WorldWideScience

Sample records for complex transcriptional landscape

  1. The transcriptional landscape

    DEFF Research Database (Denmark)

    Nielsen, Henrik

    2011-01-01

    The application of new and less biased methods to study the transcriptional output from genomes, such as tiling arrays and deep sequencing, has revealed that most of the genome is transcribed and that there is substantial overlap of transcripts derived from the two strands of DNA. In protein coding...... regions, the map of transcripts is very complex due to small transcripts from the flanking ends of the transcription unit, the use of multiple start and stop sites for the main transcript, production of multiple functional RNA molecules from the same primary transcript, and RNA molecules made...... by independent transcription from within the unit. In genomic regions separating those that encode proteins or highly abundant RNA molecules with known function, transcripts are generally of low abundance and short-lived. In most of these cases, it is unclear to what extent a function is related to transcription...

  2. Appropriate complexity landscape modeling

    NARCIS (Netherlands)

    Larsen, Laurel G.; Eppinga, Maarten B.; Passalacqua, Paola; Getz, Wayne M.; Rose, Kenneth A.; Liang, Man

    Advances in computing technology, new and ongoing restoration initiatives, concerns about climate change's effects, and the increasing interdisciplinarity of research have encouraged the development of landscape-scale mechanistic models of coupled ecological-geophysical systems. However,

  3. Transcriptional landscape estimation from tiling array data using a model of signal shift and drift

    DEFF Research Database (Denmark)

    Rasmussen, Simon; Jarmer, Hanne Østergaard; Nicolas, P

    2009-01-01

    MOTIVATION: High-density oligonucleotide tiling array technology holds the promise of a better description of the complexity and the dynamics of transcriptional landscapes. In organisms such as bacteria and yeasts, transcription can be measured on a genome-wide scale with a resolution >25 bp...

  4. Structural insights into transcription complexes

    NARCIS (Netherlands)

    Berger, I.; Blanco, A.G.; Boelens, R.; Cavarelli, J.; Coll, M.; Folkers, G.E.; Nie, Y.; Pogenberg, V.; Schultz, P.; Wilmanns, M.; Moras, D.; Poterszman, A.

    2011-01-01

    Control of transcription allows the regulation of cell activity in response to external stimuli and research in the field has greatly benefited from efforts in structural biology. In this review, based on specific examples from the European SPINE2-COMPLEXES initiative, we illustrate the impact of

  5. Transcriptional landscape of Mycobacterium tuberculosis infection in macrophages

    KAUST Repository

    Roy, Sugata

    2018-04-24

    Mycobacterium tuberculosis (Mtb) infection reveals complex and dynamic host-pathogen interactions, leading to host protection or pathogenesis. Using a unique transcriptome technology (CAGE), we investigated the promoter-based transcriptional landscape of IFNγ (M1) or IL-4/IL-13 (M2) stimulated macrophages during Mtb infection in a time-kinetic manner. Mtb infection widely and drastically altered macrophage-specific gene expression, which is far larger than that of M1 or M2 activations. Gene Ontology enrichment analysis for Mtb-induced differentially expressed genes revealed various terms, related to host-protection and inflammation, enriched in up-regulated genes. On the other hand, terms related to dis-regulation of cellular functions were enriched in down-regulated genes. Differential expression analysis revealed known as well as novel transcription factor genes in Mtb infection, many of them significantly down-regulated. IFNγ or IL-4/IL-13 pre-stimulation induce additional differentially expressed genes in Mtb-infected macrophages. Cluster analysis uncovered significant numbers, prolonging their expressional changes. Furthermore, Mtb infection augmented cytokine-mediated M1 and M2 pre-activations. In addition, we identified unique transcriptional features of Mtb-mediated differentially expressed lncRNAs. In summary we provide a comprehensive in depth gene expression/regulation profile in Mtb-infected macrophages, an important step forward for a better understanding of host-pathogen interaction dynamics in Mtb infection.

  6. Transcriptional landscape of glomerular parietal epithelial cells.

    Directory of Open Access Journals (Sweden)

    Sina A Gharib

    Full Text Available Very little is known about the function of glomerular parietal epithelial cells (PECs. In this study, we performed genome-wide expression analysis on PEC-enriched capsulated vs. PEC-deprived decapsulated rat glomeruli to determine the transcriptional state of PECs under normal conditions. We identified hundreds of differentially expressed genes that mapped to distinct biologic modules including development, tight junction, ion transport, and metabolic processes. Since developmental programs were highly enriched in PECs, we characterized several of their candidate members at the protein level. Collectively, our findings confirm that PECs are multifaceted cells and help define their diverse functional repertoire.

  7. Transcriptional landscapes of Axolotl (Ambystoma mexicanum).

    Science.gov (United States)

    Caballero-Pérez, Juan; Espinal-Centeno, Annie; Falcon, Francisco; García-Ortega, Luis F; Curiel-Quesada, Everardo; Cruz-Hernández, Andrés; Bako, Laszlo; Chen, Xuemei; Martínez, Octavio; Alberto Arteaga-Vázquez, Mario; Herrera-Estrella, Luis; Cruz-Ramírez, Alfredo

    2018-01-15

    The axolotl (Ambystoma mexicanum) is the vertebrate model system with the highest regeneration capacity. Experimental tools established over the past 100 years have been fundamental to start unraveling the cellular and molecular basis of tissue and limb regeneration. In the absence of a reference genome for the Axolotl, transcriptomic analysis become fundamental to understand the genetic basis of regeneration. Here we present one of the most diverse transcriptomic data sets for Axolotl by profiling coding and non-coding RNAs from diverse tissues. We reconstructed a population of 115,906 putative protein coding mRNAs as full ORFs (including isoforms). We also identified 352 conserved miRNAs and 297 novel putative mature miRNAs. Systematic enrichment analysis of gene expression allowed us to identify tissue-specific protein-coding transcripts. We also found putative novel and conserved microRNAs which potentially target mRNAs which are reported as important disease candidates in heart and liver. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Dataset of transcriptional landscape of B cell early activation

    Directory of Open Access Journals (Sweden)

    Alexander S. Garruss

    2015-09-01

    Full Text Available Signaling via B cell receptors (BCR and Toll-like receptors (TLRs result in activation of B cells with distinct physiological outcomes, but transcriptional regulatory mechanisms that drive activation and distinguish these pathways remain unknown. At early time points after BCR and TLR ligand exposure, 0.5 and 2 h, RNA-seq was performed allowing observations on rapid transcriptional changes. At 2 h, ChIP-seq was performed to allow observations on important regulatory mechanisms potentially driving transcriptional change. The dataset includes RNA-seq, ChIP-seq of control (Input, RNA Pol II, H3K4me3, H3K27me3, and a separate RNA-seq for miRNA expression, which can be found at Gene Expression Omnibus Dataset GSE61608. Here, we provide details on the experimental and analysis methods used to obtain and analyze this dataset and to examine the transcriptional landscape of B cell early activation.

  9. Transcription regulation by the Mediator complex.

    Science.gov (United States)

    Soutourina, Julie

    2018-04-01

    Alterations in the regulation of gene expression are frequently associated with developmental diseases or cancer. Transcription activation is a key phenomenon in the regulation of gene expression. In all eukaryotes, mediator of RNA polymerase II transcription (Mediator), a large complex with modular organization, is generally required for transcription by RNA polymerase II, and it regulates various steps of this process. The main function of Mediator is to transduce signals from the transcription activators bound to enhancer regions to the transcription machinery, which is assembled at promoters as the preinitiation complex (PIC) to control transcription initiation. Recent functional studies of Mediator with the use of structural biology approaches and functional genomics have revealed new insights into Mediator activity and its regulation during transcription initiation, including how Mediator is recruited to transcription regulatory regions and how it interacts and cooperates with PIC components to assist in PIC assembly. Novel roles of Mediator in the control of gene expression have also been revealed by showing its connection to the nuclear pore and linking Mediator to the regulation of gene positioning in the nuclear space. Clear links between Mediator subunits and disease have also encouraged studies to explore targeting of this complex as a potential therapeutic approach in cancer and fungal infections.

  10. The Mediator complex and transcription regulation

    Science.gov (United States)

    Poss, Zachary C.; Ebmeier, Christopher C.

    2013-01-01

    The Mediator complex is a multi-subunit assembly that appears to be required for regulating expression of most RNA polymerase II (pol II) transcripts, which include protein-coding and most non-coding RNA genes. Mediator and pol II function within the pre-initiation complex (PIC), which consists of Mediator, pol II, TFIIA, TFIIB, TFIID, TFIIE, TFIIF and TFIIH and is approximately 4.0 MDa in size. Mediator serves as a central scaffold within the PIC and helps regulate pol II activity in ways that remain poorly understood. Mediator is also generally targeted by sequence-specific, DNA-binding transcription factors (TFs) that work to control gene expression programs in response to developmental or environmental cues. At a basic level, Mediator functions by relaying signals from TFs directly to the pol II enzyme, thereby facilitating TF-dependent regulation of gene expression. Thus, Mediator is essential for converting biological inputs (communicated by TFs) to physiological responses (via changes in gene expression). In this review, we summarize an expansive body of research on the Mediator complex, with an emphasis on yeast and mammalian complexes. We focus on the basics that underlie Mediator function, such as its structure and subunit composition, and describe its broad regulatory influence on gene expression, ranging from chromatin architecture to transcription initiation and elongation, to mRNA processing. We also describe factors that influence Mediator structure and activity, including TFs, non-coding RNAs and the CDK8 module. PMID:24088064

  11. Aridity and decomposition processes in complex landscapes

    Science.gov (United States)

    Ossola, Alessandro; Nyman, Petter

    2015-04-01

    Decomposition of organic matter is a key biogeochemical process contributing to nutrient cycles, carbon fluxes and soil development. The activity of decomposers depends on microclimate, with temperature and rainfall being major drivers. In complex terrain the fine-scale variation in microclimate (and hence water availability) as a result of slope orientation is caused by differences in incoming radiation and surface temperature. Aridity, measured as the long-term balance between net radiation and rainfall, is a metric that can be used to represent variations in water availability within the landscape. Since aridity metrics can be obtained at fine spatial scales, they could theoretically be used to investigate how decomposition processes vary across complex landscapes. In this study, four research sites were selected in tall open sclerophyll forest along a aridity gradient (Budyko dryness index ranging from 1.56 -2.22) where microclimate, litter moisture and soil moisture were monitored continuously for one year. Litter bags were packed to estimate decomposition rates (k) using leaves of a tree species not present in the study area (Eucalyptus globulus) in order to avoid home-field advantage effects. Litter mass loss was measured to assess the activity of macro-decomposers (6mm litter bag mesh size), meso-decomposers (1 mm mesh), microbes above-ground (0.2 mm mesh) and microbes below-ground (2 cm depth, 0.2 mm mesh). Four replicates for each set of bags were installed at each site and bags were collected at 1, 2, 4, 7 and 12 months since installation. We first tested whether differences in microclimate due to slope orientation have significant effects on decomposition processes. Then the dryness index was related to decomposition rates to evaluate if small-scale variation in decomposition can be predicted using readily available information on rainfall and radiation. Decomposition rates (k), calculated fitting single pool negative exponential models, generally

  12. Transcription initiation complex structures elucidate DNA opening.

    Science.gov (United States)

    Plaschka, C; Hantsche, M; Dienemann, C; Burzinski, C; Plitzko, J; Cramer, P

    2016-05-19

    Transcription of eukaryotic protein-coding genes begins with assembly of the RNA polymerase (Pol) II initiation complex and promoter DNA opening. Here we report cryo-electron microscopy (cryo-EM) structures of yeast initiation complexes containing closed and open DNA at resolutions of 8.8 Å and 3.6 Å, respectively. DNA is positioned and retained over the Pol II cleft by a network of interactions between the TATA-box-binding protein TBP and transcription factors TFIIA, TFIIB, TFIIE, and TFIIF. DNA opening occurs around the tip of the Pol II clamp and the TFIIE 'extended winged helix' domain, and can occur in the absence of TFIIH. Loading of the DNA template strand into the active centre may be facilitated by movements of obstructing protein elements triggered by allosteric binding of the TFIIE 'E-ribbon' domain. The results suggest a unified model for transcription initiation with a key event, the trapping of open promoter DNA by extended protein-protein and protein-DNA contacts.

  13. Sequence2Vec: A novel embedding approach for modeling transcription factor binding affinity landscape

    KAUST Repository

    Dai, Hanjun; Umarov, Ramzan; Kuwahara, Hiroyuki; Li, Yu; Song, Le; Gao, Xin

    2017-01-01

    Motivation: An accurate characterization of transcription factor (TF)-DNA affinity landscape is crucial to a quantitative understanding of the molecular mechanisms underpinning endogenous gene regulation. While recent advances in biotechnology have

  14. Calculation of Configurational Entropy in Complex Landscapes

    Directory of Open Access Journals (Sweden)

    Samuel A Cushman

    2018-04-01

    Full Text Available Entropy and the second law of thermodynamics are fundamental concepts that underlie all natural processes and patterns. Recent research has shown how the entropy of a landscape mosaic can be calculated using the Boltzmann equation, with the entropy of a lattice mosaic equal to the logarithm of the number of ways a lattice with a given dimensionality and number of classes can be arranged to produce the same total amount of edge between cells of different classes. However, that work seemed to also suggest that the feasibility of applying this method to real landscapes was limited due to intractably large numbers of possible arrangements of raster cells in large landscapes. Here I extend that work by showing that: (1 the proportion of arrangements rather than the number with a given amount of edge length provides a means to calculate unbiased relative configurational entropy, obviating the need to compute all possible configurations of a landscape lattice; (2 the edge lengths of randomized landscape mosaics are normally distributed, following the central limit theorem; and (3 given this normal distribution it is possible to fit parametric probability density functions to estimate the expected proportion of randomized configurations that have any given edge length, enabling the calculation of configurational entropy on any landscape regardless of size or number of classes. I evaluate the boundary limits (4 for this normal approximation for small landscapes with a small proportion of a minority class and show it holds under all realistic landscape conditions. I further (5 demonstrate that this relationship holds for a sample of real landscapes that vary in size, patch richness, and evenness of area in each cover type, and (6 I show that the mean and standard deviation of the normally distributed edge lengths can be predicted nearly perfectly as a function of the size, patch richness and diversity of a landscape. Finally, (7 I show that the

  15. Natural enemy interactions constrain pest control in complex agricultural landscapes.

    Science.gov (United States)

    Martin, Emily A; Reineking, Björn; Seo, Bumsuk; Steffan-Dewenter, Ingolf

    2013-04-02

    Biological control of pests by natural enemies is a major ecosystem service delivered to agriculture worldwide. Quantifying and predicting its effectiveness at large spatial scales is critical for increased sustainability of agricultural production. Landscape complexity is known to benefit natural enemies, but its effects on interactions between natural enemies and the consequences for crop damage and yield are unclear. Here, we show that pest control at the landscape scale is driven by differences in natural enemy interactions across landscapes, rather than by the effectiveness of individual natural enemy guilds. In a field exclusion experiment, pest control by flying insect enemies increased with landscape complexity. However, so did antagonistic interactions between flying insects and birds, which were neutral in simple landscapes and increasingly negative in complex landscapes. Negative natural enemy interactions thus constrained pest control in complex landscapes. These results show that, by altering natural enemy interactions, landscape complexity can provide ecosystem services as well as disservices. Careful handling of the tradeoffs among multiple ecosystem services, biodiversity, and societal concerns is thus crucial and depends on our ability to predict the functional consequences of landscape-scale changes in trophic interactions.

  16. Transcriptional landscape of Mycobacterium tuberculosis infection in macrophages

    KAUST Repository

    Roy, Sugata; Schmeier, Sebastian; Kaczkowski, Bogumil; Arner, Erik; Alam, Tanvir; Ozturk, Mumin; Tamgue, Ousman; Parihar, Suraj P.; Kawaji, Hideya; Itoh, Masayoshi; Lassmann, Timo; Carninci, Piero; Hayashizaki, Yoshihide; Forrest, Alistair R. R.; Guler, Reto; Bajic, Vladimir B.; Brombacher, Frank; Suzuki, Harukazu

    2018-01-01

    landscape of IFNγ (M1) or IL-4/IL-13 (M2) stimulated macrophages during Mtb infection in a time-kinetic manner. Mtb infection widely and drastically altered macrophage-specific gene expression, which is far larger than that of M1 or M2 activations. Gene

  17. Landscape of transcriptional deregulations in the preeclamptic placenta.

    Directory of Open Access Journals (Sweden)

    Daniel Vaiman

    Full Text Available Preeclampsia is a pregnancy disease affecting 5 to 8% of pregnant women and a leading cause of both maternal and fetal mortality and morbidity. Because of a default in the process of implantation, the placenta of preeclamptic women undergoes insufficient vascularization. This results in placental ischemia, inflammation and subsequent release of placental debris and vasoactive factors in the maternal circulation causing a systemic endothelial activation. Several microarray studies have analyzed the transcriptome of the preeclamptic placentas to identify genes which could be involved in placental dysfunction. In this study, we compared the data from publicly available microarray analyses to obtain a consensus list of modified genes. This allowed to identify consistently modified genes in the preeclamptic placenta. Of these, 67 were up-regulated and 31 down-regulated. Assuming that changes in the transcription level of co-expressed genes may result from the coordinated action of a limited number of transcription factors, we looked for over-represented putative transcription factor binding sites in the promoters of these genes. Indeed, we found that the promoters of up-regulated genes are enriched in putative binding sites for NFkB, CREB, ANRT, REEB1, SP1, and AP-2. In the promoters of down-regulated genes, the most prevalent putative binding sites are those of MZF-1, NFYA, E2F1 and MEF2A. These transcriptions factors are known to regulate specific biological pathways such as cell responses to inflammation, hypoxia, DNA damage and proliferation. We discuss here the molecular mechanisms of action of these transcription factors and how they can be related to the placental dysfunction in the context of preeclampsia.

  18. The transcriptional landscape of hematopoietic stem cell ontogeny

    Science.gov (United States)

    McKinney-Freeman, Shannon; Cahan, Patrick; Li, Hu; Lacadie, Scott A.; Huang, Hsuan-Ting; Curran, Matthew; Loewer, Sabine; Naveiras, Olaia; Kathrein, Katie L.; Konantz, Martina; Langdon, Erin M.; Lengerke, Claudia; Zon, Leonard I.; Collins, James J.; Daley, George Q.

    2012-01-01

    Transcriptome analysis of adult hematopoietic stem cells (HSC) and their progeny has revealed mechanisms of blood differentiation and leukemogenesis, but a similar analysis of HSC development is lacking. Here, we acquired the transcriptomes of developing HSC purified from >2500 murine embryos and adult mice. We found that embryonic hematopoietic elements clustered into three distinct transcriptional states characteristic of the definitive yolk sac, HSCs undergoing specification, and definitive HSCs. We applied a network biology-based analysis to reconstruct the gene regulatory networks of sequential stages of HSC development and functionally validated candidate transcriptional regulators of HSC ontogeny by morpholino-mediated knock-down in zebrafish embryos. Moreover, we found that HSCs from in vitro differentiated embryonic stem cells closely resemble definitive HSC, yet lack a Notch-signaling signature, likely accounting for their defective lymphopoiesis. Our analysis and web resource (http://hsc.hms.harvard.edu) will enhance efforts to identify regulators of HSC ontogeny and facilitate the engineering of hematopoietic specification. PMID:23122293

  19. The Transcriptional Landscape of the Production Organism Pseudomonas putida

    DEFF Research Database (Denmark)

    D'Arrigo, Isotta

    Bacterial cell factories represent a valid alternative to fossil fuel-based production. A promising bacterium that can be optimized as cell factory is Pseudomonas putida. However, its development in bioproduction applications poses some challenges including a clear understanding of the bacterial...... system biology. This thesis has the aim of facilitating the development of P. putida KT2440 as a bacterial cell factory by investigating the transcriptome of the bacterium under different conditions (e.g. growth and stress). The main goals are the identification of differentially expressed genes, which...... provide information on bacterial adaptation to different environments, and the identification of non-coding RNAs, which regulate gene expression. This work focuses on several aspects of P. putida highlighting genomic features such as transcription start sites (TSSs), RNA regulatory elements...

  20. Plant Mediator complex and its critical functions in transcription regulation.

    Science.gov (United States)

    Yang, Yan; Li, Ling; Qu, Li-Jia

    2016-02-01

    The Mediator complex is an important component of the eukaryotic transcriptional machinery. As an essential link between transcription factors and RNA polymerase II, the Mediator complex transduces diverse signals to genes involved in different pathways. The plant Mediator complex was recently purified and comprises conserved and specific subunits. It functions in concert with transcription factors to modulate various responses. In this review, we summarize the recent advances in understanding the plant Mediator complex and its diverse roles in plant growth, development, defense, non-coding RNA production, response to abiotic stresses, flowering, genomic stability and metabolic homeostasis. In addition, the transcription factors interacting with the Mediator complex are also highlighted. © 2015 Institute of Botany, Chinese Academy of Sciences.

  1. Inferring the transcriptional landscape of bovine skeletal muscle by integrating co-expression networks.

    Directory of Open Access Journals (Sweden)

    Nicholas J Hudson

    Full Text Available BACKGROUND: Despite modern technologies and novel computational approaches, decoding causal transcriptional regulation remains challenging. This is particularly true for less well studied organisms and when only gene expression data is available. In muscle a small number of well characterised transcription factors are proposed to regulate development. Therefore, muscle appears to be a tractable system for proposing new computational approaches. METHODOLOGY/PRINCIPAL FINDINGS: Here we report a simple algorithm that asks "which transcriptional regulator has the highest average absolute co-expression correlation to the genes in a co-expression module?" It correctly infers a number of known causal regulators of fundamental biological processes, including cell cycle activity (E2F1, glycolysis (HLF, mitochondrial transcription (TFB2M, adipogenesis (PIAS1, neuronal development (TLX3, immune function (IRF1 and vasculogenesis (SOX17, within a skeletal muscle context. However, none of the canonical pro-myogenic transcription factors (MYOD1, MYOG, MYF5, MYF6 and MEF2C were linked to muscle structural gene expression modules. Co-expression values were computed using developing bovine muscle from 60 days post conception (early foetal to 30 months post natal (adulthood for two breeds of cattle, in addition to a nutritional comparison with a third breed. A number of transcriptional landscapes were constructed and integrated into an always correlated landscape. One notable feature was a 'metabolic axis' formed from glycolysis genes at one end, nuclear-encoded mitochondrial protein genes at the other, and centrally tethered by mitochondrially-encoded mitochondrial protein genes. CONCLUSIONS/SIGNIFICANCE: The new module-to-regulator algorithm complements our recently described Regulatory Impact Factor analysis. Together with a simple examination of a co-expression module's contents, these three gene expression approaches are starting to illuminate the in vivo

  2. Geomorphology and landscape organization of a northern peatland complex

    Science.gov (United States)

    Richardson, M. C.

    2012-12-01

    The geomorphic evolution of northern peatlands is governed by complex ecohydrological feedback mechanisms and associated hydro-climatic drivers. For example, prevailing models of bog development (i.e. Ingram's groundwater mounding hypothesis and variants) attempt to explicitly link bog dome characteristics to the regional climate based on analytical and numerical models of lateral groundwater flow and the first-order control of water table position on rates of peat accumulation. In this talk I will present new results from quantitative geomorphic analyses of a northern peatland complex at the De Beers Victor diamond mine site in the Hudson Bay Lowlands of northern Ontario. This work capitalizes on spatially-extensive, high-resolution topographic (LiDAR) data to rigorously test analytical and numerical models of bog dome development in this landscape. The analysis and discussion are then expanded beyond individual bog formations to more broadly consider ecohydrological drivers of landscape organization, with implications for understanding and modeling catchment-scale runoff response. Results show that in this landscape, drainage patterns exhibit relatively well-organized characteristics consistent with observed runoff responses in six gauged research catchments. Interpreted together, the results of these geomorphic and hydrologic analyses help refine our understanding of water balance partitioning among different landcover types within northern peatland complexes. These findings can be used to help guide the development of appropriate numerical model structures for hydrologic prediction in ungauged peatland basins of northern Canada.

  3. Sequence2Vec: A novel embedding approach for modeling transcription factor binding affinity landscape

    KAUST Repository

    Dai, Hanjun

    2017-07-26

    Motivation: An accurate characterization of transcription factor (TF)-DNA affinity landscape is crucial to a quantitative understanding of the molecular mechanisms underpinning endogenous gene regulation. While recent advances in biotechnology have brought the opportunity for building binding affinity prediction methods, the accurate characterization of TF-DNA binding affinity landscape still remains a challenging problem. Results: Here we propose a novel sequence embedding approach for modeling the transcription factor binding affinity landscape. Our method represents DNA binding sequences as a hidden Markov model (HMM) which captures both position specific information and long-range dependency in the sequence. A cornerstone of our method is a novel message passing-like embedding algorithm, called Sequence2Vec, which maps these HMMs into a common nonlinear feature space and uses these embedded features to build a predictive model. Our method is a novel combination of the strength of probabilistic graphical models, feature space embedding and deep learning. We conducted comprehensive experiments on over 90 large-scale TF-DNA data sets which were measured by different high-throughput experimental technologies. Sequence2Vec outperforms alternative machine learning methods as well as the state-of-the-art binding affinity prediction methods.

  4. A transcription factor collective defines the HSN serotonergic neuron regulatory landscape.

    Science.gov (United States)

    Lloret-Fernández, Carla; Maicas, Miren; Mora-Martínez, Carlos; Artacho, Alejandro; Jimeno-Martín, Ángela; Chirivella, Laura; Weinberg, Peter; Flames, Nuria

    2018-03-22

    Cell differentiation is controlled by individual transcription factors (TFs) that together activate a selection of enhancers in specific cell types. How these combinations of TFs identify and activate their target sequences remains poorly understood. Here, we identify the cis -regulatory transcriptional code that controls the differentiation of serotonergic HSN neurons in Caenorhabditis elegans . Activation of the HSN transcriptome is directly orchestrated by a collective of six TFs. Binding site clusters for this TF collective form a regulatory signature that is sufficient for de novo identification of HSN neuron functional enhancers. Among C. elegans neurons, the HSN transcriptome most closely resembles that of mouse serotonergic neurons. Mouse orthologs of the HSN TF collective also regulate serotonergic differentiation and can functionally substitute for their worm counterparts which suggests deep homology. Our results identify rules governing the regulatory landscape of a critically important neuronal type in two species separated by over 700 million years. © 2018, Lloret-Fernández et al.

  5. Fitness landscape complexity and the emergence of modularity in neural networks

    Science.gov (United States)

    Lowell, Jessica

    Previous research has shown that the shape of the fitness landscape can affect the evolution of modularity. We evolved neural networks to solve different tasks with different fitness landscapes, using NEAT, a popular neuroevolution algorithm that quantifies similarity between genomes in order to divide them into species. We used this speciation mechanism as a means to examine fitness landscape complexity, and to examine connections between fitness landscape complexity and the emergence of modularity.

  6. Dissection of combinatorial control by the Met4 transcriptional complex.

    Science.gov (United States)

    Lee, Traci A; Jorgensen, Paul; Bognar, Andrew L; Peyraud, Caroline; Thomas, Dominique; Tyers, Mike

    2010-02-01

    Met4 is the transcriptional activator of the sulfur metabolic network in Saccharomyces cerevisiae. Lacking DNA-binding ability, Met4 must interact with proteins called Met4 cofactors to target promoters for transcription. Two types of DNA-binding cofactors (Cbf1 and Met31/Met32) recruit Met4 to promoters and one cofactor (Met28) stabilizes the DNA-bound Met4 complexes. To dissect this combinatorial system, we systematically deleted each category of cofactor(s) and analyzed Met4-activated transcription on a genome-wide scale. We defined a core regulon for Met4, consisting of 45 target genes. Deletion of both Met31 and Met32 eliminated activation of the core regulon, whereas loss of Met28 or Cbf1 interfered with only a subset of targets that map to distinct sectors of the sulfur metabolic network. These transcriptional dependencies roughly correlated with the presence of Cbf1 promoter motifs. Quantitative analysis of in vivo promoter binding properties indicated varying levels of cooperativity and interdependency exists between members of this combinatorial system. Cbf1 was the only cofactor to remain fully bound to target promoters under all conditions, whereas other factors exhibited different degrees of regulated binding in a promoter-specific fashion. Taken together, Met4 cofactors use a variety of mechanisms to allow differential transcription of target genes in response to various cues.

  7. Leaderless Transcripts and Small Proteins Are Common Features of the Mycobacterial Translational Landscape.

    Directory of Open Access Journals (Sweden)

    Scarlet S Shell

    2015-11-01

    Full Text Available RNA-seq technologies have provided significant insight into the transcription networks of mycobacteria. However, such studies provide no definitive information on the translational landscape. Here, we use a combination of high-throughput transcriptome and proteome-profiling approaches to more rigorously understand protein expression in two mycobacterial species. RNA-seq and ribosome profiling in Mycobacterium smegmatis, and transcription start site (TSS mapping and N-terminal peptide mass spectrometry in Mycobacterium tuberculosis, provide complementary, empirical datasets to examine the congruence of transcription and translation in the Mycobacterium genus. We find that nearly one-quarter of mycobacterial transcripts are leaderless, lacking a 5' untranslated region (UTR and Shine-Dalgarno ribosome-binding site. Our data indicate that leaderless translation is a major feature of mycobacterial genomes and is comparably robust to leadered initiation. Using translational reporters to systematically probe the cis-sequence requirements of leaderless translation initiation in mycobacteria, we find that an ATG or GTG at the mRNA 5' end is both necessary and sufficient. This criterion, together with our ribosome occupancy data, suggests that mycobacteria encode hundreds of small, unannotated proteins at the 5' ends of transcripts. The conservation of small proteins in both mycobacterial species tested suggests that some play important roles in mycobacterial physiology. Our translational-reporter system further indicates that mycobacterial leadered translation initiation requires a Shine Dalgarno site in the 5' UTR and that ATG, GTG, TTG, and ATT codons can robustly initiate translation. Our combined approaches provide the first comprehensive view of mycobacterial gene structures and their non-canonical mechanisms of protein expression.

  8. Malleable machines in transcription regulation: the mediator complex.

    Directory of Open Access Journals (Sweden)

    Agnes Tóth-Petróczy

    2008-12-01

    Full Text Available The Mediator complex provides an interface between gene-specific regulatory proteins and the general transcription machinery including RNA polymerase II (RNAP II. The complex has a modular architecture (Head, Middle, and Tail and cryoelectron microscopy analysis suggested that it undergoes dramatic conformational changes upon interactions with activators and RNAP II. These rearrangements have been proposed to play a role in the assembly of the preinitiation complex and also to contribute to the regulatory mechanism of Mediator. In analogy to many regulatory and transcriptional proteins, we reasoned that Mediator might also utilize intrinsically disordered regions (IDRs to facilitate structural transitions and transmit transcriptional signals. Indeed, a high prevalence of IDRs was found in various subunits of Mediator from both Saccharomyces cerevisiae and Homo sapiens, especially in the Tail and the Middle modules. The level of disorder increases from yeast to man, although in both organisms it significantly exceeds that of multiprotein complexes of a similar size. IDRs can contribute to Mediator's function in three different ways: they can individually serve as target sites for multiple partners having distinctive structures; they can act as malleable linkers connecting globular domains that impart modular functionality on the complex; and they can also facilitate assembly and disassembly of complexes in response to regulatory signals. Short segments of IDRs, termed molecular recognition features (MoRFs distinguished by a high protein-protein interaction propensity, were identified in 16 and 19 subunits of the yeast and human Mediator, respectively. In Saccharomyces cerevisiae, the functional roles of 11 MoRFs have been experimentally verified, and those in the Med8/Med18/Med20 and Med7/Med21 complexes were structurally confirmed. Although the Saccharomyces cerevisiae and Homo sapiens Mediator sequences are only weakly conserved, the

  9. Complexity of human and ecosystem interactions in an agricultural landscape

    Science.gov (United States)

    Coupe, Richard H.; Barlow, Jeannie R.; Capel, Paul D.

    2012-01-01

    The complexity of human interaction in the commercial agricultural landscape and the resulting impacts on the ecosystem services of water quality and quantity is largely ignored by the current agricultural paradigm that maximizes crop production over other ecosystem services. Three examples at different spatial scales (local, regional, and global) are presented where human and ecosystem interactions in a commercial agricultural landscape adversely affect water quality and quantity in unintended ways in the Delta of northwestern Mississippi. In the first example, little to no regulation of groundwater use for irrigation has caused declines in groundwater levels resulting in loss of baseflow to streams and threatening future water supply. In the second example, federal policy which subsidizes corn for biofuel production has encouraged many producers to switch from cotton to corn, which requires more nutrients and water, counter to national efforts to reduce nutrient loads to the Gulf of Mexico and exacerbating groundwater level declines. The third example is the wholesale adoption of a system for weed control that relies on a single chemical, initially providing many benefits and ultimately leading to the widespread occurrence of glyphosate and its degradates in Delta streams and necessitating higher application rates of glyphosate as well as the use of other herbicides due to increasing weed resistance. Although these examples are specific to the Mississippi Delta, analogous situations exist throughout the world and point to the need for change in how we grow our food, fuel, and fiber, and manage our soil and water resources.

  10. Genomic and transcriptional landscape of P2RY8-CRLF2-positive childhood acute lymphoblastic leukemia

    Science.gov (United States)

    Vesely, C; Frech, C; Eckert, C; Cario, G; Mecklenbräuker, A; zur Stadt, U; Nebral, K; Kraler, F; Fischer, S; Attarbaschi, A; Schuster, M; Bock, C; Cavé, H; von Stackelberg, A; Schrappe, M; Horstmann, M A; Mann, G; Haas, O A; Panzer-Grümayer, R

    2017-01-01

    Children with P2RY8-CRLF2-positive acute lymphoblastic leukemia have an increased relapse risk. Their mutational and transcriptional landscape, as well as the respective patterns at relapse remain largely elusive. We, therefore, performed an integrated analysis of whole-exome and RNA sequencing in 41 major clone fusion-positive cases including 19 matched diagnosis/relapse pairs. We detected a variety of frequently subclonal and highly instable JAK/STAT but also RTK/Ras pathway-activating mutations in 76% of cases at diagnosis and virtually all relapses. Unlike P2RY8-CRLF2 that was lost in 32% of relapses, all other genomic alterations affecting lymphoid development (58%) and cell cycle (39%) remained stable. Only IKZF1 alterations predominated in relapsing cases (P=0.001) and increased from initially 36 to 58% in matched cases. IKZF1’s critical role is further corroborated by its specific transcriptional signature comprising stem cell features with signs of impaired lymphoid differentiation, enhanced focal adhesion, activated hypoxia pathway, deregulated cell cycle and increased drug resistance. Our findings support the notion that P2RY8-CRLF2 is dispensable for relapse development and instead highlight the prominent rank of IKZF1 for relapse development by mediating self-renewal and homing to the bone marrow niche. Consequently, reverting aberrant IKAROS signaling or its disparate programs emerges as an attractive potential treatment option in these leukemias. PMID:27899802

  11. Sinks without borders: Snowshoe hare dynamics in a complex landscape

    Science.gov (United States)

    Griffin, Paul C.; Mills, L. Scott

    2009-01-01

    A full understanding of population dynamics of wide-ranging animals should account for the effects that movement and habitat use have on individual contributions to population growth or decline. Quantifying the per-capita, habitat-specific contribution to population growth can clarify the value of different patch types, and help to differentiate population sources from population sinks. Snowshoe hares, Lepus americanus, routinely use various habitat types in the landscapes they inhabit in the contiguous US, where managing forests for high snowshoe hare density is a priority for conservation of Canada lynx, Lynx canadensis. We estimated density and demographic rates via mark–recapture live trapping and radio-telemetry within four forest stand structure (FSS) types at three study areas within heterogeneous managed forests in western Montana. We found support for known fate survival models with time-varying individual covariates representing the proportion of locations in each of the FSS types, with survival rates decreasing as use of open young and open mature FSS types increased. The per-capita contribution to overall population growth increased with use of the dense mature or dense young FSS types and decreased with use of the open young or open mature FSS types, and relatively high levels of immigration appear to be necessary to sustain hares in the open FSS types. Our results support a conceptual model for snowshoe hares in the southern range in which sink habitats (open areas) prevent the buildup of high hare densities. More broadly, we use this system to develop a novel approach to quantify demographic sources and sinks for animals making routine movements through complex fragmented landscapes.

  12. Unravelling spatio-temporal evapotranspiration patterns in topographically complex landscapes

    Science.gov (United States)

    Metzen, Daniel; Sheridan, Gary; Nyman, Petter; Lane, Patrick

    2016-04-01

    Vegetation co-evolves with soils and topography under a given long-term climatic forcing. Previous studies demonstrated a strong eco-hydrologic feedback between topography, vegetation and energy and water fluxes. Slope orientation (aspect and gradient) alter the magnitude of incoming solar radiation resulting in larger evaporative losses and less water availability on equator-facing slopes. Furthermore, non-local water inputs from upslope areas potentially contribute to available water at downslope positions. The combined effect of slope orientation and drainage position creates complex spatial patterns in biological productivity and pedogenesis, which in turn alter the local hydrology. In complex upland landscapes, topographic alteration of incoming radiation can cause substantial aridity index (ratio of potential evapotranspiration to precipitation) variations over small spatial extents. Most of the upland forests in south-east Australia are located in an aridity index (AI) range of 1-2, around the energy limited to water limited boundary, where forested systems are expected to be most sensitive to AI changes. In this research we aim to improve the fundamental understanding of spatio-temporal evolution of evapotranspiration (ET) patterns in complex terrain, accounting for local topographic effects on system properties (e.g. soil depth, sapwood area, leaf area) and variation in energy and water exchange processes due to slope orientation and drainage position. Six measurement plots were set-up in a mixed species eucalypt forest on a polar and equatorial-facing hillslope (AI ˜1.3 vs. 1.8) at varying drainage position (ridge, mid-slope, gully), while minimizing variations in other factors, e.g. geology and weather patterns. Sap flow, soil water content, incoming solar radiation and throughfall were continuously monitored at field sites spanning a wide range of soil depth (0.5 - >3m), maximum tree heights (17 - 51m) and LAI (1.2 - 4.6). Site-specific response curves

  13. A meta-analysis of crop pest and natural enemy response to landscape complexity.

    Science.gov (United States)

    Chaplin-Kramer, Rebecca; O'Rourke, Megan E; Blitzer, Eleanor J; Kremen, Claire

    2011-09-01

    Many studies in recent years have investigated the relationship between landscape complexity and pests, natural enemies and/or pest control. However, no quantitative synthesis of this literature beyond simple vote-count methods yet exists. We conducted a meta-analysis of 46 landscape-level studies, and found that natural enemies have a strong positive response to landscape complexity. Generalist enemies show consistent positive responses to landscape complexity across all scales measured, while specialist enemies respond more strongly to landscape complexity at smaller scales. Generalist enemy response to natural habitat also tends to occur at larger spatial scales than for specialist enemies, suggesting that land management strategies to enhance natural pest control should differ depending on whether the dominant enemies are generalists or specialists. The positive response of natural enemies does not necessarily translate into pest control, since pest abundances show no significant response to landscape complexity. Very few landscape-scale studies have estimated enemy impact on pest populations, however, limiting our understanding of the effects of landscape on pest control. We suggest focusing future research efforts on measuring population dynamics rather than static counts to better characterise the relationship between landscape complexity and pest control services from natural enemies. © 2011 Blackwell Publishing Ltd/CNRS.

  14. Pest control of aphids depends on landscape complexity and natural enemy interactions.

    Science.gov (United States)

    Martin, Emily A; Reineking, Björn; Seo, Bumsuk; Steffan-Dewenter, Ingolf

    2015-01-01

    Aphids are a major concern in agricultural crops worldwide, and control by natural enemies is an essential component of the ecological intensification of agriculture. Although the complexity of agricultural landscapes is known to influence natural enemies of pests, few studies have measured the degree of pest control by different enemy guilds across gradients in landscape complexity. Here, we use multiple natural-enemy exclosures replicated in 18 fields across a gradient in landscape complexity to investigate (1) the strength of natural pest control across landscapes, measured as the difference between pest pressure in the presence and in the absence of natural enemies; (2) the differential contributions of natural enemy guilds to pest control, and the nature of their interactions across landscapes. We show that natural pest control of aphids increased up to six-fold from simple to complex landscapes. In the absence of pest control, aphid population growth was higher in complex than simple landscapes, but was reduced by natural enemies to similar growth rates across all landscapes. The effects of enemy guilds were landscape-dependent. Particularly in complex landscapes, total pest control was supplied by the combined contribution of flying insects and ground-dwellers. Birds had little overall impact on aphid control. Despite evidence for intraguild predation of flying insects by ground-dwellers and birds, the overall effect of enemy guilds on aphid control was complementary. Understanding pest control services at large spatial scales is critical to increase the success of ecological intensification schemes. Our results suggest that, where aphids are the main pest of concern, interactions between natural enemies are largely complementary and lead to a strongly positive effect of landscape complexity on pest control. Increasing the availability of seminatural habitats in agricultural landscapes may thus benefit not only natural enemies, but also the effectiveness of

  15. The Mediator complex: a central integrator of transcription

    Science.gov (United States)

    Allen, Benjamin L.; Taatjes, Dylan J.

    2016-01-01

    The RNA polymerase II (pol II) enzyme transcribes all protein-coding and most non-coding RNA genes and is globally regulated by Mediator, a large, conformationally flexible protein complex with variable subunit composition (for example, a four-subunit CDK8 module can reversibly associate). These biochemical characteristics are fundamentally important for Mediator's ability to control various processes important for transcription, including organization of chromatin architecture and regulation of pol II pre-initiation, initiation, re-initiation, pausing, and elongation. Although Mediator exists in all eukaryotes, a variety of Mediator functions appear to be specific to metazoans, indicative of more diverse regulatory requirements. PMID:25693131

  16. Isolation and mass spectrometry of transcription factor complexes.

    Science.gov (United States)

    Sebastiaan Winkler, G; Lacomis, Lynne; Philip, John; Erdjument-Bromage, Hediye; Svejstrup, Jesper Q; Tempst, Paul

    2002-03-01

    Protocols are described that enable the isolation of novel proteins associated with a known protein and the subsequent identification of these proteins by mass spectrometry. We review the basics of nanosample handling and of two complementary approaches to mass analysis, and provide protocols for the entire process. The protein isolation procedure is rapid and based on two high-affinity chromatography steps. The method does not require previous knowledge of complex composition or activity and permits subsequent biochemical characterization of the isolated factor. As an example, we provide the procedures used to isolate and analyze yeast Elongator, a histone acetyltransferase complex important for transcript elongation, which led to the identification of three novel subunits.

  17. Dynamic-landscape metapopulation models predict complex response of wildlife populations to climate and landscape change

    Science.gov (United States)

    Thomas W. Bonnot; Frank R. Thompson; Joshua J. Millspaugh

    2017-01-01

    The increasing need to predict how climate change will impact wildlife species has exposed limitations in how well current approaches model important biological processes at scales at which those processes interact with climate. We used a comprehensive approach that combined recent advances in landscape and population modeling into dynamic-landscape metapopulation...

  18. Mimicking biochar-albedo feedback in complex Mediterranean agricultural landscapes

    International Nuclear Information System (INIS)

    Bozzi, E; Genesio, L; Miglietta, F; Toscano, P; Pieri, M

    2015-01-01

    Incorporation of charcoal produced by biomass pyrolysis (biochar) in agricultural soils is a potentially sustainable strategy for climate change mitigation. However, some side effects of large-scale biochar application need to be investigated. In particular a massive use of a low-reflecting material on large cropland areas may impact the climate via changes in surface albedo. Twelve years of MODIS-derived albedo data were analysed for three pairs of selected agricultural sites in central Italy. In each pair bright and dark coloured soil were identified, mimicking the effect of biochar application on the land surface albedo of complex agricultural landscapes. Over this period vegetation canopies never completely masked differences in background soil colour. This soil signal, expressed as an albedo difference, induced a local instantaneous radiative forcing of up to 4.7 W m −2 during periods of high solar irradiance. Biochar mitigation potential might therefore be reduced up to ∼30%. This study proves the importance of accounting for crop phenology and crop management when assessing biochar mitigation potential and provides more insights into the analysis of its environmental feedback. (letter)

  19. Epigenetic landscapes reveal transcription factors that regulate CD8+ T cell differentiation.

    Science.gov (United States)

    Yu, Bingfei; Zhang, Kai; Milner, J Justin; Toma, Clara; Chen, Runqiang; Scott-Browne, James P; Pereira, Renata M; Crotty, Shane; Chang, John T; Pipkin, Matthew E; Wang, Wei; Goldrath, Ananda W

    2017-05-01

    Dynamic changes in the expression of transcription factors (TFs) can influence the specification of distinct CD8 + T cell fates, but the observation of equivalent expression of TFs among differentially fated precursor cells suggests additional underlying mechanisms. Here we profiled the genome-wide histone modifications, open chromatin and gene expression of naive, terminal-effector, memory-precursor and memory CD8 + T cell populations induced during the in vivo response to bacterial infection. Integration of these data suggested that the expression and binding of TFs contributed to the establishment of subset-specific enhancers during differentiation. We developed a new bioinformatics method using the PageRank algorithm to reveal key TFs that influence the generation of effector and memory populations. The TFs YY1 and Nr3c1, both constitutively expressed during CD8 + T cell differentiation, regulated the formation of terminal-effector cell fates and memory-precursor cell fates, respectively. Our data define the epigenetic landscape of differentiation intermediates and facilitate the identification of TFs with previously unappreciated roles in CD8 + T cell differentiation.

  20. Epigenetic landscapes reveal transcription factors regulating CD8+ T cell differentiation

    Science.gov (United States)

    Yu, Bingfei; Zhang, Kai; Milner, J. Justin; Toma, Clara; Chen, Runqiang; Scott-Browne, James P.; Pereira, Renata M.; Crotty, Shane; Chang, John T.; Pipkin, Matthew E.; Wang, Wei; Goldrath, Ananda W.

    2017-01-01

    Dynamic changes in the expression of transcription factors (TFs) can influence specification of distinct CD8+ T cell fates, but the observation of equivalent expression of TF among differentially-fated precursor cells suggests additional underlying mechanisms. Here, we profiled genome-wide histone modifications, open chromatin and gene expression of naive, terminal-effector, memory-precursor and memory CD8+ T cell populations induced during the in vivo response to bacterial infection. Integration of these data suggested that TF expression and binding contributed to establishment of subset-specific enhancers during differentiation. We developed a new bioinformatics method using the PageRank algorithm to reveal novel TFs influencing the generation of effector and memory populations. The TFs YY1 and Nr3c1, both constitutively expressed during CD8+ T cell differentiation, regulated the formation of terminal-effector and memory-precursor cell-fates, respectively. Our data define the epigenetic landscape of differentiation intermediates, facilitating identification of TFs with previously unappreciated roles in CD8+ T cell differentiation. PMID:28288100

  1. Erosion and sedimentation effects on soil : organic carbon redistribution in a complex landscape of western Ecuador

    NARCIS (Netherlands)

    Corre, M.D.; Schoorl, J.M.; Koning, de F.; López-Ulloa, M.; Veldkamp, E.

    2015-01-01

    This study was conducted to evaluate how land-use changes affect the distribution of SOC within a complex tropical landscape through the processes of erosion and sedimentation. The objectives were: (i) to estimate the present SOC storage at a landscape scale using predictors such as slope,

  2. Complex Interdependence Regulates Heterotypic Transcription Factor Distribution and Coordinates Cardiogenesis.

    Science.gov (United States)

    Luna-Zurita, Luis; Stirnimann, Christian U; Glatt, Sebastian; Kaynak, Bogac L; Thomas, Sean; Baudin, Florence; Samee, Md Abul Hassan; He, Daniel; Small, Eric M; Mileikovsky, Maria; Nagy, Andras; Holloway, Alisha K; Pollard, Katherine S; Müller, Christoph W; Bruneau, Benoit G

    2016-02-25

    Transcription factors (TFs) are thought to function with partners to achieve specificity and precise quantitative outputs. In the developing heart, heterotypic TF interactions, such as between the T-box TF TBX5 and the homeodomain TF NKX2-5, have been proposed as a mechanism for human congenital heart defects. We report extensive and complex interdependent genomic occupancy of TBX5, NKX2-5, and the zinc finger TF GATA4 coordinately controlling cardiac gene expression, differentiation, and morphogenesis. Interdependent binding serves not only to co-regulate gene expression but also to prevent TFs from distributing to ectopic loci and activate lineage-inappropriate genes. We define preferential motif arrangements for TBX5 and NKX2-5 cooperative binding sites, supported at the atomic level by their co-crystal structure bound to DNA, revealing a direct interaction between the two factors and induced DNA bending. Complex interdependent binding mechanisms reveal tightly regulated TF genomic distribution and define a combinatorial logic for heterotypic TF regulation of differentiation. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Noncoding RNA in the Transcriptional Landscape of Human Neural Progenitor Cell Differentiation

    Directory of Open Access Journals (Sweden)

    Patrick eHecht

    2015-10-01

    Full Text Available Increasing evidence suggests that noncoding RNAs play key roles in cellular processes, particularly in the brain. The present study used RNA sequencing to identify the transcriptional landscape of two human neural progenitor cell lines, SK-N-SH and ReNcell CX, as they differentiate into human cortical projection neurons. Protein coding genes were found to account for 54.8% and 57.0% of expressed genes, respectively, and alignment of RNA sequencing reads revealed that only 25.5-28.1% mapped to exonic regions of the genome. Differential expression analysis in the two cell lines identified altered gene expression in both protein coding and noncoding RNAs as they undergo neural differentiation with 222 differentially expressed genes observed in SK-N-SH cells and 19 differentially expressed genes in ReNcell CX. Interestingly, genes showing differential expression in SK-N-SH cells are enriched in genes implicated in autism spectrum disorder, but not in gene sets related to cancer or Alzheimer’s disease. Weighted gene co-expression network analysis (WGCNA was used to detect modules of co-expressed protein coding and noncoding RNAs in SK-N-SH cells and found four modules to be associated with neural differentiation. These modules contain varying levels of noncoding RNAs ranging from 10.7% to 49.7% with gene ontology suggesting roles in numerous cellular processes important for differentiation. These results indicate that noncoding RNAs are highly expressed in human neural progenitor cells and likely hold key regulatory roles in gene networks underlying neural differentiation and neurodevelopmental disorders.

  4. Combining laser microdissection and RNA-seq to chart the transcriptional landscape of fungal development

    Science.gov (United States)

    2012-01-01

    Background During sexual development, filamentous ascomycetes form complex, three-dimensional fruiting bodies for the protection and dispersal of sexual spores. Fruiting bodies contain a number of cell types not found in vegetative mycelium, and these morphological differences are thought to be mediated by changes in gene expression. However, little is known about the spatial distribution of gene expression in fungal development. Here, we used laser microdissection (LM) and RNA-seq to determine gene expression patterns in young fruiting bodies (protoperithecia) and non-reproductive mycelia of the ascomycete Sordaria macrospora. Results Quantitative analysis showed major differences in the gene expression patterns between protoperithecia and total mycelium. Among the genes strongly up-regulated in protoperithecia were the pheromone precursor genes ppg1 and ppg2. The up-regulation was confirmed by fluorescence microscopy of egfp expression under the control of ppg1 regulatory sequences. RNA-seq analysis of protoperithecia from the sterile mutant pro1 showed that many genes that are differentially regulated in these structures are under the genetic control of transcription factor PRO1. Conclusions We have generated transcriptional profiles of young fungal sexual structures using a combination of LM and RNA-seq. This allowed a high spatial resolution and sensitivity, and yielded a detailed picture of gene expression during development. Our data revealed significant differences in gene expression between protoperithecia and non-reproductive mycelia, and showed that the transcription factor PRO1 is involved in the regulation of many genes expressed specifically in sexual structures. The LM/RNA-seq approach will also be relevant to other eukaryotic systems in which multicellular development is investigated. PMID:23016559

  5. Combining laser microdissection and RNA-seq to chart the transcriptional landscape of fungal development

    Directory of Open Access Journals (Sweden)

    Teichert Ines

    2012-09-01

    Full Text Available Abstract Background During sexual development, filamentous ascomycetes form complex, three-dimensional fruiting bodies for the protection and dispersal of sexual spores. Fruiting bodies contain a number of cell types not found in vegetative mycelium, and these morphological differences are thought to be mediated by changes in gene expression. However, little is known about the spatial distribution of gene expression in fungal development. Here, we used laser microdissection (LM and RNA-seq to determine gene expression patterns in young fruiting bodies (protoperithecia and non-reproductive mycelia of the ascomycete Sordaria macrospora. Results Quantitative analysis showed major differences in the gene expression patterns between protoperithecia and total mycelium. Among the genes strongly up-regulated in protoperithecia were the pheromone precursor genes ppg1 and ppg2. The up-regulation was confirmed by fluorescence microscopy of egfp expression under the control of ppg1 regulatory sequences. RNA-seq analysis of protoperithecia from the sterile mutant pro1 showed that many genes that are differentially regulated in these structures are under the genetic control of transcription factor PRO1. Conclusions We have generated transcriptional profiles of young fungal sexual structures using a combination of LM and RNA-seq. This allowed a high spatial resolution and sensitivity, and yielded a detailed picture of gene expression during development. Our data revealed significant differences in gene expression between protoperithecia and non-reproductive mycelia, and showed that the transcription factor PRO1 is involved in the regulation of many genes expressed specifically in sexual structures. The LM/RNA-seq approach will also be relevant to other eukaryotic systems in which multicellular development is investigated.

  6. Using RNA-seq to determine the transcriptional landscape and the hypoxic response of the pathogenic yeast Candida parapsilosis

    LENUS (Irish Health Repository)

    Guida, Alessandro

    2011-12-22

    Abstract Background Candida parapsilosis is one of the most common causes of Candida infection worldwide. However, the genome sequence annotation was made without experimental validation and little is known about the transcriptional landscape. The transcriptional response of C. parapsilosis to hypoxic (low oxygen) conditions, such as those encountered in the host, is also relatively unexplored. Results We used next generation sequencing (RNA-seq) to determine the transcriptional profile of C. parapsilosis growing in several conditions including different media, temperatures and oxygen concentrations. We identified 395 novel protein-coding sequences that had not previously been annotated. We removed > 300 unsupported gene models, and corrected approximately 900. We mapped the 5\\' and 3\\' UTR for thousands of genes. We also identified 422 introns, including two introns in the 3\\' UTR of one gene. This is the first report of 3\\' UTR introns in the Saccharomycotina. Comparing the introns in coding sequences with other species shows that small numbers have been gained and lost throughout evolution. Our analysis also identified a number of novel transcriptional active regions (nTARs). We used both RNA-seq and microarray analysis to determine the transcriptional profile of cells grown in normoxic and hypoxic conditions in rich media, and we showed that there was a high correlation between the approaches. We also generated a knockout of the UPC2 transcriptional regulator, and we found that similar to C. albicans, Upc2 is required for conferring resistance to azole drugs, and for regulation of expression of the ergosterol pathway in hypoxia. Conclusion We provide the first detailed annotation of the C. parapsilosis genome, based on gene predictions and transcriptional analysis. We identified a number of novel ORFs and other transcribed regions, and detected transcripts from approximately 90% of the annotated protein coding genes. We found that the transcription factor

  7. Global effects of the CSR-1 RNA interference pathway on the transcriptional landscape.

    Science.gov (United States)

    Cecere, Germano; Hoersch, Sebastian; O'Keeffe, Sean; Sachidanandam, Ravi; Grishok, Alla

    2014-04-01

    Argonaute proteins and their small RNA cofactors short interfering RNAs are known to inhibit gene expression at the transcriptional and post-transcriptional levels. In Caenorhabditis elegans, the Argonaute CSR-1 binds thousands of endogenous siRNAs (endo-siRNAs) that are antisense to germline transcripts. However, its role in gene expression regulation remains controversial. Here we used genome-wide profiling of nascent RNA transcripts and found that the CSR-1 RNA interference pathway promoted sense-oriented RNA polymerase II transcription. Moreover, a loss of CSR-1 function resulted in global increase in antisense transcription and ectopic transcription of silent chromatin domains, which led to reduced chromatin incorporation of centromere-specific histone H3. On the basis of these findings, we propose that the CSR-1 pathway helps maintain the directionality of active transcription, thereby propagating the distinction between transcriptionally active and silent genomic regions.

  8. Peroxisome proliferator-activated receptor gamma recruits the positive transcription elongation factor b complex to activate transcription and promote adipogenesis

    DEFF Research Database (Denmark)

    Iankova, Irena; Petersen, Rasmus K; Annicotte, Jean-Sébastien

    2006-01-01

    Positive transcription elongation factor b (P-TEFb) phosphorylates the C-terminal domain of RNA polymerase II, facilitating transcriptional elongation. In addition to its participation in general transcription, P-TEFb is recruited to specific promoters by some transcription factors such as c......-Myc or MyoD. The P-TEFb complex is composed of a cyclin-dependent kinase (cdk9) subunit and a regulatory partner (cyclin T1, cyclin T2, or cyclin K). Because cdk9 has been shown to participate in differentiation processes, such as muscle cell differentiation, we studied a possible role of cdk9...... with and phosphorylation of peroxisome proliferator-activated receptor gamma (PPARgamma), which is the master regulator of this process, on the promoter of PPARgamma target genes. PPARgamma-cdk9 interaction results in increased transcriptional activity of PPARgamma and therefore increased adipogenesis....

  9. Transcriptional Elongation Control of Hepatitis B Virus Covalently Closed Circular DNA Transcription by Super Elongation Complex and BRD4.

    Science.gov (United States)

    Francisco, Joel Celio; Dai, Qian; Luo, Zhuojuan; Wang, Yan; Chong, Roxanne Hui-Heng; Tan, Yee Joo; Xie, Wei; Lee, Guan-Huei; Lin, Chengqi

    2017-10-01

    Chronic hepatitis B virus (HBV) infection can lead to liver cirrhosis and hepatocellular carcinoma. HBV reactivation during or after chemotherapy is a potentially fatal complication for cancer patients with chronic HBV infection. Transcription of HBV is a critical intermediate step of the HBV life cycle. However, factors controlling HBV transcription remain largely unknown. Here, we found that different P-TEFb complexes are involved in the transcription of the HBV viral genome. Both BRD4 and the super elongation complex (SEC) bind to the HBV genome. The treatment of bromodomain inhibitor JQ1 stimulates HBV transcription and increases the occupancy of BRD4 on the HBV genome, suggesting the bromodomain-independent recruitment of BRD4 to the HBV genome. JQ1 also leads to the increased binding of SEC to the HBV genome, and SEC is required for JQ1-induced HBV transcription. These findings reveal a novel mechanism by which the HBV genome hijacks the host P-TEFb-containing complexes to promote its own transcription. Our findings also point out an important clinical implication, that is, the potential risk of HBV reactivation during therapy with a BRD4 inhibitor, such as JQ1 or its analogues, which are a potential treatment for acute myeloid leukemia. Copyright © 2017 American Society for Microbiology.

  10. Transcriptional landscape of ncRNA and Repeat elements in somatic cells

    KAUST Repository

    Ghosheh, Yanal

    2016-12-01

    The advancement of Nucleic acids (DNA and RNA) sequencing technology has enabled many projects targeted towards the identification of genome structure and transcriptome complexity of organisms. The first conclusions of the human and mouse projects have underscored two important, yet unexpected, findings. First, while almost the entire genome is transcribed, only 5% of it encodes for proteins. Thereby, most transcripts are noncoding RNA. This includes both short RNA (<200 nucleotides (nt)) comprising piRNAs; microRNAs (miRNAs); endogenous Short Interfering RNAs (siRNAs) among others, and includes lncRNA (>200nt). Second, a significant portion of the mammalian genome (45%) is composed of Repeat Elements (REs). RE are mostly relics of ancestral viruses that during evolution have invaded the host genome by producing thousands of copies. Their roles within their host genomes have yet to be fully explored considering that they sometimes produce lncRNA, and have been shown to influence expression at the transcriptional and post-transcriptional levels. Moreover, because some REs can still mobilize within host genomes, host genomes have evolved mechanisms, mainly epigenetic, to maintain REs under tight control. Recent reports indicate that REs activity is regulated in somatic cells, particularily in the brain, suggesting a physiological role of RE mobilization during normal development. In this thesis, I focus on the analysis of ncRNAs, specifically REs; piRNAs; lncRNAs in human and mouse post-mitotic somatic cells. The main aspects of this analysis are: Using sRNA-Seq, I show that piRNAs, a class of ncRNAs responsible for the silencing of Transposable elements (TEs) in testes, are present also in adult mouse brain. Furthermore, their regulation shows only a subset of testes piRNAs are expressed in the brain and may be controlled by known neurogenesis factors. To investigate the dynamics of the transcriptome during cellular differentiation, I examined deep RNA-Seq and Cap

  11. Creativity, Complexity, and Precision: Information Visualization for (Landscape) Architecture

    DEFF Research Database (Denmark)

    Buscher, Monika; Christensen, Michael; Mogensen, Preben Holst

    2000-01-01

    Drawing on ethnographic studies of (landscape) architects at work, this paper presents a human-centered approach to information visualization. A 3D collaborative electronic workspace allows people to configure, save and browse arrangements of heterogeneous work materials. Spatial arrangements...... and links are created and maintained as an integral part of ongoing work with `live' documents and objects. The result is an extension of the physical information space of the architects' studio that utilizes the potential of electronic data storage, visualization and network technologies to support work...... with information in context...

  12. Global effects of the CSR-1 RNA interference pathway on transcriptional landscape

    Science.gov (United States)

    Cecere, Germano; Hoersch, Sebastian; O’Keeffe, Sean; Sachidanandam, Ravi; Grishok, Alla

    2014-01-01

    Argonaute proteins and their small RNA co-factors short interfering RNAs (siRNAs) are known to inhibit gene expression at the transcriptional and post-transcriptional levels. In Caenorhabditis elegans, the Argonaute CSR-1 binds thousands of endogenous siRNAs (endo-siRNAs) antisense to germline transcripts and associates with chromatin in a siRNA-dependent manner. However, its role in gene expression regulation remains controversial. Here, we used a genome-wide profiling of nascent RNA transcripts to demonstrate that the CSR-1 RNAi pathway promotes sense-oriented Pol II transcription. Moreover, a loss of CSR-1 function resulted in global increase in antisense transcription and ectopic transcription of silent chromatin domains, which led to reduced chromatin incorporation of centromere-specific histone H3. Based on these findings, we propose that the CSR-1 pathway has a role in maintaining the directionality of active transcription thereby propagating the distinction between transcriptionally active and silent genomic regions. PMID:24681887

  13. Landscape analysis of soil methane flux across complex terrain

    Science.gov (United States)

    Kaiser, Kendra E.; McGlynn, Brian L.; Dore, John E.

    2018-05-01

    Relationships between methane (CH4) fluxes and environmental conditions have been extensively explored in saturated soils, while research has been less prevalent in aerated soils because of the relatively small magnitudes of CH4 fluxes that occur in dry soils. Our study builds on previous carbon cycle research at Tenderfoot Creek Experimental Forest, Montana, to identify how environmental conditions reflected by topographic metrics can be leveraged to estimate watershed scale CH4 fluxes from point scale measurements. Here, we measured soil CH4 concentrations and fluxes across a range of landscape positions (7 riparian, 25 upland), utilizing topographic and seasonal (29 May-12 September) gradients to examine the relationships between environmental variables, hydrologic dynamics, and CH4 emission and uptake. Riparian areas emitted small fluxes of CH4 throughout the study (median: 0.186 µg CH4-C m-2 h-1) and uplands increased in sink strength with dry-down of the watershed (median: -22.9 µg CH4-C m-2 h-1). Locations with volumetric water content (VWC) below 38 % were methane sinks, and uptake increased with decreasing VWC. Above 43 % VWC, net CH4 efflux occurred, and at intermediate VWC net fluxes were near zero. Riparian sites had near-neutral cumulative seasonal flux, and cumulative uptake of CH4 in the uplands was significantly related to topographic indices. These relationships were used to model the net seasonal CH4 flux of the upper Stringer Creek watershed (-1.75 kg CH4-C ha-1). This spatially distributed estimate was 111 % larger than that obtained by simply extrapolating the mean CH4 flux to the entire watershed area. Our results highlight the importance of quantifying the space-time variability of net CH4 fluxes as predicted by the frequency distribution of landscape positions when assessing watershed scale greenhouse gas balances.

  14. From Synergy to Complexity: The Trend Toward Integrated Value Chain and Landscape Governance.

    Science.gov (United States)

    Ros-Tonen, Mirjam A F; Reed, James; Sunderland, Terry

    2018-05-30

    This Editorial introduces a special issue that illustrates a trend toward integrated landscape approaches. Whereas two papers echo older "win-win" strategies based on the trade of non-timber forest products, ten papers reflect a shift from a product to landscape perspective. However, they differ from integrated landscape approaches in that they emanate from sectorial approaches driven primarily by aims such as forest restoration, sustainable commodity sourcing, natural resource management, or carbon emission reduction. The potential of such initiatives for integrated landscape governance and achieving landscape-level outcomes has hitherto been largely unaddressed in the literature on integrated landscape approaches. This special issue addresses this gap, with a focus on actor constellations and institutional arrangements emerging in the transition from sectorial to integrated approaches. This editorial discusses the trends arising from the papers, including the need for a commonly shared concern and sense of urgency; inclusive stakeholder engagement; accommodating and coordinating polycentric governance in landscapes beset with institutional fragmentation and jurisdictional mismatches; alignment with locally embedded initiatives and governance structures; and a framework to assess and monitor the performance of integrated multi-stakeholder approaches. We conclude that, despite a growing tendency toward integrated approaches at the landscape level, inherent landscape complexity renders persistent and significant challenges such as balancing multiple objectives, equitable inclusion of all relevant stakeholders, dealing with power and gender asymmetries, adaptive management based on participatory outcome monitoring, and moving beyond existing administrative, jurisdictional, and sectorial silos. Multi-stakeholder platforms and bridging organizations and individuals are seen as key in overcoming such challenges.

  15. The transcriptional landscape of seasonal coat colour moult in the snowshoe hare.

    Science.gov (United States)

    Ferreira, Mafalda S; Alves, Paulo C; Callahan, Colin M; Marques, João P; Mills, L Scott; Good, Jeffrey M; Melo-Ferreira, José

    2017-08-01

    Seasonal coat colour change is an important adaptation to seasonally changing environments but the evolution of this and other circannual traits remains poorly understood. In this study, we use gene expression to understand seasonal coat colour moulting in wild snowshoe hares (Lepus americanus). We used hair colour to follow the progression of the moult, simultaneously sampling skin from three moulting stages in hares collected during the peak of the spring moult from white winter to brown summer pelage. Using RNA sequencing, we tested whether patterns of expression were consistent with predictions based on the established phases of the hair growth cycle. We found functionally consistent clustering across skin types, with 766 genes differentially expressed between moult stages. "White" pelage showed more differentially expressed genes that were upregulated relative to other skin types, involved in the transition between late telogen (quiescent stage) and the onset of anagen (proliferative stage). Skin samples from transitional "intermediate" and "brown" pelage were transcriptionally similar and resembled the regressive transition to catagen (regressive stage). We also detected differential expression of several key circadian clock and pigmentation genes, providing important means to dissect the bases of alternate seasonal colour morphs. Our results reveal that pelage colour is a useful biomarker for seasonal change but that there is a consistent lag between the main gene expression waves and change in visible coat colour. These experiments establish that developmental sampling from natural populations of nonmodel organisms can provide a crucial resource to dissect the genetic basis and evolution of complex seasonally changing traits. © 2017 John Wiley & Sons Ltd.

  16. The MYST family histone acetyltransferase complex regulates stress resistance and longevity through transcriptional control of DAF-16/FOXO transcription factors.

    Science.gov (United States)

    Ikeda, Takako; Uno, Masaharu; Honjoh, Sakiko; Nishida, Eisuke

    2017-08-09

    The well-known link between longevity and the Sir2 histone deacetylase family suggests that histone deacetylation, a modification associated with repressed chromatin, is beneficial to longevity. However, the molecular links between histone acetylation and longevity remain unclear. Here, we report an unexpected finding that the MYST family histone acetyltransferase complex (MYS-1/TRR-1 complex) promotes rather than inhibits stress resistance and longevity in Caenorhabditis elegans Our results show that these beneficial effects are largely mediated through transcriptional up-regulation of the FOXO transcription factor DAF-16. MYS-1 and TRR-1 are recruited to the promoter regions of the daf-16 gene, where they play a role in histone acetylation, including H4K16 acetylation. Remarkably, we also find that the human MYST family Tip60/TRRAP complex promotes oxidative stress resistance by up-regulating the expression of FOXO transcription factors in human cells. Tip60 is recruited to the promoter regions of the foxo1 gene, where it increases H4K16 acetylation levels. Our results thus identify the evolutionarily conserved role of the MYST family acetyltransferase as a key epigenetic regulator of DAF-16/FOXO transcription factors. © 2017 The Authors.

  17. Computational design of RNAs with complex energy landscapes.

    Science.gov (United States)

    Höner zu Siederdissen, Christian; Hammer, Stefan; Abfalter, Ingrid; Hofacker, Ivo L; Flamm, Christoph; Stadler, Peter F

    2013-12-01

    RNA has become an integral building material in synthetic biology. Dominated by their secondary structures, which can be computed efficiently, RNA molecules are amenable not only to in vitro and in vivo selection, but also to rational, computation-based design. While the inverse folding problem of constructing an RNA sequence with a prescribed ground-state structure has received considerable attention for nearly two decades, there have been few efforts to design RNAs that can switch between distinct prescribed conformations. We introduce a user-friendly tool for designing RNA sequences that fold into multiple target structures. The underlying algorithm makes use of a combination of graph coloring and heuristic local optimization to find sequences whose energy landscapes are dominated by the prescribed conformations. A flexible interface allows the specification of a wide range of design goals. We demonstrate that bi- and tri-stable "switches" can be designed easily with moderate computational effort for the vast majority of compatible combinations of desired target structures. RNAdesign is freely available under the GPL-v3 license. Copyright © 2013 Wiley Periodicals, Inc.

  18. Dynamic regulation of the transcription initiation landscape at single nucleotide resolution during vertebrate embryogenesis

    NARCIS (Netherlands)

    C. Nepal (Chirag); Y. Hadzhiev (Yavor); C. Previti (Christopher); V. Haberle (Vanja); N. Li (Nan); H. Takahashi (Hiroyuki); A.M. Suzuki (Ana Maria); Y. Sheng (Ying); R.F. Abdelhamid (Rehab); S. Anand (Santosh); P.A. Gehrig (Paola A.); A. Akalin (Altuna); C. Kockx (Christel); A. Van Der Sloot (Antoine); W.F.J. van IJcken (Wilfred); O. Armant (Olivier); S. Rastegar (Sepand); C. Watson (Craig); U. Strähle (Uwe); E. Stupka (Elia); P. Carninci (Piero); B. Lenhard (Boris); F. Müller (Ferenc)

    2013-01-01

    textabstractSpatiotemporal control of gene expression is central to animal development. Core promoters represent a previously unanticipated regulatory level by interacting with cis-regulatory elements and transcription initiation in different physiological and developmental contexts. Here, we

  19. Computational complexity of the landscape II-Cosmological considerations

    Science.gov (United States)

    Denef, Frederik; Douglas, Michael R.; Greene, Brian; Zukowski, Claire

    2018-05-01

    We propose a new approach for multiverse analysis based on computational complexity, which leads to a new family of "computational" measure factors. By defining a cosmology as a space-time containing a vacuum with specified properties (for example small cosmological constant) together with rules for how time evolution will produce the vacuum, we can associate global time in a multiverse with clock time on a supercomputer which simulates it. We argue for a principle of "limited computational complexity" governing early universe dynamics as simulated by this supercomputer, which translates to a global measure for regulating the infinities of eternal inflation. The rules for time evolution can be thought of as a search algorithm, whose details should be constrained by a stronger principle of "minimal computational complexity". Unlike previously studied global measures, ours avoids standard equilibrium considerations and the well-known problems of Boltzmann Brains and the youngness paradox. We also give various definitions of the computational complexity of a cosmology, and argue that there are only a few natural complexity classes.

  20. The landscape basis of the complex monitoring of 30-km zone of NPP

    International Nuclear Information System (INIS)

    Malisheva, L.L.; Romanchuk, S.P.; Schur, U.V.; Rybalko, S.I.; Proskura, N.I.; Lury, D.I.

    1992-01-01

    This publication reviews works on the problem of creation the landscape basis of complex monitoring in 30 km zone of NPP(nuclear power plants). The objectives, subject and designation of monitoring system are considered. The monitoring network and organization of systematical observations are justified. The structure of radiation monitoring in NPP 30 km zone is considered in details. (author)

  1. A fitness landscape approach to technological complexity, modularity, and vertical disintegration

    NARCIS (Netherlands)

    Frenken, K.

    2006-01-01

    The biological evolution of complex organisms, in which the functioning of genes is interdependent, has been analysed as "hill-climbing" on NK fitness landscapes through random mutation and natural selection [Kauffman, S.A., 1993. The Origins of Order. Self-organization and Selection in Evolution.

  2. Complexity on Acute Myeloid Leukemia mRNA Transcript Variant

    Directory of Open Access Journals (Sweden)

    Carlo Cattani

    2011-01-01

    Full Text Available This paper deals with the sequence analysis of acute myeloid leukemia mRNA. Six transcript variants of mlf1 mRNA, with more than 2000 bps, are analyzed by focusing on the autocorrelation of each distribution. Through the correlation matrix, some patches and similarities are singled out and commented, with respect to similar distributions. The comparison of Kolmogorov fractal dimension will be also given in order to classify the six variants. The existence of a fractal shape, patterns, and symmetries are discussed as well.

  3. The Transcription Bubble of the RNA Polymerase-Promoter Open Complex Exhibits Conformational Heterogeneity and Millisecond-Scale Dynamics : Implications for Transcription Start-Site Selection

    NARCIS (Netherlands)

    Robb, Nicole C.; Cordes, Thorben; Hwang, Ling Chin; Gryte, Kristofer; Duchi, Diego; Craggs, Timothy D.; Santoso, Yusdi; Weiss, Shimon; Ebright, Richard H.; Kapanidis, Achillefs N.

    2013-01-01

    Bacterial transcription is initiated after RNA polymerase (RNAP) binds to promoter DNA, melts similar to 14 bp around the transcription start site and forms a single-stranded "transcription bubble" within a catalytically active RNAP-DNA open complex (RPo). There is significant flexibility in the

  4. Multiple promoters and alternative splicing: Hoxa5 transcriptional complexity in the mouse embryo.

    Directory of Open Access Journals (Sweden)

    Yan Coulombe

    2010-05-01

    Full Text Available The genomic organization of Hox clusters is fundamental for the precise spatio-temporal regulation and the function of each Hox gene, and hence for correct embryo patterning. Multiple overlapping transcriptional units exist at the Hoxa5 locus reflecting the complexity of Hox clustering: a major form of 1.8 kb corresponding to the two characterized exons of the gene and polyadenylated RNA species of 5.0, 9.5 and 11.0 kb. This transcriptional intricacy raises the question of the involvement of the larger transcripts in Hox function and regulation.We have undertaken the molecular characterization of the Hoxa5 larger transcripts. They initiate from two highly conserved distal promoters, one corresponding to the putative Hoxa6 promoter, and a second located nearby Hoxa7. Alternative splicing is also involved in the generation of the different transcripts. No functional polyadenylation sequence was found at the Hoxa6 locus and all larger transcripts use the polyadenylation site of the Hoxa5 gene. Some larger transcripts are potential Hoxa6/Hoxa5 bicistronic units. However, even though all transcripts could produce the genuine 270 a.a. HOXA5 protein, only the 1.8 kb form is translated into the protein, indicative of its essential role in Hoxa5 gene function. The Hoxa6 mutation disrupts the larger transcripts without major phenotypic impact on axial specification in their expression domain. However, Hoxa5-like skeletal anomalies are observed in Hoxa6 mutants and these defects can be explained by the loss of expression of the 1.8 kb transcript. Our data raise the possibility that the larger transcripts may be involved in Hoxa5 gene regulation.Our observation that the Hoxa5 larger transcripts possess a developmentally-regulated expression combined to the increasing sum of data on the role of long noncoding RNAs in transcriptional regulation suggest that the Hoxa5 larger transcripts may participate in the control of Hox gene expression.

  5. Global transcriptional landscape and promoter mapping of the gut commensal Bifidobacterium breve UCC2003.

    Science.gov (United States)

    Bottacini, Francesca; Zomer, Aldert; Milani, Christian; Ferrario, Chiara; Lugli, Gabriele Andrea; Egan, Muireann; Ventura, Marco; van Sinderen, Douwe

    2017-12-28

    Bifidobacterium breve represents a common member of the infant gut microbiota and its presence in the gut has been associated with host well being. For this reason it is relevant to investigate and understand the molecular mechanisms underlying the establishment, persistence and activities of this gut commensal in the host environment. The assessment of vegetative promoters in the bifidobacterial prototype Bifidobacterium breve UCC2003 was performed employing a combination of RNA tiling array analysis and cDNA sequencing. Canonical -10 (TATAAT) and -35 (TTGACA) sequences were identified upstream of transcribed genes or operons, where deviations from this consensus correspond to transcription level variations. A Random Forest analysis assigned the -10 region of B. breve promoters as the element most impacting on the level of transcription, followed by the spacer length and the 5'-UTR length of transcripts. Furthermore, our transcriptome study also identified rho-independent termination as the most common and effective termination signal of highly and moderately transcribed operons in B. breve. The present study allowed us to identify genes and operons that are actively transcribed in this organism during logarithmic growth, and link promoter elements with levels of transcription of essential genes in this organism. As homologs of many of our identified genes are present across the whole genus Bifidobacterium, our dataset constitutes a transcriptomic reference to be used for future investigations of gene expression in members of this genus.

  6. From the Beauty of Genomic Landscapes to the Strength of Transcriptional Mechanisms.

    Science.gov (United States)

    Natoli, Gioacchino

    2016-03-24

    Genomic analyses are commonly used to infer trends and broad rules underlying transcriptional control. The innovative approach by Tong et al. to interrogate genomic datasets allows extracting mechanistic information on the specific regulation of individual genes. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. The Scc2/Scc4 complex acts in sister chromatid cohesion and transcriptional regulation by maintaining nucleosome-free regions

    Science.gov (United States)

    Lopez-Serra, Lidia; Kelly, Gavin; Patel, Harshil; Stewart, Aengus; Uhlmann, Frank

    2014-01-01

    The cohesin complex is at the heart of many chromosomal activities, including sister chromatid cohesion and transcriptional regulation1-3. Cohesin loading onto chromosomes depends on the Scc2/Scc4 cohesin loader complex4-6, but the chromatin features that form cohesin loading sites remain poorly understood. Here, we show that the RSC chromatin remodeling complex recruits budding yeast Scc2/Scc4 to broad nucleosome-free regions, that the cohesin loader itself helps to maintain. Consequently, inactivation of the cohesin loader or RSC complex have similar effects on nucleosome positioning, gene expression and sister chromatid cohesion. These results reveal an intimate link between local chromatin structure and higher order chromosome architecture. Our findings pertain to the similarities between two severe human disorders, Cornelia de Lange syndrome, caused by mutations in the human cohesin loader, and Coffin-Siris syndrome, resulting from mutations in human RSC complex components7-9. Both could arise from gene misregulation due to related changes in the nucleosome landscape. PMID:25173104

  8. Enhanced conformational sampling to visualize a free-energy landscape of protein complex formation.

    Science.gov (United States)

    Iida, Shinji; Nakamura, Haruki; Higo, Junichi

    2016-06-15

    We introduce various, recently developed, generalized ensemble methods, which are useful to sample various molecular configurations emerging in the process of protein-protein or protein-ligand binding. The methods introduced here are those that have been or will be applied to biomolecular binding, where the biomolecules are treated as flexible molecules expressed by an all-atom model in an explicit solvent. Sampling produces an ensemble of conformations (snapshots) that are thermodynamically probable at room temperature. Then, projection of those conformations to an abstract low-dimensional space generates a free-energy landscape. As an example, we show a landscape of homo-dimer formation of an endothelin-1-like molecule computed using a generalized ensemble method. The lowest free-energy cluster at room temperature coincided precisely with the experimentally determined complex structure. Two minor clusters were also found in the landscape, which were largely different from the native complex form. Although those clusters were isolated at room temperature, with rising temperature a pathway emerged linking the lowest and second-lowest free-energy clusters, and a further temperature increment connected all the clusters. This exemplifies that the generalized ensemble method is a powerful tool for computing the free-energy landscape, by which one can discuss the thermodynamic stability of clusters and the temperature dependence of the cluster networks. © 2016 The Author(s).

  9. Understanding large multiprotein complexes: applying a multiple allosteric networks model to explain the function of the Mediator transcription complex.

    Science.gov (United States)

    Lewis, Brian A

    2010-01-15

    The regulation of transcription and of many other cellular processes involves large multi-subunit protein complexes. In the context of transcription, it is known that these complexes serve as regulatory platforms that connect activator DNA-binding proteins to a target promoter. However, there is still a lack of understanding regarding the function of these complexes. Why do multi-subunit complexes exist? What is the molecular basis of the function of their constituent subunits, and how are these subunits organized within a complex? What is the reason for physical connections between certain subunits and not others? In this article, I address these issues through a model of network allostery and its application to the eukaryotic RNA polymerase II Mediator transcription complex. The multiple allosteric networks model (MANM) suggests that protein complexes such as Mediator exist not only as physical but also as functional networks of interconnected proteins through which information is transferred from subunit to subunit by the propagation of an allosteric state known as conformational spread. Additionally, there are multiple distinct sub-networks within the Mediator complex that can be defined by their connections to different subunits; these sub-networks have discrete functions that are activated when specific subunits interact with other activator proteins.

  10. The South African developmental landscape: restricted potentials or expansive, complex adaptive opportunities?

    Directory of Open Access Journals (Sweden)

    C J Burman

    2013-07-01

    Full Text Available This article argues that the South African developmental landscape is currently locked into an overly technical, path dependent paradigm that is unlikely to be capable of embracing the complex challenges identified by the recent National Development Plan. The article explores the internal logic of the existing path dependent, technical condition from the perspective of complexity, in the context of the Department of Science and Technology’s Fifth Grand Challenge and “continuous change”. It is argued that drawing ideas from complexity into future developmental trajectories can add value to the National Development Plan: Vision 2030, but to do so will require dynamic mind-set shifts across multiple developmental scales and interfaces if new approaches to managing development that embraces complexity, rather than denies it, is to emerge. Keywords: development; complexity; path dependency; epistemological vigilance; sense-making; National Development Plan Disciplines: Complexity Studies; Transdisciplinary studies; Management studies; Public management; Political studies; Economics; Development Studies

  11. Single-Cell Landscape of Transcriptional Heterogeneity and Cell Fate Decisions during Mouse Early Gastrulation

    Directory of Open Access Journals (Sweden)

    Hisham Mohammed

    2017-08-01

    Full Text Available The mouse inner cell mass (ICM segregates into the epiblast and primitive endoderm (PrE lineages coincident with implantation of the embryo. The epiblast subsequently undergoes considerable expansion of cell numbers prior to gastrulation. To investigate underlying regulatory principles, we performed systematic single-cell RNA sequencing (seq of conceptuses from E3.5 to E6.5. The epiblast shows reactivation and subsequent inactivation of the X chromosome, with Zfp57 expression associated with reactivation and inactivation together with other candidate regulators. At E6.5, the transition from epiblast to primitive streak is linked with decreased expression of polycomb subunits, suggesting a key regulatory role. Notably, our analyses suggest elevated transcriptional noise at E3.5 and within the non-committed epiblast at E6.5, coinciding with exit from pluripotency. By contrast, E6.5 primitive streak cells became highly synchronized and exhibit a shortened G1 cell-cycle phase, consistent with accelerated proliferation. Our study systematically charts transcriptional noise and uncovers molecular processes associated with early lineage decisions.

  12. The forgotten D : challenges of addressing forest degradation in complex mosaic landscapes under REDD

    OpenAIRE

    Mertz, O.; Muller, D.; Sikor, T.; Hett, C.; Heinimann, A.; Castella, Jean-Christophe; Lestrelin, Guillaume; Ryan, C. M.; Reay, D. S.; Schmidt-Vogt, D.; Danielsen, F.; Theilade, I.; van Noordwijk, M.; Verchot, L. V.; Burgess, N. D.

    2012-01-01

    International climate negotiations have stressed the importance of considering emissions from forest degradation under the planned REDD+ (Reducing Emissions from Deforestation and forest Degradation + enhancing forest carbon stocks) mechanism. However, most research, pilot-REDD+ projects and carbon certification agencies have focused on deforestation and there appears to be a gap in knowledge on complex mosaic landscapes containing degraded forests, smallholder agriculture, agroforestry and p...

  13. Transcriptional landscape of ncRNA and Repeat elements in somatic cells

    KAUST Repository

    Ghosheh, Yanal

    2016-01-01

    The advancement of Nucleic acids (DNA and RNA) sequencing technology has enabled many projects targeted towards the identification of genome structure and transcriptome complexity of organisms. The first conclusions of the human and mouse projects

  14. Translational Capacity of a Cell Is Determined during Transcription Elongation via the Ccr4-Not Complex

    Directory of Open Access Journals (Sweden)

    Ishaan Gupta

    2016-05-01

    Full Text Available The current understanding of gene expression considers transcription and translation to be independent processes. Challenging this notion, we found that translation efficiency is determined during transcription elongation through the imprinting of mRNAs with Not1, the central scaffold of the Ccr4-Not complex. We determined that another subunit of the complex, Not5, defines Not1 binding to specific mRNAs, particularly those produced from ribosomal protein genes. This imprinting mechanism specifically regulates ribosomal protein gene expression, which in turn determines the translational capacity of cells. We validate our model by SILAC and polysome profiling experiments. As a proof of concept, we demonstrate that enhanced translation compensates for transcriptional elongation stress. Taken together, our data indicate that in addition to defining mRNA stability, components of the Ccr4-Not imprinting complex regulate RNA translatability, thus ensuring global gene expression homeostasis.

  15. Energy landscape scheme for an intuitive understanding of complex domain dynamics in ferroelectric thin films.

    Science.gov (United States)

    Kim, Tae Heon; Yoon, Jong-Gul; Baek, Seung Hyub; Park, Woong-kyu; Yang, Sang Mo; Yup Jang, Seung; Min, Taeyuun; Chung, Jin-Seok; Eom, Chang-Beom; Noh, Tae Won

    2015-07-01

    Fundamental understanding of domain dynamics in ferroic materials has been a longstanding issue because of its relevance to many systems and to the design of nanoscale domain-wall devices. Despite many theoretical and experimental studies, a full understanding of domain dynamics still remains incomplete, partly due to complex interactions between domain-walls and disorder. We report domain-shape-preserving deterministic domain-wall motion, which directly confirms microscopic return point memory, by observing domain-wall breathing motion in ferroelectric BiFeO3 thin film using stroboscopic piezoresponse force microscopy. Spatial energy landscape that provides new insights into domain dynamics is also mapped based on the breathing motion of domain walls. The evolution of complex domain structure can be understood by the process of occupying the lowest available energy states of polarization in the energy landscape which is determined by defect-induced internal fields. Our result highlights a pathway for the novel design of ferroelectric domain-wall devices through the engineering of energy landscape using defect-induced internal fields such as flexoelectric fields.

  16. Energy landscape scheme for an intuitive understanding of complex domain dynamics in ferroelectric thin films

    Science.gov (United States)

    Heon Kim, Tae; Yoon, Jong-Gul; Hyub Baek, Seung; Park, Woong-Kyu; Mo Yang, Sang; Yup Jang, Seung; Min, Taeyuun; Chung, Jin-Seok; Eom, Chang-Beom; Won Noh, Tae

    2015-07-01

    Fundamental understanding of domain dynamics in ferroic materials has been a longstanding issue because of its relevance to many systems and to the design of nanoscale domain-wall devices. Despite many theoretical and experimental studies, a full understanding of domain dynamics still remains incomplete, partly due to complex interactions between domain-walls and disorder. We report domain-shape-preserving deterministic domain-wall motion, which directly confirms microscopic return point memory, by observing domain-wall breathing motion in ferroelectric BiFeO3 thin film using stroboscopic piezoresponse force microscopy. Spatial energy landscape that provides new insights into domain dynamics is also mapped based on the breathing motion of domain walls. The evolution of complex domain structure can be understood by the process of occupying the lowest available energy states of polarization in the energy landscape which is determined by defect-induced internal fields. Our result highlights a pathway for the novel design of ferroelectric domain-wall devices through the engineering of energy landscape using defect-induced internal fields such as flexoelectric fields.

  17. Pan-Cancer Mutational and Transcriptional Analysis of the Integrator Complex

    Directory of Open Access Journals (Sweden)

    Antonio Federico

    2017-04-01

    Full Text Available The integrator complex has been recently identified as a key regulator of RNA Polymerase II-mediated transcription, with many functions including the processing of small nuclear RNAs, the pause-release and elongation of polymerase during the transcription of protein coding genes, and the biogenesis of enhancer derived transcripts. Moreover, some of its components also play a role in genome maintenance. Thus, it is reasonable to hypothesize that their functional impairment or altered expression can contribute to malignancies. Indeed, several studies have described the mutations or transcriptional alteration of some Integrator genes in different cancers. Here, to draw a comprehensive pan-cancer picture of the genomic and transcriptomic alterations for the members of the complex, we reanalyzed public data from The Cancer Genome Atlas. Somatic mutations affecting Integrator subunit genes and their transcriptional profiles have been investigated in about 11,000 patients and 31 tumor types. A general heterogeneity in the mutation frequencies was observed, mostly depending on tumor type. Despite the fact that we could not establish them as cancer drivers, INTS7 and INTS8 genes were highly mutated in specific cancers. A transcriptome analysis of paired (normal and tumor samples revealed that the transcription of INTS7, INTS8, and INTS13 is significantly altered in several cancers. Experimental validation performed on primary tumors confirmed these findings.

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

    Science.gov (United States)

    Yin, Jing-wen; Wang, Gang

    2014-03-01

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

  19. Comprehensive analysis of the transcriptional profile of the Mediator complex across human cancer types.

    Science.gov (United States)

    Syring, Isabella; Klümper, Niklas; Offermann, Anne; Braun, Martin; Deng, Mario; Boehm, Diana; Queisser, Angela; von Mässenhausen, Anne; Brägelmann, Johannes; Vogel, Wenzel; Schmidt, Doris; Majores, Michael; Schindler, Anne; Kristiansen, Glen; Müller, Stefan C; Ellinger, Jörg; Shaikhibrahim, Zaki; Perner, Sven

    2016-04-26

    The Mediator complex is a key regulator of gene transcription and several studies demonstrated altered expressions of particular subunits in diverse human diseases, especially cancer. However a systematic study deciphering the transcriptional expression of the Mediator across different cancer entities is still lacking.We therefore performed a comprehensive in silico cancer vs. benign analysis of the Mediator complex subunits (MEDs) for 20 tumor entities using Oncomine datasets. The transcriptional expression profiles across almost all cancer entities showed differentially expressed MEDs as compared to benign tissue. Differential expression of MED8 in renal cell carcinoma (RCC) and MED12 in lung cancer (LCa) were validated and further investigated by immunohistochemical staining on tissue microarrays containing large numbers of specimen. MED8 in clear cell RCC (ccRCC) associated with shorter survival and advanced TNM stage and showed higher expression in metastatic than primary tumors. In vitro, siRNA mediated MED8 knockdown significantly impaired proliferation and motility in ccRCC cell lines, hinting at a role for MED8 to serve as a novel therapeutic target in ccRCC. Taken together, our Mediator complex transcriptome proved to be a valid tool for identifying cancer-related shifts in Mediator complex composition, revealing that MEDs do exhibit cancer specific transcriptional expression profiles.

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

    OpenAIRE

    Malik, Sohail; Roeder, Robert G.

    2010-01-01

    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 ...

  1. Entropic algorithms and the lid method as exploration tools for complex landscapes

    DEFF Research Database (Denmark)

    Barettin, Daniele; Sibani, Paolo

    2011-01-01

    to a single valley, are key to understand the dynamical properties of such systems. In this paper we combine the lid algorithm, a tool for landscape exploration previously applied to a range of models, with the Wang-Swendsen algorithm. To test this improved exploration tool, we consider a paradigmatic complex...... system, the Edwards-Andersom model in two and three spatial dimension. We find a striking difference between the energy dependence of the local density of states in the two cases: nearly flat in the first case, and nearly exponential in the second. The lid dependence of the data is analyzed to estimate...

  2. Regulation of hepatic lipogenesis by the transcription complex Prep1-Pbx1

    OpenAIRE

    Cabaro, Serena

    2011-01-01

    Prep1 is an homeodomain transcription factor belonging to the TALE proteins, including also Pbx1, which plays an essential role in hematopoiesis, organogenesis and development. Prep1 forms transcriptionally active complexes with Pbx1 and regulates the activity of several genes. The Prep1 null mutation leads to embryonic death at a very early stage. Therefore, Prep1 hypomorphic (Prep1i/i) mice have been generated. Prep1 heterozygous (Prep1i/+) mice, which express only 55-57% of protein, have a...

  3. saRNA-guided Ago2 targets the RITA complex to promoters to stimulate transcription.

    Science.gov (United States)

    Portnoy, Victoria; Lin, Szu Hua Sharon; Li, Kathy H; Burlingame, Alma; Hu, Zheng-Hui; Li, Hao; Li, Long-Cheng

    2016-03-01

    Small activating RNAs (saRNAs) targeting specific promoter regions are able to stimulate gene expression at the transcriptional level, a phenomenon known as RNA activation (RNAa). It is known that RNAa depends on Ago2 and is associated with epigenetic changes at the target promoters. However, the precise molecular mechanism of RNAa remains elusive. Using human CDKN1A (p21) as a model gene, we characterized the molecular nature of RNAa. We show that saRNAs guide Ago2 to and associate with target promoters. saRNA-loaded Ago2 facilitates the assembly of an RNA-induced transcriptional activation (RITA) complex, which, in addition to saRNA-Ago2 complex, includes RHA and CTR9, the latter being a component of the PAF1 complex. RITA interacts with RNA polymerase II to stimulate transcription initiation and productive elongation, accompanied by monoubiquitination of histone 2B. Our results establish the existence of a cellular RNA-guided genome-targeting and transcriptional activation mechanism and provide important new mechanistic insights into the RNAa process.

  4. RNA polymerase gate loop guides the nontemplate DNA strand in transcription complexes.

    Science.gov (United States)

    NandyMazumdar, Monali; Nedialkov, Yuri; Svetlov, Dmitri; Sevostyanova, Anastasia; Belogurov, Georgiy A; Artsimovitch, Irina

    2016-12-27

    Upon RNA polymerase (RNAP) binding to a promoter, the σ factor initiates DNA strand separation and captures the melted nontemplate DNA, whereas the core enzyme establishes interactions with the duplex DNA in front of the active site that stabilize initiation complexes and persist throughout elongation. Among many core RNAP elements that participate in these interactions, the β' clamp domain plays the most prominent role. In this work, we investigate the role of the β gate loop, a conserved and essential structural element that lies across the DNA channel from the clamp, in transcription regulation. The gate loop was proposed to control DNA loading during initiation and to interact with NusG-like proteins to lock RNAP in a closed, processive state during elongation. We show that the removal of the gate loop has large effects on promoter complexes, trapping an unstable intermediate in which the RNAP contacts with the nontemplate strand discriminator region and the downstream duplex DNA are not yet fully established. We find that although RNAP lacking the gate loop displays moderate defects in pausing, transcript cleavage, and termination, it is fully responsive to the transcription elongation factor NusG. Together with the structural data, our results support a model in which the gate loop, acting in concert with initiation or elongation factors, guides the nontemplate DNA in transcription complexes, thereby modulating their regulatory properties.

  5. Structures of RNA Polymerase Closed and Intermediate Complexes Reveal Mechanisms of DNA Opening and Transcription Initiation.

    Science.gov (United States)

    Glyde, Robert; Ye, Fuzhou; Darbari, Vidya Chandran; Zhang, Nan; Buck, Martin; Zhang, Xiaodong

    2017-07-06

    Gene transcription is carried out by RNA polymerases (RNAPs). For transcription to occur, the closed promoter complex (RPc), where DNA is double stranded, must isomerize into an open promoter complex (RPo), where the DNA is melted out into a transcription bubble and the single-stranded template DNA is delivered to the RNAP active site. Using a bacterial RNAP containing the alternative σ 54 factor and cryoelectron microscopy, we determined structures of RPc and the activator-bound intermediate complex en route to RPo at 3.8 and 5.8 Å. Our structures show how RNAP-σ 54 interacts with promoter DNA to initiate the DNA distortions required for transcription bubble formation, and how the activator interacts with RPc, leading to significant conformational changes in RNAP and σ 54 that promote RPo formation. We propose that DNA melting is an active process initiated in RPc and that the RNAP conformations of intermediates are significantly different from that of RPc and RPo. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  6. A structural model of the E. coli PhoB Dimer in the transcription initiation complex

    Directory of Open Access Journals (Sweden)

    Tung Chang-Shung

    2012-03-01

    Full Text Available Abstract Background There exist > 78,000 proteins and/or nucleic acids structures that were determined experimentally. Only a small portion of these structures corresponds to those of protein complexes. While homology modeling is able to exploit knowledge-based potentials of side-chain rotomers and backbone motifs to infer structures for new proteins, no such general method exists to extend our understanding of protein interaction motifs to novel protein complexes. Results We use a Motif Binding Geometries (MBG approach, to infer the structure of a protein complex from the database of complexes of homologous proteins taken from other contexts (such as the helix-turn-helix motif binding double stranded DNA, and demonstrate its utility on one of the more important regulatory complexes in biology, that of the RNA polymerase initiating transcription under conditions of phosphate starvation. The modeled PhoB/RNAP/σ-factor/DNA complex is stereo-chemically reasonable, has sufficient interfacial Solvent Excluded Surface Areas (SESAs to provide adequate binding strength, is physically meaningful for transcription regulation, and is consistent with a variety of known experimental constraints. Conclusions Based on a straightforward and easy to comprehend concept, "proteins and protein domains that fold similarly could interact similarly", a structural model of the PhoB dimer in the transcription initiation complex has been developed. This approach could be extended to enable structural modeling and prediction of other bio-molecular complexes. Just as models of individual proteins provide insight into molecular recognition, catalytic mechanism, and substrate specificity, models of protein complexes will provide understanding into the combinatorial rules of cellular regulation and signaling.

  7. Single-Cell RNA-Seq Reveals the Transcriptional Landscape and Heterogeneity of Aortic Macrophages in Murine Atherosclerosis.

    Science.gov (United States)

    Cochain, Clément; Vafadarnejad, Ehsan; Arampatzi, Panagiota; Jaroslav, Pelisek; Winkels, Holger; Ley, Klaus; Wolf, Dennis; Saliba, Antoine-Emmanuel; Zernecke, Alma

    2018-03-15

    Rationale: It is assumed that atherosclerotic arteries contain several macrophage subsets endowed with specific functions. The precise identity of these subsets is poorly characterized as they ha ve been defined by the expression of a restricted number of markers. Objective: We have applied single-cell RNA-seq as an unbiased profiling strategy to interrogate and classify aortic macrophage heterogeneity at the single-cell level in atherosclerosis. Methods and Results: We performed single-cell RNA sequencing of total aortic CD45 + cells extracted from the non-diseased (chow fed) and atherosclerotic (11 weeks of high fat diet) aorta of Ldlr -/- mice. Unsupervised clustering singled out 13 distinct aortic cell clusters. Among the myeloid cell populations, Resident-like macrophages with a gene expression profile similar to aortic resident macrophages were found in healthy and diseased aortae, whereas monocytes, monocyte-derived dendritic cells (MoDC), and two populations of macrophages were almost exclusively detectable in atherosclerotic aortae, comprising Inflammatory macrophages showing enrichment in I l1b , and previously undescribed TREM2 hi macrophages. Differential gene expression and gene ontology enrichment analyses revealed specific gene expression patterns distinguishing these three macrophage subsets and MoDC, and uncovered putative functions of each cell type. Notably, TREM2 hi macrophages appeared to be endowed with specialized functions in lipid metabolism and catabolism, and presented a gene expression signature reminiscent of osteoclasts, suggesting a role in lesion calcification. TREM2 expression was moreover detected in human lesional macrophages. Importantly, these macrophage populations were present also in advanced atherosclerosis and in Apoe -/- aortae, indicating relevance of our findings in different stages of atherosclerosis and mouse models. Conclusions: These data unprecedentedly uncovered the transcriptional landscape and phenotypic

  8. Protection of Landscape Values of Historical Post Military Objects - Complexes in Spatial, Urban and Architectural Planning of Polish Cities

    Science.gov (United States)

    Gawryluk, Dorota; Zagroba, Marek

    2017-12-01

    Within the borders of modern Poland there are numerous barracks units erected at the turn of the 19th and 20th centuries by the invaders from Russia, Austria and Prussia. Former barracks are a clear element of the history of the place. Historical complexes have a strong influence on the urban landscape and on building their former and contemporary identity. The analysis of functional and landscape absorption of postmodern complexes allows for their adaptation and modern use without limiting the readability of historical values. For this reason, their landscape should be protected comprehensively within the scope of subsequent exposure scales. The aim of the work is to justify the conditions of comprehensive protection of the fortified landscape of the former barracks of the former Russian partition in the landscape of contemporary Polish cities. The article contains a review of the literature on the protection, supplement and access to fortified buildings from the turn of the 19th and 20th centuries in contemporary Poland. A review of current research conducted at various academic centres in Poland, concerning the exposition of fortified buildings in the landscape, is presented. Particular attention was paid to the scales and forms of exposition, proposed for the fortifications and barracks. The paper presents justification for the protection of barracks complexes from the turn of the 19th and 20th centuries in the landscape of Polish cities of the former Russian partition area. Protection of the landscape was proposed in the following scales: superregional, landscape (panorama of the centre), urban (urban structure of the complex in the context of the urban space), architectural and landscape interiors of the complex (WAK) such as alleys, alarm squares, greenery) and detail (view of the building from the outside), interior of the building (characteristic interior spaces, e.g. home chapels, staircases). Taking account of exposures analysis of individual scales

  9. The geography of malaria genetics in the Democratic Republic of Congo: A complex and fragmented landscape

    Science.gov (United States)

    Carrel, Margaret; Patel, Jaymin; Taylor, Steve M.; Janko, Mark; Mwandagalirwa, Melchior Kashamuka; Tshefu, Antoinette K.; Escalante, Ananias A.; McCollum, Andrea; Alam, Md Tauqeer; Udhayakumar, Venkatachalam; Meshnick, Steven; Emch, Michael

    2014-01-01

    Understanding how malaria parasites move between populations is important, particularly given the potential for malaria to be reintroduced into areas where it was previously eliminated. We examine the distribution of malaria genetics across seven sites within the Democratic Republic of Congo (DRC) and two nearby countries, Ghana and Kenya, in order to understand how the relatedness of malaria parasites varies across space, and whether there are barriers to the flow of malaria parasites within the DRC or across borders. Parasite DNA was retrieved from dried blood spots from 7 Demographic and Health Survey sample clusters in the DRC. Malaria genetic characteristics of parasites from Ghana and Kenya were also obtained. For each of 9 geographic sites (7 DRC, 1 Ghana and 1 Kenya), a pair-wise RST statistic was calculated, indicating the genetic distance between malaria parasites found in those locations. Mapping genetics across the spatial extent of the study area indicates a complex genetic landscape, where relatedness between two proximal sites may be relatively high (RST > 0.64) or low (RST < 0.05), and where distal sites also exhibit both high and low genetic similarity. Mantel’s tests suggest that malaria genetics differ as geographic distances increase. Principal Coordinate Analysis suggests that genetically related samples are not co-located. Barrier analysis reveals no significant barriers to gene flow between locations. Malaria genetics in the DRC have a complex and fragmented landscape. Limited exchange of genes across space is reflected in greater genetic distance between malaria parasites isolated at greater geographic distances. There is, however, evidence for close genetic ties between distally located sample locations, indicating that movement of malaria parasites and flow of genes is being driven by factors other than distance decay. This research demonstrates the contributions that spatial disease ecology and landscape genetics can make to

  10. Characterisation of major histocompatibility complex class I transcripts in an Australian dragon lizard.

    Science.gov (United States)

    Hacking, Jessica; Bertozzi, Terry; Moussalli, Adnan; Bradford, Tessa; Gardner, Michael

    2018-07-01

    Characterisation of squamate major histocompatibility complex (MHC) genes has lagged behind other taxonomic groups. MHC genes encode cell-surface glycoproteins that present self- and pathogen-derived peptides to T cells and play a critical role in pathogen recognition. Here we characterise MHC class I transcripts for an agamid lizard (Ctenophorus decresii) and investigate the evolution of MHC class I in Iguanian lizards. An iterative assembly strategy was used to identify six full-length C. decresii MHC class I transcripts, which were validated as likely to encode classical class I MHC molecules. Evidence for exon shuffling recombination was uncovered for C. decresii transcripts and Bayesian phylogenetic analysis of Iguanian MHC class I sequences revealed a pattern expected under a birth-and-death mode of evolution. This work provides a stepping stone towards further research on the agamid MHC class I region. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. Bacillus subtilis δ Factor Functions as a Transcriptional Regulator by Facilitating the Open Complex Formation.

    Science.gov (United States)

    Prajapati, Ranjit Kumar; Sengupta, Shreya; Rudra, Paulami; Mukhopadhyay, Jayanta

    2016-01-15

    Most bacterial RNA polymerases (RNAP) contain five conserved subunits, viz. 2α, β, β', and ω. However, in many Gram-positive bacteria, especially in fermicutes, RNAP is associated with an additional factor, called δ. For over three decades since its identification, it had been thought that δ functioned as a subunit of RNAP to enhance the level of transcripts by recycling RNAP. In support of the previous observations, we also find that δ is involved in recycling of RNAP by releasing the RNA from the ternary complex. We further show that δ binds to RNA and is able to recycle RNAP when the length of the nascent RNA reaches a critical length. However, in this work we decipher a new function of δ. Performing biochemical and mutational analysis, we show that Bacillus subtilis δ binds to DNA immediately upstream of the promoter element at A-rich sequences on the abrB and rrnB1 promoters and facilitates open complex formation. As a result, δ facilitates RNAP to initiate transcription in the second scale, compared with minute scale in the absence of δ. Using transcription assay, we show that δ-mediated recycling of RNAP cannot be the sole reason for the enhancement of transcript yield. Our observation that δ does not bind to RNAP holo enzyme but is required to bind to DNA upstream of the -35 promoter element for transcription activation suggests that δ functions as a transcriptional regulator. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Using Google Earth Surface Metrics to Predict Plant Species Richness in a Complex Landscape

    Directory of Open Access Journals (Sweden)

    Sebastián Block

    2016-10-01

    Full Text Available Google Earth provides a freely available, global mosaic of high-resolution imagery from different sensors that has become popular in environmental and ecological studies. However, such imagery lacks the near-infrared band often used in studying vegetation, thus its potential for estimating vegetation properties remains unclear. In this study, we assess the potential of Google Earth imagery to describe and predict vegetation attributes. Further, we compare it to the potential of SPOT imagery, which has additional spectral information. We measured basal area, vegetation height, crown cover, density of individuals, and species richness in 60 plots in the oak forests of a complex volcanic landscape in central Mexico. We modelled each vegetation attribute as a function of surface metrics derived from Google Earth and SPOT images, and selected the best-supported linear models from each source. Total species richness was the best-described and predicted variable: the best Google Earth-based model explained nearly as much variation in species richness as its SPOT counterpart (R2 = 0.44 and 0.51, respectively. However, Google Earth metrics emerged as poor predictors of all remaining vegetation attributes, whilst SPOT metrics showed potential for predicting vegetation height. We conclude that Google Earth imagery can be used to estimate species richness in complex landscapes. As it is freely available, Google Earth can broaden the use of remote sensing by researchers and managers in low-income tropical countries where most biodiversity hotspots are found.

  13. Simplified Method for Predicting a Functional Class of Proteins in Transcription Factor Complexes

    KAUST Repository

    Piatek, Marek J.

    2013-07-12

    Background:Initiation of transcription is essential for most of the cellular responses to environmental conditions and for cell and tissue specificity. This process is regulated through numerous proteins, their ligands and mutual interactions, as well as interactions with DNA. The key such regulatory proteins are transcription factors (TFs) and transcription co-factors (TcoFs). TcoFs are important since they modulate the transcription initiation process through interaction with TFs. In eukaryotes, transcription requires that TFs form different protein complexes with various nuclear proteins. To better understand transcription regulation, it is important to know the functional class of proteins interacting with TFs during transcription initiation. Such information is not fully available, since not all proteins that act as TFs or TcoFs are yet annotated as such, due to generally partial functional annotation of proteins. In this study we have developed a method to predict, using only sequence composition of the interacting proteins, the functional class of human TF binding partners to be (i) TF, (ii) TcoF, or (iii) other nuclear protein. This allows for complementing the annotation of the currently known pool of nuclear proteins. Since only the knowledge of protein sequences is required in addition to protein interaction, the method should be easily applicable to many species.Results:Based on experimentally validated interactions between human TFs with different TFs, TcoFs and other nuclear proteins, our two classification systems (implemented as a web-based application) achieve high accuracies in distinguishing TFs and TcoFs from other nuclear proteins, and TFs from TcoFs respectively.Conclusion:As demonstrated, given the fact that two proteins are capable of forming direct physical interactions and using only information about their sequence composition, we have developed a completely new method for predicting a functional class of TF interacting protein partners

  14. A Protein Complex Required for Polymerase V Transcripts and RNA- Directed DNA Methylation in Arabidopsis

    KAUST Repository

    Law, Julie A.

    2010-05-01

    DNA methylation is an epigenetic modification associated with gene silencing. In Arabidopsis, DNA methylation is established by DOMAINS REARRANGED METHYLTRANSFERASE 2 (DRM2), which is targeted by small interfering RNAs through a pathway termed RNA-directed DNA methylation (RdDM) [1, 2]. Recently, RdDM was shown to require intergenic noncoding (IGN) transcripts that are dependent on the Pol V polymerase. These transcripts are proposed to function as scaffolds for the recruitment of downstream RdDM proteins, including DRM2, to loci that produce both siRNAs and IGN transcripts [3]. However, the mechanism(s) through which Pol V is targeted to specific genomic loci remains largely unknown. Through affinity purification of two known RdDM components, DEFECTIVE IN RNA-DIRECTED DNA METHYLATION 1 (DRD1) [4] and DEFECTIVE IN MERISTEM SILENCING 3 (DMS3) [5, 6], we found that they copurify with each other and with a novel protein, RNA-DIRECTED DNA METHYLATION 1 (RDM1), forming a complex we term DDR. We also found that DRD1 copurified with Pol V subunits and that RDM1, like DRD1 [3] and DMS3 [7], is required for the production of Pol V-dependent transcripts. These results suggest that the DDR complex acts in RdDM at a step upstream of the recruitment or activation of Pol V. © 2010 Elsevier Ltd. All rights reserved.

  15. A Protein Complex Required for Polymerase V Transcripts and RNA- Directed DNA Methylation in Arabidopsis

    KAUST Repository

    Law, Julie A.; Ausí n, Israel; Johnson, Lianna M.; Vashisht, Ajay  A Amar; Zhu, Jian-Kang; Wohlschlegel, James  A A.; Jacobsen, Steven E.

    2010-01-01

    DNA methylation is an epigenetic modification associated with gene silencing. In Arabidopsis, DNA methylation is established by DOMAINS REARRANGED METHYLTRANSFERASE 2 (DRM2), which is targeted by small interfering RNAs through a pathway termed RNA-directed DNA methylation (RdDM) [1, 2]. Recently, RdDM was shown to require intergenic noncoding (IGN) transcripts that are dependent on the Pol V polymerase. These transcripts are proposed to function as scaffolds for the recruitment of downstream RdDM proteins, including DRM2, to loci that produce both siRNAs and IGN transcripts [3]. However, the mechanism(s) through which Pol V is targeted to specific genomic loci remains largely unknown. Through affinity purification of two known RdDM components, DEFECTIVE IN RNA-DIRECTED DNA METHYLATION 1 (DRD1) [4] and DEFECTIVE IN MERISTEM SILENCING 3 (DMS3) [5, 6], we found that they copurify with each other and with a novel protein, RNA-DIRECTED DNA METHYLATION 1 (RDM1), forming a complex we term DDR. We also found that DRD1 copurified with Pol V subunits and that RDM1, like DRD1 [3] and DMS3 [7], is required for the production of Pol V-dependent transcripts. These results suggest that the DDR complex acts in RdDM at a step upstream of the recruitment or activation of Pol V. © 2010 Elsevier Ltd. All rights reserved.

  16. The herpes viral transcription factor ICP4 forms a novel DNA recognition complex

    Science.gov (United States)

    Tunnicliffe, Richard B.; Lockhart-Cairns, Michael P.; Levy, Colin; Mould, A. Paul; Jowitt, Thomas A.; Sito, Hilary; Baldock, Clair; Sandri-Goldin, Rozanne M.

    2017-01-01

    Abstract The transcription factor ICP4 from herpes simplex virus has a central role in regulating the gene expression cascade which controls viral infection. Here we present the crystal structure of the functionally essential ICP4 DNA binding domain in complex with a segment from its own promoter, revealing a novel homo-dimeric fold. We also studied the complex in solution by small angle X-Ray scattering, nuclear magnetic resonance and surface-plasmon resonance which indicated that, in addition to the globular domain, a flanking intrinsically disordered region also recognizes DNA. Together the data provides a rationale for the bi-partite nature of the ICP4 DNA recognition consensus sequence as the globular and disordered regions bind synergistically to adjacent DNA motifs. Therefore in common with its eukaryotic host, the viral transcription factor ICP4 utilizes disordered regions to enhance the affinity and tune the specificity of DNA interactions in tandem with a globular domain. PMID:28505309

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

    Science.gov (United States)

    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.

  18. Analysis of the landscape complexity and heterogeneity of the Pantanal wetland.

    Science.gov (United States)

    Miranda, C S; Gamarra, R M; Mioto, C L; Silva, N M; Conceição Filho, A P; Pott, A

    2018-05-01

    This is the first report on analysis of habitat complexity and heterogeneity of the Pantanal wetland. The Pantanal encompasses a peculiar mosaic of environments, being important to evaluate and monitor this area concerning conservation of biodiversity. Our objective was to indirectly measure the habitat complexity and heterogeneity of the mosaic forming the sub-regions of the Pantanal, by means of remote sensing. We obtained free images of Normalized Difference Vegetation Index (NDVI) from the sensor MODIS and calculated the mean value (complexity) and standard deviation (heterogeneity) for each sub-region in the years 2000, 2008 and 2015. The sub-regions of Poconé, Canoeira, Paraguai and Aquidauana presented the highest values of complexity (mean NDVI), between 0.69 and 0.64 in the evaluated years. The highest horizontal heterogeneity (NDVI standard deviation) was observed in the sub-region of Tuiuiú, with values of 0.19 in the years 2000 and 2015, and 0.21 in the year 2008. We concluded that the use of NDVI to estimate landscape parameters is an efficient tool for assessment and monitoring of the complexity and heterogeneity of the Pantanal habitats, applicable in other regions.

  19. Structures of transcription pre-initiation complex with TFIIH and Mediator.

    Science.gov (United States)

    Schilbach, S; Hantsche, M; Tegunov, D; Dienemann, C; Wigge, C; Urlaub, H; Cramer, P

    2017-11-09

    For the initiation of transcription, RNA polymerase II (Pol II) assembles with general transcription factors on promoter DNA to form the pre-initiation complex (PIC). Here we report cryo-electron microscopy structures of the Saccharomyces cerevisiae PIC and PIC-core Mediator complex at nominal resolutions of 4.7 Å and 5.8 Å, respectively. The structures reveal transcription factor IIH (TFIIH), and suggest how the core and kinase TFIIH modules function in the opening of promoter DNA and the phosphorylation of Pol II, respectively. The TFIIH core subunit Ssl2 (a homologue of human XPB) is positioned on downstream DNA by the 'E-bridge' helix in TFIIE, consistent with TFIIE-stimulated DNA opening. The TFIIH kinase module subunit Tfb3 (MAT1 in human) anchors the kinase Kin28 (CDK7), which is mobile in the PIC but preferentially located between the Mediator hook and shoulder in the PIC-core Mediator complex. Open spaces between the Mediator head and middle modules may allow access of the kinase to its substrate, the C-terminal domain of Pol II.

  20. SimulaTE: simulating complex landscapes of transposable elements of populations.

    Science.gov (United States)

    Kofler, Robert

    2018-04-15

    Estimating the abundance of transposable elements (TEs) in populations (or tissues) promises to answer many open research questions. However, progress is hampered by the lack of concordance between different approaches for TE identification and thus potentially unreliable results. To address this problem, we developed SimulaTE a tool that generates TE landscapes for populations using a newly developed domain specific language (DSL). The simple syntax of our DSL allows for easily building even complex TE landscapes that have, for example, nested, truncated and highly diverged TE insertions. Reads may be simulated for the populations using different sequencing technologies (PacBio, Illumina paired-ends) and strategies (sequencing individuals and pooled populations). The comparison between the expected (i.e. simulated) and the observed results will guide researchers in finding the most suitable approach for a particular research question. SimulaTE is implemented in Python and available at https://sourceforge.net/projects/simulates/. Manual https://sourceforge.net/p/simulates/wiki/Home/#manual; Test data and tutorials https://sourceforge.net/p/simulates/wiki/Home/#walkthrough; Validation https://sourceforge.net/p/simulates/wiki/Home/#validation. robert.kofler@vetmeduni.ac.at.

  1. Roles of mono-ubiquitinated Smad4 in the formation of Smad transcriptional complexes

    International Nuclear Information System (INIS)

    Wang Bei; Suzuki, Hiroyuki; Kato, Mitsuyasu

    2008-01-01

    TGF-β activates receptor-regulated Smad (R-Smad) through phosphorylation by type I receptors. Activated R-Smad binds to Smad4 and the complex translocates into the nucleus and stimulates the transcription of target genes through association with co-activators including p300. It is not clear, however, how activated Smad complexes are removed from target genes. In this study, we show that TGF-β enhances the mono-ubiquitination of Smad4. Smad4 mono-ubiquitination was promoted by p300 and suppressed by the c-Ski co-repressor. Smad4 mono-ubiquitination disrupted the interaction with Smad2 in the presence of constitutively active TGF-β type I receptor. Furthermore, mono-ubiquitinated Smad4 was not found in DNA-binding Smad complexes. A Smad4-Ubiquitin fusion protein, which mimics mono-ubiquitinated Smad4, enhanced localization to the cytoplasm. These results suggest that mono-ubiquitination of Smad4 occurs in the transcriptional activator complex and facilitates the turnover of Smad complexes at target genes

  2. Structure-aided prediction of mammalian transcription factor complexes in conserved non-coding elements

    KAUST Repository

    Guturu, H.

    2013-11-11

    Mapping the DNA-binding preferences of transcription factor (TF) complexes is critical for deciphering the functions of cis-regulatory elements. Here, we developed a computational method that compares co-occurring motif spacings in conserved versus unconserved regions of the human genome to detect evolutionarily constrained binding sites of rigid TF complexes. Structural data were used to estimate TF complex physical plausibility, explore overlapping motif arrangements seldom tackled by non-structure-aware methods, and generate and analyse three-dimensional models of the predicted complexes bound to DNA. Using this approach, we predicted 422 physically realistic TF complex motifs at 18% false discovery rate, the majority of which (326, 77%) contain some sequence overlap between binding sites. The set of mostly novel complexes is enriched in known composite motifs, predictive of binding site configurations in TF-TF-DNA crystal structures, and supported by ChIP-seq datasets. Structural modelling revealed three cooperativity mechanisms: direct protein-protein interactions, potentially indirect interactions and \\'through-DNA\\' interactions. Indeed, 38% of the predicted complexes were found to contain four or more bases in which TF pairs appear to synergize through overlapping binding to the same DNA base pairs in opposite grooves or strands. Our TF complex and associated binding site predictions are available as a web resource at http://bejerano.stanford.edu/complex.

  3. Structure-aided prediction of mammalian transcription factor complexes in conserved non-coding elements

    KAUST Repository

    Guturu, H.; Doxey, A. C.; Wenger, A. M.; Bejerano, G.

    2013-01-01

    Mapping the DNA-binding preferences of transcription factor (TF) complexes is critical for deciphering the functions of cis-regulatory elements. Here, we developed a computational method that compares co-occurring motif spacings in conserved versus unconserved regions of the human genome to detect evolutionarily constrained binding sites of rigid TF complexes. Structural data were used to estimate TF complex physical plausibility, explore overlapping motif arrangements seldom tackled by non-structure-aware methods, and generate and analyse three-dimensional models of the predicted complexes bound to DNA. Using this approach, we predicted 422 physically realistic TF complex motifs at 18% false discovery rate, the majority of which (326, 77%) contain some sequence overlap between binding sites. The set of mostly novel complexes is enriched in known composite motifs, predictive of binding site configurations in TF-TF-DNA crystal structures, and supported by ChIP-seq datasets. Structural modelling revealed three cooperativity mechanisms: direct protein-protein interactions, potentially indirect interactions and 'through-DNA' interactions. Indeed, 38% of the predicted complexes were found to contain four or more bases in which TF pairs appear to synergize through overlapping binding to the same DNA base pairs in opposite grooves or strands. Our TF complex and associated binding site predictions are available as a web resource at http://bejerano.stanford.edu/complex.

  4. Mediator complex cooperatively regulates transcription of retinoic acid target genes with Polycomb Repressive Complex 2 during neuronal differentiation.

    Science.gov (United States)

    Fukasawa, Rikiya; Iida, Satoshi; Tsutsui, Taiki; Hirose, Yutaka; Ohkuma, Yoshiaki

    2015-11-01

    The Mediator complex (Mediator) plays key roles in transcription and functions as the nexus for integration of various transcriptional signals. Previously, we screened for Mediator cyclin-dependent kinase (CDK)-interacting factors and identified three proteins related to chromatin regulation. One of them, SUZ12 is required for both stability and activity of Polycomb Repressive Complex 2 (PRC2). PRC2 primarily suppresses gene expression through histone H3 lysine 27 trimethylation, resulting in stem cell maintenance and differentiation; perturbation of this process leads to oncogenesis. Recent work showed that Mediator contributes to the embryonic stem cell state through DNA loop formation, which is strongly associated with chromatin architecture; however, it remains unclear how Mediator regulates gene expression in cooperation with chromatin regulators (i.e. writers, readers and remodelers). We found that Mediator CDKs interact directly with the PRC2 subunit EZH2, as well as SUZ12. Known PRC2 target genes were deregulated by Mediator CDK knockdown during neuronal differentiation, and both Mediator and PRC2 complexes co-occupied the promoters of developmental genes regulated by retinoic acid. Our results provide a mechanistic link between Mediator and PRC2 during neuronal differentiation. © The Authors 2015. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  5. RNA-Interference Components Are Dispensable for Transcriptional Silencing of the Drosophila Bithorax-Complex

    KAUST Repository

    Cernilogar, Filippo M.

    2013-06-13

    Background:Beyond their role in post-transcriptional gene silencing, Dicer and Argonaute, two components of the RNA interference (RNAi) machinery, were shown to be involved in epigenetic regulation of centromeric heterochromatin and transcriptional gene silencing. In particular, RNAi mechanisms appear to play a role in repeat induced silencing and some aspects of Polycomb-mediated gene silencing. However, the functional interplay of RNAi mechanisms and Polycomb group (PcG) pathways at endogenous loci remains to be elucidated.Principal Findings:Here we show that the endogenous Dicer-2/Argonaute-2 RNAi pathway is dispensable for the PcG mediated silencing of the homeotic Bithorax Complex (BX-C). Although Dicer-2 depletion triggers mild transcriptional activation at Polycomb Response Elements (PREs), this does not induce transcriptional changes at PcG-repressed genes. Moreover, Dicer-2 is not needed to maintain global levels of methylation of lysine 27 of histone H3 and does not affect PRE-mediated higher order chromatin structures within the BX-C. Finally bioinformatic analysis, comparing published data sets of PcG targets with Argonaute-2-bound small RNAs reveals no enrichment of these small RNAs at promoter regions associated with PcG proteins.Conclusions:We conclude that the Dicer-2/Argonaute-2 RNAi pathway, despite its role in pairing sensitive gene silencing of transgenes, does not have a role in PcG dependent silencing of major homeotic gene cluster loci in Drosophila. © 2013 Cernilogar et al.

  6. Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex.

    Science.gov (United States)

    Konermann, Silvana; Brigham, Mark D; Trevino, Alexandro E; Joung, Julia; Abudayyeh, Omar O; Barcena, Clea; Hsu, Patrick D; Habib, Naomi; Gootenberg, Jonathan S; Nishimasu, Hiroshi; Nureki, Osamu; Zhang, Feng

    2015-01-29

    Systematic interrogation of gene function requires the ability to perturb gene expression in a robust and generalizable manner. Here we describe structure-guided engineering of a CRISPR-Cas9 complex to mediate efficient transcriptional activation at endogenous genomic loci. We used these engineered Cas9 activation complexes to investigate single-guide RNA (sgRNA) targeting rules for effective transcriptional activation, to demonstrate multiplexed activation of ten genes simultaneously, and to upregulate long intergenic non-coding RNA (lincRNA) transcripts. We also synthesized a library consisting of 70,290 guides targeting all human RefSeq coding isoforms to screen for genes that, upon activation, confer resistance to a BRAF inhibitor. The top hits included genes previously shown to be able to confer resistance, and novel candidates were validated using individual sgRNA and complementary DNA overexpression. A gene expression signature based on the top screening hits correlated with markers of BRAF inhibitor resistance in cell lines and patient-derived samples. These results collectively demonstrate the potential of Cas9-based activators as a powerful genetic perturbation technology.

  7. Genome-Wide Phylogenetic Comparative Analysis of Plant Transcriptional Regulation: A Timeline of Loss, Gain, Expansion, and Correlation with Complexity

    OpenAIRE

    Lang, Daniel; Weiche, Benjamin; Timmerhaus, Gerrit; Richardt, Sandra; Ria?o-Pach?n, Diego M.; Corr?a, Luiz G. G.; Reski, Ralf; Mueller-Roeber, Bernd; Rensing, Stefan A.

    2010-01-01

    Evolutionary retention of duplicated genes encoding transcription-associated proteins (TAPs, comprising transcription factors and other transcriptional regulators) has been hypothesized to be positively correlated with increasing morphological complexity and paleopolyploidizations, especially within the plant kingdom. Here, we present the most comprehensive set of classification rules for TAPs and its application for genome-wide analyses of plants and algae. Using a dated species tree and phy...

  8. Fanconi anemia core complex gene promoters harbor conserved transcription regulatory elements.

    Science.gov (United States)

    Meier, Daniel; Schindler, Detlev

    2011-01-01

    The Fanconi anemia (FA) gene family is a recent addition to the complex network of proteins that respond to and repair certain types of DNA damage in the human genome. Since little is known about the regulation of this novel group of genes at the DNA level, we characterized the promoters of the eight genes (FANCA, B, C, E, F, G, L and M) that compose the FA core complex. The promoters of these genes show the characteristic attributes of housekeeping genes, such as a high GC content and CpG islands, a lack of TATA boxes and a low conservation. The promoters functioned in a monodirectional way and were, in their most active regions, comparable in strength to the SV40 promoter in our reporter plasmids. They were also marked by a distinctive transcriptional start site (TSS). In the 5' region of each promoter, we identified a region that was able to negatively regulate the promoter activity in HeLa and HEK 293 cells in isolation. The central and 3' regions of the promoter sequences harbor binding sites for several common and rare transcription factors, including STAT, SMAD, E2F, AP1 and YY1, which indicates that there may be cross-connections to several established regulatory pathways. Electrophoretic mobility shift assays and siRNA experiments confirmed the shared regulatory responses between the prominent members of the TGF-β and JAK/STAT pathways and members of the FA core complex. Although the promoters are not well conserved, they share region and sequence specific regulatory motifs and transcription factor binding sites (TBFs), and we identified a bi-partite nature to these promoters. These results support a hypothesis based on the co-evolution of the FA core complex genes that was expanded to include their promoters.

  9. Fanconi anemia core complex gene promoters harbor conserved transcription regulatory elements.

    Directory of Open Access Journals (Sweden)

    Daniel Meier

    Full Text Available The Fanconi anemia (FA gene family is a recent addition to the complex network of proteins that respond to and repair certain types of DNA damage in the human genome. Since little is known about the regulation of this novel group of genes at the DNA level, we characterized the promoters of the eight genes (FANCA, B, C, E, F, G, L and M that compose the FA core complex. The promoters of these genes show the characteristic attributes of housekeeping genes, such as a high GC content and CpG islands, a lack of TATA boxes and a low conservation. The promoters functioned in a monodirectional way and were, in their most active regions, comparable in strength to the SV40 promoter in our reporter plasmids. They were also marked by a distinctive transcriptional start site (TSS. In the 5' region of each promoter, we identified a region that was able to negatively regulate the promoter activity in HeLa and HEK 293 cells in isolation. The central and 3' regions of the promoter sequences harbor binding sites for several common and rare transcription factors, including STAT, SMAD, E2F, AP1 and YY1, which indicates that there may be cross-connections to several established regulatory pathways. Electrophoretic mobility shift assays and siRNA experiments confirmed the shared regulatory responses between the prominent members of the TGF-β and JAK/STAT pathways and members of the FA core complex. Although the promoters are not well conserved, they share region and sequence specific regulatory motifs and transcription factor binding sites (TBFs, and we identified a bi-partite nature to these promoters. These results support a hypothesis based on the co-evolution of the FA core complex genes that was expanded to include their promoters.

  10. Electrostatic study of Alanine mutational effects on transcription: application to GATA-3:DNA interaction complex.

    Science.gov (United States)

    El-Assaad, Atlal; Dawy, Zaher; Nemer, Georges

    2015-01-01

    Protein-DNA interaction is of fundamental importance in molecular biology, playing roles in functions as diverse as DNA transcription, DNA structure formation, and DNA repair. Protein-DNA association is also important in medicine; understanding Protein-DNA binding kinetics can assist in identifying disease root causes which can contribute to drug development. In this perspective, this work focuses on the transcription process by the GATA Transcription Factor (TF). GATA TF binds to DNA promoter region represented by `G,A,T,A' nucleotides sequence, and initiates transcription of target genes. When proper regulation fails due to some mutations on the GATA TF protein sequence or on the DNA promoter sequence (weak promoter), deregulation of the target genes might lead to various disorders. In this study, we aim to understand the electrostatic mechanism behind GATA TF and DNA promoter interactions, in order to predict Protein-DNA binding in the presence of mutations, while elaborating on non-covalent binding kinetics. To generate a family of mutants for the GATA:DNA complex, we replaced every charged amino acid, one at a time, with a neutral amino acid like Alanine (Ala). We then applied Poisson-Boltzmann electrostatic calculations feeding into free energy calculations, for each mutation. These calculations delineate the contribution to binding from each Ala-replaced amino acid in the GATA:DNA interaction. After analyzing the obtained data in view of a two-step model, we are able to identify potential key amino acids in binding. Finally, we applied the model to GATA-3:DNA (crystal structure with PDB-ID: 3DFV) binding complex and validated it against experimental results from the literature.

  11. Endoplasmic reticulum stress-responsive transcription factor ATF6α directs recruitment of the Mediator of RNA polymerase II transcription and multiple histone acetyltransferase complexes.

    Science.gov (United States)

    Sela, Dotan; Chen, Lu; Martin-Brown, Skylar; Washburn, Michael P; Florens, Laurence; Conaway, Joan Weliky; Conaway, Ronald C

    2012-06-29

    The basic leucine zipper transcription factor ATF6α functions as a master regulator of endoplasmic reticulum (ER) stress response genes. Previous studies have established that, in response to ER stress, ATF6α translocates to the nucleus and activates transcription of ER stress response genes upon binding sequence specifically to ER stress response enhancer elements in their promoters. In this study, we investigate the biochemical mechanism by which ATF6α activates transcription. By exploiting a combination of biochemical and multidimensional protein identification technology-based mass spectrometry approaches, we have obtained evidence that ATF6α functions at least in part by recruiting to the ER stress response enhancer elements of ER stress response genes a collection of RNA polymerase II coregulatory complexes, including the Mediator and multiple histone acetyltransferase complexes, among which are the Spt-Ada-Gcn5 acetyltransferase (SAGA) and Ada-Two-A-containing (ATAC) complexes. Our findings shed new light on the mechanism of action of ATF6α, and they outline a straightforward strategy for applying multidimensional protein identification technology mass spectrometry to determine which RNA polymerase II transcription factors and coregulators are recruited to promoters and other regulatory elements to control transcription.

  12. Shaping the landscape of the Escherichia coli chromosome: replication-transcription encounters in cells with an ectopic replication origin

    DEFF Research Database (Denmark)

    Ivanova, Darja; Taylor, Toni; Smith, Sarah L

    2015-01-01

    Each cell division requires the unwinding of millions of DNA base pairs to allow chromosome duplication and gene transcription. As DNA replication and transcription share the same template, conflicts between both processes are unavoidable and head-on collisions are thought to be particularly...

  13. The E2F-DP1 Transcription Factor Complex Regulates Centriole Duplication in Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Jacqueline G. Miller

    2016-03-01

    Full Text Available Centrioles play critical roles in the organization of microtubule-based structures, from the mitotic spindle to cilia and flagella. In order to properly execute their various functions, centrioles are subjected to stringent copy number control. Central to this control mechanism is a precise duplication event that takes place during S phase of the cell cycle and involves the assembly of a single daughter centriole in association with each mother centriole . Recent studies have revealed that posttranslational control of the master regulator Plk4/ZYG-1 kinase and its downstream effector SAS-6 is key to ensuring production of a single daughter centriole. In contrast, relatively little is known about how centriole duplication is regulated at a transcriptional level. Here we show that the transcription factor complex EFL-1-DPL-1 both positively and negatively controls centriole duplication in the Caenorhabditis elegans embryo. Specifically, we find that down regulation of EFL-1-DPL-1 can restore centriole duplication in a zyg-1 hypomorphic mutant and that suppression of the zyg-1 mutant phenotype is accompanied by an increase in SAS-6 protein levels. Further, we find evidence that EFL-1-DPL-1 promotes the transcription of zyg-1 and other centriole duplication genes. Our results provide evidence that in a single tissue type, EFL-1-DPL-1 sets the balance between positive and negative regulators of centriole assembly and thus may be part of a homeostatic mechanism that governs centriole assembly.

  14. The Complex Transcriptional Response of Acaryochloris marina to Different Oxygen Levels

    Directory of Open Access Journals (Sweden)

    Miguel A. Hernández-Prieto

    2017-02-01

    Full Text Available Ancient oxygenic photosynthetic prokaryotes produced oxygen as a waste product, but existed for a long time under an oxygen-free (anoxic atmosphere, before an oxic atmosphere emerged. The change in oxygen levels in the atmosphere influenced the chemistry and structure of many enzymes that contained prosthetic groups that were inactivated by oxygen. In the genome of Acaryochloris marina, multiple gene copies exist for proteins that are normally encoded by a single gene copy in other cyanobacteria. Using high throughput RNA sequencing to profile transcriptome responses from cells grown under microoxic and hyperoxic conditions, we detected 8446 transcripts out of the 8462 annotated genes in the Cyanobase database. Two-thirds of the 50 most abundant transcripts are key proteins in photosynthesis. Microoxic conditions negatively affected the levels of expression of genes encoding photosynthetic complexes, with the exception of some subunits. In addition to the known regulation of the multiple copies of psbA, we detected a similar transcriptional pattern for psbJ and psbU, which might play a key role in the altered components of photosystem II. Furthermore, regulation of genes encoding proteins important for reactive oxygen species-scavenging is discussed at genome level, including, for the first time, specific small RNAs having possible regulatory roles under varying oxygen levels.

  15. The Complex Transcriptional Response of Acaryochloris marina to Different Oxygen Levels

    Science.gov (United States)

    Hernández-Prieto, Miguel A.; Lin, Yuankui; Chen, Min

    2016-01-01

    Ancient oxygenic photosynthetic prokaryotes produced oxygen as a waste product, but existed for a long time under an oxygen-free (anoxic) atmosphere, before an oxic atmosphere emerged. The change in oxygen levels in the atmosphere influenced the chemistry and structure of many enzymes that contained prosthetic groups that were inactivated by oxygen. In the genome of Acaryochloris marina, multiple gene copies exist for proteins that are normally encoded by a single gene copy in other cyanobacteria. Using high throughput RNA sequencing to profile transcriptome responses from cells grown under microoxic and hyperoxic conditions, we detected 8446 transcripts out of the 8462 annotated genes in the Cyanobase database. Two-thirds of the 50 most abundant transcripts are key proteins in photosynthesis. Microoxic conditions negatively affected the levels of expression of genes encoding photosynthetic complexes, with the exception of some subunits. In addition to the known regulation of the multiple copies of psbA, we detected a similar transcriptional pattern for psbJ and psbU, which might play a key role in the altered components of photosystem II. Furthermore, regulation of genes encoding proteins important for reactive oxygen species-scavenging is discussed at genome level, including, for the first time, specific small RNAs having possible regulatory roles under varying oxygen levels. PMID:27974439

  16. What's the FOX Got to Do with the KITten? Regulating the Lineage-Specific Transcriptional Landscape in GIST.

    Science.gov (United States)

    Lee, Donna M; Duensing, Anette

    2018-02-01

    Transcriptional regulation of the KIT receptor tyrosine kinase, a master regulator in gastrointestinal stromal tumors (GIST) and their precursors, the interstitial cells of Cajal (ICC), is part of a positive feedback loop involving the transcription factor ETV1. A new study now shows that the forkhead box (FOX) family transcription factor FOXF1 not only is an upstream regulator of ETV1 and hence ICC/GIST lineage-specific gene transcription, but also functions as lineage-specific pioneer factor with an active role in chromatin rearrangement to facilitate ETV1 binding and transcriptional activity. Cancer Discov; 8(2); 146-9. ©2018 AACR See related article by Ran et al., p. 234 . ©2018 American Association for Cancer Research.

  17. Landscape Ecology

    DEFF Research Database (Denmark)

    Christensen, Andreas Aagaard; Brandt, Jesper; Svenningsen, Stig Roar

    2017-01-01

    Landscape ecology is an interdisciplinary field of research and practice that deals with the mutual association between the spatial configuration and ecological functioning of landscapes, exploring and describing processes involved in the differentiation of spaces within landscapes......, and the ecological significance of the patterns which are generated by such processes. In landscape ecology, perspectives drawn from existing academic disciplines are integrated based on a common, spatially explicit mode of analysis developed from classical holistic geography, emphasizing spatial and landscape...... pattern analysis and ecological interaction of land units. The landscape is seen as a holon: an assemblage of interrelated phenomena, both cultural and biophysical, that together form a complex whole. Enduring challenges to landscape ecology include the need to develop a systematic approach able...

  18. Core Mediator structure at 3.4 Å extends model of transcription initiation complex.

    Science.gov (United States)

    Nozawa, Kayo; Schneider, Thomas R; Cramer, Patrick

    2017-05-11

    Mediator is a multiprotein co-activator that binds the transcription pre-initiation complex (PIC) and regulates RNA polymerase (Pol) II. The Mediator head and middle modules form the essential core Mediator (cMed), whereas the tail and kinase modules play regulatory roles. The architecture of Mediator and its position on the PIC are known, but atomic details are limited to Mediator subcomplexes. Here we report the crystal structure of the 15-subunit cMed from Schizosaccharomyces pombe at 3.4 Å resolution. The structure shows an unaltered head module, and reveals the intricate middle module, which we show is globally required for transcription. Sites of known Mediator mutations cluster at the interface between the head and middle modules, and in terminal regions of the head subunits Med6 (ref. 16) and Med17 (ref. 17) that tether the middle module. The structure led to a model for Saccharomyces cerevisiae cMed that could be combined with the 3.6 Å cryo-electron microscopy structure of the core PIC (cPIC). The resulting atomic model of the cPIC-cMed complex informs on interactions of the submodules forming the middle module, called beam, knob, plank, connector, and hook. The hook is flexibly linked to Mediator by a conserved hinge and contacts the transcription initiation factor IIH (TFIIH) kinase that phosphorylates the carboxy (C)-terminal domain (CTD) of Pol II and was recently positioned on the PIC. The hook also contains residues that crosslink to the CTD and reside in a previously described cradle. These results provide a framework for understanding Mediator function, including its role in stimulating CTD phosphorylation by TFIIH.

  19. Structural insights into the mycobacteria transcription initiation complex from analysis of X-ray crystal structures

    Energy Technology Data Exchange (ETDEWEB)

    Hubin, Elizabeth A.; Lilic, Mirjana; Darst, Seth A.; Campbell, Elizabeth A.

    2017-07-13

    The mycobacteria RNA polymerase (RNAP) is a target for antimicrobials against tuberculosis, motivating structure/function studies. Here we report a 3.2 Å-resolution crystal structure of a Mycobacterium smegmatis (Msm) open promoter complex (RPo), along with structural analysis of the Msm RPo and a previously reported 2.76 Å-resolution crystal structure of an Msm transcription initiation complex with a promoter DNA fragment. We observe the interaction of the Msm RNAP α-subunit C-terminal domain (αCTD) with DNA, and we provide evidence that the αCTD may play a role in Mtb transcription regulation. Our results reveal the structure of an Actinobacteria-unique insert of the RNAP β' subunit. Finally, our analysis reveals the disposition of the N-terminal segment of Msm σA, which may comprise an intrinsically disordered protein domain unique to mycobacteria. The clade-specific features of the mycobacteria RNAP provide clues to the profound instability of mycobacteria RPo compared with E. coli.

  20. Structural hierarchy controlling dimerization and target DNA recognition in the AHR transcriptional complex

    Energy Technology Data Exchange (ETDEWEB)

    Seok, Seung-Hyeon; Lee, Woojong; Jiang, Li; Molugu, Kaivalya; Zheng, Aiping; Li, Yitong; Park, Sanghyun; Bradfield, Christopher A.; Xing, Yongna (UW)

    2017-04-10

    he aryl hydrocarbon receptor (AHR) belongs to the PAS (PER-ARNT-SIM) family transcription factors and mediates broad responses to numerous environmental pollutants and cellular metabolites, modulating diverse biological processes from adaptive metabolism, acute toxicity, to normal physiology of vascular and immune systems. The AHR forms a transcriptionally active heterodimer with ARNT (AHR nuclear translocator), which recognizes the dioxin response element (DRE) in the promoter of downstream genes. We determined the crystal structure of the mammalian AHR–ARNT heterodimer in complex with the DRE, in which ARNT curls around AHR into a highly intertwined asymmetric architecture, with extensive heterodimerization interfaces and AHR interdomain interactions. Specific recognition of the DRE is determined locally by the DNA-binding residues, which discriminates it from the closely related hypoxia response element (HRE), and is globally affected by the dimerization interfaces and interdomain interactions. Changes at the interdomain interactions caused either AHR constitutive nuclear localization or failure to translocate to nucleus, underlying an allosteric structural pathway for mediating ligand-induced exposure of nuclear localization signal. These observations, together with the global higher flexibility of the AHR PAS-A and its loosely packed structural elements, suggest a dynamic structural hierarchy for complex scenarios of AHR activation induced by its diverse ligands.

  1. Using neutral theory to reveal the contribution of meta-community processes to assembly in complex landscapes

    Directory of Open Access Journals (Sweden)

    Dominique Gravel

    2014-04-01

    Full Text Available The metacommunity perspective appears as an appropriate conceptual framework to make ecology more predictive. It is particularly relevant to limnology, where exchanges of organisms and nutrients affect community and ecosystem properties from the local to the regional scales. The recent development of neutral theory appears as a step back in that direction because of the assumption of ecological equivalence and the absence of any effect of the environment on community organization. A remarkable strength of neutral theory is nonetheless to provide a general theory of diversity that accounts for a wide range of empirical observations. In this paper, we argue that neutral theory can be useful to understand the impact of dispersal on community assembly in landscapes of various complexities. Our analysis focus on spatially explicit landscapes conceptualized as networks of local communities (e.g., lakes connected to each other by dispersal channels (e.g., rivers. The main objective of the paper is to use neutral theory to stress the importance of landscape structure on the distribution of diversity. We refer to the landscape organization as a spatial contingency that could potentially affect the coexistence mechanisms at play. We briefly review the main approaches to describe spatial networks and describe three simple toy models of metacommunity dynamics. We take this opportunity to review their assumptions and main predictions. We then conduct simulations of these models to reveal with simple examples the impact of spatial network structure on diversity distribution. The simulation results show that competitive interactions buffer the potential impact of landscape structure. The strongest relationship between node position in the landscape and species richness was observed for the patch dynamics model without any interactions. On the other hand, strong and unequal competitive interactions minimized the effect of node position. We conclude that the

  2. A DNA-binding-site landscape and regulatory network analysis for NAC transcription factors in Arabidopsis thaliana

    DEFF Research Database (Denmark)

    Lindemose, Søren; Jensen, Michael Krogh; de Velde, Jan Van

    2014-01-01

    regulatory networks of 12 NAC transcription factors. Our data offer specific single-base resolution fingerprints for most TFs studied and indicate that NAC DNA-binding specificities might be predicted from their DNA-binding domain's sequence. The developed methodology, including the application......Target gene identification for transcription factors is a prerequisite for the systems wide understanding of organismal behaviour. NAM-ATAF1/2-CUC2 (NAC) transcription factors are amongst the largest transcription factor families in plants, yet limited data exist from unbiased approaches to resolve...... the DNA-binding preferences of individual members. Here, we present a TF-target gene identification workflow based on the integration of novel protein binding microarray data with gene expression and multi-species promoter sequence conservation to identify the DNA-binding specificities and the gene...

  3. Landscape Aesthetics and the Scenic Drivers of Amenity Migration in the New West: Naturalness, Visual Scale, and Complexity

    Directory of Open Access Journals (Sweden)

    Jelena Vukomanovic

    2014-04-01

    Full Text Available Values associated with scenic beauty are common “pull factors” for amenity migrants, however the specific landscape features that attract amenity migration are poorly understood. In this study we focused on three visual quality metrics of the intermountain West (USA, with the objective of exploring the relationship between the location of exurban homes and aesthetic landscape preference, as exemplified through greenness, viewshed size, and terrain ruggedness. Using viewshed analysis, we compared the viewsheds of actual exurban houses to the viewsheds of randomly-distributed simulated (validation houses. We found that the actual exurban households can see significantly more vegetation and a more rugged (complex terrain than simulated houses. Actual exurban homes see a more rugged terrain, but do not necessarily see the highest peaks, suggesting that visual complexity throughout the viewshed may be more important. The viewsheds visible from the actual exurban houses were significantly larger than those visible from the simulated houses, indicating that visual scale is important to the general aesthetic experiences of exurbanites. The differences in visual quality metric values between actual exurban and simulated viewsheds call into question the use of county-level scales of analysis for the study of landscape preferences, which may miss key landscape aesthetic drivers of preference.

  4. An X11alpha/FSBP complex represses transcription of the GSK3beta gene promoter.

    LENUS (Irish Health Repository)

    Lau, Kwok-Fai

    2010-08-04

    X11alpha is a neuronal adaptor protein that interacts with the amyloid precursor protein (APP) through a centrally located phosphotyrosine binding domain to inhibit the production of Abeta peptide that is deposited in Alzheimer\\'s disease brains. X11alpha also contains two C-terminal postsynaptic density-95, large discs, zona occludens 1 (PDZ) domains, and we show here that through its PDZ domains, X11alpha interacts with a novel transcription factor, fibrinogen silencer binding protein. Moreover, we show that an X11alpha\\/fibrinogen silencer binding protein complex signals to the nucleus to repress glycogen synthase kinase-3beta promoter activity. Glycogen synthase kinase-3beta is a favoured candidate kinase for phosphorylating tau in Alzheimer\\'s disease. Our findings show a new function for X11alpha that may impact on Alzheimer\\'s disease pathogenesis.

  5. Genomic binding profiles of functionally distinct RNA polymerase III transcription complexes in human cells.

    Science.gov (United States)

    Moqtaderi, Zarmik; Wang, Jie; Raha, Debasish; White, Robert J; Snyder, Michael; Weng, Zhiping; Struhl, Kevin

    2010-05-01

    Genome-wide occupancy profiles of five components of the RNA polymerase III (Pol III) machinery in human cells identified the expected tRNA and noncoding RNA targets and revealed many additional Pol III-associated loci, mostly near short interspersed elements (SINEs). Several genes are targets of an alternative transcription factor IIIB (TFIIIB) containing Brf2 instead of Brf1 and have extremely low levels of TFIIIC. Strikingly, expressed Pol III genes, unlike nonexpressed Pol III genes, are situated in regions with a pattern of histone modifications associated with functional Pol II promoters. TFIIIC alone associates with numerous ETC loci, via the B box or a novel motif. ETCs are often near CTCF binding sites, suggesting a potential role in chromosome organization. Our results suggest that human Pol III complexes associate preferentially with regions near functional Pol II promoters and that TFIIIC-mediated recruitment of TFIIIB is regulated in a locus-specific manner.

  6. A real-time view of the TAR:Tat:P-TEFb complex at HIV-1 transcription sites

    Directory of Open Access Journals (Sweden)

    Knezevich Anna

    2007-05-01

    Full Text Available Abstract HIV-1 transcription is tightly regulated: silent in long-term latency and highly active in acutely-infected cells. Transcription is activated by the viral protein Tat, which recruits the elongation factor P-TEFb by binding the TAR sequence present in nascent HIV-1 RNAs. In this study, we analyzed the dynamic of the TAR:Tat:P-TEFb complex in living cells, by performing FRAP experiments at HIV-1 transcription sites. Our results indicate that a large fraction of Tat present at these sites is recruited by Cyclin T1. We found that in the presence of Tat, Cdk9 remained bound to nascent HIV-1 RNAs for 71s. In contrast, when transcription was activated by PMA/ionomycin, in the absence of Tat, Cdk9 turned-over rapidly and resided on the HIV-1 promoter for only 11s. Thus, the mechanism of trans-activation determines the residency time of P-TEFb at the HIV-1 gene, possibly explaining why Tat is such a potent transcriptional activator. In addition, we observed that Tat occupied HIV-1 transcription sites for 55s, suggesting that the TAR:Tat:P-TEFb complex dissociates from the polymerase following transcription initiation, and undergoes subsequent cycles of association/dissociation.

  7. Landscape structure control on soil CO2 efflux variability in complex terrain: Scaling from point observations to watershed scale fluxes

    Science.gov (United States)

    Diego A. Riveros-Iregui; Brian L. McGlynn

    2009-01-01

    We investigated the spatial and temporal variability of soil CO2 efflux across 62 sites of a 393-ha complex watershed of the northern Rocky Mountains. Growing season (83 day) cumulative soil CO2 efflux varied from ~300 to ~2000 g CO2 m-2, depending upon landscape position, with a median of 879.8 g CO2 m-2. Our findings revealed that highest soil CO2 efflux rates were...

  8. Complex Landscape of Germline Variants in Brazilian Patients With Hereditary and Early Onset Breast Cancer

    Directory of Open Access Journals (Sweden)

    Giovana T. Torrezan

    2018-05-01

    Full Text Available Pathogenic variants in known breast cancer (BC predisposing genes explain only about 30% of Hereditary Breast Cancer (HBC cases, whereas the underlying genetic factors for most families remain unknown. Here, we used whole-exome sequencing (WES to identify genetic variants associated to HBC in 17 patients of Brazil with familial BC and negative for causal variants in major BC risk genes (BRCA1/2, TP53, and CHEK2 c.1100delC. First, we searched for rare variants in 27 known HBC genes and identified two patients harboring truncating pathogenic variants in ATM and BARD1. For the remaining 15 negative patients, we found a substantial vast number of rare genetic variants. Thus, for selecting the most promising variants we used functional-based variant prioritization, followed by NGS validation, analysis in a control group, cosegregation analysis in one family and comparison with previous WES studies, shrinking our list to 23 novel BC candidate genes, which were evaluated in an independent cohort of 42 high-risk BC patients. Rare and possibly damaging variants were identified in 12 candidate genes in this cohort, including variants in DNA repair genes (ERCC1 and SXL4 and other cancer-related genes (NOTCH2, ERBB2, MST1R, and RAF1. Overall, this is the first WES study applied for identifying novel genes associated to HBC in Brazilian patients, in which we provide a set of putative BC predisposing genes. We also underpin the value of using WES for assessing the complex landscape of HBC susceptibility, especially in less characterized populations.

  9. Land Cover Classification in Complex and Fragmented Agricultural Landscapes of the Ethiopian Highlands

    Directory of Open Access Journals (Sweden)

    Michael Eggen

    2016-12-01

    Full Text Available Ethiopia is a largely agrarian country with nearly 85% of its employment coming from agriculture. Nevertheless, it is not known how much land is under cultivation. Mapping land cover at finer resolution and global scales has been particularly difficult in Ethiopia. The study area falls in a region of high mapping complexity with environmental challenges which require higher quality maps. Here, remote sensing is used to classify a large area of the central and northwestern highlands into eight broad land cover classes that comprise agriculture, grassland, woodland/shrub, forest, bare ground, urban/impervious surfaces, water, and seasonal water/marsh areas. We use data from Landsat spectral bands from 2000 to 2011, the Normalized Difference Vegetation Index (NDVI and its temporal mean and variance, together with a digital elevation model, all at 30-m spatial resolution, as inputs to a supervised classifier. A Support Vector Machines algorithm (SVM was chosen to deal with the size, variability and non-parametric nature of these data stacks. In post-processing, an image segmentation algorithm with a minimum mapping unit of about 0.5 hectares was used to convert per pixel classification results into an object based final map. Although the reliability of the map is modest, its overall accuracy is 55%—encouraging results for the accuracy of agricultural uses at 85% suggest that these methods do offer great utility. Confusion among grassland, woodland and barren categories reflects the difficulty of classifying savannah landscapes, especially in east central Africa with monsoonal-driven rainfall patterns where the ground is obstructed by clouds for significant periods of time. Our analysis also points out the need for high quality reference data. Further, topographic analysis of the agriculture class suggests there is a significant amount of sloping land under cultivation. These results are important for future research and environmental monitoring in

  10. Intracytoplasmic maturation of the human immunodeficiency virus type 1 reverse transcription complexes determines their capacity to integrate into chromatin

    Directory of Open Access Journals (Sweden)

    Kashanchi Fatah

    2006-01-01

    Full Text Available Abstract Background The early events of the HIV-1 life cycle include entry of the viral core into target cell, assembly of the reverse transcription complex (RTCs performing reverse transcription, its transformation into integration-competent complexes called pre-integration complexes (PICs, trafficking of complexes into the nucleus, and finally integration of the viral DNA into chromatin. Molecular details and temporal organization of these processes remain among the least investigated and most controversial problems in the biology of HIV. Results To quantitatively evaluate maturation and nuclear translocation of the HIV-1 RTCs, nucleoprotein complexes isolated from the nucleus (nRTC and cytoplasm (cRTC of HeLa cells infected with MLV Env-pseudotyped HIV-1 were analyzed by real-time PCR. While most complexes completed reverse transcription in the cytoplasm, some got into the nucleus before completing DNA synthesis. The HIV-specific RNA complexes could get into the nucleus when reverse transcription was blocked by reverse transcriptase inhibitor, although nuclear import of RNA complexes was less efficient than of DNA-containing RTCs. Analysis of the RTC nuclear import in synchronized cells infected in the G2/M phase of the cell cycle showed enrichment in the nuclei of RTCs containing incomplete HIV-1 DNA compared to non-synchronized cells, where RTCs with complete reverse transcripts prevailed. Immunoprecipitation assays identified viral proteins IN, Vpr, MA, and cellular Ini1 and PML associated with both cRTCs and nRTCs, whereas CA was detected only in cRTCs and RT was diminished in nRTCs. Cytoplasmic maturation of the complexes was associated with increased immunoreactivity with anti-Vpr and anti-IN antibodies, and decreased reactivity with antibodies to RT. Both cRTCs and nRTCs carried out endogenous reverse transcription reaction in vitro. In contrast to cRTCs, in vitro completion of reverse transcription in nRTCs did not increase their

  11. A pp32-retinoblastoma protein complex modulates androgen receptor-mediated transcription and associates with components of the splicing machinery

    International Nuclear Information System (INIS)

    Adegbola, Onikepe; Pasternack, Gary R.

    2005-01-01

    We have previously shown pp32 and the retinoblastoma protein interact. pp32 and the retinoblastoma protein are nuclear receptor transcriptional coregulators: the retinoblastoma protein is a coactivator for androgen receptor, the major regulator of prostate cancer growth, while pp32, which is highly expressed in prostate cancer, is a corepressor of the estrogen receptor. We now show pp32 increases androgen receptor-mediated transcription and the retinoblastoma protein modulates this activity. Using affinity purification and mass spectrometry, we identify members of the pp32-retinoblastoma protein complex as PSF and nonO/p54nrb, proteins implicated in coordinate regulation of nuclear receptor-mediated transcription and splicing. We show that the pp32-retinoblastoma protein complex is modulated during TPA-induced K562 differentiation. Present evidence suggests that nuclear receptors assemble multiprotein complexes to coordinately regulate transcription and mRNA processing. Our results suggest that pp32 and the retinoblastoma protein may be part of a multiprotein complex that coordinately regulates nuclear receptor-mediated transcription and mRNA processing

  12. Isotopes, Inventories and Seasonality: Unraveling Methane Source Distribution in the Complex Landscapes of the United Kingdom.

    Science.gov (United States)

    Lowry, D.; Fisher, R. E.; Zazzeri, G.; Lanoisellé, M.; France, J.; Allen, G.; Nisbet, E. G.

    2017-12-01

    Unlike the big open landscapes of many continents with large area sources dominated by one particular methane emission type that can be isotopically characterized by flight measurements and sampling, the complex patchwork of urban, fossil and agricultural methane sources across NW Europe require detailed ground surveys for characterization (Zazzeri et al., 2017). Here we outline the findings from multiple seasonal urban and rural measurement campaigns in the United Kingdom. These surveys aim to: 1) Assess source distribution and baseline in regions of planned fracking, and relate to on-site continuous baseline climatology. 2) Characterize spatial and seasonal differences in the isotopic signatures of the UNFCCC source categories, and 3) Assess the spatial validity of the 1 x 1 km UK inventory for large continuous emitters, proposed point sources, and seasonal / ephemeral emissions. The UK inventory suggests that 90% of methane emissions are from 3 source categories, ruminants, landfill and gas distribution. Bag sampling and GC-IRMS delta13C analysis shows that landfill gives a constant signature of -57 ±3 ‰ throughout the year. Fugitive gas emissions are consistent regionally depending on the North Sea supply regions feeding the network (-41 ± 2 ‰ in N England, -37 ± 2 ‰ in SE England). Ruminant, mostly cattle, emissions are far more complex as these spend winters in barns and summers in fields, but are essentially a mix of 2 end members, breath at -68 ±3 ‰ and manure at -51 ±3 ‰, resulting in broad summer field emission plumes of -64 ‰ and point winter barn emission plumes of -58 ‰. The inventory correctly locates emission hotspots from landfill, larger sewage treatment plants and gas compressor stations, giving a broad overview of emission distribution for regional model validation. Mobile surveys are adding an extra layer of detail to this which, combined with isotopic characterization, has identified spatial distribution of gas pipe leaks

  13. Light-harvesting complex gene expression is controlled by both transcriptional and post-transcriptional mechanisms during photoacclimation in Chlamydomonas reinhardtii

    CERN Document Server

    Durnford Dion, G; McKim, Sarah M; Sarchfield, Michelle L

    2003-01-01

    To compensate for increases in photon flux density (PFD), photosynthetic organisms possess mechanisms for reversibly modulating their photosynthetic apparatus to minimize photodamage. The photoacclimation response in Chlamydomonas reinhardtii was assessed following a 10-fold increase in PFD over 24h. In addition to a 50% reduction in the amount of chlorophyll and light-harvesting complexes (LHC) per cell, the expression of genes encoding polypeptides of the light-harvesting antenna were also affected. The abundance of Lhcb (a LHCH gene), Lhcb4 (a CP29-like gene), and Lhca (a LHCI gene) transcripts were reduced by 65 to 80%, within 1-2 h; however, the RNA levels of all three genes recovered to their low-light (LL) concentrations within 6-8 h. To determine the role of transcript turnover in this transient decline in abundance, the stability of all transcripts was measured. Although there was no change in the Lhcb or Lhca transcript turnover time, the Lhcb4 mRNA stability decreased 2.5-fold immediately following...

  14. Two sides of the same coin: TFIIH complexes in transcription and DNA repair.

    Science.gov (United States)

    Zhovmer, Alexander; Oksenych, Valentyn; Coin, Frédéric

    2010-04-13

    TFIIH is organized into a seven-subunit core associated with a three-subunit Cdk-activating kinase (CAK) module. TFIIH has roles in both transcription initiation and DNA repair. During the last 15 years, several studies have been conducted to identify the composition of the TFIIH complex involved in DNA repair. Recently, a new technique combining chromatin immunoprecipitation and western blotting resolved the hidden nature of the TFIIH complex participating in DNA repair. Following the recruitment of TFIIH to the damaged site, the CAK module is released from the core TFIIH, and the core subsequently associates with DNA repair factors. The release of the CAK is specifically driven by the recruitment of the DNA repair factor XPA and is required to promote the incision/excision of the damaged DNA. Once the DNA lesions have been repaired, the CAK module returns to the core TFIIH on the chromatin, together with the release of the repair factors. These data highlight the dynamic composition of a fundamental cellular factor that adapts its subunit composition to the cell needs.

  15. Two Sides of the Same Coin: TFIIH Complexes in Transcription and DNA Repair

    Directory of Open Access Journals (Sweden)

    Alexander Zhovmer

    2010-01-01

    Full Text Available TFIIH is organized into a seven-subunit core associated with a three-subunit Cdk-activating kinase (CAK module. TFIIH has roles in both transcription initiation and DNA repair. During the last 15 years, several studies have been conducted to identify the composition of the TFIIH complex involved in DNA repair. Recently, a new technique combining chromatin immunoprecipitation and western blotting resolved the hidden nature of the TFIIH complex participating in DNA repair. Following the recruitment of TFIIH to the damaged site, the CAK module is released from the core TFIIH, and the core subsequently associates with DNA repair factors. The release of the CAK is specifically driven by the recruitment of the DNA repair factor XPA and is required to promote the incision/excision of the damaged DNA. Once the DNA lesions have been repaired, the CAK module returns to the core TFIIH on the chromatin, together with the release of the repair factors. These data highlight the dynamic composition of a fundamental cellular factor that adapts its subunit composition to the cell needs.

  16. In Situ Tagged nsp15 Reveals Interactions with Coronavirus Replication/Transcription Complex-Associated Proteins

    Directory of Open Access Journals (Sweden)

    Jeremiah Athmer

    2017-01-01

    Full Text Available Coronavirus (CoV replication and transcription are carried out in close proximity to restructured endoplasmic reticulum (ER membranes in replication/transcription complexes (RTC. Many of the CoV nonstructural proteins (nsps are required for RTC function; however, not all of their functions are known. nsp15 contains an endoribonuclease domain that is conserved in the CoV family. While the enzymatic activity and crystal structure of nsp15 are well defined, its role in replication remains elusive. nsp15 localizes to sites of RNA replication, but whether it acts independently or requires additional interactions for its function remains unknown. To begin to address these questions, we created an in situ tagged form of nsp15 using the prototypic CoV, mouse hepatitis virus (MHV. In MHV, nsp15 contains the genomic RNA packaging signal (P/S, a 95-bp RNA stem-loop structure that is not required for viral replication or nsp15 function. Utilizing this knowledge, we constructed an internal hemagglutinin (HA tag that replaced the P/S. We found that nsp15-HA was localized to discrete perinuclear puncta and strongly colocalized with nsp8 and nsp12, both well-defined members of the RTC, but not the membrane (M protein, involved in virus assembly. Finally, we found that nsp15 interacted with RTC-associated proteins nsp8 and nsp12 during infection, and this interaction was RNA independent. From this, we conclude that nsp15 localizes and interacts with CoV proteins in the RTC, suggesting it plays a direct or indirect role in virus replication. Furthermore, the use of in situ epitope tags could be used to determine novel nsp-nsp interactions in coronaviruses.

  17. The Mediator Complex: At the Nexus of RNA Polymerase II Transcription.

    Science.gov (United States)

    Jeronimo, Célia; Robert, François

    2017-10-01

    Mediator is an essential, large, multisubunit, transcriptional co-activator highly conserved across eukaryotes. Mediator interacts with gene-specific transcription factors at enhancers as well as with the RNA polymerase II (RNAPII) transcription machinery bound at promoters. It also interacts with several other factors involved in various aspects of transcription, chromatin regulation, and mRNA processing. Hence, Mediator is at the nexus of RNAPII transcription, regulating its many steps and connecting transcription with co-transcriptional events. To achieve this flexible role, Mediator, which is divided into several functional modules, reorganizes its conformation and composition while making transient contacts with other components. Here, we review the mechanisms of action of Mediator and propose a unifying model for its function. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Spatial Complexity, Resilience, and Policy Diversity: Fishing on Lake-rich Landscapes

    Directory of Open Access Journals (Sweden)

    Stephen R. Carpenter

    2004-06-01

    Full Text Available The dynamics of and policies governing spatially coupled social-ecological mosaics are considered for the case of fisheries in a lake district. A microeconomic model of households addresses agent decisions at three hierarchic levels: (1 selection of the lake district from among a larger set of alternative places to live or visit, (2 selection of a base location within the lake district, and (3 selection of a portfolio of ecosystem services to use. Ecosystem services are represented by dynamics of fish production subject to multiple stable domains and trophic cascades. Policy calculations show that optimal policies will be highly heterogeneous in space and fluid in time. The diversity of possible outcomes is illustrated by simulations for a hypothetical lake district based loosely on the Northern Highlands of the State of Wisconsin. Lake districts are frequently managed as if lakes were independent, similar, endogenously regulating systems. Our findings contradict that view. One-size-fits-all (OSFA policies erode ecological and social resilience. If regulations are too stringent, social resilience declines because of the potential rewards of overharvesting. If regulations are too lax, ecological resilience is diminished by overharvesting in some lakes. In either case, local collapses of fish populations evoke spatial shifts of angling effort that can lead to serial collapses in neighboring fisheries and degraded fisheries in most or all of the lakes. Under OSFA management, the natural resources of the entire landscape become more vulnerable to transformation because of changes in, e.g., human population, the demand for resources, or fish harvesting technology. Multiplicity of management regimes can increase the ecological resilience, social resilience, and inclusive value of a spatially heterogeneous social-ecological system. Because of the complex interactions of mobile people and multistable ecosystems, management regimes must also be flexible

  19. The Mediator Complex MED15 Subunit Mediates Activation of Downstream Lipid-Related Genes by the WRINKLED1 Transcription Factor.

    Science.gov (United States)

    Kim, Mi Jung; Jang, In-Cheol; Chua, Nam-Hai

    2016-07-01

    The Mediator complex is known to be a master coordinator of transcription by RNA polymerase II, and this complex is recruited by transcription factors (TFs) to target promoters for gene activation or repression. The plant-specific TF WRINKLED1 (WRI1) activates glycolysis-related and fatty acid biosynthetic genes during embryogenesis. However, no Mediator subunit has yet been identified that mediates WRI1 transcriptional activity. Promoter-β-glucuronidase fusion experiments showed that MEDIATOR15 (MED15) is expressed in the same cells in the embryo as WRI1. We found that the Arabidopsis (Arabidopsis thaliana) MED15 subunit of the Mediator complex interacts directly with WRI1 in the nucleus. Overexpression of MED15 or WRI1 increased transcript levels of WRI1 target genes involved in glycolysis and fatty acid biosynthesis; these genes were down-regulated in wild-type or WRI1-overexpressing plants by silencing of MED15 However, overexpression of MED15 in the wri1 mutant also increased transcript levels of WRI1 target genes, suggesting that MED15 also may act with other TFs to activate downstream lipid-related genes. Chromatin immunoprecipitation assays confirmed the association of MED15 with six WRI1 target gene promoters. Additionally, silencing of MED15 resulted in reduced fatty acid content in seedlings and mature seeds, whereas MED15 overexpression increased fatty acid content in both developmental stages. Similar results were found in wri1 mutant and WRI1 overexpression lines. Together, our results indicate that the WRI1/MED15 complex transcriptionally regulates glycolysis-related and fatty acid biosynthetic genes during embryogenesis. © 2016 American Society of Plant Biologists. All Rights Reserved.

  20. Mediator, SWI/SNF and SAGA complexes regulate Yap8-dependent transcriptional activation of ACR2 in response to arsenate.

    Science.gov (United States)

    Menezes, Regina Andrade; Pimentel, Catarina; Silva, Ana Rita Courelas; Amaral, Catarina; Merhej, Jawad; Devaux, Frédéric; Rodrigues-Pousada, Claudina

    2017-04-01

    Response to arsenic stress in Saccharomyces cerevisiae is orchestrated by the regulatory protein Yap8, which mediates transcriptional activation of ACR2 and ACR3. This study contributes to the state of art knowledge of the molecular mechanisms underlying yeast stress response to arsenate as it provides the genetic and biochemical evidences that Yap8, through cysteine residues 132, 137, and 274, is the sensor of presence of arsenate in the cytosol. Moreover, it is here reported for the first time the essential role of the Mediator complex in the transcriptional activation of ACR2 by Yap8. Based on our data, we propose an order-of-function map to recapitulate the sequence of events taking place in cells injured with arsenate. Modification of the sulfhydryl state of these cysteines converts Yap8 in its activated form, triggering the recruitment of the Mediator complex to the ACR2/ACR3 promoter, through the interaction with the tail subunit Med2. The Mediator complex then transfers the regulatory signals conveyed by Yap8 to the core transcriptional machinery, which culminates with TBP occupancy, ACR2 upregulation and cell adaptation to arsenate stress. Additional co-factors are required for the transcriptional activation of ACR2 by Yap8, particularly the nucleosome remodeling activity of SWI/SNF and SAGA complexes. Copyright © 2017. Published by Elsevier B.V.

  1. Modelling centennial sediment waves in an eroding landscape – catchment complexity

    NARCIS (Netherlands)

    Schoorl, J.M.; Temme, A.J.A.M.; Veldkamp, A.

    2014-01-01

    Sediment flux dynamics in fluvial systems have often been related to changes in external drivers of topography, climate or land cover. It is well known that these dynamics are non-linear. Recently, model simulations of fluvial activity and landscape evolution have suggested that self-organization in

  2. Hotel E-Commerce: Navigating the Complex Hospitality Digital Marketing Landscape

    Directory of Open Access Journals (Sweden)

    Leora Halpern Lanz

    2016-01-01

    Full Text Available It's challenging to be a hotel market today, let alone one who needs to understand and masterfully manage digital marketing for one or more properties. From optimized websites, paid social and digital advertising, and email marketing, a marketer must should consider these strategies when trying to find a place in the digital marketing landscape.

  3. The Not5 subunit of the ccr4-not complex connects transcription and translation.

    Directory of Open Access Journals (Sweden)

    Zoltan Villanyi

    2014-10-01

    Full Text Available Recent studies have suggested that a sub-complex of RNA polymerase II composed of Rpb4 and Rpb7 couples the nuclear and cytoplasmic stages of gene expression by associating with newly made mRNAs in the nucleus, and contributing to their translation and degradation in the cytoplasm. Here we show by yeast two hybrid and co-immunoprecipitation experiments, followed by ribosome fractionation and fluorescent microscopy, that a subunit of the Ccr4-Not complex, Not5, is essential in the nucleus for the cytoplasmic functions of Rpb4. Not5 interacts with Rpb4; it is required for the presence of Rpb4 in polysomes, for interaction of Rpb4 with the translation initiation factor eIF3 and for association of Rpb4 with mRNAs. We find that Rpb7 presence in the cytoplasm and polysomes is much less significant than that of Rpb4, and that it does not depend upon Not5. Hence Not5-dependence unlinks the cytoplasmic functions of Rpb4 and Rpb7. We additionally determine with RNA immunoprecipitation and native gel analysis that Not5 is needed in the cytoplasm for the co-translational assembly of RNA polymerase II. This stems from the importance of Not5 for the association of the R2TP Hsp90 co-chaperone with polysomes translating RPB1 mRNA to protect newly synthesized Rpb1 from aggregation. Hence taken together our results show that Not5 interconnects translation and transcription.

  4. Optimal dimensionality reduction of complex dynamics: the chess game as diffusion on a free-energy landscape.

    Science.gov (United States)

    Krivov, Sergei V

    2011-07-01

    Dimensionality reduction is ubiquitous in the analysis of complex dynamics. The conventional dimensionality reduction techniques, however, focus on reproducing the underlying configuration space, rather than the dynamics itself. The constructed low-dimensional space does not provide a complete and accurate description of the dynamics. Here I describe how to perform dimensionality reduction while preserving the essential properties of the dynamics. The approach is illustrated by analyzing the chess game--the archetype of complex dynamics. A variable that provides complete and accurate description of chess dynamics is constructed. The winning probability is predicted by describing the game as a random walk on the free-energy landscape associated with the variable. The approach suggests a possible way of obtaining a simple yet accurate description of many important complex phenomena. The analysis of the chess game shows that the approach can quantitatively describe the dynamics of processes where human decision-making plays a central role, e.g., financial and social dynamics.

  5. Deciphering Fur transcriptional regulatory network highlights its complex role beyond iron metabolism in Escherichia coli

    DEFF Research Database (Denmark)

    Seo, Sang Woo; Kim, Donghyuk; Latif, Haythem

    2014-01-01

    The ferric uptake regulator (Fur) plays a critical role in the transcriptional regulation of iron metabolism. However, the full regulatory potential of Fur remains undefined. Here we comprehensively reconstruct the Fur transcriptional regulatory network in Escherichia coli K-12 MG1655 in response...

  6. Structural and functional aspects of winged-helix domains at the core of transcription initiation complexes.

    Science.gov (United States)

    Teichmann, Martin; Dumay-Odelot, Hélène; Fribourg, Sébastien

    2012-01-01

    The winged helix (WH) domain is found in core components of transcription systems in eukaryotes and prokaryotes. It represents a sub-class of the helix-turn-helix motif. The WH domain participates in establishing protein-DNA and protein-protein-interactions. Here, we discuss possible explanations for the enrichment of this motif in transcription systems.

  7. Core Transcriptional Regulatory Circuit Controlled by the TAL1 Complex in Human T Cell Acute Lymphoblastic Leukemia

    OpenAIRE

    Sanda, Takaomi; Lawton, Lee N.; Barrasa, M. Inmaculada; Fan, Zi Peng; Kohlhammer, Holger; Gutierrez, Alejandro; Ma, Wenxue; Tatarek, Jessica; Ahn, Yebin; Kelliher, Michelle A.; Jamieson, Catriona H.M.; Staudt, Louis M.; Young, Richard A.; Look, A. Thomas

    2012-01-01

    The oncogenic transcription factor TAL1/SCL is aberrantly expressed in over 40% of cases of human T-cell acute lymphoblastic leukemia (T-ALL), emphasizing its importance in the molecular pathogenesis of T-ALL. Here we identify the core transcriptional regulatory circuit controlled by TAL1 and its regulatory partners HEB, E2A, LMO1/2, GATA3 and RUNX1. We show that TAL1 forms a positive interconnected auto-regulatory loop with GATA3 and RUNX1, and that the TAL1 complex directly activates the MY...

  8. Transcription factor 19 interacts with histone 3 lysine 4 trimethylation and controls gluconeogenesis via the nucleosome-remodeling-deacetylase complex.

    Science.gov (United States)

    Sen, Sabyasachi; Sanyal, Sulagna; Srivastava, Dushyant Kumar; Dasgupta, Dipak; Roy, Siddhartha; Das, Chandrima

    2017-12-15

    Transcription factor 19 (TCF19) has been reported as a type 1 diabetes-associated locus involved in maintenance of pancreatic β cells through a fine-tuned regulation of cell proliferation and apoptosis. TCF19 also exhibits genomic association with type 2 diabetes, although the precise molecular mechanism remains unknown. It harbors both a plant homeodomain and a forkhead-associated domain implicated in epigenetic recognition and gene regulation, a phenomenon that has remained unexplored. Here, we show that TCF19 selectively interacts with histone 3 lysine 4 trimethylation through its plant homeodomain finger. Knocking down TCF19 under high-glucose conditions affected many metabolic processes, including gluconeogenesis. We found that TCF19 overexpression represses de novo glucose production in HepG2 cells. The transcriptional repression of key genes, induced by TCF19, coincided with NuRD (nucleosome-remodeling-deacetylase) complex recruitment to the promoters of these genes. TCF19 interacted with CHD4 (chromodomain helicase DNA-binding protein 4), which is a part of the NuRD complex, in a glucose concentration-independent manner. In summary, our results show that TCF19 interacts with an active transcription mark and recruits a co-repressor complex to regulate gluconeogenic gene expression in HepG2 cells. Our study offers critical insights into the molecular mechanisms of transcriptional regulation of gluconeogenesis and into the roles of chromatin readers in metabolic homeostasis. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. The cellular transcription factor CREB corresponds to activating transcription factor 47 (ATF-47) and forms complexes with a group of polypeptides related to ATF-43.

    Science.gov (United States)

    Hurst, H C; Masson, N; Jones, N C; Lee, K A

    1990-12-01

    Promoter elements containing the sequence motif CGTCA are important for a variety of inducible responses at the transcriptional level. Multiple cellular factors specifically bind to these elements and are encoded by a multigene family. Among these factors, polypeptides termed activating transcription factor 43 (ATF-43) and ATF-47 have been purified from HeLa cells and a factor referred to as cyclic AMP response element-binding protein (CREB) has been isolated from PC12 cells and rat brain. We demonstrated that CREB and ATF-47 are identical and that CREB and ATF-43 form protein-protein complexes. We also found that the cis requirements for stable DNA binding by ATF-43 and CREB are different. Using antibodies to ATF-43 we have identified a group of polypeptides (ATF-43) in the size range from 40 to 43 kDa. ATF-43 polypeptides are related by their reactivity with anti-ATF-43, DNA-binding specificity, complex formation with CREB, heat stability, and phosphorylation by protein kinase A. Certain cell types vary in their ATF-43 complement, suggesting that CREB activity is modulated in a cell-type-specific manner through interaction with ATF-43. ATF-43 polypeptides do not appear simply to correspond to the gene products of the ATF multigene family, suggesting that the size of the ATF family at the protein level is even larger than predicted from cDNA-cloning studies.

  10. Pleiotropy constrains the evolution of protein but not regulatory sequences in a transcription regulatory network influencing complex social behaviours

    Directory of Open Access Journals (Sweden)

    Daria eMolodtsova

    2014-12-01

    Full Text Available It is increasingly apparent that genes and networks that influence complex behaviour are evolutionary conserved, which is paradoxical considering that behaviour is labile over evolutionary timescales. How does adaptive change in behaviour arise if behaviour is controlled by conserved, pleiotropic, and likely evolutionary constrained genes? Pleiotropy and connectedness are known to constrain the general rate of protein evolution, prompting some to suggest that the evolution of complex traits, including behaviour, is fuelled by regulatory sequence evolution. However, we seldom have data on the strength of selection on mutations in coding and regulatory sequences, and this hinders our ability to study how pleiotropy influences coding and regulatory sequence evolution. Here we use population genomics to estimate the strength of selection on coding and regulatory mutations for a transcriptional regulatory network that influences complex behaviour of honey bees. We found that replacement mutations in highly connected transcription factors and target genes experience significantly stronger negative selection relative to weakly connected transcription factors and targets. Adaptively evolving proteins were significantly more likely to reside at the periphery of the regulatory network, while proteins with signs of negative selection were near the core of the network. Interestingly, connectedness and network structure had minimal influence on the strength of selection on putative regulatory sequences for both transcription factors and their targets. Our study indicates that adaptive evolution of complex behaviour can arise because of positive selection on protein-coding mutations in peripheral genes, and on regulatory sequence mutations in both transcription factors and their targets throughout the network.

  11. Landscape complexity and soil moisture variation in south Georgia, USA, for remote sensing applications

    Science.gov (United States)

    Giraldo, Mario A.; Bosch, David; Madden, Marguerite; Usery, Lynn; Kvien, Craig

    2008-08-01

    SummaryThis research addressed the temporal and spatial variation of soil moisture (SM) in a heterogeneous landscape. The research objective was to investigate soil moisture variation in eight homogeneous 30 by 30 m plots, similar to the pixel size of a Landsat Thematic Mapper (TM) or Enhanced Thematic Mapper plus (ETM+) image. The plots were adjacent to eight stations of an in situ soil moisture network operated by the United States Department of Agriculture-Agriculture Research Service USDA-ARS in Tifton, GA. We also studied five adjacent agricultural fields to examine the effect of different landuses/land covers (LULC) (grass, orchard, peanuts, cotton and bare soil) on the temporal and spatial variation of soil moisture. Soil moisture field data were collected on eight occasions throughout 2005 and January 2006 to establish comparisons within and among eight homogeneous plots. Consistently throughout time, analysis of variance (ANOVA) showed high variation in the soil moisture behavior among the plots and high homogeneity in the soil moisture behavior within them. A precipitation analysis for the eight sampling dates throughout the year 2005 showed similar rainfall conditions for the eight study plots. Therefore, soil moisture variation among locations was explained by in situ local conditions. Temporal stability geostatistical analysis showed that soil moisture has high temporal stability within the small plots and that a single point reading can be used to monitor soil moisture status for the plot within a maximum 3% volume/volume (v/v) soil moisture variation. Similarly, t-statistic analysis showed that soil moisture status in the upper soil layer changes within 24 h. We found statistical differences in the soil moisture between the different LULC in the agricultural fields as well as statistical differences between these fields and the adjacent 30 by 30 m plots. From this analysis, it was demonstrated that spatial proximity is not enough to produce similar

  12. Parameterization of a complex landscape for a sediment routing model of the Le Sueur River, southern Minnesota

    Science.gov (United States)

    Belmont, P.; Viparelli, E.; Parker, G.; Lauer, W.; Jennings, C.; Gran, K.; Wilcock, P.; Melesse, A.

    2008-12-01

    Modeling sediment fluxes and pathways in complex landscapes is limited by our inability to accurately measure and integrate heterogeneous, spatially distributed sources into a single coherent, predictive geomorphic transport law. In this study, we partition the complex landscape of the Le Sueur River watershed into five distributed primary source types, bluffs (including strath terrace caps), ravines, streambanks, tributaries, and flat,agriculture-dominated uplands. The sediment contribution of each source is quantified independently and parameterized for use in a sand and mud routing model. Rigorous modeling of the evolution of this landscape and sediment flux from each source type requires consideration of substrate characteristics, heterogeneity, and spatial connectivity. The subsurface architecture of the Le Sueur drainage basin is defined by a layer cake sequence of fine-grained tills, interbedded with fluvioglacial sands. Nearly instantaneous baselevel fall of 65 m occurred at 11.5 ka, as a result of the catastrophic draining of glacial Lake Agassiz through the Minnesota River, to which the Le Sueur is a tributary. The major knickpoint that was generated from that event has propagated 40 km into the Le Sueur network, initiating an incised river valley with tall, retreating bluffs and actively incising ravines. Loading estimates constrained by river gaging records that bound the knick zone indicate that bluffs connected to the river are retreating at an average rate of less than 2 cm per year and ravines are incising at an average rate of less than 0.8 mm per year, consistent with the Holocene average incision rate on the main stem of the river of less than 0.6 mm per year. Ongoing work with cosmogenic nuclide sediment tracers, ground-based LiDAR, historic aerial photos, and field mapping will be combined to represent the diversity of erosional environments and processes in a single coherent routing model.

  13. SUMO-, MAPK- and resistance protein-signaling converge at transcription complexes that regulate plant innate immunity

    NARCIS (Netherlands)

    Burg, van den H.A.; Takken, F.L.W.

    2010-01-01

    Upon pathogen perception plant innate immune receptors activate various signaling pathways that trigger host defenses. PAMP-triggered defense signaling requires mitogen-activated protein kinase (MAPK) pathways, which modulate the activity of transcription factors through phosphorylation. Here, we

  14. SUMO-, MAPK-, and resistance protein-signaling converge at transcription complexes that regulate plant innate immunity

    NARCIS (Netherlands)

    van den Burg, H.A.; Takken, F.L.W.

    2010-01-01

    Upon pathogen perception plant innate immune receptors activate various signaling pathways that trigger host defenses. PAMP-triggered defense signaling requires mitogen-activated protein kinase (MAPK) pathways, which modulate the activity of transcription factors through phosphorylation. Here, we

  15. The Tax oncogene enhances ELL incorporation into p300 and P-TEFb containing protein complexes to activate transcription.

    Science.gov (United States)

    Fufa, Temesgen D; Byun, Jung S; Wakano, Clay; Fernandez, Alfonso G; Pise-Masison, Cynthia A; Gardner, Kevin

    2015-09-11

    The eleven-nineteen lysine-rich leukemia protein (ELL) is a key regulator of RNA polymerase II mediated transcription. ELL facilitates RNA polymerase II transcription pause site entry and release by dynamically interacting with p300 and the positive transcription elongation factor b (P-TEFb). In this study, we investigated the role of ELL during the HTLV-1 Tax oncogene induced transactivation. We show that ectopic expression of Tax enhances ELL incorporation into p300 and P-TEFb containing transcriptional complexes and the subsequent recruitment of these complexes to target genes in vivo. Depletion of ELL abrogates Tax induced transactivation of the immediate early genes Fos, Egr2 and NF-kB, suggesting that ELL is an essential cellular cofactor of the Tax oncogene. Thus, our study identifies a novel mechanism of ELL-dependent transactivation of immediate early genes by Tax and provides the rational for further defining the genome-wide targets of Tax and ELL. Published by Elsevier Inc.

  16. Subunit architecture and functional modular rearrangements of the transcriptional mediator complex.

    Science.gov (United States)

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

    2014-06-05

    The multisubunit Mediator, comprising ∼30 distinct proteins, plays an essential role in gene expression regulation by acting as a bridge between DNA-binding transcription factors and the RNA polymerase II (RNAPII) transcription machinery. Efforts to uncover the Mediator mechanism have been hindered by a poor understanding of its structure, subunit organization, and conformational rearrangements. By overcoming biochemical and image analysis hurdles, we obtained accurate EM structures of yeast and human Mediators. Subunit localization experiments, docking of partial X-ray structures, and biochemical analyses resulted in comprehensive mapping of yeast Mediator subunits and a complete reinterpretation of our previous Mediator organization model. Large-scale Mediator rearrangements depend on changes at the interfaces between previously described Mediator modules, which appear to be facilitated by factors conducive to transcription initiation. Conservation across eukaryotes of Mediator structure, subunit organization, and RNA polymerase II interaction suggest conservation of fundamental aspects of the Mediator mechanism. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Fort Collins Science Center Ecosystem Dynamics branch--interdisciplinary research for addressing complex natural resource issues across landscapes and time

    Science.gov (United States)

    Bowen, Zachary H.; Melcher, Cynthia P.; Wilson, Juliette T.

    2013-01-01

    The Ecosystem Dynamics Branch of the Fort Collins Science Center offers an interdisciplinary team of talented and creative scientists with expertise in biology, botany, ecology, geology, biogeochemistry, physical sciences, geographic information systems, and remote-sensing, for tackling complex questions about natural resources. As demand for natural resources increases, the issues facing natural resource managers, planners, policy makers, industry, and private landowners are increasing in spatial and temporal scope, often involving entire regions, multiple jurisdictions, and long timeframes. Needs for addressing these issues include (1) a better understanding of biotic and abiotic ecosystem components and their complex interactions; (2) the ability to easily monitor, assess, and visualize the spatially complex movements of animals, plants, water, and elements across highly variable landscapes; and (3) the techniques for accurately predicting both immediate and long-term responses of system components to natural and human-caused change. The overall objectives of our research are to provide the knowledge, tools, and techniques needed by the U.S. Department of the Interior, state agencies, and other stakeholders in their endeavors to meet the demand for natural resources while conserving biodiversity and ecosystem services. Ecosystem Dynamics scientists use field and laboratory research, data assimilation, and ecological modeling to understand ecosystem patterns, trends, and mechanistic processes. This information is used to predict the outcomes of changes imposed on species, habitats, landscapes, and climate across spatiotemporal scales. The products we develop include conceptual models to illustrate system structure and processes; regional baseline and integrated assessments; predictive spatial and mathematical models; literature syntheses; and frameworks or protocols for improved ecosystem monitoring, adaptive management, and program evaluation. The descriptions

  18. Elk3 from hamster-a ternary complex factor with strong transcriptional repressor activity

    DEFF Research Database (Denmark)

    Hjortoe, G.M.; Weilguny, D.; Willumsen, Berthe Marie

    2005-01-01

    the transcription of genes that are activated during entry into G1. We have isolated the Cricetulus griseus Elk3 gene from the Chinese hamster ovary (CHO) cell line and investigated the transcriptional potential of this factor. Transient transfections revealed that, in addition to its regulation of the c......-fos promoter, Elk3 from CHO cells seems to inhibit other promoters controlling expression of proteins involved in G1/S phase progression; Cyclin D1 and DHFR. As has been described for the Elk3 homologs Net (Mouse) and Sap-2 (Human), the results of the present study further indicate that hamster Elk3...

  19. Communication: Theoretical prediction of free-energy landscapes for complex self-assembly

    Energy Technology Data Exchange (ETDEWEB)

    Jacobs, William M.; Reinhardt, Aleks; Frenkel, Daan [Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW (United Kingdom)

    2015-01-14

    We present a technique for calculating free-energy profiles for the nucleation of multicomponent structures that contain as many species as building blocks. We find that a key factor is the topology of the graph describing the connectivity of the target assembly. By considering the designed interactions separately from weaker, incidental interactions, our approach yields predictions for the equilibrium yield and nucleation barriers. These predictions are in good agreement with corresponding Monte Carlo simulations. We show that a few fundamental properties of the connectivity graph determine the most prominent features of the assembly thermodynamics. Surprisingly, we find that polydispersity in the strengths of the designed interactions stabilizes intermediate structures and can be used to sculpt the free-energy landscape for self-assembly. Finally, we demonstrate that weak incidental interactions can preclude assembly at equilibrium due to the combinatorial possibilities for incorrect association.

  20. SAF-A forms a complex with BRG1 and both components are required for RNA polymerase II mediated transcription.

    Directory of Open Access Journals (Sweden)

    Dzeneta Vizlin-Hodzic

    Full Text Available BACKGROUND: Scaffold attachment factor A (SAF-A participates in the regulation of gene expression by organizing chromatin into transcriptionally active domains and by interacting directly with RNA polymerase II. METHODOLOGY: Here we use co-localization, co-immunoprecipitation (co-IP and in situ proximity ligation assay (PLA to identify Brahma Related Gene 1 (BRG1, the ATP-driven motor of the human SWI-SNF chromatin remodeling complex, as another SAF-A interaction partner in mouse embryonic stem (mES cells. We also employ RNA interference to investigate functional aspects of the SAF-A/BRG1 interaction. PRINCIPAL FINDINGS: We find that endogenous SAF-A protein interacts with endogenous BRG1 protein in mES cells, and that the interaction does not solely depend on the presence of mRNA. Moreover the interaction remains intact when cells are induced to differentiate. Functional analyses reveal that dual depletion of SAF-A and BRG1 abolishes global transcription by RNA polymerase II, while the nucleolar RNA polymerase I transcription machinery remains unaffected. CONCLUSIONS: We demonstrate that SAF-A interacts with BRG1 and that both components are required for RNA Polymerase II Mediated Transcription.

  1. Evidence that Mediator is essential for Pol II transcription, but is not a required component of the preinitiation complex in vivo.

    Science.gov (United States)

    Petrenko, Natalia; Jin, Yi; Wong, Koon Ho; Struhl, Kevin

    2017-07-12

    The Mediator complex has been described as a general transcription factor, but it is unclear if it is essential for Pol II transcription and/or is a required component of the preinitiation complex (PIC) in vivo. Here, we show that depletion of individual subunits, even those essential for cell growth, causes a general but only modest decrease in transcription. In contrast, simultaneous depletion of all Mediator modules causes a drastic decrease in transcription. Depletion of head or middle subunits, but not tail subunits, causes a downstream shift in the Pol II occupancy profile, suggesting that Mediator at the core promoter inhibits promoter escape. Interestingly, a functional PIC and Pol II transcription can occur when Mediator is not detected at core promoters. These results provide strong evidence that Mediator is essential for Pol II transcription and stimulates PIC formation, but it is not a required component of the PIC in vivo.

  2. Investments on a Rugged Landscape: The Effect of Investor Population, Network Structure, and Complexity on Technological Change

    DEFF Research Database (Denmark)

    Hain, Daniel; Mas Tur, Elena

    In this paper, we investigate which characteristics of technological and financial systems might be conductive for technological change. We are particularly in how the interplay between capabilities, resources and networks among investors with the complexity and maturity of technologies affect...... rates of technological change and diversity, and prevents technologies from getting stuck in the financial “valley of death”. In a next step, we introduce investor networks and allow agents to co-invest together in order to pool financial resources and get access to their forecasting capability...... in a specific technological domain. We compare which investor network structures lead to the high rates of technological change and diversity on a given technology landscape. Results from a Monte Carlo simulation indicate networked investor population to outperform the case of isolated stand-alone investors...

  3. The effects of black-tailed prairie dogs on plant communities within a complex urban landscape: an ecological surprise?

    Science.gov (United States)

    Beals, Stower C; Hartley, Laurel M; Prevéy, Janet S; Seastedt, Timothy R

    2014-05-01

    Historically, prairie dogs (Cynomys spp.) have been considered essential keystone species of western United States grassland ecosystems because they provide unique services and increase vegetation community richness, evenness, and diversity. However, the effects of black-tailed prairie dogs (Cynomys ludovicianus) on lands adjacent to or surrounded by urban areas may not result in the same ecosystem benefits historically associated with their presence. An urban landscape presents prairie dogs with movement challenges unparalleled in natural landscapes, as well as suites of nonnative plant species that are more common in disturbed areas. This study examined a complex ecosystem where vegetation communities are being influenced by directional environmental change, and quantified the synergistic effects resulting from the protective management of a native keystone species. The data set for this analysis was comprised of 71 paired (occupied by prairie dogs vs. unoccupied) vegetation surveys and 156 additional unpaired surveys collected from around the city of Boulder, Colorado, USA for 14 yr. Linear mixed models were used to compare data from transects occupied and unoccupied by prairie dogs, as well as to evaluate the effect of prairie dog occupation duration. In the absence of prairie dogs, vegetation in this region exhibited declines in native grasses, no changes in introduced grasses, and increases in native and nonnative forbs and bare soil over the study interval. In the presence of prairie dogs, these observed directional changes were nearly all amplified at rates four to 10 times greater than when prairie dogs were absent. Areas in Boulder occupied by prairie dogs also had significantly lower richness, evenness, and diversity of plant species, compared to unoccupied areas. Analysis of plant functional groups revealed the significant reduction of perennial native grasses, as well as a significantly higher cover of introduced forbs in occupied areas. Prairie dogs

  4. Core transcriptional regulatory circuit controlled by the TAL1 complex in human T cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Sanda, Takaomi; Lawton, Lee N; Barrasa, M Inmaculada; Fan, Zi Peng; Kohlhammer, Holger; Gutierrez, Alejandro; Ma, Wenxue; Tatarek, Jessica; Ahn, Yebin; Kelliher, Michelle A; Jamieson, Catriona H M; Staudt, Louis M; Young, Richard A; Look, A Thomas

    2012-08-14

    The oncogenic transcription factor TAL1/SCL is aberrantly expressed in over 40% of cases of human T cell acute lymphoblastic leukemia (T-ALL), emphasizing its importance in the molecular pathogenesis of T-ALL. Here we identify the core transcriptional regulatory circuit controlled by TAL1 and its regulatory partners HEB, E2A, LMO1/2, GATA3, and RUNX1. We show that TAL1 forms a positive interconnected autoregulatory loop with GATA3 and RUNX1 and that the TAL1 complex directly activates the MYB oncogene, forming a positive feed-forward regulatory loop that reinforces and stabilizes the TAL1-regulated oncogenic program. One of the critical downstream targets in this circuitry is the TRIB2 gene, which is oppositely regulated by TAL1 and E2A/HEB and is essential for the survival of T-ALL cells. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Transcriptional intermediary factor 1γ binds to the anaphase-promoting complex/cyclosome and promotes mitosis

    DEFF Research Database (Denmark)

    Sedgwick, G.G.; Townsend, K.; Martin, A.

    2013-01-01

    The anaphase-promoting complex/cyclosome (APC/C) is an ubiquitin ligase that functions during mitosis. Here we identify the transcriptional regulator, transcriptional intermediary factor 1γ, TIF1γ, as an APC/C-interacting protein that regulates APC/C function. TIF1γ is not a substrate for APC....../C-dependent ubiquitylation but instead, associates specifically with the APC/C holoenzyme and Cdc20 to affect APC/C activity and progression through mitosis. RNA interference studies indicate that TIF1γ knockdown results in a specific reduction in APC/C ubiquitin ligase activity, the stabilization of APC/C substrates......, and an increase in the time taken for cells to progress through mitosis from nuclear envelope breakdown to anaphase. TIF1γ knockdown cells are also characterized by the inappropriate presence of cyclin A at metaphase, and an increase in the number of cells that fail to undergo metaphase-to-anaphase transition...

  6. Cs-137 behaviour in landscape-geochemical structures of barrier complexes

    International Nuclear Information System (INIS)

    Strakh, L.I.; Ivashkevich, I.I.; Adamovich, A.A.; Zarubin, O.L.

    1998-01-01

    The Cs-137 distribution and cumulation accrues more actively in a marsh ecological systems of barrier complexes. The physical chemical and biogeochemical barriers influence on different way on these processes

  7. Complex spatial dynamics maintain northern leopard frog (Lithobates pipiens) genetic diversity in a temporally varying landscape

    Science.gov (United States)

    Mushet, David M.; Euliss, Ned H.; Chen, Yongjiu; Stockwell, Craig A.

    2013-01-01

    In contrast to most local amphibian populations, northeastern populations of the Northern Leopard Frog (Lithobates pipiens) have displayed uncharacteristically high levels of genetic diversity that have been attributed to large, stable populations. However, this widely distributed species also occurs in areas known for great climatic fluctuations that should be reflected in corresponding fluctuations in population sizes and reduced genetic diversity. To test our hypothesis that Northern Leopard Frog genetic diversity would be reduced in areas subjected to significant climate variability, we examined the genetic diversity of L. pipiens collected from 12 sites within the Prairie Pothole Region of North Dakota. Despite the region's fluctuating climate that includes periods of recurring drought and deluge, we found unexpectedly high levels of genetic diversity approaching that of northeastern populations. Further, genetic structure at a landscape scale was strikingly homogeneous; genetic differentiation estimates (Dest) averaged 0.10 (SD = 0.036) across the six microsatellite loci we studied, and two Bayesian assignment tests (STRUCTURE and BAPS) failed to reveal the development of significant population structure across the 68 km breadth of our study area. These results suggest that L. pipiens in the Prairie Pothole Region consists of a large, panmictic population capable of maintaining high genetic diversity in the face of marked climate variability.

  8. Unexpected complexity of the reef-building coral Acropora millepora transcription factor network.

    KAUST Repository

    Ryu, Tae Woo

    2011-04-28

    Coral reefs are disturbed on a global scale by environmental changes including rising sea surface temperatures and ocean acidification. Little is known about how corals respond or adapt to these environmental changes especially at the molecular level. This is mostly because of the paucity of genome-wide studies on corals and the application of systems approaches that incorporate the latter. Like in any other organism, the response of corals to stress is tightly controlled by the coordinated interplay of many transcription factors.

  9. Temporal regulation of Drosophila salivary gland degeneration by the Broad-Complex transcription factors

    Czech Academy of Sciences Publication Activity Database

    Kuchárová-Mahmood, S.; Raška, Ivan; Mechler, B. M.; Farkaš, R.

    2002-01-01

    Roč. 140, - (2002), s. 67-78 ISSN 1047-8477 R&D Projects: GA ČR GA304/02/0342 Grant - others:GA-(SK) VEGA:2/7194/20 Institutional research plan: CEZ:AV0Z5039906; CEZ:MSM 111100003 Keywords : programmed cell death * BR-C transcription factors * drosophila Subject RIV: EA - Cell Biology Impact factor: 4.194, year: 2002

  10. Unexpected complexity of the reef-building coral Acropora millepora transcription factor network.

    KAUST Repository

    Ryu, Tae Woo; Mavromatis, Charalampos Harris; Bayer, Till; Voolstra, Christian R.; Ravasi, Timothy

    2011-01-01

    Coral reefs are disturbed on a global scale by environmental changes including rising sea surface temperatures and ocean acidification. Little is known about how corals respond or adapt to these environmental changes especially at the molecular level. This is mostly because of the paucity of genome-wide studies on corals and the application of systems approaches that incorporate the latter. Like in any other organism, the response of corals to stress is tightly controlled by the coordinated interplay of many transcription factors.

  11. Bovine proteins containing poly-glutamine repeats are often polymorphic and enriched for components of transcriptional regulatory complexes

    LENUS (Irish Health Repository)

    Whan, Vicki

    2010-11-23

    Abstract Background About forty human diseases are caused by repeat instability mutations. A distinct subset of these diseases is the result of extreme expansions of polymorphic trinucleotide repeats; typically CAG repeats encoding poly-glutamine (poly-Q) tracts in proteins. Polymorphic repeat length variation is also apparent in human poly-Q encoding genes from normal individuals. As these coding sequence repeats are subject to selection in mammals, it has been suggested that normal variations in some of these typically highly conserved genes are implicated in morphological differences between species and phenotypic variations within species. At present, poly-Q encoding genes in non-human mammalian species are poorly documented, as are their functions and propensities for polymorphic variation. Results The current investigation identified 178 bovine poly-Q encoding genes (Q ≥ 5) and within this group, 26 genes with orthologs in both human and mouse that did not contain poly-Q repeats. The bovine poly-Q encoding genes typically had ubiquitous expression patterns although there was bias towards expression in epithelia, brain and testes. They were also characterised by unusually large sizes. Analysis of gene ontology terms revealed that the encoded proteins were strongly enriched for functions associated with transcriptional regulation and many contributed to physical interaction networks in the nucleus where they presumably act cooperatively in transcriptional regulatory complexes. In addition, the coding sequence CAG repeats in some bovine genes impacted mRNA splicing thereby generating unusual transcriptional diversity, which in at least one instance was tissue-specific. The poly-Q encoding genes were prioritised using multiple criteria for their likelihood of being polymorphic and then the highest ranking group was experimentally tested for polymorphic variation within a cattle diversity panel. Extensive and meiotically stable variation was identified

  12. ATF1 Modulates the Heat Shock Response by Regulating the Stress-Inducible Heat Shock Factor 1 Transcription Complex

    Science.gov (United States)

    Takii, Ryosuke; Fujimoto, Mitsuaki; Tan, Ke; Takaki, Eiichi; Hayashida, Naoki; Nakato, Ryuichiro; Shirahige, Katsuhiko

    2014-01-01

    The heat shock response is an evolutionally conserved adaptive response to high temperatures that controls proteostasis capacity and is regulated mainly by an ancient heat shock factor (HSF). However, the regulation of target genes by the stress-inducible HSF1 transcription complex has not yet been examined in detail in mammalian cells. In the present study, we demonstrated that HSF1 interacted with members of the ATF1/CREB family involved in metabolic homeostasis and recruited them on the HSP70 promoter in response to heat shock. The HSF1 transcription complex, including the chromatin-remodeling factor BRG1 and lysine acetyltransferases p300 and CREB-binding protein (CBP), was formed in a manner that was dependent on the phosphorylation of ATF1. ATF1-BRG1 promoted the establishment of an active chromatin state and HSP70 expression during heat shock, whereas ATF1-p300/CBP accelerated the shutdown of HSF1 DNA-binding activity during recovery from acute stress, possibly through the acetylation of HSF1. Furthermore, ATF1 markedly affected the resistance to heat shock. These results revealed the unanticipated complexity of the primitive heat shock response mechanism, which is connected to metabolic adaptation. PMID:25312646

  13. A Comprehensive Genomic Analysis Reveals the Genetic Landscape of Mitochondrial Respiratory Chain Complex Deficiencies.

    Directory of Open Access Journals (Sweden)

    Masakazu Kohda

    2016-01-01

    Full Text Available Mitochondrial disorders have the highest incidence among congenital metabolic disorders characterized by biochemical respiratory chain complex deficiencies. It occurs at a rate of 1 in 5,000 births, and has phenotypic and genetic heterogeneity. Mutations in about 1,500 nuclear encoded mitochondrial proteins may cause mitochondrial dysfunction of energy production and mitochondrial disorders. More than 250 genes that cause mitochondrial disorders have been reported to date. However exact genetic diagnosis for patients still remained largely unknown. To reveal this heterogeneity, we performed comprehensive genomic analyses for 142 patients with childhood-onset mitochondrial respiratory chain complex deficiencies. The approach includes whole mtDNA and exome analyses using high-throughput sequencing, and chromosomal aberration analyses using high-density oligonucleotide arrays. We identified 37 novel mutations in known mitochondrial disease genes and 3 mitochondria-related genes (MRPS23, QRSL1, and PNPLA4 as novel causative genes. We also identified 2 genes known to cause monogenic diseases (MECP2 and TNNI3 and 3 chromosomal aberrations (6q24.3-q25.1, 17p12, and 22q11.21 as causes in this cohort. Our approaches enhance the ability to identify pathogenic gene mutations in patients with biochemically defined mitochondrial respiratory chain complex deficiencies in clinical settings. They also underscore clinical and genetic heterogeneity and will improve patient care of this complex disorder.

  14. Post-transcriptional generation of miRNA variants by multiple nucleotidyl transferases contributes to miRNA transcriptome complexity

    OpenAIRE

    Wyman, Stacia K.; Knouf, Emily C.; Parkin, Rachael K.; Fritz, Brian R.; Lin, Daniel W.; Dennis, Lucas M.; Krouse, Michael A.; Webster, Philippa J.; Tewari, Muneesh

    2011-01-01

    Modification of microRNA sequences by the 3′ addition of nucleotides to generate so-called “isomiRs” adds to the complexity of miRNA function, with recent reports showing that 3′ modifications can influence miRNA stability and efficiency of target repression. Here, we show that the 3′ modification of miRNAs is a physiological and common post-transcriptional event that shows selectivity for specific miRNAs and is observed across species ranging from C. elegans to human. The modifications resul...

  15. The NBS1-Treacle complex controls ribosomal RNA transcription in response to DNA damage

    DEFF Research Database (Denmark)

    Larsen, Dorthe H; Hari, Flurina; Clapperton, Julie A

    2014-01-01

    Chromosome breakage elicits transient silencing of ribosomal RNA synthesis, but the mechanisms involved remained elusive. Here we discover an in trans signalling mechanism that triggers pan-nuclear silencing of rRNA transcription in response to DNA damage. This is associated with transient...... recruitment of the Nijmegen breakage syndrome protein 1 (NBS1), a central regulator of DNA damage responses, into the nucleoli. We further identify TCOF1 (also known as Treacle), a nucleolar factor implicated in ribosome biogenesis and mutated in Treacher Collins syndrome, as an interaction partner of NBS1...

  16. The Mediator complex of Caenorhabditis elegans: insights into the developmental and physiological roles of a conserved transcriptional coregulator.

    Science.gov (United States)

    Grants, Jennifer M; Goh, Grace Y S; Taubert, Stefan

    2015-02-27

    The Mediator multiprotein complex ('Mediator') is an important transcriptional coregulator that is evolutionarily conserved throughout eukaryotes. Although some Mediator subunits are essential for the transcription of all protein-coding genes, others influence the expression of only subsets of genes and participate selectively in cellular signaling pathways. Here, we review the current knowledge of Mediator subunit function in the nematode Caenorhabditis elegans, a metazoan in which established and emerging genetic technologies facilitate the study of developmental and physiological regulation in vivo. In this nematode, unbiased genetic screens have revealed critical roles for Mediator components in core developmental pathways such as epidermal growth factor (EGF) and Wnt/β-catenin signaling. More recently, important roles for C. elegans Mediator subunits have emerged in the regulation of lipid metabolism and of systemic stress responses, engaging conserved transcription factors such as nuclear hormone receptors (NHRs). We emphasize instances where similar functions for individual Mediator subunits exist in mammals, highlighting parallels between Mediator subunit action in nematode development and in human cancer biology. We also discuss a parallel between the association of the Mediator subunit MED12 with several human disorders and the role of its C. elegans ortholog mdt-12 as a regulatory hub that interacts with numerous signaling pathways. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  17. Complexity of CNC transcription factors as revealed by gene targeting of the Nrf3 locus.

    Science.gov (United States)

    Derjuga, Anna; Gourley, Tania S; Holm, Teresa M; Heng, Henry H Q; Shivdasani, Ramesh A; Ahmed, Rafi; Andrews, Nancy C; Blank, Volker

    2004-04-01

    Cap'n'collar (CNC) family basic leucine zipper transcription factors play crucial roles in the regulation of mammalian gene expression and development. To determine the in vivo function of the CNC protein Nrf3 (NF-E2-related factor 3), we generated mice deficient in this transcription factor. We performed targeted disruption of two Nrf3 exons coding for CNC homology, basic DNA-binding, and leucine zipper dimerization domains. Nrf3 null mice developed normally and revealed no obvious phenotypic differences compared to wild-type animals. Nrf3(-/-) mice were fertile, and gross anatomy as well as behavior appeared normal. The mice showed normal age progression and did not show any apparent additional phenotype during their life span. We observed no differences in various blood parameters and chemistry values. We infected wild-type and Nrf3(-/-) mice with acute lymphocytic choriomeningitis virus and found no differences in these animals with respect to their number of virus-specific CD8 and CD4 T cells as well as their B-lymphocyte response. To determine whether the mild phenotype of Nrf3 null animals is due to functional redundancy, we generated mice deficient in multiple CNC factors. Contrary to our expectations, an absence of Nrf3 does not seem to cause additional lethality in compound Nrf3(-/-)/Nrf2(-/-) and Nrf3(-/-)/p45(-/-) mice. We hypothesize that the role of Nrf3 in vivo may become apparent only after appropriate challenge to the mice.

  18. Structures of BmrR-Drug Complexes Reveal a Rigid Multidrug Binding Pocket And Transcription Activation Through Tyrosine Expulsion

    Energy Technology Data Exchange (ETDEWEB)

    Newberry, K.J.; Huffman, J.L.; Miller, M.C.; Vazquez-Laslop, N.; Neyfakh, A.A.; Brennan, R.G.

    2009-05-22

    BmrR is a member of the MerR family and a multidrug binding transcription factor that up-regulates the expression of the bmr multidrug efflux transporter gene in response to myriad lipophilic cationic compounds. The structural mechanism by which BmrR binds these chemically and structurally different drugs and subsequently activates transcription is poorly understood. Here, we describe the crystal structures of BmrR bound to rhodamine 6G (R6G) or berberine (Ber) and cognate DNA. These structures reveal each drug stacks against multiple aromatic residues with their positive charges most proximal to the carboxylate group of Glu-253 and that, unlike other multidrug binding pockets, that of BmrR is rigid. Substitution of Glu-253 with either alanine (E253A) or glutamine (E253Q) results in unpredictable binding affinities for R6G, Ber, and tetraphenylphosphonium. Moreover, these drug binding studies reveal that the negative charge of Glu-253 is not important for high affinity binding to Ber and tetraphenylphosphonium but plays a more significant, but unpredictable, role in R6G binding. In vitro transcription data show that E253A and E253Q are constitutively active, and structures of the drug-free E253A-DNA and E253Q-DNA complexes support a transcription activation mechanism requiring the expulsion of Tyr-152 from the multidrug binding pocket. In sum, these data delineate the mechanism by which BmrR binds lipophilic, monovalent cationic compounds and suggest the importance of the redundant negative electrostatic nature of this rigid drug binding pocket that can be used to discriminate against molecules that are not substrates of the Bmr multidrug efflux pump.

  19. Downregulation of RND3/RhoE in glioblastoma patients promotes tumorigenesis through augmentation of notch transcriptional complex activity

    International Nuclear Information System (INIS)

    Liu, Baohui; Lin, Xi; Yang, Xiangsheng; Dong, Huimin; Yue, Xiaojing; Andrade, Kelsey C; Guo, Zhentao; Yang, Jian; Wu, Liquan; Zhu, Xiaonan; Zhang, Shenqi; Tian, Daofeng; Wang, Junmin; Cai, Qiang; Chen, Qizuan; Mao, Shanping; Chen, Qianxue; Chang, Jiang

    2015-01-01

    Activation of Notch signaling contributes to glioblastoma multiform (GBM) tumorigenesis. However, the molecular mechanism that promotes the Notch signaling augmentation during GBM genesis remains largely unknown. Identification of new factors that regulate Notch signaling is critical for tumor treatment. The expression levels of RND3 and its clinical implication were analyzed in GBM patients. Identification of RND3 as a novel factor in GBM genesis was demonstrated in vitro by cell experiments and in vivo by a GBM xenograft model. We found that RND3 expression was significantly decreased in human glioblastoma. The levels of RND3 expression were inversely correlated with Notch activity, tumor size, and tumor cell proliferation, and positively correlated with patient survival time. We demonstrated that RND3 functioned as an endogenous repressor of the Notch transcriptional complex. RND3 physically interacted with NICD, CSL, and MAML1, the Notch transcriptional complex factors, promoted NICD ubiquitination, and facilitated the degradation of these cofactor proteins. We further revealed that RND3 facilitated the binding of NICD to FBW7, a ubiquitin ligase, and consequently enhanced NICD protein degradation. Therefore, Notch transcriptional activity was inhibited. Forced expression of RND3 repressed Notch signaling, which led to the inhibition of glioblastoma cell proliferation in vitro and tumor growth in the xenograft mice in vivo. Downregulation of RND3, however, enhanced Notch signaling activity, and subsequently promoted glioma cell proliferation. Inhibition of Notch activity abolished RND3 deficiency-mediated GBM cell proliferation. We conclude that downregulation of RND3 is responsible for the enhancement of Notch activity that promotes glioblastoma genesis

  20. Ethylene Control of Fruit Ripening: Revisiting the Complex Network of Transcriptional Regulation1

    Science.gov (United States)

    Chervin, Christian; Bouzayen, Mondher

    2015-01-01

    The plant hormone ethylene plays a key role in climacteric fruit ripening. Studies on components of ethylene signaling have revealed a linear transduction pathway leading to the activation of ethylene response factors. However, the means by which ethylene selects the ripening-related genes and interacts with other signaling pathways to regulate the ripening process are still to be elucidated. Using tomato (Solanum lycopersicum) as a reference species, the present review aims to revisit the mechanisms by which ethylene regulates fruit ripening by taking advantage of new tools available to perform in silico studies at the genome-wide scale, leading to a global view on the expression pattern of ethylene biosynthesis and response genes throughout ripening. Overall, it provides new insights on the transcriptional network by which this hormone coordinates the ripening process and emphasizes the interplay between ethylene and ripening-associated developmental factors and the link between epigenetic regulation and ethylene during fruit ripening. PMID:26511917

  1. An Evaluation of Fractal Surface Measurement Methods for Characterizing Landscape Complexity from Remote-Sensing Imagery

    Science.gov (United States)

    Lam, Nina Siu-Ngan; Qiu, Hong-Lie; Quattrochi, Dale A.; Emerson, Charles W.; Arnold, James E. (Technical Monitor)

    2001-01-01

    The rapid increase in digital data volumes from new and existing sensors necessitates the need for efficient analytical tools for extracting information. We developed an integrated software package called ICAMS (Image Characterization and Modeling System) to provide specialized spatial analytical functions for interpreting remote sensing data. This paper evaluates the three fractal dimension measurement methods: isarithm, variogram, and triangular prism, along with the spatial autocorrelation measurement methods Moran's I and Geary's C, that have been implemented in ICAMS. A modified triangular prism method was proposed and implemented. Results from analyzing 25 simulated surfaces having known fractal dimensions show that both the isarithm and triangular prism methods can accurately measure a range of fractal surfaces. The triangular prism method is most accurate at estimating the fractal dimension of higher spatial complexity, but it is sensitive to contrast stretching. The variogram method is a comparatively poor estimator for all of the surfaces, particularly those with higher fractal dimensions. Similar to the fractal techniques, the spatial autocorrelation techniques are found to be useful to measure complex images but not images with low dimensionality. These fractal measurement methods can be applied directly to unclassified images and could serve as a tool for change detection and data mining.

  2. The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

    Science.gov (United States)

    Astle, William J; Elding, Heather; Jiang, Tao; Allen, Dave; Ruklisa, Dace; Mann, Alice L; Mead, Daniel; Bouman, Heleen; Riveros-Mckay, Fernando; Kostadima, Myrto A; Lambourne, John J; Sivapalaratnam, Suthesh; Downes, Kate; Kundu, Kousik; Bomba, Lorenzo; Berentsen, Kim; Bradley, John R; Daugherty, Louise C; Delaneau, Olivier; Freson, Kathleen; Garner, Stephen F; Grassi, Luigi; Guerrero, Jose; Haimel, Matthias; Janssen-Megens, Eva M; Kaan, Anita; Kamat, Mihir; Kim, Bowon; Mandoli, Amit; Marchini, Jonathan; Martens, Joost H A; Meacham, Stuart; Megy, Karyn; O'Connell, Jared; Petersen, Romina; Sharifi, Nilofar; Sheard, Simon M; Staley, James R; Tuna, Salih; van der Ent, Martijn; Walter, Klaudia; Wang, Shuang-Yin; Wheeler, Eleanor; Wilder, Steven P; Iotchkova, Valentina; Moore, Carmel; Sambrook, Jennifer; Stunnenberg, Hendrik G; Di Angelantonio, Emanuele; Kaptoge, Stephen; Kuijpers, Taco W; Carrillo-de-Santa-Pau, Enrique; Juan, David; Rico, Daniel; Valencia, Alfonso; Chen, Lu; Ge, Bing; Vasquez, Louella; Kwan, Tony; Garrido-Martín, Diego; Watt, Stephen; Yang, Ying; Guigo, Roderic; Beck, Stephan; Paul, Dirk S; Pastinen, Tomi; Bujold, David; Bourque, Guillaume; Frontini, Mattia; Danesh, John; Roberts, David J; Ouwehand, Willem H; Butterworth, Adam S; Soranzo, Nicole

    2016-11-17

    Many common variants have been associated with hematological traits, but identification of causal genes and pathways has proven challenging. We performed a genome-wide association analysis in the UK Biobank and INTERVAL studies, testing 29.5 million genetic variants for association with 36 red cell, white cell, and platelet properties in 173,480 European-ancestry participants. This effort yielded hundreds of low frequency (<5%) and rare (<1%) variants with a strong impact on blood cell phenotypes. Our data highlight general properties of the allelic architecture of complex traits, including the proportion of the heritable component of each blood trait explained by the polygenic signal across different genome regulatory domains. Finally, through Mendelian randomization, we provide evidence of shared genetic pathways linking blood cell indices with complex pathologies, including autoimmune diseases, schizophrenia, and coronary heart disease and evidence suggesting previously reported population associations between blood cell indices and cardiovascular disease may be non-causal. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Rumblings and Rainfall, Rebels, Remittances and Roads- The complex landscape of slope failure in Nepal

    Science.gov (United States)

    McAdoo, Brian G.; Sudmeier, Karen; Devkota, Sanjaya

    2017-04-01

    During the first monsoon season following the deadly 2015 Gorkha earthquake, 27 people were killed during two events in Nepal's Western Region due to debris flows triggered by a 24-hour, 315 mm cloudburst (Devkota et al. 2015). Both events were linked with roads: the first was caused by an accumulation of water on a newly constructed road above a steep, deforested slope, the second wiped out a major road and destroyed 10 houses. These deadly landslides were not triggered solely by extreme rainfall, but rather a complex combination of earthquakes, intensified rainfall associated with climate change and an explosion of unplanned rural road construction fueled by an increase in foreign investment, remittances and decentralisation of budgets and power from the central government to local villages. This complexity is explored through a trend data analysis on the number of landslides, landslide fatalities, rainfall intensity, and the road network in Nepal between 1980-2014 (McAdoo et al, submitted). Of most concern are the poorly constructed roads in Nepal's Middle Hill districts ( 1000-3000 m above sea level, humid, subtropical) as they are proliferating at an unprecedented pace without proper alignment, drainage, grading or maintenance. They are occurring in areas which frequently receive up to 4,000-5,000 mm of precipitation per year, causing considerable loss in lives, livelihoods and investment. Landslide fatalities increased from 88 on average for the period 1982-1995 to 130 deaths per year for the period 2007-2014 (Desinventar, 2016). Contrary to numerous studies which show a strong link between rainfall and landslides, our trend analysis demonstrates a decoupling of climate and the geomorphic drivers, pointing to other factors, namely the exponential road construction trend to explain the increase in landslide fatalities. Nepal has some of the oldest manuals and well-trained cadres in low-cost green engineering practices, yet these are rarely applied. To reverse

  4. Evaluation of Different Topographic Corrections for Landsat TM Data by Prediction of Foliage Projective Cover (FPC in Topographically Complex Landscapes

    Directory of Open Access Journals (Sweden)

    Sisira Ediriweera

    2013-12-01

    Full Text Available The reflected radiance in topographically complex areas is severely affected by variations in topography; thus, topographic correction is considered a necessary pre-processing step when retrieving biophysical variables from these images. We assessed the performance of five topographic corrections: (i C correction (C, (ii Minnaert, (iii Sun Canopy Sensor (SCS, (iv SCS + C and (v the Processing Scheme for Standardised Surface Reflectance (PSSSR on the Landsat-5 Thematic Mapper (TM reflectance in the context of prediction of Foliage Projective Cover (FPC in hilly landscapes in north-eastern Australia. The performance of topographic corrections on the TM reflectance was assessed by (i visual comparison and (ii statistically comparing TM predicted FPC with ground measured FPC and LiDAR (Light Detection and Ranging-derived FPC estimates. In the majority of cases, the PSSSR method performed best in terms of eliminating topographic effects, providing the best relationship and lowest residual error when comparing ground measured FPC and LiDAR FPC with TM predicted FPC. The Minnaert, C and SCS + C showed the poorest performance. Finally, the use of TM surface reflectance, which includes atmospheric correction and broad Bidirectional Reflectance Distribution Function (BRDF effects, seemed to account for most topographic variation when predicting biophysical variables, such as FPC.

  5. A comprehensive custom panel design for routine hereditary cancer testing: preserving control, improving diagnostics and revealing a complex variation landscape.

    Science.gov (United States)

    Castellanos, Elisabeth; Gel, Bernat; Rosas, Inma; Tornero, Eva; Santín, Sheila; Pluvinet, Raquel; Velasco, Juan; Sumoy, Lauro; Del Valle, Jesús; Perucho, Manuel; Blanco, Ignacio; Navarro, Matilde; Brunet, Joan; Pineda, Marta; Feliubadaló, Lidia; Capellá, Gabi; Lázaro, Conxi; Serra, Eduard

    2017-01-04

    We wanted to implement an NGS strategy to globally analyze hereditary cancer with diagnostic quality while retaining the same degree of understanding and control we had in pre-NGS strategies. To do this, we developed the I2HCP panel, a custom bait library covering 122 hereditary cancer genes. We improved bait design, tested different NGS platforms and created a clinically driven custom data analysis pipeline. The I2HCP panel was developed using a training set of hereditary colorectal cancer, hereditary breast and ovarian cancer and neurofibromatosis patients and reached an accuracy, analytical sensitivity and specificity greater than 99%, which was maintained in a validation set. I2HCP changed our diagnostic approach, involving clinicians and a genetic diagnostics team from panel design to reporting. The new strategy improved diagnostic sensitivity, solved uncertain clinical diagnoses and identified mutations in new genes. We assessed the genetic variation in the complete set of hereditary cancer genes, revealing a complex variation landscape that coexists with the disease-causing mutation. We developed, validated and implemented a custom NGS-based strategy for hereditary cancer diagnostics that improved our previous workflows. Additionally, the existence of a rich genetic variation in hereditary cancer genes favors the use of this panel to investigate their role in cancer risk.

  6. Free energy landscape of siRNA-polycation complexation: Elucidating the effect of molecular geometry, polymer flexibility, and charge neutralization.

    Directory of Open Access Journals (Sweden)

    Gianvito Grasso

    Full Text Available The success of medical threatments with DNA and silencing interference RNA is strongly related to the design of efficient delivery technologies. Cationic polymers represent an attractive strategy to serve as nucleic-acid carriers with the envisioned advantages of efficient complexation, low cost, ease of production, well-defined size, and low polydispersity index. However, the balance between efficacy and toxicity (safety of these polymers is a challenge and in need of improvement. With the aim of designing more effective polycationic-based gene carriers, many parameters such as carrier morphology, size, molecular weight, surface chemistry, and flexibility/rigidity ratio need to be taken into consideration. In the present work, the binding mechanism of three cationic polymers (polyarginine, polylysine and polyethyleneimine to a model siRNA target is computationally investigated at the atomistic level. In order to better understand the polycationic carrier-siRNA interactions, replica exchange molecular dynamic simulations were carried out to provide an exhaustive exploration of all the possible binding sites, taking fully into account the siRNA flexibility together with the presence of explicit solvent and ions. Moreover, well-tempered metadynamics simulations were employed to elucidate how molecular geometry, polycation flexibility, and charge neutralization affect the siRNA-polycations free energy landscape in term of low-energy binding modes and unbinding free energy barriers. Significant differences among polymer binding modes have been detected, revealing the advantageous binding properties of polyarginine and polylysine compared to polyethyleneimine.

  7. Identification of a methylated oligoribonucleotide as a potent inhibitor of HIV-1 reverse transcription complex.

    Science.gov (United States)

    Grigorov, Boyan; Bocquin, Anne; Gabus, Caroline; Avilov, Sergey; Mély, Yves; Agopian, Audrey; Divita, Gilles; Gottikh, Marina; Witvrouw, Myriam; Darlix, Jean-Luc

    2011-07-01

    Upon HIV-1 infection of a target cell, the viral reverse transcriptase (RT) copies the genomic RNA to synthesize the viral DNA. The genomic RNA is within the incoming HIV-1 core where it is coated by molecules of nucleocapsid (NC) protein that chaperones the reverse transcription process. Indeed, the RT chaperoning properties of NC extend from the initiation of cDNA synthesis to completion of the viral DNA. New and effective drugs against HIV-1 continue to be required, which prompted us to search for compounds aimed at inhibiting NC protein. Here, we report that the NC chaperoning activity is extensively inhibited in vitro by small methylated oligoribonucleotides (mODN). These mODNs were delivered intracellularly using a cell-penetrating-peptide and found to impede HIV-1 replication in primary human cells at nanomolar concentrations. Extensive analysis showed that viral cDNA synthesis was severely impaired by mODNs. Partially resistant viruses with mutations in NC and RT emerged after months of passaging in cell culture. A HIV-1 molecular clone (NL4.3) bearing these mutations was found to replicate at high concentrations of mODN, albeit with a reduced fitness. Small, methylated ODNs such as mODN-11 appear to be a new type of highly potent inhibitor of HIV-1.

  8. The cellular transcription factor CREB corresponds to activating transcription factor 47 (ATF-47) and forms complexes with a group of polypeptides related to ATF-43.

    OpenAIRE

    Hurst, H C; Masson, N; Jones, N C; Lee, K A

    1990-01-01

    Promoter elements containing the sequence motif CGTCA are important for a variety of inducible responses at the transcriptional level. Multiple cellular factors specifically bind to these elements and are encoded by a multigene family. Among these factors, polypeptides termed activating transcription factor 43 (ATF-43) and ATF-47 have been purified from HeLa cells and a factor referred to as cyclic AMP response element-binding protein (CREB) has been isolated from PC12 cells and rat brain. We...

  9. Complex mutual regulation of facilitates chromatin transcription (FACT) subunits on both mRNA and protein levels in human cells.

    Science.gov (United States)

    Safina, Alfiya; Garcia, Henry; Commane, Mairead; Guryanova, Olga; Degan, Seamus; Kolesnikova, Kateryna; Gurova, Katerina V

    2013-08-01

    Facilitates chromatin transcription (FACT) is a chromatin remodeling complex with two subunits: SSRP1 and SPT16. Mechanisms controlling FACT levels are of interest, since the complex is not expressed in most differentiated cells, but is frequently upregulated in cancer, particularly in poorly differentiated, aggressive tumors. Moreover, inhibition of FACT expression or function in tumor cells interferes with their survival. Here we demonstrate that SSRP1 and SPT16 protein levels decline upon induction of cellular differentiation or senescence in vitro and that similar declines in protein levels for both SSRP1 and SPT16 occur upon RNAi-mediated knockdown of either SSRP1 or SPT16. The interdependence of SSRP1 and SPT16 protein levels was found to be due to their association with SSRP1 and SPT16 mRNAs, which stabilizes the proteins. In particular, presence of SSRP1 mRNA is critical for SPT16 protein stability. In addition, binding of SSRP1 and SPT16 mRNAs to the FACT complex increases the stability and efficiency of translation of the mRNAs. These data support a model in which the FACT complex is stable when SSRP1 mRNA is present, but quickly degrades when SSRP1 mRNA levels drop. In the absence of FACT complex, SSRP1 and SPT16 mRNAs are unstable and inefficiently translated, making reactivation of FACT function unlikely in normal cells. Thus, we have described a complex and unusual mode of regulation controlling cellular FACT levels that results in amplified and stringent control of FACT activity. The FACT dependence of tumor cells suggests that mechanisms controlling FACT levels could be targeted for anticancer therapy.

  10. Pinpointing cryptic borders: Fine-scale phylogeography and genetic landscape analysis of the Hormogaster elisae complex (Oligochaeta, Hormogastridae).

    Science.gov (United States)

    Marchán, Daniel F; Fernández, Rosa; de Sosa, Irene; Díaz Cosín, Darío J; Novo, Marta

    2017-07-01

    Spatial and temporal aspects of the evolution of cryptic species complexes have received less attention than species delimitation within them. The phylogeography of the cryptic complex Hormogaster elisae (Oligochaeta, Hormogastridae) lacks knowledge on several aspects, including the small-scale distribution of its lineages or the palaeogeographic context of their diversification. To shed light on these topics, a dense specimen collection was performed in the center of the Iberian Peninsula - resulting in 28 new H. elisae collecting points, some of them as close as 760m from each other- for a higher resolution of the distribution of the cryptic lineages and the relationships between the populations. Seven molecular regions were amplified: mitochondrial subunit 1 of cytochrome c oxidase (COI), 16S rRNA and tRNA Leu, Ala, and Ser (16S t-RNAs), one nuclear ribosomal gene (a fragment of 28S rRNA) and one nuclear protein-encoding gene (histone H3) in order to infer their phylogenetic relationships. Different representation methods of the pairwise divergence in the cytochrome oxidase I sequence (heatmap and genetic landscape graphs) were used to visualize the genetic structure of H. elisae. A nested approach sensu Mairal et al. (2015) (connecting the evolutionary rates of two datasets of different taxonomic coverage) was used to obtain one approximation to a time-calibrated phylogenetic tree based on external Clitellata fossils and a wide molecular dataset. Our results indicate that limited active dispersal ability and ecological or biotic barriers could explain the isolation of the different cryptic lineages, which never co-occur. Rare events of long distance dispersal through hydrochory appear as one of the possible causes of range expansion. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Characterizing highly dynamic conformational states: The transcription bubble in RNAP-promoter open complex as an example

    Science.gov (United States)

    Lerner, Eitan; Ingargiola, Antonino; Weiss, Shimon

    2018-03-01

    Bio-macromolecules carry out complicated functions through structural changes. To understand their mechanism of action, the structure of each step has to be characterized. While classical structural biology techniques allow the characterization of a few "structural snapshots" along the enzymatic cycle (usually of stable conformations), they do not cover all (and often fast interconverting) structures in the ensemble, where each may play an important functional role. Recently, several groups have demonstrated that structures of different conformations in solution could be solved by measuring multiple distances between different pairs of residues using single-molecule Förster resonance energy transfer (smFRET) and using them as constrains for hybrid/integrative structural modeling. However, this approach is limited in cases where the conformational dynamics is faster than the technique's temporal resolution. In this study, we combine existing tools that elucidate sub-millisecond conformational dynamics together with hybrid/integrative structural modeling to study the conformational states of the transcription bubble in the bacterial RNA polymerase-promoter open complex (RPo). We measured microsecond alternating laser excitation-smFRET of differently labeled lacCONS promoter dsDNA constructs. We used a combination of burst variance analysis, photon-by-photon hidden Markov modeling, and the FRET-restrained positioning and screening approach to identify two conformational states for RPo. The experimentally derived distances of one conformational state match the known crystal structure of bacterial RPo. The experimentally derived distances of the other conformational state have characteristics of a scrunched RPo. These findings support the hypothesis that sub-millisecond dynamics in the transcription bubble are responsible for transcription start site selection.

  12. Ecological Variation in Response to Mass-Flowering Oilseed Rape and Surrounding Landscape Composition by Members of a Cryptic Bumblebee Complex.

    Directory of Open Access Journals (Sweden)

    Dara A Stanley

    Full Text Available The Bombus sensu stricto species complex is a widespread group of cryptic bumblebee species which are important pollinators of many crops and wild plants. These cryptic species have, until now, largely been grouped together in ecological studies, and so little is known about their individual colony densities, foraging ranges or habitat requirements, which can be influenced by land use at a landscape scale. We used mass-flowering oilseed rape fields as locations to sample bees of this complex, as well as the second most common visitor to oilseed rape B. lapidarius, and molecular RFLP methods to distinguish between the cryptic species. We then used microsatellite genotyping to identify sisters and estimate colony densities, and related both proportions of cryptic species and their colony densities to the composition of the landscape surrounding the fields. We found B. lucorum was the most common member of the complex present in oilseed rape followed by B. terrestris. B. cryptarum was also present in all but one site, with higher proportions found in the east of the study area. High numbers of bumblebee colonies were estimated to be using oilseed rape fields as a forage resource, with B. terrestris colony numbers higher than previous estimates from non-mass-flowering fields. We also found that the cryptic species responded differently to surrounding landscape composition: both relative proportions of B. cryptarum in samples and colony densities of B. lucorum were negatively associated with the amount of arable land in the landscape, while proportions and colony densities of other species did not respond to landscape variables at the scale measured. This suggests that the cryptic species have different ecological requirements (which may be scale-dependent and that oilseed rape can be an important forage resource for many colonies of bumblebees. Given this, we recommend sustainable management of this crop to benefit bumblebees.

  13. Double-stranded DNA translocase activity of transcription factor TFIIH and the mechanism of RNA polymerase II open complex formation.

    Science.gov (United States)

    Fishburn, James; Tomko, Eric; Galburt, Eric; Hahn, Steven

    2015-03-31

    Formation of the RNA polymerase II (Pol II) open complex (OC) requires DNA unwinding mediated by the transcription factor TFIIH helicase-related subunit XPB/Ssl2. Because XPB/Ssl2 binds DNA downstream from the location of DNA unwinding, it cannot function using a conventional helicase mechanism. Here we show that yeast TFIIH contains an Ssl2-dependent double-stranded DNA translocase activity. Ssl2 tracks along one DNA strand in the 5' → 3' direction, implying it uses the nontemplate promoter strand to reel downstream DNA into the Pol II cleft, creating torsional strain and leading to DNA unwinding. Analysis of the Ssl2 and DNA-dependent ATPase activity of TFIIH suggests that Ssl2 has a processivity of approximately one DNA turn, consistent with the length of DNA unwound during transcription initiation. Our results can explain why maintaining the OC requires continuous ATP hydrolysis and the function of TFIIH in promoter escape. Our results also suggest that XPB/Ssl2 uses this translocase mechanism during DNA repair rather than physically wedging open damaged DNA.

  14. Regulation of the anthocyanin biosynthetic pathway by the TTG1/bHLH/Myb transcriptional complex in Arabidopsis seedlings.

    Science.gov (United States)

    Gonzalez, Antonio; Zhao, Mingzhe; Leavitt, John M; Lloyd, Alan M

    2008-03-01

    In all higher plants studied to date, the anthocyanin pigment pathway is regulated by a suite of transcription factors that include Myb, bHLH and WD-repeat proteins. However, in Arabidopsis thaliana, the Myb regulators remain to be conclusively identified, and little is known about anthocyanin pathway regulation by TTG1-dependent transcriptional complexes. Previous overexpression of the PAP1 Myb suggested that genes from the entire phenylpropanoid pathway are targets of regulation by Myb/bHLH/WD-repeat complexes in Arabidopsis, in contrast to other plants. Here we demonstrate that overexpression of Myb113 or Myb114 results in substantial increases in pigment production similar to those previously seen as a result of over-expression of PAP1, and pigment production in these overexpressors remains TTG1- and bHLH-dependent. Also, plants harboring an RNAi construct targeting PAP1 and three Myb candidates (PAP2, Myb113 and Myb114) showed downregulated Myb gene expression and obvious anthocyanin deficiencies. Correlated with these anthocyanin deficiencies is downregulation of the same late anthocyanin structural genes that are downregulated in ttg1 and bHLH anthocyanin mutants. Expression studies using GL3:GR and TTG1:GR fusions revealed direct regulation of the late biosynthetic genes only. Functional diversification between GL3 and EGL3 with regard to activation of gene targets was revealed by GL3:GR studies in single and double bHLH mutant seedlings. Expression profiles for Myb and bHLH regulators are also presented in the context of pigment production in young seedlings.

  15. Deciphering Transcriptome and Complex Alternative Splicing Transcripts in Mammary Gland Tissues from Cows Naturally Infected with Staphylococcus aureus Mastitis

    Science.gov (United States)

    Jiang, Qiang; Yang, Chun Hong; Zhang, Yan; Sun, Yan; Li, Rong Ling; Wang, Chang Fa; Zhong, Ji Feng; Huang, Jin Ming

    2016-01-01

    Alternative splicing (AS) contributes to the complexity of the mammalian proteome and plays an important role in diseases, including infectious diseases. The differential AS patterns of these transcript sequences between the healthy (HS3A) and mastitic (HS8A) cows naturally infected by Staphylococcus aureus were compared to understand the molecular mechanisms underlying mastitis resistance and susceptibility. In this study, using the Illumina paired-end RNA sequencing method, 1352 differentially expressed genes (DEGs) with higher than twofold changes were found in the HS3A and HS8A mammary gland tissues. Gene ontology and KEGG pathway analyses revealed that the cytokine–cytokine receptor interaction pathway is the most significantly enriched pathway. Approximately 16k annotated unigenes were respectively identified in two libraries, based on the bovine Bos taurus UMD3.1 sequence assembly and search. A total of 52.62% and 51.24% annotated unigenes were alternatively spliced in term of exon skipping, intron retention, alternative 5′ splicing and alternative 3ʹ splicing. Additionally, 1,317 AS unigenes were HS3A-specific, whereas 1,093 AS unigenes were HS8A-specific. Some immune-related genes, such as ITGB6, MYD88, ADA, ACKR1, and TNFRSF1B, and their potential relationships with mastitis were highlighted. From Chromosome 2, 4, 6, 7, 10, 13, 14, 17, and 20, 3.66% (HS3A) and 5.4% (HS8A) novel transcripts, which harbor known quantitative trait locus associated with clinical mastitis, were identified. Many DEGs in the healthy and mastitic mammary glands are involved in immune, defense, and inflammation responses. These DEGs, which exhibit diverse and specific splicing patterns and events, can endow dairy cattle with the potential complex genetic resistance against mastitis. PMID:27459697

  16. Chick Hairy1 protein interacts with Sap18, a component of the Sin3/HDAC transcriptional repressor complex

    Directory of Open Access Journals (Sweden)

    Andrade Raquel P

    2007-07-01

    Full Text Available Abstract Background The vertebrate adult axial skeleton, trunk and limb skeletal muscles and dermis of the back all arise from early embryonic structures called somites. Somites are symmetrically positioned flanking the embryo axial structures (neural tube and notochord and are periodically formed in a anterior-posterior direction from the presomitic mesoderm. The time required to form a somite pair is constant and species-specific. This extraordinary periodicity is proposed to depend on an underlying somitogenesis molecular clock, firstly evidenced by the cyclic expression of the chick hairy1 gene in the unsegmented presomitic mesoderm with a 90 min periodicity, corresponding to the time required to form a somite pair in the chick embryo. The number of hairy1 oscillations at any given moment is proposed to provide the cell with both temporal and positional information along the embryo's anterior-posterior axis. Nevertheless, how this is accomplished and what biological processes are involved is still unknown. Aiming at understanding the molecular events triggered by the somitogenesis clock Hairy1 protein, we have employed the yeast two-hybrid system to identify Hairy1 interaction partners. Results Sap18, an adaptor molecule of the Sin3/HDAC transcriptional repressor complex, was found to interact with the C-terminal portion of the Hairy1 protein in a yeast two-hybrid assay and the Hairy1/Sap18 interaction was independently confirmed by co-immunoprecipitation experiments. We have characterized the expression patterns of both sap18 and sin3a genes during chick embryo development, using in situ hybridization experiments. We found that both sap18 and sin3a expression patterns co-localize in vivo with hairy1 expression domains in chick rostral presomitic mesoderm and caudal region of somites. Conclusion Hairy1 belongs to the hairy-enhancer-of-split family of transcriptional repressor proteins. Our results indicate that during chick somitogenesis

  17. Satellite remote sensing of landscape freeze/thaw state dynamics for complex Topography and Fire Disturbance Areas Using multi-sensor radar and SRTM digital elevation models

    Science.gov (United States)

    Podest, Erika; McDonald, Kyle; Kimball, John; Randerson, James

    2003-01-01

    We characterize differences in radar-derived freeze/thaw state, examining transitions over complex terrain and landscape disturbance regimes. In areas of complex terrain, we explore freezekhaw dynamics related to elevation, slope aspect and varying landcover. In the burned regions, we explore the timing of seasonal freeze/thaw transition as related to the recovering landscape, relative to that of a nearby control site. We apply in situ biophysical measurements, including flux tower measurements to validate and interpret the remotely sensed parameters. A multi-scale analysis is performed relating high-resolution SAR backscatter and moderate resolution scatterometer measurements to assess trade-offs in spatial and temporal resolution in the remotely sensed fields.

  18. Environmental Risks of Landscape Botanical Complexes and Minimization of Technogenic Influence Exerted by Objects of Oil&Gas Production in Steppe Zone of the Southern Urals

    Science.gov (United States)

    Ryabukhina, M. V.; Maiski, R. A.; Salikhova, R. H.

    2017-11-01

    The modern rates of oil and gas production, developed industry, high technologies in the field of the construction and operation of wells, pipelines and other facilities of the oil and gas industry, as well as growing environmental control do not fully solve the problem of the negative impacts on natural objects, in particular, landscape botanical complexes. Taking into account the increasing oil and gas production rates, the existing objects-Orenburg NGKM and constructed ones, for example, by 2015 in the Orenburg region was organized a “new thread” oil company, LLC, the activities of which include exploration, design and preparation of the Mogutovskoye deposits, a part of the Vorontsov and a part of Gremjacheskoye deposits, as well as their exploitation, should explore and develop some effective mechanisms to minimize and eliminate the environmental risks of industrial impact. In our view the multi-component continuous monitoring of environmental risks will help to formulate an effective strategy and develop an effective preventive mechanism of technological activities, identify landscape botanical complexes which are more exposed to environmental risks as well as the regional forecast component changes in terms of a landscape botanical complex in the zone of technogenic influence exerted by the objects of the oil and gas industry.

  19. Exploring the relationships between landscape complexity, wild bee species richness and reproduction, and pollination services along a complexity gradient in the Netherlands

    NARCIS (Netherlands)

    Bukovinszki, Tibor; Verheijen, Joke; Zwerver, S.; Klop, Esther; Biesmeijer, Jacobus C.; Wäckers, Felix L.; Prins, Herbert H.T.; Kleijn, David

    2017-01-01

    Pollinator communities exhibit variable responses to changing landscape composition. A general expectation is that a decreasing cover of semi-natural habitats negatively affects pollinator reproduction, population size and pollination services, but few studies have investigated the simultaneous

  20. Condensed landscape experience

    DEFF Research Database (Denmark)

    Earon, Ofri

    2011-01-01

    ‘Re-thinking interaction between landscape and urban buildings’ participates in an interdisciplinary discourse about the theoretical and practical advantages of openly juxtaposing landscape and architecture without having one more advanced in importance. Recently, the greenification of buildings...... demands, quality of space, mixture of functions, urban complexity, public life and cultural heritage. In order to launch such an approach, an understanding of the spatial, social and environmental significance of a radical re-thinking of relationships between architecture and landscape is necessary...

  1. Phorbol-ester-induced activation of the NF-κB transcription factor involves dissociation of an apparently cytoplasmic NF-κB/inhibitor complex

    International Nuclear Information System (INIS)

    Baeuerle, P.A.; Lenardo, M.; Pierce, J.W.; Baltimore, D.

    1988-01-01

    There is increasing evidence that inducible transcription of genes is mediated through the induction of the activity of trans-acting protein factors. The NF-κB transcription factor provides a model system to study the posttranslational activation of a phorbol-ester-inducible transcription factor. The finding that NF-κB activity is undectable in subcellular fractions from unstimulated cells suggests that NF-κB exists as an inactive precursor. The authors showed that NF-κB is detectable in two different forms. After selective removal of endogenous NF-κB, they demonstrate the existence of a protein inhibitor in cytosolic fractions of unstimulated cells that is able in vitro to convert NF-κB into an inactive desoxycholate-dependent form. The data are consistent with a molecular mechanism of inducible gene expression by which an apparently cytoplasmic transcription factor-inhibitor complex is dissociated by the action of TPA-activated protein kinase C

  2. Engagement of Components of DNA-Break Repair Complex and NFκB in Hsp70A1A Transcription Upregulation by Heat Shock.

    Science.gov (United States)

    Hazra, Joyita; Mukherjee, Pooja; Ali, Asif; Poddar, Soumita; Pal, Mahadeb

    2017-01-01

    An involvement of components of DNA-break repair (DBR) complex including DNA-dependent protein kinase (DNA-PK) and poly-ADP-ribose polymerase 1 (PARP-1) in transcription regulation in response to distinct cellular signalling has been revealed by different laboratories. Here, we explored the involvement of DNA-PK and PARP-1 in the heat shock induced transcription of Hsp70A1A. We find that inhibition of both the catalytic subunit of DNA-PK (DNA-PKc), and Ku70, a regulatory subunit of DNA-PK holo-enzyme compromises transcription of Hsp70A1A under heat shock treatment. In immunoprecipitation based experiments we find that Ku70 or DNA-PK holoenzyme associates with NFκB. This NFκB associated complex also carries PARP-1. Downregulation of both NFκB and PARP-1 compromises Hsp70A1A transcription induced by heat shock treatment. Alteration of three bases by site directed mutagenesis within the consensus κB sequence motif identified on the promoter affected inducibility of Hsp70A1A transcription by heat shock treatment. These results suggest that NFκB engaged with the κB motif on the promoter cooperates in Hsp70A1A activation under heat shock in human cells as part of a DBR complex including DNA-PK and PARP-1.

  3. Using nitrogen concentration and isotopic composition in lichens to spatially assess the relative contribution of atmospheric nitrogen sources in complex landscapes

    International Nuclear Information System (INIS)

    Pinho, P.; Barros, C.; Augusto, S.; Pereira, M.J.

    2017-01-01

    Reactive nitrogen (Nr) is an important driver of global change, causing alterations in ecosystem biodiversity and functionality. Environmental assessments require monitoring the emission and deposition of both the amount and types of Nr. This is especially important in heterogeneous landscapes, as different land-cover types emit particular forms of Nr to the atmosphere, which can impact ecosystems distinctively. Such assessments require high spatial resolution maps that also integrate temporal variations, and can only be feasibly achieved by using ecological indicators. Our aim was to rank land-cover types according to the amount and form of emitted atmospheric Nr in a complex landscape with multiple sources of N. To do so, we measured and mapped nitrogen concentration and isotopic composition in lichen thalli, which we then related to land-cover data. Results suggested that, at the landscape scale, intensive agriculture and urban areas were the most important sources of Nr to the atmosphere. Additionally, the ocean greatly influences Nr in land, by providing air with low Nr concentration and a unique isotopic composition. These results have important consequences for managing air pollution at the regional level, as they provide critical information for modeling Nr emission and deposition across regional as well as continental scales. - Highlights: • Which land-cover types are reactive nitrogen sources or sinks at a landscape level? • Nitrogen concentration and isotopic composition were analyzed in lichens. • This allowed determination of the main nitrogen sources: agricultural and urban areas. • Marine sources provided persistent low concentrations of reactive nitrogen. • The typical signature of each source was also determined. - Reactive-nitrogen concentration and isotopic composition in lichens were used to rank Nr sources at a landscape level.

  4. Inland drift sand landscapes

    NARCIS (Netherlands)

    Fanta, J.; Siepel, H.

    2010-01-01

    Man has had a complex relationship with inland drift sands through the ages. For some centuries these landscapes were seen as a threat to society, especially agriculture and housing. At present we conserve these landscapes as important Natura 2000 priority habitats. In this book you may find these

  5. Nature and landscape protection

    International Nuclear Information System (INIS)

    Klinda, J.; Lieskovska, Z.

    1998-01-01

    In accordance with National Council of the Slovak Republic Act N. 287/1994 Coll. on Nature and Landscape Protection, the system of complex nature landscape protection has been designed based on five levels of protection. Categories of protected areas as well as cultural monuments in the Slovak Republic are reviewed.Slovak contribution to the world heritage is included

  6. Landscape Studio

    DEFF Research Database (Denmark)

    Hansen, Peter Lundsgaard

    2017-01-01

    Landscape studio documents is the biography of the method 'design conversation' and contributes to the way we work with landscapes. The blog communicates renewed landscape didactics and leads to the innovation of design practices.......Landscape studio documents is the biography of the method 'design conversation' and contributes to the way we work with landscapes. The blog communicates renewed landscape didactics and leads to the innovation of design practices....

  7. Role of a transductional-transcriptional processor complex involving MyD88 and IRF-7 in Toll-like receptor signaling

    Science.gov (United States)

    Honda, Kenya; Yanai, Hideyuki; Mizutani, Tatsuaki; Negishi, Hideo; Shimada, Naoya; Suzuki, Nobutaka; Ohba, Yusuke; Takaoka, Akinori; Yeh, Wen-Chen; Taniguchi, Tadatsugu

    2004-01-01

    Toll-like receptor (TLR) activation is central to immunity, wherein the activation of the TLR9 subfamily members TLR9 and TLR7 results in the robust induction of type I IFNs (IFN-α/β) by means of the MyD88 adaptor protein. However, it remains unknown how the TLR signal “input” can be processed through MyD88 to “output” the induction of the IFN genes. Here, we demonstrate that the transcription factor IRF-7 interacts with MyD88 to form a complex in the cytoplasm. We provide evidence that this complex also involves IRAK4 and TRAF6 and provides the foundation for the TLR9-dependent activation of the IFN genes. The complex defined in this study represents an example of how the coupling of the signaling adaptor and effector kinase molecules together with the transcription factor regulate the processing of an extracellular signal to evoke its versatile downstream transcriptional events in a cell. Thus, we propose that this molecular complex may function as a cytoplasmic transductional-transcriptional processor. PMID:15492225

  8. Mediator and p300/CBP-Steroid Receptor Coactivator Complexes Have Distinct Roles, but Function Synergistically, during Estrogen Receptor α-Dependent Transcription with Chromatin Templates

    OpenAIRE

    Acevedo, Mari Luz; Kraus, W. Lee

    2003-01-01

    Ligand-dependent transcriptional activation by nuclear receptors involves the recruitment of various coactivators to the promoters of hormone-regulated genes assembled into chromatin. Nuclear receptor coactivators include histone acetyltransferase complexes, such as p300/CBP-steroid receptor coactivator (SRC), as well as the multisubunit mediator complexes (“Mediator”), which may help recruit RNA polymerase II to the promoter. We have used a biochemical approach, including an in vitro chromat...

  9. NMR assignments of SPOC domain of the human transcriptional corepressor SHARP in complex with a C-terminal SMRT peptide.

    Science.gov (United States)

    Mikami, Suzuka; Kanaba, Teppei; Ito, Yutaka; Mishima, Masaki

    2013-10-01

    The transcriptional corepressor SMRT/HDAC1-associated repressor protein (SHARP) recruits histone deacetylases. Human SHARP protein is thought to function in processes involving steroid hormone responses and the Notch signaling pathway. SHARP consists of RNA recognition motifs (RRMs) in the N-terminal region and the spen paralog and ortholog C-terminal (SPOC) domain in the C-terminal region. It is known that the SPOC domain binds the LSD motif in the C-terminal tail of corepressors silencing mediator for retinoid and thyroid receptor (SMRT)/nuclear receptor corepressor (NcoR). We are interested in delineating the mechanism by which the SPOC domain recognizes the LSD motif of the C-terminal tail of SMRT/NcoR. To this end, we are investigating the tertiary structure of the SPOC/SMRT peptide using NMR. Herein, we report on the (1)H, (13)C and (15)N resonance assignments of the SPOC domain in complex with a SMRT peptide, which contributes towards a structural understanding of the SPOC/SMRT peptide and its molecular recognition.

  10. A linguistic representation of the regulation of transcription initiation. I. An ordered array of complex symbols with distinctive features.

    Science.gov (United States)

    Collado-Vides, J

    1993-01-01

    The inadequacy of context-free grammars in the description of regulatory information contained in DNA gave the formal justification for a linguistic approach to the study of gene regulation. Based on that result, we have initiated a linguistic formalization of the regulatory arrays of 107 sigma 70 E. coli promoters. The complete sequences of promoter (Pr), operator (Op) and activator binding sites (I) have previously been identified as the smallest elements, or categories, for a combinatorial analysis of the range of transcription initiation of sigma 70 promoters. These categories are conceptually equivalent to phonemes of natural language. Several features associated with these categories are required in a complete description of regulatory arrays of promoters. We have to select the best way to describe the properties that are pertinent for the description of such regulatory regions. In this paper we define distinctive features of regulatory regions based on the following criteria: identification of subclasses of substitutable elements, simplicity, selection of the most directly related information, and distinction of one array among the whole set of promoters. Alternative ways to represent distances in between regulatory sites are discussed, permitting, together with a principle of precedence, the identification of an ordered set of complex symbols as a unique representation for a promoter and its associated regulatory sites. In the accompanying paper additional distinctive features of promoters and regulatory sites are identified.

  11. Genome-wide identification and characterization of Notch transcription complex-binding sequence paired sites in leukemia cells

    Science.gov (United States)

    Severson, Eric; Arnett, Kelly L.; Wang, Hongfang; Zang, Chongzhi; Taing, Len; Liu, Hudan; Pear, Warren S.; Liu, X. Shirley; Blacklow, Stephen C.; Aster, Jon C.

    2018-01-01

    Notch transcription complexes (NTCs) drive target gene expression by binding to two distinct types of genomic response elements, NTC monomer-binding sites and sequence-paired sites (SPSs) that bind NTC dimers. SPSs are conserved and are linked to the Notch-responsiveness of a few genes, but their overall contribution to Notch-dependent gene regulation is unknown. To address this issue, we determined the DNA sequence requirements for NTC dimerization using a fluorescence resonance energy transfer (FRET) assay, and applied insights from these in vitro studies to Notch-“addicted” leukemia cells. We find that SPSs contribute to the regulation of approximately a third of direct Notch target genes. While originally described in promoters, SPSs are present mainly in long-range enhancers, including an enhancer containing a newly described SPS that regulates HES5. Our work provides a general method for identifying sequence-paired sites in genome-wide data sets and highlights the widespread role of NTC dimerization in Notch-transformed leukemia cells. PMID:28465412

  12. GCR1, a transcriptional activator in Saccharomyces cerevisiae, complexes with RAP1 and can function without its DNA binding domain.

    Science.gov (United States)

    Tornow, J; Zeng, X; Gao, W; Santangelo, G M

    1993-01-01

    In Saccharomyces cerevisiae, efficient expression of glycolytic and translational component genes requires two DNA binding proteins, RAP1 (which binds to UASRPG) and GCR1 (which binds to the CT box). We generated deletions in GCR1 to test the validity of several different models for GCR1 function. We report here that the C-terminal half of GCR1, which includes the domain required for DNA binding to the CT box in vitro, can be removed without affecting GCR1-dependent transcription of either the glycolytic gene ADH1 or the translational component genes TEF1 and TEF2. We have also identified an activation domain within a segment of the GCR1 protein (the N-terminal third) that is essential for in vivo function. RAP1 and GCR1 can be co-immunoprecipitated from whole cell extracts, suggesting that they form a complex in vivo. The data are most consistent with a model in which GCR1 is attracted to DNA through contact with RAP1. Images PMID:8508768

  13. Ctr9, a Protein in the Transcription Complex Paf1, Regulates Dopamine Transporter Activity at the Plasma Membrane.

    Science.gov (United States)

    De Gois, Stéphanie; Slama, Patrick; Pietrancosta, Nicolas; Erdozain, Amaia M; Louis, Franck; Bouvrais-Veret, Caroline; Daviet, Laurent; Giros, Bruno

    2015-07-17

    Dopamine (DA) is a major regulator of sensorimotor and cognitive functions. The DA transporter (DAT) is the key protein that regulates the spatial and temporal activity of DA release into the synaptic cleft via the rapid reuptake of DA into presynaptic termini. Several lines of evidence have suggested that transporter-interacting proteins may play a role in DAT function and regulation. Here, we identified the tetratricopeptide repeat domain-containing protein Ctr9 as a novel DAT binding partner using a yeast two-hybrid system. We showed that Ctr9 is expressed in dopaminergic neurons and forms a stable complex with DAT in vivo via GST pulldown and co-immunoprecipitation assays. In mammalian cells co-expressing both proteins, Ctr9 partially colocalizes with DAT at the plasma membrane. This interaction between DAT and Ctr9 results in a dramatic enhancement of DAT-mediated DA uptake due to an increased number of DAT transporters at the plasma membrane. We determined that the binding of Ctr9 to DAT requires residues YKF in the first half of the DAT C terminus. In addition, we characterized Ctr9, providing new insight into this protein. Using three-dimensional modeling, we identified three novel tetratricopeptide repeat domains in the Ctr9 sequence, and based on deletion mutation experiments, we demonstrated the role of the SH2 domain of Ctr9 in nuclear localization. Our results demonstrate that Ctr9 localization is not restricted to the nucleus, as previously described for the transcription complex Paf1. Taken together, our data provide evidence that Ctr9 modulates DAT function by regulating its trafficking. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Assessment of complex water pollution with heavy metals and Pyrethroid pesticides on transcript levels of metallothionein and immune related genes.

    Science.gov (United States)

    Ghazy, Haneen A; Abdel-Razek, Mohamed A S; El Nahas, Abeer F; Mahmoud, Shawky

    2017-09-01

    Alteration of immunological function of an aquatic organism can be used as an indicator for evaluating the direct effect of exposure to pollutants. The aim of this work is to assess the impact of complex water pollution with special reference to Pyrethroid pesticides and heavy metals on mRNA transcript levels of Metallothionine and some immune related genes of Nile tilapia (Oreochromas Niloticus). Residues of six heavy metals and six Pyrethroid were assessed in water as well as fish tissues at three different sites of Lake Burullus, located at Northern Egypt. Variations of water physicochemical properties associated with different levels of heavy metals at the three different sections were recorded. Tissue residues of Fe, Mn and Zn, Cu, Ni exceed water levels in contrast to elevated water level of Pb. All assessed Pyrethroids are detected in fish tissue samples with higher concentration (3-42 folds) than that found in water samples especially Cypermethrin. Significant down-regulation of expression levels of metallothionein (MT) at the three sections of the lake was observed. The expression of immune related genes (IgM) and inflammatory cytokines (TNF, IL.8 and IL.1) were affected. IgM and TNF were significantly down-regulated at eastern and western section of the lake; meanwhile the expression of IL8 is down regulated at the three sections of the lack. IL1 was significantly up-regulated at eastern and middle sections. We conclude that, variable gene expression of MT and immune-related genes at the three sections of the lack impose different response to complex water pollution in relation to variable aquatic environment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Dispersal and habitat connectivity in complex heterogeneous landscapes: an analysis with a GIS based random walk model

    NARCIS (Netherlands)

    Schippers, P.; Verboom, J.; Knaapen, J.P.; Apeldoorn, van R.

    1996-01-01

    A grid-based random walk model has been developed to simulate animal dispersal, taking landscape heterogeneity and linear barriers such as roads and rivers into account. The model can be used to estimate connectivity and has been parameterized for thebadger in the central part of the Netherlands.

  16. Ecological Catastrophes in the steppe? Landscape Archaeology at the mining and metallurgical complex of Kargaly (Region of Orenbourg, Russia

    Directory of Open Access Journals (Sweden)

    Vicent García, Juan M.

    2000-06-01

    Full Text Available Kargaly is one of the most important centers of mining and metallurgy in the great Eurasian steppe. Dr. E.N. Chernykh and his team (Institute of Archaeology, Russian Academy of Sciences, Moscow and various researchers at the CSIC and other Spanish institutions have developed a joint project to undertake a comprehensive study of the site's two main phases of occupation, the Bronze Age (2nd millenium BC and the first Russian industrialization (1745-1900 AD. The Russian members of the joint team are in charge of the archaeological investigations, while the Spanish members are studying metallurgical and mining technology and production, on the one hand, and the environmental context and impact of these activities, on the other. This article presents the research design and first results of the Palaeoenvironmental research at Kargaly. This work has two aspects. The first consisted of obtaining one of the most complete palaeoenvironmental data sets from the steppes through both the systematic sampling of archaeological sites to recover charcoal, seeds, fruits and pollen and the taking of palynological cores from natural deposits, on the other Both sampling programs were supported by radiocarbon dates. The second aspect, to which the greater part of this article is devoted, was dedicated to contextualizing the palaeobotanical evidence by studying the present-day landscape, with particular attention to understanding the processes which shape the variability of the pollen rain. Our purpose was to obtain explicit and measurable calibrative criteria which would enable us to answer the palaeoenvironmental questions raised by our archaeological and archaeometallurgical research. These questions include, most importantly, the following: what was the extent of forest (the energy base for the mining/metallurgical complex during the Bronze Age? and how do we evaluate subsistence practices? (an issue related to the origins of agriculture on the

  17. Using nitrogen concentration and isotopic composition in lichens to spatially assess the relative contribution of atmospheric nitrogen sources in complex landscapes.

    Science.gov (United States)

    Pinho, P; Barros, C; Augusto, S; Pereira, M J; Máguas, C; Branquinho, C

    2017-11-01

    Reactive nitrogen (Nr) is an important driver of global change, causing alterations in ecosystem biodiversity and functionality. Environmental assessments require monitoring the emission and deposition of both the amount and types of Nr. This is especially important in heterogeneous landscapes, as different land-cover types emit particular forms of Nr to the atmosphere, which can impact ecosystems distinctively. Such assessments require high spatial resolution maps that also integrate temporal variations, and can only be feasibly achieved by using ecological indicators. Our aim was to rank land-cover types according to the amount and form of emitted atmospheric Nr in a complex landscape with multiple sources of N. To do so, we measured and mapped nitrogen concentration and isotopic composition in lichen thalli, which we then related to land-cover data. Results suggested that, at the landscape scale, intensive agriculture and urban areas were the most important sources of Nr to the atmosphere. Additionally, the ocean greatly influences Nr in land, by providing air with low Nr concentration and a unique isotopic composition. These results have important consequences for managing air pollution at the regional level, as they provide critical information for modeling Nr emission and deposition across regional as well as continental scales. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Post-transcriptional generation of miRNA variants by multiple nucleotidyl transferases contributes to miRNA transcriptome complexity.

    Science.gov (United States)

    Wyman, Stacia K; Knouf, Emily C; Parkin, Rachael K; Fritz, Brian R; Lin, Daniel W; Dennis, Lucas M; Krouse, Michael A; Webster, Philippa J; Tewari, Muneesh

    2011-09-01

    Modification of microRNA sequences by the 3' addition of nucleotides to generate so-called "isomiRs" adds to the complexity of miRNA function, with recent reports showing that 3' modifications can influence miRNA stability and efficiency of target repression. Here, we show that the 3' modification of miRNAs is a physiological and common post-transcriptional event that shows selectivity for specific miRNAs and is observed across species ranging from C. elegans to human. The modifications result predominantly from adenylation and uridylation and are seen across tissue types, disease states, and developmental stages. To quantitatively profile 3' nucleotide additions, we developed and validated a novel assay based on NanoString Technologies' nCounter platform. For certain miRNAs, the frequency of modification was altered by processes such as cell differentiation, indicating that 3' modification is a biologically regulated process. To investigate the mechanism of 3' nucleotide additions, we used RNA interference to screen a panel of eight candidate miRNA nucleotidyl transferases for 3' miRNA modification activity in human cells. Multiple enzymes, including MTPAP, PAPD4, PAPD5, ZCCHC6, ZCCHC11, and TUT1, were found to govern 3' nucleotide addition to miRNAs in a miRNA-specific manner. Three of these enzymes-MTPAP, ZCCHC6, and TUT1-have not previously been known to modify miRNAs. Collectively, our results indicate that 3' modification observed in next-generation small RNA sequencing data is a biologically relevant process, and identify enzymatic mechanisms that may lead to new approaches for modulating miRNA activity in vivo.

  19. Cocaine- and amphetamine-regulated transcript and calcium binding proteins immunoreactivity in the subicular complex of the guinea pig.

    Science.gov (United States)

    Wasilewska, Barbara; Najdzion, Janusz; Równiak, Maciej; Bogus-Nowakowska, Krystyna; Hermanowicz, Beata; Kolenkiewicz, Małgorzata; Żakowski, Witold; Robak, Anna

    2016-03-01

    In this study we present the distribution and colocalization pattern of cocaine- and amphetamine-regulated transcript (CART) and three calcium-binding proteins: calbindin (CB), calretinin (CR) and parvalbumin (PV) in the subicular complex (SC) of the guinea pig. The subiculum (S) and presubiculum (PrS) showed higher CART-immunoreactivity (-IR) than the parasubiculum (PaS) as far as the perikarya and neuropil were concerned. CART- IR cells were mainly observed in the pyramidal layer and occasionally in the molecular layer of the S. In the PrS and PaS, single CART-IR perikarya were dispersed, however with a tendency to be found only in superficial layers. CART-IR fibers were observed throughout the entire guinea pig subicular neuropil. Double-labeling immunofluorescence showed that CART-IR perikarya, as well as fibers, did not stain positively for any of the three CaBPs. CART-IR fibers were only located near the CB-, CR-, PV-IR perikarya, whereas CART-IR fibers occasionally intersected fibers containing one of the three CaBPs. The distribution pattern of CART was more similar to that of CB and CR than to that of PV. In the PrS, the CART, CB and CR immunoreactivity showed a laminar distribution pattern. In the case of the PV, this distribution pattern in the PrS was much less prominent than that of CART, CB and CR. We conclude that a heterogeneous distribution of the CART and CaBPs in the guinea pig SC is in keeping with findings from other mammals, however species specific differences have been observed. Copyright © 2015 Elsevier GmbH. All rights reserved.

  20. Ménage à trois: the complex relationships between mitogen-activated protein kinases, WRKY transcription factors, and VQ-motif-containing proteins.

    Science.gov (United States)

    Weyhe, Martin; Eschen-Lippold, Lennart; Pecher, Pascal; Scheel, Dierk; Lee, Justin

    2014-01-01

    Out of the 34 members of the VQ-motif-containing protein (VQP) family, 10 are phosphorylated by the mitogen-activated protein kinases (MAPKs), MPK3 and MPK6. Most of these MPK3/6-targeted VQPs (MVQs) interacted with specific sub-groups of WRKY transcription factors in a VQ-motif-dependent manner. In some cases, the MAPK appears to phosphorylate either the MVQ or the WRKY, while in other cases, both proteins have been reported to act as MAPK substrates. We propose a network of dynamic interactions between members from the MAPK, MVQ and WRKY families - either as binary or as tripartite interactions. The compositions of the WRKY-MVQ transcriptional protein complexes may change - for instance, through MPK3/6-mediated modulation of protein stability - and therefore control defense gene transcription.

  1. A human Polycomb isoform lacking the Pc box does not participate to PRC1 complexes but forms protein assemblies and represses transcription

    DEFF Research Database (Denmark)

    Völkel, Pamela; Le Faou, Perrine; Vandamme, Julien

    2012-01-01

    site for the PRC1 protein complex. Drosophila core PRC1 is composed of four subunits: Polycomb (Pc), Posterior sex combs (Psc), Polyhomeotic (Ph) and Sex combs extra (Sce). Each of these proteins has multiple orthologs in vertebrates, thus generating an enormous scope for potential combinatorial...... diversity. In particular, mammalian genomes encode five Pc family members: CBX2, CBX4, CBX6, CBX7 and CBX8. To complicate matters further, distinct isoforms might arise from single genes. Here, we address the functional role of the two human CBX2 isoforms. Owing to different polyadenylation sites...... and alternative splicing events, the human CBX2 locus produces two transcripts: a 5-exon transcript that encodes the 532-amino acid CBX2-1 isoform that contains the conserved chromodomain and Pc box and a 4-exon transcript encoding a shorter isoform, CBX2-2, lacking the Pc box but still possessing a chromodomain...

  2. Hijacking of the O-GlcNAcZYME complex by the HTLV-1 Tax oncoprotein facilitates viral transcription.

    Science.gov (United States)

    Groussaud, Damien; Khair, Mostafa; Tollenaere, Armelle I; Waast, Laetitia; Kuo, Mei-Shiue; Mangeney, Marianne; Martella, Christophe; Fardini, Yann; Coste, Solène; Souidi, Mouloud; Benit, Laurence; Pique, Claudine; Issad, Tarik

    2017-07-01

    The viral Tax oncoprotein plays a key role in both Human T-cell lymphotropic virus type 1 (HTLV-1)-replication and HTLV-1-associated pathologies, notably adult T-cell leukemia. Tax governs the transcription from the viral 5'LTR, enhancing thereby its own expression, via the recruitment of dimers of phosphorylated CREB to cAMP-response elements located within the U3 region (vCRE). In addition to phosphorylation, CREB is also the target of O-GlcNAcylation, another reversible post-translational modification involved in a wide range of diseases, including cancers. O-GlcNAcylation consists in the addition of O-linked-N-acetylglucosamine (O-GlcNAc) on Serine or Threonine residues, a process controlled by two enzymes: O-GlcNAc transferase (OGT), which transfers O-GlcNAc on proteins, and O-GlcNAcase (OGA), which removes it. In this study, we investigated the status of O-GlcNAcylation enzymes in HTLV-1-transformed T cells. We found that OGA mRNA and protein expression levels are increased in HTLV-1-transformed T cells as compared to control T cell lines while OGT expression is unchanged. However, higher OGA production coincides with a reduction in OGA specific activity, showing that HTLV-1-transformed T cells produce high level of a less active form of OGA. Introducing Tax into HEK-293T cells or Tax-negative HTLV-1-transformed TL-om1 T cells is sufficient to inhibit OGA activity and increase total O-GlcNAcylation, without any change in OGT activity. Furthermore, Tax interacts with the OGT/OGA complex and inhibits the activity of OGT-bound OGA. Pharmacological inhibition of OGA increases CREB O-GlcNAcylation as well as HTLV-1-LTR transactivation by Tax and CREB recruitment to the LTR. Moreover, overexpression of wild-type CREB but not a CREB protein mutated on a previously described O-GlcNAcylation site enhances Tax-mediated LTR transactivation. Finally, both OGT and OGA are recruited to the LTR. These findings reveal the interplay between Tax and the O-GlcNAcylation pathway

  3. Historical fire regimes, reconstructed from land-survey data, led to complexity and fluctuation in sagebrush landscapes.

    Science.gov (United States)

    Bukowski, Beth E; Baker, William L

    2013-04-01

    Sagebrush landscapes provide habitat for Sage-Grouse and other sagebrush obligates, yet historical fire regimes and the structure of historical sagebrush landscapes are poorly known, hampering ecological restoration and management. To remedy this, General Land Office Survey (GLO) survey notes were used to reconstruct over two million hectares of historical vegetation for four sagebrush-dominated (Artemisia spp.) study areas in the western United States. Reconstructed vegetation was analyzed for fire indicators used to identify historical fires and reconstruct historical fire regimes. Historical fire-size distributions were inverse-J shaped, and one fire > 100 000 ha was identified. Historical fire rotations were estimated at 171-342 years for Wyoming big sagebrush (A. tridentata ssp. wyomingensis) and 137-217 years for mountain big sagebrush (A. tridentata ssp. vaseyana). Historical fire and patch sizes were significantly larger in Wyoming big sagebrush than mountain big sagebrush, and historical fire rotations were significantly longer in Wyoming big sagebrush than mountain big sagebrush. Historical fire rotations in Wyoming were longer than those in other study areas. Fine-scale mosaics of burned and unburned area and larger unburned inclusions within fire perimeters were less common than in modern fires. Historical sagebrush landscapes were dominated by large, contiguous areas of sagebrush, though large grass-dominated areas and finer-scale mosaics of grass and sagebrush were also present in smaller amounts. Variation in sagebrush density was a common source of patchiness, and areas classified as "dense" made up 24.5% of total sagebrush area, compared to 16.3% for "scattered" sagebrush. Results suggest significant differences in historical and modern fire regimes. Modern fire rotations in Wyoming big sagebrush are shorter than historical fire rotations. Results also suggest that historical sagebrush landscapes would have fluctuated, because of infrequent

  4. Genomic regulatory landscapes and chromosomal rearrangements

    DEFF Research Database (Denmark)

    Ladegaard, Elisabete L Engenheiro

    2008-01-01

    The main objectives of the PhD study are to identify and characterise chromosomal rearrangements within evolutionarily conserved regulatory landscapes around genes involved in the regulation of transcription and/or development (trans-dev genes). A frequent feature of trans-dev genes is that they ......The main objectives of the PhD study are to identify and characterise chromosomal rearrangements within evolutionarily conserved regulatory landscapes around genes involved in the regulation of transcription and/or development (trans-dev genes). A frequent feature of trans-dev genes...... the complex spatio-temporal expression of the associated trans-dev gene. Rare chromosomal breakpoints that disrupt the integrity of these regulatory landscapes may be used as a tool, not only to make genotype-phenotype associations, but also to link the associated phenotype with the position and tissue...... specificity of the individual CNEs. In this PhD study I have studied several chromosomal rearrangements with breakpoints in the vicinity of trans-dev genes. This included chromosomal rearrangements compatible with known phenotype-genotype associations (Rieger syndrome-PITX2, Mowat-Wilson syndrome-ZEB2...

  5. Complex and extensive post-transcriptional regulation revealed by integrative proteomic and transcriptomic analysis of metabolite stress response in Clostridium acetobutylicum.

    Science.gov (United States)

    Venkataramanan, Keerthi P; Min, Lie; Hou, Shuyu; Jones, Shawn W; Ralston, Matthew T; Lee, Kelvin H; Papoutsakis, E Terry

    2015-01-01

    Clostridium acetobutylicum is a model organism for both clostridial biology and solvent production. The organism is exposed to its own toxic metabolites butyrate and butanol, which trigger an adaptive stress response. Integrative analysis of proteomic and RNAseq data may provide novel insights into post-transcriptional regulation. The identified iTRAQ-based quantitative stress proteome is made up of 616 proteins with a 15 % genome coverage. The differentially expressed proteome correlated poorly with the corresponding differential RNAseq transcriptome. Up to 31 % of the differentially expressed proteins under stress displayed patterns opposite to those of the transcriptome, thus suggesting significant post-transcriptional regulation. The differential proteome of the translation machinery suggests that cells employ a different subset of ribosomal proteins under stress. Several highly upregulated proteins but with low mRNA levels possessed mRNAs with long 5'UTRs and strong RBS scores, thus supporting the argument that regulatory elements on the long 5'UTRs control their translation. For example, the oxidative stress response rubrerythrin was upregulated only at the protein level up to 40-fold without significant mRNA changes. We also identified many leaderless transcripts, several displaying different transcriptional start sites, thus suggesting mRNA-trimming mechanisms under stress. Downregulation of Rho and partner proteins pointed to changes in transcriptional elongation and termination under stress. The integrative proteomic-transcriptomic analysis demonstrated complex expression patterns of a large fraction of the proteome. Such patterns could not have been detected with one or the other omic analyses. Our analysis proposes the involvement of specific molecular mechanisms of post-transcriptional regulation to explain the observed complex stress response.

  6. Zipper-interacting protein kinase is involved in regulation of ubiquitination of the androgen receptor, thereby contributing to dynamic transcription complex assembly.

    Science.gov (United States)

    Felten, A; Brinckmann, D; Landsberg, G; Scheidtmann, K H

    2013-10-10

    We have recently identified apoptosis-antagonizing transcription factor (AATF), tumor-susceptibility gene 101 (TSG101) and zipper-interacting protein kinase (ZIPK) as novel coactivators of the androgen receptor (AR). The mechanisms of coactivation remained obscure, however. Here we investigated the interplay and interdependence between these coactivators and the AR using the endogenous prostate specific antigen (PSA) gene as model for AR-target genes. Chromatin immunoprecipitation in combination with siRNA-mediated knockdown revealed that recruitment of AATF and ZIPK to the PSA enhancer was dependent on AR, whereas recruitment of TSG101 was dependent on AATF. Association of AR and its coactivators with the PSA enhancer or promoter occurred in cycles. Dissociation of AR-transcription complexes was due to degradation because inhibition of the proteasome system by MG132 caused accumulation of AR at enhancer/promoter elements. Moreover, inhibition of degradation strongly reduced transcription, indicating that continued and efficient transcription is based on initiation, degradation and reinitiation cycles. Interestingly, knockdown of ZIPK by siRNA had a similar effect as MG132, leading to reduced transcription but enhanced accumulation of AR at androgen-response elements. In addition, knockdown of ZIPK, as well as overexpression of a dominant-negative ZIPK mutant, diminished polyubiquitination of AR. Furthermore, ZIPK cooperated with the E3 ligase Mdm2 in AR-dependent transactivation, assembled into a single complex on chromatin and phosphorylated Mdm2 in vitro. These results suggest that ZIPK has a crucial role in regulation of ubiquitination and degradation of the AR, and hence promoter clearance and efficient transcription.

  7. Multiple 5' ends of human cytomegalovirus UL57 transcripts identify a complex, cycloheximide-resistant promoter region that activates oriLyt

    International Nuclear Information System (INIS)

    Kiehl, Anita; Huang, Lili; Franchi, David; Anders, David G.

    2003-01-01

    The human cytomegalovirus (HCMV) UL57 gene lies adjacent to HCMV oriLyt, from which it is separated by an organizationally conserved, mostly noncoding region that is thought to both regulate UL57 expression and activate oriLyt function. However, the UL57 promoter has not been studied. We determined the 5' ends of UL57 transcripts toward an understanding of the potential relationship between UL57 expression and oriLyt activation. The results presented here identified three distinct 5' ends spread over 800 bp, at nt 90302, 90530, and 91138; use of these sites exhibited differential sensitivity to phosphonoformic acid treatment. Interestingly, a 10-kb UL57 transcript accumulated in cycloheximide-treated infected cells, even though other early transcripts were not detectable. However, the 10-kb transcript did not accumulate in cells treated with the more stringent translation inhibitor anisomycin. Consistent with the notion that the identified 5' ends arise from distinct transcription start sites, the sequences upstream of sites I and II functioned as promoters responsive to HCMV infection in transient assays. However, the origin-proximal promoter region III required downstream sequences for transcriptional activity. Mutation of candidate core promoter elements suggested that promoter III is regulated by an initiator region (Inr) and a downstream promoter element. Finally, a 42-bp sequence containing the candidate Inr activated a minimal oriLyt core construct in transient replication assays. Thus, these studies showed that a large, complex promoter region with novel features controls UL57 expression, and identified a sequence that regulates both UL57 transcription and oriLyt activation

  8. A human Polycomb isoform lacking the Pc box does not participate to PRC1 complexes but forms protein assemblies and represses transcription.

    Science.gov (United States)

    Völkel, Pamela; Le Faou, Perrine; Vandamme, Julien; Pira, Dorcas; Angrand, Pierre-Olivier

    2012-05-01

    Polycomb repression controls the expression of hundreds of genes involved in development and is mediated by essentially two classes of chromatin-associated protein complexes. The Polycomb repressive complex 2 (PRC2) trimethylates histone H3 at lysine 27, an epigenetic mark that serves as a docking site for the PRC1 protein complex. Drosophila core PRC1 is composed of four subunits: Polycomb (Pc), Posterior sex combs (Psc), Polyhomeotic (Ph) and Sex combs extra (Sce). Each of these proteins has multiple orthologs in vertebrates, thus generating an enormous scope for potential combinatorial diversity. In particular, mammalian genomes encode five Pc family members: CBX2, CBX4, CBX6, CBX7 and CBX8. To complicate matters further, distinct isoforms might arise from single genes. Here, we address the functional role of the two human CBX2 isoforms. Owing to different polyadenylation sites and alternative splicing events, the human CBX2 locus produces two transcripts: a 5-exon transcript that encodes the 532-amino acid CBX2-1 isoform that contains the conserved chromodomain and Pc box and a 4-exon transcript encoding a shorter isoform, CBX2-2, lacking the Pc box but still possessing a chromodomain. Using biochemical approaches and a novel in vivo imaging assay, we show that the short CBX2-2 isoform lacking the Pc box, does not participate in PRC1 protein complexes, but self-associates in vivo and forms complexes of high molecular weight. Furthermore, the CBX2 short isoform is still able to repress transcription, suggesting that Polycomb repression might occur in the absence of PRC1 formation.

  9. HYPER RECOMBINATION1 of the THO/TREX complex plays a role in controlling transcription of the REVERSION-TO-ETHYLENE SENSITIVITY1 gene in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Congyao Xu

    2015-02-01

    Full Text Available Arabidopsis REVERSION-TO-ETHYLENE SENSITIVITY1 (RTE1 represses ethylene hormone responses by promoting ethylene receptor ETHYLENE RESPONSE1 (ETR1 signaling, which negatively regulates ethylene responses. To investigate the regulation of RTE1, we performed a genetic screening for mutations that suppress ethylene insensitivity conferred by RTE1 overexpression in Arabidopsis. We isolated HYPER RECOMBINATION1 (HPR1, which is required for RTE1 overexpressor (RTE1ox ethylene insensitivity at the seedling but not adult stage. HPR1 is a component of the THO complex, which, with other proteins, forms the TRanscription EXport (TREX complex. In yeast, Drosophila, and humans, the THO/TREX complex is involved in transcription elongation and nucleocytoplasmic RNA export, but its role in plants is to be fully determined. We investigated how HPR1 is involved in RTE1ox ethylene insensitivity in Arabidopsis. The hpr1-5 mutation may affect nucleocytoplasmic mRNA export, as revealed by in vivo hybridization of fluorescein-labeled oligo(dT45 with unidentified mRNA in the nucleus. The hpr1-5 mutation reduced the total and nuclear RTE1 transcript levels to a similar extent, and RTE1 transcript reduction rate was not affected by hpr1-5 with cordycepin treatment, which prematurely terminates transcription. The defect in the THO-interacting TEX1 protein of TREX but not the mRNA export factor SAC3B also reduced the total and nuclear RTE1 levels. SERINE-ARGININE-RICH (SR proteins are involved mRNA splicing, and we found that SR protein SR33 co-localized with HPR1 in nuclear speckles, which agreed with the association of human TREX with the splicing machinery. We reveal a role for HPR1 in RTE1 expression during transcription elongation and less likely during export. Gene expression involved in ethylene signaling suppression was not reduced by the hpr1-5 mutation, which indicates selectivity of HPR1 for RTE1 expression affecting the consequent ethylene response. Thus

  10. Structure and Function of the Ankyrin Repeats in the Sw14/Sw16 Transcription Complex of Budding Yeast

    National Research Council Canada - National Science Library

    Breeden, Linda

    1998-01-01

    ANK repeats were first found in the Swi6 transcription factor of Saccharomyces cerevisiae and since then were identified in many proteins, including oncogenes and tumor suppressors We have previously...

  11. Overexpression of the PAP1 transcription factor reveals a complex regulation of flavonoid and phenylpropanoid metabolism in Nicotiana tabacum plants attacked by Spodoptera litura.

    Science.gov (United States)

    Mitsunami, Tomoko; Nishihara, Masahiro; Galis, Ivan; Alamgir, Kabir Md; Hojo, Yuko; Fujita, Kohei; Sasaki, Nobuhiro; Nemoto, Keichiro; Sawasaki, Tatsuya; Arimura, Gen-ichiro

    2014-01-01

    Anthocyanin pigments and associated flavonoids have demonstrated antioxidant properties and benefits for human health. Consequently, current plant bioengineers have focused on how to modify flavonoid metabolism in plants. Most of that research, however, does not consider the role of natural biotic stresses (e.g., herbivore attack). To understand the influence of herbivore attack on the metabolic engineering of flavonoids, we examined tobacco plants overexpressing the Arabidopsis PAP1 gene (encoding an MYB transcription factor), which accumulated anthocyanin pigments and other flavonoids/phenylpropanoids. In comparison to wild-type and control plants, transgenic plants exhibited greater resistance to Spodoptera litura. Moreover, herbivory suppressed the PAP1-induced increase of transcripts of flavonoid/phenylpropanoid biosynthetic genes (e.g., F3H) and the subsequent accumulation of these genes' metabolites, despite the unaltered PAP1 mRNA levels after herbivory. The instances of down-regulation were independent of the signaling pathways mediated by defense-related jasmonates but were relevant to the levels of PAP1-induced and herbivory-suppressed transcription factors, An1a and An1b. Although initially F3H transcripts were suppressed by herbivory, after the S. litura feeding was interrupted, F3H transcripts increased. We hypothesize that in transgenic plants responding to herbivory, there is a complex mechanism regulating enriched flavonoid/phenylpropanoid compounds, via biotic stress signals.

  12. Overexpression of the PAP1 transcription factor reveals a complex regulation of flavonoid and phenylpropanoid metabolism in Nicotiana tabacum plants attacked by Spodoptera litura.

    Directory of Open Access Journals (Sweden)

    Tomoko Mitsunami

    Full Text Available Anthocyanin pigments and associated flavonoids have demonstrated antioxidant properties and benefits for human health. Consequently, current plant bioengineers have focused on how to modify flavonoid metabolism in plants. Most of that research, however, does not consider the role of natural biotic stresses (e.g., herbivore attack. To understand the influence of herbivore attack on the metabolic engineering of flavonoids, we examined tobacco plants overexpressing the Arabidopsis PAP1 gene (encoding an MYB transcription factor, which accumulated anthocyanin pigments and other flavonoids/phenylpropanoids. In comparison to wild-type and control plants, transgenic plants exhibited greater resistance to Spodoptera litura. Moreover, herbivory suppressed the PAP1-induced increase of transcripts of flavonoid/phenylpropanoid biosynthetic genes (e.g., F3H and the subsequent accumulation of these genes' metabolites, despite the unaltered PAP1 mRNA levels after herbivory. The instances of down-regulation were independent of the signaling pathways mediated by defense-related jasmonates but were relevant to the levels of PAP1-induced and herbivory-suppressed transcription factors, An1a and An1b. Although initially F3H transcripts were suppressed by herbivory, after the S. litura feeding was interrupted, F3H transcripts increased. We hypothesize that in transgenic plants responding to herbivory, there is a complex mechanism regulating enriched flavonoid/phenylpropanoid compounds, via biotic stress signals.

  13. Overexpression of the PAP1 Transcription Factor Reveals a Complex Regulation of Flavonoid and Phenylpropanoid Metabolism in Nicotiana tabacum Plants Attacked by Spodoptera litura

    Science.gov (United States)

    Mitsunami, Tomoko; Nishihara, Masahiro; Galis, Ivan; Alamgir, Kabir Md; Hojo, Yuko; Fujita, Kohei; Sasaki, Nobuhiro; Nemoto, Keichiro; Sawasaki, Tatsuya; Arimura, Gen-ichiro

    2014-01-01

    Anthocyanin pigments and associated flavonoids have demonstrated antioxidant properties and benefits for human health. Consequently, current plant bioengineers have focused on how to modify flavonoid metabolism in plants. Most of that research, however, does not consider the role of natural biotic stresses (e.g., herbivore attack). To understand the influence of herbivore attack on the metabolic engineering of flavonoids, we examined tobacco plants overexpressing the Arabidopsis PAP1 gene (encoding an MYB transcription factor), which accumulated anthocyanin pigments and other flavonoids/phenylpropanoids. In comparison to wild-type and control plants, transgenic plants exhibited greater resistance to Spodoptera litura. Moreover, herbivory suppressed the PAP1-induced increase of transcripts of flavonoid/phenylpropanoid biosynthetic genes (e.g., F3H) and the subsequent accumulation of these genes' metabolites, despite the unaltered PAP1 mRNA levels after herbivory. The instances of down-regulation were independent of the signaling pathways mediated by defense-related jasmonates but were relevant to the levels of PAP1-induced and herbivory-suppressed transcription factors, An1a and An1b. Although initially F3H transcripts were suppressed by herbivory, after the S. litura feeding was interrupted, F3H transcripts increased. We hypothesize that in transgenic plants responding to herbivory, there is a complex mechanism regulating enriched flavonoid/phenylpropanoid compounds, via biotic stress signals. PMID:25268129

  14. CRISPR-Cas type I-A Cascade complex couples viral infection surveillance to host transcriptional regulation in the dependence of Csa3b.

    Science.gov (United States)

    He, Fei; Vestergaard, Gisle; Peng, Wenfang; She, Qunxin; Peng, Xu

    2017-02-28

    CRISPR-Cas (clustered regularly interspaced short palindromic repeats and the associated genes) constitute adaptive immune systems in bacteria and archaea and they provide sequence specific immunity against foreign nucleic acids. CRISPR-Cas systems are activated by viral infection. However, little is known about how CRISPR-Cas systems are activated in response to viral infection or how their expression is controlled in the absence of viral infection. Here, we demonstrate that both the transcriptional regulator Csa3b, and the type I-A interference complex Cascade, are required to transcriptionally repress the interference gene cassette in the archaeon Sulfolobus. Csa3b binds to two palindromic repeat sites in the promoter region of the cassette and facilitates binding of the Cascade to the promoter region. Upon viral infection, loading of Cascade complexes onto crRNA-matching protospacers leads to relief of the transcriptional repression. Our data demonstrate a mechanism coupling CRISPR-Cas surveillance of protospacers to transcriptional regulation of the interference gene cassette thereby allowing a fast response to viral infection. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  15. Preparation, crystallization and preliminary X-ray diffraction analysis of the DNA-binding domain of the Ets transcription factor in complex with target DNA

    International Nuclear Information System (INIS)

    Suwa, Yoshiaki; Nakamura, Teruya; Toma, Sachiko; Ikemizu, Shinji; Kai, Hirofumi; Yamagata, Yuriko

    2008-01-01

    The complex between the Ets domain of Ets2 and its target DNA has been crystallized. The crystals diffracted to 3.0 Å resolution. The Ets2 transcription factor is a member of the Ets transcription-factor family. Ets2 plays a role in the malignancy of cancer and in Down’s syndrome by regulating the transcription of various genes. The DNA-binding domain of Ets2 (Ets domain; ETSD), which contains residues that are highly conserved among Ets transcription-factor family members, was expressed as a GST-fusion protein. The aggregation of ETSD produced after thrombin cleavage could be prevented by treatment with NDSB-195 (nondetergent sulfobetaine 195). ETSD was crystallized in complex with DNA containing the Ets2 target sequence (GGAA) by the hanging-drop vapour-diffusion method. The best crystals were grown using 25% PEG 3350, 80 mM magnesium acetate, 50 mM sodium cacodylate pH 5.0/5.5 as the reservoir at 293 K. The crystals belonged to space group C2, with unit-cell parameters a = 85.89, b = 95.52, c = 71.89 Å, β = 101.7° and a V M value of 3.56 Å 3 Da −1 . Diffraction data were collected to a resolution of 3.0 Å

  16. Preparation, crystallization and preliminary X-ray diffraction analysis of the DNA-binding domain of the Ets transcription factor in complex with target DNA

    Energy Technology Data Exchange (ETDEWEB)

    Suwa, Yoshiaki; Nakamura, Teruya; Toma, Sachiko; Ikemizu, Shinji; Kai, Hirofumi; Yamagata, Yuriko, E-mail: yamagata@gpo.kumamoto-u.ac.jp [Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973 (Japan)

    2008-03-01

    The complex between the Ets domain of Ets2 and its target DNA has been crystallized. The crystals diffracted to 3.0 Å resolution. The Ets2 transcription factor is a member of the Ets transcription-factor family. Ets2 plays a role in the malignancy of cancer and in Down’s syndrome by regulating the transcription of various genes. The DNA-binding domain of Ets2 (Ets domain; ETSD), which contains residues that are highly conserved among Ets transcription-factor family members, was expressed as a GST-fusion protein. The aggregation of ETSD produced after thrombin cleavage could be prevented by treatment with NDSB-195 (nondetergent sulfobetaine 195). ETSD was crystallized in complex with DNA containing the Ets2 target sequence (GGAA) by the hanging-drop vapour-diffusion method. The best crystals were grown using 25% PEG 3350, 80 mM magnesium acetate, 50 mM sodium cacodylate pH 5.0/5.5 as the reservoir at 293 K. The crystals belonged to space group C2, with unit-cell parameters a = 85.89, b = 95.52, c = 71.89 Å, β = 101.7° and a V{sub M} value of 3.56 Å{sup 3} Da{sup −1}. Diffraction data were collected to a resolution of 3.0 Å.

  17. CRISPR-Cas type I-A Cascade complex couples viral infection surveillance to host transcriptional regulation in the dependence of Csa3b

    Science.gov (United States)

    He, Fei; Vestergaard, Gisle; Peng, Wenfang; She, Qunxin

    2017-01-01

    Abstract CRISPR-Cas (clustered regularly interspaced short palindromic repeats and the associated genes) constitute adaptive immune systems in bacteria and archaea and they provide sequence specific immunity against foreign nucleic acids. CRISPR-Cas systems are activated by viral infection. However, little is known about how CRISPR-Cas systems are activated in response to viral infection or how their expression is controlled in the absence of viral infection. Here, we demonstrate that both the transcriptional regulator Csa3b, and the type I-A interference complex Cascade, are required to transcriptionally repress the interference gene cassette in the archaeon Sulfolobus. Csa3b binds to two palindromic repeat sites in the promoter region of the cassette and facilitates binding of the Cascade to the promoter region. Upon viral infection, loading of Cascade complexes onto crRNA-matching protospacers leads to relief of the transcriptional repression. Our data demonstrate a mechanism coupling CRISPR-Cas surveillance of protospacers to transcriptional regulation of the interference gene cassette thereby allowing a fast response to viral infection. PMID:27980065

  18. Crystallization and preliminary crystallographic analysis of the transcriptional regulator RfaH from Escherichia coli and its complex with ops DNA

    International Nuclear Information System (INIS)

    Vassylyeva, Marina N.; Svetlov, Vladimir; Klyuyev, Sergiy; Devedjiev, Yancho D.; Artsimovitch, Irina; Vassylyev, Dmitry G.

    2006-01-01

    The E. coli transcriptional regulator RfaH was cloned, expressed, purified and crystallized and the complex of RfaH with its target DNA oligonucleotide was cocrystallized. Complete diffraction data sets were collected for the apo protein and its nucleic acid complex at 2.4 and at 1.6 Å resolution, respectively. The bacterial transcriptional factor and virulence regulator RfaH binds to rapidly moving transcription elongation complexes through specific interactions with the exposed segment of the non-template DNA strand. To elucidate this unusual mechanism of recruitment, determination of the three-dimensional structure of RfaH and its complex with DNA was initiated. To this end, the Escherichia coli rfaH gene was cloned and expressed. The purified protein was crystallized by the sitting-drop vapor-diffusion technique. The space group was P6 1 22 or P6 5 22, with unit-cell parameters a = b = 45.46, c = 599.93 Å. A complex of RfaH and a nine-nucleotide oligodeoxyribonucleotide was crystallized by the same technique, but under different crystallization conditions, yielding crystals that belonged to space group P1 (unit-cell parameters a = 36.79, b = 44.01, c = 62.37 Å, α = 80.62, β = 75.37, γ = 75.41°). Complete diffraction data sets were collected for RfaH and its complex with DNA at 2.4 and 1.6 Å resolution, respectively. Crystals of selenomethionine-labeled proteins in both crystal forms were obtained by cross-microseeding using the native microcrystals. The structure determination of RfaH and its complex with DNA is in progress

  19. A unique enhancer boundary complex on the mouse ribosomal RNA genes persists after loss of Rrn3 or UBF and the inactivation of RNA polymerase I transcription.

    Science.gov (United States)

    Herdman, Chelsea; Mars, Jean-Clement; Stefanovsky, Victor Y; Tremblay, Michel G; Sabourin-Felix, Marianne; Lindsay, Helen; Robinson, Mark D; Moss, Tom

    2017-07-01

    Transcription of the several hundred of mouse and human Ribosomal RNA (rRNA) genes accounts for the majority of RNA synthesis in the cell nucleus and is the determinant of cytoplasmic ribosome abundance, a key factor in regulating gene expression. The rRNA genes, referred to globally as the rDNA, are clustered as direct repeats at the Nucleolar Organiser Regions, NORs, of several chromosomes, and in many cells the active repeats are transcribed at near saturation levels. The rDNA is also a hotspot of recombination and chromosome breakage, and hence understanding its control has broad importance. Despite the need for a high level of rDNA transcription, typically only a fraction of the rDNA is transcriptionally active, and some NORs are permanently silenced by CpG methylation. Various chromatin-remodelling complexes have been implicated in counteracting silencing to maintain rDNA activity. However, the chromatin structure of the active rDNA fraction is still far from clear. Here we have combined a high-resolution ChIP-Seq protocol with conditional inactivation of key basal factors to better understand what determines active rDNA chromatin. The data resolve questions concerning the interdependence of the basal transcription factors, show that preinitiation complex formation is driven by the architectural factor UBF (UBTF) independently of transcription, and that RPI termination and release corresponds with the site of TTF1 binding. They further reveal the existence of an asymmetric Enhancer Boundary Complex formed by CTCF and Cohesin and flanked upstream by phased nucleosomes and downstream by an arrested RNA Polymerase I complex. We find that the Enhancer Boundary Complex is the only site of active histone modification in the 45kbp rDNA repeat. Strikingly, it not only delimits each functional rRNA gene, but also is stably maintained after gene inactivation and the re-establishment of surrounding repressive chromatin. Our data define a poised state of rDNA chromatin

  20. A unique enhancer boundary complex on the mouse ribosomal RNA genes persists after loss of Rrn3 or UBF and the inactivation of RNA polymerase I transcription.

    Directory of Open Access Journals (Sweden)

    Chelsea Herdman

    2017-07-01

    Full Text Available Transcription of the several hundred of mouse and human Ribosomal RNA (rRNA genes accounts for the majority of RNA synthesis in the cell nucleus and is the determinant of cytoplasmic ribosome abundance, a key factor in regulating gene expression. The rRNA genes, referred to globally as the rDNA, are clustered as direct repeats at the Nucleolar Organiser Regions, NORs, of several chromosomes, and in many cells the active repeats are transcribed at near saturation levels. The rDNA is also a hotspot of recombination and chromosome breakage, and hence understanding its control has broad importance. Despite the need for a high level of rDNA transcription, typically only a fraction of the rDNA is transcriptionally active, and some NORs are permanently silenced by CpG methylation. Various chromatin-remodelling complexes have been implicated in counteracting silencing to maintain rDNA activity. However, the chromatin structure of the active rDNA fraction is still far from clear. Here we have combined a high-resolution ChIP-Seq protocol with conditional inactivation of key basal factors to better understand what determines active rDNA chromatin. The data resolve questions concerning the interdependence of the basal transcription factors, show that preinitiation complex formation is driven by the architectural factor UBF (UBTF independently of transcription, and that RPI termination and release corresponds with the site of TTF1 binding. They further reveal the existence of an asymmetric Enhancer Boundary Complex formed by CTCF and Cohesin and flanked upstream by phased nucleosomes and downstream by an arrested RNA Polymerase I complex. We find that the Enhancer Boundary Complex is the only site of active histone modification in the 45kbp rDNA repeat. Strikingly, it not only delimits each functional rRNA gene, but also is stably maintained after gene inactivation and the re-establishment of surrounding repressive chromatin. Our data define a poised state

  1. Primary blood-hosts of mosquitoes are influenced by social and ecological conditions in a complex urban landscape.

    Science.gov (United States)

    Goodman, Heather; Egizi, Andrea; Fonseca, Dina M; Leisnham, Paul T; LaDeau, Shannon L

    2018-04-10

    Temperate urban landscapes support persistent and growing populations of Culex and Aedes mosquito vectors. Large urban mosquito populations can represent a significant risk for transmission of emergent arboviral infection. However, even large mosquito populations are only a risk to the animals they bite. The purpose of this study is to identify and assess spatial patterns of host-use in a temperate urban landscape with heterogeneous socio-economic and ecological conditions. Mosquito blood meals were collected from neighborhoods categorized along a socio-economic gradient in Baltimore, MD, USA. Blood meal hosts were identified for two Aedes (Ae. albopictus and Ae. japonicus) and three Culex (Cx. pipiens, Cx. restuans and Cx. salinarius) species. The brown rat (Rattus norvegicus) was the most frequently detected host in both Aedes species and Cx. salinarius. Human biting was evident in Aedes and Culex species and the proportion of human blood meals from Ae. albopictus varied significantly with neighborhood socio-economic status. Aedes albopictus was most likely to feed on human blood hosts (at 50%) in residential blocks categorized as having income above the city median, although there were still more total human bites detected from lower income blocks where Ae. albopictus was more abundant. Birds were the most frequently detected Culex blood hosts but were absent from all Aedes sampled. This study highlights fine-scale variation in host-use by medically important mosquito vectors and specifically investigates blood meal composition at spatial scales relevant to urban mosquito dispersal and human exposure. Further, the work emphasizes the importance of neighborhood economics and infrastructure management in shaping both the relative abundance of vectors and local blood feeding strategies. The invasive brown rat was an important blood source across vector species and neighborhoods in Baltimore. We show that social and economic conditions can be important predictors of

  2. Unraveling Landscape Complexity: Land Use/Land Cover Changes and Landscape Pattern Dynamics (1954-2008) in Contrasting Peri-Urban and Agro-Forest Regions of Northern Italy.

    Science.gov (United States)

    Smiraglia, D; Ceccarelli, T; Bajocco, S; Perini, L; Salvati, L

    2015-10-01

    This study implements an exploratory data analysis of landscape metrics and a change detection analysis of land use and population density to assess landscape dynamics (1954-2008) in two physiographic zones (plain and hilly-mountain area) of Emilia Romagna, northern Italy. The two areas are characterized by different landscape types: a mixed urban-rural landscape dominated by arable land and peri-urban settlements in the plain and a traditional agro-forest landscape in the hilly-mountain area with deciduous and conifer forests, scrublands, meadows, and crop mosaic. Urbanization and, to a lesser extent, agricultural intensification were identified as the processes underlying landscape change in the plain. Land abandonment determining natural forestation and re-forestation driven by man was identified as the process of change most representative of the hilly-mountain area. Trends in landscape metrics indicate a shift toward more fragmented and convoluted patterns in both areas. Number of patches, the interspersion and juxtaposition index, and the large patch index are the metrics discriminating the two areas in terms of landscape patterns in 1954. In 2008, mean patch size, edge density, interspersion and juxtaposition index, and mean Euclidean nearest neighbor distance were the metrics with the most different spatial patterns in the two areas. The exploratory data analysis of landscape metrics contributed to link changes over time in both landscape composition and configuration providing a comprehensive picture of landscape transformations in a wealthy European region. Evidence from this study are hoped to inform sustainable land management designed for homogeneous landscape units in similar socioeconomic contexts.

  3. Human RNA polymerase II associated factor 1 complex promotes tumorigenesis by activating c-MYC transcription in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Zhi, Xiuyi; Giroux-Leprieur, Etienne; Wislez, Marie; Hu, Mu; Zhang, Yi; Shi, Huaiyin; Du, Kaiqi; Wang, Lei

    2015-01-01

    Human RNA polymerase II (RNAPII)-associated factor 1 complex (hPAF1C) plays a crucial role in protein-coding gene transcription. Overexpression of hPAF1C has been implicated in the initiation and progression of various human cancers. However, the molecular pathways involved in tumorigenesis through hPAF1C remain to be elucidated. The current study suggested hPAF1C expression as a prognostic biomarker for early stage non-small cell lung cancer (NSCLC) and patients with low hPAF1C expression levels had significantly better overall survival. Furthermore, the expression of hPAF1C was found to be positively correlated with c-MYC expression in patient tumor samples and in cancer cell lines. Mechanistic studies indicated that hPAF1C could promote lung cancer cell proliferation through regulating c-MYC transcription. These results demonstrated the prognostic value of hPAF1C in early-stage NSCLC and the role of hPAF1C in the transcriptional regulation of c-MYC oncogene during NSCLC tumorigenesis. - Highlights: • hPAF1C expression is a prognostic biomarker for early stage non-small cell lung cancer. • The expression of hPAF1C was positively correlated with c-MYC in tumor samples of patients and in several NSCLC cell lines. • hPAF1C could promote lung cancer cell proliferation through regulating c-MYC transcription.

  4. A Complex Network Theory Approach for the Spatial Distribution of Fire Breaks in Heterogeneous Forest Landscapes for the Control of Wildland Fires.

    Science.gov (United States)

    Russo, Lucia; Russo, Paola; Siettos, Constantinos I

    2016-01-01

    Based on complex network theory, we propose a computational methodology which addresses the spatial distribution of fuel breaks for the inhibition of the spread of wildland fires on heterogeneous landscapes. This is a two-level approach where the dynamics of fire spread are modeled as a random Markov field process on a directed network whose edge weights are determined by a Cellular Automata model that integrates detailed GIS, landscape and meteorological data. Within this framework, the spatial distribution of fuel breaks is reduced to the problem of finding network nodes (small land patches) which favour fire propagation. Here, this is accomplished by exploiting network centrality statistics. We illustrate the proposed approach through (a) an artificial forest of randomly distributed density of vegetation, and (b) a real-world case concerning the island of Rhodes in Greece whose major part of its forest was burned in 2008. Simulation results show that the proposed methodology outperforms the benchmark/conventional policy of fuel reduction as this can be realized by selective harvesting and/or prescribed burning based on the density and flammability of vegetation. Interestingly, our approach reveals that patches with sparse density of vegetation may act as hubs for the spread of the fire.

  5. A Complex Network Theory Approach for the Spatial Distribution of Fire Breaks in Heterogeneous Forest Landscapes for the Control of Wildland Fires.

    Directory of Open Access Journals (Sweden)

    Lucia Russo

    Full Text Available Based on complex network theory, we propose a computational methodology which addresses the spatial distribution of fuel breaks for the inhibition of the spread of wildland fires on heterogeneous landscapes. This is a two-level approach where the dynamics of fire spread are modeled as a random Markov field process on a directed network whose edge weights are determined by a Cellular Automata model that integrates detailed GIS, landscape and meteorological data. Within this framework, the spatial distribution of fuel breaks is reduced to the problem of finding network nodes (small land patches which favour fire propagation. Here, this is accomplished by exploiting network centrality statistics. We illustrate the proposed approach through (a an artificial forest of randomly distributed density of vegetation, and (b a real-world case concerning the island of Rhodes in Greece whose major part of its forest was burned in 2008. Simulation results show that the proposed methodology outperforms the benchmark/conventional policy of fuel reduction as this can be realized by selective harvesting and/or prescribed burning based on the density and flammability of vegetation. Interestingly, our approach reveals that patches with sparse density of vegetation may act as hubs for the spread of the fire.

  6. Androgen receptor activation integrates complex transcriptional effects in osteoblasts, involving the growth factors TGF-β and IGF-I, and transcription factor C/EBPδ.

    Science.gov (United States)

    McCarthy, Thomas L; Centrella, Michael

    2015-11-15

    Osteoblasts respond to many growth factors including IGF-I and TGF-β, which themselves are sensitive to other bone growth regulators. Here we show that IGF-I gene promoter activity in prostaglandin E2 (PGE2) induced osteoblasts is suppressed by dihydrotestosterone (DHT) through an essential C/EBP response element (RE) in exon 1 of the igf1 gene. Inhibition by DHT fails to occur when the androgen receptor (AR) gene is mutated within its DNA binding domain. Correspondingly, DHT activated AR inhibits gene transactivation by C/EBPδ, and transgenic C/EBPδ expression inhibits AR activity. Inhibition by DHT persists when upstream Smad and Runx REs in the IGF-I gene promoter are mutated. TGF-β also enhances IGF-I gene promoter activity, although modestly relative to PGE2, and independently of the C/EBP, Smad, or Runx REs. Still, DHT suppresses TGF-β induced IGF-I promoter activity, but not its effects on DNA or collagen synthesis. Notably, DHT suppresses plasminogen activator inhibitor gene promoter activity, but synergistically increases Smad dependent gene promoter activity in TGF-β induced cells, which are differentially sensitive to AR mutations and the AR co-regulator ARA55. Finally, although the PGE2 sensitive C/EBP RE in the igf1 gene is not essential for basal TGF-β induction, C/EBPδ activity through this site is potently enhanced by TGF-β. Thus DHT suppresses the PGE2 and TGF-β induced IGF-I gene promoter and differentiates other aspects of TGF-β activity in osteoblasts. Our results extend the complex interactions among local and systemic bone growth regulators to DHT, and predict complications from anabolic steroid use in other DHT sensitive tissues. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Contradiction between plastid gene transcription and function due to complex posttranscriptional splicing: an exemplary study of ycf15 function and evolution in angiosperms.

    Directory of Open Access Journals (Sweden)

    Chao Shi

    Full Text Available Plant chloroplast genes are usually co-transcribed while its posttranscriptional splicing is fairly complex and remains largely unsolved. On basis of sequencing the three complete Camellia (Theaceae chloroplast genomes for the first time, we comprehensively analyzed the evolutionary patterns of ycf15, a plastid gene quite paradoxical in terms of its function and evolution, along the inferred angiosperm phylogeny. Although many species in separate lineages including the three species reported here contained an intact ycf15 gene in their chloroplast genomes, the phylogenetic mixture of both intact and obviously disabled ycf15 genes imply that they are all non-functional. Both intracellular gene transfer (IGT and horizontal gene transfer (HGT failed to explain such distributional anomalies. While, transcriptome analyses revealed that ycf15 was transcribed as precursor polycistronic transcript which contained ycf2, ycf15 and antisense trnL-CAA. The transcriptome assembly was surprisingly found to cover near the complete Camellia chloroplast genome. Many non-coding regions including pseudogenes were mapped by multiple transcripts, indicating the generality of pseudogene transcriptions. Our results suggest that plastid DNA posttranscriptional splicing may involve complex cleavage of non-functional genes.

  8. Members of an R2R3-MYB transcription factor family in Petunia are developmentally and environmentally regulated to control complex floral and vegetative pigmentation patterning.

    Science.gov (United States)

    Albert, Nick W; Lewis, David H; Zhang, Huaibi; Schwinn, Kathy E; Jameson, Paula E; Davies, Kevin M

    2011-03-01

    We present an investigation of anthocyanin regulation over the entire petunia plant, determining the mechanisms governing complex floral pigmentation patterning and environmentally induced vegetative anthocyanin synthesis. DEEP PURPLE (DPL) and PURPLE HAZE (PHZ) encode members of the R2R3-MYB transcription factor family that regulate anthocyanin synthesis in petunia, and control anthocyanin production in vegetative tissues and contribute to floral pigmentation. In addition to these two MYB factors, the basic helix-loop-helix (bHLH) factor ANTHOCYANIN1 (AN1) and WD-repeat protein AN11, are also essential for vegetative pigmentation. The induction of anthocyanins in vegetative tissues by high light was tightly correlated to the induction of transcripts for PHZ and AN1. Interestingly, transcripts for PhMYB27, a putative R2R3-MYB active repressor, were highly expressed during non-inductive shade conditions and repressed during high light. The competitive inhibitor PhMYBx (R3-MYB) was expressed under high light, which may provide feedback repression. In floral tissues DPL regulates vein-associated anthocyanin pigmentation in the flower tube, while PHZ determines light-induced anthocyanin accumulation on exposed petal surfaces (bud-blush). A model is presented suggesting how complex floral and vegetative pigmentation patterns are derived in petunia in terms of MYB, bHLH and WDR co-regulators. © 2011 The Authors. The Plant Journal © 2011 Blackwell Publishing Ltd.

  9. Probing the interaction between the histone methyltransferase/deacetylase subunit RBBP4/7 and the transcription factor BCL11A in epigenetic complexes.

    Science.gov (United States)

    Moody, Rebecca Reed; Lo, Miao-Chia; Meagher, Jennifer L; Lin, Chang-Ching; Stevers, Nicholas O; Tinsley, Samantha L; Jung, Inkyung; Matvekas, Aleksas; Stuckey, Jeanne A; Sun, Duxin

    2018-02-09

    The transcription factor BCL11A has recently been reported to be a driving force in triple-negative breast cancer (TNBC), contributing to the maintenance of a chemoresistant breast cancer stem cell (BCSC) population. Although BCL11A was shown to suppress γ-globin and p21 and to induce MDM2 expression in the hematopoietic system, its downstream targets in TNBC are still unclear. For its role in transcriptional repression, BCL11A was found to interact with several corepressor complexes; however, the mechanisms underlying these interactions remain unknown. Here, we reveal that BCL11A interacts with histone methyltransferase (PRC2) and histone deacetylase (NuRD and SIN3A) complexes through their common subunit, RBBP4/7. In fluorescence polarization assays, we show that BCL11A competes with histone H3 for binding to the negatively charged top face of RBBP4. To define that interaction, we solved the crystal structure of RBBP4 in complex with an N-terminal peptide of BCL11A (residues 2-16, BCL11A(2-16)). The crystal structure identifies novel interactions between BCL11A and the side of the β-propeller of RBBP4 that are not seen with histone H3. We next show that BCL11A(2-16) pulls down RBBP4, RBBP7, and other components of PRC2, NuRD, and SIN3A from the cell lysate of the TNBC cell line SUM149. Furthermore, we demonstrate the therapeutic potential of targeting the RBBP4-BCL11A binding by showing that a BCL11A peptide can decrease aldehyde dehydrogenase-positive BCSCs and mammosphere formation capacity in SUM149. Together, our findings have uncovered a previously unidentified mechanism that BCL11A may use to recruit epigenetic complexes to regulate transcription and promote tumorigenesis. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Encapsulating model complexity and landscape-scale analyses of state-and-transition simulation models: an application of ecoinformatics and juniper encroachment in sagebrush steppe ecosystems

    Science.gov (United States)

    O'Donnell, Michael

    2015-01-01

    State-and-transition simulation modeling relies on knowledge of vegetation composition and structure (states) that describe community conditions, mechanistic feedbacks such as fire that can affect vegetation establishment, and ecological processes that drive community conditions as well as the transitions between these states. However, as the need for modeling larger and more complex landscapes increase, a more advanced awareness of computing resources becomes essential. The objectives of this study include identifying challenges of executing state-and-transition simulation models, identifying common bottlenecks of computing resources, developing a workflow and software that enable parallel processing of Monte Carlo simulations, and identifying the advantages and disadvantages of different computing resources. To address these objectives, this study used the ApexRMS® SyncroSim software and embarrassingly parallel tasks of Monte Carlo simulations on a single multicore computer and on distributed computing systems. The results demonstrated that state-and-transition simulation models scale best in distributed computing environments, such as high-throughput and high-performance computing, because these environments disseminate the workloads across many compute nodes, thereby supporting analysis of larger landscapes, higher spatial resolution vegetation products, and more complex models. Using a case study and five different computing environments, the top result (high-throughput computing versus serial computations) indicated an approximate 96.6% decrease of computing time. With a single, multicore compute node (bottom result), the computing time indicated an 81.8% decrease relative to using serial computations. These results provide insight into the tradeoffs of using different computing resources when research necessitates advanced integration of ecoinformatics incorporating large and complicated data inputs and models. - See more at: http://aimspress.com

  11. Planetary Landscape Geography

    Science.gov (United States)

    Hargitai, H.

    INTRODUCTION Landscape is one of the most often used category in physical ge- ography. The term "landshap" was introduced by Dutch painters in the 15-16th cen- tury. [1] The elements that build up a landscape (or environment) on Earth consists of natural (biogenic and abiogenic - lithologic, atmospheric, hydrologic) and artificial (antropogenic) factors. Landscape is a complex system of these different elements. The same lithology makes different landscapes under different climatic conditions. If the same conditions are present, the same landscape type will appear. Landscapes build up a hierarchic system and cover the whole surface. On Earth, landscapes can be classified and qualified according to their characteristics: relief forms (morphology), and its potential economic value. Aesthetic and subjective parameters can also be considered. Using the data from landers and data from orbiters we can now classify planetary landscapes (these can be used as geologic mapping units as well). By looking at a unknown landscape, we can determine the processes that created it and its development history. This was the case in the Pathfinder/Sojourner panoramas. [2]. DISCUSSION Planetary landscape evolution. We can draw a raw landscape develop- ment history by adding the different landscape building elements to each other. This has a strong connection with the planet's thermal evolution (age of the planet or the present surface materials) and with orbital parameters (distance from the central star, orbit excentricity etc). This way we can build a complex system in which we use differ- ent evolutional stages of lithologic, atmospheric, hydrologic and biogenic conditions which determine the given - Solar System or exoplanetary - landscape. Landscape elements. "Simple" landscapes can be found on asteroids: no linear horizon is present (not differentiated body, only impact structures), no atmosphere (therefore no atmospheric scattering - black sky as part of the landscape) and no

  12. Integrated analysis of RNA-binding protein complexes using in vitro selection and high-throughput sequencing and sequence specificity landscapes (SEQRS).

    Science.gov (United States)

    Lou, Tzu-Fang; Weidmann, Chase A; Killingsworth, Jordan; Tanaka Hall, Traci M; Goldstrohm, Aaron C; Campbell, Zachary T

    2017-04-15

    RNA-binding proteins (RBPs) collaborate to control virtually every aspect of RNA function. Tremendous progress has been made in the area of global assessment of RBP specificity using next-generation sequencing approaches both in vivo and in vitro. Understanding how protein-protein interactions enable precise combinatorial regulation of RNA remains a significant problem. Addressing this challenge requires tools that can quantitatively determine the specificities of both individual proteins and multimeric complexes in an unbiased and comprehensive way. One approach utilizes in vitro selection, high-throughput sequencing, and sequence-specificity landscapes (SEQRS). We outline a SEQRS experiment focused on obtaining the specificity of a multi-protein complex between Drosophila RBPs Pumilio (Pum) and Nanos (Nos). We discuss the necessary controls in this type of experiment and examine how the resulting data can be complemented with structural and cell-based reporter assays. Additionally, SEQRS data can be integrated with functional genomics data to uncover biological function. Finally, we propose extensions of the technique that will enhance our understanding of multi-protein regulatory complexes assembled onto RNA. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Ubiquitin fusion constructs allow the expression and purification of multi-KOW domain complexes of the Saccharomyces cerevisiae transcription elongation factor Spt4/5.

    Science.gov (United States)

    Blythe, Amanda; Gunasekara, Sanjika; Walshe, James; Mackay, Joel P; Hartzog, Grant A; Vrielink, Alice

    2014-08-01

    Spt4/5 is a hetero-dimeric transcription elongation factor that can both inhibit and promote transcription elongation by RNA polymerase II (RNAPII). However, Spt4/5's mechanism of action remains elusive. Spt5 is an essential protein and the only universally-conserved RNAP-associated transcription elongation factor. The protein contains multiple Kyrpides, Ouzounis and Woese (KOW) domains. These domains, in other proteins, are thought to bind RNA although there is little direct evidence in the literature to support such a function in Spt5. This could be due, at least in part, to difficulties in expressing and purifying recombinant Spt5. When expressed in Escherichia coli (E. coli), Spt5 is innately insoluble. Here we report a new approach for the successful expression and purification of milligram quantities of three different multi-KOW domain complexes of Saccharomyces cerevisiae Spt4/5 for use in future functional studies. Using the E. coli strain Rosetta2 (DE3) we have developed strategies for co-expression of Spt4 and multi-KOW domain Spt5 complexes from the bi-cistronic pET-Duet vector. In a second strategy, Spt4/5 was expressed via co-transformation of Spt4 in the vector pET-M11 with Spt5 ubiquitin fusion constructs in the vector pHUE. We characterized the multi-KOW domain Spt4/5 complexes by Western blot, limited proteolysis, circular dichroism, SDS-PAGE and size exclusion chromatography-multiangle light scattering and found that the proteins are folded with a Spt4:Spt5 hetero-dimeric stoichiometry of 1:1. These expression constructs encompass a larger region of Spt5 than has previously been reported, and will provide the opportunity to elucidate the biological function of the multi-KOW containing Spt5. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Condensed landscape experience

    DEFF Research Database (Denmark)

    Earon, Ofri

    2011-01-01

    demands, quality of space, mixture of functions, urban complexity, public life and cultural heritage. In order to launch such an approach, an understanding of the spatial, social and environmental significance of a radical re-thinking of relationships between architecture and landscape is necessary...... is becoming a standard in contemporary architecture. Merging architecture and landscape has turned into a principle for an ecological / sustainable architecture. Yet, my aspiration is to achieve a wider interaction involving an application of a wider range of perspectives, such as: urban identity, social......‘Re-thinking interaction between landscape and urban buildings’ participates in an interdisciplinary discourse about the theoretical and practical advantages of openly juxtaposing landscape and architecture without having one more advanced in importance. Recently, the greenification of buildings...

  15. RelB and RelE of Escherichia coli Form a Tight Complex That Represses Transcription via The Ribbon-Helix-Helix Motif in RelB

    DEFF Research Database (Denmark)

    Overgaard, Martin; Borch, Jonas; Gerdes, Kenn

    2009-01-01

    RelB, the Ribbon-Helix-Helix (RHH) repressor encoded by the relBE toxin-antitoxin locus of Escherichia coli, forms a tight complex with RelE and thereby counteracts the mRNA cleavage activity of RelE. In addition, RelB dimers repress the strong relBE promoter and this repression by RelB is enhanced...... by RelE - that is - RelE functions as a transcriptional co-repressor. RelB is a Lon protease substrate and Lon is required both for activation of relBE transcription and for activation of the mRNA cleavage activity of RelE. Here we characterize the molecular interactions important for transcriptional...... motif recognizes four 6 bp repeats within the bipartite binding site. The spacing between each half-site was found to be essential for cooperative interactions between adjacently bound RelB dimers stabilized by the co-repressor RelE. Kinetic and stoichiometric measurements of the interaction between Rel...

  16. An integrated view of complex landscapes: a big data-model integration approach to trans-disciplinary science

    Science.gov (United States)

    The Earth is a complex system comprised of many interacting spatial and temporal scales. Understanding, predicting, and managing for these dynamics requires a trans-disciplinary integrated approach. Although there have been calls for this integration, a general approach is needed. We developed a Tra...

  17. Improving the Spatial Prediction of Soil Organic Carbon Stocks in a Complex Tropical Mountain Landscape by Methodological Specifications in Machine Learning Approaches.

    Directory of Open Access Journals (Sweden)

    Mareike Ließ

    Full Text Available Tropical forests are significant carbon sinks and their soils' carbon storage potential is immense. However, little is known about the soil organic carbon (SOC stocks of tropical mountain areas whose complex soil-landscape and difficult accessibility pose a challenge to spatial analysis. The choice of methodology for spatial prediction is of high importance to improve the expected poor model results in case of low predictor-response correlations. Four aspects were considered to improve model performance in predicting SOC stocks of the organic layer of a tropical mountain forest landscape: Different spatial predictor settings, predictor selection strategies, various machine learning algorithms and model tuning. Five machine learning algorithms: random forests, artificial neural networks, multivariate adaptive regression splines, boosted regression trees and support vector machines were trained and tuned to predict SOC stocks from predictors derived from a digital elevation model and satellite image. Topographical predictors were calculated with a GIS search radius of 45 to 615 m. Finally, three predictor selection strategies were applied to the total set of 236 predictors. All machine learning algorithms-including the model tuning and predictor selection-were compared via five repetitions of a tenfold cross-validation. The boosted regression tree algorithm resulted in the overall best model. SOC stocks ranged between 0.2 to 17.7 kg m-2, displaying a huge variability with diffuse insolation and curvatures of different scale guiding the spatial pattern. Predictor selection and model tuning improved the models' predictive performance in all five machine learning algorithms. The rather low number of selected predictors favours forward compared to backward selection procedures. Choosing predictors due to their indiviual performance was vanquished by the two procedures which accounted for predictor interaction.

  18. Improving the Spatial Prediction of Soil Organic Carbon Stocks in a Complex Tropical Mountain Landscape by Methodological Specifications in Machine Learning Approaches.

    Science.gov (United States)

    Ließ, Mareike; Schmidt, Johannes; Glaser, Bruno

    2016-01-01

    Tropical forests are significant carbon sinks and their soils' carbon storage potential is immense. However, little is known about the soil organic carbon (SOC) stocks of tropical mountain areas whose complex soil-landscape and difficult accessibility pose a challenge to spatial analysis. The choice of methodology for spatial prediction is of high importance to improve the expected poor model results in case of low predictor-response correlations. Four aspects were considered to improve model performance in predicting SOC stocks of the organic layer of a tropical mountain forest landscape: Different spatial predictor settings, predictor selection strategies, various machine learning algorithms and model tuning. Five machine learning algorithms: random forests, artificial neural networks, multivariate adaptive regression splines, boosted regression trees and support vector machines were trained and tuned to predict SOC stocks from predictors derived from a digital elevation model and satellite image. Topographical predictors were calculated with a GIS search radius of 45 to 615 m. Finally, three predictor selection strategies were applied to the total set of 236 predictors. All machine learning algorithms-including the model tuning and predictor selection-were compared via five repetitions of a tenfold cross-validation. The boosted regression tree algorithm resulted in the overall best model. SOC stocks ranged between 0.2 to 17.7 kg m-2, displaying a huge variability with diffuse insolation and curvatures of different scale guiding the spatial pattern. Predictor selection and model tuning improved the models' predictive performance in all five machine learning algorithms. The rather low number of selected predictors favours forward compared to backward selection procedures. Choosing predictors due to their indiviual performance was vanquished by the two procedures which accounted for predictor interaction.

  19. Distinct cargo-specific response landscapes underpin the complex and nuanced role of galectin-glycan interactions in clathrin-independent endocytosis.

    Science.gov (United States)

    Mathew, Mohit P; Donaldson, Julie G

    2018-05-11

    Clathrin-independent endocytosis (CIE) is a form of endocytosis that lacks a defined cytoplasmic machinery. Here, we asked whether glycan interactions, acting from the outside, could be a part of that endocytic machinery. We show that the perturbation of global cellular patterns of protein glycosylation by modulation of metabolic flux affects CIE. Interestingly, these changes in glycosylation had cargo-specific effects. For example, in HeLa cells, GlcNAc treatment, which increases glycan branching, increased major histocompatibility complex class I (MHCI) internalization but inhibited CIE of the glycoprotein CD59 molecule (CD59). The effects of knocking down the expression of galectin 3, a carbohydrate-binding protein and an important player in galectin-glycan interactions, were also cargo-specific and stimulated CD59 uptake. By contrast, inhibition of all galectin-glycan interactions by lactose inhibited CIE of both MHCI and CD59. None of these treatments affected clathrin-mediated endocytosis, implying that glycosylation changes specifically affect CIE. We also found that the galectin lattice tailors membrane fluidity and cell spreading. Furthermore, changes in membrane dynamics mediated by the galectin lattice affected macropinocytosis, an altered form of CIE, in HT1080 cells. Our results suggest that glycans play an important and nuanced role in CIE, with each cargo being affected uniquely by alterations in galectin and glycan profiles and their interactions. We conclude that galectin-driven effects exist on a continuum from stimulatory to inhibitory, with distinct CIE cargo proteins having unique response landscapes and with different cell types starting at different positions on these conceptual landscapes.

  20. Complex systems thinking in emergency medicine: A novel paradigm for a rapidly changing and interconnected health care landscape.

    Science.gov (United States)

    Widmer, Matthew A; Swanson, R Chad; Zink, Brian J; Pines, Jesse M

    2017-12-27

    The specialty of emergency medicine is experiencing the convergence of a number of transformational forces in the United States, including health care reform, technological advancements, and societal shifts. These bring both opportunity and uncertainty. 21ST CENTURY CHALLENGES: Persistent challenges such as the opioid epidemic, rising health care costs, misaligned incentives, patients with multiple chronic diseases, and emergency department crowding continue to plague the acute, unscheduled care system. The traditional approach to health care practice and improvement-reductionism-is not adequate for the complexity of the twenty-first century. Reductionist thinking will likely continue to produce unintended consequences and suboptimal outcomes. Complex systems thinking provides a perspective and set of tools better suited for the challenges and opportunities facing public health in general, and emergency medicine more specifically. This article introduces complex systems thinking and argues for its application in the context of emergency medicine by drawing on the history of the circumstances surrounding the formation of the specialty and by providing examples of its application to several practice challenges. © 2017 John Wiley & Sons, Ltd.

  1. Complex formation of p65/RelA with nuclear Akt1 for enhanced transcriptional activation of NF-κB

    International Nuclear Information System (INIS)

    Kwon, Osong; Kim, Kyung A; He, Long; Jung, Mira; Jeong, Sook Jung; Ahn, Jong Seog; Kim, Bo Yeon

    2008-01-01

    Akt1 was revealed to interact with Ki-Ras in the cytoplasm of Ki-Ras-transformed human prostate epithelial cells, 267B1/K-ras. Moreover, p65/RelA in the nucleus was found to interact with both Ki-Ras and Akt1, suggesting the nuclear translocation of Akt1:Ki-Ras complex for NF- κB activation. In support of this, compared with wild type Akt1, the dominant negative Akt1 mutant was decreased in its nuclear expression, reducing the Ki-Ras-induced NF-κB transcriptional activation. Moreover, inhibitors of Ras (sulindac sulfide and farnesyltransferase inhibitor I) or PI3K/Akt (wortmannin), reduced the amounts of Akt1 and Ki-Ras in the nucleus as well as partial NF-κB activity. The complete inhibition of Ki-Ras-induced NF-κB activation, however, could only be obtained by combined treatment with wortmannin and proteasome inhibitor-1. Accordingly, clonogenic assay showed Akt1 contribution to IκBα-mediated NF-κB activation for oncogenic cell growth by Ki-Ras. Our data suggest a crucial role of Ki-Ras:Akt1 complex in NF-κB transcriptional activation and enhancement of cell survival

  2. URBAN LANDSCAPE QUALITY AND FACTORS THAT HAVE INFLUENCE ON LANDSCAPE QUALITY IN LATGALE REGION

    OpenAIRE

    Matisovs, Ivars

    2005-01-01

    The paper deals with urban landscape individualities in the cities and towns of Latgale region. Also show facilities and methods of integrated assessment of urban landscape quality. Article provides information about specifics of urban landscape and factors, that have influence on landscape quality. The paper presents the results of Daugavpils and Rēzekne urban landscape quality complex assessment, that have been realised in 2003- 2005. This results don’t establish significant disparities bet...

  3. A Genome-Scale Resource for the Functional Characterization of Arabidopsis Transcription Factors

    Directory of Open Access Journals (Sweden)

    Jose L. Pruneda-Paz

    2014-07-01

    Full Text Available Extensive transcriptional networks play major roles in cellular and organismal functions. Transcript levels are in part determined by the combinatorial and overlapping functions of multiple transcription factors (TFs bound to gene promoters. Thus, TF-promoter interactions provide the basic molecular wiring of transcriptional regulatory networks. In plants, discovery of the functional roles of TFs is limited by an increased complexity of network circuitry due to a significant expansion of TF families. Here, we present the construction of a comprehensive collection of Arabidopsis TFs clones created to provide a versatile resource for uncovering TF biological functions. We leveraged this collection by implementing a high-throughput DNA binding assay and identified direct regulators of a key clock gene (CCA1 that provide molecular links between different signaling modules and the circadian clock. The resources introduced in this work will significantly contribute to a better understanding of the transcriptional regulatory landscape of plant genomes.

  4. Landscape Ecology

    DEFF Research Database (Denmark)

    Christensen, Andreas Aagaard; Brandt, Jesper; Svenningsen, Stig Roar

    2017-01-01

    , and the ecological significance of the patterns which are generated by such processes. In landscape ecology, perspectives drawn from existing academic disciplines are integrated based on a common, spatially explicit mode of analysis developed from classical holistic geography, emphasizing spatial and landscape...... to translate positivist readings of the environment and hermeneutical perspectives on socioecological interaction into a common framework or terminology....

  5. Complex Adaptive Systems, soil degradation and land sensitivity to desertification: A multivariate assessment of Italian agro-forest landscape.

    Science.gov (United States)

    Salvati, Luca; Mavrakis, Anastasios; Colantoni, Andrea; Mancino, Giuseppe; Ferrara, Agostino

    2015-07-15

    Degradation of soils and sensitivity of land to desertification are intensified in last decades in the Mediterranean region producing heterogeneous spatial patterns determined by the interplay of factors such as climate, land-use changes, and human pressure. The present study hypothesizes that rising levels of soil degradation and land sensitivity to desertification are reflected into increasingly complex (and non-linear) relationships between environmental and socioeconomic variables. To verify this hypothesis, the Complex Adaptive Systems (CAS) framework was used to explore the spatiotemporal dynamics of eleven indicators derived from a standard assessment of soil degradation and land sensitivity to desertification in Italy. Indicators were made available on a detailed spatial scale (773 agricultural districts) for various years (1960, 1990, 2000 and 2010) and analyzed through a multi-dimensional exploratory data analysis. Our results indicate that the number of significant pair-wise correlations observed between indicators increased with the level of soil and land degradation, although with marked differences between northern and southern Italy. 'Fast' and 'slow' factors underlying soil and land degradation, and 'rapidly-evolving' or 'locked' agricultural districts were identified according to the rapidity of change estimated for each of the indicators studied. In southern Italy, 'rapidly-evolving' districts show a high level of soil degradation and land sensitivity to desertification during the whole period of investigation. On the contrary, those districts in northern Italy are those experiencing a moderate soil degradation and land sensitivity to desertification with the highest increase in the level of sensitivity over time. The study framework contributes to the assessment of complex local systems' dynamics in affluent but divided countries. Results may inform thematic strategies for the mitigation of land and soil degradation in the framework of action

  6. The Value of Landscape Essence

    Directory of Open Access Journals (Sweden)

    Maria da Conceição Marques Freire

    2014-08-01

    Full Text Available A new approach to interpreting the landscape is examined by accepting its complexity through inductive reasoning. While attempting to identify the essence of the landscape in the city and municipality of Óbidos, Portugal, several architectural recommendations of Venturi (2004 have been adapted as a framework for understanding this landscape. These will then guide the process of landscape transformation through:•••using the concepts of closed and contained spaces and the concept of fluid space;•recognising the existence of interstitial open spaces;•using those elements which are common to the distinct typologies of space;•defining the components that should be respected and those that can be respected;•observing landscape as a whole , while emphasising the relationship between the parts and the whole; and•rejecting simplification in the landscape transformation process.valuing the ambiguity incorporating the complexity Underlying this approach is the belief that the process of transformation must be based on the essence of each landscape. This implies the use of elements and structures of the landscape which are related to ecological, morphological and cultural systems. These elements and structures represent points of reference which should be considered in the process of landscape transformation.

  7. Systematic clustering of transcription start site landscapes

    DEFF Research Database (Denmark)

    Zhao, Xiaobei; Valen, Eivind; Parker, Brian J

    2011-01-01

    and earlier studies have shown that the TSSDs have biological implications in both regulation and function. However, no systematic study has been made to explore how many types of TSSDs and by extension core promoters exist and to understand which biological features distinguish them. In this study, we...... two-class separations of promoter based on TSS distributions are motivated, but the ultra-sharp TSS distributions will confound downstream analyses if not removed....

  8. Landscape-Scale Disturbance: Insights into the Complexity of Catchment Hydrology in the Mountaintop Removal Mining Region of the Eastern United States

    Directory of Open Access Journals (Sweden)

    Andrew J. Miller

    2016-07-01

    Full Text Available Few land disturbances impact watersheds at the scale and extent of mountaintop removal mining (MTM. This practice removes forests, soils and bedrock to gain access to underground coal that results in likely permanent and wholesale changes that impact catchment hydrology, geochemistry and ecosystem health. MTM is the dominant driver of land cover changes in the central Appalachian Mountains region of the United States, converting forests to mine lands and burying headwater streams. Despite its dominance on the landscape, determining the hydrological impacts of MTM is complicated by underground coal mines that significantly alter groundwater hydrology. To provide insight into how coal mining impacts headwater catchments, we compared the hydrologic responses of an MTM and forested catchment using event rainfall-runoff analysis, modeling and isotopic approaches. Despite similar rainfall characteristics, hydrology in the two catchments differed in significant ways, but both catchments demonstrated threshold-mediated hydrologic behavior that was attributed to transient storage and the release of runoff from underground mines. Results suggest that underground mines are important controls for runoff generation in both obviously disturbed and seemingly undisturbed catchments and interact in uncertain ways with disturbance from MTM. This paper summarizes our results and demonstrates the complexity of catchment hydrology in the MTM region.

  9. A human transcription factor in search mode.

    Science.gov (United States)

    Hauser, Kevin; Essuman, Bernard; He, Yiqing; Coutsias, Evangelos; Garcia-Diaz, Miguel; Simmerling, Carlos

    2016-01-08

    Transcription factors (TF) can change shape to bind and recognize DNA, shifting the energy landscape from a weak binding, rapid search mode to a higher affinity recognition mode. However, the mechanism(s) driving this conformational change remains unresolved and in most cases high-resolution structures of the non-specific complexes are unavailable. Here, we investigate the conformational switch of the human mitochondrial transcription termination factor MTERF1, which has a modular, superhelical topology complementary to DNA. Our goal was to characterize the details of the non-specific search mode to complement the crystal structure of the specific binding complex, providing a basis for understanding the recognition mechanism. In the specific complex, MTERF1 binds a significantly distorted and unwound DNA structure, exhibiting a protein conformation incompatible with binding to B-form DNA. In contrast, our simulations of apo MTERF1 revealed significant flexibility, sampling structures with superhelical pitch and radius complementary to the major groove of B-DNA. Docking these structures to B-DNA followed by unrestrained MD simulations led to a stable complex in which MTERF1 was observed to undergo spontaneous diffusion on the DNA. Overall, the data support an MTERF1-DNA binding and recognition mechanism driven by intrinsic dynamics of the MTERF1 superhelical topology. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  10. Exploring complex dynamics in multi agent-based intelligent systems: Theoretical and experimental approaches using the Multi Agent-based Behavioral Economic Landscape (MABEL) model

    Science.gov (United States)

    Alexandridis, Konstantinos T.

    This dissertation adopts a holistic and detailed approach to modeling spatially explicit agent-based artificial intelligent systems, using the Multi Agent-based Behavioral Economic Landscape (MABEL) model. The research questions that addresses stem from the need to understand and analyze the real-world patterns and dynamics of land use change from a coupled human-environmental systems perspective. Describes the systemic, mathematical, statistical, socio-economic and spatial dynamics of the MABEL modeling framework, and provides a wide array of cross-disciplinary modeling applications within the research, decision-making and policy domains. Establishes the symbolic properties of the MABEL model as a Markov decision process, analyzes the decision-theoretic utility and optimization attributes of agents towards comprising statistically and spatially optimal policies and actions, and explores the probabilogic character of the agents' decision-making and inference mechanisms via the use of Bayesian belief and decision networks. Develops and describes a Monte Carlo methodology for experimental replications of agent's decisions regarding complex spatial parcel acquisition and learning. Recognizes the gap on spatially-explicit accuracy assessment techniques for complex spatial models, and proposes an ensemble of statistical tools designed to address this problem. Advanced information assessment techniques such as the Receiver-Operator Characteristic curve, the impurity entropy and Gini functions, and the Bayesian classification functions are proposed. The theoretical foundation for modular Bayesian inference in spatially-explicit multi-agent artificial intelligent systems, and the ensembles of cognitive and scenario assessment modular tools build for the MABEL model are provided. Emphasizes the modularity and robustness as valuable qualitative modeling attributes, and examines the role of robust intelligent modeling as a tool for improving policy-decisions related to land

  11. [Participation of the piRNA pathway in recruiting a component of RNA polymerase I transcription initiation complex to germline cell nucleoli].

    Science.gov (United States)

    Fefelova, E A; Stolyarenko, A D; Yakushev, E Y; Gvozdev, V A; Klenov, M S

    2017-01-01

    Proteins of the Piwi family and short Piwi-interacting RNAs (piRNAs) ensure the protection of the genome from transposable elements. We have previously shown that nuclear Piwi protein tends to concentrate in the nucleoli of the cells of Drosophila melanogaster ovaries. It could be hypothesized that the function of Piwi in the nucleolus is associated with the repression of R1 and R2 retrotransposons inserted into the rDNA cluster. Here, we show that Piwi participates in recruiting Udd protein to nucleoli. Udd is a component of the conserved Selectivity Factor I-like (SL1-like) complex, which is required for transcription initiation by RNA polymerase I. We found that Udd localization depends on Piwi in germline cells, but not in somatic cells of the ovaries. In contrast, knockdowns of the SL1-like components (Udd or TAF1b) do not disrupt Piwi localization. We also observed that the absence of Udd or TAF1b in germline cells, as well as the impairment of Piwi nuclear localization lead to the accumulation of late stage egg chambers in the ovaries, which could be explained by reduced rRNA transcription. These results allow us to propose for the first time a role for Piwi in the nucleolus that is not directly associated with transposable element repression.

  12. The upstream regulatory sequence of the light harvesting complex Lhcf2 gene of the marine diatom Phaeodactylum tricornutum enhances transcription in an orientation- and distance-independent fashion.

    Science.gov (United States)

    Russo, Monia Teresa; Annunziata, Rossella; Sanges, Remo; Ferrante, Maria Immacolata; Falciatore, Angela

    2015-12-01

    Diatoms are a key phytoplankton group in the contemporary ocean, showing extraordinary adaptation capacities to rapidly changing environments. The recent availability of whole genome sequences from representative species has revealed distinct features in their genomes, like novel combinations of genes encoding distinct metabolisms and a significant number of diatom-specific genes. However, the regulatory mechanisms driving diatom gene expression are still largely uncharacterized. Considering the wide variety of fields of study orbiting diatoms, ranging from ecology, evolutionary biology to biotechnology, it is thus essential to increase our understanding of fundamental gene regulatory processes such as transcriptional regulation. To this aim, we explored the functional properties of the 5'-flanking region of the Phaeodatylum tricornutum Lhcf2 gene, encoding a member of the Light Harvesting Complex superfamily and we showed that this region enhances transcription of a GUS reporter gene in an orientation- and distance-independent fashion. This represents the first example of a cis-regulatory sequence with enhancer-like features discovered in diatoms and it is instrumental for the generation of novel genetic tools and diatom exploitation in different areas of study. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Industrious Landscaping

    DEFF Research Database (Denmark)

    Brichet, Nathalia Sofie; Hastrup, Frida

    2018-01-01

    This article has a twofold ambition. It offers a history of landscaping at Søby brown coal beds—a former mining site in western Denmark—and a methodological discussion of how to write such a study. Exploring this specific industrial landscape through a series of projects that have made different...... natural resources appear, we show that even what is recognized as resources shifts over time according to radically different and unpredictable agendas. This indicates that the Søby landscape is fundamentally volatile, as its resourcefulness has been seen interchangeably to shift between the brown coal...... business, inexpensive estates for practically savvy people, pasture for grazing, and recreational forest, among other things. We discuss these rifts in landscape history, motivated by what we refer to as industriousness, to show that, at sites such as Søby, both natural resources and historical...

  14. Electromagnetic Landscape

    DEFF Research Database (Denmark)

    Cermak, Daniel; Okutsu, Ayaka; Jørgensen, Stina Marie Hasse

    2015-01-01

    Daniel Cermak-Sassenrath, Ayaka Okutsu, Stina Hasse. Electromagnetic Landscape - In-between Signal, Noise and Environment. Installation and artist talk. 21th International Symposium on Electronic Art (ISEA) 2015, Vancouver, CAN, Aug 14-18, 2015.......Daniel Cermak-Sassenrath, Ayaka Okutsu, Stina Hasse. Electromagnetic Landscape - In-between Signal, Noise and Environment. Installation and artist talk. 21th International Symposium on Electronic Art (ISEA) 2015, Vancouver, CAN, Aug 14-18, 2015....

  15. Nordic Landscape

    DEFF Research Database (Denmark)

    Hjortshøj, Rasmus

    2017-01-01

    This Box Set NORDIC LANDSCAPE presents Nordic Territories, a project by Rasmus Hjortshøj, exploring the man-made landscapes of the coastal territories and the entanglement of society and nature in times where it is no longer merely mankind subjected to nature, but where nature is equally being...... territories is not only their transient nature, but also the warm currents of the Gulf Stream making these northern shorelines habitable for human settlements....

  16. Cul8/Rtt101 Forms a Variety of Protein Complexes That Regulate DNA Damage Response and Transcriptional Silencing*

    OpenAIRE

    Mimura, Satoru; Yamaguchi, Tsuyoshi; Ishii, Satoru; Noro, Emiko; Katsura, Tomoya; Obuse, Chikashi; Kamura, Takumi

    2010-01-01

    The budding yeast, Saccharomyces cerevisiae, has three cullin proteins, which act as platforms for Cullin-based E3 ubiquitin ligases. Genetic evidence indicates that Cul8, together with Mms1, Mms22, and Esc4, is involved in the repair of DNA damage that can occur during DNA replication. Cul8 is thought to form a complex with these proteins, but the composition and the function of Cul8-based E3 ubiquitin ligases remain largely uncharacterized. Herein, we report a comprehensive biochemical anal...

  17. Cotton leaf curl Burewala virus with intact or mutant transcriptional activator proteins: complexity of cotton leaf curl disease.

    Science.gov (United States)

    Kumar, Jitendra; Gunapati, Samatha; Alok, Anshu; Lalit, Adarsh; Gadre, Rekha; Sharma, Naresh C; Roy, Joy K; Singh, Sudhir P

    2015-05-01

    Cotton leaf curl disease (CLCuD) is a serious disease of cotton on the Indian subcontinent. In the present study, three cotton leaf curl viruses, cotton leaf curl Burewala virus (CLCuBuV), cotton leaf curl Kokhran virus (CLCuKoV) and cotton leaf curl Multan virus (CLCuMV), and their associated satellites, cotton leaf curl Multan betasatellite (CLCuMB) and cotton leaf curl Multan alphasatellite (CLCuMA), were detected. CLCuBuV with either intact (CLCuBuV-1) or mutant (CLCuBuV-2) transcriptional activator protein (TrAP) were detected in different plants. Agroinoculation with CLCuBuV-1 or CLCuBuV-2 together with CLCuMB and CLCuMA, resulted in typical leaf curling and stunting of tobacco plants. Inoculation with CLCuKoV or an isolate of CLCuMV (CLCuMV-2), together with CLCuMB and CLCuMA, induced severe leaf curling, while the other isolate of CLCuMV (CLCuMV-1), which was recombinant in origin, showed mild leaf curling in tobacco. To investigate the effect of intact or mutant TrAP and also the recombination events, CLCuBuV-1, CLCuBuV-2, CLCuMV-1 or CLCuMV-2 together with the satellites (CLCuMA and CLCuMB) were transferred to cotton via whitefly-mediated transmission. Cotton plants containing CLCuBuV-1, CLCuBuV-2 or CLCuMV-2 together with satellites showed curling and stunting, whereas the plants having CLCuMV-1 and the satellites showed only mild and indistinguishable symptoms. CLCuBuV-1 (intact TrAP) showed severe symptoms in comparison to CLCuBuV-2 (mutant TrAP). The present study reveals that two types of CLCuBuV, one with an intact TrAP and the other with a mutant TrAP, exist in natural infection of cotton in India. Additionally, CLCuMuV-1, which has a recombinant origin, induces mild symptoms in comparison to the other CLCuMV isolates.

  18. Changes in signal transducer and activator of transcription 3 (STAT3) dynamics induced by complexation with pharmacological inhibitors of Src homology 2 (SH2) domain dimerization.

    Science.gov (United States)

    Resetca, Diana; Haftchenary, Sina; Gunning, Patrick T; Wilson, Derek J

    2014-11-21

    The activity of the transcription factor signal transducer and activator of transcription 3 (STAT3) is dysregulated in a number of hematological and solid malignancies. Development of pharmacological STAT3 Src homology 2 (SH2) domain interaction inhibitors holds great promise for cancer therapy, and a novel class of salicylic acid-based STAT3 dimerization inhibitors that includes orally bioavailable drug candidates has been recently developed. The compounds SF-1-066 and BP-1-102 are predicted to bind to the STAT3 SH2 domain. However, given the highly unstructured and dynamic nature of the SH2 domain, experimental confirmation of this prediction was elusive. We have interrogated the protein-ligand interaction of STAT3 with these small molecule inhibitors by means of time-resolved electrospray ionization hydrogen-deuterium exchange mass spectrometry. Analysis of site-specific evolution of deuterium uptake induced by the complexation of STAT3 with SF-1-066 or BP-1-102 under physiological conditions enabled the mapping of the in silico predicted inhibitor binding site to the STAT3 SH2 domain. The binding of both inhibitors to the SH2 domain resulted in significant local decreases in dynamics, consistent with solvent exclusion at the inhibitor binding site and increased rigidity of the inhibitor-complexed SH2 domain. Interestingly, inhibitor binding induced hot spots of allosteric perturbations outside of the SH2 domain, manifesting mainly as increased deuterium uptake, in regions of STAT3 important for DNA binding and nuclear localization. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. TRE5-A retrotransposition profiling reveals putative RNA polymerase III transcription complex binding sites on the Dictyostelium extrachromosomal rDNA element.

    Directory of Open Access Journals (Sweden)

    Thomas Spaller

    Full Text Available The amoeba Dictyostelium discoideum has a haploid genome in which two thirds of the DNA encodes proteins. Consequently, the space available for selfish mobile elements to expand without excess damage to the host genome is limited. The non-long terminal repeat retrotransposon TRE5-A maintains an active population in the D. discoideum genome and apparently adapted to this gene-dense environment by targeting positions ~47 bp upstream of tRNA genes that are devoid of protein-coding regions. Because only ~24% of tRNA genes are associated with a TRE5-A element in the reference genome, we evaluated whether TRE5-A retrotransposition is limited to this subset of tRNA genes. We determined that a tagged TRE5-A element (TRE5-Absr integrated at 384 of 405 tRNA genes, suggesting that expansion of the current natural TRE5-A population is not limited by the availability of targets. We further observed that TRE5-Absr targets the ribosomal 5S gene on the multicopy extrachromosomal DNA element that carries the ribosomal RNA genes, indicating that TRE5-A integration may extend to the entire RNA polymerase III (Pol III transcriptome. We determined that both natural TRE5-A and cloned TRE5-Absr retrotranspose to locations on the extrachromosomal rDNA element that contain tRNA gene-typical A/B box promoter motifs without displaying any other tRNA gene context. Based on previous data suggesting that TRE5-A targets tRNA genes by locating Pol III transcription complexes, we propose that A/B box loci reflect Pol III transcription complex assembly sites that possess a function in the biology of the extrachromosomal rDNA element.

  20. Monitoring Cloud-prone Complex Landscapes At Multiple Spatial Scales Using Medium And High Resolution Optical Data: A Case Study In Central Africa

    Science.gov (United States)

    Basnet, Bikash

    Tracking land surface dynamics over cloud-prone areas with complex mountainous terrain and a landscape that is heterogeneous at a scale of approximately 10 m, is an important challenge in the remote sensing of tropical regions in developing nations, due to the small plot sizes. Persistent monitoring of natural resources in these regions at multiple spatial scales requires development of tools to identify emerging land cover transformation due to anthropogenic causes, such as agricultural expansion and climate change. Along with the cloud cover and obstructions by topographic distortions due to steep terrain, there are limitations to the accuracy of monitoring change using available historical satellite imagery, largely due to sparse data access and the lack of high quality ground truth for classifier training. One such complex region is the Lake Kivu region in Central Africa. This work addressed these problems to create an effective process for monitoring the Lake Kivu region located in Central Africa. The Lake Kivu region is a biodiversity hotspot with a complex and heterogeneous landscape and intensive agricultural development, where individual plot sizes are often at the scale of 10m. Procedures were developed that use optical data from satellite and aerial observations at multiple scales to tackle the monitoring challenges. First, a novel processing chain was developed to systematically monitor the spatio-temporal land cover dynamics of this region over the years 1988, 2001, and 2011 using Landsat data, complemented by ancillary data. Topographic compensation was performed on Landsat reflectances to avoid the strong illumination angle impacts and image compositing was used to compensate for frequent cloud cover and thus incomplete annual data availability in the archive. A systematic supervised classification, using the state-of-the-art machine learning classifier Random Forest, was applied to the composite Landsat imagery to obtain land cover thematic maps

  1. Semiotics in landscape design

    Directory of Open Access Journals (Sweden)

    Karsten Jorgensen

    1997-03-01

    Full Text Available This paper claims that concepts of language can help us create better and more relevant landscape design. It is based on research undertaken by Karsten Jørgensen (1989, and subsequent studies carried out at the department of Land Use and Landscape Planning at the Agricultural University in Norway. The 'signs' that constitute the design language are categorised using the analytical vocabulary of landscape design; for example, elements, materials, effects and shapes. Studies of these signs are based on elements of semiotics and cognitive science, especially the Umwelt-theories developed by Jakob von Uexküll (Hoffmeyer 1994. We are constantly exposed to numerous signs of different kinds. Everywhere in society we see signs around us; for example, traffic signs, advertising signs and logos. It is therefore relevant to introduce the term 'semiosphere' in order to focus on the significance of semiosis at all levels of activity in the world, from cellular activities, to complex systems of development such as those found in a population. This study focuses on the semantic aspects of landscape architecture. In explaining the meaning of a statement, it is useful to have a set of rules or 'codes' to correlate a specific expression with a specific interpretation. These codes may be based on conventions, or on similarity between or stylisation of objects, such as natural or cultural landscapes. In any case, they are based on the interpreter's language and 'mind-structure'. At a general level, it is only possible to study sign content. To analyse meaning in landscape design you have to look at the context; for example, the overall composition of a garden or park and the situation, which includes the interpreter's cultural background, their experiences and so on. In other words, you have to analyse a specific case to be able to speak reasonably about meaning in landscape (designs.

  2. The POU homeodomain transcription factor POUM2 and broad complex isoform 2 transcription factor induced by 20-hydroxyecdysone collaboratively regulate vitellogenin gene expression and egg formation in the silkworm Bombyx mori.

    Science.gov (United States)

    Lin, Y; Liu, H; Yang, C; Gu, J; Shen, G; Zhang, H; Chen, E; Han, C; Zhang, Y; Xu, Y; Wu, J; Xia, Q

    2017-10-01

    Vitellogenin (Vg) is a source of nutrition for embryo development. Our previous study showed that the silkworm (Bombyx mori) transcription factor broad complex isoform 2 (BmBrC-Z2) regulates gene expression of the Vg gene (BmVg) by induction with 20-hydroxyecdysone (20E). However, the mechanism by which 20E regulates BmVg expression was not clarified. In this study, cell transfection experiments showed that the BmVg promoter containing the POU homeodomain transcription factor POUM2 (POUM2) and BrC-Z2 cis-response elements (CREs) showed a more significant response to 20E than that harbouring only the BrC-Z2 or POUM2 CRE. An electrophoretic mobility shift assay and chromatin immunoprecipitation assay showed that BmPOUM2 could bind to the POUM2 CRE of the BmVg promoter. Over-expression of BmPOUM2 and BmBrC-Z2 in B. mori embryo-derived cell line (BmE) could enhance the activity of the BmVg promoter carrying both the POUM2 and BrC-Z2 CREs following 20E induction. Quantitative PCR and immunofluorescence histochemistry showed that the expression pattern and tissue localization of BmPOUM2 correspond to those of BmVg. Glutathione S-transferase pull-down and co-immunoprecipitation assays confirmed that BmPOUM2 interacts only with BmBrC-Z2 to regulate BmVg expression. Down-regulation of BmPOUM2 in female silkworm by RNA interference significantly reduced BmVg expression, leading to abnormal egg formation. In summary, these results indicate that BmPOUM2 binds only to BmBrC-Z2 to collaboratively regulate BmVg expression by 20E induction to control vitellogenesis and egg formation in the silkworm. Moreover, these findings suggest that homeodomain protein POUM2 plays a novel role in regulating insect vitellogenesis. © 2017 The Royal Entomological Society.

  3. Quantification of HLA-DM-Dependent Major Histocompatibility Complex of Class II Immunopeptidomes by the Peptide Landscape Antigenic Epitope Alignment Utility

    Directory of Open Access Journals (Sweden)

    Miguel Álvaro-Benito

    2018-05-01

    Full Text Available The major histocompatibility complex of class II (MHCII immunopeptidome represents the repertoire of antigenic peptides with the potential to activate CD4+ T cells. An understanding of how the relative abundance of specific antigenic epitopes affects the outcome of T cell responses is an important aspect of adaptive immunity and offers a venue to more rationally tailor T cell activation in the context of disease. Recent advances in mass spectrometric instrumentation, computational power, labeling strategies, and software analysis have enabled an increasing number of stratified studies on HLA ligandomes, in the context of both basic and translational research. A key challenge in the case of MHCII immunopeptidomes, often determined for different samples at distinct conditions, is to derive quantitative information on consensus epitopes from antigenic peptides of variable lengths. Here, we present the design and benchmarking of a new algorithm [peptide landscape antigenic epitope alignment utility (PLAtEAU] allowing the identification and label-free quantification (LFQ of shared consensus epitopes arising from series of nested peptides. The algorithm simplifies the complexity of the dataset while allowing the identification of nested peptides within relatively short segments of protein sequences. Moreover, we apply this algorithm to the comparison of the ligandomes of cell lines with two different expression levels of the peptide-exchange catalyst HLA-DM. Direct comparison of LFQ intensities determined at the peptide level is inconclusive, as most of the peptides are not significantly enriched due to poor sampling. Applying the PLAtEAU algorithm for grouping of the peptides into consensus epitopes shows that more than half of the total number of epitopes is preferentially and significantly enriched for each condition. This simplification and deconvolution of the complex and ambiguous peptide-level dataset highlights the value of the PLAt

  4. Changing Landscapes, Changing Landscape's Story

    Czech Academy of Sciences Publication Activity Database

    Lapka, Miloslav; Cudlínová, Eva

    2003-01-01

    Roč. 28, č. 3 (2003), s. 323-328 ISSN 0142-6397. [Symposium on Sustainable Landscapes in an Enlarged Europe. Nové Hrady, 12.09.2001-14.09.2001] R&D Projects: GA MŠk ME 530 Grant - others:GA-(XE) QLK5-CT-2000-01211-SPRITE Institutional research plan: CEZ:AV0Z5039906 Keywords : Landscape stability * narrative approach * socio-economic typology Subject RIV: DO - Wilderness Conservation

  5. hCLE/C14orf166 associates with DDX1-HSPC117-FAM98B in a novel transcription-dependent shuttling RNA-transporting complex.

    Directory of Open Access Journals (Sweden)

    Alicia Pérez-González

    Full Text Available hCLE/C14orf166 is a nuclear and cytoplasmic protein that interacts with the RNAP II, modulates nuclear RNA metabolism and is present in cytoplasmic RNA granules involved in localized translation. Here we have studied whether hCLE shares common interactors in the nucleus and the cytosol, which could shed light on its participation in the sequential phases of RNA metabolism. Nuclear and cytoplasmic purified hCLE-associated factors were identified and proteins involved in mRNA metabolism, motor-related proteins, cytoskeletal and translation-related factors were found. Purified hCLE complexes also contain RNAs and as expected some hCLE-interacting proteins (DDX1, HSPC117, FAM98B were found both in the nucleus and the cytoplasm. Moreover, endogenous hCLE fractionates in protein complexes together with DDX1, HSPC117 and FAM98B and silencing of hCLE down-regulates their nuclear and cytosolic accumulation levels. Using a photoactivatable hCLE-GFP protein, nuclear import and export of hCLE was observed indicating that hCLE is a shuttling protein. Interestingly, hCLE nuclear import required active transcription, as did the import of DDX1, HSPC117 and FAM98B proteins. The data indicate that hCLE probably as a complex with DDX1, HSPC117 and FAM98B shuttles between the nucleus and the cytoplasm transporting RNAs suggesting that this complex has a prominent role on nuclear and cytoplasmic RNA fate.

  6. 25-hydroxycholesterol promotes RANKL-induced osteoclastogenesis through coordinating NFATc1 and Sp1 complex in the transcription of miR-139-5p

    International Nuclear Information System (INIS)

    Zhang, Lishan; Lv, Yinping; Xian, Guozhe; Lin, Yanliang

    2017-01-01

    25-hydroxycholesterol (25-HC) is implicated in many processes, including lipid metabolism and the immune response. However, the role of 25-HC in RANKL-induced osteoclastogenesis remains largely unknown. Our results showed that 25-HC inhibited miR-139-5p expression in mouse bone marrow macrophages (BMMs) cultured in receptor activator of NF-κB ligand (RANKL) and monocyte macrophage colony-stimulating factor (M-CSF). Further investigation suggested that 25-HC promoted the expression of nuclear factor of activated T cell cytoplasmic 1 (NFATc1) and Sp1, especially in the presence of RANKL and M-CSF. Meanwhile, 25-HC induced nuclear translocation of NFATc1, resulting in the interaction between NFATc1 and Sp1 that was confirmed by co-immunoprecipitation. Chromatin immunoprecipitation assay indicated that Sp1 could bind to miR-139-5p promoter, but NFATc1 had no binding capacity. Although forming NFATc1/Sp1 complex increased its binding to miR-139-5p promoter, the complex inhibited the transcriptional activity of Sp1. Inhibition of NFATc1 increase the expression of miR-139-5p, which might be due to the release of free Sp1 that could bind to the promoter of miR-139-5p. Enforced expression of miR-139-5p impaired osteoclastogenesis induced by co-treatment with 25-HC and RANKL. These results suggested that 25-HC induced the interaction between NFATc1 and Sp1, reducing the level of free Sp1 to inhibit miR-139-5p expression and promote osteoclastogenesis. - Highlights: • 25-hydroxycholesterol inhibited miR-139-5p expression in bone marrow macrophages. • 25-hydroxycholesterol promoted the expression of NFATc1 and Sp1. • 25-hydroxycholesterol induced the interaction between NFATc1 and Sp1. • NFATc1/Sp1 complex inhibited the transcription of miR-139-5p. • MiR-139-5p impaired osteoclastogenesis induced by 25-hydroxycholesterol and RANKL.

  7. Cocaine- and amphetamine-regulated transcript peptide increases mitochondrial respiratory chain complex II activity and protects against oxygen-glucose deprivation in neurons.

    Science.gov (United States)

    Sha, Dujuan; Wang, Luna; Zhang, Jun; Qian, Lai; Li, Qiming; Li, Jin; Qian, Jian; Gu, Shuangshuang; Han, Ling; Xu, Peng; Xu, Yun

    2014-09-25

    The mechanisms of ischemic stroke, a main cause of disability and death, are complicated. Ischemic stroke results from the interaction of various factors including oxidative stress, a key pathological mechanism that plays an important role during the acute stage of ischemic brain injury. This study demonstrated that cocaine- and amphetamine-regulated transcript (CART) peptide, specifically CART55-102, increased the survival rate, but decreased the mortality of neurons exposed to oxygen-glucose deprivation (OGD), in a dose-dependent manner. The above-mentioned effects of CART55-102 were most significant at 0.4nM. These results indicated that CART55-102 suppressed neurotoxicity and enhanced neuronal survival after oxygen-glucose deprivation. CART55-102 (0.4nM) significantly diminished reactive oxygen species levels and markedly increased the activity of mitochondrial respiratory chain complex II in oxygen-glucose deprived neurons. In summary, CART55-102 suppressed oxidative stress in oxygen-glucose deprived neurons, possibly through elevating the activity of mitochondrial respiratory chain complex II. This result provides evidence for the development of CART55-102 as an antioxidant drug. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. GW182-Free microRNA Silencing Complex Controls Post-transcriptional Gene Expression during Caenorhabditis elegans Embryogenesis.

    Directory of Open Access Journals (Sweden)

    Guillaume Jannot

    2016-12-01

    Full Text Available MicroRNAs and Argonaute form the microRNA induced silencing complex or miRISC that recruits GW182, causing mRNA degradation and/or translational repression. Despite the clear conservation and molecular significance, it is unknown if miRISC-GW182 interaction is essential for gene silencing during animal development. Using Caenorhabditis elegans to explore this question, we examined the relationship and effect on gene silencing between the GW182 orthologs, AIN-1 and AIN-2, and the microRNA-specific Argonaute, ALG-1. Homology modeling based on human Argonaute structures indicated that ALG-1 possesses conserved Tryptophan-binding Pockets required for GW182 binding. We show in vitro and in vivo that their mutations severely altered the association with AIN-1 and AIN-2. ALG-1 tryptophan-binding pockets mutant animals retained microRNA-binding and processing ability, but were deficient in reporter silencing activity. Interestingly, the ALG-1 tryptophan-binding pockets mutant phenocopied the loss of alg-1 in worms during larval stages, yet was sufficient to rescue embryonic lethality, indicating the dispensability of AINs association with the miRISC at this developmental stage. The dispensability of AINs in miRNA regulation is further demonstrated by the capacity of ALG-1 tryptophan-binding pockets mutant to regulate a target of the embryonic mir-35 microRNA family. Thus, our results demonstrate that the microRNA pathway can act independently of GW182 proteins during C. elegans embryogenesis.

  9. Adaptive evolution of transcription factor binding sites

    Directory of Open Access Journals (Sweden)

    Berg Johannes

    2004-10-01

    Full Text Available Abstract Background The regulation of a gene depends on the binding of transcription factors to specific sites located in the regulatory region of the gene. The generation of these binding sites and of cooperativity between them are essential building blocks in the evolution of complex regulatory networks. We study a theoretical model for the sequence evolution of binding sites by point mutations. The approach is based on biophysical models for the binding of transcription factors to DNA. Hence we derive empirically grounded fitness landscapes, which enter a population genetics model including mutations, genetic drift, and selection. Results We show that the selection for factor binding generically leads to specific correlations between nucleotide frequencies at different positions of a binding site. We demonstrate the possibility of rapid adaptive evolution generating a new binding site for a given transcription factor by point mutations. The evolutionary time required is estimated in terms of the neutral (background mutation rate, the selection coefficient, and the effective population size. Conclusions The efficiency of binding site formation is seen to depend on two joint conditions: the binding site motif must be short enough and the promoter region must be long enough. These constraints on promoter architecture are indeed seen in eukaryotic systems. Furthermore, we analyse the adaptive evolution of genetic switches and of signal integration through binding cooperativity between different sites. Experimental tests of this picture involving the statistics of polymorphisms and phylogenies of sites are discussed.

  10. Contemporary danish landscape research

    DEFF Research Database (Denmark)

    Vejre, H.; Brandt, J.

    2004-01-01

    Danish landscape research blossomed during the 1990’ies thanks to several transdisciplinary research programmes involving several institutions. The main themes of the programmes encompassed Landscape change, landscape and biological diversity, nature and landscape management, use and monitoring...

  11. An anatomic transcriptional atlas of human glioblastoma.

    Science.gov (United States)

    Puchalski, Ralph B; Shah, Nameeta; Miller, Jeremy; Dalley, Rachel; Nomura, Steve R; Yoon, Jae-Guen; Smith, Kimberly A; Lankerovich, Michael; Bertagnolli, Darren; Bickley, Kris; Boe, Andrew F; Brouner, Krissy; Butler, Stephanie; Caldejon, Shiella; Chapin, Mike; Datta, Suvro; Dee, Nick; Desta, Tsega; Dolbeare, Tim; Dotson, Nadezhda; Ebbert, Amanda; Feng, David; Feng, Xu; Fisher, Michael; Gee, Garrett; Goldy, Jeff; Gourley, Lindsey; Gregor, Benjamin W; Gu, Guangyu; Hejazinia, Nika; Hohmann, John; Hothi, Parvinder; Howard, Robert; Joines, Kevin; Kriedberg, Ali; Kuan, Leonard; Lau, Chris; Lee, Felix; Lee, Hwahyung; Lemon, Tracy; Long, Fuhui; Mastan, Naveed; Mott, Erika; Murthy, Chantal; Ngo, Kiet; Olson, Eric; Reding, Melissa; Riley, Zack; Rosen, David; Sandman, David; Shapovalova, Nadiya; Slaughterbeck, Clifford R; Sodt, Andrew; Stockdale, Graham; Szafer, Aaron; Wakeman, Wayne; Wohnoutka, Paul E; White, Steven J; Marsh, Don; Rostomily, Robert C; Ng, Lydia; Dang, Chinh; Jones, Allan; Keogh, Bart; Gittleman, Haley R; Barnholtz-Sloan, Jill S; Cimino, Patrick J; Uppin, Megha S; Keene, C Dirk; Farrokhi, Farrokh R; Lathia, Justin D; Berens, Michael E; Iavarone, Antonio; Bernard, Amy; Lein, Ed; Phillips, John W; Rostad, Steven W; Cobbs, Charles; Hawrylycz, Michael J; Foltz, Greg D

    2018-05-11

    Glioblastoma is an aggressive brain tumor that carries a poor prognosis. The tumor's molecular and cellular landscapes are complex, and their relationships to histologic features routinely used for diagnosis are unclear. We present the Ivy Glioblastoma Atlas, an anatomically based transcriptional atlas of human glioblastoma that aligns individual histologic features with genomic alterations and gene expression patterns, thus assigning molecular information to the most important morphologic hallmarks of the tumor. The atlas and its clinical and genomic database are freely accessible online data resources that will serve as a valuable platform for future investigations of glioblastoma pathogenesis, diagnosis, and treatment. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  12. Transcriptional regulation by competing transcription factor modules.

    Directory of Open Access Journals (Sweden)

    Rutger Hermsen

    2006-12-01

    Full Text Available Gene regulatory networks lie at the heart of cellular computation. In these networks, intracellular and extracellular signals are integrated by transcription factors, which control the expression of transcription units by binding to cis-regulatory regions on the DNA. The designs of both eukaryotic and prokaryotic cis-regulatory regions are usually highly complex. They frequently consist of both repetitive and overlapping transcription factor binding sites. To unravel the design principles of these promoter architectures, we have designed in silico prokaryotic transcriptional logic gates with predefined input-output relations using an evolutionary algorithm. The resulting cis-regulatory designs are often composed of modules that consist of tandem arrays of binding sites to which the transcription factors bind cooperatively. Moreover, these modules often overlap with each other, leading to competition between them. Our analysis thus identifies a new signal integration motif that is based upon the interplay between intramodular cooperativity and intermodular competition. We show that this signal integration mechanism drastically enhances the capacity of cis-regulatory domains to integrate signals. Our results provide a possible explanation for the complexity of promoter architectures and could be used for the rational design of synthetic gene circuits.

  13. Electromagnetic Landscape

    DEFF Research Database (Denmark)

    Cermak, Daniel; Okutsu, Ayaka; Hasse, Stina

    2015-01-01

    Electromagnetic Landscape demonstrates in direct, tangible and immediate ways effects of the disruption of the familiar. An ubiquitous technological medium, FM radio, is turned into an alien and unfamiliar one. Audience participation, the environment, radio signals and noise create a site...

  14. Changing Landscape

    DEFF Research Database (Denmark)

    Tunby Gulbrandsen, Ib; Kamstrup, Andreas; Koed Madsen, Anders

    with an analysis of the changing organizational landscape created by new ICT’s like Google, Facebook, Wikipedia, iPods, smart phones and Wi-Fi. Based on five netno- and ethno-graphic investigations of the intertwinement of ICT’s and organizational work, we point to three features that have changed the scene: new...

  15. Disposable Landscapes

    Science.gov (United States)

    Kevin T. Smith

    2008-01-01

    Whether we are a traditionalist or on the cutting edge of landscape care, we need to take a deep breath and think about what we are trying to achieve, before we select a specific treatment or practice for tree care. We should measure that treatment or practice against what we know about the tree system. I say "system" because the recent years of Modern...

  16. Combinatorial analysis of lupulin gland transcription factors from R2R3Myb, bHLH and WDR families indicates a complex regulation of chs_H1 genes essential for prenylflavonoid biosynthesis in hop (Humulus lupulus L.)

    Czech Academy of Sciences Publication Activity Database

    Matoušek, Jaroslav; Kocábek, Tomáš; Patzak, J.; Füssy, Zoltán; Procházková, Jitka; Heyerick, A.

    2012-01-01

    Roč. 12, č. 27 (2012), s. 1471-2229 ISSN 1471-2229 R&D Projects: GA ČR GA521/08/0740; GA MZe QH81052 Institutional research plan: CEZ:AV0Z50510513 Keywords : transcription factor * protein complexes * transient expression assay Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.354, year: 2012

  17. Quantification of 16S rRNAs in complex bacterial communities by multiple competitive reverse transcription-PCR in temperature gradient gel electrophoresis fingerprints.

    Science.gov (United States)

    Felske, A; Akkermans, A D; De Vos, W M

    1998-11-01

    A novel approach was developed to quantify rRNA sequences in complex bacterial communities. The main bacterial 16S rRNAs in Drentse A grassland soils (The Netherlands) were amplified by reverse transcription (RT)-PCR with bacterium-specific primers and were separated by temperature gradient gel electrophoresis (TGGE). The primer pair used (primers U968-GC and L1401) was found to amplify with the same efficiency 16S rRNAs from bacterial cultures containing different taxa and cloned 16S ribosomal DNA amplicons from uncultured soil bacteria. The sequence-specific efficiency of amplification was determined by monitoring the amplification kinetics by kinetic PCR. The primer-specific amplification efficiency was assessed by competitive PCR and RT-PCR, and identical input amounts of different 16S rRNAs resulted in identical amplicon yields. The sequence-specific detection system used for competitive amplifications was TGGE, which also has been found to be suitable for simultaneous quantification of more than one sequence. We demonstrate that this approach can be applied to TGGE fingerprints of soil bacteria to estimate the ratios of the bacterial 16S rRNAs.

  18. Axon Regeneration Is Regulated by Ets-C/EBP Transcription Complexes Generated by Activation of the cAMP/Ca2+ Signaling Pathways.

    Directory of Open Access Journals (Sweden)

    Chun Li

    2015-10-01

    Full Text Available The ability of specific neurons to regenerate their axons after injury is governed by cell-intrinsic regeneration pathways. In Caenorhabditis elegans, the JNK and p38 MAPK pathways are important for axon regeneration. Axonal injury induces expression of the svh-2 gene encoding a receptor tyrosine kinase, stimulation of which by the SVH-1 growth factor leads to activation of the JNK pathway. Here, we identify ETS-4 and CEBP-1, related to mammalian Ets and C/EBP, respectively, as transcriptional activators of svh-2 expression following axon injury. ETS-4 and CEBP-1 function downstream of the cAMP and Ca2+-p38 MAPK pathways, respectively. We show that PKA-dependent phosphorylation of ETS-4 promotes its complex formation with CEBP-1. Furthermore, activation of both cAMP and Ca2+ signaling is required for activation of svh-2 expression. Thus, the cAMP/Ca2+ signaling pathways cooperatively activate the JNK pathway, which then promotes axon regeneration.

  19. β-Catenin/POU5F1/SOX2 transcription factor complex mediates IGF-I receptor signaling and predicts poor prognosis in lung adenocarcinoma.

    Science.gov (United States)

    Xu, Chuan; Xie, Dan; Yu, Shi-Cang; Yang, Xiao-Jun; He, Li-Ru; Yang, Jing; Ping, Yi-Fang; Wang, Bin; Yang, Lang; Xu, Sen-Lin; Cui, Wei; Wang, Qing-Liang; Fu, Wen-Juan; Liu, Qing; Qian, Cheng; Cui, You-Hong; Rich, Jeremy N; Kung, Hsiang-Fu; Zhang, Xia; Bian, Xiu-Wu

    2013-05-15

    Cancer stem-like cells (CSLC) are crucial in tumor initiation and progression; however, the underlying mechanism for the self-renewal of cancer cells remains undefined. In the study, immunohistochemical analysis of specimens freshly excised from patients with lung adenocarcinoma showed that high expression of insulin-like growth factor I receptor (IGF-IR) in lung adenocarcinoma cells was positively correlated with the expressions of cancer stem cell markers CD133 and aldehyde dehydrogenase 1 family member A1 (ALDH1A1). IGF-IR activation enhanced POU class 5 homeobox 1 (POU5F1) expression on human lung adenocarcinoma stem-like cells (LACSLC) through PI3K/AKT/GSK3β/β-catenin cascade. POU5F1 could form a novel complex with β-catenin and SOX2 to bind Nanog promoter for transcription to maintain self-renewal of LACSLCs, which was dependent on the functional IGF-IR. Genetic and pharmacologic inhibition of IGF-IR abrogated LACSLC capabilities for self-renewal and tumorigenicity in vitro. In an in vivo xenograft tumor model, knockdown of either IGF-IR or POU5F1 impeded tumorigenic potentials of LACSLCs. By analyzing pathologic specimens excised from 200 patients with lung adenocarcinoma, we found that colocalization of highly expressed IGF-IR with β-catenin and POU5F1 predicted poor prognosis. Taken together, we show that IGF-IR-mediated POU5F1 expression to form a complex with β-catenin and SOX2 is crucial for the self-renewal and oncogenic potentials of LACSLCs, and the integrative clinical detection of the expressions of IGF-IR, β-catenin, and POU5F1 is indicatory for predicting prognosis in the patients of lung adenocarcinoma. ©2013 AACR.

  20. The E1A proteins of all six human adenovirus subgroups target the p300/CBP acetyltransferases and the SAGA transcriptional regulatory complex

    International Nuclear Information System (INIS)

    Shuen, Michael; Avvakumov, Nikita; Torchia, Joe; Mymryk, Joe S.

    2003-01-01

    The N-terminal/conserved region 1 (CR1) portion of the human adenovirus (Ad) 5 E1A protein was previously shown to inhibit growth in the simple eukaryote Saccharomyces cerevisiae. We now demonstrate that the corresponding regions of the E1A proteins of Ad3,-4,-9,-12, and -40, which represent the remaining five Ad subgroups, also inhibit yeast growth. These results suggest that the E1A proteins of all six human Ad subgroups share a common cellular target(s) conserved in yeast. Growth inhibition induced by either full-length or the N-terminal/CR1 portion of Ad5 E1A was relieved by coexpression of the E1A binding portions of the mammalian p300, CBP, and pCAF acetyltransferases. Similarly, growth inhibition by the N-terminal/CR1 portions of the other Ad E1A proteins was suppressed by expression of the same regions of CBP or pCAF known to bind Ad5 E1A. The physical interaction of each of the different Ad E1A proteins with CBP, p300, and pCAF was confirmed in vitro. Furthermore, deletion of the gene encoding yGcn5, the yeast homolog of pCAF and a subunit of the SAGA transcriptional regulatory complex, restored growth in yeast expressing each of the different Ad E1A proteins. This indicates that the SAGA complex is a conserved target of all Ad E1A proteins. Our results demonstrate for the first time that the p300, CBP, and pCAF acetyltransferases are common targets for the E1A proteins of all six human Ad subgroups, highlighting the importance of these interactions for E1A function

  1. Drawing time : The representation of change and dynamics in Dutch landscape architectural practice after 1985

    NARCIS (Netherlands)

    van Dooren, N.

    2017-01-01

    Landscape architect design involves drawings. The relation between drawing and new landscape seems evident, but is complex and fascinating, due to the particularities of drawings, of landscape and of landscape architecture. Landscape is essentially a time-based medium -think of the seasons (cyclical

  2. Pathological Ace2-to-Ace enzyme switch in the stressed heart is transcriptionally controlled by the endothelial Brg1–FoxM1 complex

    Science.gov (United States)

    Yang, Jin; Feng, Xuhui; Zhou, Qiong; Cheng, Wei; Shang, Ching; Han, Pei; Lin, Chiou-Hong; Chen, Huei-Sheng Vincent; Quertermous, Thomas; Chang, Ching-Pin

    2016-01-01

    Genes encoding angiotensin-converting enzymes (Ace and Ace2) are essential for heart function regulation. Cardiac stress enhances Ace, but suppresses Ace2, expression in the heart, leading to a net production of angiotensin II that promotes cardiac hypertrophy and fibrosis. The regulatory mechanism that underlies the Ace2-to-Ace pathological switch, however, is unknown. Here we report that the Brahma-related gene-1 (Brg1) chromatin remodeler and forkhead box M1 (FoxM1) transcription factor cooperate within cardiac (coronary) endothelial cells of pathologically stressed hearts to trigger the Ace2-to-Ace enzyme switch, angiotensin I-to-II conversion, and cardiac hypertrophy. In mice, cardiac stress activates the expression of Brg1 and FoxM1 in endothelial cells. Once activated, Brg1 and FoxM1 form a protein complex on Ace and Ace2 promoters to concurrently activate Ace and repress Ace2, tipping the balance to Ace2 expression with enhanced angiotensin II production, leading to cardiac hypertrophy and fibrosis. Disruption of endothelial Brg1 or FoxM1 or chemical inhibition of FoxM1 abolishes the stress-induced Ace2-to-Ace switch and protects the heart from pathological hypertrophy. In human hypertrophic hearts, BRG1 and FOXM1 expression is also activated in endothelial cells; their expression levels correlate strongly with the ACE/ACE2 ratio, suggesting a conserved mechanism. Our studies demonstrate a molecular interaction of Brg1 and FoxM1 and an endothelial mechanism of modulating Ace/Ace2 ratio for heart failure therapy. PMID:27601681

  3. Transcriptional networks and chromatin remodeling controlling adipogenesis

    DEFF Research Database (Denmark)

    Siersbæk, Rasmus; Nielsen, Ronni; Mandrup, Susanne

    2012-01-01

    Adipocyte differentiation is tightly controlled by a transcriptional cascade, which directs the extensive reprogramming of gene expression required to convert fibroblast-like precursor cells into mature lipid-laden adipocytes. Recent global analyses of transcription factor binding and chromatin...... remodeling have revealed 'snapshots' of this cascade and the chromatin landscape at specific time-points of differentiation. These studies demonstrate that multiple adipogenic transcription factors co-occupy hotspots characterized by an open chromatin structure and specific epigenetic modifications....... Such transcription factor hotspots are likely to represent key signaling nodes which integrate multiple adipogenic signals at specific chromatin sites, thereby facilitating coordinated action on gene expression....

  4. Cuban Landscapes

    DEFF Research Database (Denmark)

    Scarpaci, Joseph L.; Portela, Armando

    This accessible book offers a vivid geographic portrait of Cuba, exploring the island’s streetscapes, sugar cane fields, beaches, and rural settlements; its billboards, government buildings, and national landmarks. The authors illuminate how natural and built landscapes have shaped Cuban identity...... (cubanidad), and vice versa. They provide a unique perspective on Cuba’s distinct historical periods and political economies, from the colonial period through republicanism and today’s socialist era. Compelling topics include the legacies of slavery and the sugar industry, the past and future of urban...

  5. PESP Landscaping Initiative

    Science.gov (United States)

    Landscaping practices can positively or negatively affect local environments and human health. The Landscaping Initiative seeks to enhance benefits of landscaping while reducing need for pesticides, fertilizers, etc., by working with partners.

  6. Legislative Framework for Landscape Planning in Latvia

    Science.gov (United States)

    Nitavska, Natalija; Zigmunde, Daiga

    2017-10-01

    With the adoption and the ratification of the European Landscape Convention a legally justified need for a clear landscape policy was grounded in the European countries. It includes the elaboration of the new and the improvement of the existing legislative documents on landscape planning, protection and management. The aim of the particular study is to analyse the existing legislative documents in Latvia influencing landscape planning on different scales / and the implementation of the European Landscape Convention. The study emphasizes the complex structure of the Latvian legislative framework affected by the distribution of the normative documents under the various ministries. Therefore, the main problem is unclear responsibility levels and organizational system for solving the issues regarding landscape planning, protection and management. Thus the various discussions between the involved disciplines and responsible institutions are arising. Two groups of the legislative documents influencing the implementation of the landscape policy in Latvia are detected within the study. The first group is strategic documents determining main landscape planning principles and directions at European, national, regional and professional or sectoral level. The second group is operational documents providing a set of actions for the landscape planning, protection and management at the local or the municipality level. The study concludes that operational documents developed by the municipalities are in high importance because of their direct influence on the landscape planning in Latvia. This often leads to the different landscape planning requirements included in the normative documents of the neighbouring municipalities, although the spatial and ecological borders of the visual landscape do not fit with the formal borders of the municipalities. Thus, it is essential to develop the common principles and actions that would be incumbent on all municipalities to provide the

  7. Understanding the whole city as landscape. A multivariate approach to urban landscape morphology

    Directory of Open Access Journals (Sweden)

    Richard Stiles

    2014-05-01

    Full Text Available The European Landscape Convention implies a requirement for signatory states to identify their urban landscapes which goes beyond the traditional focus on individual parks and green spaces and the links between them. Landscape ecological approaches can provide a useful model for identifying urban landscape types across a whole territory, but the variables relevant for urban landscapes are very different to those usually addressing rural areas. This paper presents an approach to classifying the urban landscape of Vienna that was developed in a research project funded by the Austrian Ministry for Transport, Innovation and Technology: ‘Urban Fabric and Microclimate Response’. Nine landscape types and a number of sub-types were defined, using a multivariate statistical approach which takes account of both morphological and urban climate related variables. Although the variables were selected to objectively reflect the factors that could best represent the urban climatic characteristics of the urban landscape, the results also provided a widely plausible representation of the structure of the city’s landscapes. Selected examples of the landscape types that were defined in this way were used both to simulate current microclimatic conditions and also to model the effects of possible climatic amelioration measures. Finally the paper looks forward to developing a more general-purpose urban landscape typology that allows investigating a much broader complex of urban landscape functions.

  8. Landscape moderation of biodiversity patterns and processes - eight hypotheses.

    Science.gov (United States)

    Tscharntke, Teja; Tylianakis, Jason M; Rand, Tatyana A; Didham, Raphael K; Fahrig, Lenore; Batáry, Péter; Bengtsson, Janne; Clough, Yann; Crist, Thomas O; Dormann, Carsten F; Ewers, Robert M; Fründ, Jochen; Holt, Robert D; Holzschuh, Andrea; Klein, Alexandra M; Kleijn, David; Kremen, Claire; Landis, Doug A; Laurance, William; Lindenmayer, David; Scherber, Christoph; Sodhi, Navjot; Steffan-Dewenter, Ingolf; Thies, Carsten; van der Putten, Wim H; Westphal, Catrin

    2012-08-01

    Understanding how landscape characteristics affect biodiversity patterns and ecological processes at local and landscape scales is critical for mitigating effects of global environmental change. In this review, we use knowledge gained from human-modified landscapes to suggest eight hypotheses, which we hope will encourage more systematic research on the role of landscape composition and configuration in determining the structure of ecological communities, ecosystem functioning and services. We organize the eight hypotheses under four overarching themes. Section A: 'landscape moderation of biodiversity patterns' includes (1) the landscape species pool hypothesis-the size of the landscape-wide species pool moderates local (alpha) biodiversity, and (2) the dominance of beta diversity hypothesis-landscape-moderated dissimilarity of local communities determines landscape-wide biodiversity and overrides negative local effects of habitat fragmentation on biodiversity. Section B: 'landscape moderation of population dynamics' includes (3) the cross-habitat spillover hypothesis-landscape-moderated spillover of energy, resources and organisms across habitats, including between managed and natural ecosystems, influences landscape-wide community structure and associated processes and (4) the landscape-moderated concentration and dilution hypothesis-spatial and temporal changes in landscape composition can cause transient concentration or dilution of populations with functional consequences. Section C: 'landscape moderation of functional trait selection' includes (5) the landscape-moderated functional trait selection hypothesis-landscape moderation of species trait selection shapes the functional role and trajectory of community assembly, and (6) the landscape-moderated insurance hypothesis-landscape complexity provides spatial and temporal insurance, i.e. high resilience and stability of ecological processes in changing environments. Section D: 'landscape constraints on

  9. Driving the Landscape

    Science.gov (United States)

    Haff, P. K.

    2012-12-01

    Technological modification of the earth's surface (e.g., agriculture, urbanization) is an old story in human history, but what about the future? The future of landscape in an accelerating technological world, beyond a relatively short time horizon, lies hidden behind an impenetrable veil of complexity. Sufficiently complex dynamics generates not only the trajectory of a variable of interest (e.g., vegetation cover) but also the environment in which that variable evolves (e.g., background climate). There is no way to anticipate what variables will define that environment—the dynamics creates its own variables. We are always open to surprise by a change of conditions we thought or assumed were fixed or by the appearance of new phenomena of whose possible existence we had been unaware or thought unlikely. This is especially true under the influence of technology, where novelty is the rule. Lack of direct long-term predictability of landscape change does not, however, mean we cannot say anything about its future. The presence of persistence (finite time scales) in a system means that prediction by a calibrated numerical model should be good for a limited period of time barring bad luck or faulty implementation. Short-term prediction, despite its limitations, provides an option for dealing with the longer-term future. If a computer-controlled car tries to drive itself from New York to Los Angeles, no conceivable (or possible) stand-alone software can be constructed to predict a priori the space-time trajectory of the vehicle. Yet the drive is normally completed easily by most drivers. The trip is successfully completed because each in a series of very short (linear) steps can be "corrected" on the fly by the driver, who takes her cues from the environment to keep the car on the road and headed toward its destination. This metaphor differs in a fundamental way from the usual notion of predicting geomorphic change, because it involves a goal—to reach a desired

  10. The electrostatic role of the Zn-Cys2His2 complex in binding of operator DNA with transcription factors: mouse EGR-1 from the Cys2His2 family.

    Science.gov (United States)

    Chirgadze, Y N; Boshkova, E A; Polozov, R V; Sivozhelezov, V S; Dzyabchenko, A V; Kuzminsky, M B; Stepanenko, V A; Ivanov, V V

    2018-01-07

    The mouse factor Zif268, known also as early growth response protein EGR-1, is a classical representative for the Cys2His2 transcription factor family. It is required for binding the RNA polymerase with operator dsDNA to initialize the transcription process. We have shown that only in this family of total six Zn-finger protein families the Zn complex plays a significant role in the protein-DNA binding. Electrostatic feature of this complex in the binding of factor Zif268 from Mus musculus with operator DNA has been considered. The factor consists of three similar Zn-finger units which bind with triplets of coding DNA. Essential contacts of the factor with the DNA phosphates are formed by three conservative His residues, one in each finger. We describe here the results of calculations of the electrostatic potentials for the Zn-Cys2His2 complex, Zn-finger unit 1, and the whole transcription factor. The potential of Zif268 has a positive area on the factor surface, and it corresponds exactly to the binding sites of each of Zn-finger units. The main part of these areas is determined by conservative His residues, which form contacts with the DNA phosphate groups. Our result shows that the electrostatic positive potential of this histidine residue is enhanced due to the Zn complex. The other contacts of the Zn-finger with DNA are related to nucleotide bases, and they are responsible for the sequence-specific binding with DNA. This result may be extended to all other members of the Cys2His2 transcription factor family.

  11. Supra-optimal expression of the cold-regulated OsMyb4 transcription factor in transgenic rice changes the complexity of transcriptional network with major effects on stress tolerance and panicle development

    KAUST Repository

    Park, Myoungryoul

    2010-09-28

    The R2R3-type OsMyb4 transcription factor of rice has been shown to play a role in the regulation of osmotic adjustment in heterologous overexpression studies. However, the exact composition and organization of its underlying transcriptional network has not been established to be a robust tool for stress tolerance enhancement by regulon engineering. OsMyb4 network was dissected based on commonalities between the global chilling stress transcriptome and the transcriptome configured by OsMyb4 overexpression. OsMyb4 controls a hierarchical network comprised of several regulatory sub-clusters associated with cellular defense and rescue, metabolism and development. It regulates target genes either directly or indirectly through intermediary MYB, ERF, bZIP, NAC, ARF and CCAAT-HAP transcription factors. Regulatory sub-clusters have different combinations of MYB-like, GCC-box-like, ERD1-box-like, ABRE-like, G-box-like, as1/ocs/TGA-like, AuxRE-like, gibberellic acid response element (GARE)-like and JAre-like cis-elements. Cold-dependent network activity enhanced cellular antioxidant capacity through radical scavenging mechanisms and increased activities of phenylpropanoid and isoprenoid metabolic processes involving various abscisic acid (ABA), jasmonic acid (JA), salicylic acid (SA), ethylene and reactive oxygen species (ROS) responsive genes. OsMyb4 network is independent of drought response element binding protein/C-repeat binding factor (DREB/CBF) and its sub-regulons operate with possible co-regulators including nuclear factor-Y. Because of its upstream position in the network hierarchy, OsMyb4 functions quantitatively and pleiotrophically. Supra-optimal expression causes misexpression of alternative targets with costly trade-offs to panicle development. © 2010 Blackwell Publishing Ltd.

  12. Supra-optimal expression of the cold-regulated OsMyb4 transcription factor in transgenic rice changes the complexity of transcriptional network with major effects on stress tolerance and panicle development.

    Science.gov (United States)

    Park, Myoung-Ryoul; Yun, Kil-Young; Mohanty, Bijayalaxmi; Herath, Venura; Xu, Fuyu; Wijaya, Edward; Bajic, Vladimir B; Yun, Song-Joong; De Los Reyes, Benildo G

    2010-12-01

    The R2R3-type OsMyb4 transcription factor of rice has been shown to play a role in the regulation of osmotic adjustment in heterologous overexpression studies. However, the exact composition and organization of its underlying transcriptional network has not been established to be a robust tool for stress tolerance enhancement by regulon engineering. OsMyb4 network was dissected based on commonalities between the global chilling stress transcriptome and the transcriptome configured by OsMyb4 overexpression. OsMyb4 controls a hierarchical network comprised of several regulatory sub-clusters associated with cellular defense and rescue, metabolism and development. It regulates target genes either directly or indirectly through intermediary MYB, ERF, bZIP, NAC, ARF and CCAAT-HAP transcription factors. Regulatory sub-clusters have different combinations of MYB-like, GCC-box-like, ERD1-box-like, ABRE-like, G-box-like, as1/ocs/TGA-like, AuxRE-like, gibberellic acid response element (GARE)-like and JAre-like cis-elements. Cold-dependent network activity enhanced cellular antioxidant capacity through radical scavenging mechanisms and increased activities of phenylpropanoid and isoprenoid metabolic processes involving various abscisic acid (ABA), jasmonic acid (JA), salicylic acid (SA), ethylene and reactive oxygen species (ROS) responsive genes. OsMyb4 network is independent of drought response element binding protein/C-repeat binding factor (DREB/CBF) and its sub-regulons operate with possible co-regulators including nuclear factor-Y. Because of its upstream position in the network hierarchy, OsMyb4 functions quantitatively and pleiotrophically. Supra-optimal expression causes misexpression of alternative targets with costly trade-offs to panicle development. © 2010 Blackwell Publishing Ltd.

  13. Incorporating bioenergy into sustainable landscape designs

    DEFF Research Database (Denmark)

    Dale, Virginia H.; Kline, Keith L.; Buford, Marilyn A.

    2016-01-01

    The paper describes an approach to landscape design that focuses on integrating bioenergy production with other components of environmental, social and economic systems. Landscape design as used here refers to a spatially explicit, collaborative plan for management of landscapes and supply chains...... land-management objectives from a wide array of stakeholders, up-front planning requirements, and the complexity and level of effort needed for successful stakeholder involvement. A landscape design process may be stymied by insufficient data or participation. An impetus for coordination is critical....... Landscape design can involve multiple scales and build on existing practices to reduce costs or enhance services. Appropriately applied to a specific context, landscape design can help people assess trade-offs when making choices about locations, types of feedstock, transport, refining and distribution...

  14. Multi-process Late Quaternary landscape evolution modelling reveals lags in climate response over small spatial scales

    NARCIS (Netherlands)

    Temme, A.J.A.M.; Veldkamp, A.

    2009-01-01

    Landscapes evolve in complex, non-linear ways over Quaternary timespans. Integrated geomorphological field studies usually yield plausible hypotheses about timing and impact of process activity. Landscape Evolution Models (LEMs) have the potential to test and falsify these landscape evolution

  15. A PTIP-PA1 subcomplex promotes transcription for IgH class switching independently from the associated MLL3/MLL4 methyltransferase complex

    DEFF Research Database (Denmark)

    Starnes, Linda M; Su, Dan; Pikkupeura, Laura M

    2016-01-01

    Class switch recombination (CSR) diversifies antibodies for productive immune responses while maintaining stability of the B-cell genome. Transcription at the immunoglobulin heavy chain (Igh) locus targets CSR-associated DNA damage and is promoted by the BRCT domain-containing PTIP (Pax transacti...

  16. A pathway-specific microarray analysis highlights the complex and co-ordinated transcriptional networks of the developing grain of field-grown barley

    DEFF Research Database (Denmark)

    Hansen, Michael; Friis, Carsten; Bowra, Steve

    2009-01-01

    The aim of the study was to describe the molecular and biochemical interactions associated with amino acid biosynthesis and storage protein accumulation in the developing grains of field-grown barley. Our strategy was to analyse the transcription of genes associated with the biosynthesis of stora...

  17. Energy Landscape of Social Balance

    Science.gov (United States)

    Marvel, Seth A.; Strogatz, Steven H.; Kleinberg, Jon M.

    2009-11-01

    We model a close-knit community of friends and enemies as a fully connected network with positive and negative signs on its edges. Theories from social psychology suggest that certain sign patterns are more stable than others. This notion of social “balance” allows us to define an energy landscape for such networks. Its structure is complex: numerical experiments reveal a landscape dimpled with local minima of widely varying energy levels. We derive rigorous bounds on the energies of these local minima and prove that they have a modular structure that can be used to classify them.

  18. Energy landscape of social balance.

    Science.gov (United States)

    Marvel, Seth A; Strogatz, Steven H; Kleinberg, Jon M

    2009-11-06

    We model a close-knit community of friends and enemies as a fully connected network with positive and negative signs on its edges. Theories from social psychology suggest that certain sign patterns are more stable than others. This notion of social "balance" allows us to define an energy landscape for such networks. Its structure is complex: numerical experiments reveal a landscape dimpled with local minima of widely varying energy levels. We derive rigorous bounds on the energies of these local minima and prove that they have a modular structure that can be used to classify them.

  19. Epigenetic Inheritance Across the Landscape

    Directory of Open Access Journals (Sweden)

    Amy Vaughn Whipple

    2016-10-01

    Full Text Available The study of epigenomic variation at the landscape-level in plants may add important insight to studies of adaptive variation. A major goal of landscape genomic studies is to identify genomic regions contributing to adaptive variation across the landscape. Heritable variation in epigenetic marks, resulting in transgenerational plasticity, can influence fitness-related traits. Epigenetic marks are influenced by the genome, the environment, and their interaction, and can be inherited independently of the genome. Thus, epigenomic variation likely influences the heritability of many adaptive traits, but the extent of this influence remains largely unknown. Here we summarize the relevance of epigenetic inheritance to ecological and evolutionary processes, and review the literature on landscape-level patterns of epigenetic variation. Landscape-level patterns of epigenomic variation in plants generally show greater levels of isolation by distance and isolation by environment then is found for the genome, but the causes of these patterns are not yet clear. Linkage between the environment and epigenomic variation has been clearly shown within a single generation, but demonstrating transgenerational inheritance requires more complex breeding and/or experimental designs. Transgenerational epigenetic variation may alter the interpretation of landscape genomic studies that rely upon phenotypic analyses, but should have less influence on landscape genomic approaches that rely upon outlier analyses or genome-environment associations. We suggest that multi-generation common garden experiments conducted across multiple environments will allow researchers to understand which parts of the epigenome are inherited, as well as to parse out the relative contribution of heritable epigenetic variation to the phenotype.

  20. Epigenetic Inheritance across the Landscape.

    Science.gov (United States)

    Whipple, Amy V; Holeski, Liza M

    2016-01-01

    The study of epigenomic variation at the landscape-level in plants may add important insight to studies of adaptive variation. A major goal of landscape genomic studies is to identify genomic regions contributing to adaptive variation across the landscape. Heritable variation in epigenetic marks, resulting in transgenerational plasticity, can influence fitness-related traits. Epigenetic marks are influenced by the genome, the environment, and their interaction, and can be inherited independently of the genome. Thus, epigenomic variation likely influences the heritability of many adaptive traits, but the extent of this influence remains largely unknown. Here, we summarize the relevance of epigenetic inheritance to ecological and evolutionary processes, and review the literature on landscape-level patterns of epigenetic variation. Landscape-level patterns of epigenomic variation in plants generally show greater levels of isolation by distance and isolation by environment then is found for the genome, but the causes of these patterns are not yet clear. Linkage between the environment and epigenomic variation has been clearly shown within a single generation, but demonstrating transgenerational inheritance requires more complex breeding and/or experimental designs. Transgenerational epigenetic variation may alter the interpretation of landscape genomic studies that rely upon phenotypic analyses, but should have less influence on landscape genomic approaches that rely upon outlier analyses or genome-environment associations. We suggest that multi-generation common garden experiments conducted across multiple environments will allow researchers to understand which parts of the epigenome are inherited, as well as to parse out the relative contribution of heritable epigenetic variation to the phenotype.

  1. MITIE: Simultaneous RNA-Seq-based transcript identification and quantification in multiple samples.

    Science.gov (United States)

    Behr, Jonas; Kahles, André; Zhong, Yi; Sreedharan, Vipin T; Drewe, Philipp; Rätsch, Gunnar

    2013-10-15

    High-throughput sequencing of mRNA (RNA-Seq) has led to tremendous improvements in the detection of expressed genes and reconstruction of RNA transcripts. However, the extensive dynamic range of gene expression, technical limitations and biases, as well as the observed complexity of the transcriptional landscape, pose profound computational challenges for transcriptome reconstruction. We present the novel framework MITIE (Mixed Integer Transcript IdEntification) for simultaneous transcript reconstruction and quantification. We define a likelihood function based on the negative binomial distribution, use a regularization approach to select a few transcripts collectively explaining the observed read data and show how to find the optimal solution using Mixed Integer Programming. MITIE can (i) take advantage of known transcripts, (ii) reconstruct and quantify transcripts simultaneously in multiple samples, and (iii) resolve the location of multi-mapping reads. It is designed for genome- and assembly-based transcriptome reconstruction. We present an extensive study based on realistic simulated RNA-Seq data. When compared with state-of-the-art approaches, MITIE proves to be significantly more sensitive and overall more accurate. Moreover, MITIE yields substantial performance gains when used with multiple samples. We applied our system to 38 Drosophila melanogaster modENCODE RNA-Seq libraries and estimated the sensitivity of reconstructing omitted transcript annotations and the specificity with respect to annotated transcripts. Our results corroborate that a well-motivated objective paired with appropriate optimization techniques lead to significant improvements over the state-of-the-art in transcriptome reconstruction. MITIE is implemented in C++ and is available from http://bioweb.me/mitie under the GPL license.

  2. Responding to Landscape Change: Stakeholder Participation and Social Capital in Five European Landscapes

    Directory of Open Access Journals (Sweden)

    Thanasis Kizos

    2018-01-01

    Full Text Available The concept of landscape has been increasingly used, in the last decades, in policy and land use planning, both in regard to so-called “special” and to “ordinary” or “everyday” landscapes. This has raised the importance of local and public participation in all issues that refer to landscapes and the definition of the groups that “have a stake” in the landscape. In this paper, we provide insights into how stakeholders perceive the dynamics of local processes of landscape change (and continuity and which processes of landscape change they perceive as important, in positive and negative ways, from five communities within the European Union. These landscapes involve different landscape issues “at stake”, different national and local planning and decision-making traditions and practices, and varying degrees of engagement. The understanding of these complexities and the unraveling of the insights is done through the concept of social capital and its different forms. We report on three series of workshops that have been organized to discuss landscape issues and approaches or ideas for landscape management. We witnessed interactions between the different stakeholders and gained insights into how social capital affects landscape change. We found that despite differences, similarities emerged concerning the interplay between “expert” and “local” knowledge and between “insideness” and “outsideness”. Social capital plays an important part, as it provides the template for personal and collective evaluation of landscape changes, who should manage these changes and how they should be managed. These findings are important to develop in-depth insights on dynamics and values of cultural landscapes and visions for re-coupling social and ecological components in cultural landscapes and translate them into policy and management options.

  3. Decoding transcriptional enhancers: Evolving from annotation to functional interpretation.

    Science.gov (United States)

    Engel, Krysta L; Mackiewicz, Mark; Hardigan, Andrew A; Myers, Richard M; Savic, Daniel

    2016-09-01

    Deciphering the intricate molecular processes that orchestrate the spatial and temporal regulation of genes has become an increasingly major focus of biological research. The differential expression of genes by diverse cell types with a common genome is a hallmark of complex cellular functions, as well as the basis for multicellular life. Importantly, a more coherent understanding of gene regulation is critical for defining developmental processes, evolutionary principles and disease etiologies. Here we present our current understanding of gene regulation by focusing on the role of enhancer elements in these complex processes. Although functional genomic methods have provided considerable advances to our understanding of gene regulation, these assays, which are usually performed on a genome-wide scale, typically provide correlative observations that lack functional interpretation. Recent innovations in genome editing technologies have placed gene regulatory studies at an exciting crossroads, as systematic, functional evaluation of enhancers and other transcriptional regulatory elements can now be performed in a coordinated, high-throughput manner across the entire genome. This review provides insights on transcriptional enhancer function, their role in development and disease, and catalogues experimental tools commonly used to study these elements. Additionally, we discuss the crucial role of novel techniques in deciphering the complex gene regulatory landscape and how these studies will shape future research. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Characterizing European cultural landscapes

    DEFF Research Database (Denmark)

    Tieskens, Koen F.; Schulp, Catharina J E; Levers, Christian

    2017-01-01

    intensification and land abandonment. To prevent the loss of cultural landscapes, knowledge on the location of different types of cultural landscapes is needed. In this paper, we present a characterization of European cultural landscapes based on the prevalence of three key dimensions of cultural landscapes......Almost all rural areas in Europe have been shaped or altered by humans and can be considered cultural landscapes, many of which now are considered to entail valuable cultural heritage. Current dynamics in land management have put cultural landscapes under a huge pressure of agricultural...... the three dimensions into a continuous “cultural landscape index” that allows for a characterization of Europe's rural landscapes. The characterization identifies hotspots of cultural landscapes, where all three dimensions are present, such as in the Mediterranean. On the other hand, Eastern and Northern...

  5. EVERYDAY LANDSCAPE AND MEANING IN URBAN LIVING

    Directory of Open Access Journals (Sweden)

    LAKSHMI PRIYA RAJENDRAN

    2013-11-01

    Full Text Available This paper conceptualizes landscape from a temporal and spatial perspective which emphasizes peoples’ interactions and activities as an inherent part of understanding the landscape itself. Today, peoples’ interaction with the landscape has become more complex, largely owing to the changing notions of place in contemporary urban living. In this context, the paper examines the role and significance of the landscapes of everyday life in urban environment and delineates how it (reconstructs ordinary human and social meanings that are necessary conditions for our existence. The paper is presented in three sections. In the first section, it discusses the concept of everyday life and its relevance in the contemporary urban living. In the following section, it examines the complexities encountered in urban landscapes today .The third section of the paper discusses how meaningful interaction experienced with everyday landscapes offer valuable insights for addressing the challenges posed by the complexities of urban city living. The paper concludes by highlighting the need for attention towards the largely neglected or overlooked domains of ‘ordinary’ everyday landscape by designer professionals, which plays a crucial role in creating meaningful relationship between people and place.

  6. Cs-137 behaviour in landscape-geochemical structures of barrier complexes; Povedenie Cs-137 v landshaftno-geokhimicheskikh strukturakh bar`ernykh kompleksov

    Energy Technology Data Exchange (ETDEWEB)

    Strakh, L I; Ivashkevich, I I; Adamovich, A A [Akadehmiya Navuk Belarusi, Minsk (Belarus). Inst. Radyyabiyalogii; Zarubin, O L [AN Ukrainskoj SSR, Kiev (Ukraine). Inst. Yadernykh Issledovanij

    1999-12-31

    The Cs-137 distribution and cumulation accrues more actively in a marsh ecological systems of barrier complexes. The physical chemical and biogeochemical barriers influence on different way on these processes.

  7. Geomatics as a Survey Tool to Document and Enhance the Cultural and Landscaped Heritage of the Monumental Complexes in the Mountains of Abruzzo

    Science.gov (United States)

    Palestini, C.; Basso, A.

    2017-05-01

    The themes of the conference provide an opportunity to exchange views on topics of study in which multidisciplinary contributions of geomatics and restoration contribute to the cognitive process aimed at the conservation of cultural Heritage. In this regard, the contribution exposes research aimed at understanding the documentation and the enhancement of unique architectural - landscape patrimony kept in the Abruzzo mountains. It is about the numerous spiritual retreats established by Pietro da Morrone, Pope Celestino V, mounted among unpassable rocky walls, where the architecture blends with its natural environment camouflaging with it. The analysis refers, specifically to the aspects of survey conducted during the years with the aid of integrated methodologies, able to allow the acquisition, management and comparison of the data. The analysis refers, specifically, to recent digital acquisitions involving the development of San Bartolomeo in Legio, on the slopes of Majella near Roccamorice detected with the use of comparative Agisoft Photoscan and Pix4d software, with shots taken with drones of different sizes, able to mount professional photographic cameras and associate to each picture the coordinates Gps of the point of shooting. Follows a confrontation between a survey carried out with 3d laser scanner, Faro Ls1105, and described acquisitions, obtained from ground and from drone with Photoscan, in order to compare the two scans and the metric differences obtained with the two methods.

  8. GEOMATICS AS A SURVEY TOOL TO DOCUMENT AND ENHANCE THE CULTURAL AND LANDSCAPED HERITAGE OF THE MONUMENTAL COMPLEXES IN THE MOUNTAINS OF ABRUZZO

    Directory of Open Access Journals (Sweden)

    C. Palestini

    2017-05-01

    Full Text Available The themes of the conference provide an opportunity to exchange views on topics of study in which multidisciplinary contributions of geomatics and restoration contribute to the cognitive process aimed at the conservation of cultural Heritage. In this regard, the contribution exposes research aimed at understanding the documentation and the enhancement of unique architectural – landscape patrimony kept in the Abruzzo mountains. It is about the numerous spiritual retreats established by Pietro da Morrone, Pope Celestino V, mounted among unpassable rocky walls, where the architecture blends with its natural environment camouflaging with it. The analysis refers, specifically to the aspects of survey conducted during the years with the aid of integrated methodologies, able to allow the acquisition, management and comparison of the data. The analysis refers, specifically, to recent digital acquisitions involving the development of San Bartolomeo in Legio, on the slopes of Majella near Roccamorice detected with the use of comparative Agisoft Photoscan and Pix4d software, with shots taken with drones of different sizes, able to mount professional photographic cameras and associate to each picture the coordinates Gps of the point of shooting. Follows a confrontation between a survey carried out with 3d laser scanner, Faro Ls1105, and described acquisitions, obtained from ground and from drone with Photoscan, in order to compare the two scans and the metric differences obtained with the two methods.

  9. Purification, crystallization and preliminary X-ray analysis of OsAREB8 from rice, a member of the AREB/ABF family of bZIP transcription factors, in complex with its cognate DNA

    International Nuclear Information System (INIS)

    Miyazono, Ken-ichi; Koura, Tsubasa; Kubota, Keiko; Yoshida, Takuya; Fujita, Yasunari; Yamaguchi-Shinozaki, Kazuko; Tanokura, Masaru

    2012-01-01

    OsAREB8 from rice (O. sativa), a member of the AREB/ABF family of bZIP transcription factors, was expressed, purified and crystallized using the sitting-drop vapour-diffusion method. A crystal of OsAREB8 in complex with its cognate DNA diffracted X-rays to 3.65 Å resolution. The AREB/ABF family of bZIP transcription factors play a key role in drought stress response and tolerance during the vegetative stage in plants. To reveal the DNA-recognition mechanism of the AREB/ABF family of proteins, the bZIP domain of OsAREB8, an AREB/ABF-family protein from Oryza sativa, was expressed in Escherichia coli, purified and crystallized with its cognate DNA. Crystals of the OsAREB8–DNA complex were obtained by the sitting-drop vapour-diffusion method at 277 K with a reservoir solution consisting of 50 mM MES pH 6.4, 29% MPD, 2 mM spermidine, 20 mM magnesium acetate and 100 mM sodium chloride. A crystal diffracted X-rays to 3.65 Å resolution and belonged to space group C222, with unit-cell parameters a = 155.1, b = 206.7, c = 38.5 Å. The crystal contained one OsAREB8–DNA complex in the asymmetric unit

  10. Understanding the Global Cold War Legacy: Narrating through Landscape

    Directory of Open Access Journals (Sweden)

    Melanie Klein

    2004-06-01

    Full Text Available The end of the Cold War brought the shrinking and dismantling of vast nuclear weapons complexes. As a result, some landscape architects will find themselves reclaiming a new, very specific type of Cold War landscape: those degraded by nuclear arms testing, production and waste storage. Nuclear landscapes pose multiple and complex challenges. Before designing nuclear reclamations, one must ask: what are the issues? If designers misunderstand the nuclear landscape 'problem', it will be 'solved' in the wrong way. My position is based on the assumption that society desires these landscapes to be reclaimed safely and in ways that allow them to educate the public. Landscape architects can find ways to reclaim nuclear landscapes safely while leaving narratives for generations to come. Perhaps it is too early to describe how nuclear reclamations will look. It is not too early to discuss what designs for nuclear reclamations should accomplish. This paper raises questions critical to the design of nuclear reclamations, both globally and locally. Near precedents - past reclamations that narrate other types of degraded landscapes - are discussed, and it is noted how we can learn from them when considering nuclear landscape reclamation. This paper does not articulate a specific design theory or solution to Cold War nuclear landscapes, but rather, it seeks to pose critical questions that designers should ask. These questions will be broad because we consider nuclear landscapes globally. The questions will require in-depth investigation of local issues as each unique nuclear landscape is considered.

  11. Production of the 2400 kb Duchenne muscular dystrophy (DMD) gene transcript; transcription time and cotranscriptional splicing

    Energy Technology Data Exchange (ETDEWEB)

    Tennyson, C.N.; Worton, R.G. [Univ. of Toronto and the Hospital for Sick Children, Ontario (Canada)

    1994-09-01

    The largest known gene in any organism is the human DMD gene which has 79 exons that span 2400 kb. The extreme nature of the DMD gene raises questions concerning the time required for transcription and whether splicing begins before transcription is complete. DMD gene transcription is induced as cultured human myoblasts differentiate to form multinucleated myotubes, providing a system for studying the kinetics of transcription and splicing. Using quantitative RT-PCR, transcript accumulation was monitored from four different regions within the gene following induction of expression. By comparing the accumulation of transcripts from the 5{prime} and 3{prime} ends of the gene we have shown that approximately 12 hours are required to transcribe 1770 kb of the gene, extrapolating to a time of 16 hours for the transcription unit expressed in muscle. Comparison of accumulation profiles for spliced and total transcript demonstrated that transcripts are spliced at the 5{prime} end before transcription is complete, providing strong evidence for cotranscriptional splicing of DMD gene transcripts. Finally, the rate of transcript accumulation was reduced at the 3{prime} end of the gene relative to the 5{prime} end, perhaps due to premature termination of transcription complexes as they traverse this enormous transcription unit. The lag between transcription initiation and the appearance of complete transcripts could be important in limiting transcript production in dividing cells and to the timing of mRNA appearance in differentiating muscle.

  12. Research using energy landscape

    International Nuclear Information System (INIS)

    Kim, Hack Jin

    2007-01-01

    Energy landscape is a theoretical tool used for the study of systems where cooperative processes occur such as liquid, glass, clusters, and protein. Theoretical and experimental researches related to energy landscape are introduced in this review

  13. Biochemical and redox characterization of the mediator complex and its associated transcription factor GeBPL, a GLABROUS1 enhancer binding protein.

    Science.gov (United States)

    Shaikhali, Jehad; Davoine, Céline; Brännström, Kristoffer; Rouhier, Nicolas; Bygdell, Joakim; Björklund, Stefan; Wingsle, Gunnar

    2015-06-15

    The eukaryotic mediator integrates regulatory signals from promoter-bound transcription factors (TFs) and transmits them to RNA polymerase II (Pol II) machinery. Although redox signalling is important in adjusting plant metabolism and development, nothing is known about a possible redox regulation of mediator. In the present study, using pull-down and yeast two-hybrid assays, we demonstrate the association of mediator (MED) subunits MED10a, MED28 and MED32 with the GLABROUS1 (GL1) enhancer-binding protein-like (GeBPL), a plant-specific TF that binds a promoter containing cryptochrome 1 response element 2 (CryR2) element. All the corresponding recombinant proteins form various types of covalent oligomers linked by intermolecular disulfide bonds that are reduced in vitro by the thioredoxin (TRX) and/or glutathione/glutaredoxin (GRX) systems. The presence of recombinant MED10a, MED28 and MED32 subunits or changes of its redox state affect the DNA-binding capacity of GeBPL suggesting that redox-driven conformational changes might modulate its activity. Overall, these results advance our understanding of how redox signalling affects transcription and identify mediator as a novel actor in redox signalling pathways, relaying or integrating redox changes in combination with specific TFs as GeBPL. © The Authors Journal compilation © 2015 Biochemical Society.

  14. Determinants of a traditional agricultural landscape

    Directory of Open Access Journals (Sweden)

    Janina Borysiak

    2018-03-01

    Full Text Available The study aim was to define the landscape determinants as certificates of natural and cultural heritage which identify the young glacial landscape under traditional agricultural management. These studies were conducted in the upper Parsęta basin (Pomerania, Poland covered by the many annual environmental monitoring programs since 1994. The aim of this monitoring is to observe changes in geoecosystems of the temperate climate zone. The parameters of the abiotic landscape subsystem have been monitored in a wide range of terms, whereas biotic elements and cultural resources only in a very limited way. This was the reason for undertaking complementary studies. The paper presents the so-called “zero-state” for 2014, which will be a reference point from which to track the direction of landscape changes in the future. The abiotic, geobotanical, and cultural determinants of this state chosen have been characterized on the basis of field mapping data and the available literature. They were chosen based on the methodology of landscape audit to define the specificity of the traditional agricultural landscape. They were selected on the basis of assessment criteria for landscape structure: complexity (diversification of land use and cover, naturalness (syngenesis of plant communities, hydrochemical properties of surface waters, coherence of composition with natural conditions, stewardship (intensity of use, crop weeds, ecological succession, fallows, anthropogenic denudation, aesthetic and visual perception, historicity (continuity of natural landscape elements, continuation of traditional agricultural use, architectural objects, and disharmonious elements.

  15. Landscape Sustainability in a Sonoran Desert City

    Directory of Open Access Journals (Sweden)

    Chris A. Martin

    2008-01-01

    Full Text Available The objective of this paper is to discuss concepts of landscape sustainability in the Phoenix metropolitan area. Phoenix is situated in the greater Salt River Valley of the lower Sonoran Desert in the southwest United States. In this paper I use the ecological frameworks of ecosystem services and resiliency as a metric for understanding landscape sustainability. An assessment of landscape sustainability performance benchmarks were made by surveying research findings of scientists affiliated with the Central Arizona Phoenix Long Term Ecological Research Project (CAP LTER. In Phoenix, present day emphases on cultural, aesthetic, and habitat formation ecosystem services within an arid ecoregion of low natural resilience coupled to a complex matrix of socioeconomic stratification, excessive landscape water use and pruning practices has had the undesired effect of degrading landscape sustainability. This has been measured as mixed patterns of plant diversity and human-altered patterns of carbon regulation, microclimate control, and trophic dynamics. In the future, sustainable residential landscaping in desert cities such as Phoenix may be fostered through use of water-conserving irrigation technologies, oasis-style landscape design motifs, recycling of landscape green waste, and conservative plant pruning strategies.

  16. Lines of landscape organisation

    DEFF Research Database (Denmark)

    Løvschal, Mette

    2015-01-01

    This paper offers a landscape analysis of the earliest linear landscape boundaries on Skovbjerg Moraine, Denmark, during the first millennium BC. Using Delaunay triangulation as well as classic distribution analyses, it demonstrates that landscape boundaries articulated already established use-pa...

  17. The Role of Epigenetic Regulation in Transcriptional Memory in the Immune System.

    Science.gov (United States)

    Woodworth, A M; Holloway, A F

    The immune system is exquisitely poised to identify, respond to, and eradicate pathogens from the body, as well as to produce a more rapid and augmented response to a subsequent encounter with the pathogen. These cellular responses rely on the highly coordinated and rapid activation of gene expression programs as well as the ability of the cell to retain a memory of the initial gene response. It is clear that chromatin structure and epigenetic mechanisms play a crucial role in determining these gene responses, and in fact the immune system has proved an instructive model for investigating the multifaceted mechanisms through which the chromatin landscape contributes to gene expression programs. These mechanisms include modifications to the DNA and histone proteins, the positioning, composition, and remodeling of nucleosomes, as well as the formation of higher-order chromatin structures. Moreover, it is now apparent that epigenetic mechanisms also provide an instrument by which cells can retain memory of the initial transcriptional response, "priming" the genome so that it can respond more quickly to subsequent exposure to the signal. Here, we use the immune system as a model to demonstrate the complex interplay between transcription factors and the chromatin landscape required to orchestrate precise gene responses to external stimuli and further to demonstrate how these interactions can establish memory of past transcriptional events. We focus on what we have learnt from the immune system and how this can inform our understanding of other cellular systems. © 2017 Elsevier Inc. All rights reserved.

  18. E2F-Rb complexes assemble and inhibit cdc25A transcription in cervical carcinoma cells following repression of human papillomavirus oncogene expression

    DEFF Research Database (Denmark)

    Wu, L; Goodwin, E C; Naeger, L K

    2000-01-01

    in the absence of E2 expression. Expression of the E2 protein also led to posttranscriptional increase in the level of E2F4, p105(Rb), and p130 and induced the formation of nuclear E2F4-p130 and E2F4-p105(Rb) complexes. This resulted in marked rearrangement of the protein complexes that formed at the distal E2F...... site in the cdc25A promoter, including the replacement of free E2F complexes with E2F4-p105(Rb) complexes. These experiments indicated that repression of E2F-responsive promoters following HPV E6/E7 repression was mediated by activation of the Rb tumor suppressor pathway and the assembly of repressing...

  19. Do geographically isolated wetlands influence landscape functions?

    OpenAIRE

    Cohen, Matthew J.; Creed, Irena F.; Alexander, Laurie; Basu, Nandita B.; Calhoun, Aram J. K.; Craft, Christopher; D’Amico, Ellen; DeKeyser, Edward; Fowler, Laurie; Golden, Heather E.; Jawitz, James W.; Kalla, Peter; Kirkman, L. Katherine; Lane, Charles R.; Lang, Megan

    2016-01-01

    Geographically isolated wetlands (GIWs), those surrounded by uplands, exchange materials, energy, and organisms with other elements in hydrological and habitat networks, contributing to landscape functions, such as flow generation, nutrient and sediment retention, and biodiversity support. GIWs constitute most of the wetlands in many North American landscapes, provide a disproportionately large fraction of wetland edges where many functions are enhanced, and form complexes with other water bo...

  20. Flowscapes : Infrastructure as landscape, landscape as infrastructure. Graduation Lab Landscape Architecture 2012/2013

    NARCIS (Netherlands)

    Nijhuis, S.; Jauslin, D.; De Vries, C.

    2012-01-01

    Flowscapes explores infrastructure as a type of landscape and landscape as a type of infrastructure, and is focused on landscape architectonic design of transportation-, green- and water infrastructures. These landscape infrastructures are considered armatures for urban and rural development. With

  1. DNA Topoisomerases in Transcription

    DEFF Research Database (Denmark)

    Rødgaard, Morten Terpager

    2015-01-01

    This Ph.D. thesis summarizes the main results of my studies on the interplay between DNA topoisomerases and transcription. The work was performed from 2011 to 2015 at Aarhus University in the Laboratory of Genome Research, and was supervised by associate professor Anni H. Andersen. Most of the ex......This Ph.D. thesis summarizes the main results of my studies on the interplay between DNA topoisomerases and transcription. The work was performed from 2011 to 2015 at Aarhus University in the Laboratory of Genome Research, and was supervised by associate professor Anni H. Andersen. Most...... topoisomerase-DNA cleavage complex. The second study is an investigation of how topoisomerases influence gene regulation by keeping the genome in an optimal topological state....

  2. Deciphering Transcriptional Regulation

    DEFF Research Database (Denmark)

    Valen, Eivind

    The myriad of cells in the human body are all made from the same blueprint: the human genome. At the heart of this diversity lies the concept of gene regulation, the process in which it is decided which genes are used where and when. Genes do not function as on/off buttons, but more like a volume...... mostly near the start of the gene known as the promoter. This region contains patterns scattered in the DNA that the TFs can recognize and bind to. Such binding can prompt the assembly of the pre-initiation complex which ultimately leads to transcription of the gene. In order to achieve the regulation...... on what characterizes a hippocampus promoter. Pairing CAGE with TF binding site prediction we identi¿ed a likely key regulator of hippocampus. Finally, we developed a method for CAGE exploration. While the DeepCAGE library characterized a full 1.4 million transcription initiation events it did not capture...

  3. Sustainable pest regulation in agricultural landscapes: a review on landscape composition, biodiversity and natural pest control.

    Science.gov (United States)

    Bianchi, F J J A; Booij, C J H; Tscharntke, T

    2006-07-22

    Agricultural intensification has resulted in a simplification of agricultural landscapes by the expansion of agricultural land, enlargement of field size and removal of non-crop habitat. These changes are considered to be an important cause of the rapid decline in farmland biodiversity, with the remaining biodiversity concentrated in field edges and non-crop habitats. The simplification of landscape composition and the decline of biodiversity may affect the functioning of natural pest control because non-crop habitats provide requisites for a broad spectrum of natural enemies, and the exchange of natural enemies between crop and non-crop habitats is likely to be diminished in landscapes dominated by arable cropland. In this review, we test the hypothesis that natural pest control is enhanced in complex patchy landscapes with a high proportion of non-crop habitats as compared to simple large-scale landscapes with little associated non-crop habitat. In 74% and 45% of the studies reviewed, respectively, natural enemy populations were higher and pest pressure lower in complex landscapes versus simple landscapes. Landscape-driven pest suppression may result in lower crop injury, although this has rarely been documented. Enhanced natural enemy activity was associated with herbaceous habitats in 80% of the cases (e.g. fallows, field margins), and somewhat less often with wooded habitats (71%) and landscape patchiness (70%). The similar contributions of these landscape factors suggest that all are equally important in enhancing natural enemy populations. We conclude that diversified landscapes hold most potential for the conservation of biodiversity and sustaining the pest control function.

  4. Utility of computer simulations in landscape genetics

    Science.gov (United States)

    Bryan K. Epperson; Brad H. McRae; Kim Scribner; Samuel A. Cushman; Michael S. Rosenberg; Marie-Josee Fortin; Patrick M. A. James; Melanie Murphy; Stephanie Manel; Pierre Legendre; Mark R. T. Dale

    2010-01-01

    Population genetics theory is primarily based on mathematical models in which spatial complexity and temporal variability are largely ignored. In contrast, the field of landscape genetics expressly focuses on how population genetic processes are affected by complex spatial and temporal environmental heterogeneity. It is spatially explicit and relates patterns to...

  5. Monarto’s Contested Landscape

    Directory of Open Access Journals (Sweden)

    Paul Walker

    2015-11-01

    Full Text Available The proposal to develop a new city at Monarto in South Australia during the 1970s was an important project of the reforming government of Don Dunstan. Dunstan’s view was that Monarto would be a city environmentally suited to the tough conditions of its site, and to an ‘Australian way of life’. As planning and preliminary design proceeded from 1972 to 1975, the landscape potential of the city’s selected site became central to its conception. This paper draws on new research comprising interviews with key participants and archival material to examine four issues: the adoption of an environmental orientation in Australian urban planning and discourse in the 1970s; strategies in the design proposals that seemingly gave Monarto validity even as the demographic and political drivers for it dissolved away; the investigations that supported Monarto’s landscape strategies; and attitudes to social and cultural history that the Monarto project adopted. While ultimately the plan for Monarto was abandoned, the projected city’s landscape can be seen as a theatre for competing values in relation to natural and cultural heritage and design ambitions. The paper situates Monarto within national and international urban discourse that is more complex than has been previously acknowledged, indicative of competing values and ideologies in the planning, landscape and design discourses of the period.

  6. Surface fluxes in heterogeneous landscape

    Energy Technology Data Exchange (ETDEWEB)

    Bay Hasager, C

    1997-01-01

    The surface fluxes in homogeneous landscapes are calculated by similarity scaling principles. The methodology is well establish. In heterogeneous landscapes with spatial changes in the micro scale range, i e from 100 m to 10 km, advective effects are significant. The present work focus on these effects in an agricultural countryside typical for the midlatitudes. Meteorological and satellite data from a highly heterogeneous landscape in the Rhine Valley, Germany was collected in the large-scale field experiment TRACT (Transport of pollutants over complex terrain) in 1992. Classified satellite images, Landsat TM and ERS SAR, are used as basis for roughness maps. The roughnesses were measured at meteorological masts in the various cover classes and assigned pixel by pixel to the images. The roughness maps are aggregated, i e spatially averaged, into so-called effective roughness lengths. This calculation is performed by a micro scale aggregation model. The model solves the linearized atmospheric flow equations by a numerical (Fast Fourier Transform) method. This model also calculate maps of friction velocity and momentum flux pixel wise in heterogeneous landscapes. It is indicated how the aggregation methodology can be used to calculate the heat fluxes based on the relevant satellite data i e temperature and soil moisture information. (au) 10 tabs., 49 ills., 223 refs.

  7. Landscape genetics of high mountain frog metapopulations

    Science.gov (United States)

    Murphy, M.A.; Dezzani, R.; Pilliod, D.S.; Storfer, A.

    2010-01-01

    Explaining functional connectivity among occupied habitats is crucial for understanding metapopulation dynamics and species ecology. Landscape genetics has primarily focused on elucidating how ecological features between observations influence gene flow. Functional connectivity, however, may be the result of both these between-site (landscape resistance) landscape characteristics and at-site (patch quality) landscape processes that can be captured using network based models. We test hypotheses of functional connectivity that include both between-site and at-site landscape processes in metapopulations of Columbia spotted frogs (Rana luteiventris) by employing a novel justification of gravity models for landscape genetics (eight microsatellite loci, 37 sites, n = 441). Primarily used in transportation and economic geography, gravity models are a unique approach as flow (e.g. gene flow) is explained as a function of three basic components: distance between sites, production/attraction (e.g. at-site landscape process) and resistance (e.g. between-site landscape process). The study system contains a network of nutrient poor high mountain lakes where we hypothesized a short growing season and complex topography between sites limit R. luteiventris gene flow. In addition, we hypothesized production of offspring is limited by breeding site characteristics such as the introduction of predatory fish and inherent site productivity. We found that R. luteiventris connectivity was negatively correlated with distance between sites, presence of predatory fish (at-site) and topographic complexity (between-site). Conversely, site productivity (as measured by heat load index, at-site) and growing season (as measured by frost-free period between-sites) were positively correlated with gene flow. The negative effect of predation and positive effect of site productivity, in concert with bottleneck tests, support the presence of source-sink dynamics. In conclusion, gravity models provide a

  8. Learning topography with Tangible Landscape games

    Science.gov (United States)

    Petrasova, A.; Tabrizian, P.; Harmon, B. A.; Petras, V.; Millar, G.; Mitasova, H.; Meentemeyer, R. K.

    2017-12-01

    Understanding topography and its representations is crucial for correct interpretation and modeling of surface processes. However, novice earth science and landscape architecture students often find reading topographic maps challenging. As a result, many students struggle to comprehend more complex spatial concepts and processes such as flow accumulation or sediment transport.We developed and tested a new method for teaching hydrology, geomorphology, and grading using Tangible Landscape—a tangible interface for geospatial modeling. Tangible Landscape couples a physical and digital model of a landscape through a real-time cycle of hands-on modeling, 3D scanning, geospatial computation, and projection. With Tangible Landscape students can sculpt a projection-augmented topographic model of a landscape with their hands and use a variety of tangible objects to immediately see how they are changing geospatial analytics such as contours, profiles, water flow, or landform types. By feeling and manipulating the shape of the topography, while seeing projected geospatial analytics, students can intuitively learn about 3D topographic form, its representations, and how topography controls physical processes. Tangible Landscape is powered by GRASS GIS, an open source geospatial platform with extensive libraries for geospatial modeling and analysis. As such, Tangible Landscape can be used to design a wide range of learning experiences across a large number of geoscience disciplines.As part of a graduate level course that teaches grading, 16 students participated in a series of workshops, which were developed as serious games to encourage learning through structured play. These serious games included 1) diverting rain water to a specified location with minimal changes to landscape, 2) building different combinations of landforms, and 3) reconstructing landscapes based on projected contour information with feedback.In this poster, we will introduce Tangible Landscape, and

  9. Soil sorption complex influence on dynamics of 239,240Pu and 241Am mobile and fixed forms in different landscapes

    International Nuclear Information System (INIS)

    Leinova, S.L.; Sokolik, G.A.; Kilchitskaya, S.L.; Ivanova, T.G.; Zhukovich, N.V.; Kimlenko, I.M.

    1998-01-01

    The physico-chemical forms of 239,240 Pu and 241 Am in soil and radionuclide distribution between the main components of soil sorption complex were analyzed. The content of 'hot' particles in soils in Belarus is about 10-1.10 4 particles/m 2 . During the post accident period the 'hot' particles quantity decreased 40-200 times and 50-20000 times in mineral and organogenic soils, respectively. Their activity decreased 1.2-1.4 times per year in mineral soils and 1.3-1.5 times in organic soils. Their destruction velocity is determined by the soil media properties and the particle composition: the particles of 'condensed' nature are destroyed more quickly than those of fuel nature. The velocity of release of transuranium elements from the 'hot' particles increases with increasing soil acidity and humus content in soils. The radionuclides exhibiting different bond strength with soil sorption complex were determined by sequential selective extraction. The share of the most mobile exchange forms of 239,240 Pu is less than 10%. The quantity of potential mobile acid soluble forms of 239,240 Pu increases with time and changes in the sequence: peat soils 241 Am (85%) in comparison with 2 39,240 Pu (40%) was found. The content of 241 Am mobile forms increases with soil depth. It can be expected that in soils with high content of organic substances the accumulation of 239,240 Pu and 241 Am in surface soil layers will take place in future, but in mineral soils significant amounts of radionuclides will enter illuvial horizons as a result of vertical migration

  10. Combinatorial analysis of lupulin gland transcription factors from R2R3Myb, bHLH and WDR families indicates a complex regulation of chs_H1 genes essential for prenylflavonoid biosynthesis in hop (Humulus Lupulus L.

    Directory of Open Access Journals (Sweden)

    Matoušek Jaroslav

    2012-02-01

    Full Text Available Abstract Background Lupulin glands of hop produce a specific metabolome including hop bitter acids valuable for the brewing process and prenylflavonoids with promising health-beneficial activities. The detailed analysis of the transcription factor (TF-mediated regulation of the oligofamily of one of the key enzymes, i.e., chalcone synthase CHS_H1 that efficiently catalyzes the production of naringenin chalcone, a direct precursor of prenylflavonoids in hop, constitutes an important part of the dissection of the biosynthetic pathways leading to the accumulation of these compounds. Results Homologues of flavonoid-regulating TFs HlMyb2 (M2, HlbHLH2 (B2 and HlWDR1 (W1 from hop were cloned using a lupulin gland-specific cDNA library from the hop variety Osvald's 72. Using a "combinatorial" transient GUS expression system it was shown that these unique lupulin-gland-associated TFs significantly activated the promoter (P of chs_H1 in ternary combinations of B2, W1 and either M2 or the previously characterized HlMyb3 (M3. The promoter activation was strongly dependent on the Myb-P binding box TCCTACC having a core sequence CCWACC positioned on its 5' end region and it seems that the complexity of the promoter plays an important role. M2B2W1-mediated activation significantly exceeded the strength of expression of native chs_H1 gene driven by the 35S promoter of CaMV, while M3B2W1 resulted in 30% of the 35S:chs_H1 expression level, as quantified by real-time PCR. Another newly cloned hop TF, HlMyb7, containing a transcriptional repressor-like motif pdLNLD/ELxiG/S (PDLNLELRIS, was identified as an efficient inhibitor of chs_H1-activating TFs. Comparative analyses of hop and A. thaliana TFs revealed a complex activation of Pchs_H1 and Pchs4 in combinatorial or independent manners. Conclusions This study on the sequences and functions of various lupulin gland-specific transcription factors provides insight into the complex character of the regulation of the

  11. Defining the landscape of adaptive genetic diversity.

    Science.gov (United States)

    Eckert, Andrew J; Dyer, Rodney J

    2012-06-01

    Whether they are used to describe fitness, genome architecture or the spatial distribution of environmental variables, the concept of a landscape has figured prominently in our collective reasoning. The tradition of landscapes in evolutionary biology is one of fitness mapped onto axes defined by phenotypes or molecular sequence states. The characteristics of these landscapes depend on natural selection, which is structured across both genomic and environmental landscapes, and thus, the bridge among differing uses of the landscape concept (i.e. metaphorically or literally) is that of an adaptive phenotype and its distribution across geographical landscapes in relation to selective pressures. One of the ultimate goals of evolutionary biology should thus be to construct fitness landscapes in geographical space. Natural plant populations are ideal systems with which to explore the feasibility of attaining this goal, because much is known about the quantitative genetic architecture of complex traits for many different plant species. What is less known are the molecular components of this architecture. In this issue of Molecular Ecology, Parchman et al. (2012) pioneer one of the first truly genome-wide association studies in a tree that moves us closer to this form of mechanistic understanding for an adaptive phenotype in natural populations of lodgepole pine (Pinus contorta Dougl. ex Loud.). © 2012 Blackwell Publishing Ltd.

  12. Do geographically isolated wetlands influence landscape functions?

    Science.gov (United States)

    Cohen, Matthew J.; Creed, Irena F.; Alexander, Laurie C.; Basu, Nandita; Calhoun, Aram J.K.; Craft, Christopher; D’Amico, Ellen; DeKeyser, Edward S.; Fowler, Laurie; Golden, Heather E.; Jawitz, James W.; Kalla, Peter; Kirkman, L. Katherine; Lane, Charles R.; Lang, Megan; Leibowitz, Scott G.; Lewis, David Bruce; Marton, John; McLaughlin, Daniel L.; Mushet, David M.; Raanan-Kiperwas, Hadas; Rains, Mark C.; Smith, Lora; Walls, Susan C.

    2015-01-01

    Geographically isolated wetlands (GIWs), those surrounded by uplands, exchange materials, energy, and organisms with other elements in hydrological and habitat networks, contributing to landscape functions, such as flow generation, nutrient and sediment retention, and biodiversity support. GIWs constitute most of the wetlands in many North American landscapes, provide a disproportionately large fraction of wetland edges where many functions are enhanced, and form complexes with other water bodies to create spatial and temporal heterogeneity in the timing, flow paths, and magnitude of network connectivity. These attributes signal a critical role for GIWs in sustaining a portfolio of landscape functions, but legal protections remain weak despite preferential loss from many landscapes. GIWs lack persistent surface water connections, but this condition does not imply the absence of hydrological, biogeochemical, and biological exchanges with nearby and downstream waters. Although hydrological and biogeochemical connectivity is often episodic or slow (e.g., via groundwater), hydrologic continuity and limited evaporative solute enrichment suggest both flow generation and solute and sediment retention. Similarly, whereas biological connectivity usually requires overland dispersal, numerous organisms, including many rare or threatened species, use both GIWs and downstream waters at different times or life stages, suggesting that GIWs are critical elements of landscape habitat mosaics. Indeed, weaker hydrologic connectivity with downstream waters and constrained biological connectivity with other landscape elements are precisely what enhances some GIW functions and enables others. Based on analysis of wetland geography and synthesis of wetland functions, we argue that sustaining landscape functions requires conserving the entire continuum of wetland connectivity, including GIWs.

  13. Evolutionary landscape of the Mycobacterium tuberculosis complex from the viewpoint of PhoPR: implications for virulence regulation and application to vaccine development.

    Science.gov (United States)

    Broset, Esther; Martín, Carlos; Gonzalo-Asensio, Jesús

    2015-10-20

    Different members of the Mycobacterium genus have evolved to cause tuberculosis in diverse human populations and in a variety of animal species. Our cumulative knowledge of mycobacterial genomes indicates that mutations in the PhoPR two-component virulence system were acquired not only during the natural evolution of mycobacterial species but also during in vitro subculture, which has given rise to the attenuated reference strain H37Ra or to different daughter strains of Mycobacterium bovis BCG. PhoPR is a well-known regulator of pathogenic phenotypes, including secretion of the virulence factor ESAT-6, biosynthesis of acyltrehalose-based lipids, and modulation of antigen export, in members of the Mycobacterium tuberculosis complex (MTBC). Evolutionarily conserved polymorphisms in PhoPR from Mycobacterium africanum, M. bovis, or M. tuberculosis H37Ra result in loss of functional phenotypes. Interestingly, some members of the MTBC have acquired compensatory mutations to counteract these polymorphisms and, probably, to maintain their pathogenic potential. Some of these compensatory mutations include the insertion of the IS6110 element upstream from phoPR in a particular M. bovis strain that is able to transmit between humans or polymorphisms in M. africanum and M. bovis that affect the regulatory region of the espACD operon, allowing PhoPR-independent ESAT-6 secretion. This review highlights the increasing knowledge of the significance of PhoPR in the evolution of the MTBC and its potential application in the construction of new attenuated vaccines based on phoPR inactivation. In this context, the live attenuated vaccine MTBVAC, based on a phoP fadD26 deletion mutant of M. tuberculosis, is the first vaccine of this kind to successfully enter into clinical development, representing a historic milestone in the field of human vaccinology. Copyright © 2015 Broset et al.

  14. Evolutionary Landscape of the Mycobacterium tuberculosis Complex from the Viewpoint of PhoPR: Implications for Virulence Regulation and Application to Vaccine Development

    Science.gov (United States)

    Broset, Esther

    2015-01-01

    ABSTRACT Different members of the Mycobacterium genus have evolved to cause tuberculosis in diverse human populations and in a variety of animal species. Our cumulative knowledge of mycobacterial genomes indicates that mutations in the PhoPR two-component virulence system were acquired not only during the natural evolution of mycobacterial species but also during in vitro subculture, which has given rise to the attenuated reference strain H37Ra or to different daughter strains of Mycobacterium bovis BCG. PhoPR is a well-known regulator of pathogenic phenotypes, including secretion of the virulence factor ESAT-6, biosynthesis of acyltrehalose-based lipids, and modulation of antigen export, in members of the Mycobacterium tuberculosis complex (MTBC). Evolutionarily conserved polymorphisms in PhoPR from Mycobacterium africanum, M. bovis, or M. tuberculosis H37Ra result in loss of functional phenotypes. Interestingly, some members of the MTBC have acquired compensatory mutations to counteract these polymorphisms and, probably, to maintain their pathogenic potential. Some of these compensatory mutations include the insertion of the IS6110 element upstream from phoPR in a particular M. bovis strain that is able to transmit between humans or polymorphisms in M. africanum and M. bovis that affect the regulatory region of the espACD operon, allowing PhoPR-independent ESAT-6 secretion. This review highlights the increasing knowledge of the significance of PhoPR in the evolution of the MTBC and its potential application in the construction of new attenuated vaccines based on phoPR inactivation. In this context, the live attenuated vaccine MTBVAC, based on a phoP fadD26 deletion mutant of M. tuberculosis, is the first vaccine of this kind to successfully enter into clinical development, representing a historic milestone in the field of human vaccinology. PMID:26489860

  15. Using network component analysis to dissect regulatory networks mediated by transcription factors in yeast.

    Directory of Open Access Journals (Sweden)

    Chun Ye

    2009-03-01

    Full Text Available Understanding the relationship between genetic variation and gene expression is a central question in genetics. With the availability of data from high-throughput technologies such as ChIP-Chip, expression, and genotyping arrays, we can begin to not only identify associations but to understand how genetic variations perturb the underlying transcription regulatory networks to induce differential gene expression. In this study, we describe a simple model of transcription regulation where the expression of a gene is completely characterized by two properties: the concentrations and promoter affinities of active transcription factors. We devise a method that extends Network Component Analysis (NCA to determine how genetic variations in the form of single nucleotide polymorphisms (SNPs perturb these two properties. Applying our method to a segregating population of Saccharomyces cerevisiae, we found statistically significant examples of trans-acting SNPs located in regulatory hotspots that perturb transcription factor concentrations and affinities for target promoters to cause global differential expression and cis-acting genetic variations that perturb the promoter affinities of transcription factors on a single gene to cause local differential expression. Although many genetic variations linked to gene expressions have been identified, it is not clear how they perturb the underlying regulatory networks that govern gene expression. Our work begins to fill this void by showing that many genetic variations affect the concentrations of active transcription factors in a cell and their affinities for target promoters. Understanding the effects of these perturbations can help us to paint a more complete picture of the complex landscape of transcription regulation. The software package implementing the algorithms discussed in this work is available as a MATLAB package upon request.

  16. Why Landscape Beauty Matters

    Directory of Open Access Journals (Sweden)

    Angelika Krebs

    2014-11-01

    Full Text Available This philosophical paper explores the aesthetic argument for landscape conservation. The main claim is that the experience of beautiful landscapes is an essential part of the good human life. Beautiful landscapes make us feel at home in the world. Their great and irreplaceable value lies therein. To establish this claim, the concepts of landscape and “Stimmung” are clarified. It is shown how “Stimmung” (in the sense of mood is infused into landscape (as atmosphere and how we respond to it aesthetically. We respond by resonating or feeling at home. The paper ends by indicating how art can help us to better appreciate landscape beauty. This is done by way of an example from contemporary nature poetry, Michael Donhauser’s Variationen in Prosa, which begins with “Und was da war, es nahm uns an” (“And what was there accepted us”.

  17. Selecting landscape metrics as indicators of spatial heterogeneity-A comparison among Greek landscapes

    Science.gov (United States)

    Plexida, Sofia G.; Sfougaris, Athanassios I.; Ispikoudis, Ioannis P.; Papanastasis, Vasilios P.

    2014-02-01

    This paper investigates the spatial heterogeneity of three landscapes along an altitudinal gradient and different human land use. The main aim was the identification of appropriate landscape indicators using different extents. ASTER image was used to create a land cover map consisting of three landscapes which differed in altitude and land use. A number of landscape metrics quantifying patch complexity, configuration, diversity and connectivity were derived from the thematic map at the landscape level. There were significant differences among the three landscapes regarding these four aspects of landscape heterogeneity. The analysis revealed a specific pattern of land use where lowlands are being increasingly utilized by humans (percentage of agricultural land = 65.84%) characterized by physical connectedness (high values of Patch Cohesion Index) and relatively simple geometries (low values of fractal dimension index). The landscape pattern of uplands was found to be highly diverse based upon the Shannon Diversity index. After selecting the scale (600 ha) where metrics values stabilized, it was shown that metrics were more correlated at the small scale of 60 ha. From the original 24 metrics, 14 individual metrics with high Spearman correlation coefficient and Variance Inflation Factor criterion were eliminated, leaving 10 representative metrics for subsequent analysis. Data reduction analysis showed that Patch Density, Area-Weighted Mean Fractal Dimension Index and Patch Cohesion Index are suitable to describe landscape patterns irrespective of the scale. A systematic screening of these metrics could enhance a deeper understanding of the results obtained by them and contribute to a sustainable landscape management of Mediterranean landscapes.

  18. A novel zinc finger protein Zfp277 mediates transcriptional repression of the Ink4a/arf locus through polycomb repressive complex 1

    DEFF Research Database (Denmark)

    Negishi, Masamitsu; Saraya, Atsunori; Mochizuki, Shinobu

    2010-01-01

    . METHODOLOGY/PRINCIPAL FINDINGS: We examined the function of Zinc finger domain-containing protein 277 (Zfp277), a novel zinc finger protein that interacts with the PcG protein Bmi1. Zfp277 binds to the Ink4a/Arf locus in a Bmi1-independent manner and interacts with polycomb repressor complex (PRC) 1 through...... is essential for the recruitment of PRC1 to the Ink4a/Arf locus. Our findings also highlight dynamic regulation of both Zfp277 and PcG proteins by the oxidative stress pathways....

  19. Landscape function analysis as a base of rural development strategies

    Directory of Open Access Journals (Sweden)

    Filepné Kovács Krisztina

    2017-11-01

    Full Text Available Research on ecosystem services and landscape functions are highly important in landscape ecology, landscape planning and open space design. The terms of ecosystem service and landscape function have been evolved parallel to each other in the scientific literature but have different focus. The term of landscape functions evolved from the scientific field of landscape ecology; it reflects the goods and services provided by regions, landscapes where the cultural, economic factors are important as well. As a framework assessment method with additional economic assessment, a landscape function analysis could be an additional tool of rural development, as it gives a complex analysis of multiple aspects, thus it is highly appropriate to explore, analyze the potentials, resources and limits of landscapes and land use systems. In the current research a landscape function analysis was compared with the rural development strategies in Hungarian micro-regions. We focused on the level of landscape functions and the objectives of the rural development strategies of the study areas. The local development strategies do not focus on territorial differences nor potentials evolving from natural, cultural resources or local constrains. The only exception is tourism development, where in some cases there is a holistic spatial approach which intends to develop the region as a whole.

  20. Why is a landscape perspective important in studies of primates?

    Science.gov (United States)

    Arroyo-Rodríguez, Víctor; Fahrig, Lenore

    2014-10-01

    With accelerated deforestation and fragmentation through the tropics, assessing the impact that landscape spatial changes may have on biodiversity is paramount, as this information is required to design and implement effective management and conservation plans. Primates are expected to be particularly dependent on the landscape context; yet, our understanding on this topic is limited as the majority of primate studies are at the local scale, meaning that landscape-scale inferences are not possible. To encourage primatologists to assess the impact of landscape changes on primates, and help future studies on the topic, we describe the meaning of a "landscape perspective" and evaluate important assumptions of using such a methodological approach. We also summarize a number of important, but unanswered, questions that can be addressed using a landscape-scale study design. For example, it is still unclear if habitat loss has larger consistent negative effects on primates than habitat fragmentation per se. Furthermore, interaction effects between habitat area and other landscape effects (e.g., fragmentation) are unknown for primates. We also do not know if primates are affected by synergistic interactions among factors at the landscape scale (e.g., habitat loss and diseases, habitat loss and climate change, hunting, and land-use change), or whether landscape complexity (or landscape heterogeneity) is important for primate conservation. Testing for patterns in the responses of primates to landscape change will facilitate the development of new guidelines and principles for improving primate conservation. © 2014 Wiley Periodicals, Inc.

  1. Suburban landscape assessment applied to urban planning. Case study in Barcelona Metropolitan Region

    Directory of Open Access Journals (Sweden)

    David Serrano Giné

    2015-12-01

    Full Text Available Urban fringes set complex landscapes, in transition from rural to natural and urban, with fuzzy boundaries in mutual interdependence. The European Landscape Convention gives notorious importance to everyday landscapes, including those of suburban character. Few landscape evaluation researches are done in suburban areas, which is surprising considering its importance and abundance. This paper shows a methodology, yield on geographical information systems (GIS, for landscape assessment of suburban areas, useful in urban planning. Its main interest lies in a double assessment, which considers both landscape quality and landscape fragility, applied systematically. The procedure is applied in Muntanyes d’Ordal in the metropolitan area of Barcelona (Spain, an area with pronounced regional strengths and contrasted landscape values. Results are of important applicability and indicate a predominance of mean values, both for landscape quality and landscape fragility.

  2. Beyond the conventional: meeting the challenges of landscape governance within the European Landscape Convention?

    Science.gov (United States)

    Scott, Alister

    2011-10-01

    Academics and policy makers seeking to deconstruct landscape face major challenges conceptually, methodologically and institutionally. The meaning(s), identity(ies) and management of landscape are controversial and contested. The European Landscape Convention provides an opportunity for action and change set within new governance agendas addressing interdisciplinarity and spatial planning. This paper critically reviews the complex web of conceptual and methodological frameworks that characterise landscape planning and management and then focuses on emerging landscape governance in Scotland within a mixed method approach involving policy analyses, semi-structured interviews and best practice case studies. Using Dower's (2008) criteria from the Articles of the European Landscape Convention, the results show that whilst some progress has been made in landscape policy and practice, largely through the actions of key individuals and champions, there are significant institutional hurdles and resource limitations to overcome. The need to mainstream positive landscape outcomes requires a significant culture change where a one-size-fits-all approach does not work. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Integrating landscape ecology and geoinformatics to decipher landscape dynamics for regional planning.

    Science.gov (United States)

    Dikou, Angela; Papapanagiotou, Evangelos; Troumbis, Andreas

    2011-09-01

    We used remote sensing and GIS in conjunction with multivariate statistical methods to: (i) quantify landscape composition (land cover types) and configuration (patch density, diversity, fractal dimension, contagion) for five coastal watersheds of Kalloni gulf, Lesvos Island, Greece, in 1945, 1960, 1971, 1990 and 2002/2003, (ii) evaluate the relative importance of physical (slope, geologic substrate, stream order) and human (road network, population density) variables on landscape composition and configuration, and (iii) characterize processes that led to land cover changes through land cover transitions between these five successive periods in time. Distributions of land cover types did not differ among the five time periods at the five watersheds studied because the largest cumulative changes between 1945 and 2002/2003 did not take place at dominant land cover types. Landscape composition related primarily to the physical attributes of the landscape. Nevertheless, increase in population density and the road network were found to increase heterogeneity of the landscape mosaic (patchiness), complexity of patch shape (fractal dimension), and patch disaggregation (contagion). Increase in road network was also found to increase landscape diversity due to the creation of new patches. The main processes involved in land cover changes were plough-land abandonment and ecological succession. Landscape dynamics during the last 50 years corroborate the ecotouristic-agrotouristic model for regional development to reverse trends in agricultural land abandonment and human population decline and when combined with hypothetical regulatory approaches could predict how this landscape could develop in the future, thus, providing a valuable tool to regional planning.

  4. Feedbacks in human-landscape systems

    Science.gov (United States)

    Chin, Anne

    2015-04-01

    As human interactions with Earth systems intensify in the "Anthropocene", understanding the complex relationships among human activity, landscape change, and societal responses to those changes is increasingly important. Interdisciplinary research centered on the theme of "feedbacks" in human-landscape systems serves as a promising focus for unraveling these interactions. Deciphering interacting human-landscape feedbacks extends our traditional approach of considering humans as unidirectional drivers of change. Enormous challenges exist, however, in quantifying impact-feedback loops in landscapes with significant human alterations. This paper illustrates an example of human-landscape interactions following a wildfire in Colorado (USA) that elicited feedback responses. After the 2012 Waldo Canyon Fire, concerns for heightened flood potential and debris flows associated with post-fire hydrologic changes prompted local landowners to construct tall fences at the base of a burned watershed. These actions changed the sediment transport regime and promoted further landscape change and human responses in a positive feedback cycle. The interactions ultimately increase flood and sediment hazards, rather than dampening the effects of fire. A simple agent-based model, capable of integrating social and hydro-geomorphological data, demonstrates how such interacting impacts and feedbacks could be simulated. Challenges for fully capturing human-landscape feedback interactions include the identification of diffuse and subtle feedbacks at a range of scales, the availability of data linking impact with response, the identification of multiple thresholds that trigger feedback mechanisms, and the varied metrics and data needed to represent both the physical and human systems. By collaborating with social scientists with expertise in the human causes of landscape change, as well as the human responses to those changes, geoscientists could more fully recognize and anticipate the coupled

  5. The putative Agrobacterium transcriptional activator-like virulence protein VirD5 may target T-complex to prevent the degradation of coat proteins in the plant cell nucleus.

    Science.gov (United States)

    Wang, Yafei; Peng, Wei; Zhou, Xu; Huang, Fei; Shao, Lingyun; Luo, Meizhong

    2014-09-01

    Agrobacterium exports at least five virulence proteins (VirE2, VirE3, VirF, VirD2, VirD5) into host cells and hijacks some host plant factors to facilitate its transformation process. Random DNA binding selection assays (RDSAs), electrophoretic mobility shift assays (EMSAs) and yeast one-hybrid systems were used to identify protein-bound DNA elements. Bimolecular fluorescence complementation, glutathione S-transferase pull-down and yeast two-hybrid assays were used to detect protein interactions. Protoplast transformation, coprecipitation, competitive binding and cell-free degradation assays were used to analyze the relationships among proteins. We found that Agrobacterium VirD5 exhibits transcriptional activation activity in yeast, is located in the plant cell nucleus, and forms homodimers. A specific VirD5-bound DNA element designated D5RE (VirD5 response element) was identified. VirD5 interacted directly with Arabidopsis VirE2 Interacting Protein 1 (AtVIP1). However, the ternary complex of VirD5-AtVIP1-VirE2 could be detected, whereas that of VirD5-AtVIP1-VBF (AtVIP1 Binding F-box protein) could not. We demonstrated that VirD5 competes with VBF for binding to AtVIP1 and stabilizes AtVIP1 and VirE2 in the cell-free degradation system. Our results indicated that VirD5 may act as both a transcriptional activator-like effector to regulate host gene expression and a protector preventing the coat proteins of the T-complex from being quickly degraded by the host's ubiquitin proteasome system (UPS). © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

  6. An elongated model of the Xenopus laevis transcription factor IIIA-5S ribosomal RNA complex derived from neutron scattering and hydrodynamic measurements

    International Nuclear Information System (INIS)

    Timmins, P.A.; Langowski, J.; Brown, R.S.

    1988-01-01

    The precise molecular composition of the Xenopus laevis TFIIIA-5S ribosomal RNA complex (7S particle) has been established from small angle neutron and dynamic light scattering. The molecular weight of the particle was found to be 95,700±10,000 and 86,700±9,000 daltons from these two methods respectively. The observed match point of 54.4% D 2 O obtained from contrast variation experiments indicates a 1:1 molar ratio. It is concluded that only a single molecule of TFIIIA, a zinc-finger protein, and of 5S RNA are present in this complex. A simple elongated cylindrical model with dimensions of 140 angstrom length and 59 angstrom diameter is compatible with the neutron results. A globular model can be excluded by the shallow nature of the neutron scattering curves. It is proposed that the observed difference of 15 angstrom in length between the 7S particle and isolated 5S RNA most likely indicates that part(s) of the protein protrudes from the end(s) of the RNA molecule. There is no biochemical evidence for any gross alteration in 5S RNA conformation upon binding to TFIIIA

  7. The Journey of a Transcription Factor

    DEFF Research Database (Denmark)

    Pireyre, Marie

    Plants have developed astonishing networks regulating their metabolism to adapt to their environment. The complexity of these networks is illustrated by the expansion of families of regulators such as transcription factors in the plant kingdom. Transcription factors specifically impact...... transcriptional networks by integrating exogenous and endogenous stimuli and regulating gene expression accordingly. Regulation of transcription factors and their activation is thus highly important to modulate the transcriptional programs and increase fitness of the plant in a given environment. Plant metabolism....... The biosynthetic machinery of GLS is governed by interplay of six MYB and three bHLH transcription factors. MYB28, MYB29 and MYB76 regulate methionine-derived GLS, and MYB51, MYB34 and MYB122 regulate tryptophan-derived GLS. The three bHLH transcription factors MYC2, MYC3 and MYC4 physically interact with all six...

  8. The Landscape Architecture - Between the Art of the Gardens and the Science of the Landscape Interventions

    Directory of Open Access Journals (Sweden)

    Doina-Mira Dascălu

    2005-01-01

    Full Text Available The modern landscape architecture being a profession that has an important impact on the environment, tries and succeeds to cover a very wide area. Because of its complex preoccupations area, the profession of the landscape architect may find itself in a nebula regarding the comprehension and the reaction of the public and cities mayors towards it. The landscape architecture has as purpose the realization of an ambience that is favourable to the human life progress, having in view the increasing of life’s quality and of the urban comfort, the maintenance of the ecological equilibrium. Despite the complexity of its preoccupations, the landscape architecture has been often lowered to the same level with the exclusive arrangement of green spaces.

  9. DNA exit ramps are revealed in the binding landscapes obtained from simulations in helical coordinates.

    Directory of Open Access Journals (Sweden)

    Ignacia Echeverria

    2015-02-01

    Full Text Available DNA molecules are highly charged semi-flexible polymers that are involved in a wide variety of dynamical processes such as transcription and replication. Characterizing the binding landscapes around DNA molecules is essential to understanding the energetics and kinetics of various biological processes. We present a curvilinear coordinate system that fully takes into account the helical symmetry of a DNA segment. The latter naturally allows to characterize the spatial organization and motions of ligands tracking the minor or major grooves, in a motion reminiscent of sliding. Using this approach, we performed umbrella sampling (US molecular dynamics (MD simulations to calculate the three-dimensional potentials of mean force (3D-PMFs for a Na+ cation and for methyl guanidinium, an arginine analog. The computed PMFs show that, even for small ligands, the free energy landscapes are complex. In general, energy barriers of up to ~5 kcal/mol were measured for removing the ligands from the minor groove, and of ~1.5 kcal/mol for sliding along the minor groove. We shed light on the way the minor groove geometry, defined mainly by the DNA sequence, shapes the binding landscape around DNA, providing heterogeneous environments for recognition by various ligands. For example, we identified the presence of dissociation points or "exit ramps" that naturally would terminate sliding. We discuss how our findings have important implications for understanding how proteins and ligands associate and slide along DNA.

  10. Modeling disturbance and succession in forest landscapes using LANDIS: introduction

    Science.gov (United States)

    Brian R. Sturtevant; Eric J. Gustafson; Hong S. He

    2004-01-01

    Modeling forest landscape change is challenging because it involves the interaction of a variety of factors and processes, such as climate, succession, disturbance, and management. These processes occur at various spatial and temporal scales, and the interactions can be complex on heterogeneous landscapes. Because controlled field experiments designed to investigate...

  11. Using landscape disturbance and succession models to support forest management

    Science.gov (United States)

    Eric J. Gustafson; Brian R. Sturtevant; Anatoly S. Shvidenko; Robert M. Scheller

    2010-01-01

    Managers of forested landscapes must account for multiple, interacting ecological processes operating at broad spatial and temporal scales. These interactions can be of such complexity that predictions of future forest ecosystem states are beyond the analytical capability of the human mind. Landscape disturbance and succession models (LDSM) are predictive and...

  12. Exploring component-based approaches in forest landscape modeling

    Science.gov (United States)

    H. S. He; D. R. Larsen; D. J. Mladenoff

    2002-01-01

    Forest management issues are increasingly required to be addressed in a spatial context, which has led to the development of spatially explicit forest landscape models. The numerous processes, complex spatial interactions, and diverse applications in spatial modeling make the development of forest landscape models difficult for any single research group. New...

  13. Principles of landscape architecture

    NARCIS (Netherlands)

    Nijhuis, S.

    2013-01-01

    The Department of Urbanism at the Faculty of Architecture and Built Environment, TU Delft considers urbanism as a planning and design oriented activity towards urban and rural landscapes. It aims to enhance, restore or create landscapes from a perspective of sustainable development, so as to guide,

  14. Globalization and Landscape Architecture

    OpenAIRE

    Robert R. Hewitt

    2014-01-01

    The literature review examines globalization and landscape architecture as discourse, samples its various meanings, and proposes methods to identify and contextualize its specific literature. Methodologically, the review surveys published articles and books by leading authors and within the WorldCat.org Database associated with landscape architecture and globalization, analyzing survey results for comprehensive concept...

  15. Glossary on agricultural landscapes.

    NARCIS (Netherlands)

    Kruse, A.; Centeri, C.; Renes, J.; Roth, M.; Printsman, A.; Palang, H.; Benito Jorda, M.-D.; Verlarde, M.D.; Kruckenberg, H.

    2010-01-01

    T he following glossary of terms related to the European agricultural landscape shall serve as a common basis for all parties, working in or on agricultural landscapes. Some of the terms are quite common and sometimes used in our every day language, but they often have different meanings in

  16. PSEUDO-CODEWORD LANDSCAPE

    Energy Technology Data Exchange (ETDEWEB)

    CHERTKOV, MICHAEL [Los Alamos National Laboratory; STEPANOV, MIKHAIL [Los Alamos National Laboratory

    2007-01-10

    The authors discuss performance of Low-Density-Parity-Check (LDPC) codes decoded by Linear Programming (LP) decoding at moderate and large Signal-to-Noise-Ratios (SNR). Frame-Error-Rate (FER) dependence on SNR and the noise space landscape of the coding/decoding scheme are analyzed by a combination of the previously introduced instanton/pseudo-codeword-search method and a new 'dendro' trick. To reduce complexity of the LP decoding for a code with high-degree checks, {ge} 5, they introduce its dendro-LDPC counterpart, that is the code performing identifically to the original one under Maximum-A-Posteriori (MAP) decoding but having reduced (down to three) check connectivity degree. Analyzing number of popular LDPC codes and their dendro versions performing over the Additive-White-Gaussian-Noise (AWGN) channel, they observed two qualitatively different regimes: (i) error-floor sets early, at relatively low SNR, and (ii) FER decays with SNR increase faster at moderate SNR than at the largest SNR. They explain these regimes in terms of the pseudo-codeword spectra of the codes.

  17. Statistical topography of fitness landscapes

    OpenAIRE

    Franke, Jasper

    2011-01-01

    Fitness landscapes are generalized energy landscapes that play an important conceptual role in evolutionary biology. These landscapes provide a relation between the genetic configuration of an organism and that organism’s adaptive properties. In this work, global topographical features of these fitness landscapes are investigated using theoretical models. The resulting predictions are compared to empirical landscapes. It is shown that these landscapes allow, at least with respe...

  18. Urban Landscape Perspectives

    Directory of Open Access Journals (Sweden)

    Frederick Steiner

    2014-03-01

    Full Text Available Cities present significant opportunities for new landscape perspectives that can help inform conservation and development decisions. Early in the twenty-first century, the majority of the planet’s population became urban as more people lived in city-regions for the first time in our history. As the global population increases, so does this urbanization. The environmental challenges of population and urban growth are profound. Landscapes represent a synthesis of natural and cultural processes. Cities are certainly cultural phenomena. Historically, cities provided refuge from nature. The expanding field of urban ecology, coupled with landscape ecology, can enhance how the dual natural and cultural dimensions of landscapes in cities are understood. Furthermore, concepts such as ecosystem services and green infrastructure are proving useful for urban landscape planning and design. Examples from Dayton, Ohio; Brooklyn, New York; and Austin, Texas are presented.

  19. The transcriptional landscape of age in human peripheral blood

    NARCIS (Netherlands)

    M.J. Peters (Marjolein); R. Joehanes (Roby); L.C. Pilling (Luke); C. Schurmann (Claudia); K.N. Conneely (Karen N.); J.E. Powell (Joseph); E. Reinmaa (Eva); G.L. Sutphin (George L.); A. Zhernakova (Alexandra); K. Schramm (Katharina); Y.A. Wilson (Yana A.); S. Kobes (Sayuko); T. Tukiainen (Taru); Y.F.M. Ramos (Yolande); H.H.H. Göring (Harald H.); M. Fornage (Myriam); Y. Liu (YongMei); S.A. Gharib (Sina); B.E. Stranger (Barbara); P.L. de Jager (Philip); A. Aviv (Abraham); D. Levy (Daniel); J. Murabito (Joanne); P.J. Munson (Peter J.); T. Huan (Tianxiao); A. Hofman (Albert); A.G. Uitterlinden (André); F. Rivadeneira Ramirez (Fernando); J. van Rooij (Jeroen); L. Stolk (Lisette); L. Broer (Linda); M.M.P.J. Verbiest (Michael); M. Jhamai (Mila); P.P. Arp (Pascal); A. Metspalu (Andres); L. Tserel (Liina); L. Milani (Lili); N.J. Samani (Nilesh); P. Peterson (Pärt); S. Kasela (Silva); V. Codd (Veryan); A. Peters (Annette); C.K. Ward-Caviness (Cavin K.); C. Herder (Christian); M. Waldenberger (Melanie); M. Roden (Michael); P. Singmann (Paula); S. Zeilinger (Sonja); T. Illig (Thomas); G. Homuth (Georg); H.J. Grabe (Hans Jörgen); H. Völzke (Henry); L. Steil (Leif); T. Kocher (Thomas); A. Murray (Anna); D. Melzer (David); H. Yaghootkar (Hanieh); S. Bandinelli; E.K. Moses (Eric); J.W. Kent (Jack); J.E. Curran (Joanne); M.P. Johnson (Matthew); S. Williams-Blangero (Sarah); H.J. Westra (Harm-Jan); A.F. McRae (Allan F.); J.A. Smith (Jennifer A); S.L.R. Kardia (Sharon); I. Hovatta (Iiris); M. Perola (Markus); S. Ripatti (Samuli); V. Salomaa (Veikko); A.K. Henders (Anjali); N.G. Martin (Nicholas); A.K. Smith (Alicia K.); D. Mehta (Divya); E.B. Binder (Elisabeth B.); K.M. Nylocks (K. Maria); E.M. Kennedy (Elizabeth M.); T. Klengel (Torsten); J. Ding (Jingzhong); A. Suchy-Dicey (Astrid); D. Enquobahrie; J. Brody (Jennifer); J.I. Rotter (Jerome I.); Y.-D.I. Chen (Yii-Der I.); J.J. Houwing-Duistermaat (Jeanine); M. Kloppenburg (Margreet); P.E. Slagboom (Eline); Q. Helmer (Quinta); W. den Hollander (Wouter); S. Bean (Shannon); T. Raj (Towfique); N. Bakhshi (Noman); Q.P. Wang (Qiao Ping); L.J. Oyston (Lisa J.); B.M. Psaty (Bruce); R.P. Tracy (Russell); G.W. Montgomery (Grant); S.T. Turner (Stephen); J. Blangero (John); I. Meulenbelt (Ingrid); K.J. Ressler (Kerry); J. Yang (Jian); L. Franke (Lude); J. Kettunen (Johannes); P.M. Visscher (Peter); G.G. Neely (G. Gregory); R. Korstanje (Ron); R.L. Hanson (Robert L.); H. Prokisch (Holger); L. Ferrucci (Luigi); T. Esko (Tõnu); A. Teumer (Alexander); J.B.J. van Meurs (Joyce); A.D. Johnson (Andrew D.); M.A. Nalls (Michael); D.G. Hernandez (Dena); M.R. Cookson (Mark); R.J. Gibbs (Raphael J.); J. Hardy (John); A. Ramasamy (Adaikalavan); A.B. Zonderman (Alan B.); A. Dillman (Allissa); B. Traynor (Bryan); C. Smith (Colin); D.L. Longo (Dan L.); D. Trabzuni (Danyah); J.C. Troncoso (Juan); M.P. van der Brug (Marcel); M.E. Weale (Michael); R. O'Brien (Richard); R. Johnson (Robert); R. Walker (Robert); R.H. Zielke (Ronald H.); S. Arepalli (Sampath); M. Ryten (Mina); A. Singleton

    2015-01-01

    textabstractDisease incidences increase with age, but the molecular characteristics of ageing that lead to increased disease susceptibility remain inadequately understood. Here we perform a whole-blood gene expression meta-analysis in 14,983 individuals of European ancestry (including replication)

  20. The transcriptional landscape of age in human peripheral blood

    NARCIS (Netherlands)

    Peters, Marjolein J.; Joehanes, Roby; Pilling, Luke C.; Schurmann, Claudia; Conneely, Karen N.; Powell, Joseph; Reinmaa, Eva; Sutphin, George L.; Zhernakova, Alexandra; Schramm, Katharina; Wilson, Yana A.; Kobes, Sayuko; Tukiainen, Taru; Ramos, Yolande F.; Goering, Harald H. H.; Fornage, Myriam; Liu, Yongmei; Gharib, Sina A.; Stranger, Barbara E.; De Jager, Philip L.; Aviv, Abraham; Levy, Daniel; Murabito, Joanne M.; Munson, Peter J.; Huan, Tianxiao; Hofman, Albert; Uitterlinden, Andre G.; Rivadeneira, Fernando; van Rooij, Jeroen; Stolk, Lisette; Broer, Linda; Verbiest, Michael M. P. J.; Jhamai, Mila; Arp, Pascal; Metspalu, Andres; Tserel, Liina; Milani, Lili; Samani, Nilesh J.; Peterson, Paert; Kasela, Silva; Codd, Veryan; Peters, Annette; Ward-Caviness, Cavin K.; Herder, Christian; Waldenberger, Melanie; Roden, Michael; Singmann, Paula; Zeilinger, Sonja; Westra, Harm-Jan; Franke, Lude

    2015-01-01

    Disease incidences increase with age, but the molecular characteristics of ageing that lead to increased disease susceptibility remain inadequately understood. Here we perform a whole-blood gene expression meta-analysis in 14,983 individuals of European ancestry (including replication) and identify

  1. The Transcriptional Landscape of p53 Signalling Pathway

    Directory of Open Access Journals (Sweden)

    Chizu Tanikawa

    2017-06-01

    Full Text Available Although recent cancer genomics studies have identified a large number of genes that were mutated in human cancers, p53 remains as the most frequently mutated gene. To further elucidate the p53-signalling network, we performed transcriptome analysis on 24 tissues in p53+/+ or p53−/− mice after whole-body X-ray irradiation. Here we found transactivation of a total of 3551 genes in one or more of the 24 tissues only in p53+/+ mice, while 2576 genes were downregulated. p53 mRNA expression level in each tissue was significantly associated with the number of genes upregulated by irradiation. Annotation using TCGA (The Cancer Genome Atlas database revealed that p53 negatively regulated mRNA expression of several cancer therapeutic targets or pathways such as BTK, SYK, and CTLA4 in breast cancer tissues. In addition, stomach exhibited the induction of Krt6, Krt16, and Krt17 as well as loricrin, an epidermal differentiation marker, after the X-ray irradiation only in p53+/+ mice, implying a mechanism to protect damaged tissues by rapid induction of differentiation. Our comprehensive transcriptome analysis elucidated tissue specific roles of p53 and its signalling networks in DNA-damage response that will enhance our understanding of cancer biology.

  2. The single-cell transcriptional landscape of hematopoiesis

    NARCIS (Netherlands)

    Baron, Chloé Sophie

    2018-01-01

    Hematopoietic stem cells (HSCs) are responsible for the production of all mature hematopoietic cells during the entire life of an organism. It is now known that HSCs are generated from a specific subset of endothelial cells in the main arteries of the developing mouse and zebrafish embryos. In the

  3. Novel Functions for TAF7, a Regulator of TAF1-independent Transcription

    OpenAIRE

    Devaiah, Ballachanda N.; Lu, Hanxin; Gegonne, Anne; Sercan, Zeynep; Zhang, Hongen; Clifford, Robert J.; Lee, Maxwell P.; Singer, Dinah S.

    2010-01-01

    The transcription factor TFIID components TAF7 and TAF1 regulate eukaryotic transcription initiation. TAF7 regulates transcription initiation of TAF1-dependent genes by binding to the acetyltransferase (AT) domain of TAF1 and inhibiting the enzymatic activity that is essential for transcription. TAF7 is released from the TAF1-TFIID complex upon completion of preinitiation complex assembly, allowing transcription to initiate. However, not all transcription is TAF1-dependent, and the role of TA...

  4. Modelling interactions and feedback mechanisms between land use change and landscape processes

    NARCIS (Netherlands)

    Claessens, L.; Schoorl, J.M.; Verburg, P.H.; Geraedts, L.; Veldkamp, A.

    2009-01-01

    Land use changes and landscape processes are interrelated and influenced by multiple bio-physical and socio-economic driving factors, resulting in a complex, multi-scale system. Consequently in landscapes with active landscape processes such as erosion, land use changes should not be analysed in

  5. Welfare Landscape and Communities

    DEFF Research Database (Denmark)

    Braae, Ellen Marie

    2017-01-01

    Danish housing developments of the post-war era were a cornerstone in the implementation of the welfare vision and the overall urban and landscape planning in the post-war period. The new city was a horizontal city and – as it will be my primary ambition to show – a green and landscape-like city....... The landscape came, in Denmark, to play a prominent role and became synonymous with ‘The Good Life’, but it also presented a number of moral imperatives. The article concerns how communities and community feelings found their expression in the Danish ‘welfare landscapes’....

  6. Weathering and landscape evolution

    Science.gov (United States)

    Turkington, Alice V.; Phillips, Jonathan D.; Campbell, Sean W.

    2005-04-01

    In recognition of the fundamental control exerted by weathering on landscape evolution and topographic development, the 35th Binghamton Geomorphology Symposium was convened under the theme of Weathering and Landscape Evolution. The papers and posters presented at the conference imparted the state-of-the-art in weathering geomorphology, tackled the issue of scale linkage in geomorphic studies and offered a vehicle for interdisciplinary communication on research into weathering and landscape evolution. The papers included in this special issue are encapsulated here under the general themes of weathering mantles, weathering and relative dating, weathering and denudation, weathering processes and controls and the 'big picture'.

  7. DNA topology and transcription

    Science.gov (United States)

    Kouzine, Fedor; Levens, David; Baranello, Laura

    2014-01-01

    Chromatin is a complex assembly that compacts DNA inside the nucleus while providing the necessary level of accessibility to regulatory factors conscripted by cellular signaling systems. In this superstructure, DNA is the subject of mechanical forces applied by variety of molecular motors. Rather than being a rigid stick, DNA possesses dynamic structural variability that could be harnessed during critical steps of genome functioning. The strong relationship between DNA structure and key genomic processes necessitates the study of physical constrains acting on the double helix. Here we provide insight into the source, dynamics, and biology of DNA topological domains in the eukaryotic cells and summarize their possible involvement in gene transcription. We emphasize recent studies that might inspire and impact future experiments on the involvement of DNA topology in cellular functions. PMID:24755522

  8. Landscape metrics application in ecological and visual landscape assessment

    Directory of Open Access Journals (Sweden)

    Gavrilović Suzana

    2017-01-01

    Full Text Available The development of landscape-ecological approach application in spatial planning provides exact theoretical and empirical evidence for monitoring ecological consequences of natural and/or anthropogenic factors, particularly changes in spatial structures caused by them. Landscape pattern which feature diverse landscape values is the holder of the unique landscape character at different spatial levels and represents a perceptual domain for its users. Using the landscape metrics, the parameters of landscape composition and configuration are mathematical algorithms that quantify the specific spatial characteristics used for interpretation of landscape features and processes (physical and ecological aspect, as well as forms (visual aspect and the meaning (cognitive aspect of the landscape. Landscape metrics has been applied mostly in the ecological and biodiversity assessments as well as in the determination of the level of structural change of landscape, but more and more applied in the assessment of the visual character of the landscape. Based on a review of relevant literature, the aim of this work is to show the main trends of landscape metrics within the aspect of ecological and visual assessments. The research methodology is based on the analysis, classification and systematization of the research studies published from 2000 to 2016, where the landscape metrics is applied: (1 the analysis of landscape pattern and its changes, (2 the analysis of biodiversity and habitat function and (3 a visual landscape assessment. By selecting representative metric parameters for the landscape composition and configuration, for each category is formed the basis for further landscape metrics research and application for the integrated ecological and visual assessment of the landscape values. Contemporary conceptualization of the landscape is seen holistically, and the future research should be directed towards the development of integrated landscape assessment

  9. Landscape genetics and limiting factors

    Science.gov (United States)

    Samuel A. Cushman; Andrew J. Shirk; Erin L. Landguth

    2013-01-01

    Population connectivity is mediated by the movement of organisms or propagules through landscapes. However, little is known about how variation in the pattern of landscape mosaics affects the detectability of landscape genetic relationships. The goal of this paper is to explore the impacts of limiting factors on landscape genetic processes using simulation...

  10. PNW Hydrologic Landscape Class

    Data.gov (United States)

    U.S. Environmental Protection Agency — Work has been done to expand the hydrologic landscapes (HLs) concept and to develop an approach for using it to address streamflow vulnerability from climate change....

  11. Exploring Energy Landscapes

    Science.gov (United States)

    Wales, David J.

    2018-04-01

    Recent advances in the potential energy landscapes approach are highlighted, including both theoretical and computational contributions. Treating the high dimensionality of molecular and condensed matter systems of contemporary interest is important for understanding how emergent properties are encoded in the landscape and for calculating these properties while faithfully representing barriers between different morphologies. The pathways characterized in full dimensionality, which are used to construct kinetic transition networks, may prove useful in guiding such calculations. The energy landscape perspective has also produced new procedures for structure prediction and analysis of thermodynamic properties. Basin-hopping global optimization, with alternative acceptance criteria and generalizations to multiple metric spaces, has been used to treat systems ranging from biomolecules to nanoalloy clusters and condensed matter. This review also illustrates how all this methodology, developed in the context of chemical physics, can be transferred to landscapes defined by cost functions associated with machine learning.

  12. Digital landscapes of imagination

    OpenAIRE

    Starlight Vattano

    2014-01-01

    Urban landscapes that exist in the expression of an imaginative sequence define their shape through the digital representation. These hyperreal dimensions, combine imagination and representation as constituents a new reality, which follows the utopian, suprematist and constructivist theories, where the two-dimensional dynamics is transformed into an infinite space in which the imagination creates new forms. Although interpretations of the urban landscape film, put in place a correspondence be...

  13. The shifting beverage landscape.

    Science.gov (United States)

    Storey, Maureen

    2010-04-26

    STOREY, M.L. The shifting beverage landscape. PHYSIOL BEHAV, 2010. - Simultaneous lifestyle changes have occurred in the last few decades, creating an imbalance in energy intake and energy expenditure that has led to overweight and obesity. Trends in the food supply show that total daily calories available per capita increased 28% since 1970. Total energy intake among men and women has also increased dramatically since that time. Some have suggested that intake of beverages has had a disproportional impact on obesity. Data collected by the Beverage Marketing Corporation between 1988-2008 demonstrate that, in reality, fewer calories per ounce are being produced by the beverage industry. Moreover, data from the National Cancer Institute show that soft drink intake represents 5.5% of daily calories. Data from NHANES 1999-2003 vs. 2003-06 may demonstrate a shift in beverage consumption for age/gender groups, ages 6 to>60years. The beverages provided in schools have significantly changed since 2006 when the beverage industry implemented School Beverage Guidelines. This voluntary action has removed full-calorie soft drinks from participating schools across the country. This shift to lower-calorie and smaller-portion beverages in school has led to a significant decrease in total beverage calories in schools. These data support the concept that to prevent and treat obesity, public health efforts should focus on energy balance and that a narrow focus on sweetened beverages is unlikely to have any meaningful impact on this complex problem. Copyright 2010 Elsevier Inc. All rights reserved.

  14. Development of a PCR-RFLP method based on the transcription elongation factor 1-α gene to differentiate Fusarium graminearum from other species within the Fusarium graminearum species complex.

    Science.gov (United States)

    Garmendia, Gabriela; Umpierrez-Failache, Mariana; Ward, Todd J; Vero, Silvana

    2018-04-01

    Fusarium head blight (FHB) is a destructive disease of cereals crops worldwide and a major food safety concern due to grain contamination with trichothecenes and other mycotoxins. Fusarium graminearum, a member of the Fusarium graminearum species complex (FGSC) is the dominant FHB pathogen in many parts of the world. However, a number of other Fusarium species, including other members of the FGSC, may also be present for example in Argentina, New Zealand, Ethiopia, Nepal, Unites States in cereals such as wheat and barley. Proper species identification is critical to research aimed at improving disease and mycotoxin control programs. Identification of Fusarium species is are often unreliable by traditional, as many species are morphologically cryptic. DNA sequence-based methods offer a reliable means of species identification, but can be expensive when applied to the analyses of population samples. To facilitate identification of the major causative agent of FHB, this work describes an easy and inexpensive method to differentiate F. graminearum from the remaining species within the FGSC and from the other common Fusarium species causing FHB in cereals. The developed method is based on a PCR-RFLP of the transcription elongation factor (TEF 1-α) gene using the restriction enzyme BsaHI. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Assessment of hazards and risks for landscape protection planning in Sicily.

    Science.gov (United States)

    La Rosa, Daniele; Martinico, Francesco

    2013-09-01

    Landscape protection planning is a complex task that requires an integrated assessment and involves heterogeneous issues. These issues include not only the management of a considerable amount of data to describe landscape features but also the choice of appropriate tools to evaluate the hazards and risks. The landscape assessment phase can provide fundamental information for the definition of a Landscape Protection Plan, in which the selection of norms for protection or rehabilitation is strictly related to hazards, values and risks that are found. This paper describes a landscape assessment methodology conducted by using GIS, concerning landscape hazards, values and risk. Four hazard categories are introduced and assessed concerning urban sprawl and erosion: landscape transformations by new planned developments, intensification of urban sprawl patterns, loss of agriculture land and erosion. Landscape value is evaluated by using different thematic layers overlaid with GIS geoprocessing. The risk of loss of landscape value is evaluated, with reference to the potential occurrence of the previously assessed hazards. The case study is the Province of Enna (Sicily), where landscape protection is a relevant issue because of the importance of cultural and natural heritage. Results show that high value landscape features have a low risk of loss of landscape value. For this reason, landscape protection policies assume a relevant role in landscapes with low-medium values and they should be addressed to control the urban sprawl processes that are beginning in the area. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Control landscapes for observable preparation with open quantum systems

    International Nuclear Information System (INIS)

    Wu Rebing; Pechen, Alexander; Rabitz, Herschel; Hsieh, Michael; Tsou, Benjamin

    2008-01-01

    A quantum control landscape is defined as the observable as a function(al) of the system control variables. Such landscapes were introduced to provide a basis to understand the increasing number of successful experiments controlling quantum dynamics phenomena. This paper extends the concept to encompass the broader context of the environment having an influence. For the case that the open system dynamics are fully controllable, it is shown that the control landscape for open systems can be lifted to the analysis of an equivalent auxiliary landscape of a closed composite system that contains the environmental interactions. This inherent connection can be analyzed to provide relevant information about the topology of the original open system landscape. Application to the optimization of an observable expectation value reveals the same landscape simplicity observed in former studies on closed systems. In particular, no false suboptimal traps exist in the system control landscape when seeking to optimize an observable, even in the presence of complex environments. Moreover, a quantitative study of the control landscape of a system interacting with a thermal environment shows that the enhanced controllability attainable with open dynamics significantly broadens the range of the achievable observable values over the control landscape

  17. Introduction: Enquiries into Contemporary Ritual Landscapes

    Directory of Open Access Journals (Sweden)

    Pirjo Kristiina Virtanen

    2017-06-01

    Full Text Available ‘Landscape’ and ‘ritual’ have been largely discussed in the social and human sciences, although their inter-relatedness has gained li le scholarly a ention. Drawing on earlier studies of ritual and landscape, as well as the authors’ own ethnographic works, ‘ritual landscape’ is suggested here as a useful analytical tool with which to understand how landscapes are produced, and how they, in their turn, produce certain types of being. ‘Ritual landscape’ recognises di erent modalities of agency, power-relation, knowledge, emotion, and movement. The article shows how the subjectivity of other-than-human beings such as ancestors, earth formations, land, animals, plants and, in general, materiality of ritual contexts, shape landscapes. We argue that ways of perceiving landscape includes a number of material and immaterial aspects indicated by ways of moving through landscapes and interacting with di erent human and non-human subjects that come to inhabit the world, creating relations and producing agentive ensembles and complexes.

  18. Population growth, demographic change, and cultural landscapes.

    Science.gov (United States)

    Woodgate, G; Sage, C

    1994-01-01

    The inclusion of both ecological and socioeconomic components within landscapes makes possible the perception of the hierarchical character of landscape organization. A research approach is needed to conceptualize cultural landscapes as the product of interaction between society and nature. Richard Norgaard's 1984 paper on coevolutionary agricultural development attempts to meet this challenge. Coevolution is the interactive synthesis of natural and social mechanisms of change that characterize the relationship between social systems and ecosystems. The relationship between population, consumption, and environmental changes is complex. Currently industrialized countries present the biggest threat to global environmental resources. The issue of carrying capacity is the corollary of population and the environment. It is primarily the technological factor rather than population that needs to be controlled. The relationship between rich and poor countries is determined by superior economic power. An analysis of landscape change is made, tracing the coevolution of society and environment from the end of the feudal era and making comparisons with continental Europe. Over the years since 1945 the need to realize potential economies of scale has resulted in a wholesale loss of woodlands, hedgerows, and small ponds in the UK. In a global context the likely impacts of population growth and demographic change on landscapes will be influenced by such socioeconomic factors as technology and affluence; policies that ignore cause and effect; and the traditional tendency to treat the environment as a waste repository and a supply depot.

  19. New infrastructures, new landscapes

    Directory of Open Access Journals (Sweden)

    Chiara Nifosì

    2014-06-01

    Full Text Available New infrastructures, new landscapes AbstractThe paper will discuss one recent Italian project that share a common background: the relevance of the existing maritime landscape as a non negotiable value. The studies will be discussed in details a feasibility study for the new port in Monfalcone. National infrastructural policies emphasize competitiveness and connection as a central issue incultural, economic and political development of communities . Based on networks and system development along passageways that make up the European infrastructural armor; the two are considered at the meantime as cause and effect of "territorialisation”. These two views are obviously mutually dependent. It's hard to think about a strong attractiveness out of the network, and to be part of the latter encourages competitiveness. Nonetheless this has proved to be conflictual when landscape values and the related attractiveness are considered.The presented case study project, is pursuing the ambition to promote a new approach in realizing large infrastructures; its double role is to improve connectivity and to generate lasting and positive impact on the local regions. It deal with issues of inter-modality and the construction of nodes and lines which connects Europe, and its markets.Reverting the usual approach which consider landscape project as as a way to mitigate or to compensate for the infrastructure, the goal is to succeed in realizing large infrastructural works by conceiving them as an occasion to reinterpret a region or, as extraordinary opportunities, to build new landscapes.The strategy proposed consists in achieving structural images based on the reinforcement of the environmental and historical-landscape systems. Starting from the reinterpretation of local maritime context and resources it is possible not just to preserve the attractiveness of a specific landscape but also to conceive infrastructure in a more efficient way. 

  20. European landscape architecture and territorial strategies for water landscapes

    DEFF Research Database (Denmark)

    Diedrich, Lisa Babette

    2010-01-01

    This article sums up the author’s lecture at the 2009 Sydney Resilient Water Landscapes Symposium and presents a series of realized or planned European landscape architectural and urbanistic projects on water landscapes taken from the recently published book On Site/ Landscape Architecture Europe...... and accompanying reflections. The hypothesis is that further scientific research can help defining weaknesses and strengths of the existing water landscape designs in terms of resilience, extract principles and tools, improve the weak ones and communicate the strong ones and develop general quality criteria...... and tools for future resilient water landscapes....

  1. Geomorpho-Landscapes

    Science.gov (United States)

    Farabollini, Piero; Lugeri, Francesca; Amadio, Vittorio

    2014-05-01

    Landscape is the object of human perceptions, being the image of spatial organization of elements and structures: mankind lives the first approach with the environment, viewing and feeling the landscape. Many definitions of landscape have been given over time: in this case we refer to the Landscape defined as the result of interaction among physical, biotic and anthropic phenomena acting in a different spatial-temporal scale (Foreman & Godron) Following an Aristotelic approach in studying nature, we can assert that " Shape is synthesis": so it is possible to read the land features as the expression of the endogenous and exogenous processes that mould earth surfaces; moreover, Landscape is the result of the interaction of natural and cultural components, and conditions the spatial-temporal development of a region. The study of the Landscape offers results useful in order to promote sustainable development, ecotourism, enhancement of natural and cultural heritage, popularization of the scientific knowledge. In Italy, a very important GIS-based tool to represent the territory is the "Carta della Natura" ("Map of Nature", presently coordinated by the ISPRA) that aims at assessing the state of the whole Italian territory, analyzing Landscape. The methodology follows a holistic approach, taking into consideration all the components of a landscape and then integrating the information. Each individual landscape, studied at different scales, shows distinctive elements: structural, which depend on physical form and specific spatial organization; functional, which depend on relationships created between biotic and abiotic elements, and dynamic, which depend on the successive evolution of the structure. The identification of the landscape units, recognized at different scales of analysis, allows an evaluation of the state of the land, referring to the dual risk/resource which characterizes the Italian country. An interesting opportunity is to discover those areas of unusual

  2. Globalization and Landscape Architecture

    Directory of Open Access Journals (Sweden)

    Robert R. Hewitt

    2014-02-01

    Full Text Available The literature review examines globalization and landscape architecture as discourse, samples its various meanings, and proposes methods to identify and contextualize its specific literature. Methodologically, the review surveys published articles and books by leading authors and within the WorldCat.org Database associated with landscape architecture and globalization, analyzing survey results for comprehensive conceptual and co-relational frameworks. Three “higher order” dimensions frame the review’s conceptual organization, facilitating the organization of subordinate/subtopical areas of interest useful for comparative analysis. Comparative analysis of the literature suggests an uneven clustering of discipline-related subject matter across the literature’s “higher order” dimensions, with a much smaller body of literature related to landscape architecture confined primarily to topics associated with the dispersion of global phenomena. A subcomponent of this smaller body of literature is associated with other fields of study, but inferentially related to landscape architecture. The review offers separate references and bibliographies for globalization literature in general and globalization and landscape architecture literature, specifically.

  3. Using graph approach for managing connectivity in integrative landscape modelling

    Science.gov (United States)

    Rabotin, Michael; Fabre, Jean-Christophe; Libres, Aline; Lagacherie, Philippe; Crevoisier, David; Moussa, Roger

    2013-04-01

    In cultivated landscapes, a lot of landscape elements such as field boundaries, ditches or banks strongly impact water flows, mass and energy fluxes. At the watershed scale, these impacts are strongly conditionned by the connectivity of these landscape elements. An accurate representation of these elements and of their complex spatial arrangements is therefore of great importance for modelling and predicting these impacts.We developped in the framework of the OpenFLUID platform (Software Environment for Modelling Fluxes in Landscapes) a digital landscape representation that takes into account the spatial variabilities and connectivities of diverse landscape elements through the application of the graph theory concepts. The proposed landscape representation consider spatial units connected together to represent the flux exchanges or any other information exchanges. Each spatial unit of the landscape is represented as a node of a graph and relations between units as graph connections. The connections are of two types - parent-child connection and up/downstream connection - which allows OpenFLUID to handle hierarchical graphs. Connections can also carry informations and graph evolution during simulation is possible (connections or elements modifications). This graph approach allows a better genericity on landscape representation, a management of complex connections and facilitate development of new landscape representation algorithms. Graph management is fully operational in OpenFLUID for developers or modelers ; and several graph tools are available such as graph traversal algorithms or graph displays. Graph representation can be managed i) manually by the user (for example in simple catchments) through XML-based files in easily editable and readable format or ii) by using methods of the OpenFLUID-landr library which is an OpenFLUID library relying on common open-source spatial libraries (ogr vector, geos topologic vector and gdal raster libraries). Open

  4. Networks and landscapes: a framework for setting goals and evaluating performance at the large landscape scale

    Science.gov (United States)

    R Patrick Bixler; Shawn Johnson; Kirk Emerson; Tina Nabatchi; Melly Reuling; Charles Curtin; Michele Romolini; Morgan Grove

    2016-01-01

    The objective of large landscape conser vation is to mitigate complex ecological problems through interventions at multiple and overlapping scales. Implementation requires coordination among a diverse network of individuals and organizations to integrate local-scale conservation activities with broad-scale goals. This requires an understanding of the governance options...

  5. Comprehensive epigenetic landscape of rheumatoid arthritis fibroblast-like synoviocytes.

    Science.gov (United States)

    Ai, Rizi; Laragione, Teresina; Hammaker, Deepa; Boyle, David L; Wildberg, Andre; Maeshima, Keisuke; Palescandolo, Emanuele; Krishna, Vinod; Pocalyko, David; Whitaker, John W; Bai, Yuchen; Nagpal, Sunil; Bachman, Kurtis E; Ainsworth, Richard I; Wang, Mengchi; Ding, Bo; Gulko, Percio S; Wang, Wei; Firestein, Gary S

    2018-05-15

    Epigenetics contributes to the pathogenesis of immune-mediated diseases like rheumatoid arthritis (RA). Here we show the first comprehensive epigenomic characterization of RA fibroblast-like synoviocytes (FLS), including histone modifications (H3K27ac, H3K4me1, H3K4me3, H3K36me3, H3K27me3, and H3K9me3), open chromatin, RNA expression and whole-genome DNA methylation. To address complex multidimensional relationship and reveal epigenetic regulation of RA, we perform integrative analyses using a novel unbiased method to identify genomic regions with similar profiles. Epigenomically similar regions exist in RA cells and are associated with active enhancers and promoters and specific transcription factor binding motifs. Differentially marked genes are enriched for immunological and unexpected pathways, with "Huntington's Disease Signaling" identified as particularly prominent. We validate the relevance of this pathway to RA by showing that Huntingtin-interacting protein-1 regulates FLS invasion into matrix. This work establishes a high-resolution epigenomic landscape of RA and demonstrates the potential for integrative analyses to identify unanticipated therapeutic targets.

  6. Analysis of sea use landscape pattern based on GIS: a case study in Huludao, China.

    Science.gov (United States)

    Suo, Anning; Wang, Chen; Zhang, Minghui

    2016-01-01

    This study aims to analyse sea use landscape patterns on a regional scale based on methods of landscape ecology integrated with sea use spatial characteristics. Several landscape-level analysis indices, such as the dominance index, complex index, intensivity index, diversity index and sea congruency index, were established using Geographic Information System (GIS) and applied in Huludao, China. The results indicated that sea use landscape analysis indices, which were created based on the characteristics of sea use spatial patterns using GIS, are suitable to quantitatively describe the landscape patterns of sea use. They are operable tools for the landscape analysis of sea use. The sea use landscape in Huludao was dominated by fishing use with a landscape dominance index of 0.724. The sea use landscape is a complex mosaic with high diversity and plenty of fishing areas, as shown by the landscape complex index of 27.21 and the landscape diversity index of 1.25. Most sea use patches correspond to the marine functional zonation plan and the sea use congruency index is 0.89 in the fishing zone and 0.92 in the transportation zone.

  7. Nuclear stability and transcriptional directionality separate functionally distinct RNA species

    DEFF Research Database (Denmark)

    Andersson, Robin; Refsing Andersen, Peter; Valen, Eivind

    2014-01-01

    Mammalian genomes are pervasively transcribed, yielding a complex transcriptome with high variability in composition and cellular abundance. Although recent efforts have identified thousands of new long non-coding (lnc) RNAs and demonstrated a complex transcriptional repertoire produced by protei...

  8. Qualifying Urban Landscapes

    DEFF Research Database (Denmark)

    Clemmensen, Thomas Juel; Nielsen, Tom; Daugaard, Morten

    2010-01-01

    The article presents an attempt to develop alternatives to the dominant planning and design principles used in building and rebuilding the contemporary urban landscape. The basic idea is that the ‘forces of modernisation’ driving current development might result in a broader and more interesting...... for contemporary urban landscape design practice....... to the task of constructing and improving things. With this goal, a set of objectives based in important insights from recent urban theory are formulated constituting the normative spine of the analysis of a number of found situations as basis for formulating eight generic concepts of qualification...

  9. Digital landscapes of imagination

    Directory of Open Access Journals (Sweden)

    Starlight Vattano

    2014-05-01

    Full Text Available Urban landscapes that exist in the expression of an imaginative sequence define their shape through the digital representation. These hyperreal dimensions, combine imagination and representation as constituents a new reality, which follows the utopian, suprematist and constructivist theories, where the two-dimensional dynamics is transformed into an infinite space in which the imagination creates new forms. Although interpretations of the urban landscape film, put in place a correspondence between reality and virtuality, into the modeling of spatial movements, from which do not arise contraries, but only interdependencies. It is a particular type of representation that takes shape via the digital in motion and provides new tools for urban representation.

  10. Imagine A Collective Landscape

    Directory of Open Access Journals (Sweden)

    Manuela Silvia Campanini

    2010-03-01

    Full Text Available Iceland plays a key role in the circumpolar context. The research investigates the fields of both the icelandic cultural landscape perception and the icelandic cultural identity. It considers the book Ultima thule; or, a summer in Iceland and Ólafur Elíasson art works as two sides of a same medal: the Iceland on the brain concept (F. Burton. The transition from a cultural identity to a collective landscape identity is investigated analysing Imagine J. Lennon's song which inspired Yõko Ono's work art titled Imagine Peace Tower.

  11. Introduction to Ecological Landscaping: A Holistic Description and Framework to Guide the Study and Management of Urban Landscape Parcels

    Directory of Open Access Journals (Sweden)

    Parwinder Grewal

    2008-01-01

    Full Text Available Urbanized ecosystems and urban human populations are expanding around the world causing many negative environmental effects. A challenge for achieving sustainable urban social-ecological systems is understanding how urbanized landscapes can be designed and managed to minimize negative outcomes. To this end, an interdisciplinary Ecological Landscaping conference was organized to examine the interacting sociocultural and ecological causes and consequences of landscaping practices and products. This special issue of Cities and the Environment contains a diverse set of articles arising from that conference. In this introductory paper, we describe the meaning of ecological landscaping and a new conceptual framework that helps organize the topic’s complex issues. The essence of ecological landscaping is a holistic systems-thinking perspective for understanding the interrelationships among physical-ecological and sociocultural variables that give rise to the patterns and processes of biodiversity, abiotic conditions, and ecosystem processes within and among individually-managed urban landscape parcels. This perspective suggests that 1 variables not considered part of traditional landscaping and 2 the effects of landscaping within an individual parcel on variables outside of it must both be considered when making design and management decisions about a parcel. To illustrate how these points help create a more holistic, ecological approach to landscaping, a traditional ecosystem model is used to create a framework for discussing how sociocultural and physical-ecological inputs to a landscape parcel affect its characteristics and outputs. As exemplified by papers in this issue, an integrated sociocultural-ecological approach to the study of urban landscaping practices and products is needed to 1 understand why and how humans design and mange urban landscape parcels, 2 describe how the combined characteristics and outputs of many parcels give rise to the

  12. Widespread anti-sense transcription in apple is correlated with siRNA production and indicates a large potential for transcriptional and/or post-transcriptional control.

    Science.gov (United States)

    Celton, Jean-Marc; Gaillard, Sylvain; Bruneau, Maryline; Pelletier, Sandra; Aubourg, Sébastien; Martin-Magniette, Marie-Laure; Navarro, Lionel; Laurens, François; Renou, Jean-Pierre

    2014-07-01

    Characterizing the transcriptome of eukaryotic organisms is essential for studying gene regulation and its impact on phenotype. The realization that anti-sense (AS) and noncoding RNA transcription is pervasive in many genomes has emphasized our limited understanding of gene transcription and post-transcriptional regulation. Numerous mechanisms including convergent transcription, anti-correlated expression of sense and AS transcripts, and RNAi remain ill-defined. Here, we have combined microarray analysis and high-throughput sequencing of small RNAs (sRNAs) to unravel the complexity of transcriptional and potential post-transcriptional regulation in eight organs of apple (Malus × domestica). The percentage of AS transcript expression is higher than that identified in annual plants such as rice and Arabidopsis thaliana. Furthermore, we show that a majority of AS transcripts are transcribed beyond 3'UTR regions, and may cover a significant portion of the predicted sense transcripts. Finally we demonstrate at a genome-wide scale that anti-sense transcript expression is correlated with the presence of both short (21-23 nt) and long (> 30 nt) siRNAs, and that the sRNA coverage depth varies with the level of AS transcript expression. Our study provides a new insight on the functional role of anti-sense transcripts at the genome-wide level, and a new basis for the understanding of sRNA biogenesis in plants. © 2014 INRA. New Phytologist © 2014 New Phytologist Trust.

  13. Transcriptional Waves in the Yeast Cell Cycle

    OpenAIRE

    Oliva, Anna; Rosebrock, Adam; Ferrezuelo, Francisco; Pyne, Saumyadipta; Chen, Haiying; Skiena, Steve; Futcher, Bruce; Leatherwood, Janet

    2005-01-01

    Many genes are regulated as an innate part of the eukaryotic cell cycle, and a complex transcriptional network helps enable the cyclic behavior of dividing cells. This transcriptional network has been studied in Saccharomyces cerevisiae (budding yeast) and elsewhere. To provide more perspective on these regulatory mechanisms, we have used microarrays to measure gene expression through the cell cycle of Schizosaccharomyces pombe (fission yeast). The 750 genes with the most significant oscillat...

  14. Selecting Landscape Plants: Shade Trees

    OpenAIRE

    Relf, Diane; Appleton, Bonnie Lee, 1948-2012; Close, David

    2015-01-01

    Because of the permanency of trees and their importance in the landscape, care must be taken to select the best species for each situation. This publication goes over how to choose landscape trees that are shade tolerant.

  15. The landscape context of cereal aphid–parasitoid interactions

    Science.gov (United States)

    Thies, Carsten; Roschewitz, Indra; Tscharntke, Teja

    2005-01-01

    Analyses at multiple spatial scales may show how important ecosystem services such as biological control are determined by processes acting on the landscape scale. We examined cereal aphid–parasitoid interactions in wheat fields in agricultural landscapes differing in structural complexity (32–100% arable land). Complex landscapes were associated with increased aphid mortality resulting from parasitism, but also with higher aphid colonization, thereby counterbalancing possible biological control by parasitoids and lastly resulting in similar aphid densities across landscapes. Thus, undisturbed perennial habitats appeared to enhance both pests and natural enemies. Analyses at multiple spatial scales (landscape sectors of 0.5–6 km diameter) showed that correlations between parasitism and percentage of arable land were significant at scales of 0.5–2 km, whereas aphid densities responded to percentage of arable land at scales of 1–6 km diameter. Hence, the higher trophic level populations appeared to be determined by smaller landscape sectors owing to dispersal limitation, showing the ‘functional spatial scale’ for species-specific landscape management. PMID:15695212

  16. Qualifying Urban Landscapes

    DEFF Research Database (Denmark)

    Juel Clemmensen, Thomas; Daugaard, Morten; Nielsen, Tom

    This paper is based on a research project aimed at contributing to the qualification of the aesthetical value of the contemporary urban landscape. We see our work as part of a tradition within the architectural profession of making explorative projects, which combines analysis of the contemporary...

  17. A landscape analysis plan

    Science.gov (United States)

    Nancy E. Fleenor

    2002-01-01

    A Landscape Analysis Plan (LAP) sets out broad guidelines for project development within boundaries of the Kings River Sustainable Forest Ecosystems Project. The plan must be a dynamic, living document, subject to change as new information arises over the course of this very long-term project (several decades). Two watersheds, each of 32,000 acres, were dedicated to...

  18. Ecology, recreation and landscape

    Energy Technology Data Exchange (ETDEWEB)

    Satchell, J E

    1983-01-01

    The article is dedicated to the problems of combining mass tourism in certain countries of Western Europe and environmental protection (OOS) requirements. The ecological damage from recreation is examined and the throughput of the medium is evaluated. The author proposes development of regulable, managable and controllable recreation use of natural resources and landscapes using selective advertising of the recreation sites.

  19. Landscape Planning of Schoolyards

    Science.gov (United States)

    Kopeva, A.; Khrapko, O.; Ivanova, O.

    2017-11-01

    The optimal landscape architecture planning of schoolyards allows for creation of favorable conditions for children personal development and physical fitness. The key principles of schoolyard landscape planning, same as for other areas intended for children, are as follows: establishment of a favorable microclimate, safety, aesthetic and educational environment. Green spaces play an essential role in this respect as they are essential to sanitary, hygienic, structural, and spatial planning performing decorative, artistic, cognitive, and educational functions in these areas. Various types of landscape plantings are used in school areas: borders, lawns, beds, vines, ornamental arrangements, and various potted plants. Children’s safety is the key principle when selecting a landscape design type and the plants’ range. Any allergenic, poisonous, thorny, strong-smelling or life-threatening plants are excluded. Plants on school grounds can serve as visual aids for studies. Drought-resistant, attractive, colorful, abundantly blooming plants with variable leaf texture are preferred. Ornamental trees and shrubs as well as perennials and annuals provide a broad plant range for school grounds.

  20. Landscape Assessment (LA)

    Science.gov (United States)

    Carl H. Key; Nathan C. Benson

    2006-01-01

    Landscape Assessment primarily addresses the need to identify and quantify fire effects over large areas, at times involving many burns. In contrast to individual case studies, the ability to compare results is emphasized along with the capacity to aggregate information across broad regions and over time. Results show the spatial heterogeneity of burns and how fire...

  1. Landscapes in transition

    NARCIS (Netherlands)

    Padfield, Rory; Drew, Simon; Syayuti, Khadijah; Page, Susan; Evers, Stephanie; Campos-Arceiz, Ahimsa; Kangayatkarasu, Nagulendran; Sayok, Alex; Hansen, Sune; Schouten, Greetje; Maulidia, Martha; Papargyropoulou, Effie; Tham, Mun Hou

    2016-01-01

    The recent Southeast Asian haze crisis has generated intense public scrutiny over the rate, methods and types of landscape change in the tropics. Debate has centred on the environmental impacts of large-scale agricultural expansion, particularly the associated loss of high carbon stock forest and

  2. Integration Research for Shaping Sustainable Regional Landscapes

    Directory of Open Access Journals (Sweden)

    David J. Brunckhorst

    2005-01-01

    Full Text Available Ecological and social systems are complex and entwined. Complex social-ecological systems interact in a multitude of ways at many spatial scales across time. Their interactions can contribute both positive and negative consequences in terms of sustainability and the context in which they exist affecting future landscape change. Non-metropolitan landscapes are the major theatre of interactions where large-scale alteration occurs precipitated by local to global forces of economic, social, and environmental change. Such regional landscape effects are critical also to local natural resource and social sustainability. The institutions contributing pressures and responses consequently shape future landscapes and in turn influence how social systems, resource users, governments, and policy makers perceive those landscapes and their future. Science and policy for “sustainable” futures need to be integrated at the applied “on-ground” level where products and effects of system interactions are fully included, even if unobserved. Government agencies and funding bodies often consider such research as “high-risk.” This paper provides some examples of interdisciplinary research that has provided a level of holistic integration through close engagement with landholders and communities or through deliberately implementing integrative and innovative on-ground experimental models. In retrospect, such projects have to some degree integrated through spatial (if not temporal synthesis, policy analysis, and (new or changed institutional arrangements that are relevant locally and acceptable in business, as well as at broader levels of government and geography. This has provided transferable outcomes that can contribute real options and adaptive capacity for suitable positive futures.

  3. WRKY transcription factors

    Science.gov (United States)

    Bakshi, Madhunita; Oelmüller, Ralf

    2014-01-01

    WRKY transcription factors are one of the largest families of transcriptional regulators found exclusively in plants. They have diverse biological functions in plant disease resistance, abiotic stress responses, nutrient deprivation, senescence, seed and trichome development, embryogenesis, as well as additional developmental and hormone-controlled processes. WRKYs can act as transcriptional activators or repressors, in various homo- and heterodimer combinations. Here we review recent progress on the function of WRKY transcription factors in Arabidopsis and other plant species such as rice, potato, and parsley, with a special focus on abiotic, developmental, and hormone-regulated processes. PMID:24492469

  4. Landscape Evolution Modelling-LAPSUS

    Energy Technology Data Exchange (ETDEWEB)

    Baartman, J. E. M.; Temme, A. J. A. M.; Schoorl, J. M.; Claessens, L.; Viveen, W.; Gorp, W. van; Veldkamp, A.

    2009-07-01

    Landscape evolution modelling can make the consequences of landscape evolution hypotheses explicit and theoretically allows for their falsification and improvement. ideally, landscape evolution models (LEMs) combine the results of all relevant landscape forming processes into an ever-adapting digital landscape (e.g. DEM). These processes may act on different spatial and temporal scales. LAPSUS is such a LEM. Processes that have in different studies been included in LAPSUS are water erosion and deposition, landslide activity, creep, solidification, weathering, tectonics and tillage. Process descriptions are as simple and generic as possible, ensuring wide applicability. (Author) 25 refs.

  5. Landscape Evolution Modelling-LAPSUS

    International Nuclear Information System (INIS)

    Baartman, J. E. M.; Temme, A. J. A. M.; Schoorl, J. M.; Claessens, L.; Viveen, W.; Gorp, W. van; Veldkamp, A.

    2009-01-01

    Landscape evolution modelling can make the consequences of landscape evolution hypotheses explicit and theoretically allows for their falsification and improvement. ideally, landscape evolution models (LEMs) combine the results of all relevant landscape forming processes into an ever-adapting digital landscape (e.g. DEM). These processes may act on different spatial and temporal scales. LAPSUS is such a LEM. Processes that have in different studies been included in LAPSUS are water erosion and deposition, landslide activity, creep, solidification, weathering, tectonics and tillage. Process descriptions are as simple and generic as possible, ensuring wide applicability. (Author) 25 refs.

  6. Raptor, a positive regulatory subunit of mTOR complex 1, is a novel phosphoprotein of the rDNA transcription machinery in nucleoli and chromosomal nucleolus organizer regions (NORs).

    Science.gov (United States)

    Vazquez-Martin, Alejandro; Cufí, Sílvia; Oliveras-Ferraros, Cristina; Menendez, Javier A

    2011-09-15

    Raptor is the key scaffolding protein that recruits mTOR substrates to rapamycin-sensitive mTOR complex 1 (mTORC1), a molecular integrator of mitogenic and nutrient/energy environmental inputs into protein translation and cell growth. Although Raptor phosphorylation on various sites is pivotal in the regulation of mTORC1 activity, it remains to be elucidated whether site-specific phosphorylation differentially distributes Raptor to unique subcellular compartments. When exploring the spatiotemporal cell cycle dynamics of six different phospho (P)-Raptor isoforms (Thr ( 706) , Ser ( 722) , Ser ( 863) , Ser ( 792) and Ser ( 877) ), a number of remarkable events differentially defined a topological resetting of P-RaptorThr706 on interphasic and mitotic chromosomes. In interphase nuclei, P-Raptor (Thr706) co-localized with fibrillarin, a component of the nucleolar small nuclear ribonucleoprotein particle, as well as with RNA polymerase I, the enzyme that transcribes nucleolar rRNA. Upon Actinomycin D-induced nucleolar segregation and disaggregation, P-RaptorThr706 was excluded from the nucleolus to accumulate at discrete nucleoplasmic bodies. During mitosis, CDK1 inhibition-induced premature assembly of nucleoli relocated fibrillarin to the surrounding regions of chromosomal-associated P-Raptor (Thr706) , suggesting that a subpopulation of mitotic P-Raptor (Thr706) remained targeted at chromosomal loops of rDNA or nuclear organizer regions (NORs). At the end of mitosis and cytokinesis, when reassembly of incipient nucleoli begins upon NORs activation of rDNA transcription, fibrillarin spatially reorganized with P-Raptor (Thr706) to give rise to daughter nucleoli. Treatment with IGF1 exclusively hyperactivated nuclear P-Raptor (Ser706) and concomitantly promoted Ser ( 2481) autophosphorylation of mTOR, which monitors mTORC1-associated catalytic activity. Nucleolar- and NOR-associated P-Raptor (Ser706) may physically link mTORC1 signaling to ever-growing nucleolus

  7. LANDSCAPE ECOLOGICAL METHOD TO STUDY AGRICULTURAL VEGETATION: SOME EXAMPLES FROM THE PO VALLEY

    Directory of Open Access Journals (Sweden)

    E. GIGLIO

    2006-01-01

    Full Text Available Vegetation is the most important landscape component, as regards to its ability to catch solar energy and to transform it, but also to shape the landscape, to structure the space, to create the fit environment for different animal species, to contribute to the maintenance of a correct metastability level for the landscape, etc. It is a biological system which acts under the constraints of the principles of the System Theory and owns the same properties of any other living system: so, it is a complex adaptive, hierarchical, dynamic, dissipative, self-organizing, self-transcendent, autocatalytic, self-maintaining system and follows the non-equilibrium thermodynamic. Its ecological state can be investigated through the comparison between “gathered data” (pathology and “normal data” (physiology for analogous types of vegetation. The Biological Integrated School of Landscape Ecology provides an integrated methodology to define ecological threshold limits of the different Agricultural Landscape types and applies to agricultural vegetation the specific part of the new methodology already tested to studying forests (the Landscape Biological Survey of Vegetation. Ecological quality, better and worst parameters, biological territorial capacity of vegetated corridors, agricultural field, poplar groves, orchards and woody remnant patches are investigated. Some examples from diverse agricultural landscapes of the Po Valley will be discussed. KEY WORDS: agricultural landscape, vegetation, landscape ecology, landscape health, Biological Integrated Landscape Ecology, Landscape Biological Survey of vegetation.

  8. LANDSCAPE ECOLOGICAL METHOD TO STUDY AGRICULTURAL VEGETATION: SOME EXAMPLES FROM THE PO VALLEY

    Directory of Open Access Journals (Sweden)

    E. GIGLIO

    2006-05-01

    Full Text Available Vegetation is the most important landscape component, as regards to its ability to catch solar energy and to transform it, but also to shape the landscape, to structure the space, to create the fit environment for different animal species, to contribute to the maintenance of a correct metastability level for the landscape, etc. It is a biological system which acts under the constraints of the principles of the System Theory and owns the same properties of any other living system: so, it is a complex adaptive, hierarchical, dynamic, dissipative, self-organizing, self-transcendent, autocatalytic, self-maintaining system and follows the non-equilibrium thermodynamic. Its ecological state can be investigated through the comparison between “gathered data” (pathology and “normal data” (physiology for analogous types of vegetation. The Biological Integrated School of Landscape Ecology provides an integrated methodology to define ecological threshold limits of the different Agricultural Landscape types and applies to agricultural vegetation the specific part of the new methodology already tested to studying forests (the Landscape Biological Survey of Vegetation. Ecological quality, better and worst parameters, biological territorial capacity of vegetated corridors, agricultural field, poplar groves, orchards and woody remnant patches are investigated. Some examples from diverse agricultural landscapes of the Po Valley will be discussed. KEY WORDS: agricultural landscape, vegetation, landscape ecology, landscape health, Biological Integrated Landscape Ecology, Landscape Biological Survey of vegetation.

  9. Landscapes of human evolution: models and methods of tectonic geomorphology and the reconstruction of hominin landscapes.

    Science.gov (United States)

    Bailey, Geoffrey N; Reynolds, Sally C; King, Geoffrey C P

    2011-03-01

    This paper examines the relationship between complex and tectonically active landscapes and patterns of human evolution. We show how active tectonics can produce dynamic landscapes with geomorphological and topographic features that may be critical to long-term patterns of hominin land use, but which are not typically addressed in landscape reconstructions based on existing geological and paleoenvironmental principles. We describe methods of representing topography at a range of scales using measures of roughness based on digital elevation data, and combine the resulting maps with satellite imagery and ground observations to reconstruct features of the wider landscape as they existed at the time of hominin occupation and activity. We apply these methods to sites in South Africa, where relatively stable topography facilitates reconstruction. We demonstrate the presence of previously unrecognized tectonic effects and their implications for the interpretation of hominin habitats and land use. In parts of the East African Rift, reconstruction is more difficult because of dramatic changes since the time of hominin occupation, while fossils are often found in places where activity has now almost ceased. However, we show that original, dynamic landscape features can be assessed by analogy with parts of the Rift that are currently active and indicate how this approach can complement other sources of information to add new insights and pose new questions for future investigation of hominin land use and habitats. Copyright © 2010 Elsevier Ltd. All rights reserved.

  10. Nucleic Acid Analogue Induced Transcription of Double Stranded DNA

    DEFF Research Database (Denmark)

    1998-01-01

    RNA is transcribed from a double stranded DNA template by forming a complex by hybridizing to the template at a desired transcription initiation site one or more oligonucleic acid analogues of the PNA type capable of forming a transcription initiation site with the DNA and exposing the complex...... to the action of a DNA dependant RNA polymerase in the presence of nucleoside triphosphates. Equal length transcripts may be obtained by placing a block to transcription downstream from the initiation site or by cutting the template at such a selected location. The initiation site is formed by displacement...... of one strand of the DNA locally by the PNA hybridization....

  11. Ecological Functions of Landscapes

    Science.gov (United States)

    Kiryushin, V. I.

    2018-01-01

    Ecological functions of landscapes are considered a system of processes ensuring the development, preservation, and evolution of ecosystems and the biosphere as a whole. The concept of biogeocenosis can be considered a model that integrates biotic and environmental functions. The most general biogeocenotic functions specify the biodiversity, biotic links, self-organization, and evolution of ecosystems. Close interaction between biocenosis and the biotope (ecotope) is ensured by the continuous exchange of matter, energy, and information. Ecotope determines the biocenosis. The group of ecotopic functions includes atmospheric (gas exchange, heat exchange, hydroatmospheric, climate-forming), lithospheric (geodynamic, geophysical, and geochemical), hydrologic and hydrogeologic functions of landscape and ecotopic functions of soils. Bioecological functions emerge as a result of the biotope and ecotope interaction; these are the bioproductive, destructive, organoaccumulative, biochemical (gas, concentration, redox, biochemical, biopedological), pedogenetic, and energy functions

  12. Conceiving Landscape through Film

    DEFF Research Database (Denmark)

    Farsø, Mads; Munck Petersen, Rikke

    2015-01-01

    This article shows how the media of film can be integrated, explored and can add value to architectural design studios and practice. It elucidates how film may offer an alternative position in architecture, where landscapes and cities are thought, planned and developed in closer relation...... to their spatial and sensory effects on humans. It underscores that the film camera can work as a kind of amplifier of how we, with our bodies, perceive space and project space. In the “Landscape Film” Studio at University of Copenhagen the film medium was tested as a combined registration and design tool...... for a new Nature Park south of Copenhagen. The final studio films and designs show how resonate recordings of sound, time and a bodily presence may simulate an Einfühling that inspires an alternative architecture of relations: the ambient, the changeable and the volatile. They also emphasize that an ability...

  13. Landscape & Imagination: riflettere insieme

    Directory of Open Access Journals (Sweden)

    Mariella Zoppi

    2015-10-01

    Full Text Available In Paris, at La Villette University, was four-days of debate on 2-4 Mai 2013, in which faculty members of all the world discussed on methods and experiences in teaching landscape. The conference was organized in multiple sessions: history, theories, representation, process, science and governance. All the fields discussed were related to the main problem of the identity of territories in the landscape project -from the theories to the practices- and applied in a very large range of different situations: from the rural world between conservation and transformations to the coastal areas under the pressure of tourism, from the ecology in the city life renovation to the land use control and project by community and the emergency management in natural catastrophes.

  14. Colon cancer associated transcripts in human cancers.

    Science.gov (United States)

    Chen, Yincong; Xie, Haibiao; Gao, Qunjun; Zhan, Hengji; Xiao, Huizhong; Zou, Yifan; Zhang, Fuyou; Liu, Yuchen; Li, Jianfa

    2017-10-01

    Long non-coding RNAs serve as important regulators in complicated cellular activities, including cell differentiation, proliferation and death. Dysregulation of long non-coding RNAs occurs in the formation and progression of cancers. The family of colon cancer associated transcripts, long non-coding RNAs colon cancer associated transcript-1 and colon cancer associated transcript-2 are known as oncogenes involved in various cancers. Colon cancer associated transcript-1 is a novel lncRNA located in 8q24.2, and colon cancer associated transcript-2 maps to the 8q24.21 region encompassing rs6983267. Colon cancer associated transcripts have close associations with clinical characteristics, such as lymph node metastasis, high TNM stage and short overall survival. Knockdown of them can reverse the malignant phenotypes of cancer cells, including proliferation, migration, invasion and apoptosis. Moreover, they can increase the expression level of c-MYC and oncogenic microRNAs via activating a series of complex mechanisms. In brief, the family of colon cancer associated transcripts may serve as potential biomarkers or therapeutic targets for human cancers. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  15. Identification Of Minangkabau Landscape Characters

    Science.gov (United States)

    Asrina, M.; Gunawan, A.; Aris, Munandar

    2017-10-01

    Minangkabau is one of cultures in indonesia which occupies landscape intact. Landscape of Minangkabau have a very close relationship with the culture of the people. Uniqueness of Minangkabau culture and landscape forming an inseparable characterunity. The landscape is necessarily identified to know the inherent landscape characters. The objective of this study was to identify the character of the Minangkabau landscape characterizes its uniqueness. The study was conducted by using descriptive method comprised literature review and field observasion. Observed the landscape characters comprised two main features, they were major and minor features. Indetification of the features was conducted in two original areas (darek) of the Minangkabau traditional society. The research results showed that major features or natural features of the landscape were predominantly landform, landcover, and hidrology. All luhak (districts) of Minangkabau showed similar main features such as hill, canyon, lake, valley, and forest. The existence of natural features such as hills, canyon and valleys characterizes the nature of minangkabau landscape. Minor features formed by Minangkabau cultural society were agricultural land and settlement. Rumah gadang (big house) is one of famous minor features characterizes the Minangkabau culture. In addition, several historical artefacts of building and others structure may strengthen uniqueness of the Minangkabau landscape character, such as The royal palace, inscription, and tunnels.

  16. Visualizing phylogenetic tree landscapes.

    Science.gov (United States)

    Wilgenbusch, James C; Huang, Wen; Gallivan, Kyle A

    2017-02-02

    Genomic-scale sequence alignments are increasingly used to infer phylogenies in order to better understand the processes and patterns of evolution. Different partitions within these new alignments (e.g., genes, codon positions, and structural features) often favor hundreds if not thousands of competing phylogenies. Summarizing and comparing phylogenies obtained from multi-source data sets using current consensus tree methods discards valuable information and can disguise potential methodological problems. Discovery of efficient and accurate dimensionality reduction methods used to display at once in 2- or 3- dimensions the relationship among these competing phylogenies will help practitioners diagnose the limits of current evolutionary models and potential problems with phylogenetic reconstruction methods when analyzing large multi-source data sets. We introduce several dimensionality reduction methods to visualize in 2- and 3-dimensions the relationship among competing phylogenies obtained from gene partitions found in three mid- to large-size mitochondrial genome alignments. We test the performance of these dimensionality reduction methods by applying several goodness-of-fit measures. The intrinsic dimensionality of each data set is also estimated to determine whether projections in 2- and 3-dimensions can be expected to reveal meaningful relationships among trees from different data partitions. Several new approaches to aid in the comparison of different phylogenetic landscapes are presented. Curvilinear Components Analysis (CCA) and a stochastic gradient decent (SGD) optimization method give the best representation of the original tree-to-tree distance matrix for each of the three- mitochondrial genome alignments and greatly outperformed the method currently used to visualize tree landscapes. The CCA + SGD method converged at least as fast as previously applied methods for visualizing tree landscapes. We demonstrate for all three mtDNA alignments that 3D

  17. Dysfunctional transcripts are formed by alternative polyadenylation in OPMD

    OpenAIRE

    Raz, Vered; Dickson, George; ’t Hoen, Peter A.C.

    2017-01-01

    Post-transcription mRNA processing in the 3’-untranslated region (UTR) of transcripts alters mRNA landscape. Alternative polyadenylation (APA) utilization in the 3’-UTR often leads to shorter 3’-UTR affecting mRNA stability, a process that is regulated by PABPN1. In skeletal muscles PABPN1 levels reduce with age and a greater decrease in found in Oculopharyngeal muscular dystrophy (OPMD). OPMD is a late onset autosomal dominant myopathy caused by expansion mutation in PABPN1. In OPMD models a...

  18. Uncovering archaeological landscapes at Angkor using lidar.

    Science.gov (United States)

    Evans, Damian H; Fletcher, Roland J; Pottier, Christophe; Chevance, Jean-Baptiste; Soutif, Dominique; Tan, Boun Suy; Im, Sokrithy; Ea, Darith; Tin, Tina; Kim, Samnang; Cromarty, Christopher; De Greef, Stéphane; Hanus, Kasper; Bâty, Pierre; Kuszinger, Robert; Shimoda, Ichita; Boornazian, Glenn

    2013-07-30

    Previous archaeological mapping work on the successive medieval capitals of the Khmer Empire located at Angkor, in northwest Cambodia (∼9th to 15th centuries in the Common Era, C.E.), has identified it as the largest settlement complex of the preindustrial world, and yet crucial areas have remained unmapped, in particular the ceremonial centers and their surroundings, where dense forest obscures the traces of the civilization that typically remain in evidence in surface topography. Here we describe the use of airborne laser scanning (lidar) technology to create high-precision digital elevation models of the ground surface beneath the vegetation cover. We identify an entire, previously undocumented, formally planned urban landscape into which the major temples such as Angkor Wat were integrated. Beyond these newly identified urban landscapes, the lidar data reveal anthropogenic changes to the landscape on a vast scale and lend further weight to an emerging consensus that infrastructural complexity, unsustainable modes of subsistence, and climate variation were crucial factors in the decline of the classical Khmer civilization.

  19. Incorporating Bioenergy in Sustainable Landscape Designs Workshop Two: Agricultural Landscapes

    Energy Technology Data Exchange (ETDEWEB)

    None

    2015-08-01

    The Bioenergy Technologies Office hosted two workshops on Incorporating Bioenergy in Sustainable Landscape Designs with Oak Ridge and Argonne National Laboratories in 2014. The second workshop focused on agricultural landscapes and took place in Argonne, IL from June 24—26, 2014. The workshop brought together experts to discuss how landscape design can contribute to the deployment and assessment of sustainable bioenergy. This report summarizes the discussions that occurred at this particular workshop.

  20. Landscape approach to the formation of the ecological frame of Moscow

    Science.gov (United States)

    Nizovtsev, Vyacheslav; Natalia, Erman

    2015-04-01

    The territory of Moscow, in particular in its former borders, is distinct for its strong transformation of the natural properties of virtually all types of landscape complexes. The modern landscape structure is characterized by fragmentation of natural land cover. Natural and quasinatural (natural and anthropogenic) landscape complexes with preserved natural structure are represented by isolated areas and occupy small areas. During recent years landscape diversity in general and biodiversity in particular have been rapidly declining, and many of the natural landscape complexes are under ever-increasing degradation. Ecological balance is broken, and preserved natural landscapes are not able to maintain it. Effective territorial organization of Moscow and the rational use of its territory are impossible without taking into account the natural component of the city as well as the properties and potential of the landscape complexes that integrate all natural features in specific areas. The formation of the ecological framework of the city is particularly important. It should be a single system of interrelated and complementary components that make up a single environmental space: habitat-forming cores (junctions), ecological corridors and elements of environmental infrastructure. Systemic unity of the environmental framework can support the territorial ecological compensation where a break of the ecological functions of one part of the system is compensated by maintaining or restoring them in another part and contribute to the polarization of incompatible types of land use. Habitat-forming cores should include as mandatory parts all the specifically protected natural areas (SPNAs), particularly valuable landscape complexes, as well as preserved adjacent forest areas. Their most important function should be to maintain resources and area reproducing abilities of landscapes, landscape diversity and biodiversity. Ecological corridors which perform environmental and

  1. [Landscape pattern gradient dynamics and desakota features in rapid urbanization area: a case study in Panyu of Guangzhou].

    Science.gov (United States)

    Yu, Long-Sheng; Fu, Yi-Fu; Yu, Huai-Yi; Li, Zhi-Qin

    2011-01-01

    In order to understand the landscape pattern gradient dynamics and desakota features in rapid urbanization area, this paper took the rapidly urbanizing Panyu District of Guangzhou City as a case, and analyzed its land use and land cover data, based on four Landsat TM images from 1990 to 2008. With the combination of gradient analysis and landscape pattern analysis, and by using the landscape indices in both class and landscape scales, the spatial dynamics and desakota feature of this rapidly urbanizing district were quantified. In the study district, there was a significant change in the landscape pattern, and a typical desakota feature presented along buffer gradient zones. Urban landscape increased and expanded annually, accompanied with serious fragmentation of agricultural landscape. The indices patch density, contagion, and landscape diversity, etc., changed regularly in the urbanization gradient, and the peak of landscape indices appeared in the gradient zone of 4-6 km away from the urban center. The landscape patterns at time series also reflected the differences among the dynamics in different gradient zones. The landscape pattern in desakota region was characterized by complex patch shape, high landscape diversity and fragmentation, and remarkable landscape dynamics. The peaks of landscape indices spread from the urban center to border areas, and desakota region was expanding gradually. The general trend of spatiotemporal dynamics in desakota region and its driving forces were discussed, which could be benefit to the regional land use policy-making and sustainable development planning.

  2. Exploring the conformational energy landscape of proteins

    Energy Technology Data Exchange (ETDEWEB)

    Nienhaus, G.U. [Univ. of Illinois, Urbana, IL (United States)]|[Universitaet Ulm (Germany); Mueller, J.D.; McMahon, B.H. [Univ. of Illinois, Urbana, IL (United States)] [and others

    1997-04-01

    Proteins possess a complex energy landscape with a large number of local minima called conformational substates that are arranged in a hierarchical fashion. Here we discuss experiments aimed at the elucidation of the energy landscape in carbonmonoxy myoglobin (MbCO). In the highest tier of the hierarchy, a few taxonomic substates exist. Because of their small number, these substates are accessible to detailed structural investigations. Spectroscopic experiments are discussed that elucidate the role of protonations of amino acid side chains in creating the substates. The lower tiers of the hierarchy contain a large number of statistical substates. Substate interconversions are observed in the entire temperature range from below 1 K up to the denaturation temperature, indicating a wide spectrum of energy barriers that separate the substates.

  3. The Influence of Stratigraphic History on Landscape Evolution

    Science.gov (United States)

    Forte, A. M.; Yanites, B.; Whipple, K. X.

    2016-12-01

    Variation in rock erodibility can play a significant role in landscape evolution. Using a version of the CHILD landscape evolution model that allows for variations in rock erodibility, we found surprisingly complex landscape evolution in simulations with simple, two unit stratigraphies with contrasting erodibility. This work indicated that the stratigraphic order of units in terms of erodibility, the orientation of the contact with respect to the main drainage direction, and the contact dip angle all have pronounced effects on landscape evolution. Here we expand that work to explore the implications of more complicated stratigraphies on landscape evolution. Introducing multiple units adds additional controls on landscape evolution, namely the thicknesses and relative erodibility of rock layers. In models with a sequence of five alternating hard and soft units embedded within arbitrarily thick over- and underlying units, the number of individual layers that noticeably influence landscape morphology decreases as the thickness of individual layers reduces. Contacts with soft rocks over hard produce the most noticeable effect in model output such as erosion rate and channel steepness. For large contrasts in erodibility of 25 m thick layers, only one soft over hard contact is clearly manifest in the landscape. Between 50 and 75 m, two such contacts are manifest, and by 100 m thickness, all three of these contacts are manifest. However, for a given thickness of layers, more units are manifest in the landscape as the erodibility contrast between units decreases. This is true even though the magnitude of landscape effects away from steady-state erosion rates or channel steepness also decrease with decreasing erodibility contrast. Finally, we explore suites of models with alternating layers reflecting either `hardening-' or `softening-upwards' stratigraphies and find that the two scenarios result in decidedly different landscape forms. Hardening-upwards sections produce a

  4. Integrated landscape initiatives in Europe

    DEFF Research Database (Denmark)

    García-Martín, María; Bieling, Claudia; Hart, Abigail

    2016-01-01

    Landscapes are linked to human well-being in a multitude of ways, some of which are challenged by global market forces and traditional management approaches. In response to this situation there has been a rise in local initiatives to sustain the values of landscape. The aim of this paper is to pr......Landscapes are linked to human well-being in a multitude of ways, some of which are challenged by global market forces and traditional management approaches. In response to this situation there has been a rise in local initiatives to sustain the values of landscape. The aim of this paper...... searches and canvassing of European umbrella organisations; followed by an online survey of representatives from the identified initiatives (n??=??71). Our results show that the most relevant characteristics of integrated landscape initiatives in Europe are: a holistic approach to landscape management...

  5. Transcriptional and Chromatin Dynamics of Muscle Regeneration After Severe Trauma

    Science.gov (United States)

    2016-10-12

    02127. 2Broad Institute of MIT and Harvard, Cambridge , MA 02142, Harvard Stem Cell Institute, Cambridge , MA 02138, Dept. of Stem Cell and...Regenerative Biology, Harvard University, Cambridge , MA 02138. 3United States Army Institute of Environmental Medicine - Military Performance Division, Natick...throughout the regenerative process in a mouse model of traumatic muscle injury. We first illustrate how the transcriptional landscape of coding and

  6. Flowscapes: Designing infrastructure as landscape

    OpenAIRE

    Nijhuis, S.; Jauslin, D.T.; Van der Hoeven, F.D.

    2015-01-01

    Social, cultural and technological developments of our society are demanding a fundamental review of the planning and design of its landscapes and infrastructures, in particular in relation to environmental issues and sustainability. Transportation, green and water infrastructures are important agents that facilitate processes that shape the built environment and its contemporary landscapes. With movement and flows at the core, these landscape infrastructures facilitate aesthetic, functional,...

  7. Modelling Geomorphic Systems: Landscape Evolution

    OpenAIRE

    Valters, Declan

    2016-01-01

    Landscape evolution models (LEMs) present the geomorphologist with a means of investigating how landscapes evolve in response to external forcings, such as climate and tectonics, as well as internal process laws. LEMs typically incorporate a range of different geomorphic transport laws integrated in a way that simulates the evolution of a 3D terrain surface forward through time. The strengths of LEMs as research tools lie in their ability to rapidly test many different hypotheses of landscape...

  8. Transcriptional regulation by Polycomb group proteins

    DEFF Research Database (Denmark)

    Di Croce, Luciano; Helin, Kristian

    2013-01-01

    Polycomb group (PcG) proteins are epigenetic regulators of transcription that have key roles in stem-cell identity, differentiation and disease. Mechanistically, they function within multiprotein complexes, called Polycomb repressive complexes (PRCs), which modify histones (and other proteins......) and silence target genes. The dynamics of PRC1 and PRC2 components has been the focus of recent research. Here we discuss our current knowledge of the PRC complexes, how they are targeted to chromatin and how the high diversity of the PcG proteins allows these complexes to influence cell identity....

  9. Differential responses of cryptic bat species to the urban landscape.

    Science.gov (United States)

    Lintott, Paul R; Barlow, Kate; Bunnefeld, Nils; Briggs, Philip; Gajas Roig, Clara; Park, Kirsty J

    2016-04-01

    Urbanization is a key global driver in the modification of land use and has been linked to population declines even in widespread and relatively common species. Cities comprise a complex assortment of habitat types yet we know relatively little about the effects of their composition and spatial configuration on species distribution. Although many bat species exploit human resources, the majority of species are negatively impacted by urbanization. Here, we use data from the National Bat Monitoring Programme, a long-running citizen science scheme, to assess how two cryptic European bat species respond to the urban landscape. A total of 124 × 1 km(2) sites throughout Britain were surveyed. The landscape surrounding each site was mapped and classified into discrete biotope types (e.g., woodland). Generalized linear models were used to assess differences in the response to the urban environment between the two species, and which landscape factors were associated with the distributions of P. pipistrellus and P. pygmaeus. The relative prevalence of P. pygmaeus compared to P. pipistrellus was greater in urban landscapes with a higher density of rivers and lakes, whereas P. pipistrellus was frequently detected in landscapes comprising a high proportion of green space (e.g., parklands). Although P. pipistrellus is thought to be well adapted to the urban landscape, we found a strong negative response to urbanization at a relatively local scale (1 km), whilst P. pygmaeus was detected more regularly in wooded urban landscapes containing freshwater. These results show differential habitat use at a landscape scale of two morphologically similar species, indicating that cryptic species may respond differently to anthropogenic disturbance. Even species considered relatively common and well adapted to the urban landscape may respond negatively to the built environment highlighting the future challenges involved in maintaining biodiversity within an increasingly urbanized

  10. Increasing connectivity between metapopulation ecology and landscape ecology.

    Science.gov (United States)

    Howell, Paige E; Muths, Erin; Hossack, Blake R; Sigafus, Brent H; Chandler, Richard B

    2018-05-01

    Metapopulation ecology and landscape ecology aim to understand how spatial structure influences ecological processes, yet these disciplines address the problem using fundamentally different modeling approaches. Metapopulation models describe how the spatial distribution of patches affects colonization and extinction, but often do not account for the heterogeneity in the landscape between patches. Models in landscape ecology use detailed descriptions of landscape structure, but often without considering colonization and extinction dynamics. We present a novel spatially explicit modeling framework for narrowing the divide between these disciplines to advance understanding of the effects of landscape structure on metapopulation dynamics. Unlike previous efforts, this framework allows for statistical inference on landscape resistance to colonization using empirical data. We demonstrate the approach using 11 yr of data on a threatened amphibian in a desert ecosystem. Occupancy data for Lithobates chiricahuensis (Chiricahua leopard frog) were collected on the Buenos Aires National Wildlife Refuge (BANWR), Arizona, USA from 2007 to 2017 following a reintroduction in 2003. Results indicated that colonization dynamics were influenced by both patch characteristics and landscape structure. Landscape resistance increased with increasing elevation and distance to the nearest streambed. Colonization rate was also influenced by patch quality, with semi-permanent and permanent ponds contributing substantially more to the colonization of neighboring ponds relative to intermittent ponds. Ponds that only hold water intermittently also had the highest extinction rate. Our modeling framework can be widely applied to understand metapopulation dynamics in complex landscapes, particularly in systems in which the environment between habitat patches influences the colonization process. © 2018 by the Ecological Society of America.

  11. Energy landscape Allgaeu; Energielandschaft Allgaeu

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2013-04-01

    In tandems with questions on the energy policy turnaround, the topics cultural landscape history, morphology, actual land use, tourism, settlement development or infrastructure are summarized in regional concepts and designs to a consistent landscape. Thus, a true integration of renewable energies in the landscape enhances existing or creates completely new landscape qualities. Energy supply shall be understood as a component of the every day life world. The energy supply shall not be hidden any more, but it rather should be communicated as the brand 'Allgaeu'.

  12. Impressionist Landscape Cartography

    Science.gov (United States)

    Todd, Stella W.

    2018-05-01

    Cartography helps to show us the world in which we reside by providing us a framework to explore space. We can select myriad themes to represent what is relevant to our lives: physical characteristics, human behaviors, hazards, opportunities. Themes are represented on a continuum between real-world images and pure abstractions. How we define cartography and what we expect from it changes with society and technology. We are now inundated with data but we still struggle with expressing our personal geographic experiences through cartography. In this age of information we have become more cognizant of our individual experience of place and our need to determine our own paths and therefore create our own maps. In order to reflect our journey we can add individual details to cartographic products or generalize information to concentrate on what is meaningful to us. Since time and space are interrelated we experience geography by viewing the landscape as changing scenes over time. This experience is both spatial and temporal since we experience geography by moving through space. Experiencing each scene is a separate event. This paper expands the personalization of maps to include our impressions of the travel experience. Rather than add art to cartography it provides geographic reference to art. It explores the use of a series of quick sketches drawn while traveling along roads using a single drawing pad to produce a time series of interpreted landscapes. With the use of geographic time stamps from global positioning systems these sketches are converted from a drawing to a map documenting the path of movement. Although the map scale varies between sketch entries each scene impression can be linked to one or more maps of consistent scale. The result is an artistic piece that expresses a dynamic geographic experience that can be viewed in conjunction with more traditional maps. Unlike mental maps which are constructed from memory, these maps reflect our direct impressions

  13. Agroparks - The European Landscape Convention and a European way to regional sustainable landscape development through land use integration

    DEFF Research Database (Denmark)

    Christensen, Andreas Aagaard; Svennningsen, Stig R.; Brandt, Jesper

    2011-01-01

    areas of Europe, in which environmental management increasingly conforms to the principles of liberal economy. Based on a national study of privately owned largeholder manorial estates in Denmark including a detailed case study conducted in one of the survey areas, we conclude that transition...... to landscape sustainability is held back by two main inhibitors, which currently makes it a necessity for rural agency to act unsustainably: (1) The global liberalized legal system which supports individual private ownership to land and thus restrains large scale decision making at a spatial scale to match...... of production activities. These landscapes integrate nature protection, agriculture, settlement and recreation in complex structures of management. They could serve as an example for future sustainable landscape planning at a larger scale, supported by regional regulation. The European Landscape Convention (ELC...

  14. Transcription-factor occupancy at HOT regions quantitatively predicts RNA polymerase recruitment in five human cell lines.

    KAUST Repository

    Foley, Joseph W

    2013-10-20

    BACKGROUND: High-occupancy target (HOT) regions are compact genome loci occupied by many different transcription factors (TFs). HOT regions were initially defined in invertebrate model organisms, and we here show that they are a ubiquitous feature of the human gene-regulation landscape. RESULTS: We identified HOT regions by a comprehensive analysis of ChIP-seq data from 96 DNA-associated proteins in 5 human cell lines. Most HOT regions co-localize with RNA polymerase II binding sites, but many are not near the promoters of annotated genes. At HOT promoters, TF occupancy is strongly predictive of transcription preinitiation complex recruitment and moderately predictive of initiating Pol II recruitment, but only weakly predictive of elongating Pol II and RNA transcript abundance. TF occupancy varies quantitatively within human HOT regions; we used this variation to discover novel associations between TFs. The sequence motif associated with any given TF\\'s direct DNA binding is somewhat predictive of its empirical occupancy, but a great deal of occupancy occurs at sites without the TF\\'s motif, implying indirect recruitment by another TF whose motif is present. CONCLUSIONS: Mammalian HOT regions are regulatory hubs that integrate the signals from diverse regulatory pathways to quantitatively tune the promoter for RNA polymerase II recruitment.

  15. Transcription-factor occupancy at HOT regions quantitatively predicts RNA polymerase recruitment in five human cell lines.

    KAUST Repository

    Foley, Joseph W; Sidow, Arend

    2013-01-01

    BACKGROUND: High-occupancy target (HOT) regions are compact genome loci occupied by many different transcription factors (TFs). HOT regions were initially defined in invertebrate model organisms, and we here show that they are a ubiquitous feature of the human gene-regulation landscape. RESULTS: We identified HOT regions by a comprehensive analysis of ChIP-seq data from 96 DNA-associated proteins in 5 human cell lines. Most HOT regions co-localize with RNA polymerase II binding sites, but many are not near the promoters of annotated genes. At HOT promoters, TF occupancy is strongly predictive of transcription preinitiation complex recruitment and moderately predictive of initiating Pol II recruitment, but only weakly predictive of elongating Pol II and RNA transcript abundance. TF occupancy varies quantitatively within human HOT regions; we used this variation to discover novel associations between TFs. The sequence motif associated with any given TF's direct DNA binding is somewhat predictive of its empirical occupancy, but a great deal of occupancy occurs at sites without the TF's motif, implying indirect recruitment by another TF whose motif is present. CONCLUSIONS: Mammalian HOT regions are regulatory hubs that integrate the signals from diverse regulatory pathways to quantitatively tune the promoter for RNA polymerase II recruitment.

  16. Landscape encodings enhance optimization.

    Directory of Open Access Journals (Sweden)

    Konstantin Klemm

    Full Text Available Hard combinatorial optimization problems deal with the search for the minimum cost solutions (ground states of discrete systems under strong constraints. A transformation of state variables may enhance computational tractability. It has been argued that these state encodings are to be chosen invertible to retain the original size of the state space. Here we show how redundant non-invertible encodings enhance optimization by enriching the density of low-energy states. In addition, smooth landscapes may be established on encoded state spaces to guide local search dynamics towards the ground state.

  17. The Anti-Landscape

    DEFF Research Database (Denmark)

    There have always been some uninhabitable places, but in the last century human beings have produced many more of them. These anti-landscapes have proliferated to include the sandy wastes of what was once the Aral Sea, severely polluted irrigated lands, open pit mines, blighted nuclear zones...... that no longer sustain life. This history includes T. S. Eliot’s Wasteland and Cormac McCarthy’s The Road as well as air pollution, recycled railway lines, photography and landfills. It links theories of aesthetics, politics, tourism, history, geography, and literature into the new synthesis of the environmental...

  18. Landscapes of the Anthropocene

    DEFF Research Database (Denmark)

    Pawson, Eric; Christensen, Andreas Aagaard

    2014-01-01

    since the 1840s, when indigenous forests were transformed into improved landscapes of sown grass. The chapter is shaped by a broad question. What can be learned from this place about the ways in which people have exercised and are coming to terms with what Gibson-Graham and Roelvink describe as our...... of the shifting balance of ecological agency in favour of humans during the Anthropocene. Banks Peninsula on the east coast of New Zealand’s South Island was first settled by Polynesian peoples within the last few hundred years. The nature of their footprint contrasts with the dramatic change wrought by Europeans...

  19. Stonehenge and its Landscape

    Science.gov (United States)

    Ruggles, Clive L. N.

    In the 1960s and 1970s, Stonehenge polarized academic opinion between those (mainly astronomers) who claimed it demonstrated great astronomical sophistication and those (mainly archaeologists) who denied it had anything to do with astronomy apart from the solstitial alignment of its main axis. Now, several decades later, links to the annual passage of the sun are generally recognized as an essential part of the function and meaning not only of Stonehenge but also of several other nearby monuments, giving us important insights into beliefs and actions relating to the seasonal cycle by the prehistoric communities who populated this chalkland landscape in the third millennium BC Links to the moon remain more debatable.

  20. Reprogramming the chromatin landscape

    DEFF Research Database (Denmark)

    Miranda, Tina B; Voss, Ty C; Sung, Myong-Hee

    2013-01-01

    , mechanistic details defining the cellular interactions between ER and GR are poorly understood. We investigated genome-wide binding profiles for ER and GR upon coactivation and characterized the status of the chromatin landscape. We describe a novel mechanism dictating the molecular interplay between ER...... and GR. Upon induction, GR modulates access of ER to specific sites in the genome by reorganization of the chromatin configuration for these elements. Binding to these newly accessible sites occurs either by direct recognition of ER response elements or indirectly through interactions with other factors...

  1. Landscape Encodings Enhance Optimization

    Science.gov (United States)

    Klemm, Konstantin; Mehta, Anita; Stadler, Peter F.

    2012-01-01

    Hard combinatorial optimization problems deal with the search for the minimum cost solutions (ground states) of discrete systems under strong constraints. A transformation of state variables may enhance computational tractability. It has been argued that these state encodings are to be chosen invertible to retain the original size of the state space. Here we show how redundant non-invertible encodings enhance optimization by enriching the density of low-energy states. In addition, smooth landscapes may be established on encoded state spaces to guide local search dynamics towards the ground state. PMID:22496860

  2. The Mediator Complex and Lipid Metabolism

    OpenAIRE

    Zhang, Yi; Xiaoli,; Zhao, Xiaoping; Yang, Fajun

    2013-01-01

    The precise control of gene expression is essential for all biological processes. In addition to DNA-binding transcription factors, numerous transcription cofactors contribute another layer of regulation of gene transcription in eukaryotic cells. One of such transcription cofactors is the highly conserved Mediator complex, which has multiple subunits and is involved in various biological processes through directly interacting with relevant transcription factors. Although the current understan...

  3. The multitalented Mediator complex.

    Science.gov (United States)

    Carlsten, Jonas O P; Zhu, Xuefeng; Gustafsson, Claes M

    2013-11-01

    The Mediator complex is needed for regulated transcription of RNA polymerase II (Pol II)-dependent genes. Initially, Mediator was only seen as a protein bridge that conveyed regulatory information from enhancers to the promoter. Later studies have added many other functions to the Mediator repertoire. Indeed, recent findings show that Mediator influences nearly all stages of transcription and coordinates these events with concomitant changes in chromatin organization. We review the multitude of activities associated with Mediator and discuss how this complex coordinates transcription with other cellular events. We also discuss the inherent difficulties associated with in vivo characterization of a coactivator complex that can indirectly affect diverse cellular processes via changes in gene transcription. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Decomposing Oncogenic Transcriptional Signatures to Generate Maps of Divergent Cellular States.

    Science.gov (United States)

    Kim, Jong Wook; Abudayyeh, Omar O; Yeerna, Huwate; Yeang, Chen-Hsiang; Stewart, Michelle; Jenkins, Russell W; Kitajima, Shunsuke; Konieczkowski, David J; Medetgul-Ernar, Kate; Cavazos, Taylor; Mah, Clarence; Ting, Stephanie; Van Allen, Eliezer M; Cohen, Ofir; Mcdermott, John; Damato, Emily; Aguirre, Andrew J; Liang, Jonathan; Liberzon, Arthur; Alexe, Gabriella; Doench, John; Ghandi, Mahmoud; Vazquez, Francisca; Weir, Barbara A; Tsherniak, Aviad; Subramanian, Aravind; Meneses-Cime, Karina; Park, Jason; Clemons, Paul; Garraway, Levi A; Thomas, David; Boehm, Jesse S; Barbie, David A; Hahn, William C; Mesirov, Jill P; Tamayo, Pablo

    2017-08-23

    The systematic sequencing of the cancer genome has led to the identification of numerous genetic alterations in cancer. However, a deeper understanding of the functional consequences of these alterations is necessary to guide appropriate therapeutic strategies. Here, we describe Onco-GPS (OncoGenic Positioning System), a data-driven analysis framework to organize individual tumor samples with shared oncogenic alterations onto a reference map defined by their underlying cellular states. We applied the methodology to the RAS pathway and identified nine distinct components that reflect transcriptional activities downstream of RAS and defined several functional states associated with patterns of transcriptional component activation that associates with genomic hallmarks and response to genetic and pharmacological perturbations. These results show that the Onco-GPS is an effective approach to explore the complex landscape of oncogenic cellular states across cancers, and an analytic framework to summarize knowledge, establish relationships, and generate more effective disease models for research or as part of individualized precision medicine paradigms. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Editorial: Mapping the Intellectual Landscape of Landscape and Urban Planning

    Science.gov (United States)

    Paul H. Gobster; Wei-Ning. Xiang

    2012-01-01

    Maps are central to our understanding of landscapes. When this Editorship began to revise the journal's Aims and Scope for presentation in a forthcoming editorial, we sought ways in which we could identify the core knowledge base and boundaries, however permeable, of what the journal community considers to be Landscape and Urban Planning (LAND). Strategically, we...

  6. Landscape Painting in Evaluation of Changes in Landscape

    Czech Academy of Sciences Publication Activity Database

    Lacina, Jan; Halas, Petr

    2015-01-01

    Roč. 8, č. 2 (2015), s. 60-68 ISSN 1803-2427 Institutional support: RVO:68145535 Keywords : landscape painting * landscape ecology * land-use changes * biodiversity Subject RIV: DE - Earth Magnetism, Geodesy, Geography http://www.degruyter.com/view/j/jlecol.2015.8.issue-2/jlecol-2015-0009/jlecol-2015-0009. xml

  7. Cultural Landscape and Migration

    Directory of Open Access Journals (Sweden)

    Gunnar Haaland

    2011-04-01

    Full Text Available This paper focus on the way Nepalese migrants in Myanmar use features of the natural environment in their homeland in metaphoric constructions of a cultural landscape expressing ethnic identity. It is through such "symbolic work" that perceptions of "ethnoscapes" are shaped and indoctrinated. Although the appeal is to symbols that can serve to foster the importance of Nepaliness as a basis for belonging to an imagined community, this does not mean that the caste/ethnicity interaction boundaries are broken down. It does mean however that sectors of activities where such boundaries are made relevant have been changed and so has the cultural content organized through such interaction boundaries. Ethnoscapes do not exist by themselves from a 'primordial' past; they require ongoing expression and confirmation. Features of a natural environment most migrants have never seen is used as sources for spinning compelling webs of significance extolling the values of belonging to a group that shares a common past in that environment. I shall here present material of an ethnoscape very different from what is experienced in Nepal, namely Nepalese multi-caste/ethnic communities among Kachins, Shans, Burmese, Indian and Chinese traders in the Kachin state of Northern Myanmar. Keywords: Nepali migrants; Myanmar; ethnic identity; cultural landscape DOI: 10.3126/dsaj.v4i0.4515 Dhaulagiri Journal of Sociology and Anthropology Vol.4 2010 pp.99-110

  8. The Data Science Landscape

    Science.gov (United States)

    Mentzel, C.

    2017-12-01

    Modern scientific data continue to increase in volume, variety, and velocity, and though the hype of big data has subsided, its usefulness for scientific discovery has only just begun. Harnessing these data for new insights, more efficient decision making, and other mission critical uses requires a combination of skills and expertise, often labeled data science. Data science can be thought of as a combination of statistics, computation and the domain from which the data relate, and so is a true interdisciplinary pursuit. Though it has reaped large benefits in companies able to afford the high cost of the severely limited talent pool, it suffers from lack of support in mission driven organizations. Not purely in any one historical field, data science is proving difficult to find a home in traditional university academic departments and other research organizations. The landscape of data science efforts, from academia, industry and government, can be characterized as nascent, enthusiastic, uneven, and highly competitive. Part of the challenge in documenting these trends is the lack of agreement about what data science is, and who is a data scientist. Defining these terms too closely and too early runs the risk of cutting off a tremendous amount of productive creativity, but waiting too long leaves many people without a sustainable career, and many organizations without the necessary skills to gain value from their data. This talk will explore the landscape of data science efforts in the US, including how organizations are building and sustaining data science teams.

  9. Landscape Evolution of Titan

    Science.gov (United States)

    Moore, Jeffrey

    2012-01-01

    Titan may have acquired its massive atmosphere relatively recently in solar system history. The warming sun may have been key to generating Titan's atmosphere over time, starting from a thin atmosphere with condensed surface volatiles like Triton, with increased luminosity releasing methane, and then large amounts of nitrogen (perhaps suddenly), into the atmosphere. This thick atmosphere, initially with much more methane than at present, resulted in global fluvial erosion that has over time retreated towards the poles with the removal of methane from the atmosphere. Basement rock, as manifested by bright, rough, ridges, scarps, crenulated blocks, or aligned massifs, mostly appears within 30 degrees of the equator. This landscape was intensely eroded by fluvial processes as evidenced by numerous valley systems, fan-like depositional features and regularly-spaced ridges (crenulated terrain). Much of this bedrock landscape, however, is mantled by dunes, suggesting that fluvial erosion no longer dominates in equatorial regions. High midlatitude regions on Titan exhibit dissected sedimentary plains at a number of localities, suggesting deposition (perhaps by sediment eroded from equatorial regions) followed by erosion. The polar regions are mainly dominated by deposits of fluvial and lacustrine sediment. Fluvial processes are active in polar areas as evidenced by alkane lakes and occasional cloud cover.

  10. Branches of the landscape

    International Nuclear Information System (INIS)

    Dine, Michael; O'Neil, Deva; Sun Zheng

    2005-01-01

    With respect to the question of supersymmetry breaking, there are three branches of the flux landscape. On one of these, if one requires small cosmological constant, supersymmetry breaking is predominantly at the fundamental scale; on another, the distribution is roughly flat on a logarithmic scale; on the third, the preponderance of vacua are at very low scale. A priori, as we will explain, one can say little about the first branch. The vast majority of these states are not accessible even to crude, approximate analysis. On the other two branches one can hope to do better. But as a result of the lack of access to branch one, and our poor understanding of cosmology, we can at best conjecture about whether string theory predicts low energy supersymmetry or not. If we hypothesize that are on branch two or three, distinctive predictions may be possible. We comment of the status of naturalness within the landscape, deriving, for example, the statistics of the first branch from simple effective field theory reasoning

  11. Urban landscape as palimpsest

    Directory of Open Access Journals (Sweden)

    Daniel-Gabriel Vâlceanu

    2014-12-01

    Full Text Available The current urban morphology and the identity building of the city construction can be designed as a palimpsest; the spatial development stages of urban systems represent the result of their evolution over time. The characteristics of urban palimpsest depend mainly on the emergent factors that influenced the territorial dynamics and the configuration of urban bodies. Urban life and its quality are directly influenced by spatial and temporal factors of the city evolution. For this reason the study aims to achieve a research to explain the concept of urban palimpsest and the current morphology of urban tissue because they are products of landscape transformations along the history. The current knowledge on urban palimpsest characteristics is very important and useful to plan the current and future evolution of urban systems. The case study presents a vast view on the history of spatial development and urban system as well as a dynamics of the landscape interconditioned by the elements of such development in the context of reference historical eras

  12. Norwegian millstone quarry landscapes

    Science.gov (United States)

    Heldal, Tom; Meyer, Gurli; Grenne, Tor

    2013-04-01

    Rotary querns and millstones were used in Norway since just after the Roman Period until the last millstone was made in the 1930s. Throughout all this time millstone mining was fundamental for daily life: millstones were needed to grind grain, our most important food source. We can find millstone quarries in many places in the country from coast to mountain. Some of them cover many square kilometers and count hundreds of quarries as physical testimonies of a long and great production history. Other quarries are small and hardly visible. Some of this history is known through written and oral tradition, but most of it is hidden and must be reconstructed from the traces we can find in the landscape today. The Millstone project has put these quarry landscapes on the map, and conducted a range of case studies, including characterization of archaeological features connected to the quarrying, interpretation of quarrying techniques and evolution of such and establishing distribution and trade patterns by the aid of geological provenance. The project also turned out to be a successful cooperation between different disciplines, in particular geology and archaeology.

  13. A Synthetic Biology Framework for Programming Eukaryotic Transcription Functions

    Science.gov (United States)

    Khalil, Ahmad S.; Lu, Timothy K.; Bashor, Caleb J.; Ramirez, Cherie L.; Pyenson, Nora C.; Joung, J. Keith; Collins, James J.

    2013-01-01

    SUMMARY Eukaryotic transcription factors (TFs) perform complex and combinatorial functions within transcriptional networks. Here, we present a synthetic framework for systematically constructing eukaryotic transcription functions using artificial zinc fingers, modular DNA-binding domains found within many eukaryotic TFs. Utilizing this platform, we construct a library of orthogonal synthetic transcription factors (sTFs) and use these to wire synthetic transcriptional circuits in yeast. We engineer complex functions, such as tunable output strength and transcriptional cooperativity, by rationally adjusting a decomposed set of key component properties, e.g., DNA specificity, affinity, promoter design, protein-protein interactions. We show that subtle perturbations to these properties can transform an individual sTF between distinct roles (activator, cooperative factor, inhibitory factor) within a transcriptional complex, thus drastically altering the signal processing behavior of multi-input systems. This platform provides new genetic components for synthetic biology and enables bottom-up approaches to understanding the design principles of eukaryotic transcriptional complexes and networks. PMID:22863014

  14. Sustainability, Smart Growth, and Landscape Architecture

    Science.gov (United States)

    Sustainability, Smart Growth, and Landscape Architecture is an overview course for landscape architecture students interested in sustainability in landscape architecture and how it might apply to smart growth principles in urban, suburban, and rural areas

  15. Unravelling Late Pleistocene and Holocene landscape dynamics: The Upper Guadalentín Basin, SE Spain

    NARCIS (Netherlands)

    Baartman, J.E.M.; Veldkamp, A.; Schoorl, J.M.; Wallinga, J.; Cammeraat, L.H.

    2011-01-01

    Landscapes in SE Spain have developed in response to tectonics, climate fluctuations and, more recently, human activity. Fluvial and colluvial sediments such as river terraces and slope deposits found in the valleys reflect a complex interplay between landscape forming processes. Investigating these

  16. Recent developments in computer modeling add ecological realism to landscape genetics

    Science.gov (United States)

    Background / Question / Methods A factor limiting the rate of progress in landscape genetics has been the shortage of spatial models capable of linking life history attributes such as dispersal behavior to complex dynamic landscape features. The recent development of new models...

  17. Spatially explicit and stochastic simulation of forest landscape fire disturbance and succession

    Science.gov (United States)

    Hong S. He; David J. Mladenoff

    1999-01-01

    Understanding disturbance and recovery of forest landscapes is a challenge because of complex interactions over a range of temporal and spatial scales. Landscape simulation models offer an approach to studying such systems at broad scales. Fire can be simulated spatially using mechanistic or stochastic approaches. We describe the fire module in a spatially explicit,...

  18. Fitness landscapes, heuristics and technological paradigms: a critique on random search models in evolutionary economics

    NARCIS (Netherlands)

    Frenken, K.

    2001-01-01

    The biological evolution of complex organisms, in which the functioning of genes is interdependent, has been analyzed as "hill-climbing" on NK fitness landscapes through random mutation and natural selection. In evolutionary economics, NK fitness landscapes have been used to simulate the evolution

  19. Extensive polycistronism and antisense transcription in the mammalian Hox clusters.

    Directory of Open Access Journals (Sweden)

    Gaëll Mainguy

    Full Text Available The Hox clusters play a crucial role in body patterning during animal development. They encode both Hox transcription factor and micro-RNA genes that are activated in a precise temporal and spatial sequence that follows their chromosomal order. These remarkable collinear properties confer functional unit status for Hox clusters. We developed the TranscriptView platform to establish high resolution transcriptional profiling and report here that transcription in the Hox clusters is far more complex than previously described in both human and mouse. Unannotated transcripts can represent up to 60% of the total transcriptional output of a cluster. In particular, we identified 14 non-coding Transcriptional Units antisense to Hox genes, 10 of which (70% have a detectable mouse homolog. Most of these Transcriptional Units in both human and mouse present conserved sizeable sequences (>40 bp overlapping Hox transcripts, suggesting that these Hox antisense transcripts are functional. Hox clusters also display at least seven polycistronic clusters, i.e., different genes being co-transcribed on long isoforms (up to 30 kb. This work provides a reevaluated framework for understanding Hox gene function and dys-function. Such extensive transcriptions may provide a structural explanation for Hox clustering.

  20. Changing wind-power landscapes

    DEFF Research Database (Denmark)

    Möller, Bernd

    2006-01-01

    of determining the likely visual-impact on landscapes and population, taking into account that there is no clear threshold for perceived adverse visual-impact. A geographical information system (GIS) has been used to build a regional landscape model for Northern Jutland County, which is used to assess visibility...

  1. Marc Treib: Representing Landscape Architecture

    DEFF Research Database (Denmark)

    Braae, Ellen Marie

    2008-01-01

    The editor of Representing Landscape Architecture, Marc Treib, argues that there is good reason to evaluate the standard practices of representation that landscape architects have been using for so long. In the rush to the promised land of computer design these practices are now in danger of being...

  2. Caribbean landscapes and their biodiversity

    Science.gov (United States)

    A. E. Lugo; E. H. Helmer; E. Santiago Valentín

    2012-01-01

    Both the biodiversity and the landscapes of the Caribbean have been greatly modified as a consequence of human activity. In this essay we provide an overview of the natural landscapes and biodiversity of the Caribbean and discuss how human activity has affected both. Our Caribbean geographic focus is on the insular Caribbean and the biodiversity focus is on the flora,...

  3. Future landscapes: opportunities and challenges

    Science.gov (United States)

    John Stanturf

    2015-01-01

    The global magnitude of degraded and deforested areas is best approached by restoring landscapes. Heightened international perception of the importance of forests and trees outside forests (e.g., woodlands, on farms) demands new approaches to future landscapes. The current need for forest restoration is two billion ha; most opportunities are mosaic restoration in the...

  4. Landscape in a Lacquer Box

    Science.gov (United States)

    Savage, Martha

    2010-01-01

    A symbolic dry landscape garden of Eastern origin holds a special fascination for the author's middle-school students, which is why the author chose to create a project exploring this view of nature. A dry landscape garden, or "karesansui," is an arrangement of rocks, worn by nature and surrounded by a "sea" of sand, raked into patterns…

  5. Contingent Diversity on Anthropic Landscapes

    Directory of Open Access Journals (Sweden)

    William Balée

    2010-02-01

    Full Text Available Behaviorally modern human beings have lived in Amazonia for thousands of years. Significant dynamics in species turnovers due to human-mediated disturbance were associated with the ultimate emergence and expansion of agrarian technologies in prehistory. Such disturbances initiated primary and secondary landscape transformations in various locales of the Amazon region. Diversity in these locales can be understood by accepting the initial premise of contingency, expressed as unprecedented human agency and human history. These effects can be accessed through the archaeological record and in the study of living languages. In addition, landscape transformation can be demonstrated in the study of traditional knowledge (TK. One way of elucidating TK distinctions between anthropic and nonanthropic landscapes concerns elicitation of differential labeling of these landscapes and more significantly, elicitation of the specific contents, such as trees, occurring in these landscapes. Freelisting is a method which can be used to distinguish the differential species compositions of landscapes resulting from human-mediated disturbance vs. those which do not evince records of human agency and history. The TK of the Ka’apor Indians of Amazonian Brazil as revealed in freelisting exercises shows differentiation of anthropogenic from high forests as well as a recognition of diversity in the anthropogenic forests. This suggests that the agents of human-mediated disturbance and landscape transformation in traditional Amazonia encode diversity and contingency into their TK, which encoding reflects past cultural influence on landscape and society over time.

  6. LAPSUS: soil erosion - landscape evolution model

    Science.gov (United States)

    van Gorp, Wouter; Temme, Arnaud; Schoorl, Jeroen

    2015-04-01

    LAPSUS is a soil erosion - landscape evolution model which is capable of simulating landscape evolution of a gridded DEM by using multiple water, mass movement and human driven processes on multiple temporal and spatial scales. It is able to deal with a variety of human landscape interventions such as landuse management and tillage and it can model their interactions with natural processes. The complex spatially explicit feedbacks the model simulates demonstrate the importance of spatial interaction of human activity and erosion deposition patterns. In addition LAPSUS can model shallow landsliding, slope collapse, creep, solifluction, biological and frost weathering, fluvial behaviour. Furthermore, an algorithm to deal with natural depressions has been added and event-based modelling with an improved infiltration description and dust deposition has been pursued. LAPSUS has been used for case studies in many parts of the world and is continuously developing and expanding. it is now available for third-party and educational use. It has a comprehensive user interface and it is accompanied by a manual and exercises. The LAPSUS model is highly suitable to quantify and understand catchment-scale erosion processes. More information and a download link is available on www.lapsusmodel.nl.

  7. Fitness Landscapes of Functional RNAs

    Directory of Open Access Journals (Sweden)

    Ádám Kun

    2015-08-01

    Full Text Available The notion of fitness landscapes, a map between genotype and fitness, was proposed more than 80 years ago. For most of this time data was only available for a few alleles, and thus we had only a restricted view of the whole fitness landscape. Recently, advances in genetics and molecular biology allow a more detailed view of them. Here we review experimental and theoretical studies of fitness landscapes of functional RNAs, especially aptamers and ribozymes. We find that RNA structures can be divided into critical structures, connecting structures, neutral structures and forbidden structures. Such characterisation, coupled with theoretical sequence-to-structure predictions, allows us to construct the whole fitness landscape. Fitness landscapes then can be used to study evolution, and in our case the development of the RNA world.

  8. Possible landscapes in norms: how are they designed and communicated?

    Directory of Open Access Journals (Sweden)

    Camila Marques Zyngier

    2013-05-01

    Full Text Available Urban landscapes are the result of transformations which occur in different time and space scales. When considering a wider time scale, landscapes are the result of applying norms of land use and occupancy, configuring punctual volumes which form, when added together, a complex whole. In a shorter time scale, urban interventions are transformations as precise as surgeries, stirred by entrepreneurism. Considering these observations about how formally planned landscapes are formed, a few questions are raised, motivating this investigation: can a community – which inhabits, observes and constructs in any given landscape – understand, accompany and approve a new spatial configuration, transformed by interventions and controls? Is it possible to contribute, in any way, towards urban managements, promoting the science behind proposals and possibilities within the norms which model a landscape? What is the state-of-the-art of these transformations, especially in the changes promoted by urban management resulting from legislations? From these initial inquiries, a main question sums up the aim of this paper: How the possibilities which involve a designed urban landscape are communicated? Therefore, it’s interesting to analyze case studies in order to elucidate this guiding question. Two territorial realities, as pilot areas, are going to aid this investigation, regarding their similarities and differences.

  9. A Classification of Landscape Services to Support Local Landscape Planning

    Directory of Open Access Journals (Sweden)

    María Vallés-Planells

    2014-03-01

    Full Text Available The ecosystem services approach has been proven successful to measure the contributions of nature and greenery to human well-being. Ecosystems have an effect on quality of life, but landscapes also, as a broader concept, may contribute to people's well-being. The concept of landscape services, compared to ecosystem services, involves the social dimension of landscape and the spatial pattern resulting from both natural and human processes in the provision of benefits for human-well being. Our aim is to develop a classification for landscape services. The proposed typology of services is built on the Common International Classification of Ecosystem Services (CICES and on a critical review of existing literature on human well-being dimensions, existing ecosystem service classifications, and landscape perception. Three themes of landscape services are defined, each divided into several groups: provisioning, regulation and maintenance, cultural and social life fulfillment, with the latter focusing on health, enjoyment, and personal and social fulfillment. A special emphasis is made on cultural services, which are especially important when applied to landscape and which have received less attention.

  10. The Transcription Factor Encyclopedia

    DEFF Research Database (Denmark)

    Yusuf, Dimas; Butland, Stefanie L; Swanson, Magdalena I

    2012-01-01

    mini review articles on pertinent human, mouse and rat TFs. Notable features of the TFe website include a high-quality PDF generator and web API for programmatic data retrieval. TFe aims to rapidly educate scientists about the TFs they encounter through the delivery of succinct summaries written......ABSTRACT: Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130...

  11. The European nanometrology landscape.

    Science.gov (United States)

    Leach, Richard K; Boyd, Robert; Burke, Theresa; Danzebrink, Hans-Ulrich; Dirscherl, Kai; Dziomba, Thorsten; Gee, Mark; Koenders, Ludger; Morazzani, Valérie; Pidduck, Allan; Roy, Debdulal; Unger, Wolfgang E S; Yacoot, Andrew

    2011-02-11

    This review paper summarizes the European nanometrology landscape from a technical perspective. Dimensional and chemical nanometrology are discussed first as they underpin many of the developments in other areas of nanometrology. Applications for the measurement of thin film parameters are followed by two of the most widely relevant families of functional properties: measurement of mechanical and electrical properties at the nanoscale. Nanostructured materials and surfaces, which are seen as key materials areas having specific metrology challenges, are covered next. The final section describes biological nanometrology, which is perhaps the most interdisciplinary applications area, and presents unique challenges. Within each area, a review is provided of current status, the capabilities and limitations of current techniques and instruments, and future directions being driven by emerging industrial measurement requirements. Issues of traceability, standardization, national and international programmes, regulation and skills development will be discussed in a future paper.

  12. The European nanometrology landscape

    Science.gov (United States)

    Leach, Richard K.; Boyd, Robert; Burke, Theresa; Danzebrink, Hans-Ulrich; Dirscherl, Kai; Dziomba, Thorsten; Gee, Mark; Koenders, Ludger; Morazzani, Valérie; Pidduck, Allan; Roy, Debdulal; Unger, Wolfgang E. S.; Yacoot, Andrew

    2011-02-01

    This review paper summarizes the European nanometrology landscape from a technical perspective. Dimensional and chemical nanometrology are discussed first as they underpin many of the developments in other areas of nanometrology. Applications for the measurement of thin film parameters are followed by two of the most widely relevant families of functional properties: measurement of mechanical and electrical properties at the nanoscale. Nanostructured materials and surfaces, which are seen as key materials areas having specific metrology challenges, are covered next. The final section describes biological nanometrology, which is perhaps the most interdisciplinary applications area, and presents unique challenges. Within each area, a review is provided of current status, the capabilities and limitations of current techniques and instruments, and future directions being driven by emerging industrial measurement requirements. Issues of traceability, standardization, national and international programmes, regulation and skills development will be discussed in a future paper.

  13. The European nanometrology landscape

    International Nuclear Information System (INIS)

    Leach, Richard K; Boyd, Robert; Gee, Mark; Roy, Debdulal; Yacoot, Andrew; Burke, Theresa; Danzebrink, Hans-Ulrich; Dziomba, Thorsten; Koenders, Ludger; Dirscherl, Kai; Morazzani, Valerie; Pidduck, Allan; Unger, Wolfgang E S

    2011-01-01

    This review paper summarizes the European nanometrology landscape from a technical perspective. Dimensional and chemical nanometrology are discussed first as they underpin many of the developments in other areas of nanometrology. Applications for the measurement of thin film parameters are followed by two of the most widely relevant families of functional properties: measurement of mechanical and electrical properties at the nanoscale. Nanostructured materials and surfaces, which are seen as key materials areas having specific metrology challenges, are covered next. The final section describes biological nanometrology, which is perhaps the most interdisciplinary applications area, and presents unique challenges. Within each area, a review is provided of current status, the capabilities and limitations of current techniques and instruments, and future directions being driven by emerging industrial measurement requirements. Issues of traceability, standardization, national and international programmes, regulation and skills development will be discussed in a future paper. (topical review)

  14. The European nanometrology landscape

    Energy Technology Data Exchange (ETDEWEB)

    Leach, Richard K; Boyd, Robert; Gee, Mark; Roy, Debdulal; Yacoot, Andrew [National Physical Laboratory (United Kingdom); Burke, Theresa [European Society for Precision Engineering and Nanotechnology (United Kingdom); Danzebrink, Hans-Ulrich; Dziomba, Thorsten; Koenders, Ludger [Physikalisch-Technische Bundesanstalt (Germany); Dirscherl, Kai [Danish Fundamental Metrology (Denmark); Morazzani, Valerie [Laboratoire National de Metrologie et d' Essais (France); Pidduck, Allan [QinetiQ (United Kingdom); Unger, Wolfgang E S, E-mail: richard.leach@npl.co.uk [Federal Institute for Materials Research and Testing (Germany)

    2011-02-11

    This review paper summarizes the European nanometrology landscape from a technical perspective. Dimensional and chemical nanometrology are discussed first as they underpin many of the developments in other areas of nanometrology. Applications for the measurement of thin film parameters are followed by two of the most widely relevant families of functional properties: measurement of mechanical and electrical properties at the nanoscale. Nanostructured materials and surfaces, which are seen as key materials areas having specific metrology challenges, are covered next. The final section describes biological nanometrology, which is perhaps the most interdisciplinary applications area, and presents unique challenges. Within each area, a review is provided of current status, the capabilities and limitations of current techniques and instruments, and future directions being driven by emerging industrial measurement requirements. Issues of traceability, standardization, national and international programmes, regulation and skills development will be discussed in a future paper. (topical review)

  15. Data anonymization patent landscape

    Directory of Open Access Journals (Sweden)

    Mirjana Pejić Bach

    2017-01-01

    Full Text Available The omnipresent, unstoppable increase in digital data has led to a greater understanding of the importance of data privacy. Different approaches are used to implement data privacy. The goal of this paper is to develop a data anonymization patent landscape, by determining the following: (i the trend in data anonymization patenting, (ii the type of technical content protected in data anonymization, (iii the organizations and countries most active in patenting data anonymization know-how; and (iv the topics emerging most often in patent titles. Patents from the PatSeer database relating to data anonymization from 2001 to 2015 were analyzed. We used the longitudinal approach in combination with text mining techniques to develop a data anonymization patent landscape. The results indicated the following. The number of single patent families is growing with a high increase after 2010, thus indicating a positive trend in the area of patenting data anonymization solutions. The majority of patenting activities relate to the G Physics section. Organizations from the USA and Japan assigned the majority of patents related to data anonymization. The results of text mining indicate that the most often used word in titles of data anonymization patents are “anonym*, “method”, “data” and “system”. Several additional words that indicated the most frequent topics related to data anonymization were: “equipment”, “software”, “protection”, “identification”, or “encryption”, and specific topics such as “community”, “medical”, or “service”.

  16. Buildings Interoperability Landscape

    Energy Technology Data Exchange (ETDEWEB)

    Hardin, Dave [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Stephan, Eric G. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Wang, Weimin [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Corbin, Charles D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Widergren, Steven E. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2015-12-31

    Through its Building Technologies Office (BTO), the United States Department of Energy’s Office of Energy Efficiency and Renewable Energy (DOE-EERE) is sponsoring an effort to advance interoperability for the integration of intelligent buildings equipment and automation systems, understanding the importance of integration frameworks and product ecosystems to this cause. This is important to BTO’s mission to enhance energy efficiency and save energy for economic and environmental purposes. For connected buildings ecosystems of products and services from various manufacturers to flourish, the ICT aspects of the equipment need to integrate and operate simply and reliably. Within the concepts of interoperability lie the specification, development, and certification of equipment with standards-based interfaces that connect and work. Beyond this, a healthy community of stakeholders that contribute to and use interoperability work products must be developed. On May 1, 2014, the DOE convened a technical meeting to take stock of the current state of interoperability of connected equipment and systems in buildings. Several insights from that meeting helped facilitate a draft description of the landscape of interoperability for connected buildings, which focuses mainly on small and medium commercial buildings. This document revises the February 2015 landscape document to address reviewer comments, incorporate important insights from the Buildings Interoperability Vision technical meeting, and capture thoughts from that meeting about the topics to be addressed in a buildings interoperability vision. In particular, greater attention is paid to the state of information modeling in buildings and the great potential for near-term benefits in this area from progress and community alignment.

  17. Watermill and Small-Scale Hydroelectric Power Plant Landscapes Assessed According to Ecological Aspects

    Directory of Open Access Journals (Sweden)

    Lilita Lazdāne

    2013-10-01

    Full Text Available Research of watermill and small-scale hydroelectric power plant (HPP landscapes in Latvia according to ecological aspects is a part of a more complex research. The aim of this research is to examine the existing situation of watermill and small-scale HPP landscapes in Latvia by applying the ecological assessment criteria, and then try to formulate a definition of common tendencies of the landscape character. This paper provides a landscape inventory matrix for research in the field stu­dies of landscape identificati