked events can each independently contribute to DNA repair and mutagenesis, making it difficult to separate the contributions of the different events to observed phenotypes. We therefore devised a novel synthetic circuit to unlink these events and permit induction of the SOS gene network in the absence of DNA damage or RecA activation via orthogonal cleavage of LexA. Strains engineered with the synthetic SOS circuit demonstrate small-molecule inducible expression of SOS genes as well as the associated resistance to UV light. Exploiting our ability to activate SOS genes independently of upstream events, we further demonstrate that the majority of SOS-mediated mutagenesis on the chromosome does not readily occur with orthogonal pathway induction alone, but instead requires DNA damage. More generally, our approach provides an exemplar for using synthetic circuit design to separate an environmental stressor from its associated stress-response pathway.

Interplay of protein and DNA structure revealed in simulations of the lac operon.

PubMed

Czapla, Luke; Grosner, Michael A; Swigon, David; Olson, Wilma K

2013-01-01

The E. coli Lac repressor is the classic textbook example of a protein that attaches to widely spaced sites along a genome and forces the intervening DNA into a loop. The short loops implicated in the regulation of the lac operon suggest the involvement of factors other than DNA and repressor in gene control. The molecular simulations presented here examine two likely structural contributions to the in-vivo looping of bacterial DNA: the distortions of the double helix introduced upon association of the highly abundant, nonspecific nucleoid protein HU and the large-scale deformations of the repressor detected in low-resolution experiments. The computations take account of the three-dimensional arrangements of nucleotides and amino acids found in crystal structures of DNA with the two proteins, the natural rest state and deformational properties of protein-free DNA, and the constraints on looping imposed by the conformation of the repressor and the orientation of bound DNA. The predicted looping propensities capture the complex, chain-length-dependent variation in repression efficacy extracted from gene expression studies and in vitro experiments and reveal unexpected chain-length-dependent variations in the uptake of HU, the deformation of repressor, and the folding of DNA. Both the opening of repressor and the presence of HU, at levels approximating those found in vivo, enhance the probability of loop formation. HU affects the global organization of the repressor and the opening of repressor influences the levels of HU binding to DNA. The length of the loop determines whether the DNA adopts antiparallel or parallel orientations on the repressor, whether the repressor is opened or closed, and how many HU molecules bind to the loop. The collective behavior of proteins and DNA is greater than the sum of the parts and hints of ways in which multiple proteins may coordinate the packaging and processing of genetic information.

Identification of the gene transcription repressor domain of Gli3.

PubMed

Tsanev, Robert; Tiigimägi, Piret; Michelson, Piret; Metsis, Madis; Østerlund, Torben; Kogerman, Priit

2009-01-05

Gli transcription factors are downstream targets of the Hedgehog signaling pathway. Two of the three Gli proteins harbor gene transcription repressor function in the N-terminal half. We have analyzed the sequences and identified a potential repressor domain in Gli2 and Gli3 and have tested this experimentally. Overexpression studies confirm that the N-terminal parts harbor gene repression activity and we mapped the minimal repressor to residues 106 till 236 in Gli3. Unlike other mechanisms that inhibit Gli induced gene transcription, the repressor domain identified here does not utilize Histone deacetylases (HDACs) to achieve repression, as confirmed by HDAC inhibition studies and pull-down assays. This distinguishes the identified domain from other regulatory parts with negative influence on transcription.

The consequences of balanced harvesting of fish communities

PubMed Central

Jacobsen, Nis S.; Gislason, Henrik; Andersen, Ken H.

2014-01-01

Balanced harvesting, where species or individuals are exploited in accordance with their productivity, has been proposed as a way to minimize the effects of fishing on marine fish communities and ecosystems. This calls for a thorough examination of the consequences balanced harvesting has on fish community structure and yield. We use a size- and trait-based model that resolves individual interactions through competition and predation to compare balanced harvesting with traditional selective harvesting, which protects juvenile fish from fishing. Four different exploitation patterns, generated by combining selective or unselective harvesting with balanced or unbalanced fishing, are compared. We find that unselective balanced fishing, where individuals are exploited in proportion to their productivity, produces a slightly larger total maximum sustainable yield than the other exploitation patterns and, for a given yield, the least change in the relative biomass composition of the fish community. Because fishing reduces competition, predation and cannibalism within the community, the total maximum sustainable yield is achieved at high exploitation rates. The yield from unselective balanced fishing is dominated by small individuals, whereas selective fishing produces a much higher proportion of large individuals in the yield. Although unselective balanced fishing is predicted to produce the highest total maximum sustainable yield and the lowest impact on trophic structure, it is effectively a fishery predominantly targeting small forage fish. PMID:24307676

Computing with competition in biochemical networks.

PubMed

Genot, Anthony J; Fujii, Teruo; Rondelez, Yannick

2012-11-16

Cells rely on limited resources such as enzymes or transcription factors to process signals and make decisions. However, independent cellular pathways often compete for a common molecular resource. Competition is difficult to analyze because of its nonlinear global nature, and its role remains unclear. Here we show how decision pathways such as transcription networks may exploit competition to process information. Competition for one resource leads to the recognition of convex sets of patterns, whereas competition for several resources (overlapping or cascaded regulons) allows even more general pattern recognition. Competition also generates surprising couplings, such as correlating species that share no resource but a common competitor. The mechanism we propose relies on three primitives that are ubiquitous in cells: multiinput motifs, competition for a resource, and positive feedback loops.

Role of sequence encoded κB DNA geometry in gene regulation by Dorsal

PubMed Central

Mrinal, Nirotpal; Tomar, Archana; Nagaraju, Javaregowda

2011-01-01

Many proteins of the Rel family can act as both transcriptional activators and repressors. However, mechanism that discerns the ‘activator/repressor’ functions of Rel-proteins such as Dorsal (Drosophila homologue of mammalian NFκB) is not understood. Using genomic, biophysical and biochemical approaches, we demonstrate that the underlying principle of this functional specificity lies in the ‘sequence-encoded structure’ of the κB-DNA. We show that Dorsal-binding motifs exist in distinct activator and repressor conformations. Molecular dynamics of DNA-Dorsal complexes revealed that repressor κB-motifs typically have A-tract and flexible conformation that facilitates interaction with co-repressors. Deformable structure of repressor motifs, is due to changes in the hydrogen bonding in A:T pair in the ‘A-tract’ core. The sixth nucleotide in the nonameric κB-motif, ‘A’ (A6) in the repressor motifs and ‘T’ (T6) in the activator motifs, is critical to confer this functional specificity as A6 → T6 mutation transformed flexible repressor conformation into a rigid activator conformation. These results highlight that ‘sequence encoded κB DNA-geometry’ regulates gene expression by exerting allosteric effect on binding of Rel proteins which in turn regulates interaction with co-regulators. Further, we identified and characterized putative repressor motifs in Dl-target genes, which can potentially aid in functional annotation of Dorsal gene regulatory network. PMID:21890896

Diversifying evolution of competitiveness.

PubMed

Baldauf, Sebastian A; Engqvist, Leif; Weissing, Franz J

2014-10-29

In many species, individuals express phenotypic characteristics that enhance their competitiveness, that is, the ability to acquire resources in competition with others. Moreover, the degree of competitiveness varies considerably across individuals and in time. By means of an evolutionary model, we provide an explanation for this finding. We make the assumption that investment into competitiveness enhances the probability to acquire a high-quality resource, but at the same time reduces the ability of exploiting acquired resources with maximal efficiency. The model reveals that under a broad range of conditions competitiveness either converges to a polymorphic state, where individuals differing in competitive ability stably coexist, or is subject to perpetual transitions between periods of high and low competitiveness. The dynamics becomes even more complex if females can evolve preferences for (or against) competitive males. In extreme cases, such preferences can even drive the population to extinction.

Proto-oncogene FBI-1 represses transcription of p21CIP1 by inhibition of transcription activation by p53 and Sp1.

PubMed

Choi, Won-Il; Jeon, Bu-Nam; Yun, Chae-Ok; Kim, Pyung-Hwan; Kim, Sung-Eun; Choi, Kang-Yell; Kim, Se Hoon; Hur, Man-Wook

2009-05-08

Aberrant transcriptional repression through chromatin remodeling and histone deacetylation has been postulated as the driving force for tumorigenesis. FBI-1 (formerly called Pokemon) is a member of the POK family of transcriptional repressors. Recently, FBI-1 was characterized as a critical oncogenic factor that specifically represses transcription of the tumor suppressor gene ARF, potentially leading indirectly to p53 inactivation. Our investigations on transcriptional repression of the p53 pathway revealed that FBI-1 represses transcription of ARF, Hdm2 (human analogue of mouse double minute oncogene), and p21CIP1 (hereafter indicated as p21) but not of p53. FBI-1 showed a more potent repressive effect on p21 than on p53. Our data suggested that FBI-1 is a master controller of the ARF-Hdm2-p53-p21 pathway, ultimately impinging on cell cycle arrest factor p21, by inhibiting upstream regulators at the transcriptional and protein levels. FBI-1 acted as a competitive transcriptional repressor of p53 and Sp1 and was shown to bind the proximal Sp1-3 GC-box and the distal p53-responsive elements of p21. Repression involved direct binding competition of FBI-1 with Sp1 and p53. FBI-1 also interacted with corepressors, such as mSin3A, NCoR, and SMRT, thereby deacetylating Ac-H3 and Ac-H4 histones at the promoter. FBI-1 caused cellular transformation, promoted cell cycle proliferation, and significantly increased the number of cells in S phase. FBI-1 is aberrantly overexpressed in many human solid tumors, particularly in adenocarcinomas and squamous carcinomas. The role of FBI-1 as a master controller of the p53 pathway therefore makes it an attractive therapeutic target.

Proto-oncogene FBI-1 Represses Transcription of p21CIP1 by Inhibition of Transcription Activation by p53 and Sp1*S⃞

PubMed Central

Choi, Won-Il; Jeon, Bu-Nam; Yun, Chae-Ok; Kim, Pyung-Hwan; Kim, Sung-Eun; Choi, Kang-Yell; Kim, Se Hoon; Hur, Man-Wook

2009-01-01

Aberrant transcriptional repression through chromatin remodeling and histone deacetylation has been postulated as the driving force for tumorigenesis. FBI-1 (formerly called Pokemon) is a member of the POK family of transcriptional repressors. Recently, FBI-1 was characterized as a critical oncogenic factor that specifically represses transcription of the tumor suppressor gene ARF, potentially leading indirectly to p53 inactivation. Our investigations on transcriptional repression of the p53 pathway revealed that FBI-1 represses transcription of ARF, Hdm2 (human analogue of mouse double minute oncogene), and p21CIP1 (hereafter indicated as p21) but not of p53. FBI-1 showed a more potent repressive effect on p21 than on p53. Our data suggested that FBI-1 is a master controller of the ARF-Hdm2-p53-p21 pathway, ultimately impinging on cell cycle arrest factor p21, by inhibiting upstream regulators at the transcriptional and protein levels. FBI-1 acted as a competitive transcriptional repressor of p53 and Sp1 and was shown to bind the proximal Sp1–3 GC-box and the distal p53-responsive elements of p21. Repression involved direct binding competition of FBI-1 with Sp1 and p53. FBI-1 also interacted with corepressors, such as mSin3A, NCoR, and SMRT, thereby deacetylating Ac-H3 and Ac-H4 histones at the promoter. FBI-1 caused cellular transformation, promoted cell cycle proliferation, and significantly increased the number of cells in S phase. FBI-1 is aberrantly overexpressed in many human solid tumors, particularly in adenocarcinomas and squamous carcinomas. The role of FBI-1 as a master controller of the p53 pathway therefore makes it an attractive therapeutic target. PMID:19244234

Environmental structure and competitive scoring advantages in team competitions.

PubMed

Merritt, Sears; Clauset, Aaron

2013-10-29

In most professional sports, playing field structure is kept neutral so that scoring imbalances may be attributed to differences in team skill. It thus remains unknown what impact environmental heterogeneities can have on scoring dynamics or competitive advantages. Applying a novel generative model of scoring dynamics to roughly 10 million team competitions drawn from an online game, we quantify the relationship between the structure within a competition and its scoring dynamics, while controlling the impact of chance. Despite wide structural variations, we observe a common three-phase pattern in the tempo of events. Tempo and balance are highly predictable from a competition's structural features alone and teams exploit environmental heterogeneities for sustained competitive advantage. Surprisingly, the most balanced competitions are associated with specific environmental heterogeneities, not from equally skilled teams. These results shed new light on the design principles of balanced competition, and illustrate the potential of online game data for investigating social dynamics and competition.

Environmental structure and competitive scoring advantages in team competitions

NASA Astrophysics Data System (ADS)

Merritt, Sears; Clauset, Aaron

2013-10-01

In most professional sports, playing field structure is kept neutral so that scoring imbalances may be attributed to differences in team skill. It thus remains unknown what impact environmental heterogeneities can have on scoring dynamics or competitive advantages. Applying a novel generative model of scoring dynamics to roughly 10 million team competitions drawn from an online game, we quantify the relationship between the structure within a competition and its scoring dynamics, while controlling the impact of chance. Despite wide structural variations, we observe a common three-phase pattern in the tempo of events. Tempo and balance are highly predictable from a competition's structural features alone and teams exploit environmental heterogeneities for sustained competitive advantage. Surprisingly, the most balanced competitions are associated with specific environmental heterogeneities, not from equally skilled teams. These results shed new light on the design principles of balanced competition, and illustrate the potential of online game data for investigating social dynamics and competition.

A nuclear factor I-like activity and a liver-specific repressor govern estrogen-regulated in vitro transcription from the Xenopus laevis vitellogenin B1 promoter.

PubMed

Corthésy, B; Cardinaux, J R; Claret, F X; Wahli, W

1989-12-01

A hormone-controlled in vitro transcription system derived from Xenopus liver nuclear extracts was exploited to identify novel cis-acting elements within the vitellogenin gene B1 promoter region. In addition to the already well-documented estrogen-responsive element (ERE), two elements were found within the 140 base pairs upstream of the transcription initiation site. One of them, a negative regulatory element, is responsible for the lack of promoter activity in the absence of the hormone and, as demonstrated by DNA-binding assays, interacts with a liver-specific transcription factor. The second is required in association with the estrogen-responsive element to mediate hormonal induction and is recognized by the Xenopus liver homolog of nuclear factor I.

Designing forest vegetation management strategies based on the mechanisms and dynamics of crop tree competition by neighbouring vegetation

Treesearch

P. Balandier; C. Collet; James H. Miller; P.E. Reynolds; S.M. Zedaker

2006-01-01

Plant interactions can be defined as the ways plants act upon the growth, fitness, survival and reproduction of other plants, largely by modifying their environment. These interactions can be positive (facilitation) or negative (competition or exploitation). During plantation establishment or natural forest regeneration after a disturbance, high light levels and,...

A Small-Molecule Inducible Synthetic Circuit for Control of the SOS Gene Network without DNA Damage

PubMed Central

2017-01-01

The bacterial SOS stress-response pathway is a pro-mutagenic DNA repair system that mediates bacterial survival and adaptation to genotoxic stressors, including antibiotics and UV light. The SOS pathway is composed of a network of genes under the control of the transcriptional repressor, LexA. Activation of the pathway involves linked but distinct events: an initial DNA damage event leads to activation of RecA, which promotes autoproteolysis of LexA, abrogating its repressor function and leading to induction of the SOS gene network. These linked events can each independently contribute to DNA repair and mutagenesis, making it difficult to separate the contributions of the different events to observed phenotypes. We therefore devised a novel synthetic circuit to unlink these events and permit induction of the SOS gene network in the absence of DNA damage or RecA activation via orthogonal cleavage of LexA. Strains engineered with the synthetic SOS circuit demonstrate small-molecule inducible expression of SOS genes as well as the associated resistance to UV light. Exploiting our ability to activate SOS genes independently of upstream events, we further demonstrate that the majority of SOS-mediated mutagenesis on the chromosome does not readily occur with orthogonal pathway induction alone, but instead requires DNA damage. More generally, our approach provides an exemplar for using synthetic circuit design to separate an environmental stressor from its associated stress-response pathway. PMID:28826208

Nutrient acquisition, soil phosphorus partitioning and competition among trees in a lowland tropical rain forest.

PubMed

Nasto, Megan K; Osborne, Brooke B; Lekberg, Ylva; Asner, Gregory P; Balzotti, Christopher S; Porder, Stephen; Taylor, Philip G; Townsend, Alan R; Cleveland, Cory C

2017-06-01

We hypothesized that dinitrogen (N 2 )- and non-N 2 -fixing tropical trees would have distinct phosphorus (P) acquisition strategies allowing them to exploit different P sources, reducing competition. We measured root phosphatase activity and arbuscular mycorrhizal (AM) colonization among two N 2 - and two non-N 2 -fixing seedlings, and grew them alone and in competition with different inorganic and organic P forms to assess potential P partitioning. We found an inverse relationship between root phosphatase activity and AM colonization in field-collected seedlings, indicative of a trade-off in P acquisition strategies. This correlated with the predominantly exploited P sources in the seedling experiment: the N 2 fixer with high N 2 fixation and root phosphatase activity grew best on organic P, whereas the poor N 2 fixer and the two non-N 2 fixers with high AM colonization grew best on inorganic P. When grown in competition, however, AM colonization, root phosphatase activity and N 2 fixation increased in the N 2 fixers, allowing them to outcompete the non-N 2 fixers regardless of P source. Our results indicate that some tropical trees have the capacity to partition soil P, but this does not eliminate interspecific competition. Rather, enhanced P and N acquisition strategies may increase the competitive ability of N 2 fixers relative to non-N 2 fixers. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

Combination of Cyclamen persicum Mill. floral gene promoters and chimeric repressors for the modification of ornamental traits in Torenia fournieri Lind.

PubMed Central

Kasajima, Ichiro; Ohtsubo, Norihiro; Sasaki, Katsutomo

2017-01-01

Although chimeric repressors such as the Arabidopsis TCP3 repressor are known to have significant effects on flower morphology and color, their cellular-level effects on flower petals are not understood. The promoter sequences of the genes expressed in the flowers of cyclamen, a representative potted flower grown during the winter season, are also unknown. Here, we isolated eight promoters from cyclamen genes that are reportedly expressed in the petals. These promoters were then fused to four chimeric repressors and introduced into the model flower torenia to screen for effective combinations of promoters and repressors for flower breeding. As expected, some of the constructs altered flower phenotypes upon transformation. We further analyzed the effects of chimeric repressors at the cellular level. We observed that complicated petal and leaf serrations were accompanied by excessive vascular branching. Dichromatism in purple anthocyanin was inferred to result in bluish flowers, and imbalanced cell proliferation appeared to result in epinastic flowers. Thus, the genetic constructs and phenotypic changes described in this report will benefit the future breeding and characterization of ornamental flowers. PMID:28446955

Technology Assessment Need: Review on Attractiveness and Competitiveness

NASA Astrophysics Data System (ADS)

Salwa Sait, Siti; Merlinda Muharam, Farrah; Chin, Thoo Ai; Sulaiman, Zuraidah

2017-06-01

Technology assessment is crucial in managing technology for the purpose of technology exploitation. With business environment continuously changing, firms have to address this issue critically as technology is considered one of the important elements to evaluate performance and gain competitive advantage. Missteps in deciding the best technology to be developed, employed or maintained would cost the firm overall value. To fulfil the need of finding the appropriate scale to assess suitable technology, this paper summarizes that technology assessment (TA) should cover two main aspects, namely technology attractiveness and competitiveness. These components are seen capable to link the scale suggested towards evaluation of financial and non-financial performance towards competitive advantage.

TGF-{beta} signals the formation of a unique NF1/Smad4-dependent transcription repressor-complex in human diploid fibroblasts

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

Luciakova, Katarina, E-mail: katarina.luciakova@savba.sk; Kollarovic, Gabriel; Kretova, Miroslava

2011-08-05

Highlights: {yields} TGF-{beta} induces the formation of unique nuclear NF1/Smad4 complexes that repress expression of the ANT-2 gene. {yields} Repression is mediated through an NF1-dependent repressor element in the promoter. {yields} The formation of NF1/Smad4 complexes and the repression of ANT2 are prevented by inhibitors of p38 kinase and TGF-{beta} RI. {yields} NF1/Smad complexes implicate novel role for NF1 and Smad proteins in the regulation of growth. -- Abstract: We earlier reported the formation of a unique nuclear NF1/Smad complex in serum-restricted fibroblasts that acts as an NF1-dependent repressor of the human adenine nucleotide translocase-2 gene (ANT2) [K. Luciakova, G.more » Kollarovic, P. Barath, B.D. Nelson, Growth-dependent repression of human adenine nucleotide translocator-2 (ANT2) transcription: evidence for the participation of Smad and Sp family proteins in the NF1-dependent repressor complex, Biochem. J. 412 (2008) 123-130]. In the present study, we show that TGF-{beta}, like serum-restriction: (a) induces the formation of NF1/Smad repressor complexes, (b) increases binding of the complexes to the repressor elements (Go elements) in the ANT2 promoter, and (c) inhibits ANT2 expression. Repression of ANT2 by TGF-{beta} is eliminated by mutating the NF1 binding sites in the Go repressor elements. All of the above responses to TGF-{beta} are prevented by inhibitors of TGF-{beta} RI and MAPK p38. These inhibitors also prevent NF1/Smad4 repressor complex formation and repression of ANT2 expression in serum-restricted cells, suggesting that similar signaling pathways are initiated by TGF-{beta} and serum-restriction. The present finding that NF1/Smad4 repressor complexes are formed through TGF-{beta} signaling pathways suggests a new, but much broader, role for these complexes in the initiation or maintenance of the growth-inhibited state.« less

Neural correlates of strategic reasoning during competitive games.

PubMed

Seo, Hyojung; Cai, Xinying; Donahue, Christopher H; Lee, Daeyeol

2014-10-17

Although human and animal behaviors are largely shaped by reinforcement and punishment, choices in social settings are also influenced by information about the knowledge and experience of other decision-makers. During competitive games, monkeys increased their payoffs by systematically deviating from a simple heuristic learning algorithm and thereby countering the predictable exploitation by their computer opponent. Neurons in the dorsomedial prefrontal cortex (dmPFC) signaled the animal's recent choice and reward history that reflected the computer's exploitative strategy. The strength of switching signals in the dmPFC also correlated with the animal's tendency to deviate from the heuristic learning algorithm. Therefore, the dmPFC might provide control signals for overriding simple heuristic learning algorithms based on the inferred strategies of the opponent. Copyright © 2014, American Association for the Advancement of Science.

Trophic Strategies of a Non-Native and a Native Amphibian Species in Shared Ponds

PubMed Central

San Sebastián, Olatz; Navarro, Joan; Llorente, Gustavo A.; Richter-Boix, Álex

2015-01-01

One of the critical factors for understanding the establishment, success and potential impact on native species of an introduced species is a thorough knowledge of how these species manage trophic resources. Two main trophic strategies for resource acquisition have been described: competition and opportunism. In the present study our objective was to identify the main trophic strategies of the non-native amphibian Discoglossus pictus and its potential trophic impact on the native amphibian Bufo calamita. We determine whether D. pictus exploits similar trophic resources to those exploited by the native B. calamita (competition hypothesis) or alternative resources (opportunistic hypothesis). To this end, we analyzed the stable isotope values of nitrogen and carbon in larvae of both species, in natural ponds and in controlled laboratory conditions. The similarity of the δ15N and δ13C values in the two species coupled with isotopic signal variation according to pond conditions and niche partitioning when they co-occurred indicated dietary competition. Additionally, the non-native species was located at higher levels of trophic niches than the native species and B. calamita suffered an increase in its standard ellipse area when it shared ponds with D. pictus. These results suggest niche displacement of B. calamita to non-preferred resources and greater competitive capacity of D. pictus in field conditions. Moreover, D. pictus showed a broader niche than the native species in all conditions, indicating increased capacity to exploit the diversity of resources; this may indirectly favor its invasiveness. Despite the limitations of this study (derived from potential variability in pond isotopic signals), the results support previous experimental studies. All the studies indicate that D. pictus competes with B. calamita for trophic resources with potential negative effects on the fitness of the latter. PMID:26101880

Repressor logic modules assembled by rolling circle amplification platform to construct a set of logic gates

PubMed Central

Wei, Hua; Hu, Bo; Tang, Suming; Zhao, Guojie; Guan, Yifu

2016-01-01

Small molecule metabolites and their allosterically regulated repressors play an important role in many gene expression and metabolic disorder processes. These natural sensors, though valuable as good logic switches, have rarely been employed without transcription machinery in cells. Here, two pairs of repressors, which function in opposite ways, were cloned, purified and used to control DNA replication in rolling circle amplification (RCA) in vitro. By using metabolites and repressors as inputs, RCA signals as outputs, four basic logic modules were constructed successfully. To achieve various logic computations based on these basic modules, we designed series and parallel strategies of circular templates, which can further assemble these repressor modules in an RCA platform to realize twelve two-input Boolean logic gates and a three-input logic gate. The RCA-output and RCA-assembled platform was proved to be easy and flexible for complex logic processes and might have application potential in molecular computing and synthetic biology. PMID:27869177

Competitive impacts of an invasive nectar thief on plant-pollinator mutualisms

USGS Publications Warehouse

Hanna, Cause; Foote, David; Kremen, Claire

2014-01-01

Plant–pollinator mutualisms are disrupted by a variety of competitive interactions between introduced and native floral visitors. The invasive western yellowjacket wasp, Vespula pensylvanica, is an aggressive nectar thief of the dominant endemic Hawaiian tree species, Metrosideros polymorpha. We conducted a large-scale, multiyear manipulative experiment to investigate the impacts of V. pensylvanica on the structure and behavior of the M. polymorpha pollinator community, including competitive mechanisms related to resource availability. Our results demonstrate that V. pensylvanica, through both superior exploitative and interference competition, influences resource partitioning and displaces native and nonnative M. polymorpha pollinators. Furthermore, the restructuring of the pollinator community due to V. pensylvanica competition and predation results in a significant decrease in the overall pollinator effectiveness and fruit set of M. polymorpha. This research highlights both the competitive mechanisms and contrasting effects of social insect invaders on plant–pollinator mutualisms and the role of competition in pollinator community structure.

Crystallization and preliminary X-ray diffraction analysis of the arginine repressor of the hyperthermophile Thermotoga neapolitana

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

Massant, Jan, E-mail: jan.massant@vub.ac.be; Peeters, Eveline; Charlier, Daniel

2006-01-01

The arginine repressor of the hyperthermophile T. neapolitana was crystallized with and without its corepressor arginine. Both crystals diffracted to high resolution and belong to the orthorhombic space group P2{sub 1}2{sub 1}2{sub 1}, with similar unit-cell parameters. The arginine repressor of Thermotoga neapolitana (ArgRTnp) is a member of the family of multifunctional bacterial arginine repressors involved in the regulation of arginine metabolism. This hyperthermophilic repressor shows unique DNA-binding features that distinguish it from its homologues. ArgRTnp exists as a homotrimeric protein that assembles into hexamers at higher protein concentrations and/or in the presence of arginine. ArgRTnp was crystallized with andmore » without its corepressor arginine using the hanging-drop vapour-diffusion method. Crystals of the aporepressor diffracted to a resolution of 2.1 Å and belong to the orthorhombic P2{sub 1}2{sub 1}2{sub 1} space group, with unit-cell parameters a = 117.73, b = 134.15, c = 139.31 Å. Crystals of the repressor in the presence of its corepressor arginine diffracted to a resolution of 2.4 Å and belong to the same space group, with similar unit-cell parameters.« less

Normalization regulates competition for visual awareness

PubMed Central

Ling, Sam; Blake, Randolph

2012-01-01

Summary Signals in our brain are in a constant state of competition, including those that vie for motor control, sensory dominance and awareness. To shed light on the mechanisms underlying neural competition, we exploit binocular rivalry, a phenomenon that allows us to probe the competitive process that ordinarily transpires outside of our awareness. By measuring psychometric functions under different states of rivalry, we discovered a pattern of gain changes that are consistent with a model of competition in which attention interacts with normalization processes, thereby driving the ebb and flow between states of awareness. Moreover, we reveal that attention plays a crucial role in modulating competition; without attention, rivalry suppression for high-contrast stimuli is negligible. We propose a framework whereby our visual awareness of competing sensory representations is governed by a common neural computation: normalization. PMID:22884335

Streptococcus mutans copper chaperone, CopZ, is critical for biofilm formation and competitiveness.

PubMed

Garcia, S S; Du, Q; Wu, H

2016-12-01

The oral cavity is a dynamic environment characterized by hundreds of bacterial species, saliva, and an influx of nutrients and metal ions such as copper. Although there is a physiologic level of copper in the saliva, the oral cavity is often challenged with an influx of copper ions. At high concentrations copper is toxic and must therefore be strictly regulated by pathogens for them to persist and cause disease. The cariogenic pathogen Streptococcus mutans manages excess copper using the copYAZ operon that encodes a negative DNA-binding repressor (CopY), the P1-ATPase copper exporter (CopA), and the copper chaperone (CopZ). These hypothetical roles of the copYAZ operon in regulation and copper transport to receptors led us to investigate their contribution to S. mutans virulence. Mutants defective in the copper chaperone CopZ, but not CopY or CopA, were impaired in biofilm formation and competitiveness against commensal streptococci. Characterization of the CopZ mutant biofilm revealed a decreased secretion of glucosyltransferases and reduced expression of mutacin genes. These data suggest that the function of copZ on biofilm and competitiveness is independent of copper resistance and CopZ is a global regulator for biofilm and other virulence factors. Further characterization of CopZ may lead to the identification of new biofilm pathways. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The effects of facilitation and competition on group foraging in patches

PubMed Central

Laguë, Marysa; Tania, Nessy; Heath, Joel; Edelstein-Keshet, Leah

2012-01-01

Significant progress has been made towards understanding the social behaviour of animal groups, but the patch model, a foundation of foraging theory, has received little attention in a social context. The effect of competition on the optimal time to leave a foraging patch was considered as early as the original formulation of the marginal value theorem, but surprisingly, the role of facilitation (where foraging in groups decreases the time to find food in patches), has not been incorporated. Here we adapt the classic patch model to consider how the trade-off between facilitation and competition influence optimal group size. Using simple assumptions about the effect of group size on the food-finding time and the sharing of resources, we find conditions for existence of optima in patch residence time and in group size. When patches are close together (low travel times), larger group sizes are optimal. Groups are predicted to exploit patches differently than individual foragers and the degree of patch depletion at departure depends on the details of the trade-off between competition and facilitation. A variety of currencies and group-size effects are also considered and compared. Using our simple formulation, we also study the effects of social foraging on patch exploitation which to date have received little empirical study. PMID:22743132

The effects of facilitation and competition on group foraging in patches.

PubMed

Laguë, Marysa; Tania, Nessy; Heath, Joel; Edelstein-Keshet, Leah

2012-10-07

Significant progress has been made towards understanding the social behaviour of animal groups, but the patch model, a foundation of foraging theory, has received little attention in a social context. The effect of competition on the optimal time to leave a foraging patch was considered as early as the original formulation of the marginal value theorem, but surprisingly, the role of facilitation (where foraging in groups decreases the time to find food in patches), has not been incorporated. Here we adapt the classic patch model to consider how the trade-off between facilitation and competition influences optimal group size. Using simple assumptions about the effect of group size on the food-finding time and the sharing of resources, we find conditions for existence of optima in patch residence time and in group size. When patches are close together (low travel times), larger group sizes are optimal. Groups are predicted to exploit patches differently than individual foragers and the degree of patch depletion at departure depends on the details of the trade-off between competition and facilitation. A variety of currencies and group-size effects are also considered and compared. Using our simple formulation, we also study the effects of social foraging on patch exploitation which to date have received little empirical study. Copyright © 2012 Elsevier Ltd. All rights reserved.

Proto-oncogene FBI-1 (Pokemon/ZBTB7A) represses transcription of the tumor suppressor Rb gene via binding competition with Sp1 and recruitment of co-repressors.

PubMed

Jeon, Bu-Nam; Yoo, Jung-Yoon; Choi, Won-Il; Lee, Choong-Eun; Yoon, Ho-Geun; Hur, Man-Wook

2008-11-28

FBI-1 (also called Pokemon/ZBTB7A) is a BTB/POZ-domain Krüppel-like zinc-finger transcription factor. Recently, FBI-1 was characterized as a proto-oncogenic protein, which represses tumor suppressor ARF gene transcription. The expression of FBI-1 is increased in many cancer tissues. We found that FBI-1 potently represses transcription of the Rb gene, a tumor suppressor gene important in cell cycle arrest. FBI-1 binds to four GC-rich promoter elements (FREs) located at bp -308 to -188 of the Rb promoter region. The Rb promoter also contains two Sp1 binding sites: GC-box 1 (bp -65 to -56) and GC-box 2 (bp -18 to -9), the latter of which is also bound by FBI-1. We found that FRE3 (bp -244 to -236) is also a Sp1 binding element. FBI-1 represses transcription of the Rb gene not only by binding to the FREs, but also by competing with Sp1 at the GC-box 2 and the FRE3. By binding to the FREs and/or the GC-box, FBI-1 represses transcription of the Rb gene through its POZ-domain, which recruits a co-repressor-histone deacetylase complex and deacetylates histones H3 and H4 at the Rb gene promoter. FBI-1 inhibits C2C12 myoblast cell differentiation by repressing Rb gene expression.

48 CFR 22.201 - General.

Code of Federal Regulations, 2011 CFR

2011-10-01

... to avoid either the exploitation of convict labor or any unfair competition between convict labor and... Executive order if— (i) The worker is paid or is in an approved work training program on a voluntary basis...

Solution structure of dimeric Mnt repressor (1-76).

PubMed

Burgering, M J; Boelens, R; Gilbert, D E; Breg, J N; Knight, K L; Sauer, R T; Kaptein, R

1994-12-20

Wild-type Mnt repressor of Salmonella bacteriophage P22 is a tetrameric protein of 82 residues per monomer. A C-terminal deletion mutant of the repressor denoted Mnt (1-76) is a dimer in solution. The structure of this dimer has been determined using NMR. The NMR assignments of the majority of the 1H, 15N, and 13C resonances were obtained using 2D and triple-resonance 3D techniques. Elements of secondary structure were identified on the basis of characteristic sequential and medium range NOEs. For the structure determination more than 1000 NOEs per monomer were obtained, and structures were generated using distance geometry and restrained simulated annealing calculations. The discrimination of intra- vs intermonomer NOEs was based upon the observation of intersubunit NOEs in [15N,13C] double half-filtered NOESY experiments. The N-terminal part of Mnt (residues 1-44), which shows a 40% sequence homology with the Arc repressor, has a similar secondary and tertiary structure. Mnt (1-76) continues with a loop region of irregular structure, a third alpha-helix, and a random coil C-terminal peptide. Analysis of the secondary structure NOEs, the exchange rates, and the backbone chemical shifts suggests that the carboxy-terminal third helix is less stable than the remainder of the protein, but the observation of intersubunit NOEs for this part of the protein enables the positioning of this helix. The rsmd's between the backbone atoms of the N-terminal part of the Mnt repressor (residues 5-43, 5'-43') and the Arc repressor is 1.58 A, and between this region and the corresponding part of the MetJ repressor 1.43 A.

Crowd computing: using competitive dynamics to develop and refine highly predictive models.

PubMed

Bentzien, Jörg; Muegge, Ingo; Hamner, Ben; Thompson, David C

2013-05-01

A recent application of a crowd computing platform to develop highly predictive in silico models for use in the drug discovery process is described. The platform, Kaggle™, exploits a competitive dynamic that results in model optimization as the competition unfolds. Here, this dynamic is described in detail and compared with more-conventional modeling strategies. The complete and full structure of the underlying dataset is disclosed and some thoughts as to the broader utility of such 'gamification' approaches to the field of modeling are offered. Copyright © 2013 Elsevier Ltd. All rights reserved.

Structure of the MecI repressor from Staphylococcus aureus in complex with the cognate DNA operator of mec

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

Safo, Martin K., E-mail: msafo@vcu.edu; Ko, Tzu-Ping; Musayev, Faik N.

The up-and-down binding of dimeric MecI to mecA dyad DNA may account for the cooperative effect of the repressor. The dimeric repressor MecI regulates the mecA gene that encodes the penicillin-binding protein PBP-2a in methicillin-resistant Staphylococcus aureus (MRSA). MecI is similar to BlaI, the repressor for the blaZ gene of β-lactamase. MecI and BlaI can bind to both operator DNA sequences. The crystal structure of MecI in complex with the 32 base-pair cognate DNA of mec was determined to 3.8 Å resolution. MecI is a homodimer and each monomer consists of a compact N-terminal winged-helix domain, which binds to DNA,more » and a loosely packed C-terminal helical domain, which intertwines with its counter-monomer. The crystal contains horizontal layers of virtual DNA double helices extending in three directions, which are separated by perpendicular DNA segments. Each DNA segment is bound to two MecI dimers. Similar to the BlaI–mec complex, but unlike the MecI–bla complex, the MecI repressors bind to both sides of the mec DNA dyad that contains four conserved sequences of TACA/TGTA. The results confirm the up-and-down binding to the mec operator, which may account for cooperative effect of the repressor.« less

Repressor-mediated tissue-specific gene expression in plants

DOEpatents

Meagher, Richard B [Athens, GA; Balish, Rebecca S [Oxford, OH; Tehryung, Kim [Athens, GA; McKinney, Elizabeth C [Athens, GA

2009-02-17

Plant tissue specific gene expression by way of repressor-operator complexes, has enabled outcomes including, without limitation, male sterility and engineered plants having root-specific gene expression of relevant proteins to clean environmental pollutants from soil and water. A mercury hyperaccumulation strategy requires that mercuric ion reductase coding sequence is strongly expressed. The actin promoter vector, A2pot, engineered to contain bacterial lac operator sequences, directed strong expression in all plant vegetative organs and tissues. In contrast, the expression from the A2pot construct was restricted primarily to root tissues when a modified bacterial repressor (LacIn) was coexpressed from the light-regulated rubisco small subunit promoter in above-ground tissues. Also provided are analogous repressor operator complexes for selective expression in other plant tissues, for example, to produce male sterile plants.

BiFCROS: A Low-Background Fluorescence Repressor Operator System for Labeling of Genomic Loci.

PubMed

Milbredt, Sarah; Waldminghaus, Torsten

2017-06-07

Fluorescence-based methods are widely used to analyze elementary cell processes such as DNA replication or chromosomal folding and segregation. Labeling DNA with a fluorescent protein allows the visualization of its temporal and spatial organization. One popular approach is FROS (fluorescence repressor operator system). This method specifically labels DNA in vivo through binding of a fusion of a fluorescent protein and a repressor protein to an operator array, which contains numerous copies of the repressor binding site integrated into the genomic site of interest. Bound fluorescent proteins are then visible as foci in microscopic analyses and can be distinguished from the background fluorescence caused by unbound fusion proteins. Even though this method is widely used, no attempt has been made so far to decrease the background fluorescence to facilitate analysis of the actual signal of interest. Here, we present a new method that greatly reduces the background signal of FROS. BiFCROS (Bimolecular Fluorescence Complementation and Repressor Operator System) is based on fusions of repressor proteins to halves of a split fluorescent protein. Binding to a hybrid FROS array results in fluorescence signals due to bimolecular fluorescence complementation. Only proteins bound to the hybrid FROS array fluoresce, greatly improving the signal to noise ratio compared to conventional FROS. We present the development of BiFCROS and discuss its potential to be used as a fast and single-cell readout for copy numbers of genetic loci. Copyright © 2017 Milbredt and Waldminghaus.

BiFCROS: A Low-Background Fluorescence Repressor Operator System for Labeling of Genomic Loci

PubMed Central

Milbredt, Sarah; Waldminghaus, Torsten

2017-01-01

Fluorescence-based methods are widely used to analyze elementary cell processes such as DNA replication or chromosomal folding and segregation. Labeling DNA with a fluorescent protein allows the visualization of its temporal and spatial organization. One popular approach is FROS (fluorescence repressor operator system). This method specifically labels DNA in vivo through binding of a fusion of a fluorescent protein and a repressor protein to an operator array, which contains numerous copies of the repressor binding site integrated into the genomic site of interest. Bound fluorescent proteins are then visible as foci in microscopic analyses and can be distinguished from the background fluorescence caused by unbound fusion proteins. Even though this method is widely used, no attempt has been made so far to decrease the background fluorescence to facilitate analysis of the actual signal of interest. Here, we present a new method that greatly reduces the background signal of FROS. BiFCROS (Bimolecular Fluorescence Complementation and Repressor Operator System) is based on fusions of repressor proteins to halves of a split fluorescent protein. Binding to a hybrid FROS array results in fluorescence signals due to bimolecular fluorescence complementation. Only proteins bound to the hybrid FROS array fluoresce, greatly improving the signal to noise ratio compared to conventional FROS. We present the development of BiFCROS and discuss its potential to be used as a fast and single-cell readout for copy numbers of genetic loci. PMID:28450375

Body size mediated coexistence of consumers competing for resources in space

USGS Publications Warehouse

Basset, A.; Angelis, D.L.

2007-01-01

Body size is a major phenotypic trait of individuals that commonly differentiates co-occurring species. We analyzed inter-specific competitive interactions between a large consumer and smaller competitors, whose energetics, selection and giving-up behaviour on identical resource patches scaled with individual body size. The aim was to investigate whether pure metabolic constraints on patch behaviour of vagile species can determine coexistence conditions consistent with existing theoretical and experimental evidence. We used an individual-based spatially explicit simulation model at a spatial scale defined by the home range of the large consumer, which was assumed to be parthenogenic and semelparous. Under exploitative conditions, competitive coexistence occurred in a range of body size ratios between 2 and 10. Asymmetrical competition and the mechanism underlying asymmetry, determined by the scaling of energetics and patch behaviour with consumer body size, were the proximate determinant of inter-specific coexistence. The small consumer exploited patches more efficiently, but searched for profitable patches less effectively than the larger competitor. Therefore, body-size related constraints induced niche partitioning, allowing competitive coexistence within a set of conditions where the large consumer maintained control over the small consumer and resource dynamics. The model summarises and extends the existing evidence of species coexistence on a limiting resource, and provides a mechanistic explanation for decoding the size-abundance distribution patterns commonly observed at guild and community levels. ?? Oikos.

CalR is required for the expression of T6SS2 and the adhesion of Vibrio parahaemolyticus to HeLa cells.

PubMed

Zhang, Lingyu; Osei-Adjei, George; Zhang, Ying; Gao, He; Yang, Wenhui; Zhou, Dongsheng; Huang, Xinxiang; Yang, Huiying; Zhang, Yiquan

2017-08-01

Vibrio parahaemolyticus expresses one major virulence determinant T6SS2, which is constituted into three putative operons, i.e., VPA1027-1024, VPA1043-1028, and VPA1044-1046. CalR, a LysR-type transcriptional regulator, was originally identified as a repressor of the swarming motility and T3SS1 gene expression. As shown in this study, CalR binds to the promoter-proximal region of each of the three operons to activate their transcription, and moreover, CalR activates the adhesion of V. parahaemolyticus to HeLa cells. In addition, competitive EMSAs demonstrated that CalR acts as an antagonist of H-NS in V. parahaemolyticus. Collectively, these studies confirmed a new physiological role for CalR in V. parahaemolyticus.

The role of repressor kinetics in relief of transcriptional interference between convergent promoters

PubMed Central

Hao, Nan; Palmer, Adam C.; Ahlgren-Berg, Alexandra; Shearwin, Keith E.; Dodd, Ian B.

2016-01-01

Transcriptional interference (TI), where transcription from a promoter is inhibited by the activity of other promoters in its vicinity on the same DNA, enables transcription factors to regulate a target promoter indirectly, inducing or relieving TI by controlling the interfering promoter. For convergent promoters, stochastic simulations indicate that relief of TI can be inhibited if the repressor at the interfering promoter has slow binding kinetics, making it either sensitive to frequent dislodgement by elongating RNA polymerases (RNAPs) from the target promoter, or able to be a strong roadblock to these RNAPs. In vivo measurements of relief of TI by CI or Cro repressors in the bacteriophage λ PR–PRE system show strong relief of TI and a lack of dislodgement and roadblocking effects, indicative of rapid CI and Cro binding kinetics. However, repression of the same λ promoter by a catalytically dead CRISPR Cas9 protein gave either compromised or no relief of TI depending on the orientation at which it binds DNA, consistent with dCas9 being a slow kinetics repressor. This analysis shows how the intrinsic properties of a repressor can be evolutionarily tuned to set the magnitude of relief of TI. PMID:27378773

Mechanism of Metal Ion Activation of the Diphtheria Toxin Repressor DtxR

NASA Astrophysics Data System (ADS)

D'Aquino, J. Alejandro; Ringe, Dagmar

2006-08-01

The diphtheria toxin repressor, DtxR, is a metal ion-activated transcriptional regulator that has been linked to the virulence of Corynebacterium diphtheriae. Structure determination has shown that there are two metal ion binding sites per repressor monomer, and site-directed mutagenesis has demonstrated that binding site 2 (primary) is essential for recognition of the target DNA repressor, leaving the role of binding site 1 (ancillary) unclear (1 - 3). Calorimetric techniques have demonstrated that while binding site 1 (ancillary) has high affinity for metal ion with a binding constant of 2 × 10-7, binding site 2 (primary) is a low affinity binding site with a binding constant of 6.3 × 10-4. These two binding sites act independently and their contribution can be easily dissected by traditional mutational analysis. Our results clearly demonstrate that binding site 1 (ancillary) is the first one to be occupied during metal ion activation, playing a critical role in stabilization of the repressor. In addition, structural data obtained for the mutants Ni-DtxR(H79A,C102D), reported here and the previously reported DtxR(H79A) (4) has allowed us to propose a mechanism of metal ion activation for DtxR.

Face structure predicts cooperation: men with wider faces are more generous to their in-group when out-group competition is salient.

PubMed

Stirrat, M; Perrett, D I

2012-07-01

Male facial width-to-height ratio appears to correlate with antisocial tendencies, such as aggression, exploitation, cheating, and deception. We present evidence that male facial width-to-height ratio is also associated with a stereotypically male prosocial tendency: to increase cooperation with other in-group members during intergroup competition. We found that men who had wider faces, compared with men who had narrower faces, showed more self-sacrificing cooperation to help their group members when there was competition with another group. We propose that this finding makes sense given the evolutionary functions of social helpfulness and aggression.

Facultative Control of Matrix Production Optimizes Competitive Fitness in Pseudomonas aeruginosa PA14 Biofilm Models

PubMed Central

Madsen, Jonas S.; Lin, Yu-Cheng; Squyres, Georgia R.; Price-Whelan, Alexa; de Santiago Torio, Ana; Song, Angela; Cornell, William C.; Sørensen, Søren J.

2015-01-01

As biofilms grow, resident cells inevitably face the challenge of resource limitation. In the opportunistic pathogen Pseudomonas aeruginosa PA14, electron acceptor availability affects matrix production and, as a result, biofilm morphogenesis. The secreted matrix polysaccharide Pel is required for pellicle formation and for colony wrinkling, two activities that promote access to O2. We examined the exploitability and evolvability of Pel production at the air-liquid interface (during pellicle formation) and on solid surfaces (during colony formation). Although Pel contributes to the developmental response to electron acceptor limitation in both biofilm formation regimes, we found variation in the exploitability of its production and necessity for competitive fitness between the two systems. The wild type showed a competitive advantage against a non-Pel-producing mutant in pellicles but no advantage in colonies. Adaptation to the pellicle environment selected for mutants with a competitive advantage against the wild type in pellicles but also caused a severe disadvantage in colonies, even in wrinkled colony centers. Evolution in the colony center produced divergent phenotypes, while adaptation to the colony edge produced mutants with clear competitive advantages against the wild type in this O2-replete niche. In general, the structurally heterogeneous colony environment promoted more diversification than the more homogeneous pellicle. These results suggest that the role of Pel in community structure formation in response to electron acceptor limitation is unique to specific biofilm models and that the facultative control of Pel production is required for PA14 to maintain optimum benefit in different types of communities. PMID:26431965

Facultative control of matrix production optimizes competitive fitness in Pseudomonas aeruginosa PA14 biofilm models.

PubMed

Madsen, Jonas S; Lin, Yu-Cheng; Squyres, Georgia R; Price-Whelan, Alexa; de Santiago Torio, Ana; Song, Angela; Cornell, William C; Sørensen, Søren J; Xavier, Joao B; Dietrich, Lars E P

2015-12-01

As biofilms grow, resident cells inevitably face the challenge of resource limitation. In the opportunistic pathogen Pseudomonas aeruginosa PA14, electron acceptor availability affects matrix production and, as a result, biofilm morphogenesis. The secreted matrix polysaccharide Pel is required for pellicle formation and for colony wrinkling, two activities that promote access to O2. We examined the exploitability and evolvability of Pel production at the air-liquid interface (during pellicle formation) and on solid surfaces (during colony formation). Although Pel contributes to the developmental response to electron acceptor limitation in both biofilm formation regimes, we found variation in the exploitability of its production and necessity for competitive fitness between the two systems. The wild type showed a competitive advantage against a non-Pel-producing mutant in pellicles but no advantage in colonies. Adaptation to the pellicle environment selected for mutants with a competitive advantage against the wild type in pellicles but also caused a severe disadvantage in colonies, even in wrinkled colony centers. Evolution in the colony center produced divergent phenotypes, while adaptation to the colony edge produced mutants with clear competitive advantages against the wild type in this O2-replete niche. In general, the structurally heterogeneous colony environment promoted more diversification than the more homogeneous pellicle. These results suggest that the role of Pel in community structure formation in response to electron acceptor limitation is unique to specific biofilm models and that the facultative control of Pel production is required for PA14 to maintain optimum benefit in different types of communities. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Course 1: Physics of Protein-DNA Interaction

NASA Astrophysics Data System (ADS)

Bruinsma, R. F.

1 Introduction 1.1 The central dogma and bacterial gene expression 1.2 Molecular structure 2 Thermodynamics and kinetics of repressor-DNA interaction 2.1 Thermodynamics and the lac repressor 2.2 Kinetics of repressor-DNA interaction 3 DNA deformability and protein-DNA interaction 3.1 Introduction 3.2 The worm-like chain 3.3 The RST model 4 Electrostatics in water and protein-DNA interaction 4.1 Macro-ions and aqueous electrostatics 4.2 The primitive model 4.3 Manning condensation 4.4 Counter-ion release and non-specific protein-DNA interaction

Partitioning ecosystems for sustainability.

PubMed

Murray, Martyn G

2016-03-01

Decline in the abundance of renewable natural resources (RNRs) coupled with increasing demands of an expanding human population will greatly intensify competition for Earth's natural resources during this century, yet curiously, analytical approaches to the management of productive ecosystems (ecological theory of wildlife harvesting, tragedy of the commons, green economics, and bioeconomics) give only peripheral attention to the driving influence of competition on resource exploitation. Here, I apply resource competition theory (RCT) to the exploitation of RNRs and derive four general policies in support of their sustainable and equitable use: (1) regulate resource extraction technology to avoid damage to the resource base; (2) increase efficiency of resource use and reduce waste at every step in the resource supply chain and distribution network; (3) partition ecosystems with the harvesting niche as the basic organizing principle for sustainable management of natural resources by multiple users; and (4) increase negative feedback between consumer and resource to bring about long-term sustainable use. A simple policy framework demonstrates how RCT integrates with other elements of sustainability science to better manage productive ecosystems. Several problem areas of RNR management are discussed in the light of RCT, including tragedy of the commons, overharvesting, resource collapse, bycatch, single species quotas, and simplification of ecosystems.

Mutation of praR in Rhizobium leguminosarum enhances root biofilms, improving nodulation competitiveness by increased expression of attachment proteins

PubMed Central

Frederix, Marijke; Edwards, Anne; Swiderska, Anna; Stanger, Andrew; Karunakaran, Ramakrishnan; Williams, Alan; Abbruscato, Pamela; Sanchez-Contreras, Maria; Poole, Philip S; Downie, J Allan

2014-01-01

In Rhizobium leguminosarum bv. viciae, quorum-sensing is regulated by CinR, which induces the cinIS operon. CinI synthesizes an AHL, whereas CinS inactivates PraR, a repressor. Mutation of praR enhanced biofilms in vitro. We developed a light (lux)-dependent assay of rhizobial attachment to roots and demonstrated that mutation of praR increased biofilms on pea roots. The praR mutant out-competed wild-type for infection of pea nodules in mixed inoculations. Analysis of gene expression by microarrays and promoter fusions revealed that PraR represses its own transcription and mutation of praR increased expression of several genes including those encoding secreted proteins (the adhesins RapA2, RapB and RapC, two cadherins and the glycanase PlyB), the polysaccharide regulator RosR, and another protein similar to PraR. PraR bound to the promoters of several of these genes indicating direct repression. Mutations in rapA2, rapB, rapC, plyB, the cadherins or rosR did not affect the enhanced root attachment or nodule competitiveness of the praR mutant. However combinations of mutations in rapA, rapB and rapC abolished the enhanced attachment and nodule competitiveness. We conclude that relief of PraR-mediated repression determines a lifestyle switch allowing the expression of genes that are important for biofilm formation on roots and the subsequent initiation of infection of legume roots. PMID:24942546

Cancer, acute stress disorder, and repressive coping.

PubMed

Pedersen, Anette Fischer; Zachariae, Robert

2010-02-01

The purpose of this study was to investigate the association between repressive coping style and Acute Stress Disorder (ASD) in a sample of cancer patients. A total of 112 cancer patients recently diagnosed with cancer participated in the study. ASD was assessed by the Stanford Acute Stress Reaction Questionnaire, and repressive coping was assessed by a combination of scores from the Marlowe-Crowne Social Desirability Scale, and the Bendig version of the Taylor Manifest Anxiety Scale. Significantly fewer patients classified as "repressors" were diagnosed with ASD compared to patients classified as "non-repressors". However, further investigations revealed that the lower incidence of ASD in repressors apparently was caused by a low score on anxiety and not by an interaction effect between anxiety and defensiveness. Future studies have to investigate whether different psychological mechanisms are responsible for the lower incidence of ASD in repressors and true low-anxious patients.

Can we accelerate medicinal chemistry by augmenting the chemist with Big Data and artificial intelligence?

PubMed

Griffen, Edward J; Dossetter, Alexander G; Leach, Andrew G; Montague, Shane

2018-03-22

AI comes to lead optimization: medicinal chemistry in all disease areas can be accelerated by exploiting our pre-competitive knowledge in an unbiased way. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effects of payment reform in more versus less competitive markets.

PubMed

Sood, Neeraj; Alpert, Abby; Barnes, Kayleigh; Huckfeldt, Peter; Escarce, José J

2017-01-01

Policymakers are increasingly interested in reducing healthcare costs and inefficiencies through innovative payment strategies. These strategies may have heterogeneous impacts across geographic areas, potentially reducing or exacerbating geographic variation in healthcare spending. In this paper, we exploit a major payment reform for home health care to examine whether reductions in reimbursement lead to differential changes in treatment intensity and provider costs depending on the level of competition in a market. Using Medicare claims, we find that while providers in more competitive markets had higher average costs in the pre-reform period, these markets experienced larger proportional reductions in treatment intensity and costs after the reform relative to less competitive markets. This led to a convergence in spending across geographic areas. We find that much of the reduction in provider costs is driven by greater exit of "high-cost" providers in more competitive markets. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of Payment Reform in More versus Less Competitive Markets

PubMed Central

Sood, Neeraj; Alpert, Abby; Barnes, Kayleigh; Huckfeldt, Peter; Escarce, José J.

2017-01-01

Policymakers are increasingly interested in reducing healthcare costs and inefficiencies through innovative payment strategies. These strategies may have heterogeneous impacts across geographic areas, potentially reducing or exacerbating geographic variation in healthcare spending. In this paper, we exploit a major payment reform for home health care to examine whether reductions in reimbursement lead to differential changes in treatment intensity and provider costs depending on the level of competition in a market. Using Medicare claims, we find that while providers in more competitive markets had higher average costs in the pre-reform period, these markets experienced larger proportional reductions in treatment intensity and costs after the reform relative to less competitive markets. This led to a convergence in spending across geographic areas. We find that much of the reduction in provider costs is driven by greater exit of “high-cost” providers in more competitive markets. PMID:28073062

Socializing with MYC: cell competition in development and as a model for premalignant cancer.

PubMed

Johnston, Laura A

2014-04-01

Studies in Drosophila and mammals have made it clear that genetic mutations that arise in somatic tissues are rapidly recognized and eliminated, suggesting that cellular fitness is tightly monitored. During development, damaged, mutant, or otherwise unfit cells are prevented from contributing to the tissue and are instructed to die, whereas healthy cells benefit and populate the animal. This cell selection process, known as cell competition, eliminates somatic genetic heterogeneity and promotes tissue fitness during development. Yet cell competition also has a dark side. Super competition can be exploited by incipient cancers to subvert cellular cooperation and promote selfish behavior. Evidence is accumulating that MYC plays a key role in regulation of social behavior within tissues. Given the high number of tumors with deregulated MYC, studies of cell competition promise to yield insight into how the local environment yields to and participates in the early stages of tumor formation.

Materazzi effect and the strategic use of anger in competitive interactions.

PubMed

Gneezy, Uri; Imas, Alex

2014-01-28

We propose that individuals use anger strategically in interactions. We first show that in some environments angering people makes them more effective in competitions, whereas in others, anger makes them less effective. We then show that individuals anticipate these effects and strategically use the option to anger their opponents. In particular, they are more likely to anger their opponents when anger negatively affects the opponents' performances. This finding suggests people understand the effects of emotions on behavior and exploit them to their advantage.

Concurrency in product realization

NASA Astrophysics Data System (ADS)

Kelly, Michael J.

1994-03-01

Technology per se does not provide a competitive advantage. Timely exploitation of technology is what gives the competitive edge, and this demands a major shift in the product development process and management of the industrial enterprise. `Teaming to win' is more than a management theme; it is the disciplined engineering practice that is essential to success in today's global marketplace. Teaming supports the concurrent engineering practices required to integrate the activities of people responsible for product realization through achievement of shorter development cycles, lower costs, and defect-free products.

Proto-oncogene FBI-1 (Pokemon/ZBTB7A) Represses Transcription of the Tumor Suppressor Rb Gene via Binding Competition with Sp1 and Recruitment of Co-repressors*S⃞

PubMed Central

Jeon, Bu-Nam; Yoo, Jung-Yoon; Choi, Won-Il; Lee, Choong-Eun; Yoon, Ho-Geun; Hur, Man-Wook

2008-01-01

FBI-1 (also called Pokemon/ZBTB7A) is a BTB/POZ-domain Krüppel-like zinc-finger transcription factor. Recently, FBI-1 was characterized as a proto-oncogenic protein, which represses tumor suppressor ARF gene transcription. The expression of FBI-1 is increased in many cancer tissues. We found that FBI-1 potently represses transcription of the Rb gene, a tumor suppressor gene important in cell cycle arrest. FBI-1 binds to four GC-rich promoter elements (FREs) located at bp –308 to –188 of the Rb promoter region. The Rb promoter also contains two Sp1 binding sites: GC-box 1 (bp –65 to –56) and GC-box 2 (bp –18 to –9), the latter of which is also bound by FBI-1. We found that FRE3 (bp –244 to –236) is also a Sp1 binding element. FBI-1 represses transcription of the Rb gene not only by binding to the FREs, but also by competing with Sp1 at the GC-box 2 and the FRE3. By binding to the FREs and/or the GC-box, FBI-1 represses transcription of the Rb gene through its POZ-domain, which recruits a co-repressor-histone deacetylase complex and deacetylates histones H3 and H4 at the Rb gene promoter. FBI-1 inhibits C2C12 myoblast cell differentiation by repressing Rb gene expression. PMID:18801742

Murine T-box transcription factor Tbx20 acts as a repressor during heart development, and is essential for adult heart integrity, function and adaptation.

PubMed

Stennard, Fiona A; Costa, Mauro W; Lai, Donna; Biben, Christine; Furtado, Milena B; Solloway, Mark J; McCulley, David J; Leimena, Christiana; Preis, Jost I; Dunwoodie, Sally L; Elliott, David E; Prall, Owen W J; Black, Brian L; Fatkin, Diane; Harvey, Richard P

2005-05-01

The genetic hierarchies guiding lineage specification and morphogenesis of the mammalian embryonic heart are poorly understood. We now show by gene targeting that murine T-box transcription factor Tbx20 plays a central role in these pathways, and has important activities in both cardiac development and adult function. Loss of Tbx20 results in death of embryos at mid-gestation with grossly abnormal heart morphogenesis. Underlying these disturbances was a severely compromised cardiac transcriptional program, defects in the molecular pre-pattern, reduced expansion of cardiac progenitors and a block to chamber differentiation. Notably, Tbx20-null embryos showed ectopic activation of Tbx2 across the whole heart myogenic field. Tbx2 encodes a transcriptional repressor normally expressed in non-chamber myocardium, and in the atrioventricular canal it has been proposed to inhibit chamber-specific gene expression through competition with positive factor Tbx5. Our data demonstrate a repressive activity for Tbx20 and place it upstream of Tbx2 in the cardiac genetic program. Thus, hierarchical, repressive interactions between Tbx20 and other T-box genes and factors underlie the primary lineage split into chamber and non-chamber myocardium in the forming heart, an early event upon which all subsequent morphogenesis depends. Additional roles for Tbx20 in adult heart integrity and contractile function were revealed by in-vivo cardiac functional analysis of Tbx20 heterozygous mutant mice. These data suggest that mutations in human cardiac transcription factor genes, possibly including TBX20, underlie both congenital heart disease and adult cardiomyopathies.

From glue to gasoline: how competition turns perspective takers unethical.

PubMed

Pierce, Jason R; Kilduff, Gavin J; Galinsky, Adam D; Sivanathan, Niro

2013-10-01

Perspective taking is often the glue that binds people together. However, we propose that in competitive contexts, perspective taking is akin to adding gasoline to a fire: It inflames already-aroused competitive impulses and leads people to protect themselves from the potentially insidious actions of their competitors. Overall, we suggest that perspective taking functions as a relational amplifier. In cooperative contexts, it creates the foundation for prosocial impulses, but in competitive contexts, it triggers hypercompetition, leading people to prophylactically engage in unethical behavior to prevent themselves from being exploited. The experiments reported here establish that perspective taking interacts with the relational context--cooperative or competitive--to predict unethical behavior, from using insidious negotiation tactics to materially deceiving one's partner to cheating on an anagram task. In the context of competition, perspective taking can pervert the age-old axiom "do unto others as you would have them do unto you" into "do unto others as you think they will try to do unto you."

RNA interference technology in crop protection against arthropod pests, pathogens and nematodes.

PubMed

Zotti, Moises; Dos Santos, Ericmar Avila; Cagliari, Deise; Christiaens, Olivier; Taning, Clauvis Nji Tizi; Smagghe, Guy

2018-06-01

Scientists have made significant progress in understanding and unraveling several aspects of double-stranded RNA (dsRNA)-mediated gene silencing during the last two decades. Now that the RNA interference (RNAi) mechanism is well understood, it is time to consider how to apply the acquired knowledge to agriculture and crop protection. Some RNAi-based products are already available for farmers and more are expected to reach the market soon. Tailor-made dsRNA as an active ingredient for biopesticide formulations is considered a raw material that can be used for diverse purposes, from pest control and bee protection against viruses to pesticide resistance management. The RNAi mechanism works at the messenger RNA (mRNA) level, exploiting a sequence-dependent mode of action, which makes it unique in potency and selectivity compared with conventional agrochemicals. Furthermore, the use of RNAi in crop protection can be achieved by employing plant-incorporated protectants through plant transformation, but also by non-transformative strategies such as the use of formulations of sprayable RNAs as direct control agents, resistance factor repressors or developmental disruptors. In this review, RNAi is presented in an agricultural context (discussing products that have been launched on the market or will soon be available), and we go beyond the classical presentation of successful examples of RNAi in pest-insect control and comprehensively explore its potential for the control of plant pathogens, nematodes and mites, and to fight against diseases and parasites in beneficial insects. Moreover, we also discuss its use as a repressor for the management of pesticide-resistant weeds and insects. Finally, this review reports on the advances in non-transformative dsRNA delivery and the production costs of dsRNA, and discusses environmental considerations. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Mobility of the native Bacillus subtilis conjugative plasmid pLS20 is regulated by intercellular signaling.

PubMed

Singh, Praveen K; Ramachandran, Gayetri; Ramos-Ruiz, Ricardo; Peiró-Pastor, Ramón; Abia, David; Wu, Ling J; Meijer, Wilfried J J

2013-10-01

Horizontal gene transfer mediated by plasmid conjugation plays a significant role in the evolution of bacterial species, as well as in the dissemination of antibiotic resistance and pathogenicity determinants. Characterization of their regulation is important for gaining insights into these features. Relatively little is known about how conjugation of Gram-positive plasmids is regulated. We have characterized conjugation of the native Bacillus subtilis plasmid pLS20. Contrary to the enterococcal plasmids, conjugation of pLS20 is not activated by recipient-produced pheromones but by pLS20-encoded proteins that regulate expression of the conjugation genes. We show that conjugation is kept in the default "OFF" state and identified the master repressor responsible for this. Activation of the conjugation genes requires relief of repression, which is mediated by an anti-repressor that belongs to the Rap family of proteins. Using both RNA sequencing methodology and genetic approaches, we have determined the regulatory effects of the repressor and anti-repressor on expression of the pLS20 genes. We also show that the activity of the anti-repressor is in turn regulated by an intercellular signaling peptide. Ultimately, this peptide dictates the timing of conjugation. The implications of this regulatory mechanism and comparison with other mobile systems are discussed.

Mechanism of Metal Ion Activation of the Diphtheria Toxin Repressor DtxR

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

D'Aquino,J.; Tetenbaum-Novatt, J.; White, A.

2005-01-01

The diphtheria toxin repressor (DtxR) is a metal ion-activated transcriptional regulator that has been linked to the virulence of Corynebacterium diphtheriae. Structure determination has shown that there are two metal ion binding sites per repressor monomer, and site-directed mutagenesis has demonstrated that binding site 2 (primary) is essential for recognition of the target DNA repressor, leaving the role of binding site 1 (ancillary) unclear. Calorimetric techniques have demonstrated that although binding site 1 (ancillary) has high affinity for metal ion with a binding constant of 2 x 10{sup -7}, binding site 2 (primary) is a low-affinity binding site with amore » binding constant of 6.3 x 10{sup -4}. These two binding sites act in an independent fashion, and their contribution can be easily dissected by traditional mutational analysis. Our results clearly demonstrate that binding site 1 (ancillary) is the first one to be occupied during metal ion activation, playing a critical role in stabilization of the repressor. In addition, structural data obtained for the mutants Ni-DtxR(H79A, C102D), reported here, and the previously reported DtxR(H79A) have allowed us to propose a mechanism of metal activation for DtxR.« less

Structure of the Mecl Repressor from Staphylococcus aureus in Complex with the Cognate DNA Operator of mec

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

Safo,M.; Ko, T.; Musayev, F.

The dimeric repressor MecI regulates the mecA gene that encodes the penicillin-binding protein PBP-2a in methicillin-resistant Staphylococcus aureus (MRSA). MecI is similar to BlaI, the repressor for the blaZ gene of {beta}-lactamase. MecI and BlaI can bind to both operator DNA sequences. The crystal structure of MecI in complex with the 32 base-pair cognate DNA of mec was determined to 3.8 Angstroms resolution. MecI is a homodimer and each monomer consists of a compact N-terminal winged-helix domain, which binds to DNA, and a loosely packed C-terminal helical domain, which intertwines with its counter-monomer. The crystal contains horizontal layers of virtualmore » DNA double helices extending in three directions, which are separated by perpendicular DNA segments. Each DNA segment is bound to two MecI dimers. Similar to the BlaI-mec complex, but unlike the MecI-bla complex, the MecI repressors bind to both sides of the mec DNA dyad that contains four conserved sequences of TACA/TGTA. The results confirm the up-and-down binding to the mec operator, which may account for cooperative effect of the repressor.« less

Oligomeric properties and DNA binding specificities of repressor isoforms from the Streptomyces bacteriophage phiC31.

PubMed

Wilson, S E; Smith, M C

1998-05-15

Three protein isoforms (74, 54 and 42 kDa) are expressed from repressor gene c in the Streptomyces temperate bacteriophage phiC31. Because expression of the two smaller isoforms, 54 and 42 kDa, is sufficient for superinfection immunity, the interaction between these isoforms was studied. The native 42 kDa repressor (Nat42) and an N-terminally 6x histidine-tagged 54 kDa isoform (His54) were shown by co-purification on a Ni-NTA column to interact in Streptomyces lividans . In vitro three repressor preparations, containing Nat42, His54 and the native 54 and 42 kDa isoforms expressed together (Nat54&42), were subjected to chemical crosslinking and gel filtration analysis. Homo- and hetero-tetramers were observed. Previous work showed that the smallest isoform bound to 17 bp operators containing aconservedinvertedrepeat (CIR) and that the CIRs were located at 16 loci throughout the phiC31 genome. One of the CIRs (CIR6) is believed to be critical for regulating the lytic pathway. The DNA binding activities of the three repressor preparations were studied using fragments containing CIRs (CIR3-CIR6) from the essential early region as templates for DNase I footprinting. Whereas Nat42 bound to CIR6, poorly to CIR5 but undetectably to CIR3 or CIR4, the Nat54&42 preparation could bind to all CIRs tested, albeit poorly to CIR3 and CIR4. The His54 isoform bound all CIRs tested. Isoforms expressed from the phiC31 repressor gene, like those which are expressed from many eukaryotic transcription factor genes, apparently have different binding specificities.

Transcriptional co-repressor SIN3A silencing rescues decline in memory consolidation during scopolamine-induced amnesia.

PubMed

Srivas, Sweta; Thakur, Mahendra K

2018-05-01

Epigenetic modifications through methylation of DNA and acetylation of histones modulate neuronal gene expression and regulate long-term memory. Earlier we demonstrated that scopolamine-induced decrease in memory consolidation is correlated with enhanced expression of hippocampal DNA methyltransferase 1 (DNMT1) and histone deacetylase 2 (HDAC2) in mice. DNMT1 and HDAC2 act together by recruiting a co-repressor complex and deacetylating the chromatin. The catalytic activity of HDACs is mainly dependent on its incorporation into multiprotein co-repressor complexes, among which SIN3A-HDAC2 co-repressor is widely studied to regulate synaptic plasticity. However, the involvement of co-repressor complex in regulating memory loss or amnesia is unexplored. This study examines the role of co-repressor SIN3A in scopolamine-induced amnesia through epigenetic changes in the hippocampus. Scopolamine treatment remarkably enhanced hippocampal SIN3A expression in mice. To prevent such increase in SIN3A expression, we used hippocampal infusion of SIN3A-siRNA and assessed the effect of SIN3A silencing on scopolamine-induced amnesia. Silencing of SIN3A in amnesic mice reduced the binding of HDAC2 at neuronal immediate early genes (IEGs) promoter, but did not change the expression of HDAC2. Furthermore, it increased acetylation of H3K9 and H3K14 at neuronal IEGs (Arc, Egr1, Homer1 and Narp) promoter, prevented scopolamine-induced down-regulation of IEGs and improved consolidation of memory during novel object recognition task. These findings together suggest that SIN3A has a critical role in regulation of synaptic plasticity and might act as a potential therapeutic target to rescue memory decline during amnesia and other neuropsychiatric pathologies. © 2018 International Society for Neurochemistry.

Sustaining the Civil Reserve Air Fleet (CRAF) Program

DTIC Science & Technology

2003-05-01

means to build international networks and global marketing alliances. These arrangements have permitted alliances to exploit the regional competitive...next major phase occurred in the 1990s—the linking of networks in different countries through code sharing alliances and global marketing alliances

A conserved Mediator–CDK8 kinase module association regulates Mediator–RNA polymerase II interaction

PubMed Central

Tsai, Kuang-Lei; Sato, Shigeo; Tomomori-Sato, Chieri; Conaway, Ronald C.; Conaway, Joan W.; Asturias, Francisco J.

2013-01-01

The CDK8 kinase module (CKM) is a conserved, dissociable Mediator subcomplex whose component subunits were genetically linked to the RNA polymerase II (RNAPII) carboxy-terminal domain (CTD) and individually recognized as transcriptional repressors before Mediator was identified as a preeminent complex in eukaryotic transcription regulation. We used macromolecular electron microscopy and biochemistry to investigate the subunit organization, structure, and Mediator interaction of the Saccharomyces cerevisiae CKM. We found that interaction of the CKM with Mediator’s Middle module interferes with CTD-dependent RNAPII binding to a previously unknown Middle module CTD-binding site targeted early on in a multi-step holoenzyme formation process. Taken together, our results reveal the basis for CKM repression, clarify the origin of the connection between CKM subunits and the CTD, and suggest that a combination of competitive interactions and conformational changes that facilitate holoenzyme formation underlie the Mediator mechanism. PMID:23563140

Situational Discrimination in Repressor-type and Sensitizer-type Approval Seekers and the Birth Order by Subject Sex Interaction

ERIC Educational Resources Information Center

Becker, Gilbert

1970-01-01

Five experiments are reported. One conclusion in that repressor-type high need-for-approval subjects made the discrimination and permitted less favorable self-description, but sensitizer-type high need-for-approval subjects did not. (DB)

Canadian biotechnology start-ups, 1991-1997: the role of incumbents' patents and strategic alliances in controlling competition.

PubMed

Calabrese, T; Baum, J A; Silverman, B S

2000-12-01

Fligstein (1996) contends that organizations act to exploit the institutional context in which they are embedded so as to stabilize the competition they face. Drawing on Fligstein's theoretical analysis, we conceptualize incumbent biotechnology firms' patent-ing and alliance-building activities as attempts to stabilize and control potential competition and analyze how these activities shape rates of founding in the Canadian biotechnology industry. We find that increases in the level and concentration of incumbents' patenting discourage founding, particularly in human application sectors of the industry where development and approval processes are more costly and time consuming. Incumbents' horizontal alliances depress start-ups; vertical alliances stimulate start-ups. Our findings highlight how technology appropriation and strategic alliances structure the competitive dynamics and evolution of high-technology, knowledge-intensive industries.

Expression, purification and preliminary X-ray analysis of the C-terminal domain of an arginine repressor protein from Mycobacterium tuberculosis

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

Lu, George J.; Garen, Craig R.; Cherney, Maia M.

2007-11-01

The C-terminal portion of the arginine repressor protein from M. tuberculosis H37Rv has been crystallized. The complete transcriptional factor regulates arginine biosynthesis by binding operator DNA when arginine is bound at the C-terminal domain. The gene product of an open reading frame Rv1657 from Mycobacterium tuberculosis is a putative arginine repressor protein (ArgR), a transcriptional factor that regulates the expression of arginine-biosynthetic enzymes. Rv1657 was expressed and purified and a C-terminal domain was crystallized using the hanging-drop vapour-diffusion method. Diffraction data were collected and processed to a resolution of 2.15 Å. The crystals belong to space group P1 and themore » Matthews coefficient suggests that the crystals contain six C-terminal domain molecules per unit cell. Previous structural and biochemical studies on the arginine repressor proteins from other organisms have likewise shown the presence of six molecules per unit cell.« less

Genomic Mining of Prokaryotic Repressors for Orthogonal Logic Gates

PubMed Central

Stanton, Brynne C.; Nielsen, Alec A.K.; Tamsir, Alvin; Clancy, Kevin; Peterson, Todd; Voigt, Christopher A.

2014-01-01

Genetic circuits perform computational operations based on interactions between freely diffusing molecules within a cell. When transcription factors are combined to build a circuit, unintended interactions can disrupt its function. Here, we apply “part mining” to build a library of 73 TetR-family repressors gleaned from prokaryotic genomes. The operators of a subset were determined using an in vitro method and this information was used to build synthetic promoters. The promoters and repressors were screened for cross-reactions. Of these, 16 were identified that both strongly repress their cognate promoter (5- to 207-fold) and do not interact with other promoters. Each repressor:promoter pair was converted to a NOT gate and characterized. Used as a set of 16 NOR gates, there are >1054 circuits that could be built by changing the pattern of input and output promoters. This represents a large set of compatible gates that can be used to construct user-defined circuits. PMID:24316737

KPNB1 mediates PER/CRY nuclear translocation and circadian clock function.

PubMed

Lee, Yool; Jang, A Reum; Francey, Lauren J; Sehgal, Amita; Hogenesch, John B

2015-08-29

Regulated nuclear translocation of the PER/CRY repressor complex is critical for negative feedback regulation of the circadian clock of mammals. However, the precise molecular mechanism is not fully understood. Here, we report that KPNB1, an importin β component of the ncRNA repressor of nuclear factor of activated T cells (NRON) ribonucleoprotein complex, mediates nuclear translocation and repressor function of the PER/CRY complex. RNAi depletion of KPNB1 traps the PER/CRY complex in the cytoplasm by blocking nuclear entry of PER proteins in human cells. KPNB1 interacts mainly with PER proteins and directs PER/CRY nuclear transport in a circadian fashion. Interestingly, KPNB1 regulates the PER/CRY nuclear entry and repressor function, independently of importin α, its classical partner. Moreover, inducible inhibition of the conserved Drosophila importin β in lateral neurons abolishes behavioral rhythms in flies. Collectively, these data show that KPNB1 is required for timely nuclear import of PER/CRY in the negative feedback regulation of the circadian clock.

Control of developmentally primed erythroid genes by combinatorial co-repressor actions

PubMed Central

Stadhouders, Ralph; Cico, Alba; Stephen, Tharshana; Thongjuea, Supat; Kolovos, Petros; Baymaz, H. Irem; Yu, Xiao; Demmers, Jeroen; Bezstarosti, Karel; Maas, Alex; Barroca, Vilma; Kockx, Christel; Ozgur, Zeliha; van Ijcken, Wilfred; Arcangeli, Marie-Laure; Andrieu-Soler, Charlotte; Lenhard, Boris; Grosveld, Frank; Soler, Eric

2015-01-01

How transcription factors (TFs) cooperate within large protein complexes to allow rapid modulation of gene expression during development is still largely unknown. Here we show that the key haematopoietic LIM-domain-binding protein-1 (LDB1) TF complex contains several activator and repressor components that together maintain an erythroid-specific gene expression programme primed for rapid activation until differentiation is induced. A combination of proteomics, functional genomics and in vivo studies presented here identifies known and novel co-repressors, most notably the ETO2 and IRF2BP2 proteins, involved in maintaining this primed state. The ETO2–IRF2BP2 axis, interacting with the NCOR1/SMRT co-repressor complex, suppresses the expression of the vast majority of archetypical erythroid genes and pathways until its decommissioning at the onset of terminal erythroid differentiation. Our experiments demonstrate that multimeric regulatory complexes feature a dynamic interplay between activating and repressing components that determines lineage-specific gene expression and cellular differentiation. PMID:26593974

The Energy and Security Nexus: A Strategic Dilemma

DTIC Science & Technology

2011-07-15

substantial natural gas reserves which can be exploited if we solve problems associated with hydraulic fracturing and competition over water. Other parts of...between energy, water, and security. Sometimes water is diverted to produce energy as in the case of hydropower, hydraulic fracturing , irrigation of

Exploiting Instability: A Model for Managing Organizational Change.

ERIC Educational Resources Information Center

Frank, Debra; Rocks, William

In response to decreased levels of funding and declining enrollments, increased competition, and major technological advances, Allegany Community College, in Maryland, has developed a model for managing organizational change. The model incorporates the following four components for effective transition and change: conceptualization; communication;…

Purification and DNA binding properties of the blaI gene product, repressor for the beta-lactamase gene, blaP, of Bacillus licheniformis.

PubMed Central

Grossman, M J; Lampen, J O

1987-01-01

The location of the repressor gene, blaI, for the beta-lactamase gene blaP of Bacillus licheniformis 749, on the 5' side of blaP, was confirmed by sequencing the bla region of the constitutive mutant 749/C. An amber stop codon, likely to result in a nonfunctional truncated repressor, was found at codon 32 of the 128 codon blaI open reading frame (ORF) located 5' to blaP. In order to study the DNA binding activity of the repressor, the structural gene for blaI, from strain 749, with its ribosome binding site was expressed using a two plasmid T7 RNA polymerase/promotor system (S. Tabor and C. C. Richardson. Proc. Natl. Acad. Sci. 82, 1074-1078 (1985). Heat induction of this system in Escherichia coli K38 resulted in the production of BlaI as 5-10% of the soluble cell protein. Repressor protein was then purified by ammonium sulfate fractionation and cation exchange chromatography. The sequence of the N-terminal 28 amino acid residues was determined and was as predicted from the DNA. Binding of BlaI to DNA was detected by the slower migration of protein DNA complexes during polyacrylamide gel electrophoresis. BlaI was shown to selectively bind DNA fragments carrying the promoter regions of blaI and blaP. Images PMID:3498148

SPOROCYTELESS is a novel embryophyte-specific transcription repressor that interacts with TPL and TCP proteins in Arabidopsis.

PubMed

Chen, Guang-Hui; Sun, Jia-Ying; Liu, Man; Liu, Jie; Yang, Wei-Cai

2014-12-20

Germlines in plants are formed de novo during post-embryonic development, while little is known about the mechanism that controls this process. In Arabidopsis, the earliest gene controlling this process is SPOROCYTELESS (SPL). A decade ago, we showed that loss of SPL function abolished sporogenesis in both male and female organs of Arabidopsis. However, its function is unclear up to now. In this study, we showed that SPL belongs to a novel transcription repressor family specific in embryophyte, which consists of 173 members in the land plants so far. All of them contain a conserved SPL-motif in their N-terminal and an ethylene-responsive element binding factor-associated amphiphilic repression (EAR) motif in the C-terminal, therefore designated as SPL-like, EAR-containing proteins (SPEARs). Consistently, SPL acts as a transcriptional repressor in yeast and tobacco cells, and SPEAR proteins are able to form homodimer and/or heterodimer with each other in vitro. Furthermore, SPEARs interact with the TOPLESS (TPL) co-repressors via the EAR motif and TCP family transcription factors in yeast cells. Together, we propose that SPL and SPEARs most likely belong to a novel transcription repressor family in land plants which may play a variety of developmental roles in plants. Copyright © 2014 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

The biotin repressor: modulation of allostery by corepressor analogs.

PubMed

Brown, Patrick H; Cronan, John E; Grøtli, Morten; Beckett, Dorothy

2004-04-02

The Escherichia coli biotin repressor functions in biotin retention and regulation of biotin biosynthesis. Biotin retention is accomplished via the two-step biotinylation of the biotin-dependent enzyme, acetyl-CoA carboxylase. In the first step of this reaction the substrates biotin and ATP are utilized in synthesis of the activated biotin, biotinyl-5'-AMP, while in the second step this activated biotin is transferred to a unique lysine residue of the biotin carboxyl carrier protein subunit of the carboxylase. Regulation of biotin biosynthesis is accomplished through binding of the repressor to the transcription control region of the biotin biosynthetic operon. The adenylated or activated biotin functions as the corepressor in this DNA binding process. The activated biotin is a mixed anhydride and thus labile. In efforts to develop tools for structural and thermodynamic studies of the biotin regulatory interactions, two analogs of the adenylate, a sulfamoyl derivative and an ester derivative, have been synthesized and functionally characterized. Results of fluorescence measurements indicate that both analogs bind with high affinity to the repressor and that both are inactive in biotin transfer to the acceptor protein. Functional studies of their corepressor properties indicate that while the sulfamoyl is a weak allosteric activator, the ester closely mimics the physiological corepressor in activation of assembly of the transcription repression complex. Results of these studies also provide further insight into the allosteric mechanism of the biotin repressor.

Materazzi effect and the strategic use of anger in competitive interactions

PubMed Central

Gneezy, Uri; Imas, Alex

2014-01-01

We propose that individuals use anger strategically in interactions. We first show that in some environments angering people makes them more effective in competitions, whereas in others, anger makes them less effective. We then show that individuals anticipate these effects and strategically use the option to anger their opponents. In particular, they are more likely to anger their opponents when anger negatively affects the opponents’ performances. This finding suggests people understand the effects of emotions on behavior and exploit them to their advantage. PMID:24474756

The Repression-Sensitization Dimension in Relation to Impending Painful Stimulation

ERIC Educational Resources Information Center

Scarpetti, William L.

1973-01-01

The study attempted to replicate previous findings of differences between self-report and physiological indices of disturbance in repressors and sensitizers placed in threatening situations. Results indicate that repressors admit to less anxiety on the self-report measure while producing more physiological reactivity to threat of shock. No such…

Mutation of praR in Rhizobium leguminosarum enhances root biofilms, improving nodulation competitiveness by increased expression of attachment proteins.

PubMed

Frederix, Marijke; Edwards, Anne; Swiderska, Anna; Stanger, Andrew; Karunakaran, Ramakrishnan; Williams, Alan; Abbruscato, Pamela; Sanchez-Contreras, Maria; Poole, Philip S; Downie, J Allan

2014-08-01

In Rhizobium leguminosarum bv. viciae, quorum-sensing is regulated by CinR, which induces the cinIS operon. CinI synthesizes an AHL, whereas CinS inactivates PraR, a repressor. Mutation of praR enhanced biofilms in vitro. We developed a light (lux)-dependent assay of rhizobial attachment to roots and demonstrated that mutation of praR increased biofilms on pea roots. The praR mutant out-competed wild-type for infection of pea nodules in mixed inoculations. Analysis of gene expression by microarrays and promoter fusions revealed that PraR represses its own transcription and mutation of praR increased expression of several genes including those encoding secreted proteins (the adhesins RapA2, RapB and RapC, two cadherins and the glycanase PlyB), the polysaccharide regulator RosR, and another protein similar to PraR. PraR bound to the promoters of several of these genes indicating direct repression. Mutations in rapA2, rapB, rapC, plyB, the cadherins or rosR did not affect the enhanced root attachment or nodule competitiveness of the praR mutant. However combinations of mutations in rapA, rapB and rapC abolished the enhanced attachment and nodule competitiveness. We conclude that relief of PraR-mediated repression determines a lifestyle switch allowing the expression of genes that are important for biofilm formation on roots and the subsequent initiation of infection of legume roots. © 2014 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.

Contrasting impacts of competition on ecological and social trait evolution in songbirds

PubMed Central

Tobias, Joseph A.; Burns, Kevin J.; Mason, Nicholas A.; Shultz, Allison J.; Morlon, Hélène

2018-01-01

Competition between closely related species has long been viewed as a powerful selective force that drives trait diversification, thereby generating phenotypic diversity over macroevolutionary timescales. However, although the impact of interspecific competition has been documented in a handful of iconic insular radiations, most previous studies have focused on traits involved in resource use, and few have examined the role of competition across large, continental radiations. Thus, the extent to which broad-scale patterns of phenotypic diversity are shaped by competition remain largely unclear, particularly for social traits. Here, we estimate the effect of competition between interacting lineages by applying new phylogenetic models that account for such interactions to an exceptionally complete dataset of resource-use traits and social signaling traits for the entire radiation of tanagers (Aves, Thraupidae), the largest family of songbirds. We find that interspecific competition strongly influences the evolution of traits involved in resource use, with a weaker effect on plumage signals, and very little effect on song. Our results provide compelling evidence that interspecific exploitative competition contributes to ecological trait diversification among coexisting species, even in a large continental radiation. In comparison, signal traits mediating mate choice and social competition seem to diversify under different evolutionary models, including rapid diversification in the allopatric stage of speciation. PMID:29385141

Contrasting impacts of competition on ecological and social trait evolution in songbirds.

PubMed

Drury, Jonathan P; Tobias, Joseph A; Burns, Kevin J; Mason, Nicholas A; Shultz, Allison J; Morlon, Hélène

2018-01-01

Competition between closely related species has long been viewed as a powerful selective force that drives trait diversification, thereby generating phenotypic diversity over macroevolutionary timescales. However, although the impact of interspecific competition has been documented in a handful of iconic insular radiations, most previous studies have focused on traits involved in resource use, and few have examined the role of competition across large, continental radiations. Thus, the extent to which broad-scale patterns of phenotypic diversity are shaped by competition remain largely unclear, particularly for social traits. Here, we estimate the effect of competition between interacting lineages by applying new phylogenetic models that account for such interactions to an exceptionally complete dataset of resource-use traits and social signaling traits for the entire radiation of tanagers (Aves, Thraupidae), the largest family of songbirds. We find that interspecific competition strongly influences the evolution of traits involved in resource use, with a weaker effect on plumage signals, and very little effect on song. Our results provide compelling evidence that interspecific exploitative competition contributes to ecological trait diversification among coexisting species, even in a large continental radiation. In comparison, signal traits mediating mate choice and social competition seem to diversify under different evolutionary models, including rapid diversification in the allopatric stage of speciation.

PehN, a Polygalacturonase Homologue with a Low Hydrolase Activity, Is Coregulated with the Other Erwinia chrysanthemi Polygalacturonases

PubMed Central

Hugouvieux-Cotte-Pattat, Nicole; Shevchik, Vladimir E.; Nasser, William

2002-01-01

Erwinia chrysanthemi 3937 secretes an arsenal of pectinolytic enzymes, including at least eight endo-pectate lyases encoded by pel genes, which play a major role in the soft-rot disease caused by this bacterium on various plants. E. chrysanthemi also produces some hydrolases that cleave pectin. Three adjacent hydrolase genes, pehV, pehW, and pehX, encoding exo-poly-α-d-galacturonosidases, have been characterized. These enzymes liberate digalacturonides from the nonreducing end of pectin. We report the identification of a novel gene, named pehN, encoding a protein homologous to the glycosyl hydrolases of family 28, which includes mainly polygalacturonases. PehN has a low hydrolase activity on polygalacturonate and on various pectins. PehN action favors the activity of the secreted endo-pectate lyases, mainly PelB and PelC, and that of the periplasmic exo-pectate lyase PelX. However, removal of the pehN gene does not significantly alter the virulence of E. chrysanthemi. Regulation of pehN transcription was analyzed by using gene fusions. Like other pectinase genes, pehN transcription is dependent on several environmental conditions. It is induced by pectic catabolic products and is affected by growth phase, catabolite repression, osmolarity, anaerobiosis, nitrogen starvation, and the presence of calcium ions. The transcription of pehN is modulated by the repressor KdgR, which controls almost all the steps of pectin catabolism, and by cyclic AMP receptor protein (CRP), the global activator of sugar catabolism. The regulator PecS, which represses the transcription of the pel genes but activates that of pehV, pehW, and pehX, also activates transcription of pehN. The three regulators KdgR, PecS, and CRP act by direct interaction with the pehN promoter region. The sequences involved in the binding of these three regulators and of RNA polymerase have been precisely defined. Analysis of the simultaneous binding of these proteins indicates that CRP and RNA polymerase bind cooperatively and that the binding of KdgR could prevent pehN transcription. In contrast, the activator effect of PecS is not linked to competition with KdgR or to cooperation with CRP or RNA polymerase. This effect probably results from competition between PecS and an unidentified repressor involved in peh regulation. PMID:11976295

Petroleum and Political Change in Mexico,

DTIC Science & Technology

1980-01-01

and exploitation of our petroleum resources." The argument continued that "private entrepreneurs are disposed to work in this area under the control of...membership was designed to jar the non-petroleum export sector into a more competitive posture, thereby incresing exports from that sector and diminishing

Verification of Argentine ant defensive compounds and their behavioral effects on heterospecific competitors and conspecific nestmates

USDA-ARS?s Scientific Manuscript database

The invasive Argentine ant (Linepithema humile) has become established worldwide in regions with Mediterranean or subtropical climates. The species typically disrupts the balance of natural ecosystems by competitively displacing some native ant species via strong exploitation and interference compet...

Characterisation of a DNA sequence element that directs Dictyostelium stalk cell-specific gene expression.

PubMed

Ceccarelli, A; Zhukovskaya, N; Kawata, T; Bozzaro, S; Williams, J

2000-12-01

The ecmB gene of Dictyostelium is expressed at culmination both in the prestalk cells that enter the stalk tube and in ancillary stalk cell structures such as the basal disc. Stalk tube-specific expression is regulated by sequence elements within the cap-site proximal part of the promoter, the stalk tube (ST) promoter region. Dd-STATa, a member of the STAT transcription factor family, binds to elements present in the ST promoter-region and represses transcription prior to entry into the stalk tube. We have characterised an activatory DNA sequence element, that lies distal to the repressor elements and that is both necessary and sufficient for expression within the stalk tube. We have mapped this activator to a 28 nucleotide region (the 28-mer) within which we have identified a GA-containing sequence element that is required for efficient gene transcription. The Dd-STATa protein binds to the 28-mer in an in vitro binding assay, and binding is dependent upon the GA-containing sequence. However, the ecmB gene is expressed in a Dd-STATa null mutant, therefore Dd-STATa cannot be responsible for activating the 28-mer in vivo. Instead, we identified a distinct 28-mer binding activity in nuclear extracts from the Dd-STATa null mutant, the activity of this GA binding activity being largely masked in wild type extracts by the high affinity binding of the Dd-STATa protein. We suggest, that in addition to the long range repression exerted by binding to the two known repressor sites, Dd-STATa inhibits transcription by direct competition with this putative activator for binding to the GA sequence.

Sex differences in acute translational repressor 4E-BP1 activity and sprint performance in response to repeated-sprint exercise in team sport athletes.

PubMed

Dent, Jessica R; Edge, Johann A; Hawke, Emma; McMahon, Christopher; Mündel, Toby

2015-11-01

The physiological requirements underlying soccer-specific exercise are incomplete and sex-based comparisons are sparse. The aim of this study was to determine the effects of a repeated-sprint protocol on the translational repressor 4E-BP1 and sprint performance in male and female soccer players. Cross-over design involving eight female and seven male university soccer players. Participants performed four bouts of 6 × 30-m maximal sprints spread equally over 40 min. Heart rate, sprint time and sprint decrement were measured for each sprint and during the course of each bout. Venous blood samples and muscle biopsies from the vastus lateralis were taken at rest, at 15 min and 2h post-exercise. While males maintained a faster mean sprint time for each bout (P < 0.05) females exhibited a greater decrement in sprint performance for each bout (P < 0.05), indicating a superior maintenance of sprint performance in males, with no sex differences for heart rate or lactate. Muscle analyses revealed sex differences in resting total (P < 0.05) and phosphorylated (P < 0.05) 4E-BP1 Thr37/46, and 15 min post-exercise the 4E-BP1 Thr37/46 ratio decreased below resting levels in males only (P < 0.05), indicative of a decreased translation initiation following repeated sprints. We show that females have a larger sprint decrement indicating that males have a superior ability to recover sprint performance. Sex differences in resting 4E-BP1 Thr37/46 suggest diversity in the training-induced phenotype of the muscle of males and females competing in equivalent levels of team-sport competition. Copyright © 2014 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

What explains the quality and price of GP services? An investigation using linked survey and administrative data.

PubMed

Johar, Meliyanni; Jones, Glenn; Savage, Elizabeth

2014-09-01

We examine patient socioeconomic status, the strength of the patient-doctor relationship and local area competition as determinants of the quality and price of GP services. We exploit a large-sample patient data set in Australia and its linkage to administrative databases. The sample contains over 260,000 patients and over 12,600 GPs, observed between 2005 and 2010. Controlling for GP fixed effects and patient health, we find no strong evidence that quality differs by patient age, gender, country of origin, health concession card status and income, but quality is increased by stronger patient-doctor relationship. Using a competition measure that is defined at the individual GP level and not restricted to a local market, we find that competition lowers quality. Price is increasing in patient income, whereas competition has a small impact on price. Copyright © 2014 John Wiley & Sons, Ltd.

Multiple binding sites for transcriptional repressors can produce regular bursting and enhance noise suppression

NASA Astrophysics Data System (ADS)

Lengyel, Iván M.; Morelli, Luis G.

2017-04-01

Cells may control fluctuations in protein levels by means of negative autoregulation, where transcription factors bind DNA sites to repress their own production. Theoretical studies have assumed a single binding site for the repressor, while in most species it is found that multiple binding sites are arranged in clusters. We study a stochastic description of negative autoregulation with multiple binding sites for the repressor. We find that increasing the number of binding sites induces regular bursting of gene products. By tuning the threshold for repression, we show that multiple binding sites can also suppress fluctuations. Our results highlight possible roles for the presence of multiple binding sites of negative autoregulators.

Are sick individuals weak competitors? Competitive ability of snails parasitized by a gigantism-inducing trematode.

PubMed

Seppälä, Otto; Karvonen, Anssi; Kuosa, Marja; Haataja, Maarit; Jokela, Jukka

2013-01-01

Parasitized individuals are often expected to be poor competitors because they are weakened by infections. Many trematode species, however, although extensively exploiting their mollusc hosts, also induce gigantism (increased host size) by diverting host resources towards growth instead of reproduction. In such systems, alternatively to reduced competitive ability due to negative effects of parasitism on host performance, larger size could allow more efficient resource acquisition and thus increase the relative competitive ability of host individuals. We addressed this hypothesis by testing the effect of a trematode parasite Diplostomum pseudospathaceum on the competitive ability of its snail host Lymnaea stagnalis. We experimentally examined the growth of snails kept in pairs in relation to their infection status and intensity of resource competition (i.e. food availability). We found that parasitized snails grew faster and their reproduction was reduced compared to unparasitized individuals indicating parasite-induced gigantism. However, growth of the snails was faster when competing with parasitized individuals compared to unparasitized snails indicating reduced competitive ability due to parasitism. The latter effect, however, was relatively weak suggesting that the effects of the parasite on snail physiology may partly override each other in determining competitive ability.

Are Sick Individuals Weak Competitors? Competitive Ability of Snails Parasitized by a Gigantism-Inducing Trematode

PubMed Central

Seppälä, Otto; Karvonen, Anssi; Kuosa, Marja; Haataja, Maarit; Jokela, Jukka

2013-01-01

Parasitized individuals are often expected to be poor competitors because they are weakened by infections. Many trematode species, however, although extensively exploiting their mollusc hosts, also induce gigantism (increased host size) by diverting host resources towards growth instead of reproduction. In such systems, alternatively to reduced competitive ability due to negative effects of parasitism on host performance, larger size could allow more efficient resource acquisition and thus increase the relative competitive ability of host individuals. We addressed this hypothesis by testing the effect of a trematode parasite Diplostomum pseudospathaceum on the competitive ability of its snail host Lymnaea stagnalis. We experimentally examined the growth of snails kept in pairs in relation to their infection status and intensity of resource competition (i.e. food availability). We found that parasitized snails grew faster and their reproduction was reduced compared to unparasitized individuals indicating parasite-induced gigantism. However, growth of the snails was faster when competing with parasitized individuals compared to unparasitized snails indicating reduced competitive ability due to parasitism. The latter effect, however, was relatively weak suggesting that the effects of the parasite on snail physiology may partly override each other in determining competitive ability. PMID:24205383

DWARF 53 acts as a repressor of strigolactone signalling in rice

NASA Astrophysics Data System (ADS)

Jiang, Liang; Liu, Xue; Xiong, Guosheng; Liu, Huihui; Chen, Fulu; Wang, Lei; Meng, Xiangbing; Liu, Guifu; Yu, Hong; Yuan, Yundong; Yi, Wei; Zhao, Lihua; Ma, Honglei; He, Yuanzheng; Wu, Zhongshan; Melcher, Karsten; Qian, Qian; Xu, H. Eric; Wang, Yonghong; Li, Jiayang

2013-12-01

Strigolactones (SLs) are a group of newly identified plant hormones that control plant shoot branching. SL signalling requires the hormone-dependent interaction of DWARF 14 (D14), a probable candidate SL receptor, with DWARF 3 (D3), an F-box component of the Skp-Cullin-F-box (SCF) E3 ubiquitin ligase complex. Here we report the characterization of a dominant SL-insensitive rice (Oryza sativa) mutant dwarf 53 (d53) and the cloning of D53, which encodes a substrate of the SCFD3 ubiquitination complex and functions as a repressor of SL signalling. Treatments with GR24, a synthetic SL analogue, cause D53 degradation via the proteasome in a manner that requires D14 and the SCFD3 ubiquitin ligase, whereas the dominant form of D53 is resistant to SL-mediated degradation. Moreover, D53 can interact with transcriptional co-repressors known as TOPLESS-RELATED PROTEINS. Our results suggest a model of SL signalling that involves SL-dependent degradation of the D53 repressor mediated by the D14-D3 complex.

Expressing the sense of the House of Representatives that Congress should work to eliminate the facilitated sexual exploitation and trafficking of minors over the Internet.

THOMAS, 112th Congress

Rep. Barrow, John [D-GA-12

2012-05-10

House - 05/18/2012 Referred to the Subcommittee on Intellectual Property, Competition and the Internet. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

An MPI-1 Compliant Thread-Based Implementation

NASA Astrophysics Data System (ADS)

Díaz Martín, J. C.; Rico Gallego, J. A.; Álvarez Llorente, J. M.; Perogil Duque, J. F.

This work presents AzequiaMPI, the first full compliant implementation of the MPI-1 standard where the MPI node is a thread. Performance comparisons with MPICH2-Nemesis show that thread-based implementations exploit adequately the multicore architectures under oversubscription, what could make MPI competitive with OpenMP-like solutions.

Black Athletes; Educational, Economic, and Political Considerations

ERIC Educational Resources Information Center

Green, Robert L.; And Others

1974-01-01

This issue focuses on racial discrimination in athletic competition in the United States. Data supports the contention that the employment of Blacks in Big Ten universities in virtually nonexistent at every level of athletics. Articles document the unequal treatment and exploitation of Black athletes in the areas of education, academic advising,…

Collaborations, Courses, and Competitions: Developing Entrepreneurship Programmes at UCL

ERIC Educational Resources Information Center

Chapman, David; Skinner, Jeff

2006-01-01

Purpose: This paper aims to detail a range of collaborative programmes developed by University College London (UCL) and the London Business School (LBS). These schemes have been developed to exploit synergies between the two institutions with the aim of promoting entrepreneurship within the fields of science and technology.…

Regulation and Adaptive Evolution of Lactose Operon Expression in Lactobacillus delbrueckii

PubMed Central

Lapierre, Luciane; Mollet, Beat; Germond, Jacques-Edouard

2002-01-01

Lactobacillus delbrueckii subsp. bulgaricus and L. delbrueckii subsp. lactis are both used in the dairy industry as homofermentative lactic acid bacteria in the production of fermented milk products. After selective pressure for the fast fermentation of milk in the manufacture of yogurts, L. delbrueckii subsp. bulgaricus loses its ability to regulate lac operon expression. A series of mutations led to the constitutive expression of the lac genes. A complex of insertion sequence (IS) elements (ISL4 inside ISL5), inserted at the border of the lac promoter, induced the loss of the palindromic structure of one of the operators likely involved in the binding of regulatory factors. A lac repressor gene was discovered downstream of the β-galactosidase gene of L. delbrueckii subsp. lactis and was shown to be inactivated by several mutations in L. delbrueckii subsp. bulgaricus. Regulatory mechanisms of the lac gene expression of L. delbrueckii subsp. bulgaricus and L. delbrueckii subsp. lactis were compared by heterologous expression in Lactococcus lactis of the two lac promoters in front of a reporter gene (β-glucuronidase) in the presence or absence of the lac repressor gene. Insertion of the complex of IS elements in the lac promoter of L. delbrueckii subsp. bulgaricus increased the promoter's activity but did not prevent repressor binding; rather, it increased the affinity of the repressor for the promoter. Inactivation of the lac repressor by mutations was then necessary to induce the constitutive expression of the lac genes in L. delbrueckii subsp. bulgaricus. PMID:11807052

Loss of floral repressor function adapts rice to higher latitudes in Europe

PubMed Central

Gómez-Ariza, Jorge; Galbiati, Francesca; Goretti, Daniela; Brambilla, Vittoria; Shrestha, Roshi; Pappolla, Andrea; Courtois, Brigitte; Fornara, Fabio

2015-01-01

The capacity to discriminate variations in day length allows plants to align flowering with the most favourable season of the year. This capacity has been altered by artificial selection when cultivated varieties became adapted to environments different from those of initial domestication. Rice flowering is promoted by short days when HEADING DATE 1 (Hd1) and EARLY HEADING DATE 1 (Ehd1) induce the expression of florigenic proteins encoded by HEADING DATE 3a (Hd3a) and RICE FLOWERING LOCUS T 1 (RFT1). Repressors of flowering antagonize such induction under long days, maintaining vegetative growth and delaying flowering. To what extent artificial selection of long day repressor loci has contributed to expand rice cultivation to Europe is currently unclear. This study demonstrates that European varieties activate both Hd3a and RFT1 expression regardless of day length and their induction is caused by loss-of-function mutations at major long day floral repressors. However, their contribution to flowering time control varies between locations. Pyramiding of mutations is frequently observed in European germplasm, but single mutations are sufficient to adapt rice to flower at higher latitudes. Expression of Ehd1 is increased in varieties showing reduced or null Hd1 expression under natural long days, as well as in single hd1 mutants in isogenic backgrounds. These data indicate that loss of repressor genes has been a key strategy to expand rice cultivation to Europe, and that Ehd1 is a central node integrating floral repressive signals. PMID:25732533

Radiation-induced oxidative damage to the DNA-binding domain of the lactose repressor

PubMed Central

Gillard, Nathalie; Goffinont, Stephane; Buré, Corinne; Davidkova, Marie; Maurizot, Jean-Claude; Cadene, Martine; Spotheim-Maurizot, Melanie

2007-01-01

Understanding the cellular effects of radiation-induced oxidation requires the unravelling of key molecular events, particularly damage to proteins with important cellular functions. The Escherichia coli lactose operon is a classical model of gene regulation systems. Its functional mechanism involves the specific binding of a protein, the repressor, to a specific DNA sequence, the operator. We have shown previously that upon irradiation with γ-rays in solution, the repressor loses its ability to bind the operator. Water radiolysis generates hydroxyl radicals (OH· radicals) which attack the protein. Damage of the repressor DNA-binding domain, called the headpiece, is most likely to be responsible of this loss of function. Using CD, fluorescence spectroscopy and a combination of proteolytic cleavage with MS, we have examined the state of the irradiated headpiece. CD measurements revealed a dose-dependent conformational change involving metastable intermediate states. Fluorescence measurements showed a gradual degradation of tyrosine residues. MS was used to count the number of oxidations in different regions of the headpiece and to narrow down the parts of the sequence bearing oxidized residues. By calculating the relative probabilities of reaction of each amino acid with OH· radicals, we can predict the most probable oxidation targets. By comparing the experimental results with the predictions we conclude that Tyr7, Tyr12, Tyr17, Met42 and Tyr47 are the most likely hotspots of oxidation. The loss of repressor function is thus correlated with chemical modifications and conformational changes of the headpiece. PMID:17263689

Assessing the Role of ETHYLENE RESPONSE FACTOR Transcriptional Repressors in Salicylic Acid-Mediated Suppression of Jasmonic Acid-Responsive Genes.

PubMed

Caarls, Lotte; Van der Does, Dieuwertje; Hickman, Richard; Jansen, Wouter; Verk, Marcel C Van; Proietti, Silvia; Lorenzo, Oscar; Solano, Roberto; Pieterse, Corné M J; Van Wees, Saskia C M

2017-02-01

Salicylic acid (SA) and jasmonic acid (JA) cross-communicate in the plant immune signaling network to finely regulate induced defenses. In Arabidopsis, SA antagonizes many JA-responsive genes, partly by targeting the ETHYLENE RESPONSE FACTOR (ERF)-type transcriptional activator ORA59. Members of the ERF transcription factor family typically bind to GCC-box motifs in the promoters of JA- and ethylene-responsive genes, thereby positively or negatively regulating their expression. The GCC-box motif is sufficient for SA-mediated suppression of JA-responsive gene expression. Here, we investigated whether SA-induced ERF-type transcriptional repressors, which may compete with JA-induced ERF-type activators for binding at the GCC-box, play a role in SA/JA antagonism. We selected ERFs that are transcriptionally induced by SA and/or possess an EAR transcriptional repressor motif. Several of the 16 ERFs tested suppressed JA-dependent gene expression, as revealed by enhanced JA-induced PDF1.2 or VSP2 expression levels in the corresponding erf mutants, while others were involved in activation of these genes. However, SA could antagonize JA-induced PDF1.2 or VSP2 in all erf mutants, suggesting that the tested ERF transcriptional repressors are not required for SA/JA cross-talk. Moreover, a mutant in the co-repressor TOPLESS, that showed reduction in repression of JA signaling, still displayed SA-mediated antagonism of PDF1.2 and VSP2. Collectively, these results suggest that SA-regulated ERF transcriptional repressors are not essential for antagonism of JA-responsive gene expression by SA. We further show that de novo SA-induced protein synthesis is required for suppression of JA-induced PDF1.2, pointing to SA-stimulated production of an as yet unknown protein that suppresses JA-induced transcription. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Multi‐layered inhibition of Streptomyces development: BldO is a dedicated repressor of whiB

PubMed Central

Chandra, Govind; Findlay, Kim C.; Buttner, Mark J.

2017-01-01

Summary BldD‐(c‐di‐GMP) sits on top of the regulatory network that controls differentiation in Streptomyces, repressing a large regulon of developmental genes when the bacteria are growing vegetatively. In this way, BldD functions as an inhibitor that blocks the initiation of sporulation. Here, we report the identification and characterisation of BldO, an additional developmental repressor that acts to sustain vegetative growth and prevent entry into sporulation. However, unlike the pleiotropic regulator BldD, we show that BldO functions as the dedicated repressor of a single key target gene, whiB, and that deletion of bldO or constitutive expression of whiB is sufficient to induce precocious hypersporulation. PMID:28271577

Panmictic and Clonal Evolution on a Single Patchy Resource Produces Polymorphic Foraging Guilds

PubMed Central

Getz, Wayne M.; Salter, Richard; Lyons, Andrew J.; Sippl-Swezey, Nicolas

2015-01-01

We develop a stochastic, agent-based model to study how genetic traits and experiential changes in the state of agents and available resources influence individuals’ foraging and movement behaviors. These behaviors are manifest as decisions on when to stay and exploit a current resource patch or move to a particular neighboring patch, based on information of the resource qualities of the patches and the anticipated level of intraspecific competition within patches. We use a genetic algorithm approach and an individual’s biomass as a fitness surrogate to explore the foraging strategy diversity of evolving guilds under clonal versus hermaphroditic sexual reproduction. We first present the resource exploitation processes, movement on cellular arrays, and genetic algorithm components of the model. We then discuss their implementation on the Nova software platform. This platform seamlessly combines the dynamical systems modeling of consumer-resource interactions with agent-based modeling of individuals moving over a landscapes, using an architecture that lays transparent the following four hierarchical simulation levels: 1.) within-patch consumer-resource dynamics, 2.) within-generation movement and competition mitigation processes, 3.) across-generation evolutionary processes, and 4.) multiple runs to generate the statistics needed for comparative analyses. The focus of our analysis is on the question of how the biomass production efficiency and the diversity of guilds of foraging strategy types, exploiting resources over a patchy landscape, evolve under clonal versus random hermaphroditic sexual reproduction. Our results indicate greater biomass production efficiency under clonal reproduction only at higher population densities, and demonstrate that polymorphisms evolve and are maintained under random mating systems. The latter result questions the notion that some type of associative mating structure is needed to maintain genetic polymorphisms among individuals exploiting a common patchy resource on an otherwise spatially homogeneous landscape. PMID:26274613

Compete, coordinate, and cooperate: How to exploit uncertain environments with social interaction.

PubMed

Schulze, Christin; Newell, Ben R

2015-10-01

Countless decisions, from the trivial to the crucial, are made in complex social contexts while facing uncertain consequences. Yet a large portion of decision making research focuses on either the effects of social interaction or the effects of environmental uncertainty by examining strategic games against others or individual games against nature. Drawing a connection between these approaches, the authors extend a standard individual choice paradigm to include social interaction with 1 other person. In this paradigm, 2 competing decision makers repeatedly select among 2 options, each offering a particular probability of a fixed payoff. When both players choose the same, correct option, the payoff is evenly split; when they choose different options, the player choosing the correct option receives the full payoff. The addition of this social dimension gives players an opportunity to fully exploit an uncertain environment via cooperation: By consistently choosing opposite options, two players can exploit the uncertain environment more effectively than a single player could. We present 2 experiments that manipulate environmental (Experiment 1) and social (Experiment 2) aspects of the paradigm. In Experiment 1, the outcome probabilities were either known or unknown to participants; in Experiment 2, participants' attention was drawn to individual or group gains by introducing either within- or between-group competition. Efficient cooperation did not emerge spontaneously in Experiment 1. Instead, most people probability maximized, mirroring the behavior observed in individual choice. By contrast, between--group competition in Experiment 2 facilitated efficient-but not always equitable--exploitation of uncertain environments. This work links the concepts of individual risky choice and strategic decision making under both environmental and social uncertainty. (c) 2015 APA, all rights reserved).

Demographic and growth responses of a guerrilla and a phalanx perennial grass in competitive mixtures

USGS Publications Warehouse

Humphrey, L. David; Pyke, David A.

1998-01-01

The advantages of guerrilla and phalanx growth for the guerrilla Elymus lanceolatus ssp. lanceolatus and phalanx E. l. ssp. wawawaiensis were evaluated over 2 years in two taxon mixtures with a range of densities of each subspecies and under two levels of watering. Ramet numbers and biomass of the guerrilla subspecies were higher than those of the phalanx grass in the first year but in the second year declined greatly, while the phalanx grass showed no change in biomass and an increase in ramet numbers. High neighbour densities affected the phalanx subspecies more strongly than the guerrilla subspecies in the first year, but in the second year there were few differences between subspecies. Biomass of the guerrilla grass remained greater than that of the phalanx grass but ramet numbers were similar in the second year. For both subspecies in both years, probability of flowering decreased at higher neighbour densities, indicating adaptation for competitive ability. In the first year, biomass was more strongly reduced by densities than flowering was, but in the second year, when crowding was apparently greater, flowering was more severely affected. Genet survival was high and similar for both subspecies. The presumed advantage of guerrilla subspecies in exploiting open space was supported. The guerrilla grass exploited resources more quickly in the first year by faster growth and greater ramet production, but its biomass, ramet numbers and rhizome growth, and thus its advantage, were reduced in the second year. The phalanx subspecies had slower growth, produced more ramets in later years, and delayed flowering until later years. Although less able to exploit open resources, it appeared adapted to more stressful conditions, and may be able to exploit temporal resource pulses more effectively.

The economic origins of ultrasociality.

PubMed

Gowdy, John; Krall, Lisi

2016-01-01

Ultrasociality refers to the social organization of a few species, including humans and some social insects, having a complex division of labor, city-states, and an almost exclusive dependence on agriculture for subsistence. We argue that the driving forces in the evolution of these ultrasocial societies were economic. With the agricultural transition, species could directly produce their own food and this was such a competitive advantage that those species now dominate the planet. Once underway, this transition was propelled by the selection of within-species groups that could best capture the advantages of (1) actively managing the inputs to food production, (2) a more complex division of labor, and (3) increasing returns to larger scale and larger group size. Together these factors reoriented productive life and radically altered the structure of these societies. Once agriculture began, populations expanded as these economic drivers opened up new opportunities for the exploitation of resources and the active management of inputs to food production. With intensified group-level competition, larger populations and intensive resource exploitation became competitive advantages, and the "social conquest of Earth" was underway. Ultrasocial species came to dominate the earth's ecosystems. Ultrasociality also brought a loss of autonomy for individuals within the group. We argue that exploring the common causes and consequences of ultrasociality in humans and the social insects that adopted agriculture can provide fruitful insights into the evolution of complex human society.

Single Image Super-Resolution Based on Multi-Scale Competitive Convolutional Neural Network

PubMed Central

Qu, Xiaobo; He, Yifan

2018-01-01

Deep convolutional neural networks (CNNs) are successful in single-image super-resolution. Traditional CNNs are limited to exploit multi-scale contextual information for image reconstruction due to the fixed convolutional kernel in their building modules. To restore various scales of image details, we enhance the multi-scale inference capability of CNNs by introducing competition among multi-scale convolutional filters, and build up a shallow network under limited computational resources. The proposed network has the following two advantages: (1) the multi-scale convolutional kernel provides the multi-context for image super-resolution, and (2) the maximum competitive strategy adaptively chooses the optimal scale of information for image reconstruction. Our experimental results on image super-resolution show that the performance of the proposed network outperforms the state-of-the-art methods. PMID:29509666

Single Image Super-Resolution Based on Multi-Scale Competitive Convolutional Neural Network.

PubMed

Du, Xiaofeng; Qu, Xiaobo; He, Yifan; Guo, Di

2018-03-06

Deep convolutional neural networks (CNNs) are successful in single-image super-resolution. Traditional CNNs are limited to exploit multi-scale contextual information for image reconstruction due to the fixed convolutional kernel in their building modules. To restore various scales of image details, we enhance the multi-scale inference capability of CNNs by introducing competition among multi-scale convolutional filters, and build up a shallow network under limited computational resources. The proposed network has the following two advantages: (1) the multi-scale convolutional kernel provides the multi-context for image super-resolution, and (2) the maximum competitive strategy adaptively chooses the optimal scale of information for image reconstruction. Our experimental results on image super-resolution show that the performance of the proposed network outperforms the state-of-the-art methods.

The politics of managed competition: public abuse of the private interest.

PubMed

Robinson, James C

2003-01-01

The doctrine of managed competition in health care sought to achieve the social goals of access and efficiency using market incentives and consumer choice rather than governmental regulation and public administration. In retrospect, it demanded too much from both the public and the private sectors. Rather than develop choice-supporting rules and institutions, the public sector has promoted process regulation and benefit mandates. The private health insurance sector has pursued short-term profitability rather than cooperate in the development of fair competition and informed consumer choice. Purchasers have subsidized inefficient insurance designs in order to exploit tax and regulatory loopholes and to retain an image of corporate paternalism. America's health care system suffers from the public abuse of private interests and the private abuse of the public interest.

Strategic competition: the application of business planning techniques to the hospital marketplace.

PubMed

Morris, D E; Rau, S E

1985-01-01

Survival in the increasingly turbulent and uncertain health care environment should raise the application of business planning and corporate strategy to the highest levels of institutional consciousness. With hospital mergers and networking arrangements expected to account for over 60% of the hospital beds in the nation by 1990, and with government and business cost containment efforts squeezing hospital margins, the survivors are going to be those institutions able to develop and maintain a sustainable economic advantage over the competition in the programs and services that comprise the major portion of their business. The successful players will be those that allow the institution to identify and exploit new opportunities and concentrate management and financial resources in those segments of the market where competitive advantages are real and attainable.

The contradiction of space: Oil, imperialism and the accumulation of capital

NASA Astrophysics Data System (ADS)

Labban, Mazen

This essay examines the relations between the production of oil and gas, the global expansion of capital and the territorial control and division of geographical space. The main argument is that the historical expansion of capital, and the subsequent inter-capitalist competition, has produced and has come to depend on a geographical contradiction between an open and integrated world economy and its division into exclusive economic territories. This contradiction is the result of the contradiction between the conditions for accumulation for individual (national) capitals and the conditions for accumulation for capital as a whole. The objective natural conditions of accumulation are of specific importance, and they gain more importance as capital accumulation comes to rely on more intensive and expansive exploitation of natural resources---specifically crucial resources such as oil and gas. The development of productivity and the concentration of capital cause the rates of profit to decline; the exploitation of natural resources at an increasing scale results from the increase in the mass of raw material required to counter the tendency of the rate of profit ton fall and to resume the accumulation of capital at an expanded scale. This is common to all branches of industry, including the extractive industry---the competition for natural resources is ultimately determined by the competition for increasing, or at least maintaining, the profitability of competing capitals. The contemporary competition among US, Japanese, Indian, Chinese and Western European transnational oil and gas companies for investment in the oil and gas industry of Russia and Iran is examined against the ongoing competition among the US, Russia, China and India for the geopolitical control of the former Soviet republics of Central Asia and the Caucasus. This process is a development of the inter-imperialist competition that began in the late nineteenth century and which resumed in full force since the 1980s after being concealed for a while under the illusions of the Cold War. Certainly, oil and gas play an important part in this competition---particularly as domains for foreign capital investment---but the competition in Central Asia is irreducible to "geopolitics of oil". Indeed, geopolitical competition itself in this context is part of a broader geoeconomic globalization---one means in the struggle among rivals for stronger positions in the world economy. This renewed inter-imperialist rivalry, not unlike its nineteenth century precursor that lasted until the Second World War, is essentially competition among capitals at different stages of development, only that the objects of the inter-imperialist struggles of past have become active participants in the competition. In Asia, the development of China, India and Southeast Asia as major global economic competitors has only made the competition more global and more intense. Access to oil and gas resources is crucial for determining the course and outcome of the competition among developed and developing economies---this essay is an attempt at determining why should that be the case.

Role of co-regulators in metabolic and transcriptional actions of thyroid hormone.

PubMed

Astapova, Inna

2016-04-01

Thyroid hormone (TH) controls a wide range of physiological processes through TH receptor (TR) isoforms. Classically, TRs are proposed to function as tri-iodothyronine (T3)-dependent transcription factors: on positively regulated target genes, unliganded TRs mediate transcriptional repression through recruitment of co-repressor complexes, while T3 binding leads to dismissal of co-repressors and recruitment of co-activators to activate transcription. Co-repressors and co-activators were proposed to play opposite roles in the regulation of negative T3 target genes and hypothalamic-pituitary-thyroid axis, but exact mechanisms of the negative regulation by TH have remained elusive. Important insights into the roles of co-repressors and co-activators in different physiological processes have been obtained using animal models with disrupted co-regulator function. At the same time, recent studies interrogating genome-wide TR binding have generated compelling new data regarding effects of T3, local chromatin structure, and specific response element configuration on TR recruitment and function leading to the proposal of new models of transcriptional regulation by TRs. This review discusses data obtained in various mouse models with manipulated function of nuclear receptor co-repressor (NCoR or NCOR1) and silencing mediator of retinoic acid receptor and thyroid hormone receptor (SMRT or NCOR2), and family of steroid receptor co-activators (SRCs also known as NCOAs) in the context of TH action, as well as insights into the function of co-regulators that may emerge from the genome-wide TR recruitment analysis. © 2016 Society for Endocrinology.

Expanding Horizons in Higher and Technical Education to Adopt New Visions of New World: A Challenge

ERIC Educational Resources Information Center

Naik, B. M.; Kandlikar, W. S.; Shirkhedkar, M. P.

2009-01-01

Which government does not want to generate hi-tech employment, high pay international jobs, spur industrial growth, and make education globally competitive? Then it must install research parks, incubators, Patent & IPR to facilitate commercial exploitation of sunrise technologies. Industries world over are seen flocking round the advanced…

Essays on Information Technology and Value Creation: Corporate Governance, Software Firm Acquisitions, and Entrepreneurial Signaling

ERIC Educational Resources Information Center

Bandodkar, Nikhil Ramkrishna

2017-01-01

Value creation is often at the core of many organizational activities and is often reflected in the exploration and exploitation of opportunities to foster organizational growth. In modern organizations, information technology (IT) plays a significant role in creating business value and building substantial competitive advantage. While in the…

Web-Based Knowledge Exchange through Social Links in the Workplace

ERIC Educational Resources Information Center

Filipowski, Tomasz; Kazienko, Przemyslaw; Brodka, Piotr; Kajdanowicz, Tomasz

2012-01-01

Knowledge exchange between employees is an essential feature of recent commercial organisations on the competitive market. Based on the data gathered by various information technology (IT) systems, social links can be extracted and exploited in knowledge exchange systems of a new kind. Users of such a system ask their queries and the system…

Importance of positioning for microbial evolution

PubMed Central

Kim, Wook; Racimo, Fernando; Schluter, Jonas; Levy, Stuart B.; Foster, Kevin R.

2014-01-01

Microbes commonly live in dense surface-attached communities where cells layer on top of one another such that only those at the edges have unimpeded access to limiting nutrients and space. Theory predicts that this simple spatial effect, akin to plants competing for light in a forest, generates strong natural selection on microbial phenotypes. However, we require direct empirical tests of the importance of this spatial structuring. Here we show that spontaneous mutants repeatedly arise, push their way to the surface, and dominate colonies of the bacterium Pseudomonas fluorescens Pf0-1. Microscopy and modeling suggests that these mutants use secretions to expand and push themselves up to the growth surface to gain the best access to oxygen. Physically mixing the cells in the colony, or introducing space limitations, largely removes the mutant’s advantage, showing a key link between fitness and the ability of the cells to position themselves in the colony. We next follow over 500 independent adaptation events and show that all occur through mutation of a single repressor of secretions, RsmE, but that the mutants differ in competitiveness. This process allows us to map the genetic basis of their adaptation at high molecular resolution and we show how evolutionary competitiveness is explained by the specific effects of each mutation. By combining population level and molecular analyses, we demonstrate how living in dense microbial communities can generate strong natural selection to reach the growing edge. PMID:24715732

Bombyx mori E26 transformation-specific 2 (BmEts2), an Ets family protein, represses Bombyx mori Rels (BmRels)-mediated promoter activation of antimicrobial peptide genes in the silkworm Bombyx mori.

PubMed

Tanaka, H; Sagisaka, A; Suzuki, N; Yamakawa, M

2016-10-01

E26 transformation-specific (Ets) family transcription factors are known to play roles in various biological phenomena, including immunity, in vertebrates. However, the mechanisms by which Ets proteins contribute to immunity in invertebrates remain poorly understood. In this study, we identified a cDNA encoding BmEts2, which is a putative orthologue of Drosophila Yan and human translocation-ets-leukemia/Ets-variant gene 6, from the silkworm Bombyx mori. Expression of the BmEts2 gene was significantly increased in the fat bodies of silkworm larvae in response to injection with Escherichia coli and Staphylococcus aureus. BmEts2 overexpression dramatically repressed B. mori Rels (BmRels)-mediated promoter activation of antimicrobial peptide genes in silkworm cells. Conversely, gene knockdown of BmEts2 significantly enhanced BmRels activity. In addition, two κB sites located on the 5' upstream region of cecropin B1 were found to be involved in the repression of BmRels-mediated promoter activation. Protein-competition analysis further demonstrated that BmEts2 competitively inhibited binding of BmRels to κB sites. Overall, BmEts2 acts as a repressor of BmRels-mediated transactivation of antimicrobial protein genes by inhibiting the binding of BmRels to κB sites. © 2016 The Royal Entomological Society.

Competitive release of drug resistance following drug treatment of mixed Plasmodium chabaudi infections.

PubMed

de Roode, Jacobus C; Culleton, Richard; Bell, Andrew S; Read, Andrew F

2004-09-14

Malaria infections are often genetically diverse, potentially leading to competition between co-infecting strains. Such competition is of key importance in the spread of drug resistance. The effects of drug treatment on within-host competition were studied using the rodent malaria Plasmodium chabaudi. Mice were infected simultaneously with a drug-resistant and a drug-sensitive clone and were then either drug-treated or left untreated. Transmission was assessed by feeding mice to Anopheles stephensi mosquitoes. In the absence of drugs, the sensitive clone competitively suppressed the resistant clone; this resulted in lower asexual parasite densities and also reduced transmission to the mosquito vector. Drug treatment, however, allowed the resistant clone to fill the ecological space emptied by the removal of the sensitive clone, allowing it to transmit as well as it would have done in the absence of competition. These results show that under drug pressure, resistant strains can have two advantages: (1) they survive better than sensitive strains and (2) they can exploit the opportunities presented by the removal of their competitors. When mixed infections are common, such effects could increase the spread of drug resistance.

Cheating fosters species co-existence in well-mixed bacterial communities

PubMed Central

Leinweber, Anne; Fredrik Inglis, R; Kümmerli, Rolf

2017-01-01

Explaining the enormous biodiversity observed in bacterial communities is challenging because ecological theory predicts that competition between species occupying the same niche should lead to the exclusion of less competitive community members. Competitive exclusion should be particularly strong when species compete for a single limiting resource or live in unstructured habitats that offer no refuge for weaker competitors. Here, we describe the ‘cheating effect’, a form of intra-specific competition that can counterbalance between-species competition, thereby fostering biodiversity in unstructured habitats. Using experimental communities consisting of the strong competitor Pseudomonas aeruginosa (PA) and its weaker counterpart Burkholderia cenocepacia (BC), we show that co-existence is impossible when the two species compete for a single limiting resource, iron. However, when introducing a PA cheating mutant, which specifically exploits the iron-scavenging siderophores produced by the PA wild type, we found that biodiversity was preserved under well-mixed conditions where PA cheats could outcompete the PA wild type. Cheating fosters biodiversity in our system because it creates strong intra-specific competition, which equalizes fitness differences between PA and BC. Our study identifies cheating – typically considered a destructive element – as a constructive force in shaping biodiversity. PMID:28060362

Effects of Task Familiarity on Stress Responses of Repressors and Sensitizers

ERIC Educational Resources Information Center

Pagano, Don F.

1973-01-01

R.S. Lazarus's theory of coping was used to investigate appraisal and reappraisal of threat in repressors and sensitizers. Two indexes of stress, self-report ratings of affect and palmar skin conductance, were measured prior to performance on a reaction time task, after one-third of the task was completed and after two-thirds of the task was…

Structural basis for corepressor assembly by the orphan nuclear receptor TLX

PubMed Central

Zhou, X. Edward; He, Yuanzheng; Searose-Xu, Kelvin; Zhang, Chun-Li; Tsai, Chih-Cheng; Melcher, Karsten

2015-01-01

The orphan nuclear receptor TLX regulates neural stem cell self-renewal in the adult brain and functions primarily as a transcription repressor through recruitment of Atrophin corepressors, which bind to TLX via a conserved peptide motif termed the Atro box. Here we report crystal structures of the human and insect TLX ligand-binding domain in complex with Atro box peptides. In these structures, TLX adopts an autorepressed conformation in which its helix H12 occupies the coactivator-binding groove. Unexpectedly, H12 in this autorepressed conformation forms a novel binding pocket with residues from helix H3 that accommodates a short helix formed by the conserved ALXXLXXY motif of the Atro box. Mutations that weaken the TLX–Atrophin interaction compromise the repressive activity of TLX, demonstrating that this interaction is required for Atrophin to confer repressor activity to TLX. Moreover, the autorepressed conformation is conserved in the repressor class of orphan nuclear receptors, and mutations of corresponding residues in other members of this class of receptors diminish their repressor activities. Together, our results establish the functional conservation of the autorepressed conformation and define a key sequence motif in the Atro box that is essential for TLX-mediated repression. PMID:25691470

Short linear motif acquisition, exon formation and alternative splicing determine a pathway to diversity for NCoR-family co-repressors

PubMed Central

Short, Stephen; Peterkin, Tessa; Guille, Matthew; Patient, Roger; Sharpe, Colin

2015-01-01

Vertebrate NCoR-family co-repressors play central roles in the timing of embryo and stem cell differentiation by repressing the activity of a range of transcription factors. They interact with nuclear receptors using short linear motifs (SLiMs) termed co-repressor for nuclear receptor (CoRNR) boxes. Here, we identify the pathway leading to increasing co-repressor diversity across the deuterostomes. The final complement of CoRNR boxes arose in an ancestral cephalochordate, and was encoded in one large exon; the urochordates and vertebrates then split this region between 10 and 12 exons. In Xenopus, alternative splicing is prevalent in NCoR2, but absent in NCoR1. We show for one NCoR1 exon that alternative splicing can be recovered by a single point mutation, suggesting NCoR1 lost the capacity for alternative splicing. Analyses in Xenopus and zebrafish identify that cellular context, rather than gene sequence, predominantly determines species differences in alternative splicing. We identify a pathway to diversity for the NCoR family beginning with the addition of a SLiM, followed by gene duplication, the generation of alternatively spliced isoforms and their differential deployment. PMID:26289800

Repressing a Repressor

PubMed Central

Silverstone, Aron L.; Jung, Hou-Sung; Dill, Alyssa; Kawaide, Hiroshi; Kamiya, Yuji; Sun, Tai-ping

2001-01-01

RGA (for repressor of ga1-3) and SPINDLY (SPY) are likely repressors of gibberellin (GA) signaling in Arabidopsis because the recessive rga and spy mutations partially suppressed the phenotype of the GA-deficient mutant ga1-3. We found that neither rga nor spy altered the GA levels in the wild-type or the ga1-3 background. However, expression of the GA biosynthetic gene GA4 was reduced 26% by the rga mutation, suggesting that partial derepression of the GA response pathway by rga resulted in the feedback inhibition of GA4 expression. The green fluorescent protein (GFP)–RGA fusion protein was localized to nuclei in transgenic Arabidopsis. This result supports the predicted function of RGA as a transcriptional regulator based on sequence analysis. Confocal microscopy and immunoblot analyses demonstrated that the levels of both the GFP-RGA fusion protein and endogenous RGA were reduced rapidly by GA treatment. Therefore, the GA signal appears to derepress the GA signaling pathway by degrading the repressor protein RGA. The effect of rga on GA4 gene expression and the effect of GA on RGA protein level allow us to identify part of the mechanism by which GA homeostasis is achieved. PMID:11449051

Structural basis for corepressor assembly by the orphan nuclear receptor TLX

DOE PAGES

Zhi, Xiaoyong; Zhou, X. Edward; He, Yuanzheng; ...

2015-02-15

The orphan nuclear receptor TLX regulates neural stem cell self-renewal in the adult brain and functions primarily as a transcription repressor through recruitment of Atrophin corepressors, which bind to TLX via a conserved peptide motif termed the Atro box. Here we report crystal structures of the human and insect TLX ligand-binding domain in complex with Atro box peptides. In these structures, TLX adopts an autorepressed conformation in which its helix H12 occupies the coactivator-binding groove. Unexpectedly, H12 in this autorepressed conformation forms a novel binding pocket with residues from helix H3 that accommodates a short helix formed by the conservedmore » ALXXLXXY motif of the Atro box. Mutations that weaken the TLX–Atrophin interaction compromise the repressive activity of TLX, demonstrating that this interaction is required for Atrophin to confer repressor activity to TLX. Moreover, the autorepressed conformation is conserved in the repressor class of orphan nuclear receptors, and mutations of corresponding residues in other members of this class of receptors diminish their repressor activities. Together, our results establish the functional conservation of the autorepressed conformation and define a key sequence motif in the Atro box that is essential for TLX-mediated repression.« less

ATLAS computing on Swiss Cloud SWITCHengines

NASA Astrophysics Data System (ADS)

Haug, S.; Sciacca, F. G.; ATLAS Collaboration

2017-10-01

Consolidation towards more computing at flat budgets beyond what pure chip technology can offer, is a requirement for the full scientific exploitation of the future data from the Large Hadron Collider at CERN in Geneva. One consolidation measure is to exploit cloud infrastructures whenever they are financially competitive. We report on the technical solutions and the performances used and achieved running simulation tasks for the ATLAS experiment on SWITCHengines. SWITCHengines is a new infrastructure as a service offered to Swiss academia by the National Research and Education Network SWITCH. While solutions and performances are general, financial considerations and policies, on which we also report, are country specific.

Expression, Purification And Preliminary X-Ray Analysis of the C-Terminal Domain of An Arginine Repressor Protein From Mycobacterium Tuberculosis

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

Lu, G.J.; Garen, C.R.; Cherney, M.M.

2009-06-03

The gene product of an open reading frame Rv1657 from Mycobacterium tuberculosis is a putative arginine repressor protein (ArgR), a transcriptional factor that regulates the expression of arginine-biosynthetic enzymes. Rv1657 was expressed and purified and a C-terminal domain was crystallized using the hanging-drop vapour-diffusion method. Diffraction data were collected and processed to a resolution of 2.15 {angstrom}. The crystals belong to space group P1 and the Matthews coefficient suggests that the crystals contain six C-terminal domain molecules per unit cell. Previous structural and biochemical studies on the arginine repressor proteins from other organisms have likewise shown the presence of sixmore » molecules per unit cell.« less

The relationship between two types of impaired emotion processing: repressive coping and alexithymia

PubMed Central

Myers, Lynn B.; Derakshan, Nazanin

2015-01-01

The constructs of repressive coping and alexithymia are both related to impaired emotion processing, yet individuals with a repressive coping style (repressors) score lower than controls on standard self-report measures of alexithymia. A large body of evidence indicates that repressors avoid negative affect. Therefore, the current study examined the relationship between repressive coping and alexithymia by using independently-rated interviews with the aim of bypassing repressors’ tendency of avoiding negative affect. Results showed that repressors scored high on alexithymia, similar to anxious individuals on the independently-rated interview, but scored low on alexithymia on a questionnaire measure. Our findings confirm a link between alexithymia and repressive coping and stress the need for non-standard measures in exploring the nature of the relationship between repressive coping and alexithymia. PMID:26136706

GENE REGULATION. Discrete functions of nuclear receptor Rev-erbα couple metabolism to the clock.

PubMed

Zhang, Yuxiang; Fang, Bin; Emmett, Matthew J; Damle, Manashree; Sun, Zheng; Feng, Dan; Armour, Sean M; Remsberg, Jarrett R; Jager, Jennifer; Soccio, Raymond E; Steger, David J; Lazar, Mitchell A

2015-06-26

Circadian and metabolic physiology are intricately intertwined, as illustrated by Rev-erbα, a transcription factor (TF) that functions both as a core repressive component of the cell-autonomous clock and as a regulator of metabolic genes. Here, we show that Rev-erbα modulates the clock and metabolism by different genomic mechanisms. Clock control requires Rev-erbα to bind directly to the genome at its cognate sites, where it competes with activating ROR TFs. By contrast, Rev-erbα regulates metabolic genes primarily by recruiting the HDAC3 co-repressor to sites to which it is tethered by cell type-specific transcription factors. Thus, direct competition between Rev-erbα and ROR TFs provides a universal mechanism for self-sustained control of the molecular clock across all tissues, whereas Rev-erbα uses lineage-determining factors to convey a tissue-specific epigenomic rhythm that regulates metabolism tailored to the specific need of that tissue. Copyright © 2015, American Association for the Advancement of Science.

Competitive fluorescent pseudo-immunoassay exploiting molecularly imprinted polymers for the detection of biogenic amines in fish matrix.

PubMed

Mattsson, Leena; Xu, Jingjing; Preininger, Claudia; Tse Sum Bui, Bernadette; Haupt, Karsten

2018-05-01

We developed a competitive fluorescent molecularly imprinted polymer (MIP) assay to detect biogenic amines in fish samples. MIPs synthesized by precipitation polymerization using histamine as template were used in a batch binding assay analogous to competitive fluoroimmunoassays. Introducing a complex sample matrix, such as fish extract, into the assay changes the environment and the binding conditions, therefore the importance of the sample preparation is extensively discussed. Several extraction and purification methods for fish were comprehensively studied, and an optimal clean-up procedure for fish samples using liquid-liquid extraction was developed. The feasibility of the competitive MIP assay was shown in the purified fish extract over a broad histamine range (1 - 430µM). The MIP had the highest affinity towards histamine, but recognized also the structurally similar biogenic amines tyramine and tryptamine, as well as spermine and spermidine, providing simultaneous analysis and assessment of the total amount of biogenic amines. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of transgenic sterilization constructs and their repressor compounds on hatch, developmental rate and early survival of electroporated channel catfish embryos and fry.

PubMed

Su, Baofeng; Shang, Mei; Li, Chao; Perera, Dayan A; Pinkert, Carl A; Irwin, Michael H; Peatman, Eric; Grewe, Peter; Patil, Jawahar G; Dunham, Rex A

2015-04-01

Channel catfish (Ictalurus punctatus) embryos were electroporated with sterilization constructs targeting primordial germ cell proteins or with buffer. Some embryos then were treated with repressor compounds, cadmium chloride, copper sulfate, sodium chloride or doxycycline, to prevent expression of the transgene constructs. Promoters included channel catfish nanos and vasa, salmon transferrin (TF), modified yeast Saccharomyces cerevisiae copper transport protein (MCTR) and zebrafish racemase (RM). Knock-down systems were the Tet-off (nanos and vasa constructs), MCTR, RM and TF systems. Knock-down genes included shRNAi targeting 5' nanos (N1), 3' nanos (N2) or dead end (DND), or double-stranded nanos RNA (dsRNA) for overexpression of nanos mRNA. These constructs previously were demonstrated to knock down nanos, vasa and dead end, with the repressors having variable success. Exogenous DNA affected percentage hatch (% hatch), as all 14 constructs, except for the TF dsRNA, TF N1 (T), RM DND (C), vasa DND (C), vasa N1 (C) and vasa N2 (C), had lower % hatch than the control electroporated with buffer. The MCTR and RM DND (T) constructs resulted in delayed hatch, and the vasa and nanos constructs had minimal effects on time of hatch (P < 0.05). Cadmium chloride appeared to counteract the slow development caused by the TF constructs in two TF treatments (P < 0.05). The 4 ppt sodium chloride treatment for the RM system decreased % hatch (P < 0.05) and slowed development. In the case of nanos constructs, doxycycline greatly delayed hatch (P < 0.05). Adverse effects of the transgenes and repressors continued for several treatments for the first 6 days after hatch, but only in a few treatments during the next 10 days. Repressors and gene expression impacted the yield of putative transgenic channel catfish fry, and need to be considered and accounted for in the hatchery phase of producing transgenically sterilized catfish fry and their fertile counterparts. This fry output should be considered to ensure that sufficient numbers of transgenic fish are produced for future applications and for defining repressor systems that are the most successful.

Transcription factor FBI-1 acts as a dual regulator in adipogenesis by coordinated regulation of cyclin-A and E2F-4.

PubMed

Laudes, Matthias; Bilkovski, Roman; Oberhauser, Frank; Droste, Andrea; Gomolka, Matthias; Leeser, Uschi; Udelhoven, Michael; Krone, Wilhelm

2008-05-01

Generation of new adipocytes plays a major role in the development of obesity. We previously have shown that transcriptional repressor factor that binds to IST (FBI)-1 exerts a dual effect in the process of adipogenesis by inhibiting proliferation and promoting differentiation of preadipocytes. The aim of the present study was to identify FBI-1 regulated molecular effectors that could account for these effects. Overexpressing FBI-1 in preadipocytes resulted in reduced expression of the cell cycle regulator cyclin A, which may explain FBI-1 induced inhibition of proliferation. Interestingly, FBI-1 repressed cyclin A promoter activity through an indirect mechanisms that did not involve direct binding of FBI-1 to the promoter sequence, but rather FBI-1 inhibition of transcriptional activator Sp1 binding to a regulatory element at -452 to -443. We also show that FBI-1 promotes terminal preadipocyte differentiation through a mechanism involving decreased levels of expression of the PPARgamma inhibitor E2F-4. FBI-1 significantly reduced E2F-4 promoter activity. Contrary to cyclin A, we found FBI-1-induced repression of E2F-4 is mediated by a direct mechanism via a FBI-1 regulatory element at -11 to -5. As function of transcriptional repressors normally depends on the presence of regulatory co-factors we also performed expression profiling of potential FBI-1 co-repressors throughout adipogenesis. In these experiments Sin3A and histon deacetylase (HDAC)-1 showed a similar expression pattern compared to FBI-1. Strikingly, co-immunoprecipitation studies revealed that FBI-1 binds Sin3A and HDAC-1 to form a repressor complex. Furthermore, by mutational analysis the amino terminal Poxvirus (POZ) domain of FBI-1 was found to be important for Sin3A and HDAC-1 binding. Taken together, FBI-1 is the first transcriptional repressor shown to act as a dual regulator in adipogenesis exerting repressor activities on target genes by both, direct and indirect mechanisms.

Chemistry Based on Renewable Raw Materials: Perspectives for a Sugar Cane-Based Biorefinery

PubMed Central

Villela Filho, Murillo; Araujo, Carlos; Bonfá, Alfredo; Porto, Weber

2011-01-01

Carbohydrates are nowadays a very competitive feedstock for the chemical industry because their availability is compatible with world-scale chemical production and their price, based on the carbon content, is comparable to that of petrochemicals. At the same time, demand is rising for biobased products. Brazilian sugar cane is a competitive feedstock source that is opening the door to a wide range of bio-based products. This essay begins with the importance of the feedstock for the chemical industry and discusses developments in sugar cane processing that lead to low cost feedstocks. Thus, sugar cane enables a new chemical industry, as it delivers a competitive raw material and a source of energy. As a result, sugar mills are being transformed into sustainable biorefineries that fully exploit the potential of sugar cane. PMID:21637329

Chemistry based on renewable raw materials: perspectives for a sugar cane-based biorefinery.

PubMed

Villela Filho, Murillo; Araujo, Carlos; Bonfá, Alfredo; Porto, Weber

2011-01-01

Carbohydrates are nowadays a very competitive feedstock for the chemical industry because their availability is compatible with world-scale chemical production and their price, based on the carbon content, is comparable to that of petrochemicals. At the same time, demand is rising for biobased products. Brazilian sugar cane is a competitive feedstock source that is opening the door to a wide range of bio-based products. This essay begins with the importance of the feedstock for the chemical industry and discusses developments in sugar cane processing that lead to low cost feedstocks. Thus, sugar cane enables a new chemical industry, as it delivers a competitive raw material and a source of energy. As a result, sugar mills are being transformed into sustainable biorefineries that fully exploit the potential of sugar cane.

[Establishment of industry promotion technology system in Chinese medicine secondary exploitation based on "component structure theory"].

PubMed

Cheng, Xu-Dong; Feng, Liang; Zhang, Ming-Hua; Gu, Jun-Fei; Jia, Xiao-Bin

2014-10-01

The purpose of the secondary exploitation of Chinese medicine is to improve the quality of Chinese medicine products, enhance core competitiveness, for better use in clinical practice, and more effectively solve the patient suffering. Herbs, extraction, separation, refreshing, preparation and quality control are all involved in the industry promotion of Chinese medicine secondary exploitation of industrial production. The Chinese medicine quality improvement and industry promotion could be realized with the whole process of process optimization, quality control, overall processes improvement. Based on the "component structure theory", "multi-dimensional structure & process dynamic quality control system" and systematic and holistic character of Chinese medicine, impacts of whole process were discussed. Technology systems of Chinese medicine industry promotion was built to provide theoretical basis for improving the quality and efficacy of the secondary development of traditional Chinese medicine products.

Modeling of the structure and interactions of the B. anthracis antitoxin, MoxX: deletion mutant studies highlight its modular structure and repressor function

NASA Astrophysics Data System (ADS)

Chopra, Nikita; Agarwal, Shivangi; Verma, Shashikala; Bhatnagar, Sonika; Bhatnagar, Rakesh

2011-03-01

Our previous report on Bacillus anthracis toxin-antitoxin module (MoxXT) identified it to be a two component system wherein, PemK-like toxin (MoxT) functions as a ribonuclease (Agarwal S et al. JBC 285:7254-7270, 2010). The labile antitoxin (MoxX) can bind to/neutralize the action of the toxin and is also a DNA-binding protein mediating autoregulation. In this study, molecular modeling of MoxX in its biologically active dimeric form was done. It was found that it contains a conserved Ribbon-Helix-Helix (RHH) motif, consistent with its DNA-binding function. The modeled MoxX monomers dimerize to form a two-stranded antiparallel ribbon, while the C-terminal region adopts an extended conformation. Knowledge guided protein-protein docking, molecular dynamics simulation, and energy minimization was performed to obtain the structure of the MoxXT complex, which was exploited for the de novo design of a peptide capable of binding to MoxT. It was found that the designed peptide caused a decrease in MoxX binding to MoxT by 42% at a concentration of 2 μM in vitro. We also show that MoxX mediates negative transcriptional autoregulation by binding to its own upstream DNA. The interacting regions of both MoxX and DNA were identified in order to model their complex. The repressor activity of MoxX was found to be mediated by the 16 N-terminal residues that contains the ribbon of the RHH motif. Based on homology with other RHH proteins and deletion mutant studies, we propose a model of the MoxX-DNA interaction, with the antiparallel β-sheet of the MoxX dimer inserted into the major groove of its cognate DNA. The structure of the complex of MoxX with MoxT and its own upstream regulatory region will facilitate design of molecules that can disrupt these interactions, a strategy for development of novel antibacterials.

Multiple conformations of the cytidine repressor DNA-binding domain coalesce to one upon recognition of a specific DNA surface.

PubMed

Moody, Colleen L; Tretyachenko-Ladokhina, Vira; Laue, Thomas M; Senear, Donald F; Cocco, Melanie J

2011-08-09

The cytidine repressor (CytR) is a member of the LacR family of bacterial repressors with distinct functional features. The Escherichia coli CytR regulon comprises nine operons whose palindromic operators vary in both sequence and, most significantly, spacing between the recognition half-sites. This suggests a strong likelihood that protein folding would be coupled to DNA binding as a mechanism to accommodate the variety of different operator architectures to which CytR is targeted. Such coupling is a common feature of sequence-specific DNA-binding proteins, including the LacR family repressors; however, there are no significant structural rearrangements upon DNA binding within the three-helix DNA-binding domains (DBDs) studied to date. We used nuclear magnetic resonance (NMR) spectroscopy to characterize the CytR DBD free in solution and to determine the high-resolution structure of a CytR DBD monomer bound specifically to one DNA half-site of the uridine phosphorylase (udp) operator. We find that the free DBD populates multiple distinct conformations distinguished by up to four sets of NMR peaks per residue. This structural heterogeneity is previously unknown in the LacR family. These stable structures coalesce into a single, more stable udp-bound form that features a three-helix bundle containing a canonical helix-turn-helix motif. However, this structure differs from all other LacR family members whose structures are known with regard to the packing of the helices and consequently their relative orientations. Aspects of CytR activity are unique among repressors; we identify here structural properties that are also distinct and that might underlie the different functional properties. © 2011 American Chemical Society

Discussion of Planning and Operating of Chongming Qianwei Village's Nongjiale tourism site

NASA Astrophysics Data System (ADS)

Guo, Qingqing; Liu, Min

According to the sufficient market research the paper put forward the Construction and operation of Chongming Qianwei village Nongjiale tour website completed the Building program of this Business Website. Through needs analysis and feasibility analysis, this paper proposed business model for the target system, transaction mode, revenue model and competitive edge. Opening of the bridge which contact Shanghai and Chongming, coming of the shanghai expo; will bring the growth of passenger traffic of chongming's tourism industry. This article is based on this background, discussing the exploitation and plan of tour website of ChongMing, Enhancing the Popularity and Competitiveness of Chongming's Tourism.

The process of managerial control in quality improvement initiatives.

PubMed

Slovensky, D J; Fottler, M D

1994-11-01

The fundamental intent of strategic management is to position an organization with in its market to exploit organizational competencies and strengths to gain competitive advantage. Competitive advantage may be achieved through such strategies as low cost, high quality, or unique services or products. For health care organizations accredited by the Joint Commission on Accreditation of Healthcare Organizations, continually improving both processes and outcomes of organizational performance--quality improvement--in all operational areas of the organization is a mandated strategy. Defining and measuring quality and controlling the quality improvement strategy remain problematic. The article discusses the nature and processes of managerial control, some potential measures of quality, and related information needs.

Rural Policy and the New Regional Economics: Implications for Rural America.

ERIC Educational Resources Information Center

Quigley, John M.

This paper discusses gross economic and demographic trends in rural and urban America during the past 30 years, the kinds of competitive advantages enjoyed by urban and rural regions, and insights offered by the new regional economics concerning exploitation of those advantages. The importance of agriculture has declined in rural areas, while that…

Follow Us into Our World: Feminist Scholarship on the Communication of Women of Color.

ERIC Educational Resources Information Center

Houston, Marsha

In the highly competitive, racist milieu of the academy, even feminist scholars, anxious to advance their own careers, can be lured into ethnocentric research practices that exploit, rather than honor or illumine, the communication of women of color. Before feminist scholars write about such communication, they should seek to answer questions that…

Active vs. Reactive Threat Responding is Associated with Differential c-Fos Expression in Specific Regions of Amygdala and Prefrontal Cortex

ERIC Educational Resources Information Center

Martinez, Raquel C. R.; Gupta, Nikita; Lazaro-Munoz, Gabriel; Sears, Robert M.; Kim, Soojeong; Moscarello, Justin M.; LeDoux, Joseph E.; Cain, Christopher K.

2013-01-01

Active avoidance (AA) is an important paradigm for studying mechanisms of aversive instrumental learning, pathological anxiety, and active coping. Unfortunately, AA neurocircuits are poorly understood, partly because behavior is highly variable and reflects a competition between Pavlovian reactions and instrumental actions. Here we exploited the…

Purification of bacteriophage lambda repressor

PubMed Central

Gao, Ning; Shearwin, Keith; Mack, John; Finzi, Laura; Dunlap, David

2013-01-01

Bacteriophage lambda repressor controls the lysogeny/lytic growth switch after infection of E. coli by lambda phage. In order to study in detail the looping of DNA mediated by the protein, tag-free repressor and a loss-of-cooperativity mutant were expressed in E.coli and purified by (1) ammonium sulfate fractionation, (2) anion-exchange chromatography and (3) heparin affinity chromatography. This method employs more recently developed and readily available chromatography resins to produce highly pure protein in good yield. In tethered particle motion looping assays and atomic force microscopy “footprinting” assays, both the wild-type protein and a C-terminal His-tagged variant, purified using immobilized metal affinity chromatography, bound specifically to high affinity sites to mediate loop formation. In contrast the G147D loss-of-cooperativity mutant bound specifically but did not secure loops. PMID:23831434

Adaptor proteins GIR1 and GIR2. II. Interaction with the co-repressor TOPLESS and promotion of histone deacetylation of target chromatin.

PubMed

Wu, Renhong; Citovsky, Vitaly

2017-07-08

Understanding how root hair development is controlled is important for understanding of many fundamental aspects of plant biology. Previously, we identified two plant-specific adaptor proteins GIR1 and GIR2 that interact with the major regulator of root hair development GL2 and suppress formation of root hair. Here, we show that GIR1 and GIR2 also interact with the co-repressor TOPLESS (TPL). This interaction required the GIR1 protein EAR motif, and was essential for the transcriptional repressor activity of GIR1. Both GIR1 and GIR2 promoted histone hypoacetylation of their target chromatin. Potentially, GIR1 and GIR2 might may link TPL to and participate in epigenetic regulation of root hair development. Copyright © 2017 Elsevier Inc. All rights reserved.

Exploiting ecology in drug pulse sequences in favour of population reduction.

PubMed

Bauer, Marianne; Graf, Isabella R; Ngampruetikorn, Vudtiwat; Stephens, Greg J; Frey, Erwin

2017-09-01

A deterministic population dynamics model involving birth and death for a two-species system, comprising a wild-type and more resistant species competing via logistic growth, is subjected to two distinct stress environments designed to mimic those that would typically be induced by temporal variation in the concentration of a drug (antibiotic or chemotherapeutic) as it permeates through the population and is progressively degraded. Different treatment regimes, involving single or periodical doses, are evaluated in terms of the minimal population size (a measure of the extinction probability), and the population composition (a measure of the selection pressure for resistance or tolerance during the treatment). We show that there exist timescales over which the low-stress regime is as effective as the high-stress regime, due to the competition between the two species. For multiple periodic treatments, competition can ensure that the minimal population size is attained during the first pulse when the high-stress regime is short, which implies that a single short pulse can be more effective than a more protracted regime. Our results suggest that when the duration of the high-stress environment is restricted, a treatment with one or multiple shorter pulses can produce better outcomes than a single long treatment. If ecological competition is to be exploited for treatments, it is crucial to determine these timescales, and estimate for the minimal population threshold that suffices for extinction. These parameters can be quantified by experiment.

Structural basis for corepressor assembly by the orphan nuclear receptor TLX.

PubMed

Zhi, Xiaoyong; Zhou, X Edward; He, Yuanzheng; Searose-Xu, Kelvin; Zhang, Chun-Li; Tsai, Chih-Cheng; Melcher, Karsten; Xu, H Eric

2015-02-15

The orphan nuclear receptor TLX regulates neural stem cell self-renewal in the adult brain and functions primarily as a transcription repressor through recruitment of Atrophin corepressors, which bind to TLX via a conserved peptide motif termed the Atro box. Here we report crystal structures of the human and insect TLX ligand-binding domain in complex with Atro box peptides. In these structures, TLX adopts an autorepressed conformation in which its helix H12 occupies the coactivator-binding groove. Unexpectedly, H12 in this autorepressed conformation forms a novel binding pocket with residues from helix H3 that accommodates a short helix formed by the conserved ALXXLXXY motif of the Atro box. Mutations that weaken the TLX-Atrophin interaction compromise the repressive activity of TLX, demonstrating that this interaction is required for Atrophin to confer repressor activity to TLX. Moreover, the autorepressed conformation is conserved in the repressor class of orphan nuclear receptors, and mutations of corresponding residues in other members of this class of receptors diminish their repressor activities. Together, our results establish the functional conservation of the autorepressed conformation and define a key sequence motif in the Atro box that is essential for TLX-mediated repression. © 2015 Zhi et al.; Published by Cold Spring Harbor Laboratory Press.

Cu(I)-mediated Allosteric Switching in a Copper-sensing Operon Repressor (CsoR)*

PubMed Central

Chang, Feng-Ming James; Coyne, H. Jerome; Cubillas, Ciro; Vinuesa, Pablo; Fang, Xianyang; Ma, Zhen; Ma, Dejian; Helmann, John D.; García-de los Santos, Alejandro; Wang, Yun-Xing; Dann, Charles E.; Giedroc, David P.

2014-01-01

The copper-sensing operon repressor (CsoR) is representative of a major Cu(I)-sensing family of bacterial metalloregulatory proteins that has evolved to prevent cytoplasmic copper toxicity. It is unknown how Cu(I) binding to tetrameric CsoRs mediates transcriptional derepression of copper resistance genes. A phylogenetic analysis of 227 DUF156 protein members, including biochemically or structurally characterized CsoR/RcnR repressors, reveals that Geobacillus thermodenitrificans (Gt) CsoR characterized here is representative of CsoRs from pathogenic bacilli Listeria monocytogenes and Bacillus anthracis. The 2.56 Å structure of Cu(I)-bound Gt CsoR reveals that Cu(I) binding induces a kink in the α2-helix between two conserved copper-ligating residues and folds an N-terminal tail (residues 12–19) over the Cu(I) binding site. NMR studies of Gt CsoR reveal that this tail is flexible in the apo-state with these dynamics quenched upon Cu(I) binding. Small angle x-ray scattering experiments on an N-terminally truncated Gt CsoR (Δ2–10) reveal that the Cu(I)-bound tetramer is hydrodynamically more compact than is the apo-state. The implications of these findings for the allosteric mechanisms of other CsoR/RcnR repressors are discussed. PMID:24831014

Structures of ω repressors bound to direct and inverted DNA repeats explain modulation of transcription

PubMed Central

Weihofen, Wilhelm Andreas; Cicek, Aslan; Pratto, Florencia; Alonso, Juan Carlos; Saenger, Wolfram

2006-01-01

Repressor ω regulates transcription of genes required for copy number control, accurate segregation and stable maintenance of inc18 plasmids hosted by Gram-positive bacteria. ω belongs to homodimeric ribbon-helix-helix (RHH2) repressors typified by a central, antiparallel β-sheet for DNA major groove binding. Homodimeric ω2 binds cooperatively to promotors with 7 to 10 consecutive non-palindromic DNA heptad repeats (5′-A/TATCACA/T-3′, symbolized by →) in palindromic inverted, converging (→←) or diverging (←→) orientation and also, unique to ω2 and contrasting other RHH2 repressors, to non-palindromic direct (→→) repeats. Here we investigate with crystal structures how ω2 binds specifically to heptads in minimal operators with (→→) and (→←) repeats. Since the pseudo-2-fold axis relating the monomers in ω2 passes the central C–G base pair of each heptad with ∼0.3 Å downstream offset, the separation between the pseudo-2-fold axes is exactly 7 bp in (→→), ∼0.6 Å shorter in (→←) but would be ∼0.6 Å longer in (←→). These variations grade interactions between adjacent ω2 and explain modulations in cooperative binding affinity of ω2 to operators with different heptad orientations. PMID:16528102

Regulation of gene expression by manipulating transcriptional repressor activity using a novel CoSRI technology.

PubMed

Xu, Yue; Li, Song Feng; Parish, Roger W

2017-07-01

Targeted gene manipulation is a central strategy for studying gene function and identifying related biological processes. However, a methodology for manipulating the regulatory motifs of transcription factors is lacking as these factors commonly possess multiple motifs (e.g. repression and activation motifs) which collaborate with each other to regulate multiple biological processes. We describe a novel approach designated conserved sequence-guided repressor inhibition (CoSRI) that can specifically reduce or abolish the repressive activities of transcription factors in vivo. The technology was evaluated using the chimeric MYB80-EAR transcription factor and subsequently the endogenous WUS transcription factor. The technology was employed to develop a reversible male sterility system applicable to hybrid seed production. In order to determine the capacity of the technology to regulate the activity of endogenous transcription factors, the WUS repressor was chosen. The WUS repression motif could be inhibited in vivo and the transformed plants exhibited the wus-1 phenotype. Consequently, the technology can be used to manipulate the activities of transcriptional repressor motifs regulating beneficial traits in crop plants and other eukaryotic organisms. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Cytotype Control of Drosophila Melanogaster P Element Transposition: Genomic Position Determines Maternal Repression

PubMed Central

Misra, S.; Buratowski, R. M.; Ohkawa, T.; Rio, D. C.

1993-01-01

P element transposition in Drosophila is controlled by the cytotype regulatory state: in P cytotype, transposition is repressed, whereas in M cytotype, transposition can occur. P cytotype is determined by a combination of maternally inherited factors and chromosomal P elements in the zygote. Transformant strains containing single elements that encoded the 66-kD P element protein zygotically repressed transposition, but did not display the maternal repression characteristic of P cytotype. Upon mobilization to new genomic positions, some of these repressor elements showed significant maternal repression of transposition in genetic assays, involving a true maternal effect. Thus, the genomic position of repressor elements can determine the maternal vs. zygotic inheritance of P cytotype. Immunoblotting experiments indicate that this genomic position effect does not operate solely by controlling the expression level of the 66-kD repressor protein during oogenesis. Likewise, P element derivatives containing the hsp26 maternal regulator sequence expressed high levels of the 66-kD protein during oogenesis, but showed no detectable maternal repression. These data suggest that the location of a repressor element in the genome may determine maternal inheritance of P cytotype by a mechanism involving more than the overall level of expression of the 66-kD protein in the ovary. PMID:8293979

Determination of the DNA-binding kinetics of three related but heteroimmune bacteriophage repressors using EMSA and SPR analysis

PubMed Central

Henriksson-Peltola, Petri; Sehlén, Wilhelmina; Haggård-Ljungquist, Elisabeth

2007-01-01

Bacteriophages P2, P2 Hy dis and WΦ are very similar but heteroimmune Escherichia coli phages. The structural genes show over 96% identity, but the repressors show between 43 and 63% identities. Furthermore, the operators, which contain two directly repeated sequences, vary in sequence, length, location relative to the promoter and spacing between the direct repeats. We have compared the in vivo effects of the wild type and mutated operators on gene expression with the complexes formed between the repressors and their wild type or mutated operators using electrophoretic mobility shift assay (EMSA), and real-time kinetics of the protein–DNA interactions using surface plasmon resonance (SPR) analysis. Using EMSA, the repressors formed different protein–DNA complexes, and only WΦ was significantly affected by point mutations. However, SPR analysis showed a reduced association rate constant and an increased dissociation rate constant for P2 and WΦ operator mutants. The association rate constants of P2 Hy dis was too fast to be determined. The P2 Hy dis dissociation response curves were shown to be triphasic, while both P2 and WΦ C were biphasic. Thus, the kinetics of complex formation and the nature of the complexes formed differ extensively between these very closely related phages. PMID:17412705

Classifying EEG for Brain-Computer Interface: Learning Optimal Filters for Dynamical System Features

PubMed Central

Song, Le; Epps, Julien

2007-01-01

Classification of multichannel EEG recordings during motor imagination has been exploited successfully for brain-computer interfaces (BCI). In this paper, we consider EEG signals as the outputs of a networked dynamical system (the cortex), and exploit synchronization features from the dynamical system for classification. Herein, we also propose a new framework for learning optimal filters automatically from the data, by employing a Fisher ratio criterion. Experimental evaluations comparing the proposed dynamical system features with the CSP and the AR features reveal their competitive performance during classification. Results also show the benefits of employing the spatial and the temporal filters optimized using the proposed learning approach. PMID:18364986

A reformulation of the coupled perturbed self-consistent field equations entirely within a local atomic orbital density matrix-based scheme

NASA Astrophysics Data System (ADS)

Ochsenfeld, Christian; Head-Gordon, Martin

1997-05-01

To exploit the exponential decay found in numerical studies for the density matrix and its derivative with respect to nuclear displacements, we reformulate the coupled perturbed self-consistent field (CPSCF) equations and a quadratically convergent SCF (QCSCF) method for Hartree-Fock and density functional theory within a local density matrix-based scheme. Our D-CPSCF (density matrix-based CPSCF) and D-QCSCF schemes open the way for exploiting sparsity and to achieve asymptotically linear scaling of computational complexity with molecular size ( M), in case of D-CPSCF for all O( M) derivative densities. Furthermore, these methods are even for small molecules strongly competitive to conventional algorithms.

Diffusive coevolution and mutualism maintenance mechanisms in a fig-fig wasp system.

PubMed

Wang, Rui-Wu; Sun, Bao-Fa; Zheng, Qi

2010-05-01

In reciprocal mutualism systems, the exploitation events by exploiters might disrupt the reciprocal mutualism, wherein one exploiter species might even exclude other coexisting exploiter species over an evolutionary time frame. What remains unclear is how such a community is maintained. Niche partitioning, or spatial heterogeneity among the mutualists and exploiters, is generally believed to enable stability within a mutualistic system. However, our examination of a reciprocal mutualism between a fig species (Ficus racemosa) and its pollinator wasp (Ceratosolen fusciceps) shows that spatial niche partitioning does not sufficiently prevent exploiters from overexploiting the common resource (i.e., the female flowers), because of the considerable niche overlap between the mutualists and exploiters. In response to an exploiter, our experiment shows that the fig can (1) abort syconia-containing flowers that have been galled by the exploiter, Apocryptophagus testacea, which oviposits before the pollinators do; and (2) retain syconia-containing flowers galled by Apocryptophagus mayri, which oviposit later than pollinators. However, as a result of (2), there is decreased development of adult non-pollinators or pollinator species in syconia that have not been sufficiently pollinated, but not aborted. Such discriminative abortion of figs or reduction in offspring development of exploiters while rewarding cooperative individuals with higher offspring development by the fig will increase the fitness of cooperative pollinating wasps, but decrease the fitness of exploiters. The fig-fig wasp interactions are diffusively coevolved, a case in which fig wasps diversify their genotype, phenotype, or behavior as a result of competition between wasps, while figs diverge their strategies to facilitate the evolution of cooperative fig waps or lessen the detrimental behavior by associated fig wasps. In habitats or syconia that suffer overexploitation, discriminative abortion of figs or reduction in the offspring development of exploiters in syconia that are not or not sufficiently pollinated will decrease exploiter fitness and perhaps even drive the population of exploiters to local extinction, enabling the evolution and maintenance of cooperative pollinators through the movement between habitats or syconia (i.e., the metapopulations).

Directed evolution of a synthetic phylogeny of programmable Trp repressors.

PubMed

Ellefson, Jared W; Ledbetter, Michael P; Ellington, Andrew D

2018-04-01

As synthetic regulatory programs expand in sophistication, an ever increasing number of biological components with predictable phenotypes is required. Regulators are often 'part mined' from a diverse, but uncharacterized, array of genomic sequences, often leading to idiosyncratic behavior. Here, we generate an entire synthetic phylogeny from the canonical allosteric transcription factor TrpR. Iterative rounds of positive and negative compartmentalized partnered replication (CPR) led to the exponential amplification of variants that responded with high affinity and specificity to halogenated tryptophan analogs and novel operator sites. Fourteen repressor variants were evolved with unique regulatory profiles across five operators and three ligands. The logic of individual repressors can be modularly programmed by creating heterodimeric fusions, resulting in single proteins that display logic functions, such as 'NAND'. Despite the evolutionarily limited regulatory role of TrpR, vast functional spaces exist around this highly conserved protein scaffold and can be harnessed to create synthetic regulatory programs.

Pokemon decreases the transcriptional activity of RARα in the absence of ligand.

PubMed

Yang, Yutao; Li, Yueting; Di, Fei; Cui, Jiajun; Wang, Yue; David Xu, Zhi-Qing

2016-12-20

Pokemon is a transcriptional repressor that belongs to the POZ and Krüppel (POK) protein family. In this study, we investigated the potential interaction between Pokemon and retinoic acid receptor alpha (RARα) and determined the role of Pokemon in regulation of RARα transcriptional activity in the absence of ligand. We found that Pokemon could directly interact with RARα. Moreover, we demonstrated that Pokemon could decrease the transcriptional activity of RARα in the absence of ligand. Furthermore, we showed that Pokemon could repress the transcriptional activity of RARα by increasing the recruitment of nuclear receptor co-repressor (NCoR) and silencing mediator of retinoic acid and thyroid hormone receptor (SMRT) to the retinoic acid response element (RARE) element. Taken together, these data suggest that Pokemon is a novel partner of RARα that acts as a co-repressor to regulate RARα transcriptional activity in the absence of ligand.

Sensitive maintenance: a cognitive process underlying individual differences in memory for threatening information.

PubMed

Peters, Jan H; Hock, Michael; Krohne, Heinz Walter

2012-01-01

Dispositional styles of coping with threat influence memory for threatening information. In particular, sensitizers excel over repressors in their memory for threatening information after long retention intervals, but not after short ones. We therefore suggested that sensitizers, but not repressors, employ active maintenance processes during the retention interval to selectively retain threatening material. Sensitive maintenance was studied in 2 experiments in which participants were briefly exposed to threatening and nonthreatening pictures (Experiment 1, N = 128) or words (Experiment 2, N = 145). Following, we administered unannounced recognition tests before and after an intervening task that generated either high or low cognitive load, assuming that high cognitive load would impede sensitizers' memory maintenance of threatening material. Supporting our hypotheses, the same pattern of results was obtained in both experiments: Under low cognitive load, sensitizers forgot less threat material than repressors did; no such differences were observed under high cognitive load.

Effect of mutation at the interface of Trp-repressor dimeric protein: a steered molecular dynamics simulation.

PubMed

Miño, German; Baez, Mauricio; Gutierrez, Gonzalo

2013-09-01

The strength of key interfacial contacts that stabilize protein-protein interactions have been studied by computer simulation. Experimentally, changes in the interface are evaluated by generating specific mutations at one or more points of the protein structure. Here, such an evaluation is performed by means of steered molecular dynamics and use of a dimeric model of tryptophan repressor and in-silico mutants as a test case. Analysis of four particular cases shows that, in principle, it is possible to distinguish between wild-type and mutant forms by examination of the total energy and force-extension profiles. In particular, detailed atomic level structural analysis indicates that specific mutations at the interface of the dimeric model (positions 19 and 39) alter interactions that appear in the wild-type form of tryptophan repressor, reducing the energy and force required to separate both subunits.

Connecting pills and people: an ethnography of the pharmaceutical nexus in Odisha, India.

PubMed

Seeberg, Jens

2012-06-01

This article explores the impact of intensive competition within the pharmaceutical industry and among private providers on health care in an Indian city. In-depth interviewing and clinical observation were used over a period of 18 months. Private practitioners and chemists who provided regular services to inhabitants of a poor neighborhood in central Bhubaneswar were included. Fierce competition in private health in Odisha, India, reduced quality of care for the poor. The pharmaceutical industry exploited weak links in the health system to push drugs aggressively, including through illegal channels. The private health market is organized in small "network molecules" that maximize profit at the cost of health. The large private share of health care in India and stiff competition are detrimental for primary care in urban India. Free government services are urgently needed and a planned health insurance scheme should be linked to quality control measures.

Competition between relatives and the evolution of dispersal in a parasitoid wasp

PubMed Central

INNOCENT, T. M.; ABE, J.; WEST, S. A.; REECE, S. E.

2014-01-01

Evolutionary theory predicts that levels of dispersal vary in response to the extent of local competition for resources and the relatedness between potential competitors. Here, we test these predictions by making use of a female dispersal dimorphism in the parasitoid wasp Melittobia australica. We show that there are two distinct female morphs, which differ in morphology, pattern of egg production, and dispersal behaviour. As predicted by theory, we found that greater competition for resources resulted in increased production of dispersing females. In contrast, we did not find support for the prediction that high relatedness between competitors increases the production of dispersing females in Melittobia. Finally, we exploit the close links between the evolutionary processes leading to selection for dispersal and for biased sex ratios to examine whether the pattern of dispersal can help distinguish between competing hypotheses for the lack of sex ratio adjustment in Melittobia. PMID:20492084

Exploiting trait correlations for next-generation grain yield and end-use quality improvement of U.S. hard winter wheat

USDA-ARS?s Scientific Manuscript database

Since the early 1980s, the land area planted to U.S. hard winter wheat and the share of U.S. wheat in global export markets have both declined dramatically. Improved profitability of other crops relative to wheat, declining or static domestic wheat flour consumption, and an increasingly competitive ...

Competitiveness and potentials of UCG-CCS on the European energy market

NASA Astrophysics Data System (ADS)

Kempka, T.; Nakaten, N.; Schlüter, R.; Fernandez-Steeger, T.; Azzam, R.

2009-04-01

The world-wide coal reserves can satisfy the world's primary energy demand for several hundred years. However, deep coal deposits with seams of low thickness and structural complexity do currently not allow an economic exploitation of many deposits. Here, underground coal gasification (UCG) can offer an economical approach for coal extraction. The intended overall process relies on coal deposit exploitation using directed drillings located at the coal seam base and the subsequent in situ coal conversion into a synthesis gas. The resulting synthesis gas is used for electricity generation in a combined cycle plant at the surface. A reduction of the CO2 emissions resulting from the combined process is realized by subsequent CO2 capture and its injection into the previously gasified coal seams. The scope of the present study was the investigation of UCG-CCS competitiveness on the European energy market and the determination of the impacting factors. For that purpose, a modular model for calculation of UCG-CCS electricity generation costs was implemented and adapted to the most relevant process parameters. Furthermore, the range of energy supply coverage was estimated based on different German energy generation scenarios.

Artificial neural networks in models of specialization, guild evolution and sympatric speciation.

PubMed

Holmgren, Noél M A; Norrström, Niclas; Getz, Wayne M

2007-03-29

Sympatric speciation can arise as a result of disruptive selection with assortative mating as a pleiotropic by-product. Studies on host choice, employing artificial neural networks as models for the host recognition system in exploiters, illustrate how disruptive selection on host choice coupled with assortative mating can arise as a consequence of selection for specialization. Our studies demonstrate that a generalist exploiter population can evolve into a guild of specialists with an 'ideal free' frequency distribution across hosts. The ideal free distribution arises from variability in host suitability and density-dependent exploiter fitness on different host species. Specialists are less subject to inter-phenotypic competition than generalists and to harmful mutations that are common in generalists exploiting multiple hosts. When host signals used as cues by exploiters coevolve with exploiter recognition systems, our studies show that evolutionary changes may be continuous and cyclic. Selection changes back and forth between specialization and generalization in the exploiters, and weak and strong mimicry in the hosts, where non-defended hosts use the host investing in defence as a model. Thus, host signals and exploiter responses are engaged in a red-queen mimicry process that is ultimately cyclic rather then directional. In one phase, evolving signals of exploitable hosts mimic those of hosts less suitable for exploitation (i.e. the model). Signals in the model hosts also evolve through selection to escape the mimic and its exploiters. Response saturation constraints in the model hosts lead to the mimic hosts finally perfecting its mimicry, after which specialization in the exploiter guild is lost. This loss of exploiter specialization provides an opportunity for the model hosts to escape their mimics. Therefore, this cycle then repeats. We suggest that a species can readily evolve sympatrically when disruptive selection for specialization on hosts is the first step. In a sexual reproduction setting, partial reproductive isolation may first evolve by mate choice being confined to individuals on the same host. Secondly, this disruptive selection will favour assortative mate choice on genotype, thereby leading to increased reproductive isolation.

Evaluation of novel inducible promoter/repressor systems for recombinant protein expression in Lactobacillus plantarum.

PubMed

Heiss, Silvia; Hörmann, Angelika; Tauer, Christopher; Sonnleitner, Margot; Egger, Esther; Grabherr, Reingard; Heinl, Stefan

2016-03-10

Engineering lactic acid bacteria (LAB) is of growing importance for food and feed industry as well as for in vivo vaccination or the production of recombinant proteins in food grade organisms. Often, expression of a transgene is only desired at a certain time point or period, e.g. to minimize the metabolic burden for the host cell or to control the expression time span. For this purpose, inducible expression systems are preferred, though cost and availability of the inducing agent must be feasible. We selected the plasmid free strain Lactobacillus plantarum 3NSH for testing and characterization of novel inducible promoters/repressor systems. Their feasibility in recombinant protein production was evaluated. Expression of the reporter protein mCherry was monitored with the BioLector(®) micro-fermentation system. Reporter gene mCherry expression was compared under the control of different promoter/repressor systems: PlacA (an endogenous promoter/repressor system derived from L. plantarum 3NSH), PxylA (a promoter/repressor system derived from Bacillus megaterium DSMZ 319) and PlacSynth (synthetic promoter and codon-optimized repressor gene based on the Escherichia coli lac operon). We observed that PlacA was inducible solely by lactose, but not by non-metabolizable allolactose analoga. PxylA was inducible by xylose, yet showed basal expression under non-induced conditions. Growth on galactose (as compared to exponential growth phase on glucose) reduced basal mCherry expression at non-induced conditions. PlacSynth was inducible with TMG (methyl β-D-thiogalactopyranoside) and IPTG (isopropyl β-D-1-thiogalactopyranoside), but also showed basal expression without inducer. The promoter PlacSynth was used for establishment of a dual plasmid expression system, based on T7 RNA polymerase driven expression in L. plantarum. Comparative Western blot supported BioLector(®) micro-fermentation measurements. Conclusively, overall expression levels were moderate (compared to a constitutive promoter). We evaluated different inducible promoters, as well as an orthologous expression system, for controlled gene expression in L. plantarum. Furthermore, here we provide proof of concept for a T7 RNA polymerase based expression system for L. plantarum. Thereby we expanded the molecular toolbox for an industrial relevant and generally regarded as safe (GRAS) strain.

Green revolution trees: semidwarfism transgenes modify gibberellins, promote root growth, enhance morphological diversity, and reduce competitiveness in hybrid poplar.

PubMed

Elias, Ani A; Busov, Victor B; Kosola, Kevin R; Ma, Cathleen; Etherington, Elizabeth; Shevchenko, Olga; Gandhi, Harish; Pearce, David W; Rood, Stewart B; Strauss, Steven H

2012-10-01

Semidwarfism has been used extensively in row crops and horticulture to promote yield, reduce lodging, and improve harvest index, and it might have similar benefits for trees for short-rotation forestry or energy plantations, reclamation, phytoremediation, or other applications. We studied the effects of the dominant semidwarfism transgenes GA Insensitive (GAI) and Repressor of GAI-Like, which affect gibberellin (GA) action, and the GA catabolic gene, GA 2-oxidase, in nursery beds and in 2-year-old high-density stands of hybrid poplar (Populus tremula × Populus alba). Twenty-nine traits were analyzed, including measures of growth, morphology, and physiology. Endogenous GA levels were modified in most transgenic events; GA(20) and GA(8), in particular, had strong inverse associations with tree height. Nearly all measured traits varied significantly among genotypes, and several traits interacted with planting density, including aboveground biomass, root-shoot ratio, root fraction, branch angle, and crown depth. Semidwarfism promoted biomass allocation to roots over shoots and substantially increased rooting efficiency with most genes tested. The increased root proportion and increased leaf chlorophyll levels were associated with changes in leaf carbon isotope discrimination, indicating altered water use efficiency. Semidwarf trees had dramatically reduced growth when in direct competition with wild-type trees, supporting the hypothesis that semidwarfism genes could be effective tools to mitigate the spread of exotic, hybrid, and transgenic plants in wild and feral populations.

Green Revolution Trees: Semidwarfism Transgenes Modify Gibberellins, Promote Root Growth, Enhance Morphological Diversity, and Reduce Competitiveness in Hybrid Poplar1[C][W][OA

PubMed Central

Elias, Ani A.; Busov, Victor B.; Kosola, Kevin R.; Ma, Cathleen; Etherington, Elizabeth; Shevchenko, Olga; Gandhi, Harish; Pearce, David W.; Rood, Stewart B.; Strauss, Steven H.

2012-01-01

Semidwarfism has been used extensively in row crops and horticulture to promote yield, reduce lodging, and improve harvest index, and it might have similar benefits for trees for short-rotation forestry or energy plantations, reclamation, phytoremediation, or other applications. We studied the effects of the dominant semidwarfism transgenes GA Insensitive (GAI) and Repressor of GAI-Like, which affect gibberellin (GA) action, and the GA catabolic gene, GA 2-oxidase, in nursery beds and in 2-year-old high-density stands of hybrid poplar (Populus tremula × Populus alba). Twenty-nine traits were analyzed, including measures of growth, morphology, and physiology. Endogenous GA levels were modified in most transgenic events; GA20 and GA8, in particular, had strong inverse associations with tree height. Nearly all measured traits varied significantly among genotypes, and several traits interacted with planting density, including aboveground biomass, root-shoot ratio, root fraction, branch angle, and crown depth. Semidwarfism promoted biomass allocation to roots over shoots and substantially increased rooting efficiency with most genes tested. The increased root proportion and increased leaf chlorophyll levels were associated with changes in leaf carbon isotope discrimination, indicating altered water use efficiency. Semidwarf trees had dramatically reduced growth when in direct competition with wild-type trees, supporting the hypothesis that semidwarfism genes could be effective tools to mitigate the spread of exotic, hybrid, and transgenic plants in wild and feral populations. PMID:22904164

The influence of simulated exploitation on Patella vulgata populations: protandric sex change is size-dependent.

PubMed

Borges, Carla D G; Hawkins, Stephen J; Crowe, Tasman P; Doncaster, C Patrick

2016-01-01

Grazing mollusks are used as a food resource worldwide, and limpets are harvested commercially for both local consumption and export in several countries. This study describes a field experiment to assess the effects of simulated human exploitation of limpets Patella vulgata on their population ecology in terms of protandry (age-related sex change from male to female), growth, recruitment, migration, and density regulation. Limpet populations at two locations in southwest England were artificially exploited by systematic removal of the largest individuals for 18 months in plots assigned to three treatments at each site: no (control), low, and high exploitation. The shell size at sex change (L 50: the size at which there is a 50:50 sex ratio) decreased in response to the exploitation treatments, as did the mean shell size of sexual stages. Size-dependent sex change was indicated by L 50 occurring at smaller sizes in treatments than controls, suggesting an earlier switch to females. Mean shell size of P. vulgata neuters changed little under different levels of exploitation, while males and females both decreased markedly in size with exploitation. No differences were detected in the relative abundances of sexual stages, indicating some compensation for the removal of the bigger individuals via recruitment and sex change as no migratory patterns were detected between treatments. At the end of the experiment, 0-15 mm recruits were more abundant at one of the locations but no differences were detected between treatments. We conclude that sex change in P. vulgata can be induced at smaller sizes by reductions in density of the largest individuals reducing interage class competition. Knowledge of sex-change adaptation in exploited limpet populations should underpin strategies to counteract population decline and improve rocky shore conservation and resource management.

Loss of the co-repressor GPS2 sensitizes macrophage activation upon metabolic stress induced by obesity and type 2 diabetes.

PubMed

Fan, Rongrong; Toubal, Amine; Goñi, Saioa; Drareni, Karima; Huang, Zhiqiang; Alzaid, Fawaz; Ballaire, Raphaelle; Ancel, Patricia; Liang, Ning; Damdimopoulos, Anastasios; Hainault, Isabelle; Soprani, Antoine; Aron-Wisnewsky, Judith; Foufelle, Fabienne; Lawrence, Toby; Gautier, Jean-Francois; Venteclef, Nicolas; Treuter, Eckardt

2016-07-01

Humans with obesity differ in their susceptibility to developing insulin resistance and type 2 diabetes (T2D). This variation may relate to the extent of adipose tissue (AT) inflammation that develops as their obesity progresses. The state of macrophage activation has a central role in determining the degree of AT inflammation and thus its dysfunction, and these states are driven by epigenomic alterations linked to gene expression. The underlying mechanisms that regulate these alterations, however, are poorly defined. Here we demonstrate that a co-repressor complex containing G protein pathway suppressor 2 (GPS2) crucially controls the macrophage epigenome during activation by metabolic stress. The study of AT from humans with and without obesity revealed correlations between reduced GPS2 expression in macrophages, elevated systemic and AT inflammation, and diabetic status. The causality of this relationship was confirmed by using macrophage-specific Gps2-knockout (KO) mice, in which inappropriate co-repressor complex function caused enhancer activation, pro-inflammatory gene expression and hypersensitivity toward metabolic-stress signals. By contrast, transplantation of GPS2-overexpressing bone marrow into two mouse models of obesity (ob/ob and diet-induced obesity) reduced inflammation and improved insulin sensitivity. Thus, our data reveal a potentially reversible disease mechanism that links co-repressor-dependent epigenomic alterations in macrophages to AT inflammation and the development of T2D.

On the use of the T-REx tetracycline-inducible gene expression system in vivo.

PubMed

Dobrovolsky, Vasily N; Heflich, Robert H

2007-10-15

Components of the commercially available T-REx system were used to create two types of transgenic mice. The first contained the tetracycline-repressor transgene under the control of the CMV promoter/enhancer; the second type contained a green fluorescent protein (GFP) reporter transgene under the control of the CMV promoter/enhancer with a tetracycline repressor operator sequence. Transgene expression was unpredictable in animals containing the individual transgenes. Animals with the reporter transgene expressed GFP in only some tissues (e.g., pancreas, kidney), and one line of reporter transgenic animals developed kidney disease, presumably due to expression of the transgene. The two types of transgenic animals were crossbred to produce double-transgenic animals with the object of regulating the expression of the reporter in vivo. When a similar double-transgenic system was constructed in cultured cells, the repressor protein suppressed the transcription of the reporter transgene. The presence of the repressor in double-transgenic animals had no effect on the expression of the reporter; double transgenic animals developed the same kidney disease that was seen in singly transgenic mice with the reporter. Our results indicate that transgenes under the control of the CMV promoter in the T-REx system express somewhat unpredictably and in only a limited number of tissues, making the use of this system for the development of in vivo models problematical. Copyright 2007 Wiley Periodicals, Inc.

Characterization of a JAZ7 activation-tagged Arabidopsis mutant with increased susceptibility to the fungal pathogen Fusarium oxysporum

PubMed Central

Thatcher, Louise F.; Cevik, Volkan; Grant, Murray; Zhai, Bing; Jones, Jonathan D.G.; Manners, John M.; Kazan, Kemal

2016-01-01

In Arabidopsis, jasmonate (JA)-signaling plays a key role in mediating Fusarium oxysporum disease outcome. However, the roles of JASMONATE ZIM-domain (JAZ) proteins that repress JA-signaling have not been characterized in host resistance or susceptibility to this pathogen. Here, we found most JAZ genes are induced following F. oxysporum challenge, and screening T-DNA insertion lines in Arabidopsis JAZ family members identified a highly disease-susceptible JAZ7 mutant (jaz7-1D). This mutant exhibited constitutive JAZ7 expression and conferred increased JA-sensitivity, suggesting activation of JA-signaling. Unlike jaz7 loss-of-function alleles, jaz7-1D also had enhanced JA-responsive gene expression, altered development and increased susceptibility to the bacterial pathogen Pst DC3000 that also disrupts host JA-responses. We also demonstrate that JAZ7 interacts with transcription factors functioning as activators (MYC3, MYC4) or repressors (JAM1) of JA-signaling and contains a functional EAR repressor motif mediating transcriptional repression via the co-repressor TOPLESS (TPL). We propose through direct TPL recruitment, in wild-type plants JAZ7 functions as a repressor within the JA-response network and that in jaz7-1D plants, misregulated ectopic JAZ7 expression hyper-activates JA-signaling in part by disturbing finely-tuned COI1-JAZ-TPL-TF complexes. PMID:26896849

Phosphorylation of Trihelix Transcriptional Repressor ASR3 by MAP KINASE4 Negatively Regulates Arabidopsis Immunity

PubMed Central

Li, Bo; Jiang, Shan; Yu, Xiao; Cheng, Cheng; Chen, Sixue; Cheng, Yanbing; Yuan, Joshua S.; Jiang, Daohong; He, Ping; Shan, Libo

2015-01-01

Proper control of immune-related gene expression is crucial for the host to launch an effective defense response. Perception of microbe-associated molecular patterns (MAMPs) induces rapid and profound transcriptional reprogramming via unclear mechanisms. Here, we show that ASR3 (ARABIDOPSIS SH4-RELATED3) functions as a transcriptional repressor and plays a negative role in regulating pattern-triggered immunity (PTI) in Arabidopsis thaliana. ASR3 belongs to a plant-specific trihelix transcription factor family for which functional studies are lacking. MAMP treatments induce rapid phosphorylation of ASR3 at threonine 189 via MPK4, a mitogen-activated protein kinase that negatively regulates PTI responses downstream of multiple MAMP receptors. ASR3 possesses transcriptional repressor activity via its ERF-associated amphiphilic repression motifs and negatively regulates a large subset of flg22-induced genes. Phosphorylation of ASR3 by MPK4 enhances its DNA binding activity to suppress gene expression. Importantly, the asr3 mutant shows enhanced disease resistance to virulent bacterial pathogen infection, whereas transgenic plants overexpressing the wild-type or phospho-mimetic form of ASR3 exhibit compromised PTI responses. Our studies reveal a function of the trihelix transcription factors in plant innate immunity and provide evidence that ASR3 functions as a transcriptional repressor regulated by MAMP-activated MPK4 to fine-tune plant immune gene expression. PMID:25770109

Mechanisms of information decoding in a cascade system of gene expression

NASA Astrophysics Data System (ADS)

Wang, Haohua; Yuan, Zhanjiang; Liu, Peijiang; Zhou, Tianshou

2016-05-01

Biotechnology advances have allowed investigation of heterogeneity of cellular responses to stimuli on the single-cell level. Functionally, this heterogeneity can compromise cellular responses to environmental signals, and it can also enlarge the repertoire of possible cellular responses and hence increase the adaptive nature of cellular behaviors. However, the mechanism of how this response heterogeneity is generated remains elusive. Here, by systematically analyzing a representative cellular signaling system, we show that (1) the upstream activator always amplifies the downstream burst frequency (BF) but the noiseless activator performs better than the noisy one, remarkably for small or moderate input signal strengths, and the repressor always reduces the downstream BF but the difference in the reducing effect between noiseless and noise repressors is very small; (2) both the downstream burst size and mRNA mean are a monotonically increasing function of the activator strength but a monotonically decreasing function of the repressor strength; (3) for repressor-type input, there is a noisy signal strength such that the downstream mRNA noise arrives at an optimal level, but for activator-type input, the output noise intensity is fundamentally a monotonically decreasing function of the input strength. Our results reveal the essential mechanisms of both signal information decoding and cellular response heterogeneity, whereas our analysis provides a paradigm for analyzing dynamics of noisy biochemical signaling systems.

The interaction between the spatial distribution of resource patches and population density: consequences for intraspecific growth and morphology.

PubMed

Jacobson, Bailey; Grant, James W A; Peres-Neto, Pedro R

2015-07-01

How individuals within a population distribute themselves across resource patches of varying quality has been an important focus of ecological theory. The ideal free distribution predicts equal fitness amongst individuals in a 1 : 1 ratio with resources, whereas resource defence theory predicts different degrees of monopolization (fitness variance) as a function of temporal and spatial resource clumping and population density. One overlooked landscape characteristic is the spatial distribution of resource patches, altering the equitability of resource accessibility and thereby the effective number of competitors. While much work has investigated the influence of morphology on competitive ability for different resource types, less is known regarding the phenotypic characteristics conferring relative ability for a single resource type, particularly when exploitative competition predominates. Here we used young-of-the-year rainbow trout (Oncorhynchus mykiss) to test whether and how the spatial distribution of resource patches and population density interact to influence the level and variance of individual growth, as well as if functional morphology relates to competitive ability. Feeding trials were conducted within stream channels under three spatial distributions of nine resource patches (distributed, semi-clumped and clumped) at two density levels (9 and 27 individuals). Average trial growth was greater in high-density treatments with no effect of resource distribution. Within-trial growth variance had opposite patterns across resource distributions. Here, variance decreased at low-population, but increased at high-population densities as patches became increasingly clumped as the result of changes in the levels of interference vs. exploitative competition. Within-trial growth was related to both pre- and post-trial morphology where competitive individuals were those with traits associated with swimming capacity and efficiency: larger heads/bodies/caudal fins and less angled pectoral fins. The different degrees of within-population growth variance at the same density level found here, as a function of spatial resource distribution, provide an explanation for the inconsistencies in within-site growth variance and population regulation often noted with regard to density dependence in natural landscapes. © 2015 The Authors. Journal of Animal Ecology © 2015 British Ecological Society.

Situational Awareness as a Measure of Performance in Cyber Security Collaborative Work

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

Malviya, Ashish; Fink, Glenn A.; Sego, Landon H.

Cyber defense competitions arising from U.S. service academy exercises, offer a platform for collecting data that can inform research that ranges from characterizing the ideal cyber warrior to describing behaviors during certain challenging cyber defense situations. This knowledge in turn could lead to better preparation of cyber defenders in both military and civilian settings. We conducted proof of concept experimentation to collect data during the Pacific-rim Regional Collegiate Cyber Defense Competition (PRCCDC) and analyzed it to study the behavior of cyber defenders. We propose that situational awareness predicts performance of cyber security professionals, and in this paper we focus onmore » our collection and analysis of competition data to determine whether it supports our hypothesis. In addition to normal cyber data, we collected situational awareness and workload data and compared it against the performance of cyber defenders as indicated by their competition score. We conclude that there is a weak correlation between our measure of situational awareness and performance that we hope to exploit in further studies.« less

Spatial variation in the ecological relationships among the components of Beijing's carbon metabolic system.

PubMed

Xia, Linlin; Fath, Brian D; Scharler, Ursula M; Zhang, Yan

2016-02-15

In this paper, we construct a spatially explicit model of carbon metabolism for the flows of carbon among the components of an urban area. We used the model to identify spatial heterogeneity in the ecological relationships within a carbon metabolic network. We combined land-use and cover type maps for Beijing from 1990 to 2010 with empirical coefficients and socioeconomic data to quantify the flows. We used utility analysis to determine the ecological relationships between the components of the system and analyzed their changes during urban development. We used ArcGIS to analyze their spatial variation. We found that the positive utilities in Beijing decreased over time and that negative relationships mostly outweighed positive relationships after 2000. The main ecological relationships were distributed throughout the entire urban area before 2000; subsequently, exploitation, control, and mutualism relationships became concentrated in the southeast, leaving competition relationships to dominate the northwest. Mutualism relationships were most common for natural components, but were not stable because they were easily disturbed by urban expansion. Transportation and industrial land and urban land were the most important contributors to exploitation and control relationships and may be important indicators of spatial adjustment. Increasing competition relationships unbalanced the carbon metabolism, and limitations on the area of land available for development and on the water resources led to increasingly serious competition. The results provide an objective basis for planning adjustments to Beijing's land-use patterns to improve its carbon metabolism and reduce carbon emission. Copyright © 2015 Elsevier B.V. All rights reserved.

Strategy as simple rules.

PubMed

Eisenhardt, K M; Sull, D N

2001-01-01

The success of Yahoo!, eBay, Enron, and other companies that have become adept at morphing to meet the demands of changing markets can't be explained using traditional thinking about competitive strategy. These companies have succeeded by pursuing constantly evolving strategies in market spaces that were considered unattractive according to traditional measures. In this article--the third in an HBR series by Kathleen Eisenhardt and Donald Sull on strategy in the new economy--the authors ask, what are the sources of competitive advantage in high-velocity markets? The secret, they say, is strategy as simple rules. The companies know that the greatest opportunities for competitive advantage lie in market confusion, but they recognize the need for a few crucial strategic processes and a few simple rules. In traditional strategy, advantage comes from exploiting resources or stable market positions. In strategy as simple rules, advantage comes from successfully seizing fleeting opportunities. Key strategic processes, such as product innovation, partnering, or spinout creation, place the company where the flow of opportunities is greatest. Simple rules then provide the guidelines within which managers can pursue such opportunities. Simple rules, which grow out of experience, fall into five broad categories: how- to rules, boundary conditions, priority rules, timing rules, and exit rules. Companies with simple-rules strategies must follow the rules religiously and avoid the temptation to change them too frequently. A consistent strategy helps managers sort through opportunities and gain short-term advantage by exploiting the attractive ones. In stable markets, managers rely on complicated strategies built on detailed predictions of the future. But when business is complicated, strategy should be simple.

Crowding in the City: Losing and Winning Competitors of an Invasive Bird

PubMed Central

Hernández-Brito, Dailos; Carrete, Martina; Popa-Lisseanu, Ana G.; Ibáñez, Carlos; Tella, José L.

2014-01-01

Invasive species can take advantage of resources unexploited by natives (opportunism hypothesis) or they can exploit the same resources but more aggressively or efficiently (competition hypothesis), thus impacting native species. However, invasive species tend to exploit anthropogenic habitats that are inefficiently used by natives such as urban environments. Focusing on the ring-necked parakeet (Psittacula krameri), one of the most invasive birds worldwide, we combined observations of interspecific aggressions, species-specific cavity-nest preferences and the spatial distribution of the native cavity-nesting vertebrate community to determine the invasion process as well as its potential impacts on native species in a Mediterranean city. Our results support the competition hypothesis, suggesting that ring-necked parakeets are outcompeting native species sharing nest-site preferences. Parakeets initiated and won most interspecific aggressions, which were directed towards competitors but also towards predators. This behaviour could explain the spatial arrangement of natives, with most bird species breeding close to parakeets possibly to take advantage of their effective antipredatory behaviour. However, temporal and spatial patterns of segregation suggest that a threatened bat species is negatively affected by parakeets. This demonstrates that common species gain benefits and threatened ones (in this study, a bat and possibly a falcon) lose nest sites due to invaders. Therefore, the conservation status of the native species that pay the costs of competition with invaders should be considered. This scenario of winners and losers may, however, shift towards more losers if the ring-necked parakeet population continues to grow, thus requiring close monitoring and control/eradication programs to avoid further impacts. PMID:24945439

Crowding in the city: losing and winning competitors of an invasive bird.

PubMed

Hernández-Brito, Dailos; Carrete, Martina; Popa-Lisseanu, Ana G; Ibáñez, Carlos; Tella, José L

2014-01-01

Invasive species can take advantage of resources unexploited by natives (opportunism hypothesis) or they can exploit the same resources but more aggressively or efficiently (competition hypothesis), thus impacting native species. However, invasive species tend to exploit anthropogenic habitats that are inefficiently used by natives such as urban environments. Focusing on the ring-necked parakeet (Psittacula krameri), one of the most invasive birds worldwide, we combined observations of interspecific aggressions, species-specific cavity-nest preferences and the spatial distribution of the native cavity-nesting vertebrate community to determine the invasion process as well as its potential impacts on native species in a Mediterranean city. Our results support the competition hypothesis, suggesting that ring-necked parakeets are outcompeting native species sharing nest-site preferences. Parakeets initiated and won most interspecific aggressions, which were directed towards competitors but also towards predators. This behaviour could explain the spatial arrangement of natives, with most bird species breeding close to parakeets possibly to take advantage of their effective antipredatory behaviour. However, temporal and spatial patterns of segregation suggest that a threatened bat species is negatively affected by parakeets. This demonstrates that common species gain benefits and threatened ones (in this study, a bat and possibly a falcon) lose nest sites due to invaders. Therefore, the conservation status of the native species that pay the costs of competition with invaders should be considered. This scenario of winners and losers may, however, shift towards more losers if the ring-necked parakeet population continues to grow, thus requiring close monitoring and control/eradication programs to avoid further impacts.

Mind-Reading and Behavior-Reading against Agents with and without Anthropomorphic Features in a Competitive Situation

PubMed Central

Terada, Kazunori; Yamada, Seiji

2017-01-01

Humans use two distinct cognitive strategies separately to understand and predict other humans' behavior. One is mind-reading, in which an internal state such as an intention or an emotional state is assumed to be a source of a variety of behaviors. The other is behavior-reading, in which an actor's behavior is modeled based on stimulus-response associations without assuming internal states behind the behavior. We hypothesize that anthropomorphic features are key for an observer switching between these two cognitive strategies in a competitive situation. We provide support for this hypothesis through two studies using four agents with different appearances. We show that only a human agent was thought to possess both the ability to generate a variety of behaviors and internal mental states, such as minds and emotions (Study 1). We also show that humans used mixed (opposing) strategies against a human agent and exploitative strategies against the agents with mechanical appearances when they played a repeated zero-sum game (Study 2). Our findings show that humans understand that human behavior is varied; that humans have internal states, such as minds and emotions; that the behavior of machines is governed by a limited number of fixed rules; and that machines do not possess internal mental states. Our findings also suggest that the function of mind-reading is to trigger a strategy for use against agents with variable behavior and that humans exploit others who lack behavioral variability based on behavior-reading in a competitive situation. PMID:28736536

Human Freud-2/CC2D1B: a novel repressor of postsynaptic serotonin-1A receptor expression.

PubMed

Hadjighassem, Mahmoud R; Austin, Mark C; Szewczyk, Bernadeta; Daigle, Mireille; Stockmeier, Craig A; Albert, Paul R

2009-08-01

Altered expression of serotonin-1A (5-HT1A) receptors, both presynaptic in the raphe nuclei and post-synaptic in limbic and cortical target areas, has been implicated in mood disorders such as major depression and anxiety. Within the 5-HT1A receptor gene, a powerful dual repressor element (DRE) is regulated by two protein complexes: Freud-1/CC2D1A and a second, unknown repressor. Here we identify human Freud-2/CC2D1B, a Freud-1 homologue, as the second repressor. Freud-2 distribution was examined with Northern and Western blot, reverse transcriptase polymerase chain reaction, and immunohistochemistry/immunofluorescence; Freud-2 function was examined by electrophoretic mobility shift, reporter assay, and Western blot. Freud-2 RNA was widely distributed in brain and peripheral tissues. Freud-2 protein was enriched in the nuclear fraction of human prefrontal cortex and hippocampus but was weakly expressed in the dorsal raphe nucleus. Freud-2 immunostaining was co-localized with 5-HT1A receptors, neuronal and glial markers. In prefrontal cortex, Freud-2 was expressed at similar levels in control and depressed male subjects. Recombinant hFreud-2 protein bound specifically to 5' or 3' human DRE adjacent to the Freud-1 site. Human Freud-2 showed strong repressor activity at the human 5-HT1A or heterologous promoter in human HEK-293 5-HT1A-negative cells and neuronal SK-N-SH cells, a model of postsynaptic 5-HT1A receptor-positive cells. Furthermore, small interfering RNA knockdown of endogenous hFreud-2 expression de-repressed 5-HT1A promoter activity and increased levels of 5-HT1A receptor protein in SK-N-SH cells. Human Freud-2 binds to the 5-HT1A DRE and represses the human 5-HT1A receptor gene to regulate its expression in non-serotonergic cells and neurons.

Molecular dynamics studies of a DNA-binding protein: 2. An evaluation of implicit and explicit solvent models for the molecular dynamics simulation of the Escherichia coli trp repressor.

PubMed Central

Guenot, J.; Kollman, P. A.

1992-01-01

Although aqueous simulations with periodic boundary conditions more accurately describe protein dynamics than in vacuo simulations, these are computationally intensive for most proteins. Trp repressor dynamic simulations with a small water shell surrounding the starting model yield protein trajectories that are markedly improved over gas phase, yet computationally efficient. Explicit water in molecular dynamics simulations maintains surface exposure of protein hydrophilic atoms and burial of hydrophobic atoms by opposing the otherwise asymmetric protein-protein forces. This properly orients protein surface side chains, reduces protein fluctuations, and lowers the overall root mean square deviation from the crystal structure. For simulations with crystallographic waters only, a linear or sigmoidal distance-dependent dielectric yields a much better trajectory than does a constant dielectric model. As more water is added to the starting model, the differences between using distance-dependent and constant dielectric models becomes smaller, although the linear distance-dependent dielectric yields an average structure closer to the crystal structure than does a constant dielectric model. Multiplicative constants greater than one, for the linear distance-dependent dielectric simulations, produced trajectories that are progressively worse in describing trp repressor dynamics. Simulations of bovine pancreatic trypsin were used to ensure that the trp repressor results were not protein dependent and to explore the effect of the nonbonded cutoff on the distance-dependent and constant dielectric simulation models. The nonbonded cutoff markedly affected the constant but not distance-dependent dielectric bovine pancreatic trypsin inhibitor simulations. As with trp repressor, the distance-dependent dielectric model with a shell of water surrounding the protein produced a trajectory in better agreement with the crystal structure than a constant dielectric model, and the physical properties of the trajectory average structure, both with and without a nonbonded cutoff, were comparable. PMID:1304396

Adaptation to exploit nitrate in surface soils predisposes yellow-cedar to climate-induced decline while enhancing the survival of western redcedar: a new hypothesis

Treesearch

David V. D' Amore; Paul E. Hennon; Paul G. Schaberg; Gary J. Hawley

2009-01-01

Yellow-cedar (Chamaecyparis nootkatensis (D. Don) Spach) and western redcedar (Thuja plicata Donn), two valuable tree species of Pacific Northwest forests, are competitive in low productivity forests on wet, nearly saturated soils with low nitrogen (N) availability and turnover. We propose a mechanism where cedar trees survive in...

Beef cattle growing and backgrounding programs.

PubMed

Peel, Derrell S

2003-07-01

The stocker industry is one of many diverse production and marketing activities that make up the United States beef industry. The stocker industry is probably the least understood industry sector and yet it plays a vital role in helping the industry exploit its competitive advantage of using forage resources and providing an economical means of adjusting the timing and volume of cattle and meat in a complex market environment.

Solving the Traveling Salesman's Problem Using the African Buffalo Optimization.

PubMed

Odili, Julius Beneoluchi; Mohmad Kahar, Mohd Nizam

2016-01-01

This paper proposes the African Buffalo Optimization (ABO) which is a new metaheuristic algorithm that is derived from careful observation of the African buffalos, a species of wild cows, in the African forests and savannahs. This animal displays uncommon intelligence, strategic organizational skills, and exceptional navigational ingenuity in its traversal of the African landscape in search for food. The African Buffalo Optimization builds a mathematical model from the behavior of this animal and uses the model to solve 33 benchmark symmetric Traveling Salesman's Problem and six difficult asymmetric instances from the TSPLIB. This study shows that buffalos are able to ensure excellent exploration and exploitation of the search space through regular communication, cooperation, and good memory of its previous personal exploits as well as tapping from the herd's collective exploits. The results obtained by using the ABO to solve these TSP cases were benchmarked against the results obtained by using other popular algorithms. The results obtained using the African Buffalo Optimization algorithm are very competitive.

Solving the Traveling Salesman's Problem Using the African Buffalo Optimization

PubMed Central

Odili, Julius Beneoluchi; Mohmad Kahar, Mohd Nizam

2016-01-01

This paper proposes the African Buffalo Optimization (ABO) which is a new metaheuristic algorithm that is derived from careful observation of the African buffalos, a species of wild cows, in the African forests and savannahs. This animal displays uncommon intelligence, strategic organizational skills, and exceptional navigational ingenuity in its traversal of the African landscape in search for food. The African Buffalo Optimization builds a mathematical model from the behavior of this animal and uses the model to solve 33 benchmark symmetric Traveling Salesman's Problem and six difficult asymmetric instances from the TSPLIB. This study shows that buffalos are able to ensure excellent exploration and exploitation of the search space through regular communication, cooperation, and good memory of its previous personal exploits as well as tapping from the herd's collective exploits. The results obtained by using the ABO to solve these TSP cases were benchmarked against the results obtained by using other popular algorithms. The results obtained using the African Buffalo Optimization algorithm are very competitive. PMID:26880872

Intrasexual competition facilitates the evolution of alternative mating strategies in a colour polymorphic fish.

PubMed

Hurtado-Gonzales, Jorge L; Uy, J Albert C

2010-12-23

Intense competition for access to females can lead to males exploiting different components of sexual selection, and result in the evolution of alternative mating strategies (AMSs). Males of Poecilia parae, a colour polymorphic fish, exhibit five distinct phenotypes: drab-coloured (immaculata), striped (parae), structural-coloured (blue) and carotenoid-based red and yellow morphs. Previous work indicates that immaculata males employ a sneaker strategy, whereas the red and yellow morphs exploit female preferences for carotenoid-based colours. Mating strategies favouring the maintenance of the other morphs remain to be determined. Here, we report the role of agonistic male-male interactions in influencing female mating preferences and male mating success, and in facilitating the evolution of AMSs. Our study reveals variation in aggressiveness among P. parae morphs during indirect and direct interactions with sexually receptive females. Two morphs, parae and yellow, use aggression to enhance their mating success (i.e., number of copulations) by 1) directly monopolizing access to females, and 2) modifying female preferences after winning agonistic encounters. Conversely, we found that the success of the drab-coloured immaculata morph, which specializes in a sneak copulation strategy, relies in its ability to circumvent both male aggression and female choice when facing all but yellow males. Strong directional selection is expected to deplete genetic variation, yet many species show striking genetically-based polymorphisms. Most studies evoke frequency dependent selection to explain the persistence of such variation. Consistent with a growing body of evidence, our findings suggest that a complex form of balancing selection may alternatively explain the evolution and maintenance of AMSs in a colour polymorphic fish. In particular, this study demonstrates that intrasexual competition results in phenotypically distinct males exhibiting clear differences in their levels of aggression to exclude potential sexual rivals. By being dominant, the more aggressive males are able to circumvent female mating preferences for attractive males, whereas another male type incorporates subordinate behaviours that allow them to circumvent male aggression and female mating preferences. Together, these and previous results indicate that exploiting different aspects of social interactions may allow males to evolve distinct mating strategies and thus the long term maintenance of polymorphisms within populations.

Biodiversity loss in seagrass meadows due to local invertebrate fisheries and harbour activities

NASA Astrophysics Data System (ADS)

Nordlund, Lina Mtwana; Gullström, Martin

2013-12-01

Seagrass meadows provide a wide variety of ecosystem services, but their distribution and health are adversely affected by man. In the present study, we examined the influence of coastal exploitation in terms of invertebrate harvesting and harbour activity on invertebrate community composition in subtropical seagrass meadows at Inhaca Island, Mozambique, in the Western Indian Ocean. There was a fivefold higher invertebrate density and biomass, and clearly higher invertebrate species richness, in the protected (control) site compared to the two exploited sites. The causes for the clear differences between protected and exploited sites were probably a result of (1) the directional outtake of large edible or saleable invertebrates (mostly molluscs) and the absence of boat traffic in the harvested site, and (2) harbour activities. Invertebrate community composition in the two exploited sites also differed (although less clear), which was likely due to inherent distinction in type of disturbance. Our findings revealed that protection of seagrass habitat is necessary and that disturbances of different origin might require different forms of management and conservation. Designing protected areas is however a complex process due to competition for use and space with activities such as invertebrate harvesting and harbours.

Population ecology of turbot and brill: What can we learn from two rare flatfish species?

NASA Astrophysics Data System (ADS)

van der Hammen, Tessa; Poos, Jan Jaap; van Overzee, Harriët M. J.; Heessen, Henk J. L.; Magnusson, Arni; Rijnsdorp, Adriaan D.

2013-11-01

Turbot and brill are widely distributed in the Northeast Atlantic but occur at low abundance. They are ecologically very similar and closely related. The low abundance and the similarities make them particularly interesting to study the population dynamics because it raises the questions how the populations can sustain themselves at low abundances and how turbot and brill avoid strong interspecific competition. Knowledge of both species is hampered by lack of analysed data. The main objective of this study is therefore to increase the knowledge of turbot and brill and in particular to compare the two species in order to address the above questions. Based on biological samples collected in the North Sea, we calculated seasonal von Bertalanffy growth parameters, maturity ogives, monthly gonado-somatic indices (GSI) and condition factors (Fulton's K) and indices of inter- and intraspecific mean crowding and compared the results for turbot and brill. The main differences between the two species were found in their spawning period, with brill having a more protracted spawning period. Brill also showed an earlier peak in their GSI values, suggesting an earlier start of their spawning period. The mean crowding showed that interspecific competition was lower than intraspecific competition. The exploitation pattern was also studied. Turbot and brill are exploited as a bycatch species in the mixed demersal fishery. We found that productivity is highest in areas where the maximum temperature is close to the optimal temperature for growth (16-18 °C) and landings decrease where salinity falls below ~ 5 psu (turbot) and ~ 15 psu (brill). Recent fishing mortality rates of North Sea turbot are around 0.5-0.7, but there is no indication that recruitment is impaired at low levels of spawning stock biomass. We conclude that although both species have similar ecological characteristics, differences may reduce inter-specific competition.

The Role of Retinal Determination Gene Network (RDGN) in Hormone Signaling Transduction and Prostate Tumorigenesis

DTIC Science & Technology

2012-10-01

support with our hypothesis, expressions of AR co-repressors (48-50), HDAC1, HDAC3 or SirT1 inhibit the ligand-induced AR activation at different...signaling and androgen-dependent growth. We hypothesis that DACH1/Six1/Eya pathway is an endogenous regulator of AR trans- activation and contributes to...mechanism. Inhibitory function of Eya1 on AR transactivation required a phosphates activity and could be enhanced by ectopic expression of co-repressors

The effects of competition on premiums: using United Healthcare's 2015 entry into Affordable Care Act's marketplaces as an instrumental variable.

PubMed

Agirdas, Cagdas; Krebs, Robert J; Yano, Masato

2018-01-08

One goal of the Affordable Care Act is to increase insurance coverage by improving competition and lowering premiums. To facilitate this goal, the federal government enacted online marketplaces in the 395 rating areas spanning 34 states that chose not to establish their own state-run marketplaces. Few multivariate regression studies analyzing the effects of competition on premiums suffer from endogeneity, due to simultaneity and omitted variable biases. However, United Healthcare's decision to enter these marketplaces in 2015 provides the researcher with an opportunity to address this endogeneity problem. Exploiting the variation caused by United Healthcare's entry decision as an instrument for competition, we study the impact of competition on premiums during the first 2 years of these marketplaces. Combining panel data from five different sources and controlling for 12 variables, we find that one more insurer in a rating area leads to a 6.97% reduction in the second-lowest-priced silver plan premium, which is larger than the estimated effects in existing literature. Furthermore, we run a threshold analysis and find that competition's effects on premiums become statistically insignificant if there are four or more insurers in a rating area. These findings are robust to alternative measures of premiums, inclusion of a non-linear term in the regression models and a county-level analysis.

Stochastic model of template-directed elongation processes in biology.

PubMed

Schilstra, Maria J; Nehaniv, Chrystopher L

2010-10-01

We present a novel modular, stochastic model for biological template-based linear chain elongation processes. In this model, elongation complexes (ECs; DNA polymerase, RNA polymerase, or ribosomes associated with nascent chains) that span a finite number of template units step along the template, one after another, with semaphore constructs preventing overtaking. The central elongation module is readily extended with modules that represent initiation and termination processes. The model was used to explore the effect of EC span on motor velocity and dispersion, and the effect of initiation activator and repressor binding kinetics on the overall elongation dynamics. The results demonstrate that (1) motors that move smoothly are able to travel at a greater velocity and closer together than motors that move more erratically, and (2) the rate at which completed chains are released is proportional to the occupancy or vacancy of activator or repressor binding sites only when initiation or activator/repressor dissociation is slow in comparison with elongation. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Pirating conserved phage mechanisms promotes promiscuous staphylococcal pathogenicity island transfer.

PubMed

Bowring, Janine; Neamah, Maan M; Donderis, Jorge; Mir-Sanchis, Ignacio; Alite, Christian; Ciges-Tomas, J Rafael; Maiques, Elisa; Medmedov, Iltyar; Marina, Alberto; Penadés, José R

2017-08-08

Targeting conserved and essential processes is a successful strategy to combat enemies. Remarkably, the clinically important Staphylococcus aureus pathogenicity islands (SaPIs) use this tactic to spread in nature. SaPIs reside passively in the host chromosome, under the control of the SaPI-encoded master repressor, Stl. It has been assumed that SaPI de-repression is effected by specific phage proteins that bind to Stl, initiating the SaPI cycle. Different SaPIs encode different Stl repressors, so each targets a specific phage protein for its de-repression. Broadening this narrow vision, we report here that SaPIs ensure their promiscuous transfer by targeting conserved phage mechanisms. This is accomplished because the SaPI Stl repressors have acquired different domains to interact with unrelated proteins, encoded by different phages, but in all cases performing the same conserved function. This elegant strategy allows intra- and inter-generic SaPI transfer, highlighting these elements as one of nature's most fascinating subcellular parasites.

Does Information Matter? Competition, Quality, and the Impact of Nursing Home Report Cards

PubMed Central

Grabowski, David C; Town, Robert J

2011-01-01

Objective We evaluate the effects of the Nursing Home Quality Initiative (NHQI), which introduced quality measures to the Centers for Medicare and Medicaid Services' Nursing Home Compare website, on facility performance and consumer demand for services. Data Sources The nursing home Minimum Data Set facility reports from 1999 to 2005 merged with facility-level data from the On-Line Survey, Certification, and Reporting System. Study Design We rely on the staggered rollout of the report cards across pilot and nonpilot states to examine the effect of report cards on market share and quality of care. We also exploit differences in nursing home market competition at baseline to identify the impacts of the new information on nursing home quality. Results The introduction of the NHQI was generally unrelated to facility quality and consumer demand. However, nursing homes facing greater competition improved their quality more than facilities in less competitive markets. Conclusions The lack of competition in many nursing home markets may help to explain why the NHQI report card effort had a minimal effect on nursing home quality. With the introduction of market-based reforms such as report cards, this result suggests policy makers must also consider market structure in efforts to improve nursing home performance. PMID:21790590

Evolutionarily stable range limits set by interspecific competition.

PubMed

Price, Trevor D; Kirkpatrick, Mark

2009-04-22

A combination of abiotic and biotic factors probably restricts the range of many species. Recent evolutionary models and tests of those models have asked how a gradual change in environmental conditions can set the range limit, with a prominent idea being that gene flow disrupts local adaptation. We investigate how biotic factors, explicitly competition for limited resources, result in evolutionarily stable range limits even in the absence of the disruptive effect of gene flow. We model two competing species occupying different segments of the resource spectrum. If one segment of the resource spectrum declines across space, a species that specializes on that segment can be driven to extinction, even though in the absence of competition it would evolve to exploit other abundant resources and so be saved. The result is that a species range limit is set in both evolutionary and ecological time, as the resources associated with its niche decline. Factors promoting this outcome include: (i) inherent gaps in the resource distribution, (ii) relatively high fitness of the species when in its own niche, and low fitness in the alternative niche, even when resource abundances are similar in each niche, (iii) strong interspecific competition, and (iv) asymmetric interspecific competition. We suggest that these features are likely to be common in multispecies communities, thereby setting evolutionarily stable range limits.

Evolutionarily stable range limits set by interspecific competition

PubMed Central

Price, Trevor D.; Kirkpatrick, Mark

2009-01-01

A combination of abiotic and biotic factors probably restricts the range of many species. Recent evolutionary models and tests of those models have asked how a gradual change in environmental conditions can set the range limit, with a prominent idea being that gene flow disrupts local adaptation. We investigate how biotic factors, explicitly competition for limited resources, result in evolutionarily stable range limits even in the absence of the disruptive effect of gene flow. We model two competing species occupying different segments of the resource spectrum. If one segment of the resource spectrum declines across space, a species that specializes on that segment can be driven to extinction, even though in the absence of competition it would evolve to exploit other abundant resources and so be saved. The result is that a species range limit is set in both evolutionary and ecological time, as the resources associated with its niche decline. Factors promoting this outcome include: (i) inherent gaps in the resource distribution, (ii) relatively high fitness of the species when in its own niche, and low fitness in the alternative niche, even when resource abundances are similar in each niche, (iii) strong interspecific competition, and (iv) asymmetric interspecific competition. We suggest that these features are likely to be common in multispecies communities, thereby setting evolutionarily stable range limits. PMID:19324813

Does information matter? Competition, quality, and the impact of nursing home report cards.

PubMed

Grabowski, David C; Town, Robert J

2011-12-01

We evaluate the effects of the Nursing Home Quality Initiative (NHQI), which introduced quality measures to the Centers for Medicare and Medicaid Services' Nursing Home Compare website, on facility performance and consumer demand for services. The nursing home Minimum Data Set facility reports from 1999 to 2005 merged with facility-level data from the On-Line Survey, Certification, and Reporting System. We rely on the staggered rollout of the report cards across pilot and nonpilot states to examine the effect of report cards on market share and quality of care. We also exploit differences in nursing home market competition at baseline to identify the impacts of the new information on nursing home quality. The introduction of the NHQI was generally unrelated to facility quality and consumer demand. However, nursing homes facing greater competition improved their quality more than facilities in less competitive markets. The lack of competition in many nursing home markets may help to explain why the NHQI report card effort had a minimal effect on nursing home quality. With the introduction of market-based reforms such as report cards, this result suggests policy makers must also consider market structure in efforts to improve nursing home performance. © Health Research and Educational Trust.

Cyclin B Translation Depends on mTOR Activity after Fertilization in Sea Urchin Embryos

PubMed Central

Boulben, Sandrine; Glippa, Virginie; Morales, Julia; Cormier, Patrick

2016-01-01

The cyclin B/CDK1 complex is a key regulator of mitotic entry. Using PP242, a specific ATP-competitive inhibitor of mTOR kinase, we provide evidence that the mTOR signalling pathway controls cyclin B mRNA translation following fertilization in Sphaerechinus granularis and Paracentrotus lividus. We show that PP242 inhibits the degradation of the cap-dependent translation repressor 4E-BP (eukaryotic initiation factor 4E-Binding Protein). PP242 inhibits global protein synthesis, delays cyclin B accumulation, cyclin B/CDK1 complex activation and consequently entry into the mitotic phase of the cell cycle triggered by fertilization. PP242 inhibits cyclin B mRNA recruitment into active polysomes triggered by fertilization. An amount of cyclin B mRNA present in active polysomes appears to be insensitive to PP242 treatment. Taken together, our results suggest that, following sea urchin egg fertilization, cyclin B mRNA translation is controlled by two independent mechanisms: a PP242-sensitive and an additional PP242-insentitive mechanism. PMID:26962866

Regulated Formation of lncRNA-DNA Hybrids Enables Faster Transcriptional Induction and Environmental Adaptation.

PubMed

Cloutier, Sara C; Wang, Siwen; Ma, Wai Kit; Al Husini, Nadra; Dhoondia, Zuzer; Ansari, Athar; Pascuzzi, Pete E; Tran, Elizabeth J

2016-02-04

Long non-coding (lnc)RNAs, once thought to merely represent noise from imprecise transcription initiation, have now emerged as major regulatory entities in all eukaryotes. In contrast to the rapidly expanding identification of individual lncRNAs, mechanistic characterization has lagged behind. Here we provide evidence that the GAL lncRNAs in the budding yeast S. cerevisiae promote transcriptional induction in trans by formation of lncRNA-DNA hybrids or R-loops. The evolutionarily conserved RNA helicase Dbp2 regulates formation of these R-loops as genomic deletion or nuclear depletion results in accumulation of these structures across the GAL cluster gene promoters and coding regions. Enhanced transcriptional induction is manifested by lncRNA-dependent displacement of the Cyc8 co-repressor and subsequent gene looping, suggesting that these lncRNAs promote induction by altering chromatin architecture. Moreover, the GAL lncRNAs confer a competitive fitness advantage to yeast cells because expression of these non-coding molecules correlates with faster adaptation in response to an environmental switch. Copyright © 2016 Elsevier Inc. All rights reserved.

Identification and characterization of cell-specific enhancer elements for the mouse ETF/Tead2 gene.

PubMed

Tanoue, Y; Yasunami, M; Suzuki, K; Ohkubo, H

2001-12-21

We have identified and characterized by transient transfection assays the cell-specific 117-bp enhancer sequence in the first intron of the mouse ETF (Embryonic TEA domain-containing factor)/Tead2 gene required for transcriptional activation in ETF/Tead2 gene-expressing cells, such as P19 cells. The 117-bp enhancer contains one GC-rich sequence (5'-GGGGCGGGG-3'), termed the GC box, and two tandemly repeated GA-rich sequences (5'-GGGGGAGGGG-3'), termed the proximal and distal GA elements. Further analyses, including transfection studies and electrophoretic mobility shift assays using a series of deletion and mutation constructs, indicated that Sp1, a putative activator, may be required to predominate over its competition with another unknown putative repressor, termed the GA element-binding factor, for binding to both the GC box, which overlapped with the proximal GA element, and the distal GA element in the 117-bp sequence in order to achieve a full enhancer activity. We also discuss a possible mechanism underlying the cell-specific enhancer activity of the 117-bp sequence.

The Arabidopsis RING-Type E3 Ligase TEAR1 Controls Leaf Development by Targeting the TIE1 Transcriptional Repressor for Degradation[OPEN

PubMed Central

Zhang, Jinzhe; Wei, Baoye; Yuan, Rongrong; Yu, Hao

2017-01-01

The developmental plasticity of leaf size and shape is important for leaf function and plant survival. However, the mechanisms by which plants form diverse leaves in response to environmental conditions are not well understood. Here, we identified TIE1-ASSOCIATED RING-TYPE E3 LIGASE1 (TEAR1) and found that it regulates leaf development by promoting the degradation of TCP INTERACTOR-CONTAINING EAR MOTIF PROTEIN1 (TIE1), an important repressor of CINCINNATA (CIN)-like TEOSINTE BRANCHED1/CYCLOIDEA/PCF (TCP) transcription factors, which are key for leaf development. TEAR1 contains a typical C3H2C3-type RING domain and has E3 ligase activity. We show that TEAR1 interacts with the TCP repressor TIE1, which is ubiquitinated in vivo and degraded by the 26S proteasome system. We demonstrate that TEAR1 is colocalized with TIE1 in nuclei and negatively regulates TIE1 protein levels. Overexpression of TEAR1 rescued leaf defects caused by TIE1 overexpression, whereas disruption of TEAR1 resulted in leaf phenotypes resembling those caused by TIE1 overexpression or TCP dysfunction. Deficiency in TEAR partially rescued the leaf defects of TCP4 overexpression line and enhanced the wavy leaf phenotypes of jaw-5D. We propose that TEAR1 positively regulates CIN-like TCP activity to promote leaf development by mediating the degradation of the TCP repressor TIE1. PMID:28100709

The transcription repressor, ZEB1, cooperates with CtBP2 and HDAC1 to suppress IL-2 gene activation in T cells.

PubMed

Wang, Jun; Lee, Seungsoo; Teh, Charis En-Yi; Bunting, Karen; Ma, Lina; Shannon, M Frances

2009-03-01

Activation of T cells leads to the induction of many cytokine genes that are required for appropriate immune responses, including IL-2, a key cytokine for T cell proliferation and homeostasis. The activating transcription factors such as nuclear factor of activated T cells, nuclear factor kappaB/Rel and activated protein-1 family members that regulate inducible IL-2 gene expression have been well documented. However, negative regulation of the IL-2 gene is less studied. Here we examine the role of zinc finger E-box-binding protein (ZEB) 1, a homeodomain/Zn finger transcription factor, as a repressor of IL-2 gene transcription. We show here that ZEB1 is expressed in non-stimulated and stimulated T cells and using chromatin immunoprecipitation assays we show that ZEB1 binds to the IL-2 promoter. Over-expression of ZEB1 can repress IL-2 promoter activity, as well as endogenous IL-2 mRNA production in EL-4 T cells, and this repression is dependent on the ZEB-binding site at -100. ZEB1 cooperates with the co-repressor C-terminal-binding protein (CtBP) 2 and with histone deacetylase 1 to repress the IL-2 promoter and this cooperation depends on the ZEB-binding site in the promoter as well as the Pro-X-Asp-Leu-Ser protein-protein interaction domain in CtBP2. Thus, ZEB1 may function to recruit a repressor complex to the IL-2 promoter.

Ski co-repressor complexes maintain the basal repressed state of the TGF-beta target gene, SMAD7, via HDAC3 and PRMT5.

PubMed

Tabata, Takanori; Kokura, Kenji; Ten Dijke, Peter; Ishii, Shunsuke

2009-01-01

The products encoded by ski and its related gene, sno, (Ski and Sno) act as transcriptional co-repressors and interact with other co-repressors such as N-CoR/SMRT and mSin3A. Ski and Sno mediate transcriptional repression by various repressors, including Mad, Rb and Gli3. Ski/Sno also suppress transcription induced by multiple activators, such as Smads and c-Myb. In particular, the inhibition of TGF-beta-induced transcription by binding to Smads is correlated with the oncogenic activity of Ski and Sno. However, the molecular mechanism by which Ski and Sno mediate transcriptional repression remains unknown. In this study, we report the purification and characterization of Ski complexes. The Ski complexes purified from HeLa cells contained histone deacetylase 3 (HDAC3) and protein arginine methyltransferase 5 (PRMT5), in addition to multiple Smad proteins (Smad2, Smad3 and Smad4). Chromatin immunoprecipitation assays indicated that these components of the Ski complexes were localized on the SMAD7 gene promoter, which is the TGF-beta target gene, in TGF-beta-untreated HepG2 cells. Knockdown of these components using siRNA led to up-regulation of SMAD7 mRNA. These results indicate that Ski complexes serve to maintain a TGF-beta-responsive promoter at a repressed basal level via the activities of histone deacetylase and histone arginine methyltransferase.

Direct Role for the Rpd3 Complex in Transcriptional Induction of the Anaerobic DAN/TIR Genes in Yeast▿‡

PubMed Central

Sertil, Odeniel; Vemula, Arvind; Salmon, Sharon L.; Morse, Randall H.; Lowry, Charles V.

2007-01-01

Saccharomyces cerevisiae adapts to hypoxia by expressing a large group of “anaerobic” genes. Among these, the eight DAN/TIR genes are regulated by the repressors Rox1 and Mot3 and the activator Upc2/Mox4. In attempting to identify factors recruited by the DNA binding repressor Mot3 to enhance repression of the DAN/TIR genes, we found that the histone deacetylase and global repressor complex, Rpd3-Sin3-Sap30, was not required for repression. Strikingly, the complex was instead required for activation. In addition, the histone H3 and H4 amino termini, which are targets of Rpd3, were also required for DAN1 expression. Epistasis tests demonstrated that the Rpd3 complex is not required in the absence of the repressor Mot3. Furthermore, the Rpd3 complex was required for normal function and stable binding of the activator Upc2 at the DAN1 promoter. Moreover, the Swi/Snf chromatin remodeling complex was strongly required for activation of DAN1, and chromatin immunoprecipitation analysis showed an Rpd3-dependent reduction in DAN1 promoter-associated nucleosomes upon induction. Taken together, these data provide evidence that during anaerobiosis, the Rpd3 complex acts at the DAN1 promoter to antagonize the chromatin-mediated repression caused by Mot3 and Rox1 and that chromatin remodeling by Swi/Snf is necessary for normal expression. PMID:17210643

[Challenge prevention. From curative to preventive medicine-strategic and operational challenges].

PubMed

Schönermark, M P; Greif, K

2008-04-01

The potentials of preventive medicine to reduce the costs of illness have been inadequately exploited to date. Even if there is still massive dissent regarding the legal setup of a prevention law, prevention should play a significantly higher role in practice. Clinicians and practitioners could use preventive medicine as another differentiating factor in the increasingly competitive healthcare field. Prevention as a new strategic business segment allows a directed reaction to the demands of the payment system and opens up enormous value-added potential at the same time. Those who seize the chance to integrate prevention into their medical services portfolio and into the structure and processes of their respective hospitals will develop an important competitive advantage for the future.

Evidence that the Dictyostelium Dd-STATa protein is a repressor that regulates commitment to stalk cell differentiation and is also required for efficient chemotaxis.

PubMed

Mohanty, S; Jermyn, K A; Early, A; Kawata, T; Aubry, L; Ceccarelli, A; Schaap, P; Williams, J G; Firtel, R A

1999-08-01

Dd-STATa is a structural and functional homologue of the metazoan STAT (Signal Transducer and Activator of Transcription) proteins. We show that Dd-STATa null cells exhibit several distinct developmental phenotypes. The aggregation of Dd-STATa null cells is delayed and they chemotax slowly to a cyclic AMP source, suggesting a role for Dd-STATa in these early processes. In Dd-STATa null strains, slug-like structures are formed but they have an aberrant pattern of gene expression. In such slugs, ecmB/lacZ, a marker that is normally specific for cells on the stalk cell differentiation pathway, is expressed throughout the prestalk region. Stalk cell differentiation in Dictyostelium has been proposed to be under negative control, mediated by repressor elements present in the promoters of stalk cell-specific genes. Dd-STATa binds these repressor elements in vitro and the ectopic expression of ecmB/lacZ in the null strain provides in vivo evidence that Dd-STATa is the repressor protein that regulates commitment to stalk cell differentiation. Dd-STATa null cells display aberrant behavior in a monolayer assay wherein stalk cell differentiation is induced using the stalk cell morphogen DIF. The ecmB gene, a general marker for stalk cell differentiation, is greatly overinduced by DIF in Dd-STATa null cells. Also, Dd-STATa null cells are hypersensitive to DIF for expression of ST/lacZ, a marker for the earliest stages in the differentiation of one of the stalk cell sub-types. We suggest that both these manifestations of DIF hypersensitivity in the null strain result from the balance between activation and repression of the promoter elements being tipped in favor of activation when the repressor is absent. Paradoxically, although Dd-STATa null cells are hypersensitive to the inducing effects of DIF and readily form stalk cells in monolayer assay, the Dd-STATa null cells show little or no terminal stalk cell differentiation within the slug. Dd-STATa null slugs remain developmentally arrested for several days before forming very small spore masses supported by a column of apparently undifferentiated cells. Thus, complete stalk cell differentiation appears to require at least two events: a commitment step, whereby the repression exerted by Dd-STATa is lifted, and a second step that is blocked in a Dd-STATa null organism. This latter step may involve extracellular cAMP, a known repressor of stalk cell differentiation, because Dd-STATa null cells are abnormally sensitive to the inhibitory effects of extracellular cyclic AMP.

Successful Establishment of Plasmids R1 and pMV158 in a New Host Requires the Relief of the Transcriptional Repression of Their Essential rep Genes

PubMed Central

Ruiz-Masó, José Á.; Luengo, Luis M.; Moreno-Córdoba, Inmaculada; Díaz-Orejas, Ramón; del Solar, Gloria

2017-01-01

Although differing in size, encoded traits, host range, and replication mechanism, both narrow-host-range theta-type conjugative enterobacterial plasmid R1 and promiscuous rolling-circle-type mobilizable streptococcal plasmid pMV158 encode a transcriptional repressor protein, namely CopB in R1 and CopG in pMV158, involved in replication control. The gene encoding CopB or CopG is cotranscribed with a downstream gene that encodes the replication initiator Rep protein of the corresponding plasmid. However, whereas CopG is an auto-repressor that inhibits transcription of the entire copG-repB operon, CopB is expressed constitutively and represses a second, downstream promoter that directs transcription of repA. As a consequence of the distinct regulatory pathways implied by CopB and CopG, these repressor proteins play a different role in control of plasmid replication during the steady state: while CopB has an auxiliary role by keeping repressed the regulated promoter whenever the plasmid copy number is above a low threshold, CopG plays a primary role by acting coordinately with RNAII. Here, we have studied the role of the regulatory circuit mediated by these transcriptional repressors during the establishment of these two plasmids in a new host cell, and found that excess Cop repressor molecules in the recipient cell result in a severe decrease in the frequency and/or the velocity of appearance of transformant colonies for the cognate plasmid but not for unrelated plasmids. Using the pMV158 replicon as a model system, together with highly sensitive real-time qPCR and inverse PCR methods, we have also analyzed the effect of CopG on the kinetics of repopulation of the plasmid in Streptococcus pneumoniae. We show that, whereas in the absence of CopG pMV158 repopulation occurs mainly during the first 45 min following plasmid transfer, the presence of the transcriptional repressor in the recipient cell severely impairs the replicon repopulation and makes the plasmid replicate at approximately the same rate as the chromosome at any time after transformation, which results in maximal plasmid loss rate in the absence of selection. Overall, these findings indicate that unrepressed activity of the Cop-regulated promoter is crucial for the successful colonization of the recipient bacterial cells by the plasmid. PMID:29250051

Strategic alliance as a competitive tactics for biological-pharmacy industry.

PubMed

Liu, Chuanming; Wang, Ling; Qi, Ershi

2005-01-01

Biological-pharmacy industry refers to biotechnology companies and pharmacy makers. Because of the uncertainty and time-lag in the field of biological-pharmacy, the former is confronted with lacking of capital and the later is faced with improving technique-innovation and product-exploitation. This paper analyzes basic operation principle of strategic alliance, and related strategies are also put forward for biological-pharmacy enterprise to carry out.

The Role of Social Science Research Institutes in the Formulation and Execution of Soviet Foreign Policy

DTIC Science & Technology

1976-03-01

L FOREWORD In the long-term global competition between capitalism and socialism, the Soviet union designs and implements complex strategies which...successful communist resolution of the struggle by exploiting Soviet opportunities and Western vulnerabilities. Such complex strategies, involving as they...fact, a subject of controversy among Soviet theoreticians, the CPSU’s leading theoretical journal, Kommunist, has explained its appli - cation thus

Changes in interacting species with disturbance

NASA Astrophysics Data System (ADS)

Cole, Glen F.

1987-03-01

Human-influenced changes in the diversity and abundance of native wildlife in a southern boreal forest area, which became a national park in 1975, are used to develop working hypotheses for predicting and subsequently measuring the effects of disturbance or restoration programs on groups of interacting species. Changes from presettlement conditions began with early 1900 hunting, which eliminated woodland caribou ( Rangifer tarandus) and elk ( Cervus elaphus), and reduced moose ( Alces alces) to the low numbers which still persist. Increases in white-tailed deer ( Odocoileus virginianus), as these other cervid species became less abundant or absent, provided enough alternative food to sustain the system's carnivores until plant succession on previously burned or logged areas also caused deer to decline. With increased competition for reduced food, carnivore species also became less abundant or absent and overexploited some prey populations. The abilities of interacting species to maintain dynamically stable populations or persist varied with their different capacities to compensate for increased exploitation or competition. These relationships suggested a possible solution to the problem of predicting the stability of populations in disturbed systems. For the 1976 1985 period, a hypothesis that the increased protection of wildlife from exploitation in a national park would restore a more diverse, abundant, and productive fauna had to be rejected.

From metabolism to ecology: cross-feeding interactions shape the balance between polymicrobial conflict and mutualism

PubMed Central

Estrela, Sylvie; Trisos, Christopher H.; Brown, Sam P.

2012-01-01

Polymicrobial interactions are widespread in nature, and play a major role in maintaining human health and ecosystems. Whenever one organism uses metabolites produced by another organism as energy or nutrient sources, this is called cross-feeding. The ecological outcomes of cross-feeding interactions are poorly understood and potentially diverse: mutualism, competition, exploitation or commensalism. A major reason for this uncertainty is the lack of theoretical approaches linking microbial metabolism to microbial ecology. To address this issue, we explore the dynamics of a one-way interspecific cross-feeding interaction, in which food can be traded for a service (detoxification). Our results show that diverse ecological interactions (competition, mutualism, exploitation) can emerge from this simple cross-feeding interaction, and can be predicted by the metabolic, demographic and environmental parameters that govern the balance of the costs and benefits of association. In particular, our model predicts stronger mutualism for intermediate by-product toxicity because the resource-service exchange is constrained to the service being neither too vital (high toxicity impairs resource provision) nor dispensable (low toxicity reduces need for service). These results support the idea that bridging microbial ecology and metabolism is a critical step towards a better understanding of the factors governing the emergence and dynamics of polymicrobial interactions. PMID:23070318

Maximizing commonality between military and general aviation fly-by-light helicopter system designs

NASA Astrophysics Data System (ADS)

Enns, Russell; Mossman, David C.

1995-05-01

In the face of shrinking defense budgets, survival of the United States rotorcraft industry is becoming increasingly dependent on increased sales in a highly competitive civil helicopter market. As a result, only the most competitive rotorcraft manufacturers are likely to survive. A key ingredient in improving our competitive position is the ability to produce more versatile, high performance, high quality, and low cost of ownership helicopters. Fiber optic technology offers a path of achieving these objectives. Also, adopting common components and architectures for different helicopter models (while maintaining each models' uniqueness) will further decrease design and production costs. Funds saved (or generated) by exploiting this commonality can be applied to R&D used to further improve the product. In this paper, we define a fiber optics based avionics architecture which provides the pilot a fly-by-light / digital flight control system which can be implemented in both civilian and military helicopters. We then discuss the advantages of such an architecture.

SatR Is a Repressor of Fluoroquinolone Efflux Pump SatAB

PubMed Central

Escudero, Jose Antonio; San Millan, Alvaro; Montero, Natalia; Gutierrez, Belen; Ovejero, Cristina Martinez; Carrilero, Laura

2013-01-01

Streptococcus suis is an emerging zoonotic agent responsible for high-mortality outbreaks among the human population in China. In this species, the ABC transporter SatAB mediates fluoroquinolone resistance when overexpressed. Here, we describe and characterize satR, an open reading frame (ORF) encoding a MarR superfamily regulator that acts as a repressor of satAB. satR is cotranscribed with satAB, and its interruption entails the overexpression of the pump, leading to a clinically relevant increase in resistance to fluoroquinolones. PMID:23650171

Tropical forests are non-equilibrium ecosystems governed by interspecific competition based on universal 1/6 niche width.

PubMed

Fort, Hugo; Inchausti, Pablo

2013-01-01

Tropical forests are mega-diverse ecosystems that display complex and non-equilibrium dynamics. However, theoretical approaches have largely focused on explaining steady-state behaviour and fitting snapshots of data. Here we show that local and niche interspecific competition can realistically and parsimoniously explain the observed non-equilibrium regime of permanent plots of nine tropical forests, in eight different countries. Our spatially-explicit model, besides predicting with accuracy the main biodiversity metrics for these plots, can also reproduce their dynamics. A central finding is that tropical tree species have a universal niche width of approximately 1/6 of the niche axis that echoes the observed widespread convergence in their functional traits enabling them to exploit similar resources and to coexist despite of having large niche overlap. This niche width yields an average ratio of 0.25 between interspecific and intraspecific competition that corresponds to an intermediate value between the extreme claims of the neutral model and the classical niche-based model of community assembly (where interspecific competition is dominant). In addition, our model can explain and yield observed spatial patterns that classical niche-based and neutral theories cannot.

Academic health centers on the front lines: survival strategies in highly competitive markets.

PubMed

Blumenthal, D; Weissman, J S; Griner, P F

1999-09-01

The authors describe approaches that five academic health centers (AHCs) have taken to reduce costs, enhance quality, or improve their market positions since the onset of price competition and managed care. The five AHCs, all on the West Coast, were selected for study because they (1) are located in markets that had been highly competitive for the longest time; (2) are committed to all the major missions of AHCs; and (3) own or substantially control their major clinical teaching facilities. The study findings reflect the status of the five AHCs during the fall of 1998. Although some findings may no longer be current (especially in light of ongoing implementation of the Balanced Budget Act of 1997), they still provide insights into the options and opportunities available to many AHCs in highly competitive markets. The authors report on the institutions' financial viability (positive), levels of government support (advantageous), and competition from other AHCs (modest). They outline the study AHCs' survival strategies in three broad areas: increasing revenues via exploiting market niches, reducing costs, and reorganizing to improve internal governance and decision making. They also report how marketplace competition and the strategies the AHCs used to confront it have affected the AHCs' missions. The authors summarize the outstanding lessons that all AHCs can learn from the experiences of the AHCs studied, although adding that AHCs in other parts of the country should use caution in looking to the West Coast AHCs for answers.

Dissemination and exploitation - how to stand out in the information jungle

NASA Astrophysics Data System (ADS)

Walter, Sylvia

2017-04-01

EU projects are aiming on research and innovation, fostering competitiveness and growth. For the EU it is therefore essential to convert the public investment into socio-economic benefits for the society, i.e. economy and citizens. This is reflected in the obligation of participants to exploit and disseminate the outcome of their projects, which means to use and communicate results and multiply the benefit of investments. But how to do this efficiently and effectively in a world, which is more and more overloaded with information? Which audiences should be addressed and how to reach them? How to disseminate to an audience, which is "not in the field" of the research subject? And even more important: How to exploit the outcome of your project? H2020 work programmes explicitly specify that a draft "Plan for Exploitation and Dissemination of Results" should be included in a proposal, which force participants to think about presentation and use of results before they have them and to ensure that a project will benefit right from the beginning. This presentation will deal with the challenge of being visible as a consortium and the problem of having clear-sighted visions of how to spread and use results before the results have been achieved.

Eukaryotic translation initiator protein 1A isoform, CCS-3, enhances the transcriptional repression of p21CIP1 by proto-oncogene FBI-1 (Pokemon/ZBTB7A).

PubMed

Choi, Won-Il; Kim, Youngsoo; Kim, Yuri; Yu, Mi-young; Park, Jungeun; Lee, Choong-Eun; Jeon, Bu-Nam; Koh, Dong-In; Hur, Man-Wook

2009-01-01

FBI-1, a member of the POK (POZ and Kruppel) family of transcription factors, plays a role in differentiation, oncogenesis, and adipogenesis. eEF1A is a eukaryotic translation elongation factor involved in several cellular processes including embryogenesis, oncogenic transformation, cell proliferation, and cytoskeletal organization. CCS-3, a potential cervical cancer suppressor, is an isoform of eEF1A. We found that eEF1A forms a complex with FBI-1 by co-immunoprecipitation, SDS-PAGE, and MALDI-TOF Mass analysis of the immunoprecipitate. GST fusion protein pull-downs showed that FBI-1 directly interacts with eEF1A and CCS-3 via the zinc finger and POZ-domain of FBI-1. FBI-1 co-localizes with either eEF1A or CCS-3 at the nuclear periplasm. CCS-3 enhances transcriptional repression of the p21CIP1 gene (hereafter referred to as p21) by FBI-1. The POZ-domain of FBI-1 interacts with the co-repressors, SMRT and BCoR. We found that CCS-3 also interacts with the co-repressors independently. The molecular interaction between the co-repressors and CCS-3 at the POZ-domain of FBI-1 appears to enhance FBI-1 mediated transcriptional repression. Our data suggest that CCS-3 may be important in cell differentiation, tumorigenesis, and oncogenesis by interacting with the proto-oncogene FBI-1 and transcriptional co-repressors. Copyright 2009 S. Karger AG, Basel.

Backbone dynamics in an intramolecular prolylpeptide-SH3 complex from the diphtheria toxin repressor, DtxR

PubMed Central

Bhattacharya, Nilakshee; Yi, Myunggi; Zhou, Huan-Xiang; Logan, Timothy M.

2008-01-01

Summary The diphtheria toxin repressor contains an SH3-like domain that forms an intramolecular complex with a proline-rich (Pr) peptide segment and stabilizes the inactive state of the repressor. Upon activation of DtxR by transition metals, this intramolecular complex must dissociate as the SH3 domain and Pr segment form different interactions in the active repressor. In this study we investigate the dynamics of this intramolecular complex using backbone amide nuclear spin relaxation rates determined using NMR spectroscopy and molecular dynamics trajectories. The SH3 domain in the unbound and bound states showed typical dynamics in that the secondary structures were fairly ordered with high generalized order parameters and low effective correlation times while residues in the loops connecting β-strands exhibited reduced generalized order parameters and required additional motional terms to adequately model the relaxation rates. Residues forming the Pr segment exhibited low order parameters with internal rotational correlation times on the order of 0.6 – 1 ns. Further analysis showed that the SH3 domain was rich in millisecond timescale motions while the Pr segment was rich in motions on the 100s μs timescale. Molecular dynamics simultations indicated structural rearrangements that may contribute to the observed relaxation rates and, together with the observed relaxation rate data, suggested that the Pr segment exhibits a binding ↔ unbinding equilibrium. The results of this study provide new insights into the nature of the intramolecular complex and provide a better understanding of the biological role of the SH3 domain in regulating DtxR activity. PMID:17976643

SHORT VEGETATIVE PHASE Up-Regulates TEMPRANILLO2 Floral Repressor at Low Ambient Temperatures1[OPEN

PubMed Central

Marín-González, Esther; Matías-Hernández, Luis; Aguilar-Jaramillo, Andrea E.; Lee, Jeong Hwan; Ahn, Ji Hoon; Suárez-López, Paula; Pelaz, Soraya

2015-01-01

Plants integrate day length and ambient temperature to determine the optimal timing for developmental transitions. In Arabidopsis (Arabidopsis thaliana), the floral integrator FLOWERING LOCUS T (FT) and its closest homolog TWIN SISTER OF FT promote flowering in response to their activator CONSTANS under long-day inductive conditions. Low ambient temperature (16°C) delays flowering, even under inductive photoperiods, through repression of FT, revealing the importance of floral repressors acting at low temperatures. Previously, we have reported that the floral repressors TEMPRANILLO (TEM; TEM1 and TEM2) control flowering time through direct regulation of FT at 22°C. Here, we show that tem mutants are less sensitive than the wild type to changes in ambient growth temperature, indicating that TEM genes may play a role in floral repression at 16°C. Moreover, we have found that TEM2 directly represses the expression of FT and TWIN SISTER OF FT at 16°C. In addition, the floral repressor SHORT VEGETATIVE PHASE (SVP) directly regulates TEM2 but not TEM1 expression at 16°C. Flowering time analyses of svp tem mutants indicate that TEM may act in the same genetic pathway as SVP to repress flowering at 22°C but that SVP and TEM are partially independent at 16°C. Thus, TEM2 partially mediates the temperature-dependent function of SVP at low temperatures. Taken together, our results indicate that TEM genes are also able to repress flowering at low ambient temperatures under inductive long-day conditions. PMID:26243615

Field Level Computer Exploitation Package

DTIC Science & Technology

2007-03-01

to take advantage of the data retrieved from the computer. Major Barge explained that if a tool could be designed that nearly anyone could use...the study of network forensics. This has become a necessity because of the constantly growing eCommerce industry and the stiff competition between...Security. One big advantage that Insert has is the fact that it is quite small compared to most bootable CDs. At only 60 megabytes it can be burned

Temperature-dependent photoluminescence in meso-porous MCM nanotubes

NASA Astrophysics Data System (ADS)

Lee, Y. C.; Liu, Y. L.; Lee, W. Z.; Wang, C. K.; Shen, J. L.; Cheng, P. W.; Cheng, C. F.; Lin, T. Y.

2004-11-01

Temperature-dependent photoluminescence (PL) was exploited to investigate the mechanism of luminescence of MCM (Mobil Composition of Matter)-41 and MCM-48 nanotubes. The PL intensity has a maximum around 40 K. Localization of the carriers involved in the radiative recombination was deduced from the PL decay profiles at various energies. A model based on competition between radiative recombination of localized carriers and nonradiative recombination is suggested to explain the temperature-dependence of PL intensity.

Exploiting Early Intent Recognition for Competitive Advantage

DTIC Science & Technology

2009-01-01

basketball [Bhan- dari et al., 1997; Jug et al., 2003], and Robocup soccer sim- ulations [Riley and Veloso, 2000; 2002; Kuhlmann et al., 2006] and non...actions (e.g. before, after, around). Jug et al. [2003] used a similar framework for offline basketball game analysis. More recently, Hess et al...and K. Ramanujam. Advanced Scout: Data mining and knowledge discovery in NBA data. Data Mining and Knowledge Discovery, 1(1):121–125, 1997. [Chang

Competition and Cooperation in the Southwestern Indian Ocean: The View From the Islands

DTIC Science & Technology

1993-04-01

in each country sees benefits only when facilities are the exploitation of sea- based resources, especially located on its own...of the Gulf War, Operation Restore Hope Introduction in Somalia, the continued international controversy over Diego Garcia, and the persisting need...books and likely to intersect during the 1990s? articles condemned or extolled the United States In order to attempt an answer to these questions, base

The TIE1 Transcriptional Repressor Links TCP Transcription Factors with TOPLESS/TOPLESS-RELATED Corepressors and Modulates Leaf Development in Arabidopsis[W

PubMed Central

Tao, Qing; Guo, Dongshu; Wei, Baoye; Zhang, Fan; Pang, Changxu; Jiang, Hao; Zhang, Jinzhe; Wei, Tong; Gu, Hongya; Qu, Li-Jia; Qin, Genji

2013-01-01

Leaf size and shape are mainly determined by coordinated cell division and differentiation in lamina. The CINCINNATA (CIN)-like TEOSINTE BRANCHED1/CYCLOIDEA/PCF (TCP) transcription factors are key regulators of leaf development. However, the mechanisms that control TCP activities during leaf development are largely unknown. We identified the TCP Interactor containing EAR motif protein1 (TIE1), a novel transcriptional repressor, as a major modulator of TCP activities during leaf development. Overexpression of TIE1 leads to hyponastic and serrated leaves, whereas disruption of TIE1 causes epinastic leaves. TIE1 is expressed in young leaves and encodes a transcriptional repressor containing a C-terminal EAR motif, which mediates interactions with the TOPLESS (TPL)/TOPLESS-RELATED (TPR) corepressors. In addition, TIE1 physically interacts with CIN-like TCPs. We propose that TIE1 regulates leaf size and morphology by inhibiting the activities of TCPs through recruiting the TPL/TPR corepressors to form a tertiary complex at early stages of leaf development. PMID:23444332

Solution NMR investigation of the response of the lactose repressor core domain dimer to hydrostatic pressure.

PubMed

Fuglestad, Brian; Stetz, Matthew A; Belnavis, Zachary; Wand, A Joshua

2017-12-01

Previous investigations of the sensitivity of the lac repressor to high-hydrostatic pressure have led to varying conclusions. Here high-pressure solution NMR spectroscopy is used to provide an atomic level view of the pressure induced structural transition of the lactose repressor regulatory domain (LacI* RD) bound to the ligand IPTG. As the pressure is raised from ambient to 3kbar the native state of the protein is converted to a partially unfolded form. Estimates of rotational correlation times using transverse optimized relaxation indicates that a monomeric state is never reached and that the predominate form of the LacI* RD is dimeric throughout this pressure change. Spectral analysis suggests that the pressure-induced transition is localized and is associated with a volume change of approximately -115mlmol -1 and an average pressure dependent change in compressibility of approximately 30mlmol -1 kbar -1 . In addition, a subset of resonances emerge at high-pressures indicating the presence of a non-native but folded alternate state. Copyright © 2017 Elsevier B.V. All rights reserved.

Imprinting regulator DNMT3L is a transcriptional repressor associated with histone deacetylase activity.

PubMed

Aapola, Ulla; Liiv, Ingrid; Peterson, Pärt

2002-08-15

DNMT3L is a regulator of imprint establishment of normally methylated maternal genomic sequences. DNMT3L shows high similarity to the de novo DNA methyltransferases, DNMT3A and DNMT3B, however, the amino acid residues needed for DNA cytosine methyltransferase activity have been lost from the DNMT3L protein sequence. Apart from methyltransferase activity, Dnmt3a and Dnmt3b serve as transcriptional repressors associating with histone deacetylase (HDAC) activity. Here we show that DNMT3L can also repress transcription by binding directly to HDAC1 protein. We have identified the PHD-like zinc finger of the ATRX domain as a main repression motif of DNMT3L, through which DNMT3L recruits the HDAC activity needed for transcriptional silencing. Furthermore, we show that DNMT3L protein contains an active nuclear localisation signal at amino acids 156-159. These results describe DNMT3L as a co-repressor protein and suggest that a transcriptionally repressed chromatin organisation through HDAC activity is needed for establishment of genomic imprints.

A domesticated transposon mediates the effects of a single-nucleotide polymorphism responsible for enhanced muscle growth.

PubMed

Butter, Falk; Kappei, Dennis; Buchholz, Frank; Vermeulen, Michiel; Mann, Matthias

2010-04-01

Single-nucleotide polymorphisms (SNPs) in the regulatory regions of the genome can have a profound impact on phenotype. The G3072A polymorphism in intron 3 of insulin-like growth factor 2 (IGF2) is implicated in higher muscle content and reduced fat in European pigs and is bound by a putative repressor. Here, we identify this repressor--which we call muscle growth regulator (MGR)--by using a DNA protein interaction screen based on quantitative mass spectrometry. MGR has a bipartite nuclear localization signal, two BED-type zinc fingers and is highly conserved between placental mammals. Surprisingly, the gene is located in an intron and belongs to the hobo-Ac-Tam3 transposase superfamily, suggesting regulatory use of a formerly parasitic element. In transactivation assays, MGR differentially represses the expression of the two SNP variants. Knockdown of MGR in C2C12 myoblast cells upregulates Igf2 expression and mild overexpression retards growth. Thus, MGR is the repressor responsible for enhanced muscle growth in the IGF2 G3072A polymorphism in commercially bred pigs.

Crystal structure of enterococcus faecalis sly A-like transcriptional factor.

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

Wu, R.; Zhang, R.; Zagnitko, O.

2003-05-30

The crystal structure of a SlyA transcriptional regulator at 1.6 {angstrom} resolution is presented, and structural relationships between members of the MarR/SlyA family are discussed. The SlyA family, which includes SlyA, Rap, Hor, and RovA proteins, is widely distributed in bacterial and archaeal genomes. Current evidence suggests that SlyA-like factors act as repressors, activators, and modulators of gene transcription. These proteins have been shown to up-regulate the expression of molecular chaperones, acid-resistance proteins, and cytolysin, and down-regulate several biosynthetic enzymes. The structure of SlyA from Enterococcus faecalis, determined as a part of an ongoing structural genomics initiative (www.mcsg.anl.gov), revealed themore » same winged helix DNA-binding motif that was recently found in the MarR repressor from Escherichia coli and the MexR repressor from Pseudomonas aeruginosa, a sequence homologue of MarR. Phylogenetic analysis of the MarR/SlyA family suggests that Sly is placed between the SlyA and MarR subfamilies and shows significant sequence similarity to members of both subfamilies.« less

DND protein functions as a translation repressor during zebrafish embryogenesis.

PubMed

Kobayashi, Manami; Tani-Matsuhana, Saori; Ohkawa, Yasuka; Sakamoto, Hiroshi; Inoue, Kunio

2017-03-04

Germline and somatic cell distinction is regulated through a combination of microRNA and germ cell-specific RNA-binding proteins in zebrafish. An RNA-binding protein, DND, has been reported to relieve the miR-430-mediated repression of some germ plasm mRNAs such as nanos3 and tdrd7 in primordial germ cells (PGCs). Here, we showed that miR-430-mediated repression is not counteracted by the overexpression of DND protein in somatic cells. Using a λN-box B tethering assay in the embryo, we found that tethering of DND to reporter mRNA results in translation repression without affecting mRNA stability. Translation repression by DND was not dependent on another germline-specific translation repressor, Nanos3, in zebrafish embryos. Moreover, our data suggested that DND represses translation of nanog and dnd mRNAs, whereas an RNA-binding protein DAZ-like (DAZL) promotes dnd mRNA translation. Thus, our study showed that DND protein functions as a translation repressor of specific mRNAs to control PGC development in zebrafish. Copyright © 2017 Elsevier Inc. All rights reserved.

Crystal Structure of the CLOCK Transactivation Domain Exon19 in Complex with a Repressor

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

Hou, Zhiqiang; Su, Lijing; Pei, Jimin

In the canonical clock model, CLOCK:BMAL1-mediated transcriptional activation is feedback regulated by its repressors CRY and PER and, in association with other coregulators, ultimately generates oscillatory gene expression patterns. How CLOCK:BMAL1 interacts with coregulator(s) is not well understood. Here we report the crystal structures of the mouse CLOCK transactivating domain Exon19 in complex with CIPC, a potent circadian repressor that functions independently of CRY and PER. The Exon19:CIPC complex adopts a three-helical coiled-coil bundle conformation containing two Exon19 helices and one CIPC. Unique to Exon19:CIPC, three highly conserved polar residues, Asn341 of CIPC and Gln544 of the two Exon19 helices,more » are located at the mid-section of the coiled-coil bundle interior and form hydrogen bonds with each other. Combining results from protein database search, sequence analysis, and mutagenesis studies, we discovered for the first time that CLOCK Exon19:CIPC interaction is a conserved transcription regulatory mechanism among mammals, fish, flies, and other invertebrates.« less

Strategies to regulate transcription factor-mediated gene positioning and interchromosomal clustering at the nuclear periphery.

PubMed

Randise-Hinchliff, Carlo; Coukos, Robert; Sood, Varun; Sumner, Michael Chas; Zdraljevic, Stefan; Meldi Sholl, Lauren; Garvey Brickner, Donna; Ahmed, Sara; Watchmaker, Lauren; Brickner, Jason H

2016-03-14

In budding yeast, targeting of active genes to the nuclear pore complex (NPC) and interchromosomal clustering is mediated by transcription factor (TF) binding sites in the gene promoters. For example, the binding sites for the TFs Put3, Ste12, and Gcn4 are necessary and sufficient to promote positioning at the nuclear periphery and interchromosomal clustering. However, in all three cases, gene positioning and interchromosomal clustering are regulated. Under uninducing conditions, local recruitment of the Rpd3(L) histone deacetylase by transcriptional repressors blocks Put3 DNA binding. This is a general function of yeast repressors: 16 of 21 repressors blocked Put3-mediated subnuclear positioning; 11 of these required Rpd3. In contrast, Ste12-mediated gene positioning is regulated independently of DNA binding by mitogen-activated protein kinase phosphorylation of the Dig2 inhibitor, and Gcn4-dependent targeting is up-regulated by increasing Gcn4 protein levels. These different regulatory strategies provide either qualitative switch-like control or quantitative control of gene positioning over different time scales. © 2016 Randise-Hinchliff et al.

Stress-Responsive Mitogen-Activated Protein Kinases Interact with the EAR Motif of a Poplar Zinc Finger Protein and Mediate Its Degradation through the 26S Proteasome1[W][OA

PubMed Central

Hamel, Louis-Philippe; Benchabane, Meriem; Nicole, Marie-Claude; Major, Ian T.; Morency, Marie-Josée; Pelletier, Gervais; Beaudoin, Nathalie; Sheen, Jen; Séguin, Armand

2011-01-01

Mitogen-activated protein kinases (MAPKs) contribute to the establishment of plant disease resistance by regulating downstream signaling components, including transcription factors. In this study, we identified MAPK-interacting proteins, and among the newly discovered candidates was a Cys-2/His-2-type zinc finger protein named PtiZFP1. This putative transcription factor belongs to a family of transcriptional repressors that rely on an ERF-associated amphiphilic repression (EAR) motif for their repression activity. Amino acids located within this repression motif were also found to be essential for MAPK binding. Close examination of the primary protein sequence revealed a functional bipartite MAPK docking site that partially overlaps with the EAR motif. Transient expression assays in Arabidopsis (Arabidopsis thaliana) protoplasts suggest that MAPKs promote PtiZFP1 degradation through the 26S proteasome. Since features of the MAPK docking site are conserved among other EAR repressors, our study suggests a novel mode of defense mechanism regulation involving stress-responsive MAPKs and EAR repressors. PMID:21873571

Exploiting Deep Eutectic Solvents and Organolithium Reagent Partnerships: Chemoselective Ultrafast Addition to Imines and Quinolines Under Aerobic Ambient Temperature Conditions.

PubMed

Vidal, Cristian; García-Álvarez, Joaquín; Hernán-Gómez, Alberto; Kennedy, Alan R; Hevia, Eva

2016-12-23

Shattering the long-held dogma that organolithium chemistry needs to be performed under inert atmospheres in toxic organic solvents, chemoselective addition of organolithium reagents to non-activated imines and quinolines has been accomplished in green, biorenewable deep eutectic solvents (DESs) at room temperature and in the presence of air, establishing a novel and sustainable access to amines. Improving on existing methods, this approach proceeds in the absence of additives; occurs without competitive enolization, reduction or coupling processes; and reactions were completed in seconds. Comparing RLi reactivities in DESs with those observed in pure glycerol or THF suggests a kinetic anionic activation of the alkylating reagents occurs, favoring nucleophilic addition over competitive hydrolysis. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Social motives and strategic misrepresentation in social decision making.

PubMed

Steinel, Wolfgang; De Dreu, Carsten K W

2004-03-01

In 4 experiments, the authors studied the influence of social motives on deception and strategic misrepresentation. In a newly developed information provision game, individuals faced a decision maker whose decision would affect both own and other's outcomes. By withholding information or by giving (in)accurate information about payoffs, participants could try to influence other's decision making. Less accurate and more inaccurate information was given when the decision maker was competitive rather than cooperative (Experiment 1), especially when participants had a prosocial rather than selfish value orientation (Experiments 3 and 4). Accurate information was withheld because of fear of exploitation and greed, and inaccurate information was given because of greed (Experiment 2). Finally, participants engaged in strategic misrepresentation that may trick competitive others into damaging their own and increasing the participant's outcomes.

Escalated convergent artificial bee colony

NASA Astrophysics Data System (ADS)

Jadon, Shimpi Singh; Bansal, Jagdish Chand; Tiwari, Ritu

2016-03-01

Artificial bee colony (ABC) optimisation algorithm is a recent, fast and easy-to-implement population-based meta heuristic for optimisation. ABC has been proved a rival algorithm with some popular swarm intelligence-based algorithms such as particle swarm optimisation, firefly algorithm and ant colony optimisation. The solution search equation of ABC is influenced by a random quantity which helps its search process in exploration at the cost of exploitation. In order to find a fast convergent behaviour of ABC while exploitation capability is maintained, in this paper basic ABC is modified in two ways. First, to improve exploitation capability, two local search strategies, namely classical unidimensional local search and levy flight random walk-based local search are incorporated with ABC. Furthermore, a new solution search strategy, namely stochastic diffusion scout search is proposed and incorporated into the scout bee phase to provide more chance to abandon solution to improve itself. Efficiency of the proposed algorithm is tested on 20 benchmark test functions of different complexities and characteristics. Results are very promising and they prove it to be a competitive algorithm in the field of swarm intelligence-based algorithms.

Competition policy for health care provision in the Netherlands.

PubMed

Schut, Frederik T; Varkevisser, Marco

2017-02-01

In the Netherlands in 2006 a major health care reform was introduced, aimed at reinforcing regulated competition in the health care sector. Health insurers were provided with strong incentives to compete and more room to negotiate and selectively contract with health care providers. Nevertheless, the bargaining position of health insurers vis-à-vis both GPs and hospitals is still relatively weak. GPs are very well organized in a powerful national interest association (LHV) and effectively exploit the long-standing trust relationship with their patients. They have been very successful in mobilizing public support against unfavorable contracting practices of health insurers and enforcement of the competition act. The rapid establishment of multidisciplinary care groups to coordinate care for patients with chronic diseases further strengthened their position. Due to ongoing horizontal consolidation, hospital markets in the Netherlands have become highly concentrated. Only recently the Dutch competition authority prohibited the first hospital merger. Despite the highly concentrated health insurance market, it is unclear whether insurers will have sufficient countervailing buyer power vis-à-vis GPs and hospitals to effectively fulfill their role as prudent buyer of care, as envisioned in the reform. To prevent further consolidation and anticompetitive coordination, strict enforcement of competition policy is crucially important for safeguarding the potential for effective insurer-provider negotiations about quality and price. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Trait-based characterisation of soil exploitation strategies of banana, weeds and cover plant species

PubMed Central

Tardy, Florence; Damour, Gaëlle; Dorel, Marc; Moreau, Delphine

2017-01-01

Cover plants can be introduced in cropping systems to provide agroecosystem services, including weed control via competition for resources. There is currently no consensus on how to identify the best cover plant species, while trait-based approaches are promising for screening plant species due to their agroecosystem service provision potential. This study was carried out to characterize soil exploitation strategies of cover plant species in banana agroecosystems using a trait-based approach, and in turn identify cover plant species with a high weed control potential via competition for soil resources in banana cropping systems. A field experiment was conducted on 17 cover plant species, two weed species and two banana cultivars grown individually. Four functional traits were measured. Two of them (i.e., the size of the zone explored by roots and the root impact density) were used to characterize root system soil exploration patterns. Two other traits (i.e., specific root length and root diameter) were used to characterize resource acquisition within the soil zone explored by the roots. All studied traits exhibited marked variations among species. The findings suggested a trade-off between the abilities of species to develop a limited number of large diameter roots exploring a large soil zone versus many thin roots exploring a smaller soil zone. Three soil-resource exploitation strategies were identified among species: (i) with large diameter roots that explore a large soil zone; (ii) with small diameter roots and a high specific length that explore a smaller soil zone; and (iii) with a high total root-impact density and an intermediate specific root length that explore the uppermost soil layers. Interestingly, in our panel of species, no correlations with regard to belowground and aboveground strategies were noted: species with an acquisitive belowground strategy could display an acquisitive or a conservative aboveground strategy. The findings of this study illustrated that a trait-based approach could be used to identify plant species with potential for competing with weeds, while minimising competition with banana. Six of the 17 studied cover crop species were identified as having this potential. The next step will be to assess them for their weed control performances in banana cropping systems with low reliance on herbicides. PMID:28257454

Trait-based characterisation of soil exploitation strategies of banana, weeds and cover plant species.

PubMed

Tardy, Florence; Damour, Gaëlle; Dorel, Marc; Moreau, Delphine

2017-01-01

Cover plants can be introduced in cropping systems to provide agroecosystem services, including weed control via competition for resources. There is currently no consensus on how to identify the best cover plant species, while trait-based approaches are promising for screening plant species due to their agroecosystem service provision potential. This study was carried out to characterize soil exploitation strategies of cover plant species in banana agroecosystems using a trait-based approach, and in turn identify cover plant species with a high weed control potential via competition for soil resources in banana cropping systems. A field experiment was conducted on 17 cover plant species, two weed species and two banana cultivars grown individually. Four functional traits were measured. Two of them (i.e., the size of the zone explored by roots and the root impact density) were used to characterize root system soil exploration patterns. Two other traits (i.e., specific root length and root diameter) were used to characterize resource acquisition within the soil zone explored by the roots. All studied traits exhibited marked variations among species. The findings suggested a trade-off between the abilities of species to develop a limited number of large diameter roots exploring a large soil zone versus many thin roots exploring a smaller soil zone. Three soil-resource exploitation strategies were identified among species: (i) with large diameter roots that explore a large soil zone; (ii) with small diameter roots and a high specific length that explore a smaller soil zone; and (iii) with a high total root-impact density and an intermediate specific root length that explore the uppermost soil layers. Interestingly, in our panel of species, no correlations with regard to belowground and aboveground strategies were noted: species with an acquisitive belowground strategy could display an acquisitive or a conservative aboveground strategy. The findings of this study illustrated that a trait-based approach could be used to identify plant species with potential for competing with weeds, while minimising competition with banana. Six of the 17 studied cover crop species were identified as having this potential. The next step will be to assess them for their weed control performances in banana cropping systems with low reliance on herbicides.

Training modalities: impact on endurance capacity.

PubMed

Flueck, Martin; Eilers, Wouter

2010-03-01

Endurance athletes demonstrate an exceptional resistance to fatigue when exercising at high intensity. Much research has been devoted to the contribution of aerobic capacity for the economy of endurance performance. Important aspects of the fine-tuning of metabolic processes and power output in the endurance athlete have been overlooked. This review addresses how training paradigms exploit bioenergetic pathways in recruited muscle groups to promote the endurance phenotype. A special focus is laid on the genome-mediated mechanisms that underlie the conditioning of fatigue resistance and aerobic performance by training macrocycles and complements. The available data on work-induced muscle plasticity implies that different biologic strategies are exploited in athletic and untrained populations to boost endurance capacity. Olympic champions are probably endowed with a unique constitution that renders the conditioning of endurance capacity for competition particularly efficient. Copyright 2010 Elsevier Inc. All rights reserved.

Exploiting intraspecific competitive mechanisms to control invasive cane toads (Rhinella marina)

PubMed Central

Crossland, Michael R.; Haramura, Takashi; Salim, Angela A.; Capon, Robert J.; Shine, Richard

2012-01-01

If invasive species use chemical weapons to suppress the viability of conspecifics, we may be able to exploit those species-specific chemical cues for selective control of the invader. Cane toads (Rhinella marina) are spreading through tropical Australia, with negative effects on native species. The tadpoles of cane toads eliminate intraspecific competitors by locating and consuming newly laid eggs. Our laboratory trials show that tadpoles find those eggs by searching for the powerful bufadienolide toxins (especially, bufogenins) that toads use to deter predators. Using those toxins as bait, funnel-traps placed in natural waterbodies achieved near-complete eradication of cane toad tadpoles with minimal collateral damage (because most native (non-target) species are repelled by the toads' toxins). More generally, communication systems that have evolved for intraspecific conflict provide novel opportunities for invasive-species control. PMID:22696528

Automatic systems and the low-level wind hazard

NASA Technical Reports Server (NTRS)

Schaeffer, Dwight R.

1987-01-01

Automatic flight control systems provide means for significantly enhancing survivability in severe wind hazards. The technology required to produce the necessary control algorithms is available and has been made technically feasible by the advent of digital flight control systems and accurate, low-noise sensors, especially strap-down inertial sensors. The application of this technology and these means has not generally been enabled except for automatic landing systems, and even then the potential has not been fully exploited. To fully exploit the potential of automatic systems for enhancing safety in wind hazards requires providing incentives, creating demand, inspiring competition, education, and eliminating prejudicial disincentitives to overcome the economic penalties associated with the extensive and riskly development and certification of these systems. If these changes will come about at all, it will likely be through changes in the regulations provided by the certifying agencies.

Electrochemistry for biofuel generation: transformation of fatty acids and triglycerides to diesel-like olefin/ether mixtures and olefins.

PubMed

dos Santos, Tatiane R; Harnisch, Falk; Nilges, Peter; Schröder, Uwe

2015-03-01

Electroorganic synthesis can be exploited for the production of biofuels from fatty acids and triglycerides. With Coulomb efficiencies (CE) of up to 50 %, the electrochemical decarboxylation of fatty acids in methanolic and ethanolic solutions leads to the formation of diesel-like olefin/ether mixtures. Triglycerides can be directly converted in aqueous solutions by using sonoelectrochemistry, with olefins as the main products (with a CE of more than 20 %). The latter reaction, however, is terminated at around 50 % substrate conversion by the produced side-product glycerol. An energy analysis shows that the electrochemical olefin synthesis can be an energetically competitive, sustainable, and--in comparison with established processes--economically feasible alternative for the exploitation of fats and oils for biofuel production. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Selenium exposure results in reduced reproduction in an invasive ant species and altered competitive behavior for a native ant species.

PubMed

De La Riva, Deborah G; Trumble, John T

2016-06-01

Competitive ability and numerical dominance are important factors contributing to the ability of invasive ant species to establish and expand their ranges in new habitats. However, few studies have investigated the impact of environmental contamination on competitive behavior in ants as a potential factor influencing dynamics between invasive and native ant species. Here we investigated the widespread contaminant selenium to investigate its potential influence on invasion by the exotic Argentine ant, Linepithema humile, through effects on reproduction and competitive behavior. For the fecundity experiment, treatments were provided to Argentine ant colonies via to sugar water solutions containing one of three concentrations of selenium (0, 5 and 10 μg Se mL(-1)) that fall within the range found in soil and plants growing in contaminated areas. Competition experiments included both the Argentine ant and the native Dorymyrmex bicolor to determine the impact of selenium exposure (0 or 15 μg Se mL(-1)) on exploitation- and interference-competition between ant species. The results of the fecundity experiment revealed that selenium negatively impacted queen survival and brood production of Argentine ants. Viability of the developing brood was also affected in that offspring reached adulthood only in colonies that were not given selenium, whereas those in treated colonies died in their larval stages. Selenium exposure did not alter direct competitive behaviors for either species, but selenium exposure contributed to an increased bait discovery time for D. bicolor. Our results suggest that environmental toxins may not only pose problems for native ant species, but may also serve as a potential obstacle for establishment among exotic species. Copyright © 2016 Elsevier Ltd. All rights reserved.

Secondary metabolites and other small molecules as intercellular pathogenic signals.

PubMed

Dufour, Nicholas; Rao, Reeta Prusty

2011-01-01

Microorganisms often use small chemicals or secondary metabolites as informational cues to regulate gene expression. It is hypothesized that microorganisms exploit these signals to gain a competitive advantage. Here, we present examples of pathogens that use this strategy to exclude other microorganisms from the site of infection. An emerging theme is that inhibiting these systems presents a novel approach to antimicrobial therapies. © 2010 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

GPU computing in medical physics: a review.

PubMed

Pratx, Guillem; Xing, Lei

2011-05-01

The graphics processing unit (GPU) has emerged as a competitive platform for computing massively parallel problems. Many computing applications in medical physics can be formulated as data-parallel tasks that exploit the capabilities of the GPU for reducing processing times. The authors review the basic principles of GPU computing as well as the main performance optimization techniques, and survey existing applications in three areas of medical physics, namely image reconstruction, dose calculation and treatment plan optimization, and image processing.

Reinforcement learning and decision making in monkeys during a competitive game.

PubMed

Lee, Daeyeol; Conroy, Michelle L; McGreevy, Benjamin P; Barraclough, Dominic J

2004-12-01

Animals living in a dynamic environment must adjust their decision-making strategies through experience. To gain insights into the neural basis of such adaptive decision-making processes, we trained monkeys to play a competitive game against a computer in an oculomotor free-choice task. The animal selected one of two visual targets in each trial and was rewarded only when it selected the same target as the computer opponent. To determine how the animal's decision-making strategy can be affected by the opponent's strategy, the computer opponent was programmed with three different algorithms that exploited different aspects of the animal's choice and reward history. When the computer selected its targets randomly with equal probabilities, animals selected one of the targets more often, violating the prediction of probability matching, and their choices were systematically influenced by the choice history of the two players. When the computer exploited only the animal's choice history but not its reward history, animal's choice became more independent of its own choice history but was still related to the choice history of the opponent. This bias was substantially reduced, but not completely eliminated, when the computer used the choice history of both players in making its predictions. These biases were consistent with the predictions of reinforcement learning, suggesting that the animals sought optimal decision-making strategies using reinforcement learning algorithms.

Structure of the C-terminal domain of the arginine repressor protein from Mycobacterium tuberculosis

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

Cherney, Leonid T.; Cherney, Maia M.; Garen, Craig R.

2008-09-01

The structure of the core domain of the arginine repressor protein from M. tuberculosis has been determined with (1.85 Å resolution) and without (2.15 Å resolution) the arginine corepressor bound. Three additional arginine molecules have been found to bind to the core domain hexamer at high (0.2 M) arginine concentration. The Mycobacterium tuberculosis (Mtb) gene product encoded by open reading frame Rv1657 is an arginine repressor (ArgR). All genes involved in the l-arginine (hereafter arginine) biosynthetic pathway are essential for optimal growth of the Mtb pathogen, thus making MtbArgR a potential target for drug design. The C-terminal domains of argininemore » repressors (CArgR) participate in oligomerization and arginine binding. Several crystal forms of CArgR from Mtb (MtbCArgR) have been obtained. The X-ray crystal structures of MtbCArgR were determined at 1.85 Å resolution with bound arginine and at 2.15 Å resolution in the unliganded form. These structures show that six molecules of MtbCArgR are arranged into a hexamer having approximate 32 point symmetry that is formed from two trimers. The trimers rotate relative to each other by about 11° upon binding arginine. All residues in MtbCArgR deemed to be important for hexamer formation and for arginine binding have been identified from the experimentally determined structures presented. The hexamer contains six regular sites in which the arginine molecules have one common binding mode and three sites in which the arginine molecules have two overlapping binding modes. The latter sites only bind the ligand at high (200 mM) arginine concentrations.« less

tif-1 mutation alters polynucleotide recognition by the recA protein of Escherichia coli.

PubMed Central

McEntee, K; Weinstock, G M

1981-01-01

The requirements for polynucleotide-dependent hydrolysis of ATP and for proteolytic cleavage of phage lambda repressor have been examined for both the wild-type (recA+ protein) and the tif-1 mutant form [tif(recA) protein] of the recA gene product. The recA+ and tif(recA) proteins catalyze both reactions in the presence of long single-stranded DNAs or certain deoxyhomopolymers. However, short oligonucleotides [(dT)12, (dA)14] stimulate neither the protease nor the ATPase activities of the recA+ protein. In contrast, these short oligonucleotides activate tif(recA) protein to cleave lambda repressor without stimulating its ATPase activity. Moreover, both the ATPase and protease activities of the tif(recA) protein are stimulated by poly(rU) and poly(rC) whereas the recA+ protein does not respond to these ribopolymers. We have purified the recA protein from a strain in which the tif mutation is intragenically suppressed. This mutant protein (recA629) is inactive in the presence of (dT)12, (dA)14, poly(rU), and poly(rC) for lambda repressor cleavage and ATP hydrolysis. These results argue that the tif-1 mutation (or mutations) alters the DNA binding site of the recA protein. We suggest that in vivo the tif(recA) protein is activated for cleaving repressors of SOS genes by complex formation with short single-stranded regions or gaps that normally occur near the growing fork of replicating chromosomes and are too short for activating the recA+ enzyme. This mechanism can account for the expression of SOS functions in the absence of DNA damage in tif mutant strains. Images PMID:7031642

Candida albicans Hap43 Is a Repressor Induced under Low-Iron Conditions and Is Essential for Iron-Responsive Transcriptional Regulation and Virulence ▿

PubMed Central

Hsu, Po-Chen; Yang, Cheng-Yao; Lan, Chung-Yu

2011-01-01

Candida albicans is an opportunistic fungal pathogen that exists as normal flora in healthy human bodies but causes life-threatening infections in immunocompromised patients. In addition to innate and adaptive immunities, hosts also resist microbial infections by developing a mechanism of “natural resistance” that maintains a low level of free iron to restrict the growth of invading pathogens. C. albicans must overcome this iron-deprived environment to cause infections. There are three types of iron-responsive transcriptional regulators in fungi; Aft1/Aft2 activators in yeast, GATA-type repressors in many fungi, and HapX/Php4 in Schizosaccharomyces pombe and Aspergillus species. In this study, we characterized the iron-responsive regulator Hap43, which is the C. albicans homolog of HapX/Php4 and is repressed by the GATA-type repressor Sfu1 under iron-sufficient conditions. We provide evidence that Hap43 is essential for the growth of C. albicans under low-iron conditions and for C. albicans virulence in a mouse model of infection. Hap43 was not required for iron acquisition under low-iron conditions. Instead, it was responsible for repression of genes that encode iron-dependent proteins involved in mitochondrial respiration and iron-sulfur cluster assembly. We also demonstrated that Hap43 executes its function by becoming a transcriptional repressor and accumulating in the nucleus in response to iron deprivation. Finally, we found a connection between Hap43 and the global corepressor Tup1 in low-iron-induced flavinogenesis. Taken together, our data suggest a complex interplay among Hap43, Sfu1, and Tup1 to coordinately regulate iron acquisition, iron utilization, and other iron-responsive metabolic activities. PMID:21131439

Glycosulfatase-Encoding Gene Cluster in Bifidobacterium breve UCC2003.

PubMed

Egan, Muireann; Jiang, Hao; O'Connell Motherway, Mary; Oscarson, Stefan; van Sinderen, Douwe

2016-11-15

Bifidobacteria constitute a specific group of commensal bacteria typically found in the gastrointestinal tract (GIT) of humans and other mammals. Bifidobacterium breve strains are numerically prevalent among the gut microbiota of many healthy breastfed infants. In the present study, we investigated glycosulfatase activity in a bacterial isolate from a nursling stool sample, B. breve UCC2003. Two putative sulfatases were identified on the genome of B. breve UCC2003. The sulfated monosaccharide N-acetylglucosamine-6-sulfate (GlcNAc-6-S) was shown to support the growth of B. breve UCC2003, while N-acetylglucosamine-3-sulfate, N-acetylgalactosamine-3-sulfate, and N-acetylgalactosamine-6-sulfate did not support appreciable growth. By using a combination of transcriptomic and functional genomic approaches, a gene cluster designated ats2 was shown to be specifically required for GlcNAc-6-S metabolism. Transcription of the ats2 cluster is regulated by a repressor open reading frame kinase (ROK) family transcriptional repressor. This study represents the first description of glycosulfatase activity within the Bifidobacterium genus. Bifidobacteria are saccharolytic organisms naturally found in the digestive tract of mammals and insects. Bifidobacterium breve strains utilize a variety of plant- and host-derived carbohydrates that allow them to be present as prominent members of the infant gut microbiota as well as being present in the gastrointestinal tract of adults. In this study, we introduce a previously unexplored area of carbohydrate metabolism in bifidobacteria, namely, the metabolism of sulfated carbohydrates. B. breve UCC2003 was shown to metabolize N-acetylglucosamine-6-sulfate (GlcNAc-6-S) through one of two sulfatase-encoding gene clusters identified on its genome. GlcNAc-6-S can be found in terminal or branched positions of mucin oligosaccharides, the glycoprotein component of the mucous layer that covers the digestive tract. The results of this study provide further evidence of the ability of this species to utilize mucin-derived sugars, a trait which may provide a competitive advantage in both the infant gut and adult gut. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Glycosulfatase-Encoding Gene Cluster in Bifidobacterium breve UCC2003

PubMed Central

Egan, Muireann; Jiang, Hao; O'Connell Motherway, Mary; Oscarson, Stefan

2016-01-01

ABSTRACT Bifidobacteria constitute a specific group of commensal bacteria typically found in the gastrointestinal tract (GIT) of humans and other mammals. Bifidobacterium breve strains are numerically prevalent among the gut microbiota of many healthy breastfed infants. In the present study, we investigated glycosulfatase activity in a bacterial isolate from a nursling stool sample, B. breve UCC2003. Two putative sulfatases were identified on the genome of B. breve UCC2003. The sulfated monosaccharide N-acetylglucosamine-6-sulfate (GlcNAc-6-S) was shown to support the growth of B. breve UCC2003, while N-acetylglucosamine-3-sulfate, N-acetylgalactosamine-3-sulfate, and N-acetylgalactosamine-6-sulfate did not support appreciable growth. By using a combination of transcriptomic and functional genomic approaches, a gene cluster designated ats2 was shown to be specifically required for GlcNAc-6-S metabolism. Transcription of the ats2 cluster is regulated by a repressor open reading frame kinase (ROK) family transcriptional repressor. This study represents the first description of glycosulfatase activity within the Bifidobacterium genus. IMPORTANCE Bifidobacteria are saccharolytic organisms naturally found in the digestive tract of mammals and insects. Bifidobacterium breve strains utilize a variety of plant- and host-derived carbohydrates that allow them to be present as prominent members of the infant gut microbiota as well as being present in the gastrointestinal tract of adults. In this study, we introduce a previously unexplored area of carbohydrate metabolism in bifidobacteria, namely, the metabolism of sulfated carbohydrates. B. breve UCC2003 was shown to metabolize N-acetylglucosamine-6-sulfate (GlcNAc-6-S) through one of two sulfatase-encoding gene clusters identified on its genome. GlcNAc-6-S can be found in terminal or branched positions of mucin oligosaccharides, the glycoprotein component of the mucous layer that covers the digestive tract. The results of this study provide further evidence of the ability of this species to utilize mucin-derived sugars, a trait which may provide a competitive advantage in both the infant gut and adult gut. PMID:27590817

Functional and numerical responses of shrews to competition vary with mouse density.

PubMed

Eckrich, Carolyn A; Flaherty, Elizabeth A; Ben-David, Merav

2018-01-01

For decades, ecologists have debated the importance of biotic interactions (e.g., competition) and abiotic factors in regulating populations. Competition can influence patterns of distribution, abundance, and resource use in many systems but remains difficult to measure. We quantified competition between two sympatric small mammals, Keen's mice (Peromyscus keeni) and dusky shrews (Sorex monticolus), in four habitat types on Prince of Wales Island in Southeast Alaska. We related shrew density to that of mice using standardized regression models while accounting for habitat variables in each year from 2010-2012, during which mice populations peaked (2011) and then crashed (2012). Additionally, we measured dietary overlap and segregation using stable isotope analysis and kernel utilization densities and estimated the change in whole community energy consumption among years. We observed an increase in densities of dusky shrews after mice populations crashed in 2012 as expected under competitive release. In addition, competition coefficients revealed that the influence of Keen's mice was dependent on their density. Also in 2012, shrew diets shifted, indicating that they were able to exploit resources previously used by mice. Nonetheless, increases in shrew numbers only partially compensated for the community energy consumption because, as insectivores, they are unlikely to utilize all food types consumed by their competitors. In pre-commercially thinned stands, which exhibit higher diversity of resources compared to other habitat types, shrew populations were less affected by changes in mice densities. These spatially and temporally variable interactions between unlikely competitors, observed in a relatively simple, high-latitude island ecosystem, highlight the difficulty in assessing the role of biotic factors in structuring communities.

Dispersal-competition tradeoff in microbiomes in the quest for land colonization.

PubMed

Dini-Andreote, Francisco; van Elsas, Jan Dirk; Olff, Han; Salles, Joana Falcão

2018-06-21

Ancestor microbes started colonizing inland habitats approximately 2.7 to 3.5 billion years ago. With some exceptions, the key physiological adaptations of microbiomes associated with marine-to-land transitions have remained elusive. This is essentially caused by the lack of suitable systems that depict changes in microbiomes across sufficiently large time scales. Here, we investigate the adaptive routes taken by microbiomes along a contemporary gradient of land formation. Using functional trait-based metagenomics, we show that a switch from a microbial 'dispersal' to a 'competition' response modus best characterizes the microbial trait changes during this eco-evolutionary trajectory. The 'dispersal' modus prevails in microbiomes at the boundary sites between land and sea. It encompasses traits conferring cell chemosensory and motile behaviors, thus allowing the local microbes to exploit short-lived nutritional patches in high-diffusion microhabitats. A systematic transition towards the 'competition' modus occurs progressively as the soil matures, which is likely due to forces of viscosity or strain that favor traits for competition and chemical defense. Concomitantly, progressive increases in the abundances of genes encoding antibiotic resistance and complex organic substrate degradation were found. Our findings constitute a novel perspective on the ecology and evolution of microbiome traits, tracking back one of the most seminal transitions in the evolutionary history of life.

Diet overlap between harbour porpoise and bottlenose dolphin: An argument in favour of interference competition for food?

NASA Astrophysics Data System (ADS)

Spitz, Jérôme; Rousseau, Yann; Ridoux, Vincent

2006-10-01

In aquatic ecosystems, competitive interactions are occasionally described. Violent attacks on harbour porpoises by bottlenose dolphins were reported and it was proposed that this behavior could result from competitive interactions for food. This hypothesis implies that the two predators should share all or part of they prey range. In this work, we describe the diets of each predator in the Bay of Biscay and adjacent areas from stomach content analysis of stranded animals. The diet of the harbour porpoise was mostly composed of small schooling fish living close to the seafloor (98 percent by mass). The diet of the bottlenose dolphin was characterised by the presence of large specimens of demersal fish (91 percent by mass) and cephalopods. Several prey species are common in the two diets and even the length distributions of some of them, such as sardine or scads, are very similar. However, global indices such as the Mantel test or the Pianka's index indicate no or weak overlap. The dietary results suggest that the two predators show partial dietary overlap over several major dimensions of the foraging niche: prey profile, foraging habitats, prey species and size range. We suggest interference competition is plausible at the scale of a prey school that would be exploited jointly by groups of the two predators.

Body mass of prefledging Emperor Geese Chen canagica: Large-scale effects of interspecific densities and food availability

USGS Publications Warehouse

Lake, B.C.; Schmutz, J.A.; Lindberg, M.S.; Ely, Craig R.; Eldridge, W.D.; Broerman, F.J.

2008-01-01

We studied body mass of prefledging Emperor Geese Chen canagica at three locations across the Yukon-Kuskokwim Delta, Alaska, during 1990-2004 to investigate whether large-scale variation in body mass was related to interspecific competition for food. From 1990 to 2004, densities of Cackling Geese Branta hutchinsii minima more than doubled and were c. 2-5?? greater than densities of Emperor Geese, which were relatively constant over time. Body mass of prefledging Emperor Geese was strongly related (negatively) to interspecific densities of geese (combined density of Cackling and Emperor Geese) and positively related to measures of food availability (grazing lawn extent and net above-ground primary productivity (NAPP)). Grazing by geese resulted in consumption of ??? 90% of the NAPP that occurred in grazing lawns during the brood-rearing period, suggesting that density-dependent interspecific competition was from exploitation of common food resources. Efforts to increase the population size of Emperor Geese would benefit from considering competitive interactions among goose species and with forage plants. ?? 2008 The Authors.

Safe leads and lead changes in competitive team sports.

PubMed

Clauset, A; Kogan, M; Redner, S

2015-06-01

We investigate the time evolution of lead changes within individual games of competitive team sports. Exploiting ideas from the theory of random walks, the number of lead changes within a single game follows a Gaussian distribution. We show that the probability that the last lead change and the time of the largest lead size are governed by the same arcsine law, a bimodal distribution that diverges at the start and at the end of the game. We also determine the probability that a given lead is "safe" as a function of its size L and game time t. Our predictions generally agree with comprehensive data on more than 1.25 million scoring events in roughly 40,000 games across four professional or semiprofessional team sports, and are more accurate than popular heuristics currently used in sports analytics.

Safe leads and lead changes in competitive team sports

NASA Astrophysics Data System (ADS)

Clauset, A.; Kogan, M.; Redner, S.

2015-06-01

We investigate the time evolution of lead changes within individual games of competitive team sports. Exploiting ideas from the theory of random walks, the number of lead changes within a single game follows a Gaussian distribution. We show that the probability that the last lead change and the time of the largest lead size are governed by the same arcsine law, a bimodal distribution that diverges at the start and at the end of the game. We also determine the probability that a given lead is "safe" as a function of its size L and game time t . Our predictions generally agree with comprehensive data on more than 1.25 million scoring events in roughly 40 000 games across four professional or semiprofessional team sports, and are more accurate than popular heuristics currently used in sports analytics.

APETALA2 regulates the stem cell niche in the Arabidopsis shoot meristem.

PubMed

Würschum, Tobias; Gross-Hardt, Rita; Laux, Thomas

2006-02-01

Postembryonic organ formation in higher plants relies on the activity of stem cell niches in shoot and root meristems where differentiation of the resident cells is repressed by signals from surrounding cells. We searched for mutations affecting stem cell maintenance and isolated the semidominant l28 mutant, which displays premature termination of the shoot meristem and differentiation of the stem cells. Allele competition experiments suggest that l28 is a dominant-negative allele of the APETALA2 (AP2) gene, which previously has been implicated in floral patterning and seed development. Expression of both WUSCHEL (WUS) and CLAVATA3 (CLV3) genes, which regulate stem cell maintenance in the wild type, were disrupted in l28 shoot apices from early stages on. Unlike in floral patterning, AP2 mRNA is active in the center of the shoot meristem and acts via a mechanism independent of AGAMOUS, which is a repressor of WUS and stem cell maintenance in the floral meristem. Genetic analysis shows that termination of the primary shoot meristem in l28 mutants requires an active CLV signaling pathway, indicating that AP2 functions in stem cell maintenance by modifying the WUS-CLV3 feedback loop.

Light-induced carotenogenesis in Myxococcus xanthus: evidence that CarS acts as an anti-repressor of CarA.

PubMed

Whitworth, D E; Hodgson, D A

2001-11-01

In the bacterium Myxococcus xanthus, carotenoids are produced in response to illumination, as a result of expression of the crt carotenoid biosynthesis genes. The majority of crt genes are clustered in the crtEBDC operon, which is repressed in the dark by CarA. Genetic data suggest that, in the light, CarS is synthesized and achieves activation of the crtEBDC operon by removing the repressive action of CarA. As CarS contains no known DNA-binding motif, the relief of CarA-mediated repression was postulated to result from a direct interaction between these two proteins. Use of the yeast two-hybrid system demonstrated direct interaction between CarA and CarS. The two-hybrid system also implied that CarA and, possibly, CarS are capable of homodimerization. Direct evidence for CarS anti-repressor action was provided in vitro. A glutathione S-transferase (GST)-CarA protein fusion was shown to bind specifically to a palindromic operator sequence within the crtEBDC promoter. CarA was prevented from binding to its operator, and prebound CarA was removed by the addition of purified CarS. CarS is therefore an anti-repressor.

Design, Synthesis, and Evaluation of Novel p-(methylthio)styryl Substituted Quindoline Derivatives as Neuroblastoma RAS (NRAS) Repressors via Specific Stabilizing the RNA G-Quadruplex.

PubMed

Peng, Wang; Sun, Zhi-Yin; Zhang, Qi; Cheng, Sui-Qi; Wang, Shi-Ke; Wang, Xiao-Na; Kuang, Guo-Tao; Su, Xiao-Xuan; Tan, Jia-Heng; Huang, Zhi-Shu; Ou, Tian-Miao

2018-05-25

The human proto-oncogene neuroblastoma RAS (NRAS) contains a guanine-rich sequence in the 5'-untranslated regions (5'-UTR) of the mRNA that could form an RNA G-quadruplex structure. This structure acts as a repressor for NRAS translation and could be a potential target for anti-cancer drugs. Our previous studies found an effective scaffold, the quindoline scaffold, for binding and stabilizing the DNA G-quadruplex structures. Here, basing on the previous studies and reported RNA-specific probes, a series of novel p-(methylthio)styryl substituted quindoline (MSQ) derivatives were designed, synthesized and evaluated as NRAS RNA G-quadruplex ligands. Panels of experiments turned out that the introduction of p-(methylthio)styryl side chain could enhance the specific binding to the NRAS RNA G-quadruplex. One of the hits, 4a-10, showed strong stabilizing activity on the G-quadruplex, and subsequently repressed NRAS's translation and inhibited tumor cells proliferation. Our finding provided a novel strategy to discover novel NRAS repressors by specifically binding to the RNA G-quadruplex in the 5'-UTR of mRNA.

Cntnap2 expression in the cerebellum of Foxp2(R552H) mice, with a mutation related to speech-language disorder.

PubMed

Fujita, Eriko; Tanabe, Yuko; Momoi, Mariko Y; Momoi, Takashi

2012-01-11

Foxp2(R552H) knock-in (KI) mice carrying a mutation related to human speech-language disorder exhibit impaired ultrasonic vocalization and poor Purkinje cell development. Foxp2 is a forkhead domain-containing transcriptional repressor that associates with its co-repressor CtBP; Foxp2(R552H) displays reduced DNA binding activity. A genetic connection between FOXP2 and CNTNAP2 has been demonstrated in vitro, but not in vivo. Here we show that Cntnap2 mRNA levels significantly increased in the cerebellum of Foxp2(R552H) KI pups, although the cerebellar population of Foxp2-positive Purkinje cells was very small. Furthermore, Cntnap2 immunofluorescence did not decrease in the poorly developed Purkinje cells of Foxp2(R552H) KI pups, although synaptophysin immunofluorescence decreased. Cntnap2 and CtBP were ubiquitously expressed, while Foxp2 co-localized with CtBP only in Purkinje cells. Taken together, these observations suggest that Foxp2 may regulate ultrasonic vocalization by associating with CtBP in Purkinje cells; Cntnap2 may be a target of this co-repressor. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Integration host factor is necessary for lysogenization of Escherichia coli by bacteriophage P2.

PubMed

Saha, S; Haggård-Ljungquist, E; Nordström, K

1990-01-01

Whether infection by bacteriophage P2 results in lysogenization of the host or vegetative growth of the phage depends upon a race between transcription from the repressor promoter Pc and the early promoter Pe; transcription from these promoters is mutually exclusive, since the Pc repressor Cox is formed from the Pe transcript and the Pe repressor C from the Pc transcript. The involvement of integration host factor (IHF) in the lysogenization of Escherichia coli K12 by P2 was tested by comparing wild-type and IHF-deficient (himA and himD) mutants. No lysogenic clones were formed following infection of the mutant bacteria. A switch plasmid that contains Pc-C-cat and Pe-cox-kan was used to test the choice for expression of Pc versus Pe. In the wild-type K12 bacteria, 20% of the clones expressed Pe transcription and 80% Pc transcription, whereas all transformed IHF-defective clones expressed transcription from Pe only. The effects of IHF on the in vivo expression of the Pe and Pc promoters were only marginal. The IHF protein was found to bind upstream of the Pe promoter, where a potential ihf sequence is located.

Functional requirements for bacteriophage growth: gene essentiality and expression in mycobacteriophage Giles.

PubMed

Dedrick, Rebekah M; Marinelli, Laura J; Newton, Gerald L; Pogliano, Kit; Pogliano, Joseph; Hatfull, Graham F

2013-05-01

Bacteriophages represent a majority of all life forms, and the vast, dynamic population with early origins is reflected in their enormous genetic diversity. A large number of bacteriophage genomes have been sequenced. They are replete with novel genes without known relatives. We know little about their functions, which genes are required for lytic growth, and how they are expressed. Furthermore, the diversity is such that even genes with required functions - such as virion proteins and repressors - cannot always be recognized. Here we describe a functional genomic dissection of mycobacteriophage Giles, in which the virion proteins are identified, genes required for lytic growth are determined, the repressor is identified, and the transcription patterns determined. We find that although all of the predicted phage genes are expressed either in lysogeny or in lytic growth, 45% of the predicted genes are non-essential for lytic growth. We also describe genes required for DNA replication, show that recombination is required for lytic growth, and that Giles encodes a novel repressor. RNAseq analysis reveals abundant expression of a small non-coding RNA in a lysogen and in late lytic growth, although it is non-essential for lytic growth and does not alter lysogeny. © 2013 Blackwell Publishing Ltd.

Molecular dynamics simulation of trp-repressor/operator complex: analysis of hydrogen bond patterns of protein DNA interaction

NASA Astrophysics Data System (ADS)

Suenaga, A.; Yatsu, C.; Komeiji, Y.; Uebayasi, M.; Meguro, T.; Yamato, I.

2000-08-01

Molecular dynamics simulation of Escherichia colitrp-repressor/operator complex was performed to elucidate protein-DNA interactions in solution for 800 ps on special-purpose computer MD-GRAPE. The Ewald summation method was employed to treat the electrostatic interaction without cutoff. DNA kept stable conformation in comparison with the result of the conventional cutoff method. Thus, the trajectories obtained were used to analyze the protein-DNA interaction and to understand the role of dynamics of water molecules forming sequence specific recognition interface. The dynamical cross-correlation map showed a significant positive correlation between the helix-turn-helix DNA-binding motifs and the major grooves of operator DNA. The extensive contact surface was stable during the simulation. Most of the contacts consisted of direct interactions between phosphates of DNA and the protein, but several water-mediated polar contacts were also observed. These water-mediated interactions, which were also seen in the crystal structure (Z. Otwinowski, et al., Nature, 335 (1998) 321) emerged spontaneously from the randomized initial configuration of the solvent. This result suggests the importance of the water-mediated interaction in specific recognition of DNA by the trp-repressor, consistent with X-ray structural information.

Functional domains of the Drosophila Engrailed protein.

PubMed Central

Han, K; Manley, J L

1993-01-01

We have studied the transcriptional activity of the Drosophila homeodomain protein Engrailed (En) by using a transient expression assay employing Schneider L2 cells. En was found to very strongly repress promoters activated by a variety of different activator proteins. However, unlike another Drosophila homeodomain-containing repressor, Even-skipped (Eve), En was unable to repress the activity of several basal promoters in the absence of activator expression. These findings indicate that En is a specific repressor of activated transcription, and suggest that En may repress transcription by a different mechanism than Eve, perhaps by interfering with interactions between transcriptional activators and the general transcription machinery. By analyzing the properties of a variety of En mutants, we identified a minimal repression domain composed of 55 residues, which can function when fused to a heterologous DNA binding domain. Like repression domains identified in the Drosophila repressors Eve and Krüppel, the En repression domain is rich in alanine residues (26%), but unlike these other domains, is moderately charged (six arginine and three glutamic acid residues). Separate regions of En that may in some circumstances function in transcriptional activation were also identified. Images PMID:8334991

Modeling the Lac repressor-operator assembly: The influence of DNA looping on Lac repressor conformation

PubMed Central

Swigon, David; Coleman, Bernard D.; Olson, Wilma K.

2006-01-01

Repression of transcription of the Escherichia coli Lac operon by the Lac repressor (LacR) is accompanied by the simultaneous binding of LacR to two operators and the formation of a DNA loop. A recently developed theory of sequence-dependent DNA elasticity enables one to relate the fine structure of the LacR–DNA complex to a wide range of heretofore-unconnected experimental observations. Here, that theory is used to calculate the configuration and free energy of the DNA loop as a function of its length and base-pair sequence, its linking number, and the end conditions imposed by the LacR tetramer. The tetramer can assume two types of conformations. Whereas a rigid V-shaped structure is observed in the crystal, EM images show extended forms in which two dimer subunits are flexibly joined. Upon comparing our computed loop configurations with published experimental observations of permanganate sensitivities, DNase I cutting patterns, and loop stabilities, we conclude that linear DNA segments of short-to-medium chain length (50–180 bp) give rise to loops with the extended form of LacR and that loops formed within negatively supercoiled plasmids induce the V-shaped structure. PMID:16785444

SnoN co-repressor binds and represses smad7 gene promoter.

PubMed

Briones-Orta, Marco A; Sosa-Garrocho, Marcela; Moreno-Alvarez, Paola; Fonseca-Sánchez, Miguel A; Macías-Silva, Marina

2006-03-17

SnoN and Ski oncoproteins are co-repressors for Smad proteins and repress TGF-beta-responsive gene expression. The smad7 gene is a TGF-beta target induced by Smad signaling, and its promoter contains the Smad-binding element (SBE) required for a positive regulation by the TGF-beta/Smad pathway. SnoN and Ski co-repressors also bind SBE but regulate negatively smad7 gene. Ski along with Smad4 binds and represses the smad7 promoter, whereas the repression mechanism by SnoN is not clear. Ski and SnoN overexpression inhibits smad7 reporter expression induced through TGF-beta signaling. Using chromatin immunoprecipitation assays, we found that SnoN binds smad7 promoter at the basal condition, whereas after a short TGF-beta treatment for 15-30 min SnoN is downregulated and no longer bound smad7 promoter. Interestingly, after a prolonged TGF-beta treatment SnoN is upregulated and returns to its position on the smad7 promoter, functioning probably as a negative feedback control. Thus, SnoN also seems to regulate negatively the TGF-beta-responsive smad7 gene by binding and repressing its promoter in a similar way to Ski.

Liquefaction Of Coal With Surfactant And Disposable Catalyst

NASA Technical Reports Server (NTRS)

Hickey, Gregory S.; Sharma, Pramod K.

1996-01-01

Fuels derived from coal more competitive with petroleum products. Improved coal-liquefaction process exploits synergistic effects of disposable iron oxide catalyst and cheap anionic surfactant. Efficiency of conversion achieved in significantly higher than efficiencies obtained with addition of either surfactant or catalyst alone. No costly pretreatment necessary, and increase in conversion achieved under processing conditions milder than those used heretofore in liquefaction of coal. Quality of distillates obtained after liquefaction in process expected superior to distillates obtained after liquefaction by older techniques.

Sustainment and Net-ready Key Performance Parameters (KPP) in an Enterprise Information System (EIS) Value Assurance Framework (VAF)

DTIC Science & Technology

2014-04-01

adapts the concept of “Communities of Interest” (COI) identified in DoD GIG policy for this purpose. In the VAF construct COIs become hands-on beta...developers. This approach both leverages COTS economy of scale and nudges COTS development in directions useful to the government. Programs can write...schedule  Exploit new GIG acquisition policies  Extend and expand pure COTS competition  Issue simple use cases in lieu of traditional RFI/RFP

Using adhesives as a means to reduce costs and increase performance in the production of photovoltaic electricity.

PubMed

Thorey, Claire

2013-01-01

Although adhesives have been used for many years to manufacture cars in more efficient ways, their potential has not yet been fully exploited by the renewable energy industry. We argue in this article that photovoltaic module manufacturers can save costs and differentiate from competition by careful selection and use of their bonding systems. Clever adhesives can enable new, more effective product designs and can play a major role in the longevity of the complete product.

The myth of managed care. Moving beyond managing costs to really managing care.

PubMed

Houck, S

1997-01-01

Today's managed care manages costs, not care. Care is lopsided with costly physician and provider control of the information, decision-making and treatment processes that are built on outdated fee-for-service incentives. Fast moving providers who exploit opportunities to redesign care, shifting more responsibility and control to non-physician providers and to patients will gain a major competitive advantage. These providers are much more likely to stand out from their peers, enabling them to attract patients and contracts.

Exploiting temporal gradients of antibiotic concentration against the emergence of resistance

NASA Astrophysics Data System (ADS)

Bauer, Marianne; Ngampruetikorn, Vudtiwat; Frey, Erwin; Stephens, Greg

A very simple model for antibiotic resistance - involving one normal and one more resistant species interacting indirectly through a carrying capacity - shows that the temporal variation of the antibiotic can affect the effect of the antibiotic. For a single antibiotic pulse, we find that for different minimal inhibitory concentrations of the two species an optimal pulse shape may exist, which increases the likelihood of bacterial extinction. For a long series of pulses, efficiency does not vary monotonically with the length of the gap between two individual pulses, but instead, the gap length can be optimised by exploiting the competition between the two species. Finally, a series of pulses is not always more efficient than a single pulse. Shorter pulses may be more efficient in an initial time window without risking population level resistance. We elucidate this behaviour with a phase diagram, and discuss the meaning of this work for current experiments. (equally contributing author).

A novel hybrid meta-heuristic technique applied to the well-known benchmark optimization problems

NASA Astrophysics Data System (ADS)

Abtahi, Amir-Reza; Bijari, Afsane

2017-03-01

In this paper, a hybrid meta-heuristic algorithm, based on imperialistic competition algorithm (ICA), harmony search (HS), and simulated annealing (SA) is presented. The body of the proposed hybrid algorithm is based on ICA. The proposed hybrid algorithm inherits the advantages of the process of harmony creation in HS algorithm to improve the exploitation phase of the ICA algorithm. In addition, the proposed hybrid algorithm uses SA to make a balance between exploration and exploitation phases. The proposed hybrid algorithm is compared with several meta-heuristic methods, including genetic algorithm (GA), HS, and ICA on several well-known benchmark instances. The comprehensive experiments and statistical analysis on standard benchmark functions certify the superiority of the proposed method over the other algorithms. The efficacy of the proposed hybrid algorithm is promising and can be used in several real-life engineering and management problems.

Stable switching among high-order modes in polariton condensates

NASA Astrophysics Data System (ADS)

Sun, Yongbao; Yoon, Yoseob; Khan, Saeed; Ge, Li; Steger, Mark; Pfeiffer, Loren N.; West, Ken; Türeci, Hakan E.; Snoke, David W.; Nelson, Keith A.

2018-01-01

We report multistate optical switching among high-order bouncing-ball modes ("ripples") and whispering-gallery modes ("petals") of exciton-polariton condensates in a laser-generated annular trap. By tailoring the diameter and power of the annular trap, the polariton condensate can be switched among different trapped modes, accompanied by redistribution of spatial densities and superlinear increase in the emission intensities, implying that polariton condensates in this geometry could be exploited for an all-optical multistate switch. A model based on non-Hermitian modes of the generalized Gross-Pitaevskii equation reveals that this mode switching arises from competition between pump-induced gain and in-plane polariton loss. The parameters for reproducible switching among trapped modes have been measured experimentally, giving us a phase diagram for mode switching. Taken together, the experimental result and theoretical modeling advance our fundamental understanding of the spontaneous emergence of coherence and move us toward its practical exploitation.

Objects tell us what action we can expect: dissociating brain areas for retrieval and exploitation of action knowledge during action observation in fMRI

PubMed Central

Schubotz, Ricarda I.; Wurm, Moritz F.; Wittmann, Marco K.; von Cramon, D. Yves

2014-01-01

Objects are reminiscent of actions often performed with them: knife and apple remind us on peeling the apple or cutting it. Mnemonic representations of object-related actions (action codes) evoked by the sight of an object may constrain and hence facilitate recognition of unrolling actions. The present fMRI study investigated if and how action codes influence brain activation during action observation. The average number of action codes (NAC) of 51 sets of objects was rated by a group of n = 24 participants. In an fMRI study, different volunteers were asked to recognize actions performed with the same objects presented in short videos. To disentangle areas reflecting the storage of action codes from those exploiting them, we showed object-compatible and object-incompatible (pantomime) actions. Areas storing action codes were considered to positively co-vary with NAC in both object-compatible and object-incompatible action; due to its role in tool-related tasks, we here hypothesized left anterior inferior parietal cortex (aIPL). In contrast, areas exploiting action codes were expected to show this correlation only in object-compatible but not incompatible action, as only object-compatible actions match one of the active action codes. For this interaction, we hypothesized ventrolateral premotor cortex (PMv) to join aIPL due to its role in biasing competition in IPL. We found left anterior intraparietal sulcus (IPS) and left posterior middle temporal gyrus (pMTG) to co-vary with NAC. In addition to these areas, action codes increased activity in object-compatible action in bilateral PMv, right IPS, and lateral occipital cortex (LO). Findings suggest that during action observation, the brain derives possible actions from perceived objects, and uses this information to shape action recognition. In particular, the number of expectable actions quantifies the activity level at PMv, IPL, and pMTG, but only PMv reflects their biased competition while observed action unfolds. PMID:25009519

Tri-track: free software for large-scale particle tracking.

PubMed

Vallotton, Pascal; Olivier, Sandra

2013-04-01

The ability to correctly track objects in time-lapse sequences is important in many applications of microscopy. Individual object motions typically display a level of dynamic regularity reflecting the existence of an underlying physics or biology. Best results are obtained when this local information is exploited. Additionally, if the particle number is known to be approximately constant, a large number of tracking scenarios may be rejected on the basis that they are not compatible with a known maximum particle velocity. This represents information of a global nature, which should ideally be exploited too. Some time ago, we devised an efficient algorithm that exploited both types of information. The tracking task was reduced to a max-flow min-cost problem instance through a novel graph structure that comprised vertices representing objects from three consecutive image frames. The algorithm is explained here for the first time. A user-friendly implementation is provided, and the specific relaxation mechanism responsible for the method's effectiveness is uncovered. The software is particularly competitive for complex dynamics such as dense antiparallel flows, or in situations where object displacements are considerable. As an application, we characterize a remarkable vortex structure formed by bacteria engaged in interstitial motility.

Patterns of resource exploitation in four coexisting globeflower fly species ( Chiastocheta sp.)

NASA Astrophysics Data System (ADS)

Pompanon, François; Pettex, Emeline; Després, Laurence

2006-03-01

Life history and spatio-temporal patterns of resource utilisation were characterised in four Chiastocheta (Diptera: Anthomyiidae) species, whose larvae compete as seed predators on Trollius europaeus fruits. Interspecific co-occurrence was observed in 80% of the resource patches (= Trollius fruits) in the two communities studied. Isolated larvae from all species had a similar food intake, but differed in development time and size at emergence. Different species exhibit contrasting resource exploitation strategies with specific mining patterns and a partial temporal shift. Two species exhibited particularly singular strategies. C. rotundiventris escaped from strong interactions with other species because it was the first species to develop and the only one to exploit the central pith of Trollius fruits. The key role of this species as the main pollinator of the host-plant appears to be a by-product of constraints imposed by occupying a restricted niche. Although the resource is ephemeral due to seed dispersal, C. dentifera, the last species to oviposit, is not disadvantaged because it has a short development time and rapid food intake. The different patterns can partly explain the stability of Chiastocheta communities, but do not prevent competition to occur at high larval densities.

Self-organized discrimination of resources.

PubMed

Campo, Alexandre; Garnier, Simon; Dédriche, Olivier; Zekkri, Mouhcine; Dorigo, Marco

2011-01-01

When selecting a resource to exploit, an insect colony must take into account at least two constraints: the resource must be abundant enough to sustain the whole group, but not too large to limit exploitation costs, and risks of conflicts with other colonies. Following recent results on cockroaches and ants, we introduce here a behavioral mechanism that satisfies these two constraints. Individuals simply modulate their probability to switch to another resource as a function of the local density of conspecifics locally detected. As a result, the individuals gather at the smallest resource that can host the whole group, hence reducing competition and exploitation costs while fulfilling the overall group's needs. Our analysis reveals that the group becomes better at discriminating between similar resources as it grows in size. Also, the discrimination mechanism is flexible and the group readily switches to a better suited resource as it appears in the environment. The collective decision emerges through the self-organization of individuals, that is, in absence of any centralized control. It also requires a minimal individual cognitive investment, making the proposed mechanism likely to occur in other social species and suitable for the development of distributed decision making tools.

Self-Organized Discrimination of Resources

PubMed Central

Campo, Alexandre; Garnier, Simon; Dédriche, Olivier; Zekkri, Mouhcine; Dorigo, Marco

2011-01-01

When selecting a resource to exploit, an insect colony must take into account at least two constraints: the resource must be abundant enough to sustain the whole group, but not too large to limit exploitation costs, and risks of conflicts with other colonies. Following recent results on cockroaches and ants, we introduce here a behavioral mechanism that satisfies these two constraints. Individuals simply modulate their probability to switch to another resource as a function of the local density of conspecifics locally detected. As a result, the individuals gather at the smallest resource that can host the whole group, hence reducing competition and exploitation costs while fulfilling the overall group's needs. Our analysis reveals that the group becomes better at discriminating between similar resources as it grows in size. Also, the discrimination mechanism is flexible and the group readily switches to a better suited resource as it appears in the environment. The collective decision emerges through the self-organization of individuals, that is, in absence of any centralized control. It also requires a minimal individual cognitive investment, making the proposed mechanism likely to occur in other social species and suitable for the development of distributed decision making tools. PMID:21625643

Exact lower and upper bounds on stationary moments in stochastic biochemical systems

NASA Astrophysics Data System (ADS)

Ghusinga, Khem Raj; Vargas-Garcia, Cesar A.; Lamperski, Andrew; Singh, Abhyudai

2017-08-01

In the stochastic description of biochemical reaction systems, the time evolution of statistical moments for species population counts is described by a linear dynamical system. However, except for some ideal cases (such as zero- and first-order reaction kinetics), the moment dynamics is underdetermined as lower-order moments depend upon higher-order moments. Here, we propose a novel method to find exact lower and upper bounds on stationary moments for a given arbitrary system of biochemical reactions. The method exploits the fact that statistical moments of any positive-valued random variable must satisfy some constraints that are compactly represented through the positive semidefiniteness of moment matrices. Our analysis shows that solving moment equations at steady state in conjunction with constraints on moment matrices provides exact lower and upper bounds on the moments. These results are illustrated by three different examples—the commonly used logistic growth model, stochastic gene expression with auto-regulation and an activator-repressor gene network motif. Interestingly, in all cases the accuracy of the bounds is shown to improve as moment equations are expanded to include higher-order moments. Our results provide avenues for development of approximation methods that provide explicit bounds on moments for nonlinear stochastic systems that are otherwise analytically intractable.

A super-family of transcriptional activators regulates bacteriophage packaging and lysis in Gram-positive bacteria

PubMed Central

Quiles-Puchalt, Nuria; Tormo-Más, María Ángeles; Campoy, Susana; Toledo-Arana, Alejandro; Monedero, Vicente; Lasa, Íñigo; Novick, Richard P.; Christie, Gail E.; Penadés, José R.

2013-01-01

The propagation of bacteriophages and other mobile genetic elements requires exploitation of the phage mechanisms involved in virion assembly and DNA packaging. Here, we identified and characterized four different families of phage-encoded proteins that function as activators required for transcription of the late operons (morphogenetic and lysis genes) in a large group of phages infecting Gram-positive bacteria. These regulators constitute a super-family of proteins, here named late transcriptional regulators (Ltr), which share common structural, biochemical and functional characteristics and are unique to this group of phages. They are all small basic proteins, encoded by genes present at the end of the early gene cluster in their respective phage genomes and expressed under cI repressor control. To control expression of the late operon, the Ltr proteins bind to a DNA repeat region situated upstream of the terS gene, activating its transcription. This involves the C-terminal part of the Ltr proteins, which control specificity for the DNA repeat region. Finally, we show that the Ltr proteins are the only phage-encoded proteins required for the activation of the packaging and lysis modules. In summary, we provide evidence that phage packaging and lysis is a conserved mechanism in Siphoviridae infecting a wide variety of Gram-positive bacteria. PMID:23771138

Evolutionary Relationships among Actinophages and a Putative Adaptation for Growth in Streptomyces spp.

PubMed Central

Hendrix, Roger W.; Dedrick, Rebekah; Mitchell, Kaitlin; Ko, Ching-Chung; Russell, Daniel; Bell, Emma; Gregory, Matthew; Bibb, Maureen J.; Pethick, Florence; Jacobs-Sera, Deborah; Herron, Paul; Buttner, Mark J.; Hatfull, Graham F.

2013-01-01

The genome sequences of eight Streptomyces phages are presented, four of which were isolated for this study. Phages R4, TG1, ϕHau3, and SV1 were isolated previously and have been exploited as tools for understanding and genetically manipulating Streptomyces spp. We also extracted five apparently intact prophages from recent Streptomyces spp. genome projects and, together with six phage genomes in the database, we analyzed all 19 Streptomyces phage genomes with a view to understanding their relationships to each other and to other actinophages, particularly the mycobacteriophages. Fifteen of the Streptomyces phages group into four clusters of related genomes. Although the R4-like phages do not share nucleotide sequence similarity with other phages, they clearly have common ancestry with cluster A mycobacteriophages, sharing many protein homologues, common gene syntenies, and similar repressor-stoperator regulatory systems. The R4-like phage ϕHau3 and the prophage StrepC.1 (from Streptomyces sp. strain C) appear to have hijacked a unique adaptation of the streptomycetes, i.e., use of the rare UUA codon, to control translation of the essential phage protein, the terminase. The Streptomyces venezuelae generalized transducing phage SV1 was used to predict the presence of other generalized transducing phages for different Streptomyces species. PMID:23995638

Thiol-Based Redox Switches and Gene Regulation

PubMed Central

2011-01-01

Abstract Cysteine is notable among the universal, proteinogenic amino acids for its facile redox chemistry. Cysteine thiolates are readily modified by reactive oxygen species (ROS), reactive electrophilic species (RES), and reactive nitrogen species (RNS). Although thiol switches are commonly triggered by disulfide bond formation, they can also be controlled by S-thiolation, S-alkylation, or modification by RNS. Thiol-based switches are common in both prokaryotic and eukaryotic organisms and activate functions that detoxify reactive species and restore thiol homeostasis while repressing functions that would be deleterious if expressed under oxidizing conditions. Here, we provide an overview of the best-understood examples of thiol-based redox switches that affect gene expression. Intra- or intermolecular disulfide bond formation serves as a direct regulatory switch for several bacterial transcription factors (OxyR, OhrR/2-Cys, Spx, YodB, CrtJ, and CprK) and indirectly regulates others (the RsrA anti-σ factor and RegB sensory histidine kinase). In eukaryotes, thiol-based switches control the yeast Yap1p transcription factor, the Nrf2/Keap1 electrophile and oxidative stress response, and the Chlamydomonas NAB1 translational repressor. Collectively, these regulators reveal a remarkable range of chemical modifications exploited by Cys residues to effect changes in gene expression. Antioxid. Redox Signal. 14, 1049—1063. PMID:20626317

Description of a nanobody-based competitive immunoassay to detect tsetse fly exposure.

PubMed

Caljon, Guy; Hussain, Shahid; Vermeiren, Lieve; Van Den Abbeele, Jan

2015-02-01

Tsetse flies are the main vectors of human and animal African trypanosomes. The Tsal proteins in tsetse fly saliva were previously identified as suitable biomarkers of bite exposure. A new competitive assay was conceived based on nanobody (Nb) technology to ameliorate the detection of anti-Tsal antibodies in mammalian hosts. A camelid-derived Nb library was generated against the Glossina morsitans morsitans sialome and exploited to select Tsal specific Nbs. One of the three identified Nb families (family III, TsalNb-05 and TsalNb-11) was found suitable for anti-Tsal antibody detection in a competitive ELISA format. The competitive ELISA was able to detect exposure to a broad range of tsetse species (G. morsitans morsitans, G. pallidipes, G. palpalis gambiensis and G. fuscipes) and did not cross-react with the other hematophagous insects (Stomoxys calcitrans and Tabanus yao). Using a collection of plasmas from tsetse-exposed pigs, the new test characteristics were compared with those of the previously described G. m. moristans and rTsal1 indirect ELISAs, revealing equally good specificities (> 95%) and positive predictive values (> 98%) but higher negative predictive values and hence increased sensitivity (> 95%) and accuracy (> 95%). We have developed a highly accurate Nb-based competitive immunoassay to detect specific anti-Tsal antibodies induced by various tsetse fly species in a range of hosts. We propose that this competitive assay provides a simple serological indicator of tsetse fly presence without the requirement of test adaptation to the vertebrate host species. In addition, the use of monoclonal Nbs for antibody detection is innovative and could be applied to other tsetse fly salivary biomarkers in order to achieve a multi-target immunoprofiling of hosts. In addition, this approach could be broadened to other pathogenic organisms for which accurate serological diagnosis remains a bottleneck.

Transcriptional activation of NAD+-dependent protein deacetylase SIRT1 by nuclear receptor TLX.

PubMed

Iwahara, Naotoshi; Hisahara, Shin; Hayashi, Takashi; Horio, Yoshiyuki

2009-09-04

An orphan nuclear receptor TLX is a transcriptional repressor that promotes the proliferation and self-renewal of neural precursor cells (NPCs). SIRT1, an NAD(+)-dependent protein deacetylase, is highly expressed in the NPCs and participates in neurogenesis. Here, we found that TLX colocalized with SIRT1 and knockdown of TLX by small interfering RNAs decreased SIRT1 levels in NPCs. TLX increased the SIRT1 expression by binding to the newly identified TLX-activating element in the SIRT1 gene promoter in HEK293 cells. Thus, TLX is an inducer of SIRT1 and may contribute to neurogenesis both as a transactivator and as a repressor.

Negative Regulation of Violacein Biosynthesis in Chromobacterium violaceum.

PubMed

Devescovi, Giulia; Kojic, Milan; Covaceuszach, Sonia; Cámara, Miguel; Williams, Paul; Bertani, Iris; Subramoni, Sujatha; Venturi, Vittorio

2017-01-01

In Chromobacteium violaceum , the purple pigment violacein is under positive regulation by the N -acylhomoserine lactone CviI/R quorum sensing system and negative regulation by an uncharacterized putative repressor. In this study we report that the biosynthesis of violacein is negatively controlled by a novel repressor protein, VioS. The violacein operon is regulated negatively by VioS and positively by the CviI/R system in both C. violaceum and in a heterologous Escherichia coli genetic background. VioS does not regulate the CviI/R system and apart from violacein, VioS, and quorum sensing regulate other phenotypes antagonistically. Quorum sensing regulated phenotypes in C. violaceum are therefore further regulated providing an additional level of control.

Mitosis-associated repression in development.

PubMed

Esposito, Emilia; Lim, Bomyi; Guessous, Ghita; Falahati, Hanieh; Levine, Michael

2016-07-01

Transcriptional repression is a pervasive feature of animal development. Here, we employ live-imaging methods to visualize the Snail repressor, which establishes the boundary between the presumptive mesoderm and neurogenic ectoderm of early Drosophila embryos. Snail target enhancers were attached to an MS2 reporter gene, permitting detection of nascent transcripts in living embryos. The transgenes exhibit initially broad patterns of transcription but are refined by repression in the mesoderm following mitosis. These observations reveal a correlation between mitotic silencing and Snail repression. We propose that mitosis and other inherent discontinuities in transcription boost the activities of sequence-specific repressors, such as Snail. © 2016 Esposito et al.; Published by Cold Spring Harbor Laboratory Press.

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

PubMed

Malik, Sohail; Roeder, Robert G

2010-11-01

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

High density growth of T7 expression strains with auto-induction option

DOEpatents

Studier, F. William

2010-07-20

A bacterial growth medium for promoting auto-induction of transcription of cloned DNA in cultures of bacterial cells grown batchwise is disclosed. The transcription is under the control of a lac repressor. Also disclosed is a bacterial growth medium for improving the production of a selenomethionine-containing protein or polypeptide in a bacterial cell, the protein or polypeptide being produced by recombinant DNA techniques from a lac or T7lac promoter, the bacterial cell encoding a vitamin B12-dependent homocysteine methylase. Finally, disclosed is a bacterial growth medium for suppressing auto-induction of expression in cultures of bacterial cells grown batchwise, said transcription being under the control of lac repressor.

Transcriptional activation of NAD{sup +}-dependent protein deacetylase SIRT1 by nuclear receptor TLX

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

Iwahara, Naotoshi; Hisahara, Shin; Hayashi, Takashi

2009-09-04

An orphan nuclear receptor TLX is a transcriptional repressor that promotes the proliferation and self-renewal of neural precursor cells (NPCs). SIRT1, an NAD{sup +}-dependent protein deacetylase, is highly expressed in the NPCs and participates in neurogenesis. Here, we found that TLX colocalized with SIRT1 and knockdown of TLX by small interfering RNAs decreased SIRT1 levels in NPCs. TLX increased the SIRT1 expression by binding to the newly identified TLX-activating element in the SIRT1 gene promoter in HEK293 cells. Thus, TLX is an inducer of SIRT1 and may contribute to neurogenesis both as a transactivator and as a repressor.

Ants and ant scent reduce bumblebee pollination of artificial flowers.

PubMed

Cembrowski, Adam R; Tan, Marcus G; Thomson, James D; Frederickson, Megan E

2014-01-01

Ants on flowers can disrupt pollination by consuming rewards or harassing pollinators, but it is difficult to disentangle the effects of these exploitative and interference forms of competition on pollinator behavior. Using highly rewarding and quickly replenishing artificial flowers that simulate male or female function, we allowed bumblebees (Bombus impatiens) to forage (1) on flowers with or without ants (Myrmica rubra) and (2) on flowers with or without ant scent cues. Bumblebees transferred significantly more pollen analogue both to and from ant-free flowers, demonstrating that interference competition with ants is sufficient to modify pollinator foraging behavior. Bees also removed significantly less pollen analogue from ant-scented flowers than from controls, making this the first study to show that bees can use ant scent to avoid harassment at flowers. Ant effects on pollinator behavior, possibly in addition to their effects on pollen viability, may contribute to the evolution of floral traits minimizing ant visitation.

Marine Mammal Impacts in Exploited Ecosystems: Would Large Scale Culling Benefit Fisheries?

PubMed Central

Morissette, Lyne; Christensen, Villy; Pauly, Daniel

2012-01-01

Competition between marine mammals and fisheries for marine resources—whether real or perceived—has become a major issue for several countries and in international fora. We examined trophic interactions between marine mammals and fisheries based on a resource overlap index, using seven Ecopath models including marine mammal groups. On a global scale, most food consumed by marine mammals consisted of prey types that were not the main target of fisheries. For each ecosystem, the primary production required (PPR) to sustain marine mammals was less than half the PPR to sustain fisheries catches. We also developed an index representing the mean trophic level of marine mammal's consumption (TLQ) and compared it with the mean trophic level of fisheries' catches (TLC). Our results showed that overall TLQ was lower than TLC (2.88 versus 3.42). As fisheries increasingly exploit lower-trophic level species, the competition with marine mammals may become more important. We used mixed trophic impact analysis to evaluate indirect trophic effects of marine mammals, and in some cases found beneficial effects on some prey. Finally, we assessed the change in the trophic structure of an ecosystem after a simulated extirpation of marine mammal populations. We found that this lead to alterations in the structure of the ecosystems, and that there was no clear and direct relationship between marine mammals' predation and the potential catch by fisheries. Indeed, total biomass, with no marine mammals in the ecosystem, generally remained surprisingly similar, or even decreased for some species. PMID:22970153

Marine mammal impacts in exploited ecosystems: would large scale culling benefit fisheries?

PubMed

Morissette, Lyne; Christensen, Villy; Pauly, Daniel

2012-01-01

Competition between marine mammals and fisheries for marine resources-whether real or perceived-has become a major issue for several countries and in international fora. We examined trophic interactions between marine mammals and fisheries based on a resource overlap index, using seven Ecopath models including marine mammal groups. On a global scale, most food consumed by marine mammals consisted of prey types that were not the main target of fisheries. For each ecosystem, the primary production required (PPR) to sustain marine mammals was less than half the PPR to sustain fisheries catches. We also developed an index representing the mean trophic level of marine mammal's consumption (TL(Q)) and compared it with the mean trophic level of fisheries' catches (TL(C)). Our results showed that overall TL(Q) was lower than TL(C) (2.88 versus 3.42). As fisheries increasingly exploit lower-trophic level species, the competition with marine mammals may become more important. We used mixed trophic impact analysis to evaluate indirect trophic effects of marine mammals, and in some cases found beneficial effects on some prey. Finally, we assessed the change in the trophic structure of an ecosystem after a simulated extirpation of marine mammal populations. We found that this lead to alterations in the structure of the ecosystems, and that there was no clear and direct relationship between marine mammals' predation and the potential catch by fisheries. Indeed, total biomass, with no marine mammals in the ecosystem, generally remained surprisingly similar, or even decreased for some species.

Evidence for competitive dominance of Pink salmon (Oncorhynchus gorbuscha) over other Salmonids in the North Pacific Ocean

USGS Publications Warehouse

Ruggerone, G.T.; Nielsen, J.L.

2004-01-01

Relatively little is known about fish species interactions in offshore areas of the world's oceans because adequate experimental controls are typically unavailable in such vast areas. However, pink salmon (Oncorhynchus gorbuscha) are numerous and have an alternating-year pattern of abundance that provides a natural experimental control to test for interspecific competition in the North Pacific Ocean and Bering Sea. Since a number of studies have recently examined pink salmon interactions with other salmon, we reviewed them in an effort to describe patterns of interaction over broad regions of the ocean. Research consistently indicated that pink salmon significantly altered prey abundance of other salmon species (e.g., zooplankton, squid), leading to altered diet, reduced total prey consumption and growth, delayed maturation, and reduced survival, depending on species and locale. Reduced survival was observed in chum salmon (O. keta) and Chinook salmon (O. tshawytscha) originating from Puget Sound and in Bristol Bay sockeye salmon (O. nerka). Growth of pink salmon was not measurably affected by other salmon species, but their growth was sometimes inversely related to their own abundance. In all marine studies, pink salmon affected other species through exploitation of prey resources rather than interference. Interspecific competition was observed in nearshore and offshore waters of the North Pacific Ocean and Bering Sea, and one study documented competition between species originating from different continents. Climate change had variable effects on competition. In the North Pacific Ocean, competition was observed before and after the ocean regime shift in 1977 that significantly altered abundances of many marine species, whereas a study in the Pacific Northwest reported a shift from predation- to competition-based mortality in response to the 1982/1983 El Nino. Key traits of pink salmon that influenced competition with other salmonids included great abundance, high consumption rates and rapid growth, degree of diet overlap or consumption of lower trophic level prey, and early migration timing into the ocean. The consistent pattern of findings from multiple regions of the ocean provides evidence that interspecific competition can significantly influence salmon population dynamics and that pink salmon may be the dominant competitor among salmon in marine waters. ?? Springer 2005.

Disruption of Foraging by a Dominant Invasive Species to Decrease Its Competitive Ability

PubMed Central

Westermann, Fabian Ludwig; Suckling, David Maxwell; Lester, Philip John

2014-01-01

Invasive species are a major threat to biodiversity when dominant within their newly established habitat. The globally distributed Argentine ant Linepithema humile has been reported to break the trade-off between interference and exploitative competition, achieve high population densities, and overpower nests of many endemic ant species. We have used the sensitivity of the Argentine ant to the synthetic trail pheromone (Z)-9-hexadecanal to investigate species interactions for the first time. We predicted that disrupting Argentine ant trail following behaviour would reduce their competitive ability and create an opportunity for three other resident species to increase their foraging success. Argentine ant success in the control was reduced with increasing pheromone concentration, as predicted, but interactions varied among competing resident species. These behavioural variations provide an explanation for observed differences in foraging success of the competing resident species and how much each of these individual competitors can increase their foraging if the competitive ability of the dominant invader is decreased. The mechanism for the observed increase in resource acquisition of resident species appears to be a decrease in aggressive behaviour displayed by the Argentine ant, which may create an opportunity for other resident species to forage more successfully. Our demonstration of species interactions with trail pheromone disruption is the first known case of reduced dominance under a pheromone treatment in ants. PMID:24594633

TLX activates MASH1 for induction of neuronal lineage commitment of adult hippocampal neuroprogenitors.

PubMed

Elmi, Muna; Matsumoto, Yoshiki; Zeng, Zhao-jun; Lakshminarasimhan, Pavithra; Yang, Weiwen; Uemura, Akiyoshi; Nishikawa, Shin-ichi; Moshiri, Alicia; Tajima, Nobuyoshi; Agren, Hans; Funa, Keiko

2010-10-01

The orphan nuclear receptor TLX has been proposed to act as a repressor of cell cycle inhibitors to maintain the neural stem cells in an undifferentiated state, and prevents commitment into astrocyte lineages. However, little is known about the mechanism of TLX in neuronal lineage commitment and differentiation. A majority of adult rat hippocampus-derived progenitors (AHPs) cultured in the presence of FGF express a high level of TLX and a fraction of these cells also express the proneural gene MASH1. Upon FGF withdrawal, TLX rapidly decreased, while MASH1 was intensely expressed within 1h, decreasing gradually to disappear at 24h. Adenoviral transduction of TLX in AHP cells in the absence of FGF transiently increased cell proliferation, however, later resulted in neuronal differentiation by inducing MASH1, Neurogenin1, DCX, and MAP2ab. Furthermore, TLX directly targets and activates the MASH1 promoter through interaction with Sp1, recruiting co-activators whereas dismissing the co-repressor HDAC4. Conversely, silencing of TLX in AHPs decreased beta-III tubulin and DCX expression and promoted glial differentiation. Our results thus suggest that TLX not only acts as a repressor of cell cycle and glial differentiation but also activates neuronal lineage commitment in AHPs. Copyright 2010 Elsevier Inc. All rights reserved.

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

PubMed Central

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

2016-01-01

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

A Negative-Feedback Loop between the Detoxification/Antioxidant Response Factor SKN-1 and Its Repressor WDR-23 Matches Organism Needs with Environmental Conditions

PubMed Central

Leung, Chi K.; Wang, Ying; Deonarine, Andrew; Tang, Lanlan; Prasse, Stephanie

2013-01-01

Negative-feedback loops between transcription factors and repressors in responses to xenobiotics, oxidants, heat, hypoxia, DNA damage, and infection have been described. Although common, the function of feedback is largely unstudied. Here, we define a negative-feedback loop between the Caenorhabditis elegans detoxification/antioxidant response factor SKN-1/Nrf and its repressor wdr-23 and investigate its function in vivo. Although SKN-1 promotes stress resistance and longevity, we find that tight regulation by WDR-23 is essential for growth and reproduction. By disabling SKN-1 transactivation of wdr-23, we reveal that feedback is required to set the balance between growth/reproduction and stress resistance/longevity. We also find that feedback is required to set the sensitivity of a core SKN-1 target gene to an electrophile. Interestingly, the effect of feedback on target gene induction is greatly reduced when the stress response is strongly activated, presumably to ensure maximum activation of cytoprotective genes during potentially fatal conditions. Our work provides a framework for understanding the function of negative feedback in inducible stress responses and demonstrates that manipulation of feedback alone can shift the balance of competing animal processes toward cell protection, health, and longevity. PMID:23836880

Adaptive style and differences in parent and child report of health-related quality of life in children with cancer.

PubMed

Jurbergs, Nichole; Russell, Kathryn M W; Long, Alanna; Phipps, Sean

2008-01-01

The objective of this study was to examine the self-reported health-related quality of life (HRQL) of children with cancer, and the consistency between child and parent reports of child HRQL, as a function of the child's adaptive style. Participants included 199 children with cancer, 108 healthy children, and their parents. Children completed self-report measures of HRQL and adaptive style. Measures of adaptive style were used to categorize children as high anxious, low anxious, defensive high anxious or repressor. Parents completed measures reporting their children's HRQL. Adaptive style was a significant predictor of child-reported HRQL, particularly on the psychosocial scales, with children identified as repressors reporting the best HRQL. Adaptive style was also predictive of discrepancies between parent and child report of child HRQL. Repressor and low anxious children reported better HRQL than did their parents, while high anxious children reported poorer HRQL, regardless of health status. Adaptive style is a significant determinant of self-reported HRQL in children, particularly in psychosocial domains, while health status (i.e. cancer patient vs healthy control) is predictive only of physical health domains. Researchers and clinicians should be aware of the impact of child adaptive style when assessing HRQL outcomes using self- or parent report.

Bacillus subtilis IolQ (DegA) is a transcriptional repressor of iolX encoding NAD+-dependent scyllo-inositol dehydrogenase.

PubMed

Kang, Dong-Min; Michon, Christophe; Morinaga, Tetsuro; Tanaka, Kosei; Takenaka, Shinji; Ishikawa, Shu; Yoshida, Ken-Ichi

2017-07-11

Bacillus subtilis is able to utilize at least three inositol stereoisomers as carbon sources, myo-, scyllo-, and D-chiro-inositol (MI, SI, and DCI, respectively). NAD + -dependent SI dehydrogenase responsible for SI catabolism is encoded by iolX. Even in the absence of functional iolX, the presence of SI or MI in the growth medium was found to induce the transcription of iolX through an unknown mechanism. Immediately upstream of iolX, there is an operon that encodes two genes, yisR and iolQ (formerly known as degA), each of which could encode a transcriptional regulator. Here we performed an inactivation analysis of yisR and iolQ and found that iolQ encodes a repressor of the iolX transcription. The coding sequence of iolQ was expressed in Escherichia coli and the gene product was purified as a His-tagged fusion protein, which bound to two sites within the iolX promoter region in vitro. IolQ is a transcriptional repressor of iolX. Genetic evidences allowed us to speculate that SI and MI might possibly be the intracellular inducers, however they failed to antagonize DNA binding of IolQ in in vitro experiments.

Differential temporal control of Foxa.a and Zic-r.b specifies brain versus notochord fate in the ascidian embryo.

PubMed

Ikeda, Tatsuro; Satou, Yutaka

2017-01-01

In embryos of an invertebrate chordate, Ciona intestinalis, two transcription factors, Foxa.a and Zic-r.b, are required for specification of the brain and the notochord, which are derived from distinct cell lineages. In the brain lineage, Foxa.a and Zic-r.b are expressed with no temporal overlap. In the notochord lineage, Foxa.a and Zic-r.b are expressed simultaneously. In the present study, we found that the temporally non-overlapping expression of Foxa.a and Zic-r.b in the brain lineage was regulated by three repressors: Prdm1-r.a (formerly called BZ1), Prdm1-r.b (BZ2) and Hes.a. In morphant embryos of these three repressor genes, Foxa.a expression was not terminated at the normal time, and Zic-r.b was precociously expressed. Consequently, Foxa.a and Zic-r.b were expressed simultaneously, which led to ectopic activation of Brachyury and its downstream pathways for notochord differentiation. Thus, temporal controls by transcriptional repressors are essential for specification of the two distinct fates of brain and notochord by Foxa.a and Zic-r.b Such a mechanism might enable the repeated use of a limited repertoire of transcription factors in developmental gene regulatory networks. © 2017. Published by The Company of Biologists Ltd.

A chimeric repressor of petunia PH4 R2R3-MYB family transcription factor generates margined flowers in torenia.

PubMed

Kasajima, Ichiro; Sasaki, Katsutomo

2016-05-03

The development of new phenotypes is key to the commercial development of the main floricultural species and cultivars. Important new phenotypes include features such as multiple-flowers, color variations, increased flower size, new petal shapes, variegation and distinctive petal margin colourations. Although their commercial use is not yet common, the transgenic technologies provide a potentially rapid means of generating interesting new phenotypes. In this report, we construct 5 vectors which we expected to change the color of the flower anthocyanins, from purple to blue, regulating vacuolar pH. When these constructs were transformed into purple torenia, we unexpectedly recovered some genotypes having slightly margined petals. These transgenic lines expressed a chimeric repressor of the petunia PhPH4 gene under the control of Cauliflower mosaic virus 35 S RNA promoter. PhPH4 is an R2R3-type MYB transcription factor. The transgenic lines lacked pigmentation in the petal margin cells both on the adaxial and abaxial surfaces. Expressions of Flavanone 3-hydroxylase (F3H), Flavonoid 3'-hydroxylase (F3'H) and Flavonoid 3'5'-hydroxylase (F3'5'H) genes were reduced in the margins of these transgenic lines, suggesting an inhibitory effect of PhPH4 repressor on anthocyanin synthesis.

Foxp1/2/4 regulate endochondral ossification as a suppresser complex

PubMed Central

Zhao, Haixia; Zhou, Wenrong; Yao, Zhengju; Wan, Yong; Cao, Jingjing; Zhang, Lingling; Zhao, Jianzhi; Li, Hanjun; Zhou, Rujiang; Li, Baojie; Wei, Gang; Zhang, Zhenlin; French, Catherine A.; Dekker, Joseph D.; Yang, Yingzi; Fisher, Simon E.; lucker, Haley O.; Guo, Xizhi

2015-01-01

Osteoblast induction and differentiation in developing long bones is dynamically controlled by the opposing action of transcriptional activators and repressors. In contrast to the long list of activators that have been discovered over past decades, the network of repressors is not well-defined. Here we identify the expression of Foxp1/2/4 proteins, comprised of Forkhead-box (Fox) transcription factors of the Foxp subfamily, in both perichondrial skeletal progenitors and proliferating chondrocytes during endochondral ossification. Mice carrying loss-of-function and gain-of-function Foxp mutations had gross defects in appendicular skeleton formation. At the cellular level, over-expression of Foxp1/2/4 in chondroctyes abrogated osteoblast formation and chondrocyte hypertrophy. Conversely, single or compound deficiency of Foxp1/2/4 in skeletal progenitors or chondrocytes resulted in premature osteoblast differentiation in the perichondrium, coupled with impaired proliferation, survival, and hypertrophy of chondrocytes in the growth plate. Foxp1/2/4 and Runx2 proteins interacted in vitro and in vivo, and Foxp1/2/4 repressed Runx2 transactivation function in heterologous cells. This study establishes Foxp1/2/4 proteins as coordinators of osteogenesis and chondrocyte hypertrophy in developing long bones and suggests that a novel transcriptional repressor network involving Foxp1/2/4 may regulate Runx2 during endochondral ossification. PMID:25527076

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

PubMed

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

2016-01-15

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

A stationary-phase protein of Escherichia coli that affects the mode of association between the trp repressor protein and operator-bearing DNA.

PubMed

Yang, W; Ni, L; Somerville, R L

1993-06-15

Highly purified preparations of trp repressor (TrpR) protein derived from Escherichia coli strains that were engineered to overexpress this material were found to contain another protein, of 21 kDa. The second protein, designated WrbA [for tryptophan (W) repressor-binding protein] remained associated with its namesake through several sequential protein fractionation steps. The N-terminal amino acid sequence of the WrbA protein guided the design of two degenerate oligonucleotides that were used as probes in the cloning of the wrbA gene (198 codons). The WrbA protein, in purified form, was found by several criteria to enhance the formation and/or stability of noncovalent complexes between TrpR holorepressor and its primary operator targets. The formation of an operator-holorepressor-WrbA ternary complex was demonstrated by gel mobility-shift analysis. The WrbA protein alone does not interact with the trp operator. During the stationary phase, cells deficient in the WrbA protein were less efficient than wild type in their ability to repress the trp promoter. It is proposed that the WrbA protein functions as an accessory element in blocking TrpR-specific transcriptional processes that might be physiologically disadvantageous in the stationary phase of the bacterial life cycle.

RDR1 and SGS3, components of RNA-mediated gene silencing, are required for the regulation of cuticular wax biosynthesis in developing inflorescence stems of Arabidopsis.

PubMed

Lam, Patricia; Zhao, Lifang; McFarlane, Heather E; Aiga, Mytyl; Lam, Vivian; Hooker, Tanya S; Kunst, Ljerka

2012-08-01

The cuticle is a protective layer that coats the primary aerial surfaces of land plants and mediates plant interactions with the environment. It is synthesized by epidermal cells and is composed of a cutin polyester matrix that is embedded and covered with cuticular waxes. Recently, we have discovered a novel regulatory mechanism of cuticular wax biosynthesis that involves the ECERIFERUM7 (CER7) ribonuclease, a core subunit of the exosome. We hypothesized that at the onset of wax production, the CER7 ribonuclease degrades an mRNA specifying a repressor of CER3, a wax biosynthetic gene whose protein product is required for wax formation via the decarbonylation pathway. In the absence of this repressor, CER3 is expressed, leading to wax production. To identify the putative repressor of CER3 and to unravel the mechanism of CER7-mediated regulation of wax production, we performed a screen for suppressors of the cer7 mutant. Our screen resulted in the isolation of components of the RNA-silencing machinery, RNA-DEPENDENT RNA POLYMERASE1 and SUPPRESSOR OF GENE SILENCING3, implicating RNA silencing in the control of cuticular wax deposition during inflorescence stem development in Arabidopsis (Arabidopsis thaliana).

A Single Molecule Study of Two Bacteriophage Epigenetic Switches

NASA Astrophysics Data System (ADS)

Wang, Haowei

Epigenetic switches allow organisms to evolve into different states by activating/repressing different sets of genes without mutations of the underlying DNA sequence. The study of epigenetic switches is very important to understand the mechanism of human development, the origin of cancer, mental illness and fundamental processes such as gene regulation. The coliphage lambda epigenetic switch, which allows switching from lysogeny to lysis, has been studied for more than 50 years as a paradigm, and has recently received renewed attention. Atomic force microscopy (AFM) was used here to show that the lambda repressor oligomerizes on DNA, primarily as a dodecamer, to secure a DNA loop, which is the basis of the lambda switch. This study also provides support for the idea that specifically bound repressor stabilizes adjacent, non-specifically bound repressor molecules, which confers robustness to the switch. 186 is a member of a different coliphage family. One of the major differences between the two coliphage families is that lambda phages can be induced to switch from the lysogenic to the lytic state by UV radiation, but most coliphages of P2 family, to which 186 belongs, cannot. Interaction between coliphage 186 repressor and DNA is characterized by AFM and tethered particle motion (TPM). To expedite analysis of the AFM data, MatLab codes were written to automate the laborious, manual tracing procedures. The programs automatically recognize DNA segments and protein particles in an image, in order to measure the DNA length and position of bound particles as well as their height, diameter and volume. Application of these algorithms greatly improved the efficiency of AFM analysis. It was showed that 186 CI dimers form heptameric wheels, which induce DNA wrapping and different kinds of DNA looping producing various conformations of nucleoprotein complexes. Information about the dynamics of DNA wrapping and looping on 186 CI particles was also obtained by TPM.

The Phenylpropanoid Pathway Is Controlled at Different Branches by a Set of R2R3-MYB C2 Repressors in Grapevine1

PubMed Central

Cavallini, Erika; Matus, José Tomás; Finezzo, Laura; Zenoni, Sara; Loyola, Rodrigo; Guzzo, Flavia; Schlechter, Rudolf; Ageorges, Agnès; Arce-Johnson, Patricio

2015-01-01

Because of the vast range of functions that phenylpropanoids possess, their synthesis requires precise spatiotemporal coordination throughout plant development and in response to the environment. The accumulation of these secondary metabolites is transcriptionally controlled by positive and negative regulators from the MYB and basic helix-loop-helix protein families. We characterized four grapevine (Vitis vinifera) R2R3-MYB proteins from the C2 repressor motif clade, all of which harbor the ethylene response factor-associated amphiphilic repression domain but differ in the presence of an additional TLLLFR repression motif found in the strong flavonoid repressor Arabidopsis (Arabidopsis thaliana) AtMYBL2. Constitutive expression of VvMYB4a and VvMYB4b in petunia (Petunia hybrida) repressed general phenylpropanoid biosynthetic genes and selectively reduced the amount of small-weight phenolic compounds. Conversely, transgenic petunia lines expressing VvMYBC2-L1 and VvMYBC2-L3 showed a severe reduction in petal anthocyanins and seed proanthocyanidins together with a higher pH of crude petal extracts. The distinct function of these regulators was further confirmed by transient expression in tobacco (Nicotiana benthamiana) leaves and grapevine plantlets. Finally, VvMYBC2-L3 was ectopically expressed in grapevine hairy roots, showing a reduction in proanthocyanidin content together with the down-regulation of structural and regulatory genes of the flavonoid pathway as revealed by a transcriptomic analysis. The physiological role of these repressors was inferred by combining the results of the functional analyses and their expression patterns in grapevine during development and in response to ultraviolet B radiation. Our results indicate that VvMYB4a and VvMYB4b may play a key role in negatively regulating the synthesis of small-weight phenolic compounds, whereas VvMYBC2-L1 and VvMYBC2-L3 may additionally fine tune flavonoid levels, balancing the inductive effects of transcriptional activators. PMID:25659381

CaAP2 transcription factor is a candidate gene for a flowering repressor and a candidate for controlling natural variation of flowering time in Capsicum annuum.

PubMed

Borovsky, Yelena; Sharma, Vinod K; Verbakel, Henk; Paran, Ilan

2015-06-01

The APETALA2 transcription factor homolog CaAP2 is a candidate gene for a flowering repressor in pepper, as revealed by induced-mutation phenotype, and a candidate underlying a major QTL controlling natural variation in flowering time. To decipher the genetic control of transition to flowering in pepper (Capsicum spp.) and determine the extent of gene function conservation compared to model species, we isolated and characterized several ethyl methanesulfonate (EMS)-induced mutants that vary in their flowering time compared to the wild type. In the present study, we report on the isolation of an early-flowering mutant that flowers after four leaves on the primary stem compared to nine leaves in the wild-type 'Maor'. By genetic mapping and sequencing of putative candidate genes linked to the mutant phenotype, we identified a member of the APETALA2 (AP2) transcription factor family, CaAP2, which was disrupted in the early-flowering mutant. CaAP2 is a likely ortholog of AP2 that functions as a repressor of flowering in Arabidopsis. To test whether CaAP2 has an effect on controlling natural variation in the transition to flowering in pepper, we performed QTL mapping for flowering time in a cross between early and late-flowering C. annuum accessions. We identified a major QTL in a region of chromosome 2 in which CaAP2 was the most significant marker, explaining 52 % of the phenotypic variation of the trait. Sequence comparison of the CaAP2 open reading frames in the two parents used for QTL mapping did not reveal significant variation. In contrast, significant differences in expression level of CaAP2 were detected between near-isogenic lines that differ for the flowering time QTL, supporting the putative function of CaAP2 as a major repressor of flowering in pepper.

Solution structure of Mycobacterium tuberculosis NmtR in the apo-state: Insights into Ni(II)-mediated allostery

PubMed Central

Lee, Chul Won; Chakravorty, Dhruva K.; Chang, Feng-Ming James; Reyes-Caballero, Hermes; Ye, Yuzhen; Merz, Kenneth M.; Giedroc, David P.

2012-01-01

Mycobacterium tuberculosis is an obligate human respiratory pathogen that encodes approximately ten arsenic repressor (ArsR) family regulatory proteins that allow the organism to respond to a wide range of changes in its immediate microenvironment. How individual ArsR repressors have evolved to respond to selective stimuli is of intrinsic interest. The Ni(II)/Co(II)-specific repressor NmtR and related actinomycete nickel sensors harbor a conserved N-terminal αNH2-Gly2-His3-Gly4 sequence. Here, we present the solution structure of homodimeric apo-NmtR and show that the core of the molecule adopts a typical winged-helix ArsR repressor (α1-α2-α3-αR-β1-β2-α5) “open conformation” that is similar to the related zinc sensor Staphylococcus aureus CzrA, but harboring long, flexible N-terminal (residues 2-16) and C-terminal (residues 109-120) extensions. Ni(II) binding to the regulatory sites induces strong paramagnetic broadening of the α5 helical region and the extreme N-terminal tail to residue 10. Ratiometric pulse chase amidination mass spectrometry reveals that the rate of amidination of the Gly2 α-amino group is strongly attenuated in the Ni(II) complex relative to the apo-state and non-cognate Zn(II) complex. Ni(II) binding also induces dynamic disorder in the μs-ms timescale of key DNA interacting regions that likely contributes to the negative regulation of DNA binding by Ni(II). Molecular dynamics simulations and quantum chemical calculations reveal that NmtR readily accommodates a distal Ni(II) hexacoordination model involving the α-amine and His3 of the N-terminal region and α5 residues Asp91′, His93′, His104 and His107, which collectively define a new metal sensing site configuration in ArsR family regulators. PMID:22394357

Nuclear IL-33 regulates soluble ST2 receptor and IL-6 expression in primary human arterial endothelial cells and is decreased in idiopathic pulmonary arterial hypertension

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

Shao, Dongmin; Perros, Frédéric; Caramori, Gaetano

Highlights: • Nuclear IL-33 expression is reduced in vascular endothelial cells from PAH patients. • Knockdown of IL-33 leads to increased IL-6 and sST2 mRNA expression. • IL-33 binds homeobox motifs in target gene promoters and recruits repressor proteins. - Abstract: Idiopathic pulmonary arterial hypertension (IPAH) is an incurable condition leading to right ventricular failure and death and inflammation is postulated to be associated with vascular remodelling. Interleukin (IL)-33, a member of the “alarmin” family can either act on the membrane ST2 receptor or as a nuclear repressor, to regulate inflammation. We show, using immunohistochemistry, that IL-33 expression is nuclearmore » in the vessels of healthy subjects whereas nuclear IL-33 is markedly diminished in the vessels of IPAH patients. This correlates with reduced IL-33 mRNA expression in their lung. In contrast, serum levels of IL-33 are unchanged in IPAH. However, the expression of the soluble form of ST2, sST2, is enhanced in the serum of IPAH patients. Knock-down of IL-33 in human endothelial cells (ECs) using siRNA is associated with selective modulation of inflammatory genes involved in vascular remodelling including IL-6. Additionally, IL-33 knock-down significantly increased sST2 release from ECs. Chromatin immunoprecipitation demonstrated that IL-33 bound multiple putative homeodomain protein binding motifs in the proximal and distal promoters of ST2 genes. IL-33 formed a complex with the histone methyltransferase SUV39H1, a transcriptional repressor. In conclusion, IL-33 regulates the expression of IL-6 and sST2, an endogenous IL-33 inhibitor, in primary human ECs and may play an important role in the pathogenesis of PAH through recruitment of transcriptional repressor proteins.« less

Asymmetric competition for nectar between a large nectar thief and a small pollinator: an energetic point of view.

PubMed

Padyšáková, Eliška; Okrouhlík, Jan; Brown, Mark; Bartoš, Michael; Janeček, Štěpán

2017-04-01

There are two alternative hypotheses related to body size and competition for restricted food sources. The first one supposes that larger animals are superior competitors because of their increased feeding abilities, whereas the second one assumes superiority of smaller animals because of their lower food requirements. We examined the relationship between two unrelated species of different size, drinking technique, energy requirements and roles in plant pollination system, to reveal the features of their competitive interaction and mechanisms enabling their co-existence while utilising the same nectar source. We observed diurnal feeding behaviour of the main pollinator, the carpenter bee Xylocopa caffra and a nectar thief, the northern double-collared sunbird Cinnyris reichenowi on 19 clumps of Hypoestes aristata (Acanthaceae) in Bamenda Highlands, Cameroon. For comparative purpose, we established a simplistic model of daily energy expenditure and daily energy intake by both visitor species assuming that they spend all available daytime feeding on H. aristata. We revealed the energetic gain-expenditure balance of the studied visitor species in relation to diurnal changes in nectar quality and quantity. In general, smaller energy requirements and related ability to utilise smaller resources made the main pollinator X. caffra competitively superior to the larger nectar thief C. reichenowi. Nevertheless, sunbirds are endowed with several mechanisms to reduce asymmetry in exploitative competition, such as the use of nectar resources in times of the day when rivals are inactive, aggressive attacks on carpenter bees while defending the nectar plants, and higher speed of nectar consumption.

Antibody Competition Reveals Surface Location of HPV L2 Minor Capsid Protein Residues 17–36

PubMed Central

Bywaters, Stephanie M.; Brendle, Sarah A.; Tossi, Kerstin P.; Biryukov, Jennifer; Meyers, Craig; Christensen, Neil D.

2017-01-01

The currently available nonavalent human papillomavirus (HPV) vaccine exploits the highly antigenic L1 major capsid protein to promote high-titer neutralizing antibodies, but is limited to the HPV types included in the vaccine since the responses are highly type-specific. The limited cross-protection offered by the L1 virus-like particle (VLP) vaccine warrants further investigation into cross-protective L2 epitopes. The L2 proteins are yet to be fully characterized as to their precise placement in the virion. Adding to the difficulties in localizing L2, studies have suggested that L2 epitopes are not well exposed on the surface of the mature capsid prior to cellular engagement. Using a series of competition assays between previously mapped anti-L1 monoclonal antibodies (mAbs) (H16.V5, H16.U4 and H16.7E) and novel anti-L2 mAbs, we probed the capsid surface for the location of an L2 epitope (aa17–36). The previously characterized L1 epitopes together with our competition data is consistent with a proposed L2 epitope within the canyons of pentavalent capsomers. PMID:29125554

Character displacement and the evolution of niche complementarity in a model biofilm community

PubMed Central

Ellis, Crystal N; Traverse, Charles C; Mayo-Smith, Leslie; Buskirk, Sean W; Cooper, Vaughn S

2015-01-01

Colonization of vacant environments may catalyze adaptive diversification and be followed by competition within the nascent community. How these interactions ultimately stabilize and affect productivity are central problems in evolutionary ecology. Diversity can emerge by character displacement, in which selection favors phenotypes that exploit an alternative resource and reduce competition, or by facilitation, in which organisms change the environment and enable different genotypes or species to become established. We previously developed a model of long-term experimental evolution in which bacteria attach to a plastic bead, form a biofilm, and disperse to a new bead. Here, we focus on the evolution of coexisting mutants within a population of Burkholderia cenocepacia and how their interactions affected productivity. Adaptive mutants initially competed for space, but later competition declined, consistent with character displacement and the predicted effects of the evolved mutations. The community reached a stable equilibrium as each ecotype evolved to inhabit distinct, complementary regions of the biofilm. Interactions among ecotypes ultimately became facilitative and enhanced mixed productivity. Observing the succession of genotypes within niches illuminated changing selective forces within the community, including a fundamental role for genotypes producing small colony variants that underpin chronic infections caused by B. cenocepacia. PMID:25494960

Antibody Competition Reveals Surface Location of HPV L2 Minor Capsid Protein Residues 17-36.

PubMed

Bywaters, Stephanie M; Brendle, Sarah A; Tossi, Kerstin P; Biryukov, Jennifer; Meyers, Craig; Christensen, Neil D

2017-11-10

The currently available nonavalent human papillomavirus (HPV) vaccine exploits the highly antigenic L1 major capsid protein to promote high-titer neutralizing antibodies, but is limited to the HPV types included in the vaccine since the responses are highly type-specific. The limited cross-protection offered by the L1 virus-like particle (VLP) vaccine warrants further investigation into cross-protective L2 epitopes. The L2 proteins are yet to be fully characterized as to their precise placement in the virion. Adding to the difficulties in localizing L2, studies have suggested that L2 epitopes are not well exposed on the surface of the mature capsid prior to cellular engagement. Using a series of competition assays between previously mapped anti-L1 monoclonal antibodies (mAbs) (H16.V5, H16.U4 and H16.7E) and novel anti-L2 mAbs, we probed the capsid surface for the location of an L2 epitope (aa17-36). The previously characterized L1 epitopes together with our competition data is consistent with a proposed L2 epitope within the canyons of pentavalent capsomers.

Competition between nonindigenous ruffe and native yellow perch in laboratory studies

USGS Publications Warehouse

Savino, Jacqueline F.; Kolar, Cynthia S.

1996-01-01

The ruffe Gymnocephalus cernuus is a European percid that was accidently introduced in Duluth Harbor, Lake Superior. This nonindigenous species is closely related to yellow perch Perca flavescens, and because the two species have similar diets and habitat requirements, they are potential competitors. Laboratory studies in aquaria and pools were conducted to determine whether ruffe can compete with yellow perch for food. Ruffe had capture rates similar to those of yellow perch when food was unlimited. Ruffe spent more time than yellow perch over a feeding container before leaving it and searching again, and they also required less time to ingest (or handle) prey. However, the presence of yellow perch shortened the time ruffe spent over foraging areas when food was more limited. In addition, yellow perch were more active than ruffe, as indicated by their more frequent visits to a feeding container. Hence, the outcome of exploitative competition was not conclusive; ruffe appear to have the advantage in some behaviors, yellow perch in others. Ruffe were much more aggressive than yellow perch, and interference competition may be important in the interactions between these species. Our results indicate that ruffe might compete with native yellow perch.

Modulation of the gut microbiota by prebiotic fibres and bacteriocins

PubMed Central

Umu, Özgün C. O.; Rudi, Knut; Diep, Dzung B.

2017-01-01

ABSTRACT The gut microbiota is considered an organ that co-develops with the host throughout its life. The composition and metabolic activities of the gut microbiota are subject to a complex interplay between the host genetics and environmental factors, such as lifestyle, diet, stress and antimicrobials. It is evident that certain prebiotics, and antimicrobials produced by lactic acid bacteria (LAB), can shape the composition of the gut microbiota and its metabolic activities to promote host health and/or prevent diseases. In this review, we aim to give an overview of the impact of prebiotic fibres, and bacteriocins from LAB, on the gut microbiota and its activities, which affect the physiology and health of the host. These represent two different mechanisms in modulating the gut microbiota, the first involving exploitative competition by which the growth of beneficial bacteria is promoted and the latter involving interference competition by which the growth of pathogens and other unwanted bacteria is prevented. For interference competition in the gut, bacteriocins offer special advantages over traditional antibiotics, in that they can be designed to act towards specific unwanted bacteria and other pathogens, without any remarkable collateral effects on beneficial microbes sharing the same niche. PMID:28959178

Limiting opportunities for cheating stabilizes virulence in insect parasitic nematodes.

PubMed

Shapiro-Ilan, David; Raymond, Ben

2016-03-01

Cooperative secretion of virulence factors by pathogens can lead to social conflict when cheating mutants exploit collective secretion, but do not contribute to it. If cheats outcompete cooperators within hosts, this can cause loss of virulence. Insect parasitic nematodes are important biocontrol tools that secrete a range of significant virulence factors. Critically, effective nematodes are hard to maintain without live passage, which can lead to virulence attenuation. Using experimental evolution, we tested whether social cheating might explain unstable virulence in the nematode Heterorhabditis floridensis by manipulating relatedness via multiplicity of infection (MOI), and the scale of competition. Passage at high MOI, which should reduce relatedness, led to loss of fitness: virulence and reproductive rate declined together and all eight independent lines suffered premature extinction. As theory predicts, relatedness treatments had more impact under stronger global competition. In contrast, low MOI passage led to more stable virulence and increased reproduction. Moreover, low MOI lineages showed a trade-off between virulence and reproduction, particularly for lines under stronger between-host competition. Overall, this study indicates that evolution of virulence theory is valuable for the culture of biocontrol agents: effective nematodes can be improved and maintained if passage methods mitigate possible social conflicts.

Generation of Non-Homogeneous Poisson Processes by Thinning: Programming Considerations and Comparision with Competing Algorithms.

DTIC Science & Technology

1978-12-01

Poisson processes . The method is valid for Poisson processes with any given intensity function. The basic thinning algorithm is modified to exploit several refinements which reduce computer execution time by approximately one-third. The basic and modified thinning programs are compared with the Poisson decomposition and gap-statistics algorithm, which is easily implemented for Poisson processes with intensity functions of the form exp(a sub 0 + a sub 1t + a sub 2 t-squared. The thinning programs are competitive in both execution

Forecasting Electricity Prices in an Optimization Hydrothermal Problem

NASA Astrophysics Data System (ADS)

Matías, J. M.; Bayón, L.; Suárez, P.; Argüelles, A.; Taboada, J.

2007-12-01

This paper presents an economic dispatch algorithm in a hydrothermal system within the framework of a competitive and deregulated electricity market. The optimization problem of one firm is described, whose objective function can be defined as its profit maximization. Since next-day price forecasting is an aspect crucial, this paper proposes an efficient yet highly accurate next-day price new forecasting method using a functional time series approach trying to exploit the daily seasonal structure of the series of prices. For the optimization problem, an optimal control technique is applied and Pontryagin's theorem is employed.

Beefing up operations in service firms.

PubMed

Chase, R B; Hayes, R H

1991-01-01

Many articles exhort service firm managers to empower workers and first-line supervisors, exploit technology, focus on the customer, and, above all, provide outstanding service. This article proposes a framework to help you evaluate your company's competitive standing in each of these areas. It discusses four types of companies on a continuum, from the company that is simply "available for service" to the firm that delivers world class service. The authors focus on operations, the function that controls the service encounter, and apply the manufacturing strategy paradigm to services as a means of implementing change.

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

Sanfilippo, Antonio P.; Riensche, Roderick M.; Haack, Jereme N.

“Gamification”, the application of gameplay to real-world problems, enables the development of human computation systems that support decision-making through the integration of social and machine intelligence. One of gamification’s major benefits includes the creation of a problem solving environment where the influence of cognitive and cultural biases on human judgment can be curtailed through collaborative and competitive reasoning. By reducing biases on human judgment, gamification allows human computation systems to exploit human creativity relatively unhindered by human error. Operationally, gamification uses simulation to harvest human behavioral data that provide valuable insights for the solution of real-world problems.

Aeon: Synthesizing Scheduling Algorithms from High-Level Models

NASA Astrophysics Data System (ADS)

Monette, Jean-Noël; Deville, Yves; van Hentenryck, Pascal

This paper describes the aeon system whose aim is to synthesize scheduling algorithms from high-level models. A eon, which is entirely written in comet, receives as input a high-level model for a scheduling application which is then analyzed to generate a dedicated scheduling algorithm exploiting the structure of the model. A eon provides a variety of synthesizers for generating complete or heuristic algorithms. Moreover, synthesizers are compositional, making it possible to generate complex hybrid algorithms naturally. Preliminary experimental results indicate that this approach may be competitive with state-of-the-art search algorithms.

Negative Regulation of Violacein Biosynthesis in Chromobacterium violaceum

PubMed Central

Devescovi, Giulia; Kojic, Milan; Covaceuszach, Sonia; Cámara, Miguel; Williams, Paul; Bertani, Iris; Subramoni, Sujatha; Venturi, Vittorio

2017-01-01

In Chromobacteium violaceum, the purple pigment violacein is under positive regulation by the N-acylhomoserine lactone CviI/R quorum sensing system and negative regulation by an uncharacterized putative repressor. In this study we report that the biosynthesis of violacein is negatively controlled by a novel repressor protein, VioS. The violacein operon is regulated negatively by VioS and positively by the CviI/R system in both C. violaceum and in a heterologous Escherichia coli genetic background. VioS does not regulate the CviI/R system and apart from violacein, VioS, and quorum sensing regulate other phenotypes antagonistically. Quorum sensing regulated phenotypes in C. violaceum are therefore further regulated providing an additional level of control. PMID:28326068

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

Kamitani, Shinya; Ohbayashi, Norihiko; Ikeda, Osamu

Signal transducers and activators of transcription (STATs) mediate cell proliferation, differentiation, and survival in immune responses, hematopoiesis, neurogenesis, and other biological processes. Recently, we showed that KAP1 is a novel STAT-binding partner that regulates STAT3-mediated transactivation. KAP1 is a universal co-repressor protein for the KRAB zinc finger protein superfamily of transcriptional repressors. In this study, we found KAP1-dependent repression of interferon (IFN)/STAT1-mediated signaling. We also demonstrated that endogenous KAP1 associates with endogenous STAT1 in vivo. Importantly, a small-interfering RNA-mediated reduction in KAP1 expression enhanced IFN-induced STAT1-dependent IRF-1 gene expression. These results indicate that KAP1 may act as an endogenous regulatormore » of the IFN/STAT1 signaling pathway.« less

Comprehensive Interrogation of Natural TALE DNA Binding Modules and Transcriptional Repressor Domains

PubMed Central

Cong, Le; Zhou, Ruhong; Kuo, Yu-chi; Cunniff, Margaret; Zhang, Feng

2012-01-01

Transcription activator-like effectors (TALE) are sequence-specific DNA binding proteins that harbor modular, repetitive DNA binding domains. TALEs have enabled the creation of customizable designer transcriptional factors and sequence-specific nucleases for genome engineering. Here we report two improvements of the TALE toolbox for achieving efficient activation and repression of endogenous gene expression in mammalian cells. We show that the naturally occurring repeat variable diresidue (RVD) Asn-His (NH) has high biological activity and specificity for guanine, a highly prevalent base in mammalian genomes. We also report an effective TALE transcriptional repressor architecture for targeted inhibition of transcription in mammalian cells. These findings will improve the precision and effectiveness of genome engineering that can be achieved using TALEs. PMID:22828628

Antagonistic Rgg regulators mediate quorum sensing via competitive DNA binding in Streptococcus pyogenes.

PubMed

Lasarre, Breah; Aggarwal, Chaitanya; Federle, Michael J

2013-01-02

Recent studies have established the fact that multiple members of the Rgg family of transcriptional regulators serve as key components of quorum sensing (QS) pathways that utilize peptides as intercellular signaling molecules. We previously described a novel QS system in Streptococcus pyogenes which utilizes two Rgg-family regulators (Rgg2 and Rgg3) that respond to neighboring signaling peptides (SHP2 and SHP3) to control gene expression and biofilm formation. We have shown that Rgg2 is a transcriptional activator of target genes, whereas Rgg3 represses expression of these genes, and that SHPs function to activate the QS system. The mechanisms by which Rgg proteins regulate both QS-dependent and QS-independent processes remain poorly defined; thus, we sought to further elucidate how Rgg2 and Rgg3 mediate gene regulation. Here we provide evidence that S. pyogenes employs a unique mechanism of direct competition between the antagonistic, peptide-responsive proteins Rgg2 and Rgg3 for binding at target promoters. The highly conserved, shared binding sites for Rgg2 and Rgg3 are located proximal to the -35 nucleotide in the target promoters, and the direct competition between the two regulators results in concentration-dependent, exclusive occupation of the target promoters that can be skewed in favor of Rgg2 in vitro by the presence of SHP. These results suggest that exclusionary binding of target promoters by Rgg3 may prevent Rgg2 binding under SHP-limiting conditions, thereby preventing premature induction of the quorum sensing circuit. Rgg-family transcriptional regulators are widespread among low-G+C Gram-positive bacteria and in many cases contribute to bacterial physiology and virulence. Only recently was it discovered that several Rgg proteins function in cell-to-cell communication (quorum sensing [QS]) via direct interaction with signaling peptides. The mechanism(s) by which Rgg proteins mediate regulation is poorly understood, and further insight into Rgg function is anticipated to be of great importance for the understanding of both regulatory-network architecture and intercellular communication in Rgg-containing species. The results of this study on the Rgg2/3 QS circuit of S. pyogenes demonstrate that DNA binding of target promoters by the activator Rgg2 is directly inhibited by competitive binding by the repressor Rgg3, thereby preventing transcriptional activation of the target genes and premature induction of the QS circuit. This is a unique regulatory mechanism among Rgg proteins and other peptide-responsive QS regulators.

Molecular basis for the wide range of affinity found in Csr/Rsm protein-RNA recognition.

PubMed

Duss, Olivier; Michel, Erich; Diarra dit Konté, Nana; Schubert, Mario; Allain, Frédéric H-T

2014-04-01

The carbon storage regulator/regulator of secondary metabolism (Csr/Rsm) type of small non-coding RNAs (sRNAs) is widespread throughout bacteria and acts by sequestering the global translation repressor protein CsrA/RsmE from the ribosome binding site of a subset of mRNAs. Although we have previously described the molecular basis of a high affinity RNA target bound to RsmE, it remains unknown how other lower affinity targets are recognized by the same protein. Here, we have determined the nuclear magnetic resonance solution structures of five separate GGA binding motifs of the sRNA RsmZ of Pseudomonas fluorescens in complex with RsmE. The structures explain how the variation of sequence and structural context of the GGA binding motifs modulate the binding affinity for RsmE by five orders of magnitude (∼10 nM to ∼3 mM, Kd). Furthermore, we see that conformational adaptation of protein side-chains and RNA enable recognition of different RNA sequences by the same protein contributing to binding affinity without conferring specificity. Overall, our findings illustrate how the variability in the Csr/Rsm protein-RNA recognition allows a fine-tuning of the competition between mRNAs and sRNAs for the CsrA/RsmE protein.

AllR Controls the Expression of Streptomyces coelicolor Allantoin Pathway Genes.

PubMed

Navone, Laura; Macagno, Juan Pablo; Licona-Cassani, Cuauhtémoc; Marcellin, Esteban; Nielsen, Lars K; Gramajo, Hugo; Rodriguez, Eduardo

2015-10-01

Streptomyces species are native inhabitants of soil, a natural environment where nutrients can be scarce and competition fierce. They have evolved ways to metabolize unusual nutrients, such as purines and its derivatives, which are highly abundant in soil. Catabolism of these uncommon carbon and nitrogen sources needs to be tightly regulated in response to nutrient availability and environmental stimulus. Recently, the allantoin degradation pathway was characterized in Streptomyces coelicolor. However, there are questions that remained unanswered, particularly regarding pathway regulation. Here, using a combination of proteomics and genetic approaches, we identified the negative regulator of the allantoin pathway, AllR. In vitro studies confirmed that AllR binds to the promoter regions of allantoin catabolic genes and determined the AllR DNA binding motif. In addition, effector studies showed that allantoic acid, and glyoxylate, to a lesser extent, inhibit the binding of AllR to the DNA. Inactivation of AllR repressor leads to the constitutive expression of the AllR regulated genes and intriguingly impairs actinorhodin and undecylprodigiosin production. Genetics and proteomics analysis revealed that among all genes from the allantoin pathway that are upregulated in the allR mutant, the hyi gene encoding a hydroxypyruvate isomerase (Hyi) is responsible of the impairment of antibiotic production. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Development of a high-throughput screen to detect inhibitors of TRPS1 sumoylation.

PubMed

Brandt, Martin; Szewczuk, Lawrence M; Zhang, Hong; Hong, Xuan; McCormick, Patricia M; Lewis, Tia S; Graham, Taylor I; Hung, Sunny T; Harper-Jones, Amber D; Kerrigan, John J; Wang, Da-Yuan; Dul, Edward; Hou, Wangfang; Ho, Thau F; Meek, Thomas D; Cheung, Mui H; Johanson, Kyung O; Jones, Christopher S; Schwartz, Benjamin; Kumar, Sanjay; Oliff, Allen I; Kirkpatrick, Robert B

2013-06-01

Small ubiquitin-like modifier (SUMO) belongs to the family of ubiquitin-like proteins (Ubls) that can be reversibly conjugated to target-specific lysines on substrate proteins. Although covalently sumoylated products are readily detectible in gel-based assays, there has been little progress toward the development of robust quantitative sumoylation assay formats for the evaluation of large compound libraries. In an effort to identify inhibitors of ubiquitin carrier protein 9 (Ubc9)-dependent sumoylation, a high-throughput fluorescence polarization assay was developed, which allows detection of Lys-1201 sumoylation, corresponding to the major site of functional sumoylation within the transcriptional repressor trichorhino-phalangeal syndrome type I protein (TRPS1). A minimal hexapeptide substrate peptide, TMR-VVK₁₂₀₁TEK, was used in this assay format to afford high-throughput screening of the GlaxoSmithKline diversity compound collection. A total of 728 hits were confirmed but no specific noncovalent inhibitors of Ubc9 dependent trans-sumoylation were found. However, several diaminopyrimidine compounds were identified as inhibitors in the assay with IC₅₀ values of 12.5 μM. These were further characterized to be competent substrates which were subject to sumoylation by SUMO-Ubc9 and which were competitive with the sumoylation of the TRPS1 peptide substrates.

AllR Controls the Expression of Streptomyces coelicolor Allantoin Pathway Genes

PubMed Central

Navone, Laura; Macagno, Juan Pablo; Licona-Cassani, Cuauhtémoc; Marcellin, Esteban; Nielsen, Lars K.; Gramajo, Hugo

2015-01-01

Streptomyces species are native inhabitants of soil, a natural environment where nutrients can be scarce and competition fierce. They have evolved ways to metabolize unusual nutrients, such as purines and its derivatives, which are highly abundant in soil. Catabolism of these uncommon carbon and nitrogen sources needs to be tightly regulated in response to nutrient availability and environmental stimulus. Recently, the allantoin degradation pathway was characterized in Streptomyces coelicolor. However, there are questions that remained unanswered, particularly regarding pathway regulation. Here, using a combination of proteomics and genetic approaches, we identified the negative regulator of the allantoin pathway, AllR. In vitro studies confirmed that AllR binds to the promoter regions of allantoin catabolic genes and determined the AllR DNA binding motif. In addition, effector studies showed that allantoic acid, and glyoxylate, to a lesser extent, inhibit the binding of AllR to the DNA. Inactivation of AllR repressor leads to the constitutive expression of the AllR regulated genes and intriguingly impairs actinorhodin and undecylprodigiosin production. Genetics and proteomics analysis revealed that among all genes from the allantoin pathway that are upregulated in the allR mutant, the hyi gene encoding a hydroxypyruvate isomerase (Hyi) is responsible of the impairment of antibiotic production. PMID:26187964

Sulfamethazine Suppresses Epigenetic Silencing in Arabidopsis by Impairing Folate Synthesis[W

PubMed Central

Zhang, Huiming; Deng, Xiangyang; Miki, Daisuke; Cutler, Sean; La, Honggui; Hou, Yueh-Ju; Oh, JeeEun; Zhu, Jian-Kang

2012-01-01

DNA methylation is a critical, dynamically regulated epigenetic mark. Small chemicals can be valuable tools in probing cellular processes, but the set of chemicals with broad effects on epigenetic regulation is very limited. Using the Arabidopsis thaliana repressor of silencing1 mutant, in which transgenes are transcriptionally silenced, we performed chemical genetic screens and found sulfamethazine (SMZ) as a chemical suppressor of epigenetic silencing. SMZ treatment released the silencing of transgenes as well as endogenous transposons and other repetitive elements. Plants treated with SMZ exhibit substantially reduced levels of DNA methylation and histone H3 Lys-9 dimethylation, but heterochromatic siRNA levels were not affected. SMZ is a structural analog and competitive antagonist to p-aminobenzoic acid (PABA), which is a precursor of folates. SMZ decreased the plant folate pool size and caused methyl deficiency, as demonstrated by reductions in S-adenosylmethionine levels and in global DNA methylation. Exogenous application of PABA or compounds downstream in the folate biosynthesis pathway restored transcriptional silencing in SMZ-treated plants. Together, our results revealed a novel type of chemical suppressor of epigenetic silencing, which may serve as a valuable tool for studying the roles and mechanisms of epigenetic regulation and underscores an important linkage between primary metabolism and epigenetic gene regulation. PMID:22447685

Investigation of repressive and enhancive effects of fruit extracts on the activity of glucose-6-phophatase.

PubMed

Zahoor, Muhammad; Jan, Muhammad Rasul; Naz, Sumaira

2016-11-01

Glucose-6-phosphatase is a key enzyme of glucose metabolic pathways. Deficiency of this enzyme leads to glycogen storage disease. This enzyme also plays a negative role in diabetes mellitus disorder in which the catalytic activity of this enzyme increases. Thus there is need for activators to enhance the activity of glucose-6-phosphatase in glycogen storage disease of type 1b while in diabetes mellitus repressors are needed to reduce its activity. Crude extracts of apricot, fig, mulberry and apple fruits were investigated for their repressive/enhancive effects on glucose-6-phosphatase in vivo. Albino mice were used as experimental animal. All the selected extracts showed depressive effects on glucose-6-phosphatase, which shows that all these extracts can be used as antidiabetic supplement of food. The inhibitory pattern was competitive one, which was evident from the effect of increasing dose from 1g/Kg body weight to 3g/Kg body weight for all the selected fruit extracts. However fig and apple fruit extracts showed high repressive effects for high doses as compared to apricot and mulberry fruit extracts. None of these selected fruit extracts showed enhancive effect on glucose-6-phosphatase activity. All these fruits or their extracts can be used as antidiabetic dietary supplement for diabetes mellitus.

Spatial self-organization favors heterotypic cooperation over cheating.

PubMed

Momeni, Babak; Waite, Adam James; Shou, Wenying

2013-11-12

Heterotypic cooperation-two populations exchanging distinct benefits that are costly to produce-is widespread. Cheaters, exploiting benefits while evading contribution, can undermine cooperation. Two mechanisms can stabilize heterotypic cooperation. In 'partner choice', cooperators recognize and choose cooperating over cheating partners; in 'partner fidelity feedback', fitness-feedback from repeated interactions ensures that aiding your partner helps yourself. How might a spatial environment, which facilitates repeated interactions, promote fitness-feedback? We examined this process through mathematical models and engineered Saccharomyces cerevisiae strains incapable of recognition. Here, cooperators and their heterotypic cooperative partners (partners) exchanged distinct essential metabolites. Cheaters exploited partner-produced metabolites without reciprocating, and were competitively superior to cooperators. Despite initially random spatial distributions, cooperators gained more partner neighbors than cheaters did. The less a cheater contributed, the more it was excluded and disfavored. This self-organization, driven by asymmetric fitness effects of cooperators and cheaters on partners during cell growth into open space, achieves assortment. DOI: http://dx.doi.org/10.7554/eLife.00960.001.

Spatial self-organization favors heterotypic cooperation over cheating

PubMed Central

Momeni, Babak; Waite, Adam James; Shou, Wenying

2013-01-01

Heterotypic cooperation—two populations exchanging distinct benefits that are costly to produce—is widespread. Cheaters, exploiting benefits while evading contribution, can undermine cooperation. Two mechanisms can stabilize heterotypic cooperation. In ‘partner choice’, cooperators recognize and choose cooperating over cheating partners; in ‘partner fidelity feedback’, fitness-feedback from repeated interactions ensures that aiding your partner helps yourself. How might a spatial environment, which facilitates repeated interactions, promote fitness-feedback? We examined this process through mathematical models and engineered Saccharomyces cerevisiae strains incapable of recognition. Here, cooperators and their heterotypic cooperative partners (partners) exchanged distinct essential metabolites. Cheaters exploited partner-produced metabolites without reciprocating, and were competitively superior to cooperators. Despite initially random spatial distributions, cooperators gained more partner neighbors than cheaters did. The less a cheater contributed, the more it was excluded and disfavored. This self-organization, driven by asymmetric fitness effects of cooperators and cheaters on partners during cell growth into open space, achieves assortment. DOI: http://dx.doi.org/10.7554/eLife.00960.001 PMID:24220506

Testing MacArthur's minimisation principle: do communities minimise energy wastage during succession?

PubMed

Ghedini, Giulia; Loreau, Michel; White, Craig R; Marshall, Dustin J

2018-05-20

Robert MacArthur developed a theory of community assembly based on competition. By incorporating energy flow, MacArthur's theory allows for predictions of community function. A key prediction is that communities minimise energy wastage over time, but this minimisation is a trade-off between two conflicting processes: exploiting food resources, and maintaining low metabolism and mortality. Despite its simplicity and elegance, MacArthur's principle has not been tested empirically despite having long fascinated theoreticians. We used a combination of field chronosequence experiments and laboratory assays to estimate how the energy wastage of a community changes during succession. We found that older successional stages wasted more energy in maintenance, but there was no clear pattern in how communities of different age exploited food resources. We identify several reasons for why MacArthur's original theory may need modification and new avenues to further explore community efficiency, an understudied component of ecosystem functioning. © 2018 John Wiley & Sons Ltd/CNRS.

Regulated expression of a repressor protein: FadR activates iclR.

PubMed Central

Gui, L; Sunnarborg, A; LaPorte, D C

1996-01-01

The control of the glyoxylate bypass operon (aceBAK) of Escherichia coli is mediated by two regulatory proteins, IclMR and FadR. IclMR is a repressor protein which has previously been shown to bind to a site which overlaps the aceBAK promoter. FAR is a repressor/activator protein which participates in control of the genes of fatty acid metabolism. A sequence just upstream of the iclR promoter bears a striking resemblance to FadR binding sites found in the fatty acid metabolic genes. The in vitro binding specificity of FadR, determined by oligonucleotide selection, was in good agreement with the sequences of these sites. The ability of FadR to bind to the site associated with iclR was demonstrated by gel shift and DNase I footprint analyses. Disruption of FadR or inactivation of the FadR binding site of iclR decreased the expression of an iclR::lacZ operon fusion, indicating that FadR activates the expression of iclR. It has been reported that disruption of fadR increases the expression of aceBAK. We observed a similar increase when we inactivated the FadR binding site of an iclR+ allele. This result suggests that FadR regulates aceBAK indirectly by altering the expression of IclR. PMID:8755903

The CsoR-like sulfurtransferase repressor (CstR) is a persulfide sensor in Staphylococcus aureus.

PubMed

Luebke, Justin L; Shen, Jiangchuan; Bruce, Kevin E; Kehl-Fie, Thomas E; Peng, Hui; Skaar, Eric P; Giedroc, David P

2014-12-01

How cells regulate the bioavailability of utilizable sulfur while mitigating the effects of hydrogen sulfide toxicity is poorly understood. CstR [Copper-sensing operon repressor (CsoR)-like sulfurtransferase repressor] represses the expression of the cst operon encoding a putative sulfide oxidation system in Staphylococcus aureus. Here, we show that the cst operon is strongly and transiently induced by cellular sulfide stress in an acute phase and specific response and that cst-encoded genes are necessary to mitigate the effects of sulfide toxicity. Growth defects are most pronounced when S. aureus is cultured in chemically defined media with thiosulfate (TS) as a sole sulfur source, but are also apparent when cystine is used or in rich media. Under TS growth conditions, cells fail to grow as a result of either unregulated expression of the cst operon in a ΔcstR strain or transformation with a non-inducible C31A/C60A CstR that blocks cst induction. This suggests that the cst operon contributes to cellular sulfide homeostasis. Tandem high-resolution mass spectrometry reveals derivatization of CstR by both inorganic tetrasulfide and an organic persulfide, glutathione persulfide, to yield a mixture of Cys31-Cys60' interprotomer cross-links, including di-, tri- and tetrasulfide bonds, which allosterically inhibit cst operator DNA binding by CstR. © 2014 John Wiley & Sons Ltd.

The CsoR-like sulfurtransferase repressor (CstR) is a persulfide sensor in Staphylococcus aureus

PubMed Central

Luebke, Justin L.; Shen, Jiangchuan; Bruce, Kevin E.; Kehl-Fie, Thomas E.; Peng, Hui; Skaar, Eric P.; Giedroc, David P.

2014-01-01

How cells regulate the bioavailability of utilizable sulfur while mitigating the effects of hydrogen sulfide toxicity is poorly understood. CstR (Copper-sensing operon repressor (CsoR)-like sulfurtransferase repressor) represses the expression of the cst operon encoding a putative sulfide oxidation system in Staphylococcus aureus. Here, we show that the cst operon is strongly and transiently induced by cellular sulfide stress in an acute phase and specific response and that cst-encoded genes are necessary to mitigate the effects of sulfide toxicity. Growth defects are most pronounced when S. aureus is cultured in chemically defined media with thiosulfate (TS) as a sole sulfur source, but are also apparent when cystine is used or in rich media. Under TS growth conditions, cells fail to grow as a result of either unregulated expression of the cst operon in a ΔcstR strain or transformation with a non-inducible C31A/C60A CstR that blocks cst induction. This suggests that the cst operon contributes to cellular sulfide homeostasis. Tandem high resolution mass spectrometry reveals derivatization of CstR by both inorganic tetrasulfide and an organic persulfide, glutathione persulfide, to yield a mixture of Cys31-Cys60’ interprotomer crosslinks, including di-, tri- and tetrasulfide bonds, which allosterically inhibit cst operator DNA binding by CstR. PMID:25318663

Flexibility of KorA, a plasmid-encoded, global transcription regulator, in the presence and the absence of its operator

PubMed Central

Rajasekar, Karthik V.; Lovering, Andrew L.; Dancea, Felician; Scott, David J.; Harris, Sarah A.; Bingle, Lewis E.H.; Roessle, Manfred; Thomas, Christopher M.; Hyde, Eva I.; White, Scott A.

2016-01-01

Abstract The IncP (Incompatibility group P) plasmids are important carriers in the spread of antibiotic resistance across Gram-negative bacteria. Gene expression in the IncP-1 plasmids is stringently controlled by a network of four global repressors, KorA, KorB, TrbA and KorC interacting cooperatively. Intriguingly, KorA and KorB can act as co-repressors at varying distances between their operators, even when they are moved to be on opposite sides of the DNA. KorA is a homodimer with the 101-amino acid subunits, folding into an N-terminal DNA-binding domain and a C-terminal dimerization domain. In this study, we have determined the structures of the free KorA repressor and two complexes each bound to a 20-bp palindromic DNA duplex containing its consensus operator sequence. Using a combination of X-ray crystallography, nuclear magnetic resonance spectroscopy, SAXS and molecular dynamics calculations, we show that the linker between the two domains is very flexible and the protein remains highly mobile in the presence of DNA. This flexibility allows the DNA-binding domains of the dimer to straddle the operator DNA on binding and is likely to be important in cooperative binding to KorB. Unexpectedly, the C-terminal domain of KorA is structurally similar to the dimerization domain of the tumour suppressor p53. PMID:27016739

Dissecting the link between the enzymatic activity and the SaPI inducing capacity of the phage 80α dUTPase.

PubMed

Alite, Christian; Humphrey, Suzanne; Donderis, Jordi; Maiques, Elisa; Ciges-Tomas, J Rafael; Penadés, José R; Marina, Alberto

2017-09-11

The trimeric staphylococcal phage-encoded dUTPases (Duts) are signalling molecules that induce the cycle of some Staphylococcal pathogenicity islands (SaPIs) by binding to the SaPI-encoded Stl repressor. To perform this regulatory role, these Duts require an extra motif VI, as well as the Dut conserved motifs IV and V. While the apo form of Dut is required for the interaction with the Stl repressor, usually only those Duts with normal enzymatic activity can induce the SaPI cycle. To understand the link between the enzymatic activities and inducing capacities of the Dut protein, we analysed the structural, biochemical and physiological characteristics of the Dut80α D95E mutant, which loses the SaPI cycle induction capacity despite retaining enzymatic activity. Asp95 is located at the threefold central channel of the trimeric Dut where it chelates a divalent ion. Here, using state-of-the-art techniques, we demonstrate that D95E mutation has an epistatic effect on the motifs involved in Stl binding. Thus, ion binding in the central channel correlates with the capacity of motif V to twist and order in the SaPI-inducing disposition, while the tip of motif VI is disturbed. These alterations in turn reduce the affinity for the Stl repressor and the capacity to induce the SaPI cycle.

Molecular basis for repression of liver X receptor-mediated gene transcription by receptor-interacting protein 140

PubMed Central

Jakobsson, Tomas; Osman, Waffa; Gustafsson, Jan-Åke; Zilliacus, Johanna; Wärnmark, Anette

2007-01-01

Similarities in physiological roles of LXR (liver X receptors) and co-repressor RIP140 (receptor-interacting protein 140) in regulating energy homoeostasis and lipid and glucose metabolism suggest that the effects of LXR could at least partly be mediated by recruitment of the co-repressor RIP140. In the present study, we have elucidated the molecular basis for regulation of LXR transcriptional activity by RIP140. LXR is evenly localized in the nucleus and neither the N-terminal domain nor the LBD (ligand-binding domain) is necessary for nuclear localization. Both LXR subtypes, LXRα and LXRβ, interact with RIP140 and co-localize in diffuse large nuclear domains. Interaction and co-localization are dependent on the LBD of the receptor. The C-terminal domain of RIP140 is sufficient for full repressive effect. None of the C-terminal NR (nuclear receptor)-boxes is required for the co-repressor activity, whereas the NR-box-like motif as well as additional elements in the C-terminal region are required for full repressive function. The C-terminal NR-box-like motif is necessary for interaction with LXRβ, whereas additional elements are needed for strong interaction with LXRα. In conclusion, our results suggest that co-repression of LXR activity by RIP140 involves an atypical binding mode of RIP140 and a repression element in the RIP140 C-terminus. PMID:17391100

Loss of Wild-Type ATRX Expression in Somatic Cell Hybrids Segregates with Activation of Alternative Lengthening of Telomeres

PubMed Central

Cole, Sara L.; Dagg, Rebecca A.; Lau, Loretta M. S.; Duncan, Emma L.; Moy, Elsa L.; Reddel, Roger R.

2012-01-01

Alternative Lengthening of Telomeres (ALT) is a non-telomerase mechanism of telomere lengthening that occurs in about 10% of cancers overall and is particularly common in astrocytic brain tumors and specific types of sarcomas. Somatic cell hybridization analyses have previously shown that normal telomerase-negative fibroblasts and telomerase-positive immortalized cell lines contain repressors of ALT activity, indicating that activation of ALT results from loss of one or more unidentified repressors. More recently, ATRX or DAXX was shown to be mutated both in tumors with telomere lengths suggestive of ALT activity and in ALT cell lines. Here, an ALT cell line was separately fused to each of four telomerase-positive cell lines, and four or five independent hybrid lines from each fusion were examined for expression of ATRX and DAXX and for telomere lengthening mechanism. The hybrid lines expressed either telomerase or ALT, with the other mechanism being repressed. DAXX was expressed normally in all parental cell lines and in all of the hybrids. ATRX was expressed normally in each of the four telomerase-positive parental cell lines and in every telomerase-positive hybrid line, and was abnormal in the ALT parental cells and in all but one of the ALT hybrids. This correlation between ALT activity and loss of ATRX expression is consistent with ATRX being a repressor of ALT. PMID:23185534

Crystal Structure of the Arginine Repressor Protein in Complex With the DNA Operator From Mycobacterium Tuberculosis

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

Cherney, L.T.; Cherney, M.M.; Garen, C.R.

2009-05-12

The Mycobacterium tuberculosis (Mtb) gene product encoded by open reading frame Rv1657 is an arginine repressor (ArgR). All genes involved in the L-arginine (hereafter arginine) biosynthetic pathway are essential for optimal growth of the Mtb pathogen, thus making MtbArgR a potential target for drug design. The C-terminal domains of arginine repressors (CArgR) participate in oligomerization and arginine binding. Several crystal forms of CArgR from Mtb (MtbCArgR) have been obtained. The X-ray crystal structures of MtbCArgR were determined at 1.85 {angstrom} resolution with bound arginine and at 2.15 {angstrom} resolution in the unliganded form. These structures show that six molecules ofmore » MtbCArgR are arranged into a hexamer having approximate 32 point symmetry that is formed from two trimers. The trimers rotate relative to each other by about 11{sup o} upon binding arginine. All residues in MtbCArgR deemed to be important for hexamer formation and for arginine binding have been identified from the experimentally determined structures presented. The hexamer contains six regular sites in which the arginine molecules have one common binding mode and three sites in which the arginine molecules have two overlapping binding modes. The latter sites only bind the ligand at high (200 mM) arginine concentrations.« less

A Set of Activators and Repressors Control Peripheral Glucose Pathways in Pseudomonas putida To Yield a Common Central Intermediate▿

PubMed Central

del Castillo, Teresa; Duque, Estrella; Ramos, Juan L.

2008-01-01

Pseudomonas putida KT2440 channels glucose to the central Entner-Doudoroff intermediate 6-phosphogluconate through three convergent pathways. The genes for these convergent pathways are clustered in three independent regions on the host chromosome. A number of monocistronic units and operons coexist within each of these clusters, favoring coexpression of catabolic enzymes and transport systems. Expression of the three pathways is mediated by three transcriptional repressors, HexR, GnuR, and PtxS, and by a positive transcriptional regulator, GltR-2. In this study, we generated mutants in each of the regulators and carried out transcriptional assays using microarrays and transcriptional fusions. These studies revealed that HexR controls the genes that encode glucokinase/glucose 6-phosphate dehydrogenase that yield 6-phosphogluconate; the genes for the Entner-Doudoroff enzymes that yield glyceraldehyde-3-phosphate and pyruvate; and gap-1, which encodes glyceraldehyde-3-phosphate dehydrogenase. GltR-2 is the transcriptional regulator that controls specific porins for the entry of glucose into the periplasmic space, as well as the gtsABCD operon for glucose transport through the inner membrane. GnuR is the repressor of gluconate transport and gluconokinase responsible for the conversion of gluconate into 6-phosphogluconate. PtxS, however, controls the enzymes for oxidation of gluconate to 2-ketogluconate, its transport and metabolism, and a set of genes unrelated to glucose metabolism. PMID:18245293

A stationary-phase protein of Escherichia coli that affects the mode of association between the trp repressor protein and operator-bearing DNA.

PubMed Central

Yang, W; Ni, L; Somerville, R L

1993-01-01

Highly purified preparations of trp repressor (TrpR) protein derived from Escherichia coli strains that were engineered to overexpress this material were found to contain another protein, of 21 kDa. The second protein, designated WrbA [for tryptophan (W) repressor-binding protein] remained associated with its namesake through several sequential protein fractionation steps. The N-terminal amino acid sequence of the WrbA protein guided the design of two degenerate oligonucleotides that were used as probes in the cloning of the wrbA gene (198 codons). The WrbA protein, in purified form, was found by several criteria to enhance the formation and/or stability of noncovalent complexes between TrpR holorepressor and its primary operator targets. The formation of an operator-holorepressor-WrbA ternary complex was demonstrated by gel mobility-shift analysis. The WrbA protein alone does not interact with the trp operator. During the stationary phase, cells deficient in the WrbA protein were less efficient than wild type in their ability to repress the trp promoter. It is proposed that the WrbA protein functions as an accessory element in blocking TrpR-specific transcriptional processes that might be physiologically disadvantageous in the stationary phase of the bacterial life cycle. Images Fig. 1 Fig. 3 Fig. 4 Fig. 5 PMID:8516330

Animal-specific C-terminal domain links myeloblastosis oncoprotein (Myb) to an ancient repressor complex

PubMed Central

Andrejka, Laura; Wen, Hong; Ashton, Jonathan; Grant, Megan; Iori, Kevin; Wang, Amy; Manak, J. Robert; Lipsick, Joseph S.

2011-01-01

Members of the Myb oncoprotein and E2F-Rb tumor suppressor protein families are present within the same highly conserved multiprotein transcriptional repressor complex, named either as Myb and synthetic multivuval class B (Myb-MuvB) or as Drosophila Rb E2F and Myb-interacting proteins (dREAM). We now report that the animal-specific C terminus of Drosophila Myb but not the more highly conserved N-terminal DNA-binding domain is necessary and sufficient for (i) adult viability, (ii) proper localization to chromosomes in vivo, (iii) regulation of gene expression in vivo, and (iv) interaction with the highly conserved core of the MuvB/dREAM transcriptional repressor complex. In addition, we have identified a conserved peptide motif that is required for this interaction. Our results imply that an ancient function of Myb in regulating G2/M genes in both plants and animals appears to have been transferred from the DNA-binding domain to the animal-specific C-terminal domain. Increased expression of B-MYB/MYBL2, the human ortholog of Drosophila Myb, correlates with poor prognosis in human patients with breast cancer. Therefore, our results imply that the specific interaction of the C terminus of Myb with the MuvB/dREAM core complex may provide an attractive target for the development of cancer therapeutics. PMID:21969598

Suppressor of Fused Chaperones Gli Proteins To Generate Transcriptional Responses to Sonic Hedgehog Signaling

PubMed Central

Zhang, Ziyu; Shen, Longyan; Law, Kelvin; Zhang, Zengdi; Liu, Xiaotong; Hua, Hu; Li, Sanen; Huang, Huijie; Yue, Shen; Hui, Chi-chung

2016-01-01

ABSTRACT Cellular responses to the graded Sonic Hedgehog (Shh) morphogenic signal are orchestrated by three Gli genes that give rise to both transcription activators and repressors. An essential downstream regulator of the pathway, encoded by the tumor suppressor gene Suppressor of fused (Sufu), plays critical roles in the production, trafficking, and function of Gli proteins, but the mechanism remains controversial. Here, we show that Sufu is upregulated in active Shh responding tissues and accompanies Gli activators translocating into and Gli repressors out of the nucleus. Trafficking of Sufu to the primary cilium, potentiated by Gli activators but not repressors, was found to be coupled to its nuclear import. We have identified a nuclear export signal (NES) motif of Sufu in juxtaposition to the protein kinase A (PKA) and glycogen synthase kinase 3 (GSK3) dual phosphorylation sites and show that Sufu binds the chromatin with both Gli1 and Gli3. Close comparison of neural tube development among individual Ptch1−/−, Sufu−/−, and Ptch1−/−; Sufu−/− double mutant embryos indicates that Sufu is critical for the maximal activation of Shh signaling essential to the specification of the most-ventral neurons. These data define Sufu as a novel class of molecular chaperone required for every aspect of Gli regulation and function. PMID:27849569

Structure of the effector-binding domain of the arabinose repressor AraR from Bacillus subtilis

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

Procházková, Kateřina; Čermáková, Kateřina; Pachl, Petr

2012-02-01

The crystal structure of the effector-binding domain of the transcriptional repressor AraR from B. subtilis in complex with the effector molecule (l-arabinose) was determined at 2.2 Å resolution. A detailed analysis of the crystal identified a dimer organization that is distinctive from that of other members of the GalR/LacI family. In Bacillus subtilis, the arabinose repressor AraR negatively controls the expression of genes in the metabolic pathway of arabinose-containing polysaccharides. The protein is composed of two domains of different phylogenetic origin and function: an N-terminal DNA-binding domain belonging to the GntR family and a C-terminal effector-binding domain that shows similaritymore » to members of the GalR/LacI family. The crystal structure of the C-terminal effector-binding domain of AraR in complex with the effector l-arabinose has been determined at 2.2 Å resolution. The l-arabinose binding affinity was characterized by isothermal titration calorimetry and differential scanning fluorimetry; the K{sub d} value was 8.4 ± 0.4 µM. The effect of l-arabinose on the protein oligomeric state was investigated in solution and detailed analysis of the crystal identified a dimer organization which is distinctive from that of other members of the GalR/LacI family.« less

Isolating intrinsic noise sources in a stochastic genetic switch.

PubMed

Newby, Jay M

2012-01-01

The stochastic mutual repressor model is analysed using perturbation methods. This simple model of a gene circuit consists of two genes and three promotor states. Either of the two protein products can dimerize, forming a repressor molecule that binds to the promotor of the other gene. When the repressor is bound to a promotor, the corresponding gene is not transcribed and no protein is produced. Either one of the promotors can be repressed at any given time or both can be unrepressed, leaving three possible promotor states. This model is analysed in its bistable regime in which the deterministic limit exhibits two stable fixed points and an unstable saddle, and the case of small noise is considered. On small timescales, the stochastic process fluctuates near one of the stable fixed points, and on large timescales, a metastable transition can occur, where fluctuations drive the system past the unstable saddle to the other stable fixed point. To explore how different intrinsic noise sources affect these transitions, fluctuations in protein production and degradation are eliminated, leaving fluctuations in the promotor state as the only source of noise in the system. The process without protein noise is then compared to the process with weak protein noise using perturbation methods and Monte Carlo simulations. It is found that some significant differences in the random process emerge when the intrinsic noise source is removed.

A homozygous mutation in HESX1 is associated with evolving hypopituitarism due to impaired repressor-corepressor interaction

PubMed Central

Carvalho, Luciani R.; Woods, Kathryn S.; Mendonca, Berenice B.; Marcal, Nathalie; Zamparini, Andrea L.; Stifani, Stefano; Brickman, Joshua M.; Arnhold, Ivo J.P.; Dattani, Mehul T.

2003-01-01

The paired-like homeobox gene expressed in embryonic stem cells Hesx1/HESX1 encodes a developmental repressor and is expressed in early development in a region fated to form the forebrain, with subsequent localization to Rathke’s pouch, the primordium of the anterior pituitary gland. Mutations within the gene have been associated with septo-optic dysplasia, a constellation of phenotypes including eye, forebrain, and pituitary abnormalities, or milder degrees of hypopituitarism. We identified a novel homozygous nonconservative missense mutation (I26T) in the critical Engrailed homology repressor domain (eh1) of HESX1, the first, to our knowledge, to be described in humans, in a girl with evolving combined pituitary hormone deficiency born to consanguineous parents. Neuroimaging revealed a thin pituitary stalk with anterior pituitary hypoplasia and an ectopic posterior pituitary, but no midline or optic nerve abnormalities. This I26T mutation did not affect the DNA-binding ability of HESX1 but led to an impaired ability to recruit the mammalian Groucho homolog/Transducin-like enhancer of split-1 (Gro/TLE1), a crucial corepressor for HESX1, thereby leading to partial loss of repression. Thus, the novel pituitary phenotype highlighted here appears to be a specific consequence of the inability of HESX1 to recruit Groucho-related corepressors, suggesting that other molecular mechanisms govern HESX1 function in the forebrain. PMID:14561704

Building effective R&D capabilities abroad.

PubMed

Kuemmerle, W

1997-01-01

In the past, companies kept most of their research and development activities in their home country because they thought it important to have R&D close to where strategic decisions were being made. But today many companies choose to establish R&D networks in foreign countries in order to tap the knowledge there or to commercialize products for those markets at a competitive speed. Adopting a global approach entails new, complex managerial challenges. It means linking R&D strategy to a company's overall business strategy. The first step in adopting such an approach is to build a team to lead the initiative--a team whose members are sufficiently senior to be able to mobilize resources at short notice. Second, companies must determine whether an R&D site's primary objective is to augment the expertise that the home base has the offer or to exploit that knowledge for use in the foreign country. That determination affects the choice of location and staff. For example, to augment the home base laboratory, a company would want to be near a foreign university; to exploit the home base laboratory it would need to be near large markets and manufacturing facilities. The best individual for managing both types of site combines the qualities of good scientist and good manager, knows how to integrate the new site with existing sites, understand technology trends, and is good at gaining access to foreign scientific communities. As more pockets of knowledge emerge around the globe and competition in foreign markets mounts, only those companies that embrace an informed approach to global R&D will be able to meet the new challenges.

Sustainable production of biologically active molecules of marine based origin.

PubMed

Murray, Patrick M; Moane, Siobhan; Collins, Catherine; Beletskaya, Tanya; Thomas, Olivier P; Duarte, Alysson W F; Nobre, Fernando S; Owoyemi, Ifeloju O; Pagnocca, Fernando C; Sette, L D; McHugh, Edward; Causse, Eric; Pérez-López, Paula; Feijoo, Gumersindo; Moreira, Ma T; Rubiolo, Juan; Leirós, Marta; Botana, Luis M; Pinteus, Susete; Alves, Celso; Horta, André; Pedrosa, Rui; Jeffryes, Clayton; Agathos, Spiros N; Allewaert, Celine; Verween, Annick; Vyverman, Wim; Laptev, Ivan; Sineoky, Sergei; Bisio, Angela; Manconi, Renata; Ledda, Fabio; Marchi, Mario; Pronzato, Roberto; Walsh, Daniel J

2013-09-25

The marine environment offers both economic and scientific potential which are relatively untapped from a biotechnological point of view. These environments whilst harsh are ironically fragile and dependent on a harmonious life form balance. Exploitation of natural resources by exhaustive wild harvesting has obvious negative environmental consequences. From a European industry perspective marine organisms are a largely underutilised resource. This is not due to lack of interest but due to a lack of choice the industry faces for cost competitive, sustainable and environmentally conscientious product alternatives. Knowledge of the biotechnological potential of marine organisms together with the development of sustainable systems for their cultivation, processing and utilisation are essential. In 2010, the European Commission recognised this need and funded a collaborative RTD/SME project under the Framework 7-Knowledge Based Bio-Economy (KBBE) Theme 2 Programme 'Sustainable culture of marine microorganisms, algae and/or invertebrates for high value added products'. The scope of that project entitled 'Sustainable Production of Biologically Active Molecules of Marine Based Origin' (BAMMBO) is outlined. Although the Union is a global leader in many technologies, it faces increasing competition from traditional rivals and emerging economies alike and must therefore improve its innovation performance. For this reason innovation is placed at the heart of a European Horizon 2020 Strategy wherein the challenge is to connect economic performance to eco performance. This article provides a synopsis of the research activities of the BAMMBO project as they fit within the wider scope of sustainable environmentally conscientious marine resource exploitation for high-value biomolecules. Copyright © 2013 Elsevier B.V. All rights reserved.

Alanine racemase is essential for the growth and interspecies competitiveness of Streptococcus mutans.

PubMed

Wei, Yuan; Qiu, Wei; Zhou, Xue-Dong; Zheng, Xin; Zhang, Ke-Ke; Wang, Shi-Da; Li, Yu-Qing; Cheng, Lei; Li, Ji-Yao; Xu, Xin; Li, Ming-Yun

2016-12-16

D-alanine (D-Ala) is an essential amino acid that has a key role in bacterial cell wall synthesis. Alanine racemase (Alr) is a unique enzyme that interconverts L-alanine and D-alanine in most bacteria, making this enzyme a potential target for antimicrobial drug development. Streptococcus mutans is a major causative factor of dental caries. The factors involved in the survival, virulence and interspecies interactions of S. mutans could be exploited as potential targets for caries control. The current study aimed to investigate the physiological role of Alr in S. mutans. We constructed alr mutant strain of S. mutans and evaluated its phenotypic traits and interspecies competitiveness compared with the wild-type strain. We found that alr deletion was lethal to S. mutans. A minimal supplement of D-Ala (150 μg·mL -1 ) was required for the optimal growth of the alr mutant. The depletion of D-alanine in the growth medium resulted in cell wall perforation and cell lysis in the alr mutant strain. We also determined the compromised competitiveness of the alr mutant strain relative to the wild-type S. mutans against other oral streptococci (S. sanguinis or S. gordonii), demonstrated using either conditioned medium assays or dual-species fluorescent in situ hybridization analysis. Given the importance and necessity of alr to the growth and competitiveness of S. mutans, Alr may represent a promising target to modulate the cariogenicity of oral biofilms and to benefit the management of dental caries.

New parasitoid-predator associations: female parasitoids do not avoid competition with generalist predators when sharing invasive prey

NASA Astrophysics Data System (ADS)

Chailleux, Anaïs; Wajnberg, Eric; Zhou, Yuxiang; Amiens-Desneux, Edwige; Desneux, Nicolas

2014-12-01

Optimal habitat selection is essential for species survival in ecosystems, and interspecific competition is a key ecological mechanism for many observed species association patterns. Specialized animal species are commonly affected by resource and interference competition with generalist and/or omnivorous competitors, so avoidance behavior could be expected. We hypothesize that specialist species may exploit broad range cues from such potential resource competitors (i.e., cues possibly common to various generalist and/or omnivorous predators) to avoid costly competition regarding food or reproduction, even in new species associations. We tested this hypothesis by studying short-term interactions between a native larval parasitoid and a native generalist omnivorous predator recently sharing the same invasive host/prey, the leaf miner Tuta absoluta. We observed a strong negative effect of kleptoparasitism (food resource stealing) instead of classical intraguild predation on immature parasitoids. There was no evidence that parasitoid females avoided the omnivorous predator when searching for oviposition sites, although we studied both long- and short-range known detection mechanisms. Therefore, we conclude that broad range cue avoidance may not exist in our biological system, probably because it would lead to too much oviposition site avoidance which would not be an efficient and, thus, beneficial strategy. If confirmed in other parasitoids or specialist predators, our findings may have implications for population dynamics, especially in the current context of increasing invasive species and the resulting creation of many new species associations.

Plant neighbour identity matters to belowground interactions under controlled conditions.

PubMed

Armas, Cristina; Pugnaire, Francisco Ignacio

2011-01-01

Root competition is an almost ubiquitous feature of plant communities with profound effects on their structure and composition. Far beyond the traditional view that plants interact mainly through resource depletion (exploitation competition), roots are known to be able to interact with their environment using a large variety of mechanisms that may inhibit or enhance access of other roots to the resource or affect plant growth (contest interactions). However, an extensive analysis on how these contest root interactions may affect species interaction abilities is almost lacking. In a common garden experiment with ten perennial plant species we forced pairs of plants of the same or different species to overlap their roots and analyzed how belowground contest interactions affected plant performance, biomass allocation patterns, and competitive abilities under abundant resource supply. Our results showed that net interaction outcome ranged from negative to positive, affecting total plant mass and allocation patterns. A species could be a strong competitor against one species, weaker against another one, and even facilitator to a third species. This leads to sets of species where competitive hierarchies may be clear but also to groups where such rankings are not, suggesting that intransitive root interactions may be crucial for species coexistence. The outcome of belowground contest interactions is strongly dependent on neighbours' identity. In natural plant communities this conditional outcome may hypothetically help species to interact in non-hierarchical and intransitive networks, which in turn might promote coexistence.

Asymmetric predictability and cognitive competition in football penalty shootouts.

PubMed

Misirlisoy, Erman; Haggard, Patrick

2014-08-18

Sports provide powerful demonstrations of cognitive strategies underlying competitive behavior. Penalty shootouts in football (soccer) involve direct competition between elite players and absorb the attention of millions. The penalty shootout between Germany and England in the 1990 World Cup semifinal was viewed by an estimated 46.49% of the UK population. In a penalty shootout, a goalkeeper must defend their goal without teammate assistance while an opposing series of kickers aim to kick the ball past them into the net. As in many sports, the ball during a penalty kick often approaches too quickly for the goalkeeper to react to its direction of motion; instead, the goalkeeper must guess the likely direction of the kick, and dive in anticipation, if they are to have a chance of saving the shot. We examined all 361 kicks from the 37 penalty shootouts that occurred in World Cup and Euro Cup matches over a 36-year period from 1976 to 2012 and show that goalkeepers displayed a clear sequential bias. Following repeated kicks in the same direction, goalkeepers became increasingly likely to dive in the opposite direction on the next kick. Surprisingly, kickers failed to exploit these goalkeeper biases. Our findings highlight the importance of monitoring and predicting sequential behavior in real-world competition. Penalty shootouts pit one goalkeeper against several kickers in rapid succession. Asymmetries in the cognitive capacities of an individual versus a group could produce significant advantages over opponents. Copyright © 2014 Elsevier Ltd. All rights reserved.

Competition and dental services.

PubMed

Grytten, J; Sørensen, R

2000-07-01

Dental services for adults are different from all other Norwegian health services in that they are provided by private producers (dentists) who have full freedom to establish a practice. They have had this freedom since the end of World War II. A further liberalization of the market for dental services occurred in November 1995, when the so-called normal tariff was repealed. The system changed from a fixed fee system to a deregulated fee system. In principle, the market for dental services for adults operates as a free competitive market, in which dentists must compete for a market share. The aim of this study was to study the short-term effects of competition. A comprehensive set of data on fees, practice characteristics, treatment profiles and factors that dentists take into account when determining fees was analysed. The main finding was that competition has a weak effect. No support was found for the theory that the level of fees is the result of monopolistic competition or monopoly. The results also provided some evidence against the inducement hypothesis. At this stage, it is interesting to notice that dentists do not seem to exploit the power they have to control the market. One explanation, which is consistent with the more recent literature, is that physicians' behaviour to a large extent is influenced by professional norms and caring concerns about their patients. Financial incentives are important, but these incentives are constrained by norms other than self-interest. The interpretation of the results should also take into account that the deregulation has operated for a short time and that dentists and patients may not yet have adjusted to changes in the characteristics of the market. Copyright 2000 John Wiley & Sons, Ltd.

Development of a Tightly Controlled Off Switch for Saccharomyces cerevisiae Regulated by Camphor, a Low-Cost Natural Product

PubMed Central

Ikushima, Shigehito; Zhao, Yu; Boeke, Jef D.

2015-01-01

Here we describe the engineering of a distant homolog of the Tet repressor, CamR, isolated from Pseudomonas putida, that is regulated by camphor, a very inexpensive small molecule (at micromolar concentrations) for use in Saccharomyces cerevisiae. The repressor was engineered by expression from a constitutive yeast promoter, fusion to a viral activator protein cassette, and codon optimization. A suitable promoter responsive to the CamR fusion protein was engineered by embedding a P. putida operator binding sequence within an upstream activating sequence (UAS)-less CYC1 promoter from S. cerevisiae. The switch, named the Camphor-Off switch, activates expression of a reporter gene in camphor-free media and represses it with micromolar concentrations of camphor. PMID:26206350

Dosage compensation proteins targeted to X chromosomes by a determinant of hermaphrodite fate.

PubMed

Dawes, H E; Berlin, D S; Lapidus, D M; Nusbaum, C; Davis, T L; Meyer, B J

1999-06-11

In many organisms, master control genes coordinately regulate sex-specific aspects of development. SDC-2 was shown to induce hermaphrodite sexual differentiation and activate X chromosome dosage compensation in Caenorhabditis elegans. To control these distinct processes, SDC-2 acts as a strong gene-specific repressor and a weaker chromosome-wide repressor. To initiate hermaphrodite development, SDC-2 associates with the promoter of the male sex-determining gene her-1 to repress its transcription. To activate dosage compensation, SDC-2 triggers assembly of a specialized protein complex exclusively on hermaphrodite X chromosomes to reduce gene expression by half. SDC-2 can localize to X chromosomes without other components of the dosage compensation complex, suggesting that SDC-2 targets dosage compensation machinery to X chromosomes.

Beta-Lactamase Repressor BlaI Modulates Staphylococcus aureus Cathelicidin Antimicrobial Peptide Resistance and Virulence.

PubMed

Pence, Morgan A; Haste, Nina M; Meharena, Hiruy S; Olson, Joshua; Gallo, Richard L; Nizet, Victor; Kristian, Sascha A

2015-01-01

BlaI is a repressor of BlaZ, the beta-lactamase responsible for penicillin resistance in Staphylococcus aureus. Through screening a transposon library in S. aureus Newman for susceptibility to cathelicidin antimicrobial peptide, we discovered BlaI as a novel cathelicidin resistance factor. Additionally, through integrational mutagenesis in S. aureus Newman and MRSA Sanger 252 strains, we confirmed the role of BlaI in resistance to human and murine cathelidicin and showed that it contributes to virulence in human whole blood and murine infection models. We further demonstrated that BlaI could be a target for innate immune-based antimicrobial therapies; by removing BlaI through subinhibitory concentrations of 6-aminopenicillanic acid, we were able to sensitize S. aureus to LL-37 killing.

Two bHLH-type transcription factors, JA-ASSOCIATED MYC2-LIKE2 and JAM3, are transcriptional repressors and affect male fertility

PubMed Central

Nakata, Masaru; Ohme-Takagi, Masaru

2013-01-01

The jasmonate (JA) plant hormones regulate responses to biotic and abiotic stress and aspects of plant development, including male fertility in Arabidopsis thaliana. The bHLH-type transcription factor JA-ASSOCIATED MYC2-LIKE1 (JAM1) negatively regulates JA signaling and gain-of-function JAM1 transgenic plants have impaired JA-mediated male fertility. Here we report that JAM2 and JAM3, 2 bHLHs closely related to JAM1, also act as transcriptional repressors. Moreover, overexpression of JAM2 and JAM3 also results in reduced male fertility. These results suggest that JAM1, JAM2, and JAM3 act redundantly as negative regulators of JA-mediated male fertility. PMID:24056034

Differential Top10 promoter regulation by six tetracycline analogues in plant cells

NASA Technical Reports Server (NTRS)

Love, John; Allen, George C.; Gatz, Christiane; Thompson, William F.; Brown, C. S. (Principal Investigator)

2002-01-01

The effects of five tetracycline analogues, anhydrotetracycline, doxycycline, minocycline, oxytetracycline, and tetracycline, on Top10 promoter activity in NT1 tobacco tissue culture cells have been analysed. The concentration that repressed Top10 promoter activity, the level of transgene repression and the kinetics of transgene de-repression were determined for each analogue, and could not be predicted from in vitro binding affinity to the tetracycline repressor or from comparison with animal cells. Doxycycline had the most potent effect on the Top10 promoter and completely inhibited transgene expression at 4 nmol l(-1). Tetracycline was the most versatile of the analogues tested; tetracycline inhibited the Top10 promoter at 10 nmol l(-1) and was easily washed out to restore Top10-driven expression in 12-24 h. A study was also made of the suitability for plant research of a novel tetracycline analogue, GR33076X. In animal cells, GR33076X de-repressed Top10 promoter activity in the presence of inhibitory concentrations of anhydrotetracycline. In NT1, it is shown that GR 33076X can antagonize repression of the Top10 promoter in the presence of tetracycline, but not of anhydrotetracycline or of doxycycline. Different tetracycline analogues can therefore be used to regulate the Top10 promoter in plant cells and this property may be exploited in planning an optimum course of transgene regulation.

Differential Top10 promoter regulation by six tetracycline analogues in plant cells.

PubMed

Love, John; Allen, George C; Gatz, Christiane; Thompson, William F

2002-09-01

The effects of five tetracycline analogues, anhydrotetracycline, doxycycline, minocycline, oxytetracycline, and tetracycline, on Top10 promoter activity in NT1 tobacco tissue culture cells have been analysed. The concentration that repressed Top10 promoter activity, the level of transgene repression and the kinetics of transgene de-repression were determined for each analogue, and could not be predicted from in vitro binding affinity to the tetracycline repressor or from comparison with animal cells. Doxycycline had the most potent effect on the Top10 promoter and completely inhibited transgene expression at 4 nmol l(-1). Tetracycline was the most versatile of the analogues tested; tetracycline inhibited the Top10 promoter at 10 nmol l(-1) and was easily washed out to restore Top10-driven expression in 12-24 h. A study was also made of the suitability for plant research of a novel tetracycline analogue, GR33076X. In animal cells, GR33076X de-repressed Top10 promoter activity in the presence of inhibitory concentrations of anhydrotetracycline. In NT1, it is shown that GR 33076X can antagonize repression of the Top10 promoter in the presence of tetracycline, but not of anhydrotetracycline or of doxycycline. Different tetracycline analogues can therefore be used to regulate the Top10 promoter in plant cells and this property may be exploited in planning an optimum course of transgene regulation.

Description of a Nanobody-based Competitive Immunoassay to Detect Tsetse Fly Exposure

PubMed Central

Caljon, Guy; Hussain, Shahid; Vermeiren, Lieve; Van Den Abbeele, Jan

2015-01-01

Background Tsetse flies are the main vectors of human and animal African trypanosomes. The Tsal proteins in tsetse fly saliva were previously identified as suitable biomarkers of bite exposure. A new competitive assay was conceived based on nanobody (Nb) technology to ameliorate the detection of anti-Tsal antibodies in mammalian hosts. Methodology/Principal Findings A camelid-derived Nb library was generated against the Glossina morsitans morsitans sialome and exploited to select Tsal specific Nbs. One of the three identified Nb families (family III, TsalNb-05 and TsalNb-11) was found suitable for anti-Tsal antibody detection in a competitive ELISA format. The competitive ELISA was able to detect exposure to a broad range of tsetse species (G. morsitans morsitans, G. pallidipes, G. palpalis gambiensis and G. fuscipes) and did not cross-react with the other hematophagous insects (Stomoxys calcitrans and Tabanus yao). Using a collection of plasmas from tsetse-exposed pigs, the new test characteristics were compared with those of the previously described G. m. moristans and rTsal1 indirect ELISAs, revealing equally good specificities (> 95%) and positive predictive values (> 98%) but higher negative predictive values and hence increased sensitivity (> 95%) and accuracy (> 95%). Conclusion/Significance We have developed a highly accurate Nb-based competitive immunoassay to detect specific anti-Tsal antibodies induced by various tsetse fly species in a range of hosts. We propose that this competitive assay provides a simple serological indicator of tsetse fly presence without the requirement of test adaptation to the vertebrate host species. In addition, the use of monoclonal Nbs for antibody detection is innovative and could be applied to other tsetse fly salivary biomarkers in order to achieve a multi-target immunoprofiling of hosts. In addition, this approach could be broadened to other pathogenic organisms for which accurate serological diagnosis remains a bottleneck. PMID:25658871

Individual Foraging Strategies Reveal Niche Overlap between Endangered Galapagos Pinnipeds

PubMed Central

Villegas-Amtmann, Stella; Jeglinski, Jana W. E.; Costa, Daniel P.; Robinson, Patrick W.; Trillmich, Fritz

2013-01-01

Most competition studies between species are conducted from a population-level approach. Few studies have examined inter-specific competition in conjunction with intra-specific competition, with an individual-based approach. To our knowledge, none has been conducted on marine top predators. Sympatric Galapagos fur seals (Arctocephalus galapagoensis) and sea lions (Zalophus wollebaeki) share similar geographic habitats and potentially compete. We studied their foraging niche overlap at Cabo Douglas, Fernandina Island from simultaneously collected dive and movement data to examine spatial and temporal inter- and intra-specific competition. Sea lions exhibited 3 foraging strategies (shallow, intermediate and deep) indicating intra-specific competition. Fur seals exhibited one foraging strategy, diving predominantly at night, between 0–80 m depth and mostly at 19–22 h. Most sea lion dives also occurred at night (63%), between 0–40 m, within fur seals' diving depth range. 34% of sea lions night dives occurred at 19–22 h, when fur seals dived the most, but most of them occurred at dawn and dusk, when fur seals exhibited the least amount of dives. Fur seals and sea lions foraging behavior overlapped at 19 and 21 h between 0–30 m depths. Sea lions from the deep diving strategy exhibited the greatest foraging overlap with fur seals, in time (19 h), depth during overlapping time (21–24 m), and foraging range (37.7%). Fur seals foraging range was larger. Cabo Douglas northwest coastal area, region of highest diving density, is a foraging “hot spot” for both species. Fur seals and sea lions foraging niche overlap occurred, but segregation also occurred; fur seals primarily dived at night, while sea lions exhibited night and day diving. Both species exploited depths and areas exclusive to their species. Niche breadth generally increases with environmental uncertainty and decreased productivity. Potential competition between these species could be greater during warmer periods when prey availability is reduced. PMID:23967096

XIPE: the x-ray imaging polarimetry explorer

NASA Astrophysics Data System (ADS)

Soffitta, P.; Bellazzini, R.; Bozzo, E.; Burwitz, V.; Castro-Tirado, A.; Costa, E.; Courvoisier, T.; Feng, H.; Gburek, S.; Goosmann, R.; Karas, V.; Matt, G.; Muleri, F.; Nandra, K.; Pearce, M.; Poutanen, J.; Reglero, V.; Sabau Maria, D.; Santangelo, A.; Tagliaferri, G.; Tenzer, C.; Vink, J.; Weisskopf, M. C.; Zane, S.; Agudo, I.; Antonelli, A.; Attina, P.; Baldini, L.; Bykov, A.; Carpentiero, R.; Cavazzuti, E.; Churazov, E.; Del Monte, E.; De Martino, D.; Donnarumma, I.; Doroshenko, V.; Evangelista, Y.; Ferreira, I.; Gallo, E.; Grosso, N.; Kaaret, P.; Kuulkers, E.; Laranaga, J.; Latronico, L.; Lumb, D. H.; Macian, J.; Malzac, J.; Marin, F.; Massaro, E.; Minuti, M.; Mundell, C.; Ness, J. U.; Oosterbroek, T.; Paltani, S.; Pareschi, G.; Perna, R.; Petrucci, P.-O.; Pinazo, H. B.; Pinchera, M.; Rodriguez, J. P.; Roncadelli, M.; Santovincenzo, A.; Sazonov, S.; Sgro, C.; Spiga, D.; Svoboda, J.; Theobald, C.; Theodorou, T.; Turolla, R.; Wilhelmi de Ona, E.; Winter, B.; Akbar, A. M.; Allan, H.; Aloisio, R.; Altamirano, D.; Amati, L.; Amato, E.; Angelakis, E.; Arezu, J.; Atteia, J.-L.; Axelsson, M.; Bachetti, M.; Ballo, L.; Balman, S.; Bandiera, R.; Barcons, X.; Basso, S.; Baykal, A.; Becker, W.; Behar, E.; Beheshtipour, B.; Belmont, R.; Berger, E.; Bernardini, F.; Bianchi, S.; Bisnovatyi-Kogan, G.; Blasi, P.; Blay, P.; Bodaghee, A.; Boer, M.; Boettcher, M.; Bogdanov, S.; Bombaci, I.; Bonino, R.; Braga, J.; Brandt, W.; Brez, A.; Bucciantini, N.; Burderi, L.; Caiazzo, I.; Campana, R.; Campana, S.; Capitanio, F.; Cappi, M.; Cardillo, M.; Casella, P.; Catmabacak, O.; Cenko, B.; Cerda-Duran, P.; Cerruti, C.; Chaty, S.; Chauvin, M.; Chen, Y.; Chenevez, J.; Chernyakova, M.; Cheung, C. C. Teddy; Christodoulou, D.; Connell, P.; Corbet, R.; Coti Zelati, F.; Covino, S.; Cui, W.; Cusumano, G.; D'Ai, A.; D'Ammando, F.; Dadina, M.; Dai, Z.; De Rosa, A.; de Ruvo, L.; Degenaar, N.; Del Santo, M.; Del Zanna, L.; Dewangan, G.; Di Cosimo, S.; Di Lalla, N.; Di Persio, G.; Di Salvo, T.; Dias, T.; Done, C.; Dovciak, M.; Doyle, G.; Ducci, L.; Elsner, R.; Enoto, T.; Escada, J.; Esposito, P.; Eyles, C.; Fabiani, S.; Falanga, M.; Falocco, S.; Fan, Y.; Fender, R.; Feroci, M.; Ferrigno, C.; Forman, W.; Foschini, L.; Fragile, C.; Fuerst, F.; Fujita, Y.; Gasent-Blesa, J. L.; Gelfand, J.; Gendre, B.; Ghirlanda, G.; Ghisellini, G.; Giroletti, M.; Goetz, D.; Gogus, E.; Gomez, J.-L.; Gonzalez, D.; Gonzalez-Riestra, R.; Gotthelf, E.; Gou, L.; Grandi, P.; Grinberg, V.; Grise, F.; Guidorzi, C.; Gurlebeck, N.; Guver, T.; Haggard, D.; Hardcastle, M.; Hartmann, D.; Haswell, C.; Heger, A.; Hernanz, M.; Heyl, J.; Ho, L.; Hoormann, J.; Horak, J.; Huovelin, J.; Huppenkothen, D.; Iaria, R.; Inam Sitki, C.; Ingram, A.; Israel, G.; Izzo, L.; Burgess, M.; Jackson, M.; Ji, L.; Jiang, J.; Johannsen, T.; Jones, C.; Jorstad, S.; Kajava, J. J. E.; Kalamkar, M.; Kalemci, E.; Kallman, T.; Kamble, A.; Kislat, F.; Kiss, M.; Klochkov, D.; Koerding, E.; Kolehmainen, M.; Koljonen, K.; Komossa, S.; Kong, A.; Korpela, S.; Kowalinski, M.; Krawczynski, H.; Kreykenbohm, I.; Kuss, M.; Lai, D.; Lan, M.; Larsson, J.; Laycock, S.; Lazzati, D.; Leahy, D.; Li, H.; Li, J.; Li, L.-X.; Li, T.; Li, Z.; Linares, M.; Lister, M.; Liu, H.; Lodato, G.; Lohfink, A.; Longo, F.; Luna, G.; Lutovinov, A.; Mahmoodifar, S.; Maia, J.; Mainieri, V.; Maitra, C.; Maitra, D.; Majczyna, A.; Maldera, S.; Malyshev, D.; Manfreda, A.; Manousakis, A.; Manuel, R.; Margutti, R.; Marinucci, A.; Markoff, S.; Marscher, A.; Marshall, H.; Massaro, F.; McLaughlin, M.; Medina-Tanco, G.; Mehdipour, M.; Middleton, M.; Mignani, R.; Mimica, P.; Mineo, T.; Mingo, B.; Miniutti, G.; Mirac, S. M.; Morlino, G.; Motlagh, A. V.; Motta, S.; Mushtukov, A.; Nagataki, S.; Nardini, F.; Nattila, J.; Navarro, G. J.; Negri, B.; Negro, Matteo; Nenonen, S.; Neustroev, V.; Nicastro, F.; Norton, A.; Nucita, A.; O'Brien, P.; O'Dell, S.

2016-07-01

XIPE, the X-ray Imaging Polarimetry Explorer, is a mission dedicated to X-ray Astronomy. At the time of writing XIPE is in a competitive phase A as fourth medium size mission of ESA (M4). It promises to reopen the polarimetry window in high energy Astrophysics after more than 4 decades thanks to a detector that efficiently exploits the photoelectric effect and to X-ray optics with large effective area. XIPE uniqueness is time-spectrally-spatially- resolved X-ray polarimetry as a breakthrough in high energy astrophysics and fundamental physics. Indeed the payload consists of three Gas Pixel Detectors at the focus of three X-ray optics with a total effective area larger than one XMM mirror but with a low weight. The payload is compatible with the fairing of the Vega launcher. XIPE is designed as an observatory for X-ray astronomers with 75 % of the time dedicated to a Guest Observer competitive program and it is organized as a consortium across Europe with main contributions from Italy, Germany, Spain, United Kingdom, Poland, Sweden.

The power of brand equity: Exploiting a singular incumbent advantage

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

Almquist, E.; Piotroski, S.A.

The US utility ``brandscape`` resembles feudal Europe: There are numerous adjacent fiefdoms where the brand equity within each falls off precipitously outside territory borders. Those who want to ``go national`` face a protracted, expensive task dislodging local incumbents. With the onset of competition in retail electric power markets, America`s last great deregulation is well under way. Customers are pressing their suppliers to reduce energy bills by opening markets to competition. Deregulation of power generation, which has moved quickly in recent years throughout North America and Europe, is eroding the traditional pillars of value: franchise protection, cost-based pricing, and rate-of-return regulation.more » The stakes are high for incumbent utilities, given that electric sales in the United States alone total more than $200 billion, greater than sales in telecommunications, air transportation, or railroads. Add in natural gas ($5 billion or so) and related energy products and services, and it is clear why upstart entrepreneurs and outsider firms are attracted to the opportunities opened up by deregulation.« less

Aggression in Tephritidae Flies: Where, When, Why? Future Directions for Research in Integrated Pest Management.

PubMed

Benelli, Giovanni

2014-12-30

True fruit flies (Diptera: Tephritidae) include over 4000 species, many of which constitute enormous threats to fruit and vegetable production worldwide. A number of Tephritidae are lekking species, forming aggregations in which males fight to defend a small territory where they court females and mate. Male-male contests also occur in non-lekking species, characterized by resource defense polygyny. Tephritidae females display agonistic behavior to maintain single oviposition sites and reduce larval competition for food. Here, how, where, when and why aggressive interactions occur in Tephritidae flies is reviewed. A number of neglected issues deserving further research are highlighted, with a special focus on diel periodicity of aggression, cues evoking aggressive behavior, the role of previous experience on fighting success and the evolution of behavioral lateralization of aggressive displays. In the final section, future directions to exploit this knowledge in Integrated Pest Management, with particular emphasis on enhancement of Sterile Insect Technique and interspecific competitive displacement in the field are suggested.

Competition among cooperators: Altruism and reciprocity

PubMed Central

Danielson, Peter

2002-01-01

Levine argues that neither self-interest nor altruism explains experimental results in bargaining and public goods games. Subjects' preferences appear also to be sensitive to their opponents' perceived altruism. Sethi and Somanathan provide a general account of reciprocal preferences that survive under evolutionary pressure. Although a wide variety of reciprocal strategies pass this evolutionary test, Sethi and Somanthan conjecture that fewer are likely to survive when reciprocal strategies compete with each other. This paper develops evolutionary agent-based models to test their conjecture in cases where reciprocal preferences can differ in a variety of games. We confirm that reciprocity is necessary but not sufficient for optimal cooperation. We explore the theme of competition among reciprocal cooperators and display three interesting emergent organizations: racing to the “moral high ground,” unstable cycles of preference change, and, when we implement reciprocal mechanisms, hierarchies resulting from exploiting fellow cooperators. If reciprocity is a basic mechanism facilitating cooperation, we can expect interaction that evolves around it to be complex, non-optimal, and resistant to change. PMID:12011403

Aggression in Tephritidae Flies: Where, When, Why? Future Directions for Research in Integrated Pest Management

PubMed Central

Benelli, Giovanni

2014-01-01

True fruit flies (Diptera: Tephritidae) include over 4000 species, many of which constitute enormous threats to fruit and vegetable production worldwide. A number of Tephritidae are lekking species, forming aggregations in which males fight to defend a small territory where they court females and mate. Male-male contests also occur in non-lekking species, characterized by resource defense polygyny. Tephritidae females display agonistic behavior to maintain single oviposition sites and reduce larval competition for food. Here, how, where, when and why aggressive interactions occur in Tephritidae flies is reviewed. A number of neglected issues deserving further research are highlighted, with a special focus on diel periodicity of aggression, cues evoking aggressive behavior, the role of previous experience on fighting success and the evolution of behavioral lateralization of aggressive displays. In the final section, future directions to exploit this knowledge in Integrated Pest Management, with particular emphasis on enhancement of Sterile Insect Technique and interspecific competitive displacement in the field are suggested. PMID:26463064

Climate change, future Arctic Sea ice, and the competitiveness of European Arctic offshore oil and gas production on world markets.

PubMed

Petrick, Sebastian; Riemann-Campe, Kathrin; Hoog, Sven; Growitsch, Christian; Schwind, Hannah; Gerdes, Rüdiger; Rehdanz, Katrin

2017-12-01

A significant share of the world's undiscovered oil and natural gas resources are assumed to lie under the seabed of the Arctic Ocean. Up until now, the exploitation of the resources especially under the European Arctic has largely been prevented by the challenges posed by sea ice coverage, harsh weather conditions, darkness, remoteness of the fields, and lack of infrastructure. Gradual warming has, however, improved the accessibility of the Arctic Ocean. We show for the most resource-abundant European Arctic Seas whether and how a climate induced reduction in sea ice might impact future accessibility of offshore natural gas and crude oil resources. Based on this analysis we show for a number of illustrative but representative locations which technology options exist based on a cost-minimization assessment. We find that under current hydrocarbon prices, oil and gas from the European offshore Arctic is not competitive on world markets.

Quorum-sensing control of antibiotic resistance stabilizes cooperation in Chromobacterium violaceum.

PubMed

Evans, Kara C; Benomar, Saida; Camuy-Vélez, Lennel A; Nasseri, Ellen B; Wang, Xiaofei; Neuenswander, Benjamin; Chandler, Josephine R

2018-05-01

Many Proteobacteria use quorum sensing to regulate production of public goods, such as antimicrobials and proteases, that are shared among members of a community. Public goods are vulnerable to exploitation by cheaters, such as quorum sensing-defective mutants. Quorum sensing- regulated private goods, goods that benefit only producing cells, can prevent the emergence of cheaters under certain growth conditions. Previously, we developed a laboratory co-culture model to investigate the importance of quorum-regulated antimicrobials during interspecies competition. In our model, Burkholderia thailandensis and Chromobacterium violaceum each use quorum sensing-controlled antimicrobials to inhibit the other species' growth. Here, we show that C. violaceum uses quorum sensing to increase resistance to bactobolin, a B. thailandensis antibiotic, by increasing transcription of a putative antibiotic efflux pump. We demonstrate conditions where C. violaceum quorum-defective cheaters emerge and show that in these conditions, bactobolin restrains cheaters. We also demonstrate that bactobolin restrains quorum-defective mutants in our co-culture model, and the increase in antimicrobial-producing cooperators drives the C. violaceum population to become more competitive. Our results describe a mechanism of cheater restraint involving quorum control of efflux pumps and demonstrate that interspecies competition can reinforce cooperative behaviors by placing constraints on quorum sensing-defective mutants.

Fluorescent sperm offer a method for tracking the real-time success of ejaculates when they compete to fertilise eggs.

PubMed

Lymbery, Rowan A; Kennington, W Jason; Evans, Jonathan P

2016-03-04

Despite intensive research effort, many uncertainties remain in the field of gamete-level sexual selection, particularly in understanding how sperm from different males interact when competing for fertilisations. Here, we demonstrate the utility of broadcast spawning marine invertebrates for unravelling these mysteries, highlighting their mode of reproduction and, in some species, unusual patterns of mitochondrial inheritance. We present a method utilising both properties in the blue mussel, Mytilus galloprovincialis. In mytilids and many other bivalves, both sperm and egg mitochondria are inherited. We exploit this, using the vital mitochondrial dye MitoTracker, to track the success of sperm from individual males when they compete with those from rivals to fertilise eggs. We confirm that dying mitochondria has no adverse effects on in vitro measures of sperm motility (reflecting mitochondrial energetics) or sperm competitive fertilisation success. Therefore, we propose the technique as a powerful and logistically tractable tool for sperm competition studies. Importantly, our method allows the competitive fertilisation success of sperm from any male to be measured directly and disentangled from confounding effects of post-fertilisation embryo survival. Moreover, the mitochondrial dye has broader applications in taxa without paternal mitochondrial inheritance, for example by tracking the dynamics of competing ejaculates prior to fertilisation.

The eco-evolutionary responses of a generalist consumer to resource competition.

PubMed

Abrams, Peter A

2012-10-01

This article explores the combined evolutionary and ecological responses of resource uptake abilities in a generalist consumer to exploitative competition for one resource using a simple 2-resource model. It compares the sizes of ecologically and evolutionarily caused changes in population densities in cases where the original consumer has a strong or a weak trade-off in its abilities to consume the two resources. The analysis also compares the responses of the original species to competition when the competitor's population size is or is not limited by the shared resource. Although divergence in resource use traits in the resident generalist consumer is expected under all scenarios when resources are substitutable, the changes in population densities of the resources and resident consumer frequently differ between scenarios. The population of the original consumer often decreases as a result of its own adaptive divergence, and this decrease is often much greater than the initial ecological decrease. If the evolving consumer has a strong trade-off, the overlapped resource increases in equilibrium population density in response to being consumed by a generalist competitor. Some of these predictions differ qualitatively in alternative scenarios involving sustained variation in population densities or nutritionally essential resources. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

Fluorescent sperm offer a method for tracking the real-time success of ejaculates when they compete to fertilise eggs

PubMed Central

Lymbery, Rowan A.; Kennington, W. Jason; Evans, Jonathan P.

2016-01-01

Despite intensive research effort, many uncertainties remain in the field of gamete-level sexual selection, particularly in understanding how sperm from different males interact when competing for fertilisations. Here, we demonstrate the utility of broadcast spawning marine invertebrates for unravelling these mysteries, highlighting their mode of reproduction and, in some species, unusual patterns of mitochondrial inheritance. We present a method utilising both properties in the blue mussel, Mytilus galloprovincialis. In mytilids and many other bivalves, both sperm and egg mitochondria are inherited. We exploit this, using the vital mitochondrial dye MitoTracker, to track the success of sperm from individual males when they compete with those from rivals to fertilise eggs. We confirm that dying mitochondria has no adverse effects on in vitro measures of sperm motility (reflecting mitochondrial energetics) or sperm competitive fertilisation success. Therefore, we propose the technique as a powerful and logistically tractable tool for sperm competition studies. Importantly, our method allows the competitive fertilisation success of sperm from any male to be measured directly and disentangled from confounding effects of post-fertilisation embryo survival. Moreover, the mitochondrial dye has broader applications in taxa without paternal mitochondrial inheritance, for example by tracking the dynamics of competing ejaculates prior to fertilisation. PMID:26941059

Social selection parapatry in Afrotropical sunbirds.

PubMed

McEntee, Jay P; Peñalba, Joshua V; Werema, Chacha; Mulungu, Elia; Mbilinyi, Maneno; Moyer, David; Hansen, Louis; Fjeldså, Jon; Bowie, Rauri C K

2016-06-01

The extent of range overlap of incipient and recent species depends on the type and magnitude of phenotypic divergence that separates them, and the consequences of phenotypic divergence on their interactions. Signal divergence by social selection likely initiates many speciation events, but may yield niche-conserved lineages predisposed to limit each others' ranges via ecological competition. Here, we examine this neglected aspect of social selection speciation theory in relation to the discovery of a nonecotonal species border between sunbirds. We find that Nectarinia moreaui and Nectarinia fuelleborni meet in a ∼6 km wide contact zone, as estimated by molecular cline analysis. These species exploit similar bioclimatic niches, but sing highly divergent learned songs, consistent with divergence by social selection. Cline analyses suggest that within-species stabilizing social selection on song-learning predispositions maintains species differences in song despite both hybridization and cultural transmission. We conclude that ecological competition between moreaui and fuelleborni contributes to the stabilization of the species border, but that ecological competition acts in conjunction with reproductive interference. The evolutionary maintenance of learned song differences in a hybrid zone recommend this study system for future studies on the mechanisms of learned song divergence and its role in speciation. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

Structural insights into human heme oxygenase-1 inhibition by potent and selective azole-based compounds

PubMed Central

Rahman, Mona N.; Vukomanovic, Dragic; Vlahakis, Jason Z.; Szarek, Walter A.; Nakatsu, Kanji; Jia, Zongchao

2013-01-01

The development of heme oxygenase (HO) inhibitors, especially those that are isozyme-selective, promises powerful pharmacological tools to elucidate the regulatory characteristics of the HO system. It is already known that HO has cytoprotective properties and may play a role in several disease states, making it an enticing therapeutic target. Traditionally, the metalloporphyrins have been used as competitive HO inhibitors owing to their structural similarity with the substrate, heme. However, given heme's important role in several other proteins (e.g. cytochromes P450, nitric oxide synthase), non-selectivity is an unfortunate side-effect. Reports that azalanstat and other non-porphyrin molecules inhibited HO led to a multi-faceted effort to develop novel compounds as potent, selective inhibitors of HO. This resulted in the creation of non-competitive inhibitors with selectivity for HO, including a subset with isozyme selectivity for HO-1. Using X-ray crystallography, the structures of several complexes of HO-1 with novel inhibitors have been elucidated, which provided insightful information regarding the salient features required for inhibitor binding. This included the structural basis for non-competitive inhibition, flexibility and adaptability of the inhibitor binding pocket, and multiple, potential interaction subsites, all of which can be exploited in future drug-design strategies. PMID:23097500

Consumer price sensitivity and health plan choice in a regulated competition setting.

PubMed

Bischof, Tamara; Schmid, Christian P R

2018-05-21

We estimate premium elasticities in a regulated competition market based on a quasi-exogenous premium increase for young adults in Switzerland. We exploit that individuals born before the turn of the year ("treatment group") face a larger increase in premiums than individuals born after the turn of the year ("control group"). We find that the treatment group is 1.5 times more likely to switch their health plan than the control group. Overall, individuals respond to premium increases by choosing more frequently health plans with managed care features, increasing the deductible, and by switching the insurer. Regarding health plan choice, we find an average elasticity of -0.56 with regard to the relative premium difference of any plan to the status quo contract. The elasticity is up to 5 times larger for the treated (-1.03) than for the controls (-0.19). Our results are not driven by health status as measured by health care expenditures and chronic conditions. Rather, our findings suggest that the difference in the premium elasticity is driven by the salience of the premium increase. We argue that this finding is of high relevance for health care policies that aim at fostering health plan competition. Copyright © 2018 John Wiley & Sons, Ltd.

FOREVER YOUNG FLOWER Negatively Regulates Ethylene Response DNA-Binding Factors by Activating an Ethylene-Responsive Factor to Control Arabidopsis Floral Organ Senescence and Abscission1

PubMed Central

Li, Pei-Fang; Lee, Yung-I; Yang, Chang-Hsien

2015-01-01

In this study of Arabidopsis (Arabidopsis thaliana), we investigated the relationship between FOREVER YOUNG FLOWER (FYF) and Ethylene Response DNA-binding Factors (EDFs) and functionally analyzed a key FYF target, an Ethylene-Responsive Factor (ERF), that controls flower senescence/abscission. Ectopic expression of EDF1/2/3/4 caused promotion of flower senescence/abscission and the activation of the senescence-associated genes. The presence of a repressor domain in EDFs and the enhancement of the promotion of senescence/abscission in EDF1/2/3/4+SRDX (converting EDFs to strong repressors by fusion with the ERF-associated amphiphilic repression motif repression domain SRDX) transgenic plants suggested that EDFs act as repressors. The significant reduction of β-glucuronidase (GUS) expression by 35S:FYF in EDF1/2/3/4:GUS plants indicates that EDF1/2/3/4 functions downstream of FYF in regulating flower senescence/abscission. In this study, we also characterized an ERF gene, FOREVER YOUNG FLOWER UP-REGULATING FACTOR1 (FUF1), which is up-regulated by FYF during flower development. Ectopic expression of FUF1 caused similar delayed flower senescence/abscission as seen in 35S:FYF plants. This phenotype was correlated with deficient abscission zone formation, ethylene insensitivity, and down-regulation of EDF1/2/3/4 and abscission-associated genes in 35S:FUF1 flowers. In contrast, significant promotion of flower senescence/abscission and up-regulation of EDF1/2/3/4 were observed in 35S:FUF1+SRDX transgenic dominant-negative plants, in which FUF1 is converted to a potent repressor by fusion to an SRDX-suppressing motif. Thus, FUF1 acts as an activator in suppressing EDF1/2/3/4 function and senescence/abscission of the flowers. Our results reveal that FYF regulates flower senescence/abscission by negatively regulating EDF1/2/3/4, which is the downstream gene in the ethylene response, by activating FUF1 in Arabidopsis. PMID:26063506

FOREVER YOUNG FLOWER Negatively Regulates Ethylene Response DNA-Binding Factors by Activating an Ethylene-Responsive Factor to Control Arabidopsis Floral Organ Senescence and Abscission.

PubMed

Chen, Wei-Han; Li, Pei-Fang; Chen, Ming-Kun; Lee, Yung-I; Yang, Chang-Hsien

2015-08-01

In this study of Arabidopsis (Arabidopsis thaliana), we investigated the relationship between FOREVER YOUNG FLOWER (FYF) and Ethylene Response DNA-binding Factors (EDFs) and functionally analyzed a key FYF target, an Ethylene-Responsive Factor (ERF), that controls flower senescence/abscission. Ectopic expression of EDF1/2/3/4 caused promotion of flower senescence/abscission and the activation of the senescence-associated genes. The presence of a repressor domain in EDFs and the enhancement of the promotion of senescence/abscission in EDF1/2/3/4+SRDX (converting EDFs to strong repressors by fusion with the ERF-associated amphiphilic repression motif repression domain SRDX) transgenic plants suggested that EDFs act as repressors. The significant reduction of β-glucuronidase (GUS) expression by 35S:FYF in EDF1/2/3/4:GUS plants indicates that EDF1/2/3/4 functions downstream of FYF in regulating flower senescence/abscission. In this study, we also characterized an ERF gene, FOREVER YOUNG FLOWER UP-REGULATING FACTOR1 (FUF1), which is up-regulated by FYF during flower development. Ectopic expression of FUF1 caused similar delayed flower senescence/abscission as seen in 35S:FYF plants. This phenotype was correlated with deficient abscission zone formation, ethylene insensitivity, and down-regulation of EDF1/2/3/4 and abscission-associated genes in 35S:FUF1 flowers. In contrast, significant promotion of flower senescence/abscission and up-regulation of EDF1/2/3/4 were observed in 35S:FUF1+SRDX transgenic dominant-negative plants, in which FUF1 is converted to a potent repressor by fusion to an SRDX-suppressing motif. Thus, FUF1 acts as an activator in suppressing EDF1/2/3/4 function and senescence/abscission of the flowers. Our results reveal that FYF regulates flower senescence/abscission by negatively regulating EDF1/2/3/4, which is the downstream gene in the ethylene response, by activating FUF1 in Arabidopsis. © 2015 American Society of Plant Biologists. All Rights Reserved.

Water-mediated contacts in the trp-repressor operator complex recognition process.

PubMed

Wibowo, Fajar R; Rauch, Christine; Trieb, Michael; Wellenzohn, Bernd; Liedl, Klaus R

2004-04-15

Water-mediated contacts are known as an important recognition tool in trp-repressor operator systems. One of these contacts involves two conserved base pairs (G(6).C(-6) and A(5). T(-5)) and three amino acids (Lys 72, Ile 79, and Ala 80). To investigate the nature of these contacts, we analyzed the X-ray structure (PDB code: 1TRO) of the trp-repressor operator complex by means of molecular dynamics simulations. This X-ray structure contains two dimers that exhibit structural differences. From these two different starting structures, two 10 ns molecular dynamics simulations have been performed. Both of our simulations show an increase of water molecules in the major groove at one side of the dimer, while the other side remains unchanged compared to the X-ray structure. Though the maximum residence time of the concerned water molecules decreases with an increase of solvent at the interface, these water molecules continue to play an important role in mediating DNA-protein contacts. This is shown by new stable amino acids-DNA distances and a long water residence time compared to free DNA simulation. To maintain stability of the new contacts, the preferential water binding site on O6(G6) is extended. This extension agrees with mutation experiment data on A5 and G6, which shows different relative affinity due to mutation on these bases [A. Joachimiak, T. E. Haran, P. B. Sigler, EMBO Journal 1994, Vol. 13, No. (2) pp. 367-372]. Due to the rearrangements in the system, the phosphate of the base G6 is able to interconvert to the B(II) substate, which is not observed on the other half side of the complex. The decrease of the number of hydrogen bonds between protein and DNA backbone could be the initial step of the dissociation process of the complex, or in other words an intermediate complex conformation of the association process. Thus, we surmise that these features show the importance of water-mediated contacts in the trp-repressor operator recognition process. Copyright 2004 Wiley Periodicals, Inc.

The place of space technology in economic development: Reflections on present and future aspects

NASA Technical Reports Server (NTRS)

Lebeau, A.; Reuter, K. E.

1980-01-01

The effects of the development of satellite applications on the orientation of the space effort were examined. The gap between available and exploited technology, the impact of the current economic climate and future trends are discussed. Europe's low level of public funding for its space effort, in comparison to other space powers, and the dangers of complacency regarding Europe's competitiveness in the space market are illustrated. A proposal for the general direction which Europe's future strategy must take if European independence in this field is to be preserved is presented.

Interacting parasites

USGS Publications Warehouse

Lafferty, Kevin D.

2010-01-01

Parasitism is the most popular life-style on Earth, and many vertebrates host more than one kind of parasite at a time. A common assumption is that parasite species rarely interact, because they often exploit different tissues in a host, and this use of discrete resources limits competition (1). On page 243 of this issue, however, Telfer et al. (2) provide a convincing case of a highly interactive parasite community in voles, and show how infection with one parasite can affect susceptibility to others. If some human parasites are equally interactive, our current, disease-by-disease approach to modeling and treating infectious diseases is inadequate (3).

Habitual control of goal selection in humans

PubMed Central

Cushman, Fiery; Morris, Adam

2015-01-01

Humans choose actions based on both habit and planning. Habitual control is computationally frugal but adapts slowly to novel circumstances, whereas planning is computationally expensive but can adapt swiftly. Current research emphasizes the competition between habits and plans for behavioral control, yet many complex tasks instead favor their integration. We consider a hierarchical architecture that exploits the computational efficiency of habitual control to select goals while preserving the flexibility of planning to achieve those goals. We formalize this mechanism in a reinforcement learning setting, illustrate its costs and benefits, and experimentally demonstrate its spontaneous application in a sequential decision-making task. PMID:26460050

Industrial platforms--a unique feature of the European Commission's biotechnology R&D programme.

PubMed

Aguilar, A; Ingemansson, T; Hogan, S; Magnien, E

1998-09-01

The European Commission's research, technological development and demonstration programmes aim to strengthen European research and technological development, and to increase the competitiveness of European industries. The creation and development of Industrial Platforms play an important role in these processes by improving the transition from research to commercial application. Industrial Platforms are technology-based industrial groupings established by industry with the aims of enabling the exploitation or dissemination of research results, encouraging academic-industrial collaborations and providing their members with a means of voicing their opinion on present and future research policies.

High Order Entropy-Constrained Residual VQ for Lossless Compression of Images

NASA Technical Reports Server (NTRS)

Kossentini, Faouzi; Smith, Mark J. T.; Scales, Allen

1995-01-01

High order entropy coding is a powerful technique for exploiting high order statistical dependencies. However, the exponentially high complexity associated with such a method often discourages its use. In this paper, an entropy-constrained residual vector quantization method is proposed for lossless compression of images. The method consists of first quantizing the input image using a high order entropy-constrained residual vector quantizer and then coding the residual image using a first order entropy coder. The distortion measure used in the entropy-constrained optimization is essentially the first order entropy of the residual image. Experimental results show very competitive performance.

Mycotoxigenic Fusarium and Deoxynivalenol Production Repress Chitinase Gene Expression in the Biocontrol Agent Trichoderma atroviride P1

PubMed Central

Lutz, Matthias P.; Feichtinger, Georg; Défago, Geneviève; Duffy, Brion

2003-01-01

Mycotoxin contamination associated with head blight of wheat and other grains caused by Fusarium culmorum and F. graminearum is a chronic threat to crop, human, and animal health throughout the world. One of the most important toxins in terms of human exposure is deoxynivalenol (DON) (formerly called vomitoxin), an inhibitor of protein synthesis with a broad spectrum of toxigenicity against animals. Certain Fusarium toxins have additional antimicrobial activity, and the phytotoxin fusaric acid has recently been shown to modulate fungus-bacterium interactions that affect plant health (Duffy and Défago, Phytopathology 87:1250-1257, 1997). The potential impact of DON on Fusarium competition with other microorganisms has not been described previously. Any competitive advantage conferred by DON would complicate efforts to control Fusarium during its saprophytic growth on crop residues that are left after harvest and constitute the primary inoculum reservoir for outbreaks in subsequent plantings. We examined the effect of the DON mycotoxin on ecological interactions between pathogenic Fusarium and Trichoderma atroviride strain P1, a competitor fungus with biocontrol activity against a wide range of plant diseases. Expression of the Trichoderma chitinase genes, ech42 and nag1, which contribute to biocontrol activity, was monitored in vitro and on crop residues of two maize cultivars by using goxA reporter gene fusions. We found that DON-producing F. culmorum and F. graminearum strains repressed expression of nag1-gox. DON-negative wild-type Fusarium strains and a DON-negative mutant with an insertional disruption in the tricothecene biosynthetic gene, tri5, had no effect on antagonist gene expression. The role of DON as the principal repressor above other pathogen factors was confirmed. Exposure of Trichoderma to synthetic DON or to a non-DON-producing Fusarium mutant resulted in the same level of nag1-gox repression as the level observed with DON-producing Fusarium. DON repression was specific for nag1-gox and had no effect, either positive or negative, on expression of another key chitinase gene, ech42. This is the first demonstration that a target pathogen down-regulates genes in a fungal biocontrol agent, and our results provide evidence that mycotoxins have a novel ecological function as factors in Fusarium competitiveness. PMID:12788701

Corepressive interaction and clustering of degrade-and-fire oscillators

PubMed Central

Fernandez, Bastien; Tsimring, Lev S.

2016-01-01

Strongly nonlinear degrade-and-fire (DF) oscillations may emerge in genetic circuits having a delayed negative feedback loop as their core element. Here we study the synchronization of DF oscillators coupled through a common repressor field. For weak coupling, initially distinct oscillators remain desynchronized. For stronger coupling, oscillators can be forced to wait in the repressed state until the global repressor field is sufficiently degraded, and then they fire simultaneously forming a synchronized cluster. Our analytical theory provides necessary and sufficient conditions for clustering and specifies the maximum number of clusters that can be formed in the asymptotic regime. We find that in the thermodynamic limit a phase transition occurs at a certain coupling strength from the weakly clustered regime with only microscopic clusters to a strongly clustered regime where at least one giant cluster has to be present. PMID:22181453

FBI-1 functions as a novel AR co-repressor in prostate cancer cells.

PubMed

Cui, Jiajun; Yang, Yutao; Zhang, Chuanfu; Hu, Pinliang; Kan, Wei; Bai, Xianhong; Liu, Xuelin; Song, Hongbin

2011-03-01

The pro-oncogene FBI-1, encoded by Zbtb7a, is a transcriptional repressor that belongs to the POK (POZ/BTB and Krüppel) protein family. In this study, we investigated a potential interaction between androgen receptor (AR) signaling and FBI-1 and demonstrated that overexpression of FBI-1 inhibited ligand-dependent AR activation. A protein-protein interaction was identified between FBI-1 and AR in a ligand-dependent manner. Furthermore, FBI-1, AR and SMRT formed a ternary complex and FBI-1 enhanced the recruitment of NCoR and SMRT to endogenous PSA upstream sequences. Our data also indicated that the FBI-1-mediated inhibition of AR transcriptional activity is partially dependent on HDAC. Interestingly, FBI-1 plays distinct roles in regulating LNCaP (androgen-dependent) and PC-3 cell (androgen-independent) proliferation.

Cdyl: a new transcriptional co-repressor

PubMed Central

Caron, Cécile; Pivot-Pajot, Christophe; van Grunsven, Leo A.; Col, Edwige; Lestrat, Cécile; Rousseaux, Sophie; Khochbin, Saadi

2003-01-01

Cdyl (chromodomain-Y-like) is a chromodomain-containing protein that is predominantly expressed during mouse spermiogenesis. In its carboxy-terminal portion, there is a domain with homology to the coenzyme A (CoA) pocket of the enoyl-CoA hydratase/isomerase, which is shown here to be able to bind CoA and histone deacetylases (HDACs). It also efficiently represses transcription. Moreover, the binding of Hdac1 represses the ability of Cdyl to bind CoA, and a Cdyl–CoA interaction only occurs in the absence of HDACs. These data suggest that Cdyl is primarily a transcriptional co-repressor. However, the degradation of cellular Hdac1 and Hdac2, as observed here in the elongating spermatids, may provide an HDAC-free environment in which Cdyl could bind CoA and participate in the global chromatin remodelling that occurs in these cells. PMID:12947414

λ-Repressor Oligomerization Kinetics at High Concentrations Using Fluorescence Correlation Spectroscopy in Zero-Mode Waveguides

PubMed Central

Samiee, K. T.; Foquet, M.; Guo, L.; Cox, E. C.; Craighead, H. G.

2005-01-01

Fluorescence correlation spectroscopy (FCS) has demonstrated its utility for measuring transport properties and kinetics at low fluorophore concentrations. In this article, we demonstrate that simple optical nanostructures, known as zero-mode waveguides, can be used to significantly reduce the FCS observation volume. This, in turn, allows FCS to be applied to solutions with significantly higher fluorophore concentrations. We derive an empirical FCS model accounting for one-dimensional diffusion in a finite tube with a simple exponential observation profile. This technique is used to measure the oligomerization of the bacteriophage λ repressor protein at micromolar concentrations. The results agree with previous studies utilizing conventional techniques. Additionally, we demonstrate that the zero-mode waveguides can be used to assay biological activity by measuring changes in diffusion constant as a result of ligand binding. PMID:15613638

Molecular brake pad hypothesis: pulling off the brakes for emotional memory

PubMed Central

Vogel-Ciernia, Annie

2015-01-01

Under basal conditions histone deacetylases (HDACs) and their associated co-repressor complexes serve as molecular ‘brake pads’ to prevent the gene expression required for long-term memory formation. Following a learning event, HDACs and their co-repressor complexes are removed from a subset of specific gene promoters, allowing the histone acetylation and active gene expression required for long-term memory formation. Inhibition of HDACs increases histone acetylation, extends gene expression profiles, and allows for the formation of persistent long-term memories for training events that are otherwise forgotten. We propose that emotionally salient experiences have utilized this system to form strong and persistent memories for behaviorally significant events. Consequently, the presence or absence of HDACs at a selection of specific gene promoters could serve as a critical barrier for permitting the formation of long-term memories. PMID:23096102

DAX1 suppresses FXR transactivity as a novel co-repressor

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

Li, Jin; Lu, Yan; Liu, Ruya

2011-09-09

Highlights: {yields} DAX1 is co-localized with FXR and interacts with FXR. {yields} DAX1 acts as a negative regulator of FXR. {yields} Three LXXLL motifs in the N-terminus of DAX1 were required. {yields} DAX1 suppresses FXR transactivation by competing with co-activators. -- Abstract: Bile acid receptor FXR (farnesoid X receptor) is a key regulator of hepatic bile acid, glucose and lipid homeostasis through regulation of numerous genes involved in the process of bile acid, triglyceride and glucose metabolism. DAX1 (dosage-sensitive sex reversal adrenal hypoplasia congenital critical region on X chromosome, gene 1) is an atypical member of the nuclear receptor familymore » due to lack of classical DNA-binding domains and acts primarily as a co-repressor of many nuclear receptors. Here, we demonstrated that DAX1 is co-localized with FXR in the nucleus and acted as a negative regulator of FXR through a physical interaction with FXR. Our study showed that over-expression of DAX1 down-regulated the expression of FXR target genes, whereas knockdown of DAX1 led to their up-regulation. Furthermore, three LXXLL motifs in the N-terminus of DAX1 were required for the full repression of FXR transactivation. In addition, our study characterized that DAX1 suppresses FXR transactivation via competing with co-activators such as SRC-1 and PGC-1{alpha}. In conclusion, DAX1 acts as a co-repressor to negatively modulate FXR transactivity.« less

Transcriptional repressor foxl1 regulates central nervous system development by suppressing shh expression in zebra fish.

PubMed

Nakada, Chisako; Satoh, Shinya; Tabata, Yoko; Arai, Ken-ichi; Watanabe, Sumiko

2006-10-01

We identified zebra fish forkhead transcription factor l1 (zfoxl1) as a gene strongly expressed in neural tissues such as midbrain, hindbrain, and the otic vesicle at the early embryonic stage. Loss of the function of zfoxl1 effected by morpholino antisense oligonucleotide resulted in defects in midbrain and eye development, and in that of formation of the pectoral fins. Interestingly, ectopic expression of shh in the midbrain and elevated pax2a expression in the optic stalk were observed in foxl1 MO-injected embryos. In contrast, expression of pax6a, which is negatively regulated by shh, was suppressed in the thalamus and pretectum regions, supporting the idea of augmentation of the shh signaling pathway by suppression of foxl1. Expression of zfoxl1-EnR (repressing) rather than zfoxl1-VP16 (activating) resulted in a phenotype similar to that induced by foxl1-mRNA, suggesting that foxl1 may act as a transcriptional repressor of shh in zebra fish embryos. Supporting this notion, foxl1 suppressed isolated 2.7-kb shh promoter activity in PC12 cells, and the minimal region of foxl1 required for its transcriptional repressor activity showed strong homology with the groucho binding motif, which is found in genes encoding various homeodomain proteins. In view of all of our data taken together, we propose zfoxl1 to be a novel regulator of neural development that acts by suppressing shh expression.

Transcriptional Repressor foxl1 Regulates Central Nervous System Development by Suppressing shh Expression in Zebra Fish†

PubMed Central

Nakada, Chisako; Satoh, Shinya; Tabata, Yoko; Arai, Ken-ichi; Watanabe, Sumiko

2006-01-01

We identified zebra fish forkhead transcription factor l1 (zfoxl1) as a gene strongly expressed in neural tissues such as midbrain, hindbrain, and the otic vesicle at the early embryonic stage. Loss of the function of zfoxl1 effected by morpholino antisense oligonucleotide resulted in defects in midbrain and eye development, and in that of formation of the pectoral fins. Interestingly, ectopic expression of shh in the midbrain and elevated pax2a expression in the optic stalk were observed in foxl1 MO-injected embryos. In contrast, expression of pax6a, which is negatively regulated by shh, was suppressed in the thalamus and pretectum regions, supporting the idea of augmentation of the shh signaling pathway by suppression of foxl1. Expression of zfoxl1-EnR (repressing) rather than zfoxl1-VP16 (activating) resulted in a phenotype similar to that induced by foxl1-mRNA, suggesting that foxl1 may act as a transcriptional repressor of shh in zebra fish embryos. Supporting this notion, foxl1 suppressed isolated 2.7-kb shh promoter activity in PC12 cells, and the minimal region of foxl1 required for its transcriptional repressor activity showed strong homology with the groucho binding motif, which is found in genes encoding various homeodomain proteins. In view of all of our data taken together, we propose zfoxl1 to be a novel regulator of neural development that acts by suppressing shh expression. PMID:16980626

Transcriptional repression mediated by the KRAB domain of the human C2H2 zinc finger protein Kox1/ZNF10 does not require histone deacetylation.

PubMed

Lorenz, P; Koczan, D; Thiesen, H J

2001-04-01

The KRAB domain of human Kox1, a member of the KRAB C2H2 zinc finger family, confers strong transcriptional repressor activities even to remote promoter positions. Here, HDAC inhibitors were used to demonstrate that histone deacetylation is not required for mediating transcriptional repression of KRAB zinc finger proteins. Two reporter systems with either stably integrated or transiently transfected templates, both under control of strong viral promoters, were analyzed. Under all circumstances, HDAC inhibition did not alter the repression potential of the KRAB domain. In case of the stably integrated luciferase reporter gene system, neither expression levels of the KRAB fusion protein nor complex formation with its putative co-repressor TIF1beta were significantly changed. Furthermore, the TIF1beta/KRAB complex was devoid of mSin3A and HDAC1. In the transient transfection system, the transcriptional repression induced by TIF1beta and HP1alpha was not diminished by HDAC inhibitors, whereas the repressory activity of TIF1alpha was significantly affected. Thus, KRAB, TIF1beta and HP1alpha are likely to be functionally linked. In conclusion, HDAC activity is not essential for the strong transcriptional repressor activity mediated by the KRAB domain of Kox1 in particular and, presumably, by KRAB domains in general. This feature might be helpful in identifying and characterizing target genes under the control of

The Dual Estrogen Receptor α Inhibitory Effects of the Tissue-Selective Estrogen Complex for Endometrial and Breast Safety

PubMed Central

Han, Sang Jun; Begum, Khurshida; Foulds, Charles E.; Hamilton, Ross A.; Bailey, Suzanna; Malovannaya, Anna; Chan, Doug; Qin, Jun

2016-01-01

The conjugated estrogen/bazedoxifene tissue-selective estrogen complex (TSEC) is designed to minimize the undesirable effects of estrogen in the uterus and breast tissues and to allow the beneficial effects of estrogen in other estrogen-target tissues, such as the bone and brain. However, the molecular mechanism underlying endometrial and breast safety during TSEC use is not fully understood. Estrogen receptor α (ERα)–estrogen response element (ERE)–DNA pull-down assays using HeLa nuclear extracts followed by mass spectrometry–immunoblotting analyses revealed that, upon TSEC treatment, ERα interacted with transcriptional repressors rather than coactivators. Therefore, the TSEC-mediated recruitment of transcriptional repressors suppresses ERα-mediated transcription in the breast and uterus. In addition, TSEC treatment also degraded ERα protein in uterine tissue and breast cancer cells, but not in bone cells. Interestingly, ERα-ERE-DNA pull-down assays also revealed that, upon TSEC treatment, ERα interacted with the F-box protein 45 (FBXO45) E3 ubiquitin ligase. The loss-of- and gain-of-FBXO45 function analyses indicated that FBXO45 is involved in TSEC-mediated degradation of the ERα protein in endometrial and breast cells. In preclinical studies, these synergistic effects of TSEC on ERα inhibition also suppressed the estrogen-dependent progression of endometriosis. Therefore, the endometrial and breast safety effects of TSEC are associated with synergy between the selective recruitment of transcriptional repressors to ERα and FBXO45-mediated degradation of the ERα protein. PMID:26487511

Evidence for a non-canonical role of HDAC5 in regulation of the cardiac Ncx1 and Bnp genes.

PubMed

Harris, Lillianne G; Wang, Sabina H; Mani, Santhosh K; Kasiganesan, Harinath; Chou, C James; Menick, Donald R

2016-05-05

Class IIa histone deacetylases (HDACs) are very important for tissue specific gene regulation in development and pathology. Because class IIa HDAC catalytic activity is low, their exact molecular roles have not been fully elucidated. Studies have suggested that class IIa HDACs may serve as a scaffold to recruit the catalytically active class I HDAC complexes to their substrate. Here we directly address whether the class IIa HDAC, HDAC5 may function as a scaffold to recruit co-repressor complexes to promoters. We examined two well-characterized cardiac promoters, the sodium calcium exchanger (Ncx1) and the brain natriuretic peptide (Bnp) whose hypertrophic upregulation is mediated by both class I and IIa HDACs. Selective inhibition of class IIa HDACs did not prevent adrenergic stimulated Ncx1 upregulation, however HDAC5 knockout prevented pressure overload induced Ncx1 upregulation. Using the HDAC5((-/-)) mouse we show that HDAC5 is required for the interaction of the HDAC1/2/Sin3a co-repressor complexes with the Nkx2.5 and YY1 transcription factors and critical for recruitment of the HDAC1/Sin3a co-repressor complex to either the Ncx1 or Bnp promoter. Our novel findings support a non-canonical role of class IIa HDACs in the scaffolding of transcriptional regulatory complexes, which may be relevant for therapeutic intervention for pathologies. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Evolution of Metal(Loid) Binding Sites in Transcriptional Regulators

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

Ordonez, E.; Thiyagarajan, S.; Cook, J.D.

2009-05-22

Expression of the genes for resistance to heavy metals and metalloids is transcriptionally regulated by the toxic ions themselves. Members of the ArsR/SmtB family of small metalloregulatory proteins respond to transition metals, heavy metals, and metalloids, including As(III), Sb(III), Cd(II), Pb(II), Zn(II), Co(II), and Ni(II). These homodimeric repressors bind to DNA in the absence of inducing metal(loid) ion and dissociate from the DNA when inducer is bound. The regulatory sites are often three- or four-coordinate metal binding sites composed of cysteine thiolates. Surprisingly, in two different As(III)-responsive regulators, the metalloid binding sites were in different locations in the repressor, andmore » the Cd(II) binding sites were in two different locations in two Cd(II)-responsive regulators. We hypothesize that ArsR/SmtB repressors have a common backbone structure, that of a winged helix DNA-binding protein, but have considerable plasticity in the location of inducer binding sites. Here we show that an As(III)-responsive member of the family, CgArsR1 from Corynebacterium glutamicum, binds As(III) to a cysteine triad composed of Cys{sup 15}, Cys{sup 16}, and Cys{sup 55}. This binding site is clearly unrelated to the binding sites of other characterized ArsR/SmtB family members. This is consistent with our hypothesis that metal(loid) binding sites in DNA binding proteins evolve convergently in response to persistent environmental pressures.« less

Safety mechanism assisted by the repressor of tetracycline (SMART) vaccinia virus vectors for vaccines and therapeutics.

PubMed

Grigg, Patricia; Titong, Allison; Jones, Leslie A; Yilma, Tilahun D; Verardi, Paulo H

2013-09-17

Replication-competent viruses, such as Vaccinia virus (VACV), are powerful tools for the development of oncolytic viral therapies and elicit superior immune responses when used as vaccine and immunotherapeutic vectors. However, severe complications from uncontrolled viral replication can occur, particularly in immunocompromised individuals or in those with other predisposing conditions. VACVs constitutively expressing interferon-γ (IFN-γ) replicate in cell culture indistinguishably from control viruses; however, they replicate in vivo to low or undetectable levels, and are rapidly cleared even in immunodeficient animals. In an effort to develop safe and highly effective replication-competent VACV vectors, we established a system to inducibly express IFN-γ. Our SMART (safety mechanism assisted by the repressor of tetracycline) vectors are designed to express the tetracycline repressor under a constitutive VACV promoter and IFN-γ under engineered tetracycline-inducible promoters. Immunodeficient SCID mice inoculated with VACVs not expressing IFN-γ demonstrated severe weight loss, whereas those given VACVs expressing IFN-γ under constitutive VACV promoters showed no signs of infection. Most importantly, mice inoculated with a VACV expressing the IFN-γ gene under an inducible promoter remained healthy in the presence of doxycycline, but exhibited severe weight loss in the absence of doxycycline. In this study, we developed a safety mechanism for VACV based on the conditional expression of IFN-γ under a tightly controlled tetracycline-inducible VACV promoter for use in vaccines and oncolytic cancer therapies.

CCN5, a Novel Transcriptional Repressor of the Transforming Growth Factor β Signaling Pathway ▿

PubMed Central

Sabbah, Michèle; Prunier, Céline; Ferrand, Nathalie; Megalophonos, Virginie; Lambein, Kathleen; De Wever, Olivier; Nazaret, Nicolas; Lachuer, Joël; Dumont, Sylvie; Redeuilh, Gérard

2011-01-01

CCN5 is a member of the CCN (connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed) family and was identified as an estrogen-inducible gene in estrogen receptor-positive cell lines. However, the role of CCN5 in breast carcinogenesis remains unclear. We report here that the CCN5 protein is localized mostly in the cytoplasm and in part in the nucleus of human tumor breast tissue. Using a heterologous transcription assay, we demonstrate that CCN5 can act as a transcriptional repressor presumably through association with histone deacetylase 1 (HDAC1). Microarray gene expression analysis showed that CCN5 represses expression of genes associated with epithelial-mesenchymal transition (EMT) as well as expression of key components of the transforming growth factor β (TGF-β) signaling pathway, prominent among them TGF-βRII receptor. We show that CCN5 is recruited to the TGF-βRII promoter, thereby providing a mechanism by which CCN5 restricts transcription of the TGF-βRII gene. Consistent with this finding, CCN5, we found, functions to suppress TGF-β-induced transcriptional responses and invasion that is concomitant with EMT. Thus, our data uncovered CCN5 as a novel transcriptional repressor that plays an important role in regulating tumor progression functioning, at least in part, by inhibiting the expression of genes involved in the TGF-β signaling cascade that is known to promote EMT. PMID:21262769

Structural dynamics of the lac repressor-DNA complex revealed by a multiscale simulation.

PubMed

Villa, Elizabeth; Balaeff, Alexander; Schulten, Klaus

2005-05-10

A multiscale simulation of a complex between the lac repressor protein (LacI) and a 107-bp-long DNA segment is reported. The complex between the repressor and two operator DNA segments is described by all-atom molecular dynamics; the size of the simulated system comprises either 226,000 or 314,000 atoms. The DNA loop connecting the operators is modeled as a continuous elastic ribbon, described mathematically by the nonlinear Kirchhoff differential equations with boundary conditions obtained from the coordinates of the terminal base pairs of each operator. The forces stemming from the looped DNA are included in the molecular dynamics simulations; the loop structure and the forces are continuously recomputed because the protein motions during the simulations shift the operators and the presumed termini of the loop. The simulations reveal the structural dynamics of the LacI-DNA complex in unprecedented detail. The multiple domains of LacI exhibit remarkable structural stability during the simulation, moving much like rigid bodies. LacI is shown to absorb the strain from the looped DNA mainly through its mobile DNA-binding head groups. Even with large fluctuating forces applied, the head groups tilt strongly and keep their grip on the operator DNA, while the remainder of the protein retains its V-shaped structure. A simulated opening of the cleft of LacI by 500-pN forces revealed the interactions responsible for locking LacI in the V-conformation.

Identification of a Signal-Responsive Nuclear Export Sequence in Class II Histone Deacetylases

PubMed Central

McKinsey, Timothy A.; Zhang, Chun Li; Olson, Eric N.

2001-01-01

Activation of muscle-specific genes by the MEF2 transcription factor is inhibited by class II histone deacetylases (HDACs) 4 and 5, which contain carboxy-terminal deacetylase domains and amino-terminal extensions required for association with MEF2. The inhibitory action of HDACs is overcome by myogenic signals which disrupt MEF2-HDAC interactions and stimulate nuclear export of these transcriptional repressors. Nucleocytoplasmic trafficking of HDAC5 is mediated by binding of the chaperone protein 14-3-3 to two phosphoserine residues (Ser-259 and Ser-498) in its amino-terminal extension. Here we show that HDAC4 and -5 each contain a signal-responsive nuclear export sequence (NES) at their extreme carboxy termini. The NES is conserved in another class II HDAC, HDAC7, but is absent in class I HDACs and the HDAC-related corepressor, MEF2-interacting transcription repressor. Our results suggest that this conserved NES is inactive in unphosphorylated HDAC5, which is localized to the nucleus, and that calcium-calmodulin-dependent protein kinase (CaMK)-dependent binding of 14-3-3 to phosphoserines 259 and 498 activates the NES, with consequent export of the transcriptional repressor to the cytoplasm. A single amino acid substitution in this NES is sufficient to retain HDAC5 in the nucleus in the face of CaMK signaling. These findings provide molecular insight into the mechanism by which extracellular cues alter chromatin structure to promote muscle differentiation and other MEF2-regulated processes. PMID:11509672

Observation of Complete Pressure-Jump Protein Refolding in Molecular Dynamics Simulation and Experiment

PubMed Central

2015-01-01

Density is an easily adjusted variable in molecular dynamics (MD) simulations. Thus, pressure-jump (P-jump)-induced protein refolding, if it could be made fast enough, would be ideally suited for comparison with MD. Although pressure denaturation perturbs secondary structure less than temperature denaturation, protein refolding after a fast P-jump is not necessarily faster than that after a temperature jump. Recent P-jump refolding experiments on the helix bundle λ-repressor have shown evidence of a <3 μs burst phase, but also of a ∼1.5 ms “slow” phase of refolding, attributed to non-native helical structure frustrating microsecond refolding. Here we show that a λ-repressor mutant is nonetheless capable of refolding in a single explicit solvent MD trajectory in about 19 μs, indicating that the burst phase observed in experiments on the same mutant could produce native protein. The simulation reveals that after about 18.5 μs of conformational sampling, the productive structural rearrangement to the native state does not occur in a single swift step but is spread out over a brief series of helix and loop rearrangements that take about 0.9 μs. Our results support the molecular time scale inferred for λ-repressor from near-downhill folding experiments, where transition-state population can be seen experimentally, and also agrees with the transition-state transit time observed in slower folding proteins by single-molecule spectroscopy. PMID:24437525

Viral Ubiquitin Ligase Stimulates Selective Host MicroRNA Expression by Targeting ZEB Transcriptional Repressors

PubMed Central

Kim, Ju Youn; Leader, Andrew; Stoller, Michelle L.; Coen, Donald M.; Wilson, Angus C.

2017-01-01

Infection with herpes simplex virus-1 (HSV-1) brings numerous changes in cellular gene expression. Levels of most host mRNAs are reduced, limiting synthesis of host proteins, especially those involved in antiviral defenses. The impact of HSV-1 on host microRNAs (miRNAs), an extensive network of short non-coding RNAs that regulate mRNA stability/translation, remains largely unexplored. Here we show that transcription of the miR-183 cluster (miR-183, miR-96, and miR-182) is selectively induced by HSV-1 during productive infection of primary fibroblasts and neurons. ICP0, a viral E3 ubiquitin ligase expressed as an immediate-early protein, is both necessary and sufficient for this induction. Nuclear exclusion of ICP0 or removal of the RING (really interesting new gene) finger domain that is required for E3 ligase activity prevents induction. ICP0 promotes the degradation of numerous host proteins and for the most part, the downstream consequences are unknown. Induction of the miR-183 cluster can be mimicked by depletion of host transcriptional repressors zinc finger E-box binding homeobox 1 (ZEB1)/δ-crystallin enhancer binding factor 1 (δEF1) and zinc finger E-box binding homeobox 2 (ZEB2)/Smad-interacting protein 1 (SIP1), which we establish as new substrates for ICP0-mediated degradation. Thus, HSV-1 selectively stimulates expression of the miR-183 cluster by ICP0-mediated degradation of ZEB transcriptional repressors. PMID:28783105

Therapeutic fetal-globin inducers reduce transcriptional repression in hemoglobinopathy erythroid progenitors through distinct mechanisms.

PubMed

Dai, Yan; Sangerman, Jose; Luo, Hong Yuan; Fucharoen, Suthat; Chui, David H K; Faller, Douglas V; Perrine, Susan P

2016-01-01

Pharmacologic augmentation of γ-globin expression sufficient to reduce anemia and clinical severity in patients with diverse hemoglobinopathies has been challenging. In studies here, representative molecules from four chemical classes, representing several distinct primary mechanisms of action, were investigated for effects on γ-globin transcriptional repressors, including components of the NuRD complex (LSD1 and HDACs 2-3), and the downstream repressor BCL11A, in erythroid progenitors from hemoglobinopathy patients. Two HDAC inhibitors (MS-275 and SB939), a short-chain fatty acid derivative (sodium dimethylbutyrate [SDMB]), and an agent identified in high-throughput screening, Benserazide, were studied. These therapeutics induced γ-globin mRNA in progenitors above same subject controls up to 20-fold, and increased F-reticulocytes up to 20%. Cellular protein levels of BCL11A, LSD-1, and KLF1 were suppressed by the compounds. Chromatin immunoprecipitation assays demonstrated a 3.6-fold reduction in LSD1 and HDAC3 occupancy in the γ-globin gene promoter with Benserazide exposure, 3-fold reduction in LSD-1 and HDAC2 occupancy in the γ-globin gene promoter with SDMB exposure, while markers of gene activation (histone H3K9 acetylation and H3K4 demethylation), were enriched 5.7-fold. These findings identify clinical-stage oral therapeutics which inhibit or displace major co-repressors of γ-globin gene transcription and may suggest a rationale for combination therapy to produce enhanced efficacy. Copyright © 2015 Elsevier Inc. All rights reserved.

Therapeutic γ-globin inducers reduce transcriptional repression in hemoglobinopathy erythroid progenitors through distinct mechanisms

PubMed Central

Dai, Yan; Sangerman, Jose; Hong, Yuan Luo; Fuchareon, Suthat; Chui, David H.K.; Faller, Douglas V.; Perrine, Susan P.

2015-01-01

Pharmacologic augmentation of γ-globin expression sufficient to reduce anemia and clinical severity in patients with diverse hemoglobinopathies has been challenging. In studies here, representative molecules from four chemical classes, representing several distinct primary mechanisms of action, were investigated for effects on γ-globin transcriptional repressors, including components of the NuRD complex (LSD1 and HDACs 2-3), and the downstream repressor BCL11A, in erythroid progenitors from hemoglobinopathy patients. Two HDAC inhibitors (MS-275 and SB939), a short-chain fatty acid derivative (sodium dimethylbutyrate [SDMB]), and an agent identified in high-throughput screening, Benserazide, were studied. These therapeutics induced γ globin mRNA in progenitors above same subject controls up to 20-fold, and increased F-reticulocytes up to 20%. Cellular protein levels of BCL11A, LSD-1, and KLF1 were suppressed by the compounds. Chromatin immunoprecipitation assays demonstrated a 3.6-fold reduction in LSD1 and HDAC3 occupancy in the γ-globin gene promoter with Benserazide exposure, 3-fold reduction in LSD-1 and HDAC2 occupancy in the γ-globin gene promoter with SDMB exposure, while markers of gene activation (histone H3K9 acetylation and H3K4 demethylation), were enriched 5.7-fold. These findings identify clinical-stage oral therapeutics which inhibit or displace major co-repressors of γ-globin gene transcription and may suggest a rationale for combination therapy to produce enhanced efficacy. PMID:26603726

Regulatory T cells facilitate the nuclear accumulation of inducible cAMP early repressor (ICER) and suppress nuclear factor of activated T cell c1 (NFATc1)

PubMed Central

Vaeth, Martin; Gogishvili, Tea; Bopp, Tobias; Klein, Matthias; Berberich-Siebelt, Friederike; Gattenloehner, Stefan; Avots, Andris; Sparwasser, Tim; Grebe, Nadine; Schmitt, Edgar; Hünig, Thomas; Serfling, Edgar; Bodor, Josef

2011-01-01

Inducible cAMP early repressor (ICER) is a transcriptional repressor, which, because of alternate promoter use, is generated from the 3′ region of the cAMP response modulator (Crem) gene. Its expression and nuclear occurrence are elevated by high cAMP levels in naturally occurring regulatory T cells (nTregs). Using two mouse models, we demonstrate that nTregs control the cellular localization of ICER/CREM, and thereby inhibit IL-2 synthesis in conventional CD4+ T cells. Ablation of nTregs in depletion of regulatory T-cell (DEREG) mice resulted in cytosolic localization of ICER/CREM and increased IL-2 synthesis upon stimulation. Direct contacts between nTregs and conventional CD4+ T cells led to nuclear accumulation of ICER/CREM and suppression of IL-2 synthesis on administration of CD28 superagonistic (CD28SA) Ab. In a similar way, nTregs communicated with B cells and induced the cAMP-driven nuclear localization of ICER/CREM. High levels of ICER suppressed the induction of nuclear factor of activated T cell c1 (Nfatc1) gene in T cells whose inducible Nfatc1 P1 promoter bears two highly conserved cAMP-responsive elements to which ICER/CREM can bind. These findings suggest that nTregs suppress T-cell responses by the cAMP-dependent nuclear accumulation of ICER/CREM and inhibition of NFATc1 and IL-2 induction. PMID:21262800

Evidence for exploitative competition: Comparative foraging behavior and roosting ecology of short-tailed fruit bats (Phyllostomidae)

USGS Publications Warehouse

Bonaccorso, F.J.; Winkelmann, J.R.; Shin, D.; Agrawal, C.I.; Aslami, N.; Bonney, C.; Hsu, A.; Jekielek, P.E.; Knox, A.K.; Kopach, S.J.; Jennings, T.D.; Lasky, J.R.; Menesale, S.A.; Richards, J.H.; Rutland, J.A.; Sessa, A.K.; Zhaurova, L.; Kunz, T.H.

2007-01-01

Chestnut short-tailed bats, Carollia castanea, and Seba's short-tailed bats, C. perspicillata (Phyllostomidae), were radio-tracked (N = 1593 positions) in lowland rain forest at Tiputini Biodiversity Station, Orellana Province, Ecuador. For 11 C. castanea, mean home range was 6.8 ?? 2.2 ha, mean core-use area was 1.7 ?? 0.8 ha, and mean long axis across home range was 438 ?? 106 m. For three C. perspicillata, mean home range was 5.5 ?? 1.7 ha, mean core-use area was 1.3 ?? 0.6 ha, and mean long axis was 493 ?? 172 m. Groups of less than five C. castanea occupied day-roosts in earthen cavities that undercut banks the Tiputini River. Carollia perspicillata used tree hollows and buildings as day-roosts. Interspecific and intraspecific overlap among short-tailed bats occurred in core-use areas associated with clumps of fruiting Piper hispidum (peppers) and Cecropia sciadophylla. Piper hispidum seeds were present in 80 percent of the fecal samples from C. castanea and 56 percent of samples from C. perspicillata. Carollia perspicillata handled pepper fruits significantly faster than C. castanea; however, C. castanea commenced foraging before C. perspicillata emerged from day-roosts. Evidence for exploitative competition between C. castanea and C. perspicillata is suggested by our observations that 95 percent of ripe P. hispidum fruits available at sunset disappear before sunrise (N = 74 marked fruits). Piper hispidum plants produced zero to 12 ripe infructescences per plant each night during peak production. Few ripe infructescences of P. hispidum were available during the dry season; however, ripe infructescences of C. sciadophylla, remained abundant. ?? 2007 The Author(s) Journal compilation ?? 2007 by The Association for Tropical Biology and Conservation.

The expression of virulence during double infections by different parasites with conflicting host exploitation and transmission strategies.

PubMed

Ben-Ami, F; Rigaud, T; Ebert, D

2011-06-01

In many natural populations, hosts are found to be infected by more than one parasite species. When these parasites have different host exploitation strategies and transmission modes, a conflict among them may arise. Such a conflict may reduce the success of both parasites, but could work to the benefit of the host. For example, the less-virulent parasite may protect the host against the more-virulent competitor. We examine this conflict using the waterflea Daphnia magna and two of its sympatric parasites: the blood-infecting bacterium Pasteuria ramosa that transmits horizontally and the intracellular microsporidium Octosporea bayeri that can concurrently transmit horizontally and vertically after infecting ovaries and fat tissues of the host. We quantified host and parasite fitness after exposing Daphnia to one or both parasites, both simultaneously and sequentially. Under conditions of strict horizontal transmission, Pasteuria competitively excluded Octosporea in both simultaneous and sequential double infections, regardless of the order of exposure. Host lifespan, host reproduction and parasite spore production in double infections resembled those of single infection by Pasteuria. When hosts became first vertically (transovarilly) infected with O. bayeri, Octosporea was able to withstand competition with P. ramosa to some degree, but both parasites produced less transmission stages than they did in single infections. At the same time, the host suffered from reduced fecundity and longevity. Our study demonstrates that even when competing parasite species utilize different host tissues to proliferate, double infections lead to the expression of higher virulence and ultimately may select for higher virulence. Furthermore, we found no evidence that the less-virulent and vertically transmitting O. bayeri protects its host against the highly virulent P. ramosa. © 2011 The Authors. Journal of Evolutionary Biology © 2011 European Society For Evolutionary Biology.

Competition in size-structured populations: mechanisms inducing cohort formation and population cycles.

PubMed

de Roos, André M; Persson, Lennart

2003-02-01

In this paper we investigate the consequences of size-dependent competition among the individuals of a consumer population by analyzing the dynamic properties of a physiologically structured population model. Only 2 size-classes of individuals are distinguished: juveniles and adults. Juveniles and adults both feed on one and the same resource and hence interact by means of exploitative competition. Juvenile individuals allocate all assimilated energy into development and mature on reaching a fixed developmental threshold. The combination of this fixed threshold and the resource-dependent developmental rate, implies that the juvenile delay between birth and the onset of reproduction may vary in time. Adult individuals allocate all assimilated energy to reproduction. Mortality of both juveniles and adults is assumed to be inversely proportional to the amount of energy assimilated. In this setting we study how the dynamics of the population are influenced by the relative foraging capabilities of juveniles and adults. In line with results that we previously obtained in size-structured consumer-resource models with pulsed reproduction, population cycles primarily occur when either juveniles or adults have a distinct competitive advantage. When adults have a larger per capita feeding rate and are hence competitively superior to juveniles, population oscillations occur that are primarily induced by the fact that the duration of the juvenile period changes with changing food conditions. These cycles do not occur when the juvenile delay is a fixed parameter. When juveniles are competitively superior, two different types of population fluctuations can occur: (1) rapid, low-amplitude fluctuations having a period of half the juvenile delay and (2) slow, large-amplitude fluctuations characterized by a period, which is roughly equal to the juvenile delay. The analysis of simplified versions of the structured model indicates that these two types of oscillations also occur if mortality and/or development is independent of food density, i.e. in a situation with a constant juvenile developmental delay and a constant, food-independent background mortality. Thus, the oscillations that occur when juveniles are more competitive are induced by the juvenile delay per se. When juveniles exert a larger foraging pressure on the shared resource, maturation implies an increase not only in adult density, but also in food density and consequently fecundity. Our analysis suggests that this correlation in time between adult density and fecundity is crucial for the occurrence of population cycles when juveniles are competitively superior.

An effective PSO-based memetic algorithm for flow shop scheduling.

PubMed

Liu, Bo; Wang, Ling; Jin, Yi-Hui

2007-02-01

This paper proposes an effective particle swarm optimization (PSO)-based memetic algorithm (MA) for the permutation flow shop scheduling problem (PFSSP) with the objective to minimize the maximum completion time, which is a typical non-deterministic polynomial-time (NP) hard combinatorial optimization problem. In the proposed PSO-based MA (PSOMA), both PSO-based searching operators and some special local searching operators are designed to balance the exploration and exploitation abilities. In particular, the PSOMA applies the evolutionary searching mechanism of PSO, which is characterized by individual improvement, population cooperation, and competition to effectively perform exploration. On the other hand, the PSOMA utilizes several adaptive local searches to perform exploitation. First, to make PSO suitable for solving PFSSP, a ranked-order value rule based on random key representation is presented to convert the continuous position values of particles to job permutations. Second, to generate an initial swarm with certain quality and diversity, the famous Nawaz-Enscore-Ham (NEH) heuristic is incorporated into the initialization of population. Third, to balance the exploration and exploitation abilities, after the standard PSO-based searching operation, a new local search technique named NEH_1 insertion is probabilistically applied to some good particles selected by using a roulette wheel mechanism with a specified probability. Fourth, to enrich the searching behaviors and to avoid premature convergence, a simulated annealing (SA)-based local search with multiple different neighborhoods is designed and incorporated into the PSOMA. Meanwhile, an effective adaptive meta-Lamarckian learning strategy is employed to decide which neighborhood to be used in SA-based local search. Finally, to further enhance the exploitation ability, a pairwise-based local search is applied after the SA-based search. Simulation results based on benchmarks demonstrate the effectiveness of the PSOMA. Additionally, the effects of some parameters on optimization performances are also discussed.

Examining spatial patterns of selection and use for an altered predator guild

USGS Publications Warehouse

Organ, John F.; Mumma, Matthew; Holbrook, Joseph D.; Rayl, Nathaniel D.; Zieminski, Christopher J.; Fuller, Todd K.; Mahoney, Shane P.; Waits, Lisette P.

2017-01-01

Anthropogenic disturbances have altered species’ distributions potentially impacting interspecific interactions. Interference competition is when one species denies a competing species access to a resource. One mechanism of interference competition is aggression, which can result in altered space-use of a subordinate species due to the threat of harm, otherwise known as a ‘landscape of fear’. Alternatively, subordinates might outcompete dominant species in resource-poor environments via a superior ability to extract resources. Our goal was to evaluate spatial predictions of the ‘landscape of fear’ hypothesis for a carnivore guild in Newfoundland, Canada, where coyotes recently immigrated. Native Newfoundland carnivores include red foxes, Canada lynx, and black bears. We predicted foxes and lynx would avoid coyotes because of their larger size and similar dietary niches. We used scat-detecting dogs and genetic techniques to locate and identify predator scats. We then built resource selection functions and tested for avoidance by incorporating predicted values of selection for the alternative species into the best supported models of each species. We found multiple negative relationships, but notably did not find avoidance by foxes of areas selected by coyotes. While we did find that lynx avoided coyotes, we also found a reciprocal relationship. The observed patterns suggest spatial partitioning and not coyote avoidance, although avoidance could still be occurring at different spatial or temporal scales. Furthermore, Newfoundland’s harsh climate and poor soils may swing the pendulum of interspecific interactions from interference competition to exploitative competition, where subordinates outcompete dominant competitors through a superior ability to extract resources.

Examining spatial patterns of selection and use for an altered predator guild.

PubMed

Mumma, Matthew A; Holbrook, Joseph D; Rayl, Nathaniel D; Zieminski, Christopher J; Fuller, Todd K; Organ, John F; Mahoney, Shane P; Waits, Lisette P

2017-12-01

Anthropogenic disturbances have altered species' distributions potentially impacting interspecific interactions. Interference competition is when one species denies a competing species access to a resource. One mechanism of interference competition is aggression, which can result in altered space-use of a subordinate species due to the threat of harm, otherwise known as a 'landscape of fear'. Alternatively, subordinates might outcompete dominant species in resource-poor environments via a superior ability to extract resources. Our goal was to evaluate spatial predictions of the 'landscape of fear' hypothesis for a carnivore guild in Newfoundland, Canada, where coyotes recently immigrated. Native Newfoundland carnivores include red foxes, Canada lynx, and black bears. We predicted foxes and lynx would avoid coyotes because of their larger size and similar dietary niches. We used scat-detecting dogs and genetic techniques to locate and identify predator scats. We then built resource selection functions and tested for avoidance by incorporating predicted values of selection for the alternative species into the best supported models of each species. We found multiple negative relationships, but notably did not find avoidance by foxes of areas selected by coyotes. While we did find that lynx avoided coyotes, we also found a reciprocal relationship. The observed patterns suggest spatial partitioning and not coyote avoidance, although avoidance could still be occurring at different spatial or temporal scales. Furthermore, Newfoundland's harsh climate and poor soils may swing the pendulum of interspecific interactions from interference competition to exploitative competition, where subordinates outcompete dominant competitors through a superior ability to extract resources.

dynGENIE3: dynamical GENIE3 for the inference of gene networks from time series expression data.

PubMed

Huynh-Thu, Vân Anh; Geurts, Pierre

2018-02-21

The elucidation of gene regulatory networks is one of the major challenges of systems biology. Measurements about genes that are exploited by network inference methods are typically available either in the form of steady-state expression vectors or time series expression data. In our previous work, we proposed the GENIE3 method that exploits variable importance scores derived from Random forests to identify the regulators of each target gene. This method provided state-of-the-art performance on several benchmark datasets, but it could however not specifically be applied to time series expression data. We propose here an adaptation of the GENIE3 method, called dynamical GENIE3 (dynGENIE3), for handling both time series and steady-state expression data. The proposed method is evaluated extensively on the artificial DREAM4 benchmarks and on three real time series expression datasets. Although dynGENIE3 does not systematically yield the best performance on each and every network, it is competitive with diverse methods from the literature, while preserving the main advantages of GENIE3 in terms of scalability.

CubiCal - Fast radio interferometric calibration suite exploiting complex optimisation

NASA Astrophysics Data System (ADS)

Kenyon, J. S.; Smirnov, O. M.; Grobler, T. L.; Perkins, S. J.

2018-05-01

It has recently been shown that radio interferometric gain calibration can be expressed succinctly in the language of complex optimisation. In addition to providing an elegant framework for further development, it exposes properties of the calibration problem which can be exploited to accelerate traditional non-linear least squares solvers such as Gauss-Newton and Levenberg-Marquardt. We extend existing derivations to chains of Jones terms: products of several gains which model different aberrant effects. In doing so, we find that the useful properties found in the single term case still hold. We also develop several specialised solvers which deal with complex gains parameterised by real values. The newly developed solvers have been implemented in a Python package called CubiCal, which uses a combination of Cython, multiprocessing and shared memory to leverage the power of modern hardware. We apply CubiCal to both simulated and real data, and perform both direction-independent and direction-dependent self-calibration. Finally, we present the results of some rudimentary profiling to show that CubiCal is competitive with respect to existing calibration tools such as MeqTrees.

Three-Dimensional, Live-Cell Imaging of Chromatin Dynamics in Plant Nuclei Using Chromatin Tagging Systems.

PubMed

Hirakawa, Takeshi; Matsunaga, Sachihiro

2016-01-01

In plants, chromatin dynamics spatiotemporally change in response to various environmental stimuli. However, little is known about chromatin dynamics in the nuclei of plants. Here, we introduce a three-dimensional, live-cell imaging method that can monitor chromatin dynamics in nuclei via a chromatin tagging system that can visualize specific genomic loci in living plant cells. The chromatin tagging system is based on a bacterial operator/repressor system in which the repressor is fused to fluorescent proteins. A recent refinement of promoters for the system solved the problem of gene silencing and abnormal pairing frequencies between operators. Using this system, we can detect the spatiotemporal dynamics of two homologous loci as two fluorescent signals within a nucleus and monitor the distance between homologous loci. These live-cell imaging methods will provide new insights into genome organization, development processes, and subnuclear responses to environmental stimuli in plants.

Repressive coping among British college women: A potential protective factor against body image concerns, drive for thinness, and bulimia symptoms.

PubMed

Mohiyeddini, Changiz

2017-09-01

Repressive coping, as a means of preserving a positive self-image, has been widely explored in the context of dealing with self-evaluative cues. The current study extends this research by exploring whether repressive coping is associated with lower levels of body image concerns, drive for thinness, bulimic symptoms, and higher positive rational acceptance. A sample of 229 female college students was recruited in South London. Repressive coping was measured via the interaction between trait anxiety and defensiveness. The results of moderated regression analysis with simple slope analysis show that compared to non-repressors, repressors reported lower levels of body image concerns, drive for thinness, and bulimic symptoms while exhibiting a higher use of positive rational acceptance. These findings, in line with previous evidence, suggest that repressive coping may be adaptive particularly in the context of body image. Copyright © 2017 Elsevier Ltd. All rights reserved.

Expression of a repressor form of the Arabidopsis thaliana transcription factor TCP16 induces the formation of ectopic meristems.

PubMed

Uberti-Manassero, Nora G; Coscueta, Ezequiel R; Gonzalez, Daniel H

2016-11-01

Plants that express a fusion of the Arabidopsis thaliana class I TCP transcription factor TCP16 to the EAR repressor domain develop several phenotypic alterations, including rounder leaves, short petioles and pedicels, and delayed elongation of sepals, petals and anthers. In addition, these plants develop lobed cotyledons and ectopic meristems. Ectopic meristems are formed on the adaxial side of cotyledon petioles and arise from a cleft that is formed at this site. Analysis of the expression of reporter genes indicated that meristem genes are reactivated at the site of emergence of ectopic meristems, located near the bifurcation of cotyledon veins. The plants also show increased transcript levels of the boundary-specific CUP-SHAPED COTYLEDON (CUC) genes. The results suggest that TCP16 is able to modulate the induction of meristematic programs and the differentiation state of plant cells. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Parallel states of pathological Wnt signaling in neonatal brain injury and colon cancer

PubMed Central

Fancy, Stephen P.J.; Harrington, Emily P.; Baranzini, Sergio E.; Silbereis, John C.; Shiow, Lawrence R.; Yuen, Tracy J.; Huang, Eric J.; Lomvardas, Stavros; Rowitch, David H.

2014-01-01

In colon cancer, mutation of the Wnt repressor Adenomatous polyposis coli (APC) leads to a state of aberrant and unrestricted “high-activity” signaling. However, relevance of high Wnt tone in non-genetic human disease is unknown. Here we demonstrate that distinct Wnt activity functional states determine oligodendrocyte precursor (OPC) differentiation and myelination. Murine OPCs with genetic Wnt dysregulation (high tone) express multiple genes in common with colon cancer including Lef1, SP5, Ets2, Rnf43 and Dusp4. Surprisingly, we find that OPCs in lesions of hypoxic human neonatal white matter injury upregulate markers of high Wnt activity and lack expression of APC. Finally, we show lack of Wnt repressor tone promotes permanent white matter injury after mild hypoxic insult. These findings suggest a state of pathological high-activity Wnt signaling in human disease tissues that lack pre-disposing genetic mutation. PMID:24609463

A regulatory network to segregate the identity of neuronal subtypes.

PubMed

Lee, Seunghee; Lee, Bora; Joshi, Kaumudi; Pfaff, Samuel L; Lee, Jae W; Lee, Soo-Kyung

2008-06-01

Spinal motor neurons (MNs) and V2 interneurons (V2-INs) are specified by two related LIM-complexes, MN-hexamer and V2-tetramer, respectively. Here we show how multiple parallel and complementary feedback loops are integrated to assign these two cell fates accurately. While MN-hexamer response elements (REs) are specific to MN-hexamer, V2-tetramer-REs can bind both LIM-complexes. In embryonic MNs, however, two factors cooperatively suppress the aberrant activation of V2-tetramer-REs. First, LMO4 blocks V2-tetramer assembly. Second, MN-hexamer induces a repressor, Hb9, which binds V2-tetramer-REs and suppresses their activation. V2-INs use a similar approach; V2-tetramer induces a repressor, Chx10, which binds MN-hexamer-REs and blocks their activation. Thus, our study uncovers a regulatory network to segregate related cell fates, which involves reciprocal feedforward gene regulatory loops.

A mutation-led search for novel functional domains in MeCP2.

PubMed

Guy, Jacky; Alexander-Howden, Beatrice; FitzPatrick, Laura; DeSousa, Dina; Koerner, Martha V; Selfridge, Jim; Bird, Adrian

2018-04-27

Most missense mutations causing Rett syndrome affect domains of MeCP2 that have been shown to either bind methylated DNA or interact with a transcriptional co-repressor complex. Several mutations, however, including the C-terminal truncations that account for ∼10% of cases, fall outside these characterised domains. We studied the molecular consequences of four of these "non-canonical" mutations in cultured neurons and mice to see if they reveal additional essential domains without affecting known properties of MeCP2. The results show that the mutations partially or strongly deplete the protein and also in some cases interfere with co-repressor recruitment. These mutations therefore impact the activity of known functional domains and do not invoke new molecular causes of Rett syndrome. The finding that a stable C-terminal truncation does not compromise MeCP2 function raises the possibility that small molecules which stabilise these mutant proteins may be of therapeutic value.

Drosophila arginine methyltransferase 1 (DART1) is an ecdysone receptor co-repressor

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

Kimura, Shuhei; Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574; Sawatsubashi, Shun

2008-07-11

Histone arginine methylation is an epigenetic marker that regulates gene expression by defining the chromatin state. Arginine methyltransferases, therefore, serve as transcriptional co-regulators. However, unlike other transcriptional co-regulators, the physiological roles of arginine methyltransferases are poorly understood. Drosophila arginine methyltransferase 1 (DART1), the mammalian PRMT1 homologue, methylates the arginine residue of histone H4 (H4R3me2). Disruption of DART1 in Drosophila by imprecise P-element excision resulted in low viability during metamorphosis in the pupal stages. In the pupal stage, an ecdysone hormone signal is critical for developmental progression. DART1 interacted with the nuclear ecdysone receptor (EcR) in a ligand-dependent manner, and co-repressedmore » EcR in intact flies. These findings suggest that DART1, a histone arginine methyltransferase, is a co-repressor of EcR that is indispensable for normal pupal development in the intact fly.« less

Adaptor proteins GIR1 and GIR2. I. Interaction with the repressor GLABRA2 and regulation of root hair development.

PubMed

Wu, Renhong; Citovsky, Vitaly

2017-07-01

Plants use specialized root outgrowths, termed root hairs, to enhance acquisition of nutrients and water, help secure anchorage, and facilitate interactions with soil microbiome. One of the major regulators of this process is GLABRA2 (GL2), a transcriptional repressor of root hair differentiation. However, regulation of the GL2-function is relatively well characterized, it remains completely unknown whether GL2 itself functions in complex with other transcriptional regulators. We identified GIR1 and GIR2, a plant-specific two-member family of closely related proteins that interact with GL2. Loss-of-function mutants of GIR1 and GIR2 enhanced development of root hair whereas gain-of-function mutants repressed it. Thus, GIR1 and GIR2 might function as adaptor proteins that associate with GL2 and participate in control of root hair formation. Copyright © 2017 Elsevier Inc. All rights reserved.

Transcription factor clusters regulate genes in eukaryotic cells

PubMed Central

Hedlund, Erik G; Friemann, Rosmarie; Hohmann, Stefan

2017-01-01

Transcription is regulated through binding factors to gene promoters to activate or repress expression, however, the mechanisms by which factors find targets remain unclear. Using single-molecule fluorescence microscopy, we determined in vivo stoichiometry and spatiotemporal dynamics of a GFP tagged repressor, Mig1, from a paradigm signaling pathway of Saccharomyces cerevisiae. We find the repressor operates in clusters, which upon extracellular signal detection, translocate from the cytoplasm, bind to nuclear targets and turnover. Simulations of Mig1 configuration within a 3D yeast genome model combined with a promoter-specific, fluorescent translation reporter confirmed clusters are the functional unit of gene regulation. In vitro and structural analysis on reconstituted Mig1 suggests that clusters are stabilized by depletion forces between intrinsically disordered sequences. We observed similar clusters of a co-regulatory activator from a different pathway, supporting a generalized cluster model for transcription factors that reduces promoter search times through intersegment transfer while stabilizing gene expression. PMID:28841133

Structural characterization of Staphylococcus aureus biotin protein ligase and interaction partners: an antibiotic target.

PubMed

Pendini, Nicole R; Yap, Min Y; Traore, D A K; Polyak, Steven W; Cowieson, Nathan P; Abell, Andrew; Booker, Grant W; Wallace, John C; Wilce, Jacqueline A; Wilce, Matthew C J

2013-06-01

The essential metabolic enzyme biotin protein ligase (BPL) is a potential target for the development of new antibiotics required to combat drug-resistant pathogens. Staphylococcus aureus BPL (SaBPL) is a bifunctional protein, possessing both biotin ligase and transcription repressor activities. This positions BPL as a key regulator of several important metabolic pathways. Here, we report the structural analysis of both holo- and apo-forms of SaBPL using X-ray crystallography. We also present small-angle X-ray scattering data of SaBPL in complex with its biotin-carboxyl carrier protein substrate as well as the SaBPL:DNA complex that underlies repression. This has revealed the molecular basis of ligand (biotinyl-5'-AMP) binding and conformational changes associated with catalysis and repressor function. These data provide new information to better understand the bifunctional activities of SaBPL and to inform future strategies for antibiotic discovery. © 2013 The Protein Society.

Structural characterization of Staphylococcus aureus biotin protein ligase and interaction partners: An antibiotic target

PubMed Central

Pendini, Nicole R; Yap, Min Y; Polyak, Steven W; Cowieson, Nathan P; Abell, Andrew; Booker, Grant W; Wallace, John C; Wilce, Jacqueline A; Wilce, Matthew C J

2013-01-01

The essential metabolic enzyme biotin protein ligase (BPL) is a potential target for the development of new antibiotics required to combat drug-resistant pathogens. Staphylococcus aureus BPL (SaBPL) is a bifunctional protein, possessing both biotin ligase and transcription repressor activities. This positions BPL as a key regulator of several important metabolic pathways. Here, we report the structural analysis of both holo- and apo-forms of SaBPL using X-ray crystallography. We also present small-angle X-ray scattering data of SaBPL in complex with its biotin-carboxyl carrier protein substrate as well as the SaBPL:DNA complex that underlies repression. This has revealed the molecular basis of ligand (biotinyl-5′-AMP) binding and conformational changes associated with catalysis and repressor function. These data provide new information to better understand the bifunctional activities of SaBPL and to inform future strategies for antibiotic discovery. PMID:23559560

DNA replication checkpoint promotes G1-S transcription by inactivating the MBF repressor Nrm1

PubMed Central

de Bruin, R. A. M.; Kalashnikova, T. I.; Aslanian, A.; Wohlschlegel, J.; Chahwan, C.; Yates, J. R.; Russell, P.; Wittenberg, C.

2008-01-01

The cell cycle transcriptional program imposes order on events of the cell-cycle and is a target for signals that regulate cell-cycle progression, including checkpoints required to maintain genome integrity. Neither the mechanism nor functional significance of checkpoint regulation of the cell-cycle transcription program are established. We show that Nrm1, an MBF-specific transcriptional repressor acting at the transition from G1 to S phase of the cell cycle, is at the nexus between the cell cycle transcriptional program and the DNA replication checkpoint in fission yeast. Phosphorylation of Nrm1 by the Cds1 (Chk2) checkpoint protein kinase, which is activated in response to DNA replication stress, promotes its dissociation from the MBF transcription factor. This leads to the expression of genes encoding components that function in DNA replication and repair pathways important for cell survival in response to arrested DNA replication. PMID:18682565

Application of TALE-Based Approach for Dissecting Functional MicroRNA-302/367 in Cellular Reprogramming.

PubMed

Zhang, Zhonghui; Wu, Wen-Shu

2018-01-01

MicroRNAs are small 18-24 nt single-stranded noncoding RNA molecules involved in many biological processes, including stemness maintenance and cellular reprogramming. Current methods used in loss-of-function studies of microRNAs have several limitations. Here, we describe a new approach for dissecting miR-302/367 functions by transcription activator-like effectors (TALEs), which are natural effector proteins secreted by Xanthomonas and Ralstonia bacteria. Knockdown of the miR-302/367 cluster uses the Kruppel-associated box repressor domain fused with specific TALEs designed to bind the miR-302/367 cluster promoter. Knockout of the miR-302/367 cluster uses two pairs of TALE nucleases (TALENs) to delete the miR-302/367 cluster in human primary cells. Together, both TALE-based transcriptional repressor and TALENs are two promising approaches for loss-of-function studies of microRNA cluster in human primary cells.

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

Nishino, Tomonori G.; Department of Biotechnology, University of Tokyo, Bunkyo-ku, Tokyo 113-8657; Miyazaki, Masaya

Class IIa histone deacetylases (HDACs) form complexes with a class of transcriptional repressors in the nucleus. While screening for compounds that could block the association of HDAC4 with the BTB domain-containing transcriptional repressor Bach2, we discovered that phorbol 12-myristate 13-acetate (PMA) induced the cytoplasmic retention of HDAC4 mutants lacking a nuclear export signal (NES). Although PMA treatment and PKD overexpression has been proposed to facilitate the nuclear export of class IIa HDACs by creating 14-3-3 binding sites containing phosphoserines, our experiments using HDAC mutants demonstrated that PMA greatly reduces nuclear import. PMA treatment repressed the NLS activity in a mannermore » dependent on 14-3-3 binding. These results suggest that nuclear HDAC4 is not tethered in the nucleus, but instead shuttles between the nucleus and the cytoplasm. Phosphorylation-induced 14-3-3 binding biases the balance of nucleo-cytoplasmic shuttling toward the cytoplasm by inhibiting nuclear import.« less

Molecular characterization of group A Streptococcus maltodextrin catabolism and its role in pharyngitis

PubMed Central

Shelburne, Samuel A.; Keith, David B.; Davenport, Michael T.; Horstmann, Nicola; Brennan, Richard G.; Musser, James M.

2008-01-01

Summary We previously demonstrated that the cell-surface lipoprotein MalE contributes to GAS maltose/maltodextrin utilization, but MalE inactivation does not completely abrogate GAS catabolism of maltose or maltotriose. Using a genome-wide approach, we identified the GAS phosphotransferase system (PTS) responsible for non-MalE maltose/maltotriose transport. This PTS is encoded by an open reading frame (M5005_spy1692) previously annotated as ptsG based on homology with the glucose PTS in Bacillus subtilis. Genetic inactivation of M5005_spy1692 significantly reduced transport rates of radiolabeled maltose and maltotriose, but not glucose, leading us to propose its reannotation as malT for maltose transporter. The ΔmalT, ΔmalE, and ΔmalE:malT strains were significantly attenuated in their growth in human saliva and in their ability to catabolize α-glucans digested by purified human salivary α-amylase. Compared to wild-type, the three isogenic mutant strains were significantly impaired in their ability to colonize the mouse oropharynx. Finally, we discovered that the transcript levels of maltodextrin utilization genes are regulated by competitive binding of the maltose repressor MalR and catabolite control protein A. These data provide novel insights into regulation of the GAS maltodextrin genes and their role in GAS host-pathogen interaction, thereby increasing the understanding of links between nutrient acquisition and virulence in common human pathogens. PMID:18485073

Campylobacter jejuni CsrA Regulates Metabolic and Virulence Associated Proteins and Is Necessary for Mouse Colonization.

PubMed

Fields, Joshua A; Li, Jiaqi; Gulbronson, Connor J; Hendrixson, David R; Thompson, Stuart A

2016-01-01

Campylobacter jejuni infection is a leading bacterial cause of gastroenteritis and a common antecedent leading to Gullian-Barré syndrome. Our previous data suggested that the RNA-binding protein CsrA plays an important role in regulating several important phenotypes including motility, biofilm formation, and oxidative stress resistance. In this study, we compared the proteomes of wild type, csrA mutant, and complemented csrA mutant C. jejuni strains in an effort to elucidate the mechanisms by which CsrA affects virulence phenotypes. The putative CsrA regulon was more pronounced at stationary phase (111 regulated proteins) than at mid-log phase (25 regulated proteins). Proteins displaying altered expression in the csrA mutant included diverse metabolic functions, with roles in amino acid metabolism, TCA cycle, acetate metabolism, and various other cell processes, as well as pathogenesis-associated characteristics such as motility, chemotaxis, oxidative stress resistance, and fibronectin binding. The csrA mutant strain also showed altered autoagglutination kinetics when compared to the wild type. CsrA specifically bound the 5' end of flaA mRNA, and we demonstrated that CsrA is a growth-phase dependent repressor of FlaA expression. Finally, the csrA mutant exhibited reduced ability to colonize in a mouse model when in competition with the wild type, further underscoring the role of CsrA in C. jejuni colonization and pathogenesis.

Campylobacter jejuni CsrA Regulates Metabolic and Virulence Associated Proteins and Is Necessary for Mouse Colonization

PubMed Central

Fields, Joshua A.; Li, Jiaqi; Gulbronson, Connor J.; Hendrixson, David R.

2016-01-01

Campylobacter jejuni infection is a leading bacterial cause of gastroenteritis and a common antecedent leading to Gullian-Barré syndrome. Our previous data suggested that the RNA-binding protein CsrA plays an important role in regulating several important phenotypes including motility, biofilm formation, and oxidative stress resistance. In this study, we compared the proteomes of wild type, csrA mutant, and complemented csrA mutant C. jejuni strains in an effort to elucidate the mechanisms by which CsrA affects virulence phenotypes. The putative CsrA regulon was more pronounced at stationary phase (111 regulated proteins) than at mid-log phase (25 regulated proteins). Proteins displaying altered expression in the csrA mutant included diverse metabolic functions, with roles in amino acid metabolism, TCA cycle, acetate metabolism, and various other cell processes, as well as pathogenesis-associated characteristics such as motility, chemotaxis, oxidative stress resistance, and fibronectin binding. The csrA mutant strain also showed altered autoagglutination kinetics when compared to the wild type. CsrA specifically bound the 5’ end of flaA mRNA, and we demonstrated that CsrA is a growth-phase dependent repressor of FlaA expression. Finally, the csrA mutant exhibited reduced ability to colonize in a mouse model when in competition with the wild type, further underscoring the role of CsrA in C. jejuni colonization and pathogenesis. PMID:27257952

Some estimation formulae for continuous time-invariant linear systems

NASA Technical Reports Server (NTRS)

Bierman, G. J.; Sidhu, G. S.

1975-01-01

In this brief paper we examine a Riccati equation decomposition due to Reid and Lainiotis and apply the result to the continuous time-invariant linear filtering problem. Exploitation of the time-invariant structure leads to integration-free covariance recursions which are of use in covariance analyses and in filter implementations. A super-linearly convergent iterative solution to the algebraic Riccati equation (ARE) is developed. The resulting algorithm, arranged in a square-root form, is thought to be numerically stable and competitive with other ARE solution methods. Certain covariance relations that are relevant to the fixed-point and fixed-lag smoothing problems are also discussed.

Eastern geothermal resources: should we pursue them?

PubMed

Tillman, J E

1980-11-07

A geothermal resource that consists of hot water at moderate temperatures (below 125 degrees C) underlies many areas in the central and eastern United States. Programs funded by the Department of Energy have revealed that this resource is definable and economically competitive with conventional fuels for use in direct heat applications. The resource, therefore, has the potential for reducing our dependence on the imported oil used for space heating. However, front-end costs and risks to explore, drill, test, and evaluate the magnitude of the resource have inhibited development. The question is, therefore, how much federal stimulation will be needed to convince private capital to exploit this widespread low-quality energy source.

German national femtosecond technology project (FST)

NASA Astrophysics Data System (ADS)

Dausinger, Friedrich

2002-06-01

The German federal government started the funding of a national project intended to exploit the potential of femtosecond technology. In a forgoing competition five research consortia had been successful and have started now together with an adjoin research consortium their investigations in the following fields: (i) micro-machining of technical materials for microstructuring and drilling, (ii) medical therapy in: ophthalmology, dentistry, neurology and ear surgery, (iii) metrology, (iv) laser safety, (v) x- ray generation. Lasers, systems and technologies required in these potential fields of applications will be investigated. The program aims at industrial success and is dominated by industrial partners, therefore. The more fundamental research is done in university institutes and research centers.

Femtosecond pulses for medicine and production technology: overview of a German national project

NASA Astrophysics Data System (ADS)

Dausinger, Friedrich

2002-02-01

With the beginning of the new century the German federal government started the funding of a program intended to exploit the potential of femtosecond technology. In a foregoing competition, five research consortia had been successful and have started their investigations in the following fields. - micro-machining of technical materials for microstructure and drilling - medical therapy in : ophthalmology, dentistry, neurology and ear surgery - metrology - laser safety. Lasers, systems and technologies required in these potential fields of applications will be investigated. The program aims at industrial success and is dominated by industrial partners, therefore. The more fundamental research is done in university institutes and research centers.

Simplified models for dark matter face their consistent completions

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

Gonçalves, Dorival; Machado, Pedro A. N.; No, Jose Miguel

Simplified dark matter models have been recently advocated as a powerful tool to exploit the complementarity between dark matter direct detection, indirect detection and LHC experimental probes. Focusing on pseudoscalar mediators between the dark and visible sectors, we show that the simplified dark matter model phenomenology departs significantly from that of consistentmore » $${SU(2)_{\\mathrm{L}} \\times U(1)_{\\mathrm{Y}}}$$ gauge invariant completions. We discuss the key physics simplified models fail to capture, and its impact on LHC searches. Notably, we show that resonant mono-Z searches provide competitive sensitivities to standard mono-jet analyses at $13$ TeV LHC.« less

Stability and Control Properties of an Aeroelastic Fixed Wing Micro Aerial Vehicle

NASA Technical Reports Server (NTRS)

Waszak, Martin R.; Jenkins, Luther N.; Ifju, Peter

2001-01-01

Micro aerial vehicles have been the subject of considerable interest and development over the last several years. The majority of current vehicle concepts rely on rigid fixed wings or rotors. An alternate design based on an aeroelastic membrane wing concept has also been developed that has exhibited desired characteristics in flight test demonstrations and competition. This paper presents results from a wind tunnel investigation that sought to quantify stability and control properties for a family of vehicles using the aeroelastic design. The results indicate that the membrane wing does exhibit potential benefits that could be exploited to enhance the design of future flight vehicles.

Character displacement and the evolution of niche complementarity in a model biofilm community.

PubMed

Ellis, Crystal N; Traverse, Charles C; Mayo-Smith, Leslie; Buskirk, Sean W; Cooper, Vaughn S

2015-02-01

Colonization of vacant environments may catalyze adaptive diversification and be followed by competition within the nascent community. How these interactions ultimately stabilize and affect productivity are central problems in evolutionary ecology. Diversity can emerge by character displacement, in which selection favors phenotypes that exploit an alternative resource and reduce competition, or by facilitation, in which organisms change the environment and enable different genotypes or species to become established. We previously developed a model of long-term experimental evolution in which bacteria attach to a plastic bead, form a biofilm, and disperse to a new bead. Here, we focus on the evolution of coexisting mutants within a population of Burkholderia cenocepacia and how their interactions affected productivity. Adaptive mutants initially competed for space, but later competition declined, consistent with character displacement and the predicted effects of the evolved mutations. The community reached a stable equilibrium as each ecotype evolved to inhabit distinct, complementary regions of the biofilm. Interactions among ecotypes ultimately became facilitative and enhanced mixed productivity. Observing the succession of genotypes within niches illuminated changing selective forces within the community, including a fundamental role for genotypes producing small colony variants that underpin chronic infections caused by B. cenocepacia. © 2014 The Author(s). Evolution published by Wiley Periodicals, Inc. on behalf of The Society for the Study of Evolution.

Systematic Transfer of Prokaryotic Sensors and Circuits to Mammalian Cells

PubMed Central

2015-01-01

Prokaryotic regulatory proteins respond to diverse signals and represent a rich resource for building synthetic sensors and circuits. The TetR family contains >105 members that use a simple mechanism to respond to stimuli and bind distinct DNA operators. We present a platform that enables the transfer of these regulators to mammalian cells, which is demonstrated using human embryonic kidney (HEK293) and Chinese hamster ovary (CHO) cells. The repressors are modified to include nuclear localization signals (NLS) and responsive promoters are built by incorporating multiple operators. Activators are also constructed by modifying the protein to include a VP16 domain. Together, this approach yields 15 new regulators that demonstrate 19- to 551-fold induction and retain both the low levels of crosstalk in DNA binding specificity observed between the parent regulators in Escherichia coli, as well as their dynamic range of activity. By taking advantage of the DAPG small molecule sensing mediated by the PhlF repressor, we introduce a new inducible system with 50-fold induction and a threshold of 0.9 μM DAPG, which is comparable to the classic Dox-induced TetR system. A set of NOT gates is constructed from the new repressors and their response function quantified. Finally, the Dox- and DAPG- inducible systems and two new activators are used to build a synthetic enhancer (fuzzy AND gate), requiring the coordination of 5 transcription factors organized into two layers. This work introduces a generic approach for the development of mammalian genetic sensors and circuits to populate a toolbox that can be applied to diverse applications from biomanufacturing to living therapeutics. PMID:25360681

Kcnip1 a Ca²⁺-dependent transcriptional repressor regulates the size of the neural plate in Xenopus.

PubMed

Néant, Isabelle; Mellström, Britt; Gonzalez, Paz; Naranjo, Jose R; Moreau, Marc; Leclerc, Catherine

2015-09-01

In amphibian embryos, our previous work has demonstrated that calcium transients occurring in the dorsal ectoderm at the onset of gastrulation are necessary and sufficient to engage the ectodermal cells into a neural fate by inducing neural specific genes. Some of these genes are direct targets of calcium. Here we search for a direct transcriptional mechanism by which calcium signals are acting. The only known mechanism responsible for a direct action of calcium on gene transcription involves an EF-hand Ca²⁺ binding protein which belongs to a group of four proteins (Kcnip1 to 4). Kcnip protein can act in a Ca²⁺-dependent manner as a transcriptional repressor by binding to a specific DNA sequence, the Downstream Regulatory Element (DRE) site. In Xenopus, among the four kcnips, we show that only kcnip1 is timely and spatially present in the presumptive neural territories and is able to bind DRE sites in a Ca²⁺-dependent manner. The loss of function of kcnip1 results in the expansion of the neural plate through an increased proliferation of neural progenitors. Later on, this leads to an impairment in the development of anterior neural structures. We propose that, in the embryo, at the onset of neurogenesis Kcnip1 is the Ca²⁺-dependent transcriptional repressor that controls the size of the neural plate. This article is part of a Special Issue entitled: 13th European Symposium on Calcium. Copyright © 2014. Published by Elsevier B.V.

Genome-wide mapping and analysis of aryl hydrocarbon receptor (AHR)- and aryl hydrocarbon receptor repressor (AHRR)-binding sites in human breast cancer cells.

PubMed

Yang, Sunny Y; Ahmed, Shaimaa; Satheesh, Somisetty V; Matthews, Jason

2018-01-01

The aryl hydrocarbon receptor (AHR) mediates the toxic actions of environmental contaminants, such as 2,3,7,8-tetrachlorodibenzo-ρ-dioxin (TCDD), and also plays roles in vascular development, the immune response, and cell cycle regulation. The AHR repressor (AHRR) is an AHR-regulated gene and a negative regulator of AHR; however, the mechanisms of AHRR-dependent repression of AHR are unclear. In this study, we compared the genome-wide binding profiles of AHR and AHRR in MCF-7 human breast cancer cells treated for 24 h with TCDD using chromatin immunoprecipitation followed by next-generation sequencing (ChIP-Seq). We identified 3915 AHR- and 2811 AHRR-bound regions, of which 974 (35%) were common to both datasets. When these 24-h datasets were also compared with AHR-bound regions identified after 45 min of TCDD treatment, 67% (1884) of AHRR-bound regions overlapped with those of AHR. This analysis identified 994 unique AHRR-bound regions. AHRR-bound regions mapped closer to promoter regions when compared with AHR-bound regions. The AHRE was identified and overrepresented in AHR:AHRR-co-bound regions, AHR-only regions, and AHRR-only regions. Candidate unique AHR- and AHRR-bound regions were validated by ChIP-qPCR and their ability to regulate gene expression was confirmed by luciferase reporter gene assays. Overall, this study reveals that AHR and AHRR exhibit similar but also distinct genome-wide binding profiles, supporting the notion that AHRR is a context- and gene-specific repressor of AHR activity.

Epithelial-mesenchymal transition, a novel target of sulforaphane via COX-2/MMP2, 9/Snail, ZEB1 and miR-200c/ZEB1 pathways in human bladder cancer cells.

PubMed

Shan, Yujuan; Zhang, Lanwei; Bao, Yongping; Li, Baolong; He, Canxia; Gao, Mingming; Feng, Xue; Xu, Weili; Zhang, Xiaohong; Wang, Shuran

2013-06-01

Metastasis and recurrence of bladder cancer are the main reasons for its poor prognosis and high mortality rates. Because of its biological activity and high metabolic accumulation in urine, sulforaphane, a phytochemical exclusively occurring in cruciferous vegetables, has a powerful and specific potential for preventing bladder cancer. In this paper, sulforaphane is shown to significantly suppress a variety of biochemical pathways including the attachment, invasion, migration and chemotaxis motion in malignant transitional bladder cancer T24 cells. Transfection with cyclooxygenase-2 (COX-2) overexpression plasmid largely abolished inhibition of MMP2/9 expression as well as cell invasive capability by sulforaphane. Moreover, sulforaphane inhibited the epithelial-to-mesenchymal transition (EMT) process which underlies tumor cell invasion and migration mediated by E-cadherin induction through reducing transcriptional repressors, such as ZEB1 and Snail. Under conditions of over-expression of COX-2 and/or MMP2/9, sulforaphane was still able to induce E-cadherin or reduce Snail/ZEB1 expression, suggesting that additional pathways might be involved. Further studies indicated that miR-200c played a role in the regulation of E-cadherin via the ZEB1 repressor but not by the Snail repressor. In conclusion, the EMT and two recognized signaling pathways (COX-2/MMP2,9/ ZEB1, Snail and miR-200c/ZEB1) are all targets for sulforaphane. This study indicated that sulforaphane may possess therapeutic potential in preventing recurrence of human bladder cancer. Copyright © 2013 Elsevier Inc. All rights reserved.

Regulation of neural macroRNAs by the transcriptional repressor REST

PubMed Central

Johnson, Rory; Teh, Christina Hui-Leng; Jia, Hui; Vanisri, Ravi Raj; Pandey, Tridansh; Lu, Zhong-Hao; Buckley, Noel J.; Stanton, Lawrence W.; Lipovich, Leonard

2009-01-01

The essential transcriptional repressor REST (repressor element 1-silencing transcription factor) plays central roles in development and human disease by regulating a large cohort of neural genes. These have conventionally fallen into the class of known, protein-coding genes; recently, however, several noncoding microRNA genes were identified as REST targets. Given the widespread transcription of messenger RNA-like, noncoding RNAs (“macroRNAs”), some of which are functional and implicated in disease in mammalian genomes, we sought to determine whether this class of noncoding RNAs can also be regulated by REST. By applying a new, unbiased target gene annotation pipeline to computationally discovered REST binding sites, we find that 23% of mammalian REST genomic binding sites are within 10 kb of a macroRNA gene. These putative target genes were overlooked by previous studies. Focusing on a set of 18 candidate macroRNA targets from mouse, we experimentally demonstrate that two are regulated by REST in neural stem cells. Flanking protein-coding genes are, at most, weakly repressed, suggesting specific targeting of the macroRNAs by REST. Similar to the majority of known REST target genes, both of these macroRNAs are induced during nervous system development and have neurally restricted expression profiles in adult mouse. We observe a similar phenomenon in human: the DiGeorge syndrome-associated noncoding RNA, DGCR5, is repressed by REST through a proximal upstream binding site. Therefore neural macroRNAs represent an additional component of the REST regulatory network. These macroRNAs are new candidates for understanding the role of REST in neuronal development, neurodegeneration, and cancer. PMID:19050060

Regulation of neural macroRNAs by the transcriptional repressor REST.

PubMed

Johnson, Rory; Teh, Christina Hui-Leng; Jia, Hui; Vanisri, Ravi Raj; Pandey, Tridansh; Lu, Zhong-Hao; Buckley, Noel J; Stanton, Lawrence W; Lipovich, Leonard

2009-01-01

The essential transcriptional repressor REST (repressor element 1-silencing transcription factor) plays central roles in development and human disease by regulating a large cohort of neural genes. These have conventionally fallen into the class of known, protein-coding genes; recently, however, several noncoding microRNA genes were identified as REST targets. Given the widespread transcription of messenger RNA-like, noncoding RNAs ("macroRNAs"), some of which are functional and implicated in disease in mammalian genomes, we sought to determine whether this class of noncoding RNAs can also be regulated by REST. By applying a new, unbiased target gene annotation pipeline to computationally discovered REST binding sites, we find that 23% of mammalian REST genomic binding sites are within 10 kb of a macroRNA gene. These putative target genes were overlooked by previous studies. Focusing on a set of 18 candidate macroRNA targets from mouse, we experimentally demonstrate that two are regulated by REST in neural stem cells. Flanking protein-coding genes are, at most, weakly repressed, suggesting specific targeting of the macroRNAs by REST. Similar to the majority of known REST target genes, both of these macroRNAs are induced during nervous system development and have neurally restricted expression profiles in adult mouse. We observe a similar phenomenon in human: the DiGeorge syndrome-associated noncoding RNA, DGCR5, is repressed by REST through a proximal upstream binding site. Therefore neural macroRNAs represent an additional component of the REST regulatory network. These macroRNAs are new candidates for understanding the role of REST in neuronal development, neurodegeneration, and cancer.

Systematic transfer of prokaryotic sensors and circuits to mammalian cells.

PubMed

Stanton, Brynne C; Siciliano, Velia; Ghodasara, Amar; Wroblewska, Liliana; Clancy, Kevin; Trefzer, Axel C; Chesnut, Jonathan D; Weiss, Ron; Voigt, Christopher A

2014-12-19

Prokaryotic regulatory proteins respond to diverse signals and represent a rich resource for building synthetic sensors and circuits. The TetR family contains >10(5) members that use a simple mechanism to respond to stimuli and bind distinct DNA operators. We present a platform that enables the transfer of these regulators to mammalian cells, which is demonstrated using human embryonic kidney (HEK293) and Chinese hamster ovary (CHO) cells. The repressors are modified to include nuclear localization signals (NLS) and responsive promoters are built by incorporating multiple operators. Activators are also constructed by modifying the protein to include a VP16 domain. Together, this approach yields 15 new regulators that demonstrate 19- to 551-fold induction and retain both the low levels of crosstalk in DNA binding specificity observed between the parent regulators in Escherichia coli, as well as their dynamic range of activity. By taking advantage of the DAPG small molecule sensing mediated by the PhlF repressor, we introduce a new inducible system with 50-fold induction and a threshold of 0.9 μM DAPG, which is comparable to the classic Dox-induced TetR system. A set of NOT gates is constructed from the new repressors and their response function quantified. Finally, the Dox- and DAPG- inducible systems and two new activators are used to build a synthetic enhancer (fuzzy AND gate), requiring the coordination of 5 transcription factors organized into two layers. This work introduces a generic approach for the development of mammalian genetic sensors and circuits to populate a toolbox that can be applied to diverse applications from biomanufacturing to living therapeutics.

Suppression and restoration of male fertility using a transcription factor.

PubMed

Li, Song Feng; Iacuone, Sylvana; Parish, Roger W

2007-03-01

The Arabidopsis AtMYB103 gene codes for an R2R3 MYB domain protein whose expression is restricted to the tapetum of developing anthers and to trichomes. Down-regulation of expression using anti-sense leads to abnormal tapetum and pollen development, although seed setting still occurs (Higginson, T., Li, S.F. and Parish, R.W. (2003) AtMYB103 regulates tapetum and trichome development in Arabidopsis thaliana. Plant J. 35, 177-192). In this study, we show that blocking the function of the AtMYB103 gene, employing either an insertion mutant or an AtMYB103EAR chimeric repressor construct under the control of the AtMYB103 promoter, results in complete male sterility and failure to set seed. These plants exhibit similar abnormalities in tapetum and pollen development, with the tapetum becoming highly vacuolated at early stages and degenerating prematurely. No exine is deposited on to the pollen wall. The degeneration of pollen grains commences prior to pollen mitosis, the pollen collapsing and largely lacking cytoplasmic content. A restorer containing the AtMYB103 gene under the control of a stronger anther-specific promoter was introduced into pollen donor plants and crossed into the male sterile plants transgenic for the repressor. The male fertility of F1 plants was restored. The chimeric repressor and the restorer constitute a reversible male sterility system which could be adapted for hybrid seed production. This is the first reversible male sterility system targeting a transcription factor essential for pollen development. Strategies for generating inducible male sterility and maintainable male sterility for the production of hybrid crops are discussed.

Mi2β Is Required for γ-Globin Gene Silencing: Temporal Assembly of a GATA-1-FOG-1-Mi2 Repressor Complex in β-YAC Transgenic Mice

PubMed Central

Costa, Flávia C.; Fedosyuk, Halyna; Chazelle, Allen M.; Neades, Renee Y.; Peterson, Kenneth R.

2012-01-01

Activation of γ-globin gene expression in adults is known to be therapeutic for sickle cell disease. Thus, it follows that the converse, alleviation of repression, would be equally effective, since the net result would be the same: an increase in fetal hemoglobin. A GATA-1-FOG-1-Mi2 repressor complex was recently demonstrated to be recruited to the −566 GATA motif of the Aγ-globin gene. We show that Mi2β is essential for γ-globin gene silencing using Mi2β conditional knockout β-YAC transgenic mice. In addition, increased expression of Aγ-globin was detected in adult blood from β-YAC transgenic mice containing a T>G HPFH point mutation at the −566 GATA silencer site. ChIP experiments demonstrated that GATA-1 is recruited to this silencer at day E16, followed by recruitment of FOG-1 and Mi2 at day E17 in wild-type β-YAC transgenic mice. Recruitment of the GATA-1–mediated repressor complex was disrupted by the −566 HPFH mutation at developmental stages when it normally binds. Our data suggest that a temporal repression mechanism is operative in the silencing of γ-globin gene expression and that either a trans-acting Mi2β knockout deletion mutation or the cis-acting −566 Aγ-globin HPFH point mutation disrupts establishment of repression, resulting in continued γ-globin gene transcription during adult definitive erythropoiesis. PMID:23284307

Mi2β is required for γ-globin gene silencing: temporal assembly of a GATA-1-FOG-1-Mi2 repressor complex in β-YAC transgenic mice.

PubMed

Costa, Flávia C; Fedosyuk, Halyna; Chazelle, Allen M; Neades, Renee Y; Peterson, Kenneth R

2012-01-01

Activation of γ-globin gene expression in adults is known to be therapeutic for sickle cell disease. Thus, it follows that the converse, alleviation of repression, would be equally effective, since the net result would be the same: an increase in fetal hemoglobin. A GATA-1-FOG-1-Mi2 repressor complex was recently demonstrated to be recruited to the -566 GATA motif of the (A)γ-globin gene. We show that Mi2β is essential for γ-globin gene silencing using Mi2β conditional knockout β-YAC transgenic mice. In addition, increased expression of (A)γ-globin was detected in adult blood from β-YAC transgenic mice containing a T>G HPFH point mutation at the -566 GATA silencer site. ChIP experiments demonstrated that GATA-1 is recruited to this silencer at day E16, followed by recruitment of FOG-1 and Mi2 at day E17 in wild-type β-YAC transgenic mice. Recruitment of the GATA-1-mediated repressor complex was disrupted by the -566 HPFH mutation at developmental stages when it normally binds. Our data suggest that a temporal repression mechanism is operative in the silencing of γ-globin gene expression and that either a trans-acting Mi2β knockout deletion mutation or the cis-acting -566 (A)γ-globin HPFH point mutation disrupts establishment of repression, resulting in continued γ-globin gene transcription during adult definitive erythropoiesis.

Comparative genomics of bacterial zinc regulons: enhanced ion transport, pathogenesis, and rearrangement of ribosomal proteins.

PubMed

Panina, Ekaterina M; Mironov, Andrey A; Gelfand, Mikhail S

2003-08-19

Zinc is an important component of many proteins, but in large concentrations it is poisonous to the cell. Thus its transport is regulated by zinc repressors ZUR of proteobacteria and Gram-positive bacteria from the Bacillus group and AdcR of bacteria from the Streptococcus group. Comparative computational analysis allowed us to identify binding signals of ZUR repressors GAAATGTTATANTATAACATTTC for gamma-proteobacteria, GTAATGTAATAACATTAC for the Agrobacterium group, GATATGTTATAACATATC for the Rhododoccus group, TAAATCGTAATNATTACGATTTA for Gram-positive bacteria, and TTAACYRGTTAA of the streptococcal AdcR repressor. In addition to known transporters and their paralogs, zinc regulons were predicted to contain a candidate component of the ATP binding cassette, zinT (b1995 in Escherichia coli and yrpE in Bacillus subtilis). Candidate AdcR-binding sites were identified upstream of genes encoding pneumococcal histidine triad (PHT) proteins from a number of pathogenic streptococci. Protein functional analysis of this family suggests that PHT proteins are involved in the invasion process. Finally, repression by zinc was predicted for genes encoding a variety of paralogs of ribosomal proteins. The original copies of all these proteins contain zinc-ribbon motifs and thus likely bind zinc, whereas these motifs are destroyed in zinc-regulated paralogs. We suggest that the induction of these paralogs in conditions of zinc starvation leads to their incorporation in a fraction of ribosomes instead of the original ribosomal proteins; the latter are then degraded with subsequent release of some zinc for the utilization by other proteins. Thus we predict a mechanism for maintaining zinc availability for essential enzymes.

Sp1 is a transcription repressor to stanniocalcin-1 expression in TSA-treated human colon cancer cells, HT29.

PubMed

Law, Alice Y S; Yeung, B H Y; Ching, L Y; Wong, Chris K C

2011-08-01

Our previous study demonstrated that, stanniocalcin-1 (STC1) was a target of histone deacetylase (HDAC) inhibitors and was involved in trichostatin A (TSA) induced apoptosis in the human colon cancer cells, HT29. In this study, we reported that the transcriptional factor, specificity protein 1 (Sp1) in association with retinoblastoma (Rb) repressed STC1 gene transcription in TSA-treated HT29 cells. Our data demonstrated that, a co-treatment of the cells with TSA and Sp1 inhibitor, mithramycin A (MTM) led to a marked synergistic induction of STC1 transcript levels, STC1 promoter (1 kb)-driven luciferase activity and an increase of apoptotic cell population. The knockdown of Sp1 gene expression in TSA treated cells, revealed the repressor role of Sp1 in STC1 transcription. Using a protein phosphatase inhibitor okadaic acid (OKA), an increase of Sp1 hyperphosphorylation and so a reduction of its transcriptional activity, led to a significant induction of STC1 gene expression. Chromatin immunoprecipitation (ChIP) assay revealed that Sp1 binding on STC1 proximal promoter in TSA treated cells. The binding of Sp1 to STC1 promoter was abolished by the co-treatment of MTM or OKA in TSA-treated cells. Re-ChIP assay illustrated that Sp1-mediated inhibition of STC1 transcription was associated with the recruitment of another repressor molecule, Rb. Collectively our findings identify STC1 is a downstream target of Sp1. Copyright © 2011 Wiley-Liss, Inc.

Effects of atorvastatin metabolites on induction of drug-metabolizing enzymes and membrane transporters through human pregnane X receptor

PubMed Central

Hoffart, E; Ghebreghiorghis, L; Nussler, AK; Thasler, WE; Weiss, TS; Schwab, M; Burk, O

2012-01-01

BACKGROUND AND PURPOSE Atorvastatin metabolites differ in their potential for drug interaction because of differential inhibition of drug-metabolizing enzymes and transporters. We here investigate whether they exert differential effects on the induction of these genes via activation of pregnane X receptor (PXR) and constitutive androstane receptor (CAR). EXPERIMENTAL APPROACH Ligand binding to PXR or CAR was analysed by mammalian two-hybrid assembly and promoter/reporter gene assays. Additionally, surface plasmon resonance was used to analyse ligand binding to CAR. Primary human hepatocytes were treated with atorvastatin metabolites, and mRNA and protein expression of PXR-regulated genes was measured. Two-hybrid co-activator interaction and co-repressor release assays were utilized to elucidate the molecular mechanism of PXR activation. KEY RESULTS All atorvastatin metabolites induced the assembly of PXR and activated CYP3A4 promoter activity. Ligand binding to CAR could not be proven. In primary human hepatocytes, the para-hydroxy metabolite markedly reduced or abolished induction of cytochrome P450 and transporter genes. While significant differences in co-activator recruitment were not observed, para-hydroxy atorvastatin demonstrated only 50% release of co-repressors. CONCLUSIONS AND IMPLICATIONS Atorvastatin metabolites are ligands of PXR but not of CAR. Atorvastatin metabolites demonstrate differential induction of PXR target genes, which results from impaired release of co-repressors. Consequently, the properties of drug metabolites have to be taken into account when analysing PXR-dependent induction of drug metabolism and transport. The drug interaction potential of the active metabolite, para-hydroxy atorvastatin, might be lower than that of the parent compound. PMID:21913896

Promoter/repressor system of Lactobacillus plantarum phage og1e: characterization of the promoters pR49-pR-pL and overproduction of the cro-like protein cng in Escherichia coli.

PubMed

Kakikawa, M; Watanabe, N; Funawatashi, T; Oki, M; Yasukawa, H; Taketo, A; Kodaira, K I

1998-07-30

The Lactobacillus plantarum phage og1e (42259bp) has two repressor-like genes cng and cpg oriented oppositely, accompanied by three potential promoters pR, pL and pR49, and seven operator-like sequences (GATAC-boxes) (Kodaira et al., 1997). In this study, the og1e putative promoters were introduced into the Escherichia coli promoter-detecting plasmid pKK232-8. In E. coli CK111, pR (pKPR1), pL (pKPL1) and pR49 (pKPR49) exhibited distinct CAT activities. When pKPR1 or pKPL1 was coexistent with a compatible plasmid pACYC184 carrying pR-cng (pA4PRCN1), the CAT activity was decreased significantly. On the other hand, cng directed a protein (Cng) of 10.1 kDa in E. coli under the control of T7 promoter. Gel mobility-shift assays demonstrated that Cng binds specifically to a DNA region containing the GATAC-boxes. In addition, primer extension analyses demonstrated that the two sequences pR and pL act as a promoter in L. plantarum as well as in E. coli. These results suggested that the potential promoters pR and pL probably function for the lytic and lysogenic pathways, respectively, and Cng may act as a repressor presumably through the GATAC-boxes as operators.

The transcription repressor NmrA is subject to proteolysis by three Aspergillus nidulans proteases

PubMed Central

Zhao, Xiao; Hume, Samantha L; Johnson, Christopher; Thompson, Paul; Huang, Junyong; Gray, Joe; Lamb, Heather K; Hawkins, Alastair R

2010-01-01

The role of specific cleavage of transcription repressor proteins by proteases and how this may be related to the emerging theme of dinucleotides as cellular signaling molecules is poorly characterized. The transcription repressor NmrA of Aspergillus nidulans discriminates between oxidized and reduced dinucleotides, however, dinucleotide binding has no effect on its interaction with the zinc finger in the transcription activator AreA. Protease activity in A. nidulans was assayed using NmrA as the substrate, and was absent in mycelium grown under nitrogen sufficient conditions but abundant in mycelium starved of nitrogen. One of the proteases was purified and identified as the protein Q5BAR4 encoded by the gene AN2366.2. Fluorescence confocal microscopy showed that the nuclear levels of NmrA were reduced approximately 38% when mycelium was grown on nitrate compared to ammonium and absent when starved of nitrogen. Proteolysis of NmrA occurred in an ordered manner by preferential digestion within a C-terminal surface exposed loop and subsequent digestion at other sites. NmrA digested at the C-terminal site was unable to bind to the AreA zinc finger. These data reveal a potential new layer of control of nitrogen metabolite repression by the ordered proteolytic cleavage of NmrA. NmrA digested at the C-terminal site retained the ability to bind NAD+ and showed a resistance to further digestion that was enhanced by the presence of NAD+. This is the first time that an effect of dinucleotide binding to NmrA has been demonstrated. PMID:20506376

Light-dependent gene regulation by a coenzyme B12-based photoreceptor

PubMed Central

Ortiz-Guerrero, Juan Manuel; Polanco, María Carmen; Murillo, Francisco J.; Padmanabhan, S.; Elías-Arnanz, Montserrat

2011-01-01

Cobalamin (B12) typically functions as an enzyme cofactor but can also regulate gene expression via RNA-based riboswitches. B12-directed gene regulatory mechanisms via protein factors have, however, remained elusive. Recently, we reported down-regulation of a light-inducible promoter in the bacterium Myxococcus xanthus by two paralogous transcriptional repressors, of which one, CarH, but not the other, CarA, absolutely requires B12 for activity even though both have a canonical B12-binding motif. Unanswered were what underlies this striking difference, what is the specific cobalamin used, and how it acts. Here, we show that coenzyme B12 (5′-deoxyadenosylcobalamin, AdoB12), specifically dictates CarH function in the dark and on exposure to light. In the dark, AdoB12-binding to the autonomous domain containing the B12-binding motif foments repressor oligomerization, enhances operator binding, and blocks transcription. Light, at various wavelengths at which AdoB12 absorbs, dismantles active repressor oligomers by photolysing the bound AdoB12 and weakens repressor–operator binding to allow transcription. By contrast, AdoB12 alters neither CarA oligomerization nor operator binding, thus accounting for its B12-independent activity. Our findings unveil a functional facet of AdoB12 whereby it serves as the chromophore of a unique photoreceptor protein class acting in light-dependent gene regulation. The prevalence of similar proteins of unknown function in microbial genomes suggests that this distinct B12-based molecular mechanism for photoregulation may be widespread in bacteria. PMID:21502508

Grantee Spotlight: Dr. Meena Jaggi - Investigating Curcumin (Turmeric) as HPV Repressor for Native A

Cancer.gov

Dr. Meena Jaggi’s research, funded by an NCI/CRCHD U01 grant, involves the use of curcumin (commonly known as turmeric) to inhibit human papillomavirus (HPV) infection among Native American (NA) women.

Brassinosteroids antagonize gibberellin- and salicylate-mediated root immunity in rice.

PubMed

De Vleesschauwer, David; Van Buyten, Evelien; Satoh, Kouji; Balidion, Johny; Mauleon, Ramil; Choi, Il-Ryong; Vera-Cruz, Casiana; Kikuchi, Shoshi; Höfte, Monica

2012-04-01

Brassinosteroids (BRs) are a unique class of plant steroid hormones that orchestrate myriad growth and developmental processes. Although BRs have long been known to protect plants from a suite of biotic and abiotic stresses, our understanding of the underlying molecular mechanisms is still rudimentary. Aiming to further decipher the molecular logic of BR-modulated immunity, we have examined the dynamics and impact of BRs during infection of rice (Oryza sativa) with the root oomycete Pythium graminicola. Challenging the prevailing view that BRs positively regulate plant innate immunity, we show that P. graminicola exploits BRs as virulence factors and hijacks the rice BR machinery to inflict disease. Moreover, we demonstrate that this immune-suppressive effect of BRs is due, at least in part, to negative cross talk with salicylic acid (SA) and gibberellic acid (GA) pathways. BR-mediated suppression of SA defenses occurred downstream of SA biosynthesis, but upstream of the master defense regulators NONEXPRESSOR OF PATHOGENESIS-RELATED GENES1 and OsWRKY45. In contrast, BR alleviated GA-directed immune responses by interfering at multiple levels with GA metabolism, resulting in indirect stabilization of the DELLA protein and central GA repressor SLENDER RICE1 (SLR1). Collectively, these data favor a model whereby P. graminicola coopts the plant BR pathway as a decoy to antagonize effectual SA- and GA-mediated defenses. Our results highlight the importance of BRs in modulating plant immunity and uncover pathogen-mediated manipulation of plant steroid homeostasis as a core virulence strategy.

Brassinosteroids Antagonize Gibberellin- and Salicylate-Mediated Root Immunity in Rice1[C][W][OA

PubMed Central

De Vleesschauwer, David; Van Buyten, Evelien; Satoh, Kouji; Balidion, Johny; Mauleon, Ramil; Choi, Il-Ryong; Vera-Cruz, Casiana; Kikuchi, Shoshi; Höfte, Monica

2012-01-01

Brassinosteroids (BRs) are a unique class of plant steroid hormones that orchestrate myriad growth and developmental processes. Although BRs have long been known to protect plants from a suite of biotic and abiotic stresses, our understanding of the underlying molecular mechanisms is still rudimentary. Aiming to further decipher the molecular logic of BR-modulated immunity, we have examined the dynamics and impact of BRs during infection of rice (Oryza sativa) with the root oomycete Pythium graminicola. Challenging the prevailing view that BRs positively regulate plant innate immunity, we show that P. graminicola exploits BRs as virulence factors and hijacks the rice BR machinery to inflict disease. Moreover, we demonstrate that this immune-suppressive effect of BRs is due, at least in part, to negative cross talk with salicylic acid (SA) and gibberellic acid (GA) pathways. BR-mediated suppression of SA defenses occurred downstream of SA biosynthesis, but upstream of the master defense regulators NONEXPRESSOR OF PATHOGENESIS-RELATED GENES1 and OsWRKY45. In contrast, BR alleviated GA-directed immune responses by interfering at multiple levels with GA metabolism, resulting in indirect stabilization of the DELLA protein and central GA repressor SLENDER RICE1 (SLR1). Collectively, these data favor a model whereby P. graminicola coopts the plant BR pathway as a decoy to antagonize effectual SA- and GA-mediated defenses. Our results highlight the importance of BRs in modulating plant immunity and uncover pathogen-mediated manipulation of plant steroid homeostasis as a core virulence strategy. PMID:22353574

Ikaros controls isotype selection during immunoglobulin class switch recombination.

PubMed

Sellars, MacLean; Reina-San-Martin, Bernardo; Kastner, Philippe; Chan, Susan

2009-05-11

Class switch recombination (CSR) allows the humoral immune response to exploit different effector pathways through specific secondary antibody isotypes. However, the molecular mechanisms and factors that control immunoglobulin (Ig) isotype choice for CSR are unclear. We report that deficiency for the Ikaros transcription factor results in increased and ectopic CSR to IgG(2b) and IgG(2a), and reduced CSR to all other isotypes, regardless of stimulation. Ikaros suppresses active chromatin marks, transcription, and activation-induced cytidine deaminase (AID) accessibility at the gamma2b and gamma2a genes to inhibit class switching to these isotypes. Further, Ikaros directly regulates isotype gene transcription as it directly binds the Igh 3' enhancer and interacts with isotype gene promoters. Finally, Ikaros-mediated repression of gamma2b and gamma2a transcription promotes switching to other isotype genes by allowing them to compete for AID-mediated recombination at the single-cell level. Thus, our results reveal transcriptional competition between constant region genes in individual cells to be a critical and general mechanism for isotype specification during CSR. We show that Ikaros is a master regulator of this competition.

Creating knowledge structures in the pharmaceutical industry: the increasing significance of virtual organisation.

PubMed

Salazar, A; Howells, J

2000-01-01

This paper explores the specific trend and challenges facing the pharmaceutical industry regarding the exploitation of Internet e-commerce technology and virtual organisation to develop and maintain competitive advantage. There are two important facets of the current trend. One is the rapid development of a complex network of alliances between the established pharmaceutical companies and the specialised biotechnology company start-ups. The other is the rapid growth of internet e-commerce companies dedicated to developing specialised technological platforms for acquiring and selling genetic and biochemical knowledge. The underlying challenge is how big pharmaceutical companies can emulate some of the innovation processes of smaller biotechnology company start-ups, and how they can appropriate and applied new technological knowledge on the development of new drugs. Pharmaceutical companies in order to retain competitive advantage need to continuously monitor all aspects of knowledge management with regard to the R&D and manufacturing process (as well as customer management and marketing). Technological change and organisational restructuring should be aimed at boosting the capacity of large firms to innovate rapidly.

Interspecific Competition for Shelters in Territorial and Gregarious Intertidal Grazers: Consequences for Individual Behaviour

PubMed Central

Aguilera, Moisés A.; Navarrete, Sergio A.

2012-01-01

Experiments have shown that interspecific interactions within consumer guilds can alter patterns of distribution, abundance and size of species. Plastic behavioural responses can be modulated by agonistic interactions. In many cases, consumers compete for space and shelters, and these interactions change the manner in which they exploit food. This study investigates the consequences of competition in the spatial and temporal organization of behaviour of intertidal grazers, which share algal resources and the use of rock crevices while resting, but exhibit different body sizes, spatial behaviour and foraging modes. We evaluate interaction strength between small gregarious Siphonaria lessoni and the larger territorial keyhole limpet Fissurella crassa and between S. lessoni and the medium-size gregarious chiton Chiton granosus. Using field manipulations and artificial arenas in the laboratory, we tested whether the use of crevices, micro-spatial distribution and activity are modified by the density of conspecifics and the presence of heterospecifics. Our results show that small-scale spatial segregation observed in the field between S. lessoni and C. granosus result from species-specific differences in habitat use. In turn, we found evidence that spatial segregation between F. crassa and S. lessoni results from highly asymmetric interference competition in the use of shelters. The presence of F. crassa reduced the use of crevices and growth rates of S. lessoni. Effects on growth rates are assumed to result from exposure to harsh environmental conditions rather than food limitation. Thus, neither gregarious behaviour nor differences in activity were sufficient to prevent competition with the larger grazer. Our study illustrates the importance of competition for shelters, which results in behavioural changes of the smaller-sized species, and how these plastic responses can translate into differences in growth rates. Use of shelters can thus be modulated by environmental conditions in a species-specific as well as an interactive manner within consumers’ guilds. PMID:23049980

Energy for lunar resource exploitation

NASA Astrophysics Data System (ADS)

Glaser, Peter E.

1992-02-01

Humanity stands at the threshold of exploiting the known lunar resources that have opened up with the access to space. America's role in the future exploitation of space, and specifically of lunar resources, may well determine the level of achievement in technology development and global economic competition. Space activities during the coming decades will significantly influence the events on Earth. The 'shifting of history's tectonic plates' is a process that will be hastened by the increasingly insistent demands for higher living standards of the exponentially growing global population. Key to the achievement of a peaceful world in the 21st century, will be the development of a mix of energy resources at a societally acceptable and affordable cost within a realistic planning horizon. This must be the theme for the globally applicable energy sources that are compatible with the Earth's ecology. It is in this context that lunar resources development should be a primary goal for science missions to the Moon, and for establishing an expanding human presence. The economic viability and commercial business potential of mining, extracting, manufacturing, and transporting lunar resource based materials to Earth, Earth orbits, and to undertake macroengineering projects on the Moon remains to be demonstrated. These extensive activities will be supportive of the realization of the potential of space energy sources for use on Earth. These may include generating electricity for use on Earth based on beaming power from Earth orbits and from the Moon to the Earth, and for the production of helium 3 as a fuel for advanced fusion reactors.

Energy for lunar resource exploitation

NASA Technical Reports Server (NTRS)

Glaser, Peter E.

1992-01-01

Humanity stands at the threshold of exploiting the known lunar resources that have opened up with the access to space. America's role in the future exploitation of space, and specifically of lunar resources, may well determine the level of achievement in technology development and global economic competition. Space activities during the coming decades will significantly influence the events on Earth. The 'shifting of history's tectonic plates' is a process that will be hastened by the increasingly insistent demands for higher living standards of the exponentially growing global population. Key to the achievement of a peaceful world in the 21st century, will be the development of a mix of energy resources at a societally acceptable and affordable cost within a realistic planning horizon. This must be the theme for the globally applicable energy sources that are compatible with the Earth's ecology. It is in this context that lunar resources development should be a primary goal for science missions to the Moon, and for establishing an expanding human presence. The economic viability and commercial business potential of mining, extracting, manufacturing, and transporting lunar resource based materials to Earth, Earth orbits, and to undertake macroengineering projects on the Moon remains to be demonstrated. These extensive activities will be supportive of the realization of the potential of space energy sources for use on Earth. These may include generating electricity for use on Earth based on beaming power from Earth orbits and from the Moon to the Earth, and for the production of helium 3 as a fuel for advanced fusion reactors.

The Lion King and the Hyaena Queen: large carnivore interactions and coexistence.

PubMed

Périquet, Stéphanie; Fritz, Hervé; Revilla, Eloy

2015-11-01

Interactions among species, which range from competition to facilitation, have profound effects on ecosystem functioning. Large carnivores are of particular importance in shaping community structure since they are at the top of the food chain, and many efforts are made to conserve such keystone species. Despite this, the mechanisms of carnivore interactions are far from understood, yet they are key to enabling or hindering their coexistence and hence are highly relevant for their conservation. The goal of this review is thus to provide detailed information on the extents of competition and facilitation between large carnivores and their impact in shaping their life histories. Here, we use the example of spotted hyaenas (Crocuta crocuta) and lions (Panthera leo) and provide a comprehensive knowledge of their interactions based on meta-analyses from available literature (148 publications). Despite their strong potential for both exploitation and interference competition (range and diet overlap, intraguild predation and kleptoparasitism), we underline some mechanisms facilitating their coexistence (different prey-age selection and scavenging opportunities). We stress the fact that prey abundance is key to their coexistence and that hyaenas forming very large groups in rich ecosystems could have a negative impact on lions. We show that the coexistence of spotted hyaenas and lions is a complex balance between competition and facilitation, and that prey availability within the ecosystem determines which predator is dominant. However, there are still many gaps in our knowledge such as the spatio-temporal dynamics of their interactions. As both species' survival becomes increasingly dependent on protected areas, where their densities can be high, it is critical to understand their interactions to inform both reintroduction programs and protected area management. © 2014 Cambridge Philosophical Society.

Indirect effects of phorid fly parasitoids on the mechanisms of interspecific competition among ants.

PubMed

Morrison, Lloyd W

1999-10-01

Indirect effects, which occur when the impact of one species upon another requires the existence of an intermediary species, are apparently very common and may be of greater magnitude than direct effects. Behaviorally mediated indirect effects occur when one species affects the behavior of a second, which in turn affects how that species interacts with a third. I studied behaviorally mediated indirect effects on the mechanisms of competition in two congeneric fire ant species in the presence and absence of parasitoid phorid flies, which parasitized only one ant species. In observational and experimental field studies, the presence of native Texas phorid flies in the genus Pseudacteon decreased food retrieval by their host, Solenopsis geminata (F.), by as much as 50%. In the presence of phorid flies, many S. geminata workers assumed a stationary, curled defensive posture and did not forage. Although the phorid parasitoids had a relatively large effect on exploitative competition, there was no measurable effect on interference competition. Fierce interspecific aggression was observed between S. geminata and S. invicta Buren, and the presence of phorids had no effect on the outcome of these contests. The indirect effects of Pseudacteon parasitoids on Solenopsis fire ant resource retrieval appear to be larger than the direct effect of mortality. Some aspects of the foraging behavior of these Solenopsis species may be, in part, evolutionary adaptations to phorid parasitoid pressure. Because of the relatively large indirect effects, South American Pseudacteon phorids may be promising biocontrol agents of imported fire ants, S. invicta, in the USA. In a laboratory study, a single South American Pseudacteon female was able to significantly decrease food retrieval rates of a North American population of the imported fire ant, S. invicta.

Competitive Traits Are More Important than Stress-Tolerance Traits in a Cadmium-Contaminated Rhizosphere: A Role for Trait Theory in Microbial Ecology.

PubMed

Wood, Jennifer L; Tang, Caixian; Franks, Ashley E

2018-01-01

Understanding how biotic and abiotic factors govern the assembly of rhizosphere-microbial communities is a long-standing goal in microbial ecology. In phytoremediation research, where plants are used to remediate heavy metal-contaminated soils, a deeper understanding of rhizosphere-microbial ecology is needed to fully exploit the potential of microbial-assisted phytoremediation. This study investigated whether Grime's competitor/stress-tolerator/ruderal (CSR) theory could be used to describe the impact of cadmium (Cd) and the presence of a Cd-accumulating plant, Carpobrotus rossii (Haw.) Schwantes, on the assembly of soil-bacterial communities using Illumina 16S rRNA profiling and the predictive metagenomic-profiling program, PICRUSt. Using predictions based on CSR theory, we hypothesized that Cd and the presence of a rhizosphere would affect community assembly. We predicted that the additional resource availability in the rhizosphere would enrich for competitive life strategists, while the presence of Cd would select for stress-tolerators. Traits identified as competitive followed CSR predictions, discriminating between rhizosphere and bulk-soil communities whilst stress-tolerance traits increased with Cd dose, but only in bulk-soil communities. These findings suggest that a bacterium's competitive attributes are critical to its ability to occupy and proliferate in a Cd-contaminated rhizosphere. Ruderal traits, which relate to community re-colonization potential, were synergistically decreased by the presence of the rhizosphere and Cd dose. Taken together this microcosm study suggests that the CSR theory is broadly applicable to microbial communities. Further work toward developing a simplified and robust strategy for microbial CSR classification will provide an ecologically meaningful framework to interpret community-level changes across a range of biomes.

Size- and food-dependent growth drives patterns of competitive dominance along productivity gradients.

PubMed

Huss, Magnus; Gårdmark, Anna; Van Leeuwen, Anieke; de Roos, André M

2012-04-01

Patterns of coexistence among competing species exhibiting size- and food-dependent growth remain largely unexplored. Here we studied mechanisms behind coexistence and shifts in competitive dominance in a size-structured fish guild, representing sprat and herring stocks in the Baltic Sea, using a physiologically structured model of competing populations. The influence of degree of resource overlap and the possibility of undergoing ontogenetic diet shifts were studied as functions of zooplankton and zoobenthos productivity. By imposing different size-dependent mortalities, we could study the outcome of competition under contrasting environmental regimes representing poor and favorable growth conditions. We found that the identity of the dominant species shifted between low and high productivity. Adding a herring-exclusive benthos resource only provided a competitive advantage over sprat when size-dependent mortality was high enough to allow for rapid growth in the zooplankton niche. Hence, the importance of a bottom-up effect of varying productivity was dependent on a strong top-down effect. Although herring could depress shared resources to lower levels than could sprat and also could access an exclusive resource, the smaller size at maturation of sprat allowed it to coexist with herring and, in some cases, exclude it. Our model system, characterized by interactions among size cohorts, allowed for consumer coexistence even at full resource overlap at intermediate productivities when size-dependent mortality was low. Observed shifts in community patterns were crucially dependent on the explicit consideration of size- and food-dependent growth. Accordingly, we argue that accounting for food-dependent growth and size-dependent interactions is necessary to better predict changes in community structure and dynamics following changes in major ecosystem drivers such as resource productivity and mortality, which are fundamental for our ability to manage exploitation of living resources in, e.g., fisheries.

Non-local competition drives both rapid divergence and prolonged stasis in a model of speciation in populations with degenerate resource consumption

PubMed Central

2012-01-01

The theory of speciation is dominated by adaptationist thinking, with less attention to mechanisms that do not affect species adaptation. Degeneracy – the imperfect specificity of interactions between diverse elements of biological systems and their environments – is key to the adaptability of populations. A mathematical model was explored in which population and resource were distributed one-dimensionally according to trait value. Resource consumption was degenerate – neither strictly location-specific nor location-independent. As a result, the competition for resources among the elements of the population was non-local. Two modeling approaches, a modified differential-integral Verhulstian equation and a cellular automata model, showed similar results: narrower degeneracy led to divergent dynamics with suppression of intermediate forms, whereas broader degeneracy led to suppression of diversifying forms, resulting in population stasis with increasing phenotypic homogeneity. Such behaviors did not increase overall adaptation because they continued after the model populations achieved maximal resource consumption rates, suggesting that degeneracy-driven distributed competition for resources rather than selective pressure toward more efficient resource exploitation was the driving force. The solutions were stable in the presence of limited environmental stochastic variability or heritable phenotypic variability. A conclusion was made that both dynamic diversification and static homogeneity of populations may be outcomes of the same process – distributed competition for resource not affecting the overall adaptation – with the difference between them defined by the spread of trait degeneracy in a given environment. Thus, biological degeneracy is a driving force of both speciation and stasis in biology, which, by themselves, are not necessarily adaptive in nature. PMID:23268831

Interactions among filamentous fungi Aspergillus niger, Fusarium verticillioides and Clonostachys rosea: fungal biomass, diversity of secreted metabolites and fumonisin production.

PubMed

Chatterjee, Subhankar; Kuang, Yi; Splivallo, Richard; Chatterjee, Paramita; Karlovsky, Petr

2016-05-10

Interactions among fungi colonizing dead organic matter involve exploitation competition and interference competition. Major mechanism of interference competition is antibiosis caused by secreted secondary metabolites. The effect of competition on secondary metabolite production by fungi is however poorly understood. Fungal biomass was rarely monitored in interaction studies; it is not known whether dominance in pairwise interactions follows congruent patterns. Pairwise interactions of three fungal species with different life styles were studied. The saprophyte Aspergillus niger (A.n.), the plant pathogen Fusarium verticillioides (F.v.), and the mycoparasite Clonostachys rosea (C.r.) were grown in single and dual cultures in minimal medium with asparagine as nitrogen source. Competitive fitness shifted with time: in dual C.r./F.v. cultures after 10 d F.v. grew well while C.r. was suppressed; after 20 d C.r. recovered while F.v. became suppressed; and after 30 d most F.v. was destroyed. At certain time points fungal competitive fitness exhibited a rock-paper-scissors pattern: F.v. > A.n., A.n. > C.r., and C.r. > F.v. Most metabolites secreted to the medium at early stages in single and dual cultures were not found at later times. Many metabolites occurring in supernatants of single cultures were suppressed in dual cultures and many new metabolites not occurring in single cultures were found in dual cultures. A. niger showed the greatest ability to suppress the accumulation of metabolites produced by the other fungi. A. niger was also the species with the largest capacity of transforming metabolites produced by other fungi. Fumonisin production by F. verticillioides was suppressed in co-cultures with C. rosea but fumonisin B1 was not degraded by C. rosea nor did it affect the growth of C. rosea up to a concentration of 160 μg/ml. Competitive fitness in pairwise interactions among fungi is incongruent, indicating that species-specific factors and/or effects are involved. Many metabolites secreted by fungi are catabolized by their producers at later growth stages. Diversity of metabolites accumulating in the medium is stimulated by fungus/fungus interactions. C. rosea suppresses the synthesis of fumonisins by F. verticillioides but does not degrade fumonisins.