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Sample records for highly conserved cis-regulatory

  1. BLSSpeller: exhaustive comparative discovery of conserved cis-regulatory elements.

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    De Witte, Dieter; Van de Velde, Jan; Decap, Dries; Van Bel, Michiel; Audenaert, Pieter; Demeester, Piet; Dhoedt, Bart; Vandepoele, Klaas; Fostier, Jan

    2015-12-01

    The accurate discovery and annotation of regulatory elements remains a challenging problem. The growing number of sequenced genomes creates new opportunities for comparative approaches to motif discovery. Putative binding sites are then considered to be functional if they are conserved in orthologous promoter sequences of multiple related species. Existing methods for comparative motif discovery usually rely on pregenerated multiple sequence alignments, which are difficult to obtain for more diverged species such as plants. As a consequence, misaligned regulatory elements often remain undetected. We present a novel algorithm that supports both alignment-free and alignment-based motif discovery in the promoter sequences of related species. Putative motifs are exhaustively enumerated as words over the IUPAC alphabet and screened for conservation using the branch length score. Additionally, a confidence score is established in a genome-wide fashion. In order to take advantage of a cloud computing infrastructure, the MapReduce programming model is adopted. The method is applied to four monocotyledon plant species and it is shown that high-scoring motifs are significantly enriched for open chromatin regions in Oryza sativa and for transcription factor binding sites inferred through protein-binding microarrays in O.sativa and Zea mays. Furthermore, the method is shown to recover experimentally profiled ga2ox1-like KN1 binding sites in Z.mays. BLSSpeller was written in Java. Source code and manual are available at http://bioinformatics.intec.ugent.be/blsspeller Klaas.Vandepoele@psb.vib-ugent.be or jan.fostier@intec.ugent.be. Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press.

  2. Conserved cis-regulatory regions in a large genomic landscape control SHH and BMP-regulated Gremlin1 expression in mouse limb buds

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    Zuniga Aimée

    2012-08-01

    Full Text Available Abstract Background Mouse limb bud is a prime model to study the regulatory interactions that control vertebrate organogenesis. Major aspects of limb bud development are controlled by feedback loops that define a self-regulatory signalling system. The SHH/GREM1/AER-FGF feedback loop forms the core of this signalling system that operates between the posterior mesenchymal organiser and the ectodermal signalling centre. The BMP antagonist Gremlin1 (GREM1 is a critical node in this system, whose dynamic expression is controlled by BMP, SHH, and FGF signalling and key to normal progression of limb bud development. Previous analysis identified a distant cis-regulatory landscape within the neighbouring Formin1 (Fmn1 locus that is required for Grem1 expression, reminiscent of the genomic landscapes controlling HoxD and Shh expression in limb buds. Results Three highly conserved regions (HMCO1-3 were identified within the previously defined critical genomic region and tested for their ability to regulate Grem1 expression in mouse limb buds. Using a combination of BAC and conventional transgenic approaches, a 9 kb region located ~70 kb downstream of the Grem1 transcription unit was identified. This region, termed Grem1 Regulatory Sequence 1 (GRS1, is able to recapitulate major aspects of Grem1 expression, as it drives expression of a LacZ reporter into the posterior and, to a lesser extent, in the distal-anterior mesenchyme. Crossing the GRS1 transgene into embryos with alterations in the SHH and BMP pathways established that GRS1 depends on SHH and is modulated by BMP signalling, i.e. integrates inputs from these pathways. Chromatin immunoprecipitation revealed interaction of endogenous GLI3 proteins with the core cis-regulatory elements in the GRS1 region. As GLI3 is a mediator of SHH signal transduction, these results indicated that SHH directly controls Grem1 expression through the GRS1 region. Finally, all cis-regulatory regions within the Grem1

  3. Mapping cis-Regulatory Domains in the Human Genome UsingMulti-Species Conservation of Synteny

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    Ahituv, Nadav; Prabhakar, Shyam; Poulin, Francis; Rubin, EdwardM.; Couronne, Olivier

    2005-06-13

    Our inability to associate distant regulatory elements with the genes that they regulate has largely precluded their examination for sequence alterations contributing to human disease. One major obstacle is the large genomic space surrounding targeted genes in which such elements could potentially reside. In order to delineate gene regulatory boundaries we used whole-genome human-mouse-chicken (HMC) and human-mouse-frog (HMF) multiple alignments to compile conserved blocks of synteny (CBS), under the hypothesis that these blocks have been kept intact throughout evolution at least in part by the requirement of regulatory elements to stay linked to the genes that they regulate. A total of 2,116 and 1,942 CBS>200 kb were assembled for HMC and HMF respectively, encompassing 1.53 and 0.86 Gb of human sequence. To support the existence of complex long-range regulatory domains within these CBS we analyzed the prevalence and distribution of chromosomal aberrations leading to position effects (disruption of a genes regulatory environment), observing a clear bias not only for mapping onto CBS but also for longer CBS size. Our results provide a genome wide data set characterizing the regulatory domains of genes and the conserved regulatory elements within them.

  4. Mouse transgenesis identifies conserved functional enhancers and cis-regulatory motif in the vertebrate LIM homeobox gene Lhx2 locus.

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    Alison P Lee

    Full Text Available The vertebrate Lhx2 is a member of the LIM homeobox family of transcription factors. It is essential for the normal development of the forebrain, eye, olfactory system and liver as well for the differentiation of lymphoid cells. However, despite the highly restricted spatio-temporal expression pattern of Lhx2, nothing is known about its transcriptional regulation. In mammals and chicken, Crb2, Dennd1a and Lhx2 constitute a conserved linkage block, while the intervening Dennd1a is lost in the fugu Lhx2 locus. To identify functional enhancers of Lhx2, we predicted conserved noncoding elements (CNEs in the human, mouse and fugu Crb2-Lhx2 loci and assayed their function in transgenic mouse at E11.5. Four of the eight CNE constructs tested functioned as tissue-specific enhancers in specific regions of the central nervous system and the dorsal root ganglia (DRG, recapitulating partial and overlapping expression patterns of Lhx2 and Crb2 genes. There was considerable overlap in the expression domains of the CNEs, which suggests that the CNEs are either redundant enhancers or regulating different genes in the locus. Using a large set of CNEs (810 CNEs associated with transcription factor-encoding genes that express predominantly in the central nervous system, we predicted four over-represented 8-mer motifs that are likely to be associated with expression in the central nervous system. Mutation of one of them in a CNE that drove reporter expression in the neural tube and DRG abolished expression in both domains indicating that this motif is essential for expression in these domains. The failure of the four functional enhancers to recapitulate the complete expression pattern of Lhx2 at E11.5 indicates that there must be other Lhx2 enhancers that are either located outside the region investigated or divergent in mammals and fishes. Other approaches such as sequence comparison between multiple mammals are required to identify and characterize such enhancers.

  5. Functional dissection of the promoter of the pollen-specific gene NTP303 reveals a novel pollen-specific, and conserved cis-regulatory element.

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    Weterings, K; Schrauwen, J; Wullems, G; Twell, D

    1995-07-01

    Regulatory elements within the promoter of the pollen-specific NTP303 gene from tobacco were analysed by transient and stable expression analyses. Analysis of precisely targeted mutations showed that the NTP303 promoter is not regulated by any of the previously described pollen-specific cis-regulatory elements. However, two adjacent regions from -103 to -86 bp and from -86 to -59 bp were shown to contain sequences which positively regulated the NTP303 promoter. Both of these regions were capable of driving pollen-specific expression from a heterologous promoter, independent of orientation and in an additive manner. The boundaries of the minimal, functional NTP303 promoter were determined to lie within the region -86 to -51 bp. The sequence AAATGA localized from -94 to -89 bp was identified as a novel cis-acting element, of which the TGA triplet was shown to comprise an active part. This element was shown to be completely conserved in the similarly regulated promoter of the Bp 10 gene from Brassica napus encoding a homologue of the NTP303 gene.

  6. RNA-ID, a highly sensitive and robust method to identify cis-regulatory sequences using superfolder GFP and a fluorescence-based assay.

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    Dean, Kimberly M; Grayhack, Elizabeth J

    2012-12-01

    We have developed a robust and sensitive method, called RNA-ID, to screen for cis-regulatory sequences in RNA using fluorescence-activated cell sorting (FACS) of yeast cells bearing a reporter in which expression of both superfolder green fluorescent protein (GFP) and yeast codon-optimized mCherry red fluorescent protein (RFP) is driven by the bidirectional GAL1,10 promoter. This method recapitulates previously reported progressive inhibition of translation mediated by increasing numbers of CGA codon pairs, and restoration of expression by introduction of a tRNA with an anticodon that base pairs exactly with the CGA codon. This method also reproduces effects of paromomycin and context on stop codon read-through. Five key features of this method contribute to its effectiveness as a selection for regulatory sequences: The system exhibits greater than a 250-fold dynamic range, a quantitative and dose-dependent response to known inhibitory sequences, exquisite resolution that allows nearly complete physical separation of distinct populations, and a reproducible signal between different cells transformed with the identical reporter, all of which are coupled with simple methods involving ligation-independent cloning, to create large libraries. Moreover, we provide evidence that there are sequences within a 9-nt library that cause reduced GFP fluorescence, suggesting that there are novel cis-regulatory sequences to be found even in this short sequence space. This method is widely applicable to the study of both RNA-mediated and codon-mediated effects on expression.

  7. Statistical significance of cis-regulatory modules

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    Smith Andrew D

    2007-01-01

    Full Text Available Abstract Background It is becoming increasingly important for researchers to be able to scan through large genomic regions for transcription factor binding sites or clusters of binding sites forming cis-regulatory modules. Correspondingly, there has been a push to develop algorithms for the rapid detection and assessment of cis-regulatory modules. While various algorithms for this purpose have been introduced, most are not well suited for rapid, genome scale scanning. Results We introduce methods designed for the detection and statistical evaluation of cis-regulatory modules, modeled as either clusters of individual binding sites or as combinations of sites with constrained organization. In order to determine the statistical significance of module sites, we first need a method to determine the statistical significance of single transcription factor binding site matches. We introduce a straightforward method of estimating the statistical significance of single site matches using a database of known promoters to produce data structures that can be used to estimate p-values for binding site matches. We next introduce a technique to calculate the statistical significance of the arrangement of binding sites within a module using a max-gap model. If the module scanned for has defined organizational parameters, the probability of the module is corrected to account for organizational constraints. The statistical significance of single site matches and the architecture of sites within the module can be combined to provide an overall estimation of statistical significance of cis-regulatory module sites. Conclusion The methods introduced in this paper allow for the detection and statistical evaluation of single transcription factor binding sites and cis-regulatory modules. The features described are implemented in the Search Tool for Occurrences of Regulatory Motifs (STORM and MODSTORM software.

  8. Comparative genomics of metabolic capacities of regulons controlled by cis-regulatory RNA motifs in bacteria.

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    Sun, Eric I; Leyn, Semen A; Kazanov, Marat D; Saier, Milton H; Novichkov, Pavel S; Rodionov, Dmitry A

    2013-09-02

    In silico comparative genomics approaches have been efficiently used for functional prediction and reconstruction of metabolic and regulatory networks. Riboswitches are metabolite-sensing structures often found in bacterial mRNA leaders controlling gene expression on transcriptional or translational levels.An increasing number of riboswitches and other cis-regulatory RNAs have been recently classified into numerous RNA families in the Rfam database. High conservation of these RNA motifs provides a unique advantage for their genomic identification and comparative analysis. A comparative genomics approach implemented in the RegPredict tool was used for reconstruction and functional annotation of regulons controlled by RNAs from 43 Rfam families in diverse taxonomic groups of Bacteria. The inferred regulons include ~5200 cis-regulatory RNAs and more than 12000 target genes in 255 microbial genomes. All predicted RNA-regulated genes were classified into specific and overall functional categories. Analysis of taxonomic distribution of these categories allowed us to establish major functional preferences for each analyzed cis-regulatory RNA motif family. Overall, most RNA motif regulons showed predictable functional content in accordance with their experimentally established effector ligands. Our results suggest that some RNA motifs (including thiamin pyrophosphate and cobalamin riboswitches that control the cofactor metabolism) are widespread and likely originated from the last common ancestor of all bacteria. However, many more analyzed RNA motifs are restricted to a narrow taxonomic group of bacteria and likely represent more recent evolutionary innovations. The reconstructed regulatory networks for major known RNA motifs substantially expand the existing knowledge of transcriptional regulation in bacteria. The inferred regulons can be used for genetic experiments, functional annotations of genes, metabolic reconstruction and evolutionary analysis. The obtained genome

  9. Cis-regulatory somatic mutations and gene-expression alteration in B-cell lymphomas.

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    Mathelier, Anthony; Lefebvre, Calvin; Zhang, Allen W; Arenillas, David J; Ding, Jiarui; Wasserman, Wyeth W; Shah, Sohrab P

    2015-04-23

    With the rapid increase of whole-genome sequencing of human cancers, an important opportunity to analyze and characterize somatic mutations lying within cis-regulatory regions has emerged. A focus on protein-coding regions to identify nonsense or missense mutations disruptive to protein structure and/or function has led to important insights; however, the impact on gene expression of mutations lying within cis-regulatory regions remains under-explored. We analyzed somatic mutations from 84 matched tumor-normal whole genomes from B-cell lymphomas with accompanying gene expression measurements to elucidate the extent to which these cancers are disrupted by cis-regulatory mutations. We characterize mutations overlapping a high quality set of well-annotated transcription factor binding sites (TFBSs), covering a similar portion of the genome as protein-coding exons. Our results indicate that cis-regulatory mutations overlapping predicted TFBSs are enriched in promoter regions of genes involved in apoptosis or growth/proliferation. By integrating gene expression data with mutation data, our computational approach culminates with identification of cis-regulatory mutations most likely to participate in dysregulation of the gene expression program. The impact can be measured along with protein-coding mutations to highlight key mutations disrupting gene expression and pathways in cancer. Our study yields specific genes with disrupted expression triggered by genomic mutations in either the coding or the regulatory space. It implies that mutated regulatory components of the genome contribute substantially to cancer pathways. Our analyses demonstrate that identifying genomically altered cis-regulatory elements coupled with analysis of gene expression data will augment biological interpretation of mutational landscapes of cancers.

  10. ChIP-Seq-Annotated Heliconius erato Genome Highlights Patterns of cis-Regulatory Evolution in Lepidoptera

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    James J. Lewis

    2016-09-01

    Full Text Available Uncovering phylogenetic patterns of cis-regulatory evolution remains a fundamental goal for evolutionary and developmental biology. Here, we characterize the evolution of regulatory loci in butterflies and moths using chromatin immunoprecipitation sequencing (ChIP-seq annotation of regulatory elements across three stages of head development. In the process we provide a high-quality, functionally annotated genome assembly for the butterfly, Heliconius erato. Comparing cis-regulatory element conservation across six lepidopteran genomes, we find that regulatory sequences evolve at a pace similar to that of protein-coding regions. We also observe that elements active at multiple developmental stages are markedly more conserved than elements with stage-specific activity. Surprisingly, we also find that stage-specific proximal and distal regulatory elements evolve at nearly identical rates. Our study provides a benchmark for genome-wide patterns of regulatory element evolution in insects, and it shows that developmental timing of activity strongly predicts patterns of regulatory sequence evolution.

  11. Computational and molecular dissection of an X-box cis-Regulatory module

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    Warrington, Timothy Burton

    2015-01-01

    Ciliopathies are a class of human diseases marked by dysfunction of the cellular organelle, cilia. While many of the molecular components that make up cilia have been identified and studied, comparatively little is understood about the transcriptional regulation of genes encoding these components. The conserved transcription factor Regulatory Factor X (RFX)/DAF-19, which acts through binding to the cis-regulatory motif known as X-box, has been shown to regulate ciliary genes in many animals f...

  12. Genetic mapping uncovers cis-regulatory landscape of RNA editing.

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    Ramaswami, Gokul; Deng, Patricia; Zhang, Rui; Anna Carbone, Mary; Mackay, Trudy F C; Li, Jin Billy

    2015-09-16

    Adenosine-to-inosine (A-to-I) RNA editing, catalysed by ADAR enzymes conserved in metazoans, plays an important role in neurological functions. Although the fine-tuning mechanism provided by A-to-I RNA editing is important, the underlying rules governing ADAR substrate recognition are not well understood. We apply a quantitative trait loci (QTL) mapping approach to identify genetic variants associated with variability in RNA editing. With very accurate measurement of RNA editing levels at 789 sites in 131 Drosophila melanogaster strains, here we identify 545 editing QTLs (edQTLs) associated with differences in RNA editing. We demonstrate that many edQTLs can act through changes in the local secondary structure for edited dsRNAs. Furthermore, we find that edQTLs located outside of the edited dsRNA duplex are enriched in secondary structure, suggesting that distal dsRNA structure beyond the editing site duplex affects RNA editing efficiency. Our work will facilitate the understanding of the cis-regulatory code of RNA editing.

  13. Genome-wide prediction of cis-regulatory regions using supervised deep learning methods.

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    Li, Yifeng; Shi, Wenqiang; Wasserman, Wyeth W

    2018-05-31

    In the human genome, 98% of DNA sequences are non-protein-coding regions that were previously disregarded as junk DNA. In fact, non-coding regions host a variety of cis-regulatory regions which precisely control the expression of genes. Thus, Identifying active cis-regulatory regions in the human genome is critical for understanding gene regulation and assessing the impact of genetic variation on phenotype. The developments of high-throughput sequencing and machine learning technologies make it possible to predict cis-regulatory regions genome wide. Based on rich data resources such as the Encyclopedia of DNA Elements (ENCODE) and the Functional Annotation of the Mammalian Genome (FANTOM) projects, we introduce DECRES based on supervised deep learning approaches for the identification of enhancer and promoter regions in the human genome. Due to their ability to discover patterns in large and complex data, the introduction of deep learning methods enables a significant advance in our knowledge of the genomic locations of cis-regulatory regions. Using models for well-characterized cell lines, we identify key experimental features that contribute to the predictive performance. Applying DECRES, we delineate locations of 300,000 candidate enhancers genome wide (6.8% of the genome, of which 40,000 are supported by bidirectional transcription data), and 26,000 candidate promoters (0.6% of the genome). The predicted annotations of cis-regulatory regions will provide broad utility for genome interpretation from functional genomics to clinical applications. The DECRES model demonstrates potentials of deep learning technologies when combined with high-throughput sequencing data, and inspires the development of other advanced neural network models for further improvement of genome annotations.

  14. Evolution of Cis-Regulatory Elements and Regulatory Networks in Duplicated Genes of Arabidopsis.

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    Arsovski, Andrej A; Pradinuk, Julian; Guo, Xu Qiu; Wang, Sishuo; Adams, Keith L

    2015-12-01

    Plant genomes contain large numbers of duplicated genes that contribute to the evolution of new functions. Following duplication, genes can exhibit divergence in their coding sequence and their expression patterns. Changes in the cis-regulatory element landscape can result in changes in gene expression patterns. High-throughput methods developed recently can identify potential cis-regulatory elements on a genome-wide scale. Here, we use a recent comprehensive data set of DNase I sequencing-identified cis-regulatory binding sites (footprints) at single-base-pair resolution to compare binding sites and network connectivity in duplicated gene pairs in Arabidopsis (Arabidopsis thaliana). We found that duplicated gene pairs vary greatly in their cis-regulatory element architecture, resulting in changes in regulatory network connectivity. Whole-genome duplicates (WGDs) have approximately twice as many footprints in their promoters left by potential regulatory proteins than do tandem duplicates (TDs). The WGDs have a greater average number of footprint differences between paralogs than TDs. The footprints, in turn, result in more regulatory network connections between WGDs and other genes, forming denser, more complex regulatory networks than shown by TDs. When comparing regulatory connections between duplicates, WGDs had more pairs in which the two genes are either partially or fully diverged in their network connections, but fewer genes with no network connections than the TDs. There is evidence of younger TDs and WGDs having fewer unique connections compared with older duplicates. This study provides insights into cis-regulatory element evolution and network divergence in duplicated genes. © 2015 American Society of Plant Biologists. All Rights Reserved.

  15. Identifying cis-regulatory modules by combining comparative and compositional analysis of DNA.

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    Pierstorff, Nora; Bergman, Casey M; Wiehe, Thomas

    2006-12-01

    Predicting cis-regulatory modules (CRMs) in higher eukaryotes is a challenging computational task. Commonly used methods to predict CRMs based on the signal of transcription factor binding sites (TFBS) are limited by prior information about transcription factor specificity. More general methods that bypass the reliance on TFBS models are needed for comprehensive CRM prediction. We have developed a method to predict CRMs called CisPlusFinder that identifies high density regions of perfect local ungapped sequences (PLUSs) based on multiple species conservation. By assuming that PLUSs contain core TFBS motifs that are locally overrepresented, the method attempts to capture the expected features of CRM structure and evolution. Applied to a benchmark dataset of CRMs involved in early Drosophila development, CisPlusFinder predicts more annotated CRMs than all other methods tested. Using the REDfly database, we find that some 'false positive' predictions in the benchmark dataset correspond to recently annotated CRMs. Our work demonstrates that CRM prediction methods that combine comparative genomic data with statistical properties of DNA may achieve reasonable performance when applied genome-wide in the absence of an a priori set of known TFBS motifs. The program CisPlusFinder can be downloaded at http://jakob.genetik.uni-koeln.de/bioinformatik/people/nora/nora.html. All software is licensed under the Lesser GNU Public License (LGPL).

  16. Functional evolution of cis-regulatory modules at a homeotic gene in Drosophila.

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    Margaret C W Ho

    2009-11-01

    Full Text Available It is a long-held belief in evolutionary biology that the rate of molecular evolution for a given DNA sequence is inversely related to the level of functional constraint. This belief holds true for the protein-coding homeotic (Hox genes originally discovered in Drosophila melanogaster. Expression of the Hox genes in Drosophila embryos is essential for body patterning and is controlled by an extensive array of cis-regulatory modules (CRMs. How the regulatory modules functionally evolve in different species is not clear. A comparison of the CRMs for the Abdominal-B gene from different Drosophila species reveals relatively low levels of overall sequence conservation. However, embryonic enhancer CRMs from other Drosophila species direct transgenic reporter gene expression in the same spatial and temporal patterns during development as their D. melanogaster orthologs. Bioinformatic analysis reveals the presence of short conserved sequences within defined CRMs, representing gap and pair-rule transcription factor binding sites. One predicted binding site for the gap transcription factor KRUPPEL in the IAB5 CRM was found to be altered in Superabdominal (Sab mutations. In Sab mutant flies, the third abdominal segment is transformed into a copy of the fifth abdominal segment. A model for KRUPPEL-mediated repression at this binding site is presented. These findings challenge our current understanding of the relationship between sequence evolution at the molecular level and functional activity of a CRM. While the overall sequence conservation at Drosophila CRMs is not distinctive from neighboring genomic regions, functionally critical transcription factor binding sites within embryonic enhancer CRMs are highly conserved. These results have implications for understanding mechanisms of gene expression during embryonic development, enhancer function, and the molecular evolution of eukaryotic regulatory modules.

  17. Identification of a cis-regulatory element by transient analysis of co-ordinately regulated genes

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    Allan Andrew C

    2008-07-01

    Full Text Available Abstract Background Transcription factors (TFs co-ordinately regulate target genes that are dispersed throughout the genome. This co-ordinate regulation is achieved, in part, through the interaction of transcription factors with conserved cis-regulatory motifs that are in close proximity to the target genes. While much is known about the families of transcription factors that regulate gene expression in plants, there are few well characterised cis-regulatory motifs. In Arabidopsis, over-expression of the MYB transcription factor PAP1 (PRODUCTION OF ANTHOCYANIN PIGMENT 1 leads to transgenic plants with elevated anthocyanin levels due to the co-ordinated up-regulation of genes in the anthocyanin biosynthetic pathway. In addition to the anthocyanin biosynthetic genes, there are a number of un-associated genes that also change in expression level. This may be a direct or indirect consequence of the over-expression of PAP1. Results Oligo array analysis of PAP1 over-expression Arabidopsis plants identified genes co-ordinately up-regulated in response to the elevated expression of this transcription factor. Transient assays on the promoter regions of 33 of these up-regulated genes identified eight promoter fragments that were transactivated by PAP1. Bioinformatic analysis on these promoters revealed a common cis-regulatory motif that we showed is required for PAP1 dependent transactivation. Conclusion Co-ordinated gene regulation by individual transcription factors is a complex collection of both direct and indirect effects. Transient transactivation assays provide a rapid method to identify direct target genes from indirect target genes. Bioinformatic analysis of the promoters of these direct target genes is able to locate motifs that are common to this sub-set of promoters, which is impossible to identify with the larger set of direct and indirect target genes. While this type of analysis does not prove a direct interaction between protein and DNA

  18. Bounded search for de novo identification of degenerate cis-regulatory elements

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    Khetani Radhika S

    2006-05-01

    Full Text Available Abstract Background The identification of statistically overrepresented sequences in the upstream regions of coregulated genes should theoretically permit the identification of potential cis-regulatory elements. However, in practice many cis-regulatory elements are highly degenerate, precluding the use of an exhaustive word-counting strategy for their identification. While numerous methods exist for inferring base distributions using a position weight matrix, recent studies suggest that the independence assumptions inherent in the model, as well as the inability to reach a global optimum, limit this approach. Results In this paper, we report PRISM, a degenerate motif finder that leverages the relationship between the statistical significance of a set of binding sites and that of the individual binding sites. PRISM first identifies overrepresented, non-degenerate consensus motifs, then iteratively relaxes each one into a high-scoring degenerate motif. This approach requires no tunable parameters, thereby lending itself to unbiased performance comparisons. We therefore compare PRISM's performance against nine popular motif finders on 28 well-characterized S. cerevisiae regulons. PRISM consistently outperforms all other programs. Finally, we use PRISM to predict the binding sites of uncharacterized regulons. Our results support a proposed mechanism of action for the yeast cell-cycle transcription factor Stb1, whose binding site has not been determined experimentally. Conclusion The relationship between statistical measures of the binding sites and the set as a whole leads to a simple means of identifying the diverse range of cis-regulatory elements to which a protein binds. This approach leverages the advantages of word-counting, in that position dependencies are implicitly accounted for and local optima are more easily avoided. While we sacrifice guaranteed optimality to prevent the exponential blowup of exhaustive search, we prove that the error

  19. Identification of putative cis-regulatory elements in Cryptosporidium parvum by de novo pattern finding

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    Kissinger Jessica C

    2007-01-01

    Full Text Available Abstract Background Cryptosporidium parvum is a unicellular eukaryote in the phylum Apicomplexa. It is an obligate intracellular parasite that causes diarrhea and is a significant AIDS-related pathogen. Cryptosporidium parvum is not amenable to long-term laboratory cultivation or classical molecular genetic analysis. The parasite exhibits a complex life cycle, a broad host range, and fundamental mechanisms of gene regulation remain unknown. We have used data from the recently sequenced genome of this organism to uncover clues about gene regulation in C. parvum. We have applied two pattern finding algorithms MEME and AlignACE to identify conserved, over-represented motifs in the 5' upstream regions of genes in C. parvum. To support our findings, we have established comparative real-time -PCR expression profiles for the groups of genes examined computationally. Results We find that groups of genes that share a function or belong to a common pathway share upstream motifs. Different motifs are conserved upstream of different groups of genes. Comparative real-time PCR studies show co-expression of genes within each group (in sub-sets during the life cycle of the parasite, suggesting co-regulation of these genes may be driven by the use of conserved upstream motifs. Conclusion This is one of the first attempts to characterize cis-regulatory elements in the absence of any previously characterized elements and with very limited expression data (seven genes only. Using de novo pattern finding algorithms, we have identified specific DNA motifs that are conserved upstream of genes belonging to the same metabolic pathway or gene family. We have demonstrated the co-expression of these genes (often in subsets using comparative real-time-PCR experiments thus establishing evidence for these conserved motifs as putative cis-regulatory elements. Given the lack of prior information concerning expression patterns and organization of promoters in C. parvum we

  20. Implications of duplicated cis-regulatory elements in the evolution of metazoans: the DDI model or how simplicity begets novelty.

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    Jiménez-Delgado, Senda; Pascual-Anaya, Juan; Garcia-Fernàndez, Jordi

    2009-07-01

    The discovery that most regulatory genes were conserved among animals from distant phyla challenged the ideas that gene duplication and divergence of homologous coding sequences were the basis for major morphological changes in metazoan evolution. In recent years, however, the interest for the roles, conservation and changes of non-coding sequences grew-up in parallel with genome sequencing projects. Presently, many independent studies are highlighting the importance that subtle changes in cis-regulatory regions had in the evolution of morphology trough the Animal Kingdom. Here we will show and discuss some of these studies, and underscore the future of cis-Evo-Devo research. Nevertheless, we would also explore how gene duplication, which includes duplication of regulatory regions, may have been critical for spatial or temporal co-option of new regulatory networks, causing the deployment of new transcriptome scenarios, and how these induced morphological changes were critical for the evolution of new forms. Forty years after Susumu Ohno famous sentence 'natural selection merely modifies, while redundancy creates', we suggest the alternative: 'natural selection modifies, while redundancy of cis-regulatory elements innovates', and propose the Duplication-Degeneration-Innovation model to explain the increased evolvability of duplicated cis-regulatory regions. Paradoxically, making regulation simpler by subfunctionalization paved the path for future complexity or, in other words, 'to make it simple to make it complex'.

  1. Alignment and prediction of cis-regulatory modules based on a probabilistic model of evolution.

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    Xin He

    2009-03-01

    Full Text Available Cross-species comparison has emerged as a powerful paradigm for predicting cis-regulatory modules (CRMs and understanding their evolution. The comparison requires reliable sequence alignment, which remains a challenging task for less conserved noncoding sequences. Furthermore, the existing models of DNA sequence evolution generally do not explicitly treat the special properties of CRM sequences. To address these limitations, we propose a model of CRM evolution that captures different modes of evolution of functional transcription factor binding sites (TFBSs and the background sequences. A particularly novel aspect of our work is a probabilistic model of gains and losses of TFBSs, a process being recognized as an important part of regulatory sequence evolution. We present a computational framework that uses this model to solve the problems of CRM alignment and prediction. Our alignment method is similar to existing methods of statistical alignment but uses the conserved binding sites to improve alignment. Our CRM prediction method deals with the inherent uncertainties of binding site annotations and sequence alignment in a probabilistic framework. In simulated as well as real data, we demonstrate that our program is able to improve both alignment and prediction of CRM sequences over several state-of-the-art methods. Finally, we used alignments produced by our program to study binding site conservation in genome-wide binding data of key transcription factors in the Drosophila blastoderm, with two intriguing results: (i the factor-bound sequences are under strong evolutionary constraints even if their neighboring genes are not expressed in the blastoderm and (ii binding sites in distal bound sequences (relative to transcription start sites tend to be more conserved than those in proximal regions. Our approach is implemented as software, EMMA (Evolutionary Model-based cis-regulatory Module Analysis, ready to be applied in a broad biological context.

  2. Evolution of New cis-Regulatory Motifs Required for Cell-Specific Gene Expression in Caenorhabditis.

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    Michalis Barkoulas

    2016-09-01

    Full Text Available Patterning of C. elegans vulval cell fates relies on inductive signaling. In this induction event, a single cell, the gonadal anchor cell, secretes LIN-3/EGF and induces three out of six competent precursor cells to acquire a vulval fate. We previously showed that this developmental system is robust to a four-fold variation in lin-3/EGF genetic dose. Here using single-molecule FISH, we find that the mean level of expression of lin-3 in the anchor cell is remarkably conserved. No change in lin-3 expression level could be detected among C. elegans wild isolates and only a low level of change-less than 30%-in the Caenorhabditis genus and in Oscheius tipulae. In C. elegans, lin-3 expression in the anchor cell is known to require three transcription factor binding sites, specifically two E-boxes and a nuclear-hormone-receptor (NHR binding site. Mutation of any of these three elements in C. elegans results in a dramatic decrease in lin-3 expression. Yet only a single E-box is found in the Drosophilae supergroup of Caenorhabditis species, including C. angaria, while the NHR-binding site likely only evolved at the base of the Elegans group. We find that a transgene from C. angaria bearing a single E-box is sufficient for normal expression in C. elegans. Even a short 58 bp cis-regulatory fragment from C. angaria with this single E-box is able to replace the three transcription factor binding sites at the endogenous C. elegans lin-3 locus, resulting in the wild-type expression level. Thus, regulatory evolution occurring in cis within a 58 bp lin-3 fragment, results in a strict requirement for the NHR binding site and a second E-box in C. elegans. This single-cell, single-molecule, quantitative and functional evo-devo study demonstrates that conserved expression levels can hide extensive change in cis-regulatory site requirements and highlights the evolution of new cis-regulatory elements required for cell-specific gene expression.

  3. Changes in cis-regulatory elements of a key floral regulator are associated with divergence of inflorescence architectures.

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    Kusters, Elske; Della Pina, Serena; Castel, Rob; Souer, Erik; Koes, Ronald

    2015-08-15

    Higher plant species diverged extensively with regard to the moment (flowering time) and position (inflorescence architecture) at which flowers are formed. This seems largely caused by variation in the expression patterns of conserved genes that specify floral meristem identity (FMI), rather than changes in the encoded proteins. Here, we report a functional comparison of the promoters of homologous FMI genes from Arabidopsis, petunia, tomato and Antirrhinum. Analysis of promoter-reporter constructs in petunia and Arabidopsis, as well as complementation experiments, showed that the divergent expression of leafy (LFY) and the petunia homolog aberrant leaf and flower (ALF) results from alterations in the upstream regulatory network rather than cis-regulatory changes. The divergent expression of unusual floral organs (UFO) from Arabidopsis, and the petunia homolog double top (DOT), however, is caused by the loss or gain of cis-regulatory promoter elements, which respond to trans-acting factors that are expressed in similar patterns in both species. Introduction of pUFO:UFO causes no obvious defects in Arabidopsis, but in petunia it causes the precocious and ectopic formation of flowers. This provides an example of how a change in a cis-regulatory region can account for a change in the plant body plan. © 2015. Published by The Company of Biologists Ltd.

  4. Brachyury, Foxa2 and the cis-Regulatory Origins of the Notochord.

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    Diana S José-Edwards

    2015-12-01

    Full Text Available A main challenge of modern biology is to understand how specific constellations of genes are activated to differentiate cells and give rise to distinct tissues. This study focuses on elucidating how gene expression is initiated in the notochord, an axial structure that provides support and patterning signals to embryos of humans and all other chordates. Although numerous notochord genes have been identified, the regulatory DNAs that orchestrate development and propel evolution of this structure by eliciting notochord gene expression remain mostly uncharted, and the information on their configuration and recurrence is still quite fragmentary. Here we used the simple chordate Ciona for a systematic analysis of notochord cis-regulatory modules (CRMs, and investigated their composition, architectural constraints, predictive ability and evolutionary conservation. We found that most Ciona notochord CRMs relied upon variable combinations of binding sites for the transcription factors Brachyury and/or Foxa2, which can act either synergistically or independently from one another. Notably, one of these CRMs contains a Brachyury binding site juxtaposed to an (AC microsatellite, an unusual arrangement also found in Brachyury-bound regulatory regions in mouse. In contrast, different subsets of CRMs relied upon binding sites for transcription factors of widely diverse families. Surprisingly, we found that neither intra-genomic nor interspecific conservation of binding sites were reliably predictive hallmarks of notochord CRMs. We propose that rather than obeying a rigid sequence-based cis-regulatory code, most notochord CRMs are rather unique. Yet, this study uncovered essential elements recurrently used by divergent chordates as basic building blocks for notochord CRMs.

  5. Brachyury, Foxa2 and the cis-Regulatory Origins of the Notochord.

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    José-Edwards, Diana S; Oda-Ishii, Izumi; Kugler, Jamie E; Passamaneck, Yale J; Katikala, Lavanya; Nibu, Yutaka; Di Gregorio, Anna

    2015-12-01

    A main challenge of modern biology is to understand how specific constellations of genes are activated to differentiate cells and give rise to distinct tissues. This study focuses on elucidating how gene expression is initiated in the notochord, an axial structure that provides support and patterning signals to embryos of humans and all other chordates. Although numerous notochord genes have been identified, the regulatory DNAs that orchestrate development and propel evolution of this structure by eliciting notochord gene expression remain mostly uncharted, and the information on their configuration and recurrence is still quite fragmentary. Here we used the simple chordate Ciona for a systematic analysis of notochord cis-regulatory modules (CRMs), and investigated their composition, architectural constraints, predictive ability and evolutionary conservation. We found that most Ciona notochord CRMs relied upon variable combinations of binding sites for the transcription factors Brachyury and/or Foxa2, which can act either synergistically or independently from one another. Notably, one of these CRMs contains a Brachyury binding site juxtaposed to an (AC) microsatellite, an unusual arrangement also found in Brachyury-bound regulatory regions in mouse. In contrast, different subsets of CRMs relied upon binding sites for transcription factors of widely diverse families. Surprisingly, we found that neither intra-genomic nor interspecific conservation of binding sites were reliably predictive hallmarks of notochord CRMs. We propose that rather than obeying a rigid sequence-based cis-regulatory code, most notochord CRMs are rather unique. Yet, this study uncovered essential elements recurrently used by divergent chordates as basic building blocks for notochord CRMs.

  6. Using hexamers to predict cis-regulatory motifs in Drosophila

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    Kibler Dennis

    2005-10-01

    Full Text Available Abstract Background Cis-regulatory modules (CRMs are short stretches of DNA that help regulate gene expression in higher eukaryotes. They have been found up to 1 megabase away from the genes they regulate and can be located upstream, downstream, and even within their target genes. Due to the difficulty of finding CRMs using biological and computational techniques, even well-studied regulatory systems may contain CRMs that have not yet been discovered. Results We present a simple, efficient method (HexDiff based only on hexamer frequencies of known CRMs and non-CRM sequence to predict novel CRMs in regulatory systems. On a data set of 16 gap and pair-rule genes containing 52 known CRMs, predictions made by HexDiff had a higher correlation with the known CRMs than several existing CRM prediction algorithms: Ahab, Cluster Buster, MSCAN, MCAST, and LWF. After combining the results of the different algorithms, 10 putative CRMs were identified and are strong candidates for future study. The hexamers used by HexDiff to distinguish between CRMs and non-CRM sequence were also analyzed and were shown to be enriched in regulatory elements. Conclusion HexDiff provides an efficient and effective means for finding new CRMs based on known CRMs, rather than known binding sites.

  7. Changes in Cis-regulatory Elements during Morphological Evolution

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    Yu-Lee Paul

    2012-10-01

    Full Text Available How have animals evolved new body designs (morphological evolution? This requires explanations both for simple morphological changes, such as differences in pigmentation and hair patterns between different Drosophila populations and species, and also for more complex changes, such as differences in the forelimbs of mice and bats, and the necks of amphibians and reptiles. The genetic changes and pathways involved in these evolutionary steps require identification. Many, though not all, of these events occur by changes in cis-regulatory (enhancer elements within developmental genes. Enhancers are modular, each affecting expression in only one or a few tissues. Therefore it is possible to add, remove or alter an enhancer without producing changes in multiple tissues, and thereby avoid widespread (pleiotropic deleterious effects. Ideally, for a given step in morphological evolution it is necessary to identify (i the change in phenotype, (ii the changes in gene expression, (iii the DNA region, enhancer or otherwise, affected, (iv the mutation involved, (v the nature of the transcription or other factors that bind to this site. In practice these data are incomplete for most of the published studies upon morphological evolution. Here, the investigations are categorized according to how far these analyses have proceeded.

  8. Validation of Skeletal Muscle cis-Regulatory Module Predictions Reveals Nucleotide Composition Bias in Functional Enhancers

    Science.gov (United States)

    Kwon, Andrew T.; Chou, Alice Yi; Arenillas, David J.; Wasserman, Wyeth W.

    2011-01-01

    We performed a genome-wide scan for muscle-specific cis-regulatory modules (CRMs) using three computational prediction programs. Based on the predictions, 339 candidate CRMs were tested in cell culture with NIH3T3 fibroblasts and C2C12 myoblasts for capacity to direct selective reporter gene expression to differentiated C2C12 myotubes. A subset of 19 CRMs validated as functional in the assay. The rate of predictive success reveals striking limitations of computational regulatory sequence analysis methods for CRM discovery. Motif-based methods performed no better than predictions based only on sequence conservation. Analysis of the properties of the functional sequences relative to inactive sequences identifies nucleotide sequence composition can be an important characteristic to incorporate in future methods for improved predictive specificity. Muscle-related TFBSs predicted within the functional sequences display greater sequence conservation than non-TFBS flanking regions. Comparison with recent MyoD and histone modification ChIP-Seq data supports the validity of the functional regions. PMID:22144875

  9. Validation of skeletal muscle cis-regulatory module predictions reveals nucleotide composition bias in functional enhancers.

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    Andrew T Kwon

    2011-12-01

    Full Text Available We performed a genome-wide scan for muscle-specific cis-regulatory modules (CRMs using three computational prediction programs. Based on the predictions, 339 candidate CRMs were tested in cell culture with NIH3T3 fibroblasts and C2C12 myoblasts for capacity to direct selective reporter gene expression to differentiated C2C12 myotubes. A subset of 19 CRMs validated as functional in the assay. The rate of predictive success reveals striking limitations of computational regulatory sequence analysis methods for CRM discovery. Motif-based methods performed no better than predictions based only on sequence conservation. Analysis of the properties of the functional sequences relative to inactive sequences identifies nucleotide sequence composition can be an important characteristic to incorporate in future methods for improved predictive specificity. Muscle-related TFBSs predicted within the functional sequences display greater sequence conservation than non-TFBS flanking regions. Comparison with recent MyoD and histone modification ChIP-Seq data supports the validity of the functional regions.

  10. [Analysis of cis-regulatory element distribution in gene promoters of Gossypium raimondii and Arabidopsis thaliana].

    Science.gov (United States)

    Sun, Gao-Fei; He, Shou-Pu; Du, Xiong-Ming

    2013-10-01

    Cotton genomic studies have boomed since the release of Gossypium raimondii draft genome. In this study, cis-regulatory element (CRE) in 1 kb length sequence upstream 5' UTR of annotated genes were selected and scanned in the Arabidopsis thaliana (At) and Gossypium raimondii (Gr) genomes, based on the database of PLACE (Plant cis-acting Regulatory DNA Elements). According to the definition of this study, 44 (12.3%) and 57 (15.5%) CREs presented "peak-like" distribution in the 1 kb selected sequences of both genomes, respectively. Thirty-four of them were peak-like distributed in both genomes, which could be further categorized into 4 types based on their core sequences. The coincidence of TATABOX peak position and their actual position ((-) -30 bp) indicated that the position of a common CRE was conservative in different genes, which suggested that the peak position of these CREs was their possible actual position of transcription factors. The position of a common CRE was also different between the two genomes due to stronger length variation of 5' UTR in Gr than At. Furthermore, most of the peak-like CREs were located in the region of -110 bp-0 bp, which suggested that concentrated distribution might be conductive to the interaction of transcription factors, and then regulate the gene expression in downstream.

  11. Characterization of Putative cis-Regulatory Elements in Genes Preferentially Expressed in Arabidopsis Male Meiocytes

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    Junhua Li

    2014-01-01

    Full Text Available Meiosis is essential for plant reproduction because it is the process during which homologous chromosome pairing, synapsis, and meiotic recombination occur. The meiotic transcriptome is difficult to investigate because of the size of meiocytes and the confines of anther lobes. The recent development of isolation techniques has enabled the characterization of transcriptional profiles in male meiocytes of Arabidopsis. Gene expression in male meiocytes shows unique features. The direct interaction of transcription factors (TFs with DNA regulatory sequences forms the basis for the specificity of transcriptional regulation. Here, we identified putative cis-regulatory elements (CREs associated with male meiocyte-expressed genes using in silico tools. The upstream regions (1 kb of the top 50 genes preferentially expressed in Arabidopsis meiocytes possessed conserved motifs. These motifs are putative binding sites of TFs, some of which share common functions, such as roles in cell division. In combination with cell-type-specific analysis, our findings could be a substantial aid for the identification and experimental verification of the protein-DNA interactions for the specific TFs that drive gene expression in meiocytes.

  12. Characterization of Cer-1 cis-regulatory region during early Xenopus development.

    Science.gov (United States)

    Silva, Ana Cristina; Filipe, Mário; Steinbeisser, Herbert; Belo, José António

    2011-05-01

    Cerberus-related molecules are well-known Wnt, Nodal, and BMP inhibitors that have been implicated in different processes including anterior–posterior patterning and left–right asymmetry. In both mouse and frog, two Cerberus-related genes have been isolated, mCer-1 and mCer-2, and Xcer and Xcoco, respectively. Until now, little is known about the mechanisms involved in their transcriptional regulation. Here, we report a heterologous analysis of the mouse Cerberus-1 gene upstream regulatory regions, responsible for its expression in the visceral endodermal cells. Our analysis showed that the consensus sequences for a TATA, CAAT, or GC boxes were absent but a TGTGG sequence was present at position -172 to -168 bp, relative to the ATG. Using a series of deletion constructs and transient expression in Xenopus embryos, we found that a fragment of 1.4 kb of Cer-1 promoter sequence could reproduce the endogenous expression pattern of Xenopus cerberus. A 0.7-kb mcer-1 upstream region was able to drive reporter expression to the involuting mesendodermal cells, while further deletions abolished reporter gene expression. Our results suggest that although no sequence similarity was found between mouse and Xenopus cerberus cis-regulatory regions, the signaling cascades regulating cerberus expression, during gastrulation, is conserved.

  13. PReMod: a database of genome-wide mammalian cis-regulatory module predictions.

    Science.gov (United States)

    Ferretti, Vincent; Poitras, Christian; Bergeron, Dominique; Coulombe, Benoit; Robert, François; Blanchette, Mathieu

    2007-01-01

    We describe PReMod, a new database of genome-wide cis-regulatory module (CRM) predictions for both the human and the mouse genomes. The prediction algorithm, described previously in Blanchette et al. (2006) Genome Res., 16, 656-668, exploits the fact that many known CRMs are made of clusters of phylogenetically conserved and repeated transcription factors (TF) binding sites. Contrary to other existing databases, PReMod is not restricted to modules located proximal to genes, but in fact mostly contains distal predicted CRMs (pCRMs). Through its web interface, PReMod allows users to (i) identify pCRMs around a gene of interest; (ii) identify pCRMs that have binding sites for a given TF (or a set of TFs) or (iii) download the entire dataset for local analyses. Queries can also be refined by filtering for specific chromosomal regions, for specific regions relative to genes or for the presence of CpG islands. The output includes information about the binding sites predicted within the selected pCRMs, and a graphical display of their distribution within the pCRMs. It also provides a visual depiction of the chromosomal context of the selected pCRMs in terms of neighboring pCRMs and genes, all of which are linked to the UCSC Genome Browser and the NCBI. PReMod: http://genomequebec.mcgill.ca/PReMod.

  14. Barcoded DNA-tag reporters for multiplex cis-regulatory analysis.

    Directory of Open Access Journals (Sweden)

    Jongmin Nam

    Full Text Available Cis-regulatory DNA sequences causally mediate patterns of gene expression, but efficient experimental analysis of these control systems has remained challenging. Here we develop a new version of "barcoded" DNA-tag reporters, "Nanotags" that permit simultaneous quantitative analysis of up to 130 distinct cis-regulatory modules (CRMs. The activities of these reporters are measured in single experiments by the NanoString RNA counting method and other quantitative procedures. We demonstrate the efficiency of the Nanotag method by simultaneously measuring hourly temporal activities of 126 CRMs from 46 genes in the developing sea urchin embryo, otherwise a virtually impossible task. Nanotags are also used in gene perturbation experiments to reveal cis-regulatory responses of many CRMs at once. Nanotag methodology can be applied to many research areas, ranging from gene regulatory networks to functional and evolutionary genomics.

  15. Patterns of cis regulatory variation in diverse human populations.

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    Barbara E Stranger

    Full Text Available The genetic basis of gene expression variation has long been studied with the aim to understand the landscape of regulatory variants, but also more recently to assist in the interpretation and elucidation of disease signals. To date, many studies have looked in specific tissues and population-based samples, but there has been limited assessment of the degree of inter-population variability in regulatory variation. We analyzed genome-wide gene expression in lymphoblastoid cell lines from a total of 726 individuals from 8 global populations from the HapMap3 project and correlated gene expression levels with HapMap3 SNPs located in cis to the genes. We describe the influence of ancestry on gene expression levels within and between these diverse human populations and uncover a non-negligible impact on global patterns of gene expression. We further dissect the specific functional pathways differentiated between populations. We also identify 5,691 expression quantitative trait loci (eQTLs after controlling for both non-genetic factors and population admixture and observe that half of the cis-eQTLs are replicated in one or more of the populations. We highlight patterns of eQTL-sharing between populations, which are partially determined by population genetic relatedness, and discover significant sharing of eQTL effects between Asians, European-admixed, and African subpopulations. Specifically, we observe that both the effect size and the direction of effect for eQTLs are highly conserved across populations. We observe an increasing proximity of eQTLs toward the transcription start site as sharing of eQTLs among populations increases, highlighting that variants close to TSS have stronger effects and therefore are more likely to be detected across a wider panel of populations. Together these results offer a unique picture and resource of the degree of differentiation among human populations in functional regulatory variation and provide an estimate for

  16. Using reporter gene assays to identify cis regulatory differences between humans and chimpanzees.

    Science.gov (United States)

    Chabot, Adrien; Shrit, Ralla A; Blekhman, Ran; Gilad, Yoav

    2007-08-01

    Most phenotypic differences between human and chimpanzee are likely to result from differences in gene regulation, rather than changes to protein-coding regions. To date, however, only a handful of human-chimpanzee nucleotide differences leading to changes in gene regulation have been identified. To hone in on differences in regulatory elements between human and chimpanzee, we focused on 10 genes that were previously found to be differentially expressed between the two species. We then designed reporter gene assays for the putative human and chimpanzee promoters of the 10 genes. Of seven promoters that we found to be active in human liver cell lines, human and chimpanzee promoters had significantly different activity in four cases, three of which recapitulated the gene expression difference seen in the microarray experiment. For these three genes, we were therefore able to demonstrate that a change in cis influences expression differences between humans and chimpanzees. Moreover, using site-directed mutagenesis on one construct, the promoter for the DDA3 gene, we were able to identify three nucleotides that together lead to a cis regulatory difference between the species. High-throughput application of this approach can provide a map of regulatory element differences between humans and our close evolutionary relatives.

  17. BET Bromodomain Inhibition Releases the Mediator Complex from Select cis-Regulatory Elements.

    Science.gov (United States)

    Bhagwat, Anand S; Roe, Jae-Seok; Mok, Beverly Y L; Hohmann, Anja F; Shi, Junwei; Vakoc, Christopher R

    2016-04-19

    The bromodomain and extraterminal (BET) protein BRD4 can physically interact with the Mediator complex, but the relevance of this association to the therapeutic effects of BET inhibitors in cancer is unclear. Here, we show that BET inhibition causes a rapid release of Mediator from a subset of cis-regulatory elements in the genome of acute myeloid leukemia (AML) cells. These sites of Mediator eviction were highly correlated with transcriptional suppression of neighboring genes, which are enriched for targets of the transcription factor MYB and for functions related to leukemogenesis. A shRNA screen of Mediator in AML cells identified the MED12, MED13, MED23, and MED24 subunits as performing a similar regulatory function to BRD4 in this context, including a shared role in sustaining a block in myeloid maturation. These findings suggest that the interaction between BRD4 and Mediator has functional importance for gene-specific transcriptional activation and for AML maintenance. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  18. CRX ChIP-seq reveals the cis-regulatory architecture of mouse photoreceptors

    NARCIS (Netherlands)

    J.C. Corbo (Joseph); K.A. Lawrence (Karen); M. Karlstetter (Marcus); C.A. Myers (Connie); M. Abdelaziz (Musa); W. Dirkes (William); K. Weigelt (Karin); M. Seifert (Martin); V. Benes (Vladimir); L.G. Fritsche (Lars); B.H.F. Weber (Bernhard); T. Langmann (Thomas)

    2010-01-01

    textabstractApproximately 98% of mammalian DNA is noncoding, yet we understand relatively little about the function of this enigmatic portion of the genome. The cis-regulatory elements that control gene expression reside in noncoding regions and can be identified by mapping the binding sites of

  19. Cis-regulatory elements in the primate brain: from functional specialization to neurodegeneration

    NARCIS (Netherlands)

    Vermunt, Marit W.

    2017-01-01

    Over the last decade, the noncoding part of the genome has been shown to harbour thousands of cis-regulatory elements, such as enhancers, that activate well-defined gene expression programs. Here, we charted active enhancers in a multiplicity of human brain regions to understand the role of

  20. The lncRNA Malat1 Is Dispensable for Mouse Development but Its Transcription Plays a cis-Regulatory Role in the Adult

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    Bin Zhang

    2012-07-01

    Full Text Available Genome-wide studies have identified thousands of long noncoding RNAs (lncRNAs lacking protein-coding capacity. However, most lncRNAs are expressed at a very low level, and in most cases there is no genetic evidence to support their in vivo function. Malat1 (metastasis associated lung adenocarcinoma transcript 1 is among the most abundant and highly conserved lncRNAs, and it exhibits an uncommon 3′-end processing mechanism. In addition, its specific nuclear localization, developmental regulation, and dysregulation in cancer are suggestive of it having a critical biological function. We have characterized a Malat1 loss-of-function genetic model that indicates that Malat1 is not essential for mouse pre- and postnatal development. Furthermore, depletion of Malat1 does not affect global gene expression, splicing factor level and phosphorylation status, or alternative pre-mRNA splicing. However, among a small number of genes that were dysregulated in adult Malat1 knockout mice, many were Malat1 neighboring genes, thus indicating a potential cis-regulatory role of Malat1 gene transcription.

  1. An integrative and applicable phylogenetic footprinting framework for cis-regulatory motifs identification in prokaryotic genomes.

    Science.gov (United States)

    Liu, Bingqiang; Zhang, Hanyuan; Zhou, Chuan; Li, Guojun; Fennell, Anne; Wang, Guanghui; Kang, Yu; Liu, Qi; Ma, Qin

    2016-08-09

    Phylogenetic footprinting is an important computational technique for identifying cis-regulatory motifs in orthologous regulatory regions from multiple genomes, as motifs tend to evolve slower than their surrounding non-functional sequences. Its application, however, has several difficulties for optimizing the selection of orthologous data and reducing the false positives in motif prediction. Here we present an integrative phylogenetic footprinting framework for accurate motif predictions in prokaryotic genomes (MP(3)). The framework includes a new orthologous data preparation procedure, an additional promoter scoring and pruning method and an integration of six existing motif finding algorithms as basic motif search engines. Specifically, we collected orthologous genes from available prokaryotic genomes and built the orthologous regulatory regions based on sequence similarity of promoter regions. This procedure made full use of the large-scale genomic data and taxonomy information and filtered out the promoters with limited contribution to produce a high quality orthologous promoter set. The promoter scoring and pruning is implemented through motif voting by a set of complementary predicting tools that mine as many motif candidates as possible and simultaneously eliminate the effect of random noise. We have applied the framework to Escherichia coli k12 genome and evaluated the prediction performance through comparison with seven existing programs. This evaluation was systematically carried out at the nucleotide and binding site level, and the results showed that MP(3) consistently outperformed other popular motif finding tools. We have integrated MP(3) into our motif identification and analysis server DMINDA, allowing users to efficiently identify and analyze motifs in 2,072 completely sequenced prokaryotic genomes. The performance evaluation indicated that MP(3) is effective for predicting regulatory motifs in prokaryotic genomes. Its application may enhance

  2. Deciphering Cis-Regulatory Element Mediated Combinatorial Regulation in Rice under Blast Infected Condition.

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    Arindam Deb

    Full Text Available Combinations of cis-regulatory elements (CREs present at the promoters facilitate the binding of several transcription factors (TFs, thereby altering the consequent gene expressions. Due to the eminent complexity of the regulatory mechanism, the combinatorics of CRE-mediated transcriptional regulation has been elusive. In this work, we have developed a new methodology that quantifies the co-occurrence tendencies of CREs present in a set of promoter sequences; these co-occurrence scores are filtered in three consecutive steps to test their statistical significance; and the significantly co-occurring CRE pairs are presented as networks. These networks of co-occurring CREs are further transformed to derive higher order of regulatory combinatorics. We have further applied this methodology on the differentially up-regulated gene-sets of rice tissues under fungal (Magnaporthe infected conditions to demonstrate how it helps to understand the CRE-mediated combinatorial gene regulation. Our analysis includes a wide spectrum of biologically important results. The CRE pairs having a strong tendency to co-occur often exhibit very similar joint distribution patterns at the promoters of rice. We couple the network approach with experimental results of plant gene regulation and defense mechanisms and find evidences of auto and cross regulation among TF families, cross-talk among multiple hormone signaling pathways, similarities and dissimilarities in regulatory combinatorics between different tissues, etc. Our analyses have pointed a highly distributed nature of the combinatorial gene regulation facilitating an efficient alteration in response to fungal attack. All together, our proposed methodology could be an important approach in understanding the combinatorial gene regulation. It can be further applied to unravel the tissue and/or condition specific combinatorial gene regulation in other eukaryotic systems with the availability of annotated genomic

  3. Cis-regulatory RNA elements that regulate specialized ribosome activity.

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    Xue, Shifeng; Barna, Maria

    2015-01-01

    Recent evidence has shown that the ribosome itself can play a highly regulatory role in the specialized translation of specific subpools of mRNAs, in particular at the level of ribosomal proteins (RP). However, the mechanism(s) by which this selection takes place has remained poorly understood. In our recent study, we discovered a combination of unique RNA elements in the 5'UTRs of mRNAs that allows for such control by the ribosome. These mRNAs contain a Translation Inhibitory Element (TIE) that inhibits general cap-dependent translation, and an Internal Ribosome Entry Site (IRES) that relies on a specific RP for activation. The unique combination of an inhibitor of general translation and an activator of specialized translation is key to ribosome-mediated control of gene expression. Here we discuss how these RNA regulatory elements provide a new level of control to protein expression and their implications for gene expression, organismal development and evolution.

  4. Prediction of tissue-specific cis-regulatory modules using Bayesian networks and regression trees

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    Chen Xiaoyu

    2007-12-01

    Full Text Available Abstract Background In vertebrates, a large part of gene transcriptional regulation is operated by cis-regulatory modules. These modules are believed to be regulating much of the tissue-specificity of gene expression. Results We develop a Bayesian network approach for identifying cis-regulatory modules likely to regulate tissue-specific expression. The network integrates predicted transcription factor binding site information, transcription factor expression data, and target gene expression data. At its core is a regression tree modeling the effect of combinations of transcription factors bound to a module. A new unsupervised EM-like algorithm is developed to learn the parameters of the network, including the regression tree structure. Conclusion Our approach is shown to accurately identify known human liver and erythroid-specific modules. When applied to the prediction of tissue-specific modules in 10 different tissues, the network predicts a number of important transcription factor combinations whose concerted binding is associated to specific expression.

  5. Creating and validating cis-regulatory maps of tissue-specific gene expression regulation

    Science.gov (United States)

    O'Connor, Timothy R.; Bailey, Timothy L.

    2014-01-01

    Predicting which genomic regions control the transcription of a given gene is a challenge. We present a novel computational approach for creating and validating maps that associate genomic regions (cis-regulatory modules–CRMs) with genes. The method infers regulatory relationships that explain gene expression observed in a test tissue using widely available genomic data for ‘other’ tissues. To predict the regulatory targets of a CRM, we use cross-tissue correlation between histone modifications present at the CRM and expression at genes within 1 Mbp of it. To validate cis-regulatory maps, we show that they yield more accurate models of gene expression than carefully constructed control maps. These gene expression models predict observed gene expression from transcription factor binding in the CRMs linked to that gene. We show that our maps are able to identify long-range regulatory interactions and improve substantially over maps linking genes and CRMs based on either the control maps or a ‘nearest neighbor’ heuristic. Our results also show that it is essential to include CRMs predicted in multiple tissues during map-building, that H3K27ac is the most informative histone modification, and that CAGE is the most informative measure of gene expression for creating cis-regulatory maps. PMID:25200088

  6. Pathogenic adaptation of intracellular bacteria by rewiring a cis-regulatory input function.

    Science.gov (United States)

    Osborne, Suzanne E; Walthers, Don; Tomljenovic, Ana M; Mulder, David T; Silphaduang, Uma; Duong, Nancy; Lowden, Michael J; Wickham, Mark E; Waller, Ross F; Kenney, Linda J; Coombes, Brian K

    2009-03-10

    The acquisition of DNA by horizontal gene transfer enables bacteria to adapt to previously unexploited ecological niches. Although horizontal gene transfer and mutation of protein-coding sequences are well-recognized forms of pathogen evolution, the evolutionary significance of cis-regulatory mutations in creating phenotypic diversity through altered transcriptional outputs is not known. We show the significance of regulatory mutation for pathogen evolution by mapping and then rewiring a cis-regulatory module controlling a gene required for murine typhoid. Acquisition of a binding site for the Salmonella pathogenicity island-2 regulator, SsrB, enabled the srfN gene, ancestral to the Salmonella genus, to play a role in pathoadaptation of S. typhimurium to a host animal. We identified the evolved cis-regulatory module and quantified the fitness gain that this regulatory output accrues for the bacterium using competitive infections of host animals. Our findings highlight a mechanism of pathogen evolution involving regulatory mutation that is selected because of the fitness advantage the new regulatory output provides the incipient clones.

  7. Dynamic SPR monitoring of yeast nuclear protein binding to a cis-regulatory element

    International Nuclear Information System (INIS)

    Mao, Grace; Brody, James P.

    2007-01-01

    Gene expression is controlled by protein complexes binding to short specific sequences of DNA, called cis-regulatory elements. Expression of most eukaryotic genes is controlled by dozens of these elements. Comprehensive identification and monitoring of these elements is a major goal of genomics. In pursuit of this goal, we are developing a surface plasmon resonance (SPR) based assay to identify and monitor cis-regulatory elements. To test whether we could reliably monitor protein binding to a regulatory element, we immobilized a 16 bp region of Saccharomyces cerevisiae chromosome 5 onto a gold surface. This 16 bp region of DNA is known to bind several proteins and thought to control expression of the gene RNR1, which varies through the cell cycle. We synchronized yeast cell cultures, and then sampled these cultures at a regular interval. These samples were processed to purify nuclear lysate, which was then exposed to the sensor. We found that nuclear protein binds this particular element of DNA at a significantly higher rate (as compared to unsynchronized cells) during G1 phase. Other time points show levels of DNA-nuclear protein binding similar to the unsynchronized control. We also measured the apparent association complex of the binding to be 0.014 s -1 . We conclude that (1) SPR-based assays can monitor DNA-nuclear protein binding and that (2) for this particular cis-regulatory element, maximum DNA-nuclear protein binding occurs during G1 phase

  8. An in vivo cis-regulatory screen at the type 2 diabetes associated TCF7L2 locus identifies multiple tissue-specific enhancers.

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    Daniel Savic

    Full Text Available Genome-wide association studies (GWAS have repeatedly shown an association between non-coding variants in the TCF7L2 locus and risk for type 2 diabetes (T2D, implicating a role for cis-regulatory variation within this locus in disease etiology. Supporting this hypothesis, we previously localized complex regulatory activity to the TCF7L2 T2D-associated interval using an in vivo bacterial artificial chromosome (BAC enhancer-trapping reporter strategy. To follow-up on this broad initial survey of the TCF7L2 regulatory landscape, we performed a fine-mapping enhancer scan using in vivo mouse transgenic reporter assays. We functionally interrogated approximately 50% of the sequences within the T2D-associated interval, utilizing sequence conservation within this 92-kb interval to determine the regulatory potential of all evolutionary conserved sequences that exhibited conservation to the non-eutherian mammal opossum. Included in this study was a detailed functional interrogation of sequences spanning both protective and risk alleles of single nucleotide polymorphism (SNP rs7903146, which has exhibited allele-specific enhancer function in pancreatic beta cells. Using these assays, we identified nine segments regulating various aspects of the TCF7L2 expression profile and that constitute nearly 70% of the sequences tested. These results highlight the regulatory complexity of this interval and support the notion that a TCF7L2 cis-regulatory disruption leads to T2D predisposition.

  9. Cis-regulatory element based targeted gene finding: genome-wide identification of abscisic acid- and abiotic stress-responsive genes in Arabidopsis thaliana.

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    Zhang, Weixiong; Ruan, Jianhua; Ho, Tuan-Hua David; You, Youngsook; Yu, Taotao; Quatrano, Ralph S

    2005-07-15

    A fundamental problem of computational genomics is identifying the genes that respond to certain endogenous cues and environmental stimuli. This problem can be referred to as targeted gene finding. Since gene regulation is mainly determined by the binding of transcription factors and cis-regulatory DNA sequences, most existing gene annotation methods, which exploit the conservation of open reading frames, are not effective in finding target genes. A viable approach to targeted gene finding is to exploit the cis-regulatory elements that are known to be responsible for the transcription of target genes. Given such cis-elements, putative target genes whose promoters contain the elements can be identified. As a case study, we apply the above approach to predict the genes in model plant Arabidopsis thaliana which are inducible by a phytohormone, abscisic acid (ABA), and abiotic stress, such as drought, cold and salinity. We first construct and analyze two ABA specific cis-elements, ABA-responsive element (ABRE) and its coupling element (CE), in A.thaliana, based on their conservation in rice and other cereal plants. We then use the ABRE-CE module to identify putative ABA-responsive genes in A.thaliana. Based on RT-PCR verification and the results from literature, this method has an accuracy rate of 67.5% for the top 40 predictions. The cis-element based targeted gene finding approach is expected to be widely applicable since a large number of cis-elements in many species are available.

  10. On the Concept of Cis-regulatory Information: From Sequence Motifs to Logic Functions

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    Tarpine, Ryan; Istrail, Sorin

    The regulatory genome is about the “system level organization of the core genomic regulatory apparatus, and how this is the locus of causality underlying the twin phenomena of animal development and animal evolution” (E.H. Davidson. The Regulatory Genome: Gene Regulatory Networks in Development and Evolution, Academic Press, 2006). Information processing in the regulatory genome is done through regulatory states, defined as sets of transcription factors (sequence-specific DNA binding proteins which determine gene expression) that are expressed and active at the same time. The core information processing machinery consists of modular DNA sequence elements, called cis-modules, that interact with transcription factors. The cis-modules “read” the information contained in the regulatory state of the cell through transcription factor binding, “process” it, and directly or indirectly communicate with the basal transcription apparatus to determine gene expression. This endowment of each gene with the information-receiving capacity through their cis-regulatory modules is essential for the response to every possible regulatory state to which it might be exposed during all phases of the life cycle and in all cell types. We present here a set of challenges addressed by our CYRENE research project aimed at studying the cis-regulatory code of the regulatory genome. The CYRENE Project is devoted to (1) the construction of a database, the cis-Lexicon, containing comprehensive information across species about experimentally validated cis-regulatory modules; and (2) the software development of a next-generation genome browser, the cis-Browser, specialized for the regulatory genome. The presentation is anchored on three main computational challenges: the Gene Naming Problem, the Consensus Sequence Bottleneck Problem, and the Logic Function Inference Problem.

  11. Cis-regulatory signatures of orthologous stress-associated bZIP transcription factors from rice, sorghum and Arabidopsis based on phylogenetic footprints

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    Xu Fuyu

    2012-09-01

    Full Text Available Abstract Background The potential contribution of upstream sequence variation to the unique features of orthologous genes is just beginning to be unraveled. A core subset of stress-associated bZIP transcription factors from rice (Oryza sativa formed ten clusters of orthologous groups (COG with genes from the monocot sorghum (Sorghum bicolor and dicot Arabidopsis (Arabidopsis thaliana. The total cis-regulatory information content of each stress-associated COG was examined by phylogenetic footprinting to reveal ortholog-specific, lineage-specific and species-specific conservation patterns. Results The most apparent pattern observed was the occurrence of spatially conserved ‘core modules’ among the COGs but not among paralogs. These core modules are comprised of various combinations of two to four putative transcription factor binding site (TFBS classes associated with either developmental or stress-related functions. Outside the core modules are specific stress (ABA, oxidative, abiotic, biotic or organ-associated signals, which may be functioning as ‘regulatory fine-tuners’ and further define lineage-specific and species-specific cis-regulatory signatures. Orthologous monocot and dicot promoters have distinct TFBS classes involved in disease and oxidative-regulated expression, while the orthologous rice and sorghum promoters have distinct combinations of root-specific signals, a pattern that is not particularly conserved in Arabidopsis. Conclusions Patterns of cis-regulatory conservation imply that each ortholog has distinct signatures, further suggesting that they are potentially unique in a regulatory context despite the presumed conservation of broad biological function during speciation. Based on the observed patterns of conservation, we postulate that core modules are likely primary determinants of basal developmental programming, which may be integrated with and further elaborated by additional intrinsic or extrinsic signals in

  12. Retinal Expression of the Drosophila eyes absent Gene Is Controlled by Several Cooperatively Acting Cis-regulatory Elements

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    Neuman, Sarah D.; Bashirullah, Arash; Kumar, Justin P.

    2016-01-01

    The eyes absent (eya) gene of the fruit fly, Drosophila melanogaster, is a member of an evolutionarily conserved gene regulatory network that controls eye formation in all seeing animals. The loss of eya leads to the complete elimination of the compound eye while forced expression of eya in non-retinal tissues is sufficient to induce ectopic eye formation. Within the developing retina eya is expressed in a dynamic pattern and is involved in tissue specification/determination, cell proliferation, apoptosis, and cell fate choice. In this report we explore the mechanisms by which eya expression is spatially and temporally governed in the developing eye. We demonstrate that multiple cis-regulatory elements function cooperatively to control eya transcription and that spacing between a pair of enhancer elements is important for maintaining correct gene expression. Lastly, we show that the loss of eya expression in sine oculis (so) mutants is the result of massive cell death and a progressive homeotic transformation of retinal progenitor cells into head epidermis. PMID:27930646

  13. Plasticity of the cis-regulatory input function of a gene.

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    Avraham E Mayo

    2006-04-01

    Full Text Available The transcription rate of a gene is often controlled by several regulators that bind specific sites in the gene's cis-regulatory region. The combined effect of these regulators is described by a cis-regulatory input function. What determines the form of an input function, and how variable is it with respect to mutations? To address this, we employ the well-characterized lac operon of Escherichia coli, which has an elaborate input function, intermediate between Boolean AND-gate and OR-gate logic. We mapped in detail the input function of 12 variants of the lac promoter, each with different point mutations in the regulator binding sites, by means of accurate expression measurements from living cells. We find that even a few mutations can significantly change the input function, resulting in functions that resemble Pure AND gates, OR gates, or single-input switches. Other types of gates were not found. The variant input functions can be described in a unified manner by a mathematical model. The model also lets us predict which functions cannot be reached by point mutations. The input function that we studied thus appears to be plastic, in the sense that many of the mutations do not ruin the regulation completely but rather result in new ways to integrate the inputs.

  14. A New Algorithm for Identifying Cis-Regulatory Modules Based on Hidden Markov Model

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    Haitao Guo

    2017-01-01

    Full Text Available The discovery of cis-regulatory modules (CRMs is the key to understanding mechanisms of transcription regulation. Since CRMs have specific regulatory structures that are the basis for the regulation of gene expression, how to model the regulatory structure of CRMs has a considerable impact on the performance of CRM identification. The paper proposes a CRM discovery algorithm called ComSPS. ComSPS builds a regulatory structure model of CRMs based on HMM by exploring the rules of CRM transcriptional grammar that governs the internal motif site arrangement of CRMs. We test ComSPS on three benchmark datasets and compare it with five existing methods. Experimental results show that ComSPS performs better than them.

  15. A New Algorithm for Identifying Cis-Regulatory Modules Based on Hidden Markov Model

    Science.gov (United States)

    2017-01-01

    The discovery of cis-regulatory modules (CRMs) is the key to understanding mechanisms of transcription regulation. Since CRMs have specific regulatory structures that are the basis for the regulation of gene expression, how to model the regulatory structure of CRMs has a considerable impact on the performance of CRM identification. The paper proposes a CRM discovery algorithm called ComSPS. ComSPS builds a regulatory structure model of CRMs based on HMM by exploring the rules of CRM transcriptional grammar that governs the internal motif site arrangement of CRMs. We test ComSPS on three benchmark datasets and compare it with five existing methods. Experimental results show that ComSPS performs better than them. PMID:28497059

  16. In silico modeling of epigenetic-induced changes in photoreceptor cis-regulatory elements.

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    Hossain, Reafa A; Dunham, Nicholas R; Enke, Raymond A; Berndsen, Christopher E

    2018-01-01

    DNA methylation is a well-characterized epigenetic repressor of mRNA transcription in many plant and vertebrate systems. However, the mechanism of this repression is not fully understood. The process of transcription is controlled by proteins that regulate recruitment and activity of RNA polymerase by binding to specific cis-regulatory sequences. Cone-rod homeobox (CRX) is a well-characterized mammalian transcription factor that controls photoreceptor cell-specific gene expression. Although much is known about the functions and DNA binding specificity of CRX, little is known about how DNA methylation modulates CRX binding affinity to genomic cis-regulatory elements. We used bisulfite pyrosequencing of human ocular tissues to measure DNA methylation levels of the regulatory regions of RHO , PDE6B, PAX6 , and LINE1 retrotransposon repeats. To describe the molecular mechanism of repression, we used molecular modeling to illustrate the effect of DNA methylation on human RHO regulatory sequences. In this study, we demonstrate an inverse correlation between DNA methylation in regulatory regions adjacent to the human RHO and PDE6B genes and their subsequent transcription in human ocular tissues. Docking of CRX to the DNA models shows that CRX interacts with the grooves of these sequences, suggesting changes in groove structure could regulate binding. Molecular dynamics simulations of the RHO promoter and enhancer regions show changes in the flexibility and groove width upon epigenetic modification. Models also demonstrate changes in the local dynamics of CRX binding sites within RHO regulatory sequences which may account for the repression of CRX-dependent transcription. Collectively, these data demonstrate epigenetic regulation of CRX binding sites in human retinal tissue and provide insight into the mechanism of this mode of epigenetic regulation to be tested in future experiments.

  17. Unveiling combinatorial regulation through the combination of ChIP information and in silico cis-regulatory module detection

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    Sun, Hong; Guns, Tias; Fierro, Ana Carolina; Thorrez, Lieven; Nijssen, Siegfried; Marchal, Kathleen

    2012-01-01

    Computationally retrieving biologically relevant cis-regulatory modules (CRMs) is not straightforward. Because of the large number of candidates and the imperfection of the screening methods, many spurious CRMs are detected that are as high scoring as the biologically true ones. Using ChIP-information allows not only to reduce the regions in which the binding sites of the assayed transcription factor (TF) should be located, but also allows restricting the valid CRMs to those that contain the assayed TF (here referred to as applying CRM detection in a query-based mode). In this study, we show that exploiting ChIP-information in a query-based way makes in silico CRM detection a much more feasible endeavor. To be able to handle the large datasets, the query-based setting and other specificities proper to CRM detection on ChIP-Seq based data, we developed a novel powerful CRM detection method ‘CPModule’. By applying it on a well-studied ChIP-Seq data set involved in self-renewal of mouse embryonic stem cells, we demonstrate how our tool can recover combinatorial regulation of five known TFs that are key in the self-renewal of mouse embryonic stem cells. Additionally, we make a number of new predictions on combinatorial regulation of these five key TFs with other TFs documented in TRANSFAC. PMID:22422841

  18. Mapping of cis-regulatory sites in the promoter of testis-specific stellate genes of Drosophila melanogaster.

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    Olenkina, O M; Egorova, K S; Aravin, A A; Naumova, N M; Gvozdev, V A; Olenina, L V

    2012-11-01

    Tandem Stellate genes organized into two clusters in heterochromatin and euchromatin of the X-chromosome are part of the Ste-Su(Ste) genetic system required for maintenance of male fertility and reproduction of Drosophila melanogaster. Stellate genes encode a regulatory subunit of protein kinase CK2 and are the main targets of germline-specific piRNA-silencing; their derepression leads to appearance of protein crystals in spermatocytes, meiotic disturbances, and male sterility. A short promoter region of 134 bp appears to be sufficient for testis-specific transcription of Stellate, and it contains three closely located cis-regulatory elements called E-boxes. By using reporter analysis, we confirmed a strong functionality of the E-boxes in the Stellate promoter for in vivo transcription. Using selective mutagenesis, we have shown that the presence of the central E-box 2 is preferable to maintain a high-level testis-specific transcription of the reporter gene under the Stellate promoter. The Stellate promoter provides transcription even in heterochromatin, and corresponding mRNAs are translated with the generation of full-size protein products in case of disturbances in the piRNA-silencing process. We have also shown for the first time that the activity of the Stellate promoter is determined by chromatin context of the X-chromosome in male germinal cells, and it increases at about twofold when relocating in autosomes.

  19. Nutritional control of gene expression in Drosophila larvae via TOR, Myc and a novel cis-regulatory element

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    Grewal Savraj S

    2010-01-01

    Full Text Available Abstract Background Nutrient availability is a key determinant of eukaryotic cell growth. In unicellular organisms many signaling and transcriptional networks link nutrient availability to the expression of metabolic genes required for growth. However, less is known about the corresponding mechanisms that operate in metazoans. We used gene expression profiling to explore this issue in developing Drosophila larvae. Results We found that starvation for dietary amino acids (AA's leads to dynamic changes in transcript levels of many metabolic genes. The conserved insulin/PI3K and TOR signaling pathways mediate nutrition-dependent growth in Drosophila and other animals. We found that many AA starvation-responsive transcripts were also altered in TOR mutants. In contrast, although PI3K overexpression induced robust changes in the expression of many metabolic genes, these changes showed limited overlap with the AA starvation expression profile. We did however identify a strong overlap between genes regulated by the transcription factor, Myc, and AA starvation-responsive genes, particularly those involved in ribosome biogenesis, protein synthesis and mitochondrial function. The consensus Myc DNA binding site is enriched in promoters of these AA starvation genes, and we found that Myc overexpression could bypass dietary AA to induce expression of these genes. We also identified another sequence motif (Motif 1 enriched in the promoters of AA starvation-responsive genes. We showed that Motif 1 was both necessary and sufficient to mediate transcriptional responses to dietary AA in larvae. Conclusions Our data suggest that many of the transcriptional effects of amino acids are mediated via signaling through the TOR pathway in Drosophila larvae. We also find that these transcriptional effects are mediated through at least two mechanisms: via the transcription factor Myc, and via the Motif 1 cis-regulatory element. These studies begin to elucidate a nutrient

  20. Nomadic enhancers: tissue-specific cis-regulatory elements of yellow have divergent genomic positions among Drosophila species.

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    Gizem Kalay

    2010-11-01

    Full Text Available cis-regulatory DNA sequences known as enhancers control gene expression in space and time. They are central to metazoan development and are often responsible for changes in gene regulation that contribute to phenotypic evolution. Here, we examine the sequence, function, and genomic location of enhancers controlling tissue- and cell-type specific expression of the yellow gene in six Drosophila species. yellow is required for the production of dark pigment, and its expression has evolved largely in concert with divergent pigment patterns. Using Drosophila melanogaster as a transgenic host, we examined the expression of reporter genes in which either 5' intergenic or intronic sequences of yellow from each species controlled the expression of Green Fluorescent Protein. Surprisingly, we found that sequences controlling expression in the wing veins, as well as sequences controlling expression in epidermal cells of the abdomen, thorax, and wing, were located in different genomic regions in different species. By contrast, sequences controlling expression in bristle-associated cells were located in the intron of all species. Differences in the precise pattern of spatial expression within the developing epidermis of D. melanogaster transformants usually correlated with adult pigmentation in the species from which the cis-regulatory sequences were derived, which is consistent with cis-regulatory evolution affecting yellow expression playing a central role in Drosophila pigmentation divergence. Sequence comparisons among species favored a model in which sequential nucleotide substitutions were responsible for the observed changes in cis-regulatory architecture. Taken together, these data demonstrate frequent changes in yellow cis-regulatory architecture among Drosophila species. Similar analyses of other genes, combining in vivo functional tests of enhancer activity with in silico comparative genomics, are needed to determine whether the pattern of

  1. Lmx1b-targeted cis-regulatory modules involved in limb dorsalization.

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    Haro, Endika; Watson, Billy A; Feenstra, Jennifer M; Tegeler, Luke; Pira, Charmaine U; Mohan, Subburaman; Oberg, Kerby C

    2017-06-01

    Lmx1b is a homeodomain transcription factor responsible for limb dorsalization. Despite striking double-ventral (loss-of-function) and double-dorsal (gain-of-function) limb phenotypes, no direct gene targets in the limb have been confirmed. To determine direct targets, we performed a chromatin immunoprecipitation against Lmx1b in mouse limbs at embryonic day 12.5 followed by next-generation sequencing (ChIP-seq). Nearly 84% ( n =617) of the Lmx1b-bound genomic intervals (LBIs) identified overlap with chromatin regulatory marks indicative of potential cis -regulatory modules (PCRMs). In addition, 73 LBIs mapped to CRMs that are known to be active during limb development. We compared Lmx1b-bound PCRMs with genes regulated by Lmx1b and found 292 PCRMs within 1 Mb of 254 Lmx1b-regulated genes. Gene ontological analysis suggests that Lmx1b targets extracellular matrix production, bone/joint formation, axonal guidance, vascular development, cell proliferation and cell movement. We validated the functional activity of a PCRM associated with joint-related Gdf5 that provides a mechanism for Lmx1b-mediated joint modification and a PCRM associated with Lmx1b that suggests a role in autoregulation. This is the first report to describe genome-wide Lmx1b binding during limb development, directly linking Lmx1b to targets that accomplish limb dorsalization. © 2017. Published by The Company of Biologists Ltd.

  2. Identifying Cis-Regulatory Changes Involved in the Evolution of Aerobic Fermentation in Yeasts

    Science.gov (United States)

    Lin, Zhenguo; Wang, Tzi-Yuan; Tsai, Bing-Shi; Wu, Fang-Ting; Yu, Fu-Jung; Tseng, Yu-Jung; Sung, Huang-Mo; Li, Wen-Hsiung

    2013-01-01

    Gene regulation change has long been recognized as an important mechanism for phenotypic evolution. We used the evolution of yeast aerobic fermentation as a model to explore how gene regulation has evolved and how this process has contributed to phenotypic evolution and adaptation. Most eukaryotes fully oxidize glucose to CO2 and H2O in mitochondria to maximize energy yield, whereas some yeasts, such as Saccharomyces cerevisiae and its relatives, predominantly ferment glucose into ethanol even in the presence of oxygen, a phenomenon known as aerobic fermentation. We examined the genome-wide gene expression levels among 12 different yeasts and found that a group of genes involved in the mitochondrial respiration process showed the largest reduction in gene expression level during the evolution of aerobic fermentation. Our analysis revealed that the downregulation of these genes was significantly associated with massive loss of binding motifs of Cbf1p in the fermentative yeasts. Our experimental assays confirmed the binding of Cbf1p to the predicted motif and the activator role of Cbf1p. In summary, our study laid a foundation to unravel the long-time mystery about the genetic basis of evolution of aerobic fermentation, providing new insights into understanding the role of cis-regulatory changes in phenotypic evolution. PMID:23650209

  3. Bioinformatic analysis of cis-regulatory interactions between progesterone and estrogen receptors in breast cancer

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    Matloob Khushi

    2014-11-01

    Full Text Available Chromatin factors interact with each other in a cell and sequence-specific manner in order to regulate transcription and a wealth of publically available datasets exists describing the genomic locations of these interactions. Our recently published BiSA (Binding Sites Analyser database contains transcription factor binding locations and epigenetic modifications collected from published studies and provides tools to analyse stored and imported data. Using BiSA we investigated the overlapping cis-regulatory role of estrogen receptor alpha (ERα and progesterone receptor (PR in the T-47D breast cancer cell line. We found that ERα binding sites overlap with a subset of PR binding sites. To investigate further, we re-analysed raw data to remove any biases introduced by the use of distinct tools in the original publications. We identified 22,152 PR and 18,560 ERα binding sites (<5% false discovery rate with 4,358 overlapping regions among the two datasets. BiSA statistical analysis revealed a non-significant overall overlap correlation between the two factors, suggesting that ERα and PR are not partner factors and do not require each other for binding to occur. However, Monte Carlo simulation by Binary Interval Search (BITS, Relevant Distance, Absolute Distance, Jaccard and Projection tests by Genometricorr revealed a statistically significant spatial correlation of binding regions on chromosome between the two factors. Motif analysis revealed that the shared binding regions were enriched with binding motifs for ERα, PR and a number of other transcription and pioneer factors. Some of these factors are known to co-locate with ERα and PR binding. Therefore spatially close proximity of ERα binding sites with PR binding sites suggests that ERα and PR, in general function independently at the molecular level, but that their activities converge on a specific subset of transcriptional targets.

  4. A HLA class I cis-regulatory element whose activity can be modulated by hormones.

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    Sim, B C; Hui, K M

    1994-12-01

    To elucidate the basis of the down-regulation in major histocompatibility complex (MHC) class I gene expression and to identify possible DNA-binding regulatory elements that have the potential to interact with class I MHC genes, we have studied the transcriptional regulation of class I HLA genes in human breast carcinoma cells. A 9 base pair (bp) negative cis-regulatory element (NRE) has been identified using band-shift assays employing DNA sequences derived from the 5'-flanking region of HLA class I genes. This 9-bp element, GTCATGGCG, located within exon I of the HLA class I gene, can potently inhibit the expression of a heterologous thymidine kinase (TK) gene promoter and the HLA enhancer element. Furthermore, this regulatory element can exert its suppressive function in either the sense or anti-sense orientation. More interestingly, NRE can suppress dexamethasone-mediated gene activation in the context of the reported glucocorticoid-responsive element (GRE) in MCF-7 cells but has no influence on the estrogen-mediated transcriptional activation of MCF-7 cells in the context of the reported estrogen-responsive element (ERE). Furthermore, the presence of such a regulatory element within the HLA class I gene whose activity can be modulated by hormones correlates well with our observation that the level of HLA class I gene expression can be down-regulated by hormones in human breast carcinoma cells. Such interactions between negative regulatory elements and specific hormone trans-activators are novel and suggest a versatile form of transcriptional control.

  5. Direct activation of a notochord cis-regulatory module by Brachyury and FoxA in the ascidian Ciona intestinalis.

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    Passamaneck, Yale J; Katikala, Lavanya; Perrone, Lorena; Dunn, Matthew P; Oda-Ishii, Izumi; Di Gregorio, Anna

    2009-11-01

    The notochord is a defining feature of the chordate body plan. Experiments in ascidian, frog and mouse embryos have shown that co-expression of Brachyury and FoxA class transcription factors is required for notochord development. However, studies on the cis-regulatory sequences mediating the synergistic effects of these transcription factors are complicated by the limited knowledge of notochord genes and cis-regulatory modules (CRMs) that are directly targeted by both. We have identified an easily testable model for such investigations in a 155-bp notochord-specific CRM from the ascidian Ciona intestinalis. This CRM contains functional binding sites for both Ciona Brachyury (Ci-Bra) and FoxA (Ci-FoxA-a). By combining point mutation analysis and misexpression experiments, we demonstrate that binding of both transcription factors to this CRM is necessary and sufficient to activate transcription. To gain insights into the cis-regulatory criteria controlling its activity, we investigated the organization of the transcription factor binding sites within the 155-bp CRM. The 155-bp sequence contains two Ci-Bra binding sites with identical core sequences but opposite orientations, only one of which is required for enhancer activity. Changes in both orientation and spacing of these sites substantially affect the activity of the CRM, as clusters of identical sites found in the Ciona genome with different arrangements are unable to activate transcription in notochord cells. This work presents the first evidence of a synergistic interaction between Brachyury and FoxA in the activation of an individual notochord CRM, and highlights the importance of transcription factor binding site arrangement for its function.

  6. Characterization of a putative cis-regulatory element that controls transcriptional activity of the pig uroplakin II gene promoter

    International Nuclear Information System (INIS)

    Kwon, Deug-Nam; Park, Mi-Ryung; Park, Jong-Yi; Cho, Ssang-Goo; Park, Chankyu; Oh, Jae-Wook; Song, Hyuk; Kim, Jae-Hwan; Kim, Jin-Hoi

    2011-01-01

    Highlights: → The sequences of -604 to -84 bp of the pUPII promoter contained the region of a putative negative cis-regulatory element. → The core promoter was located in the 5F-1. → Transcription factor HNF4 can directly bind in the pUPII core promoter region, which plays a critical role in controlling promoter activity. → These features of the pUPII promoter are fundamental to development of a target-specific vector. -- Abstract: Uroplakin II (UPII) is a one of the integral membrane proteins synthesized as a major differentiation product of mammalian urothelium. UPII gene expression is bladder specific and differentiation dependent, but little is known about its transcription response elements and molecular mechanism. To identify the cis-regulatory elements in the pig UPII (pUPII) gene promoter region, we constructed pUPII 5' upstream region deletion mutants and demonstrated that each of the deletion mutants participates in controlling the expression of the pUPII gene in human bladder carcinoma RT4 cells. We also identified a new core promoter region and putative negative cis-regulatory element within a minimal promoter region. In addition, we showed that hepatocyte nuclear factor 4 (HNF4) can directly bind in the pUPII core promoter (5F-1) region, which plays a critical role in controlling promoter activity. Transient cotransfection experiments showed that HNF4 positively regulates pUPII gene promoter activity. Thus, the binding element and its binding protein, HNF4 transcription factor, may be involved in the mechanism that specifically regulates pUPII gene transcription.

  7. Genes involved in complex adaptive processes tend to have highly conserved upstream regions in mammalian genomes

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    Kohane Isaac

    2005-11-01

    Full Text Available Abstract Background Recent advances in genome sequencing suggest a remarkable conservation in gene content of mammalian organisms. The similarity in gene repertoire present in different organisms has increased interest in studying regulatory mechanisms of gene expression aimed at elucidating the differences in phenotypes. In particular, a proximal promoter region contains a large number of regulatory elements that control the expression of its downstream gene. Although many studies have focused on identification of these elements, a broader picture on the complexity of transcriptional regulation of different biological processes has not been addressed in mammals. The regulatory complexity may strongly correlate with gene function, as different evolutionary forces must act on the regulatory systems under different biological conditions. We investigate this hypothesis by comparing the conservation of promoters upstream of genes classified in different functional categories. Results By conducting a rank correlation analysis between functional annotation and upstream sequence alignment scores obtained by human-mouse and human-dog comparison, we found a significantly greater conservation of the upstream sequence of genes involved in development, cell communication, neural functions and signaling processes than those involved in more basic processes shared with unicellular organisms such as metabolism and ribosomal function. This observation persists after controlling for G+C content. Considering conservation as a functional signature, we hypothesize a higher density of cis-regulatory elements upstream of genes participating in complex and adaptive processes. Conclusion We identified a class of functions that are associated with either high or low promoter conservation in mammals. We detected a significant tendency that points to complex and adaptive processes were associated with higher promoter conservation, despite the fact that they have emerged

  8. cisMEP: an integrated repository of genomic epigenetic profiles and cis-regulatory modules in Drosophila.

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    Yang, Tzu-Hsien; Wang, Chung-Ching; Hung, Po-Cheng; Wu, Wei-Sheng

    2014-01-01

    Cis-regulatory modules (CRMs), or the DNA sequences required for regulating gene expression, play the central role in biological researches on transcriptional regulation in metazoan species. Nowadays, the systematic understanding of CRMs still mainly resorts to computational methods due to the time-consuming and small-scale nature of experimental methods. But the accuracy and reliability of different CRM prediction tools are still unclear. Without comparative cross-analysis of the results and combinatorial consideration with extra experimental information, there is no easy way to assess the confidence of the predicted CRMs. This limits the genome-wide understanding of CRMs. It is known that transcription factor binding and epigenetic profiles tend to determine functions of CRMs in gene transcriptional regulation. Thus integration of the genome-wide epigenetic profiles with systematically predicted CRMs can greatly help researchers evaluate and decipher the prediction confidence and possible transcriptional regulatory functions of these potential CRMs. However, these data are still fragmentary in the literatures. Here we performed the computational genome-wide screening for potential CRMs using different prediction tools and constructed the pioneer database, cisMEP (cis-regulatory module epigenetic profile database), to integrate these computationally identified CRMs with genomic epigenetic profile data. cisMEP collects the literature-curated TFBS location data and nine genres of epigenetic data for assessing the confidence of these potential CRMs and deciphering the possible CRM functionality. cisMEP aims to provide a user-friendly interface for researchers to assess the confidence of different potential CRMs and to understand the functions of CRMs through experimentally-identified epigenetic profiles. The deposited potential CRMs and experimental epigenetic profiles for confidence assessment provide experimentally testable hypotheses for the molecular mechanisms

  9. Dynamic in vivo binding of transcription factors to cis-regulatory modules of cer and gsc in the stepwise formation of the Spemann–Mangold organizer

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    Sudou, Norihiro; Yamamoto, Shinji; Ogino, Hajime; Taira, Masanori

    2012-01-01

    How multiple developmental cues are integrated on cis-regulatory modules (CRMs) for cell fate decisions remains uncertain. The Spemann–Mangold organizer in Xenopus embryos expresses the transcription factors Lim1/Lhx1, Otx2, Mix1, Siamois (Sia) and VegT. Reporter analyses using sperm nuclear transplantation and DNA injection showed that cerberus (cer) and goosecoid (gsc) are activated by the aforementioned transcription factors through CRMs conserved between X. laevis and X. tropicalis. ChIP-qPCR analysis for the five transcription factors revealed that cer and gsc CRMs are initially bound by both Sia and VegT at the late blastula stage, and subsequently bound by all five factors at the gastrula stage. At the neurula stage, only binding of Lim1 and Otx2 to the gsc CRM, among others, persists, which corresponds to their co-expression in the prechordal plate. Based on these data, together with detailed expression pattern analysis, we propose a new model of stepwise formation of the organizer, in which (1) maternal VegT and Wnt-induced Sia first bind to CRMs at the blastula stage; then (2) Nodal-inducible Lim1, Otx2, Mix1 and zygotic VegT are bound to CRMs in the dorsal endodermal and mesodermal regions where all these genes are co-expressed; and (3) these two regions are combined at the gastrula stage to form the organizer. Thus, the in vivo dynamics of multiple transcription factors highlight their roles in the initiation and maintenance of gene expression, and also reveal the stepwise integration of maternal, Nodal and Wnt signaling on CRMs of organizer genes to generate the organizer. PMID:22492356

  10. Dynamic in vivo binding of transcription factors to cis-regulatory modules of cer and gsc in the stepwise formation of the Spemann-Mangold organizer.

    Science.gov (United States)

    Sudou, Norihiro; Yamamoto, Shinji; Ogino, Hajime; Taira, Masanori

    2012-05-01

    How multiple developmental cues are integrated on cis-regulatory modules (CRMs) for cell fate decisions remains uncertain. The Spemann-Mangold organizer in Xenopus embryos expresses the transcription factors Lim1/Lhx1, Otx2, Mix1, Siamois (Sia) and VegT. Reporter analyses using sperm nuclear transplantation and DNA injection showed that cerberus (cer) and goosecoid (gsc) are activated by the aforementioned transcription factors through CRMs conserved between X. laevis and X. tropicalis. ChIP-qPCR analysis for the five transcription factors revealed that cer and gsc CRMs are initially bound by both Sia and VegT at the late blastula stage, and subsequently bound by all five factors at the gastrula stage. At the neurula stage, only binding of Lim1 and Otx2 to the gsc CRM, among others, persists, which corresponds to their co-expression in the prechordal plate. Based on these data, together with detailed expression pattern analysis, we propose a new model of stepwise formation of the organizer, in which (1) maternal VegT and Wnt-induced Sia first bind to CRMs at the blastula stage; then (2) Nodal-inducible Lim1, Otx2, Mix1 and zygotic VegT are bound to CRMs in the dorsal endodermal and mesodermal regions where all these genes are co-expressed; and (3) these two regions are combined at the gastrula stage to form the organizer. Thus, the in vivo dynamics of multiple transcription factors highlight their roles in the initiation and maintenance of gene expression, and also reveal the stepwise integration of maternal, Nodal and Wnt signaling on CRMs of organizer genes to generate the organizer.

  11. PlantPAN: Plant promoter analysis navigator, for identifying combinatorial cis-regulatory elements with distance constraint in plant gene groups

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    Huang Hsien-Da

    2008-11-01

    Full Text Available Abstract Background The elucidation of transcriptional regulation in plant genes is important area of research for plant scientists, following the mapping of various plant genomes, such as A. thaliana, O. sativa and Z. mays. A variety of bioinformatic servers or databases of plant promoters have been established, although most have been focused only on annotating transcription factor binding sites in a single gene and have neglected some important regulatory elements (tandem repeats and CpG/CpNpG islands in promoter regions. Additionally, the combinatorial interaction of transcription factors (TFs is important in regulating the gene group that is associated with the same expression pattern. Therefore, a tool for detecting the co-regulation of transcription factors in a group of gene promoters is required. Results This study develops a database-assisted system, PlantPAN (Plant Promoter Analysis Navigator, for recognizing combinatorial cis-regulatory elements with a distance constraint in sets of plant genes. The system collects the plant transcription factor binding profiles from PLACE, TRANSFAC (public release 7.0, AGRIS, and JASPER databases and allows users to input a group of gene IDs or promoter sequences, enabling the co-occurrence of combinatorial transcription factor binding sites (TFBSs within a defined distance (20 bp to 200 bp to be identified. Furthermore, the new resource enables other regulatory features in a plant promoter, such as CpG/CpNpG islands and tandem repeats, to be displayed. The regulatory elements in the conserved regions of the promoters across homologous genes are detected and presented. Conclusion In addition to providing a user-friendly input/output interface, PlantPAN has numerous advantages in the analysis of a plant promoter. Several case studies have established the effectiveness of PlantPAN. This novel analytical resource is now freely available at http://PlantPAN.mbc.nctu.edu.tw.

  12. Systematic identification of cis-regulatory sequences active in mouse and human embryonic stem cells.

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    Marica Grskovic

    2007-08-01

    Full Text Available Understanding the transcriptional regulation of pluripotent cells is of fundamental interest and will greatly inform efforts aimed at directing differentiation of embryonic stem (ES cells or reprogramming somatic cells. We first analyzed the transcriptional profiles of mouse ES cells and primordial germ cells and identified genes upregulated in pluripotent cells both in vitro and in vivo. These genes are enriched for roles in transcription, chromatin remodeling, cell cycle, and DNA repair. We developed a novel computational algorithm, CompMoby, which combines analyses of sequences both aligned and non-aligned between different genomes with a probabilistic segmentation model to systematically predict short DNA motifs that regulate gene expression. CompMoby was used to identify conserved overrepresented motifs in genes upregulated in pluripotent cells. We show that the motifs are preferentially active in undifferentiated mouse ES and embryonic germ cells in a sequence-specific manner, and that they can act as enhancers in the context of an endogenous promoter. Importantly, the activity of the motifs is conserved in human ES cells. We further show that the transcription factor NF-Y specifically binds to one of the motifs, is differentially expressed during ES cell differentiation, and is required for ES cell proliferation. This study provides novel insights into the transcriptional regulatory networks of pluripotent cells. Our results suggest that this systematic approach can be broadly applied to understanding transcriptional networks in mammalian species.

  13. Cis-regulatory PLETHORA promoter elements directing root and nodule expression are conserved between Arabidopsis thaliana and Medicago truncatula

    NARCIS (Netherlands)

    Franssen, H.G.J.M.; Kulikova, O.; Willemsen, V.A.; Heidstra, R.

    2017-01-01

    Nodules are unique organs formed on roots of legumes by soil-borne bacteria, collectively known as rhizobium. Recently, we have shown that orthologs of the AINTEGUMENTA-like (AIL) AP2 transcription factors PLETHORA (PLT) 1 to 4, that redundantly regulate Arabidopsis thaliana root development are

  14. Identification of cis-regulatory sequences that activate transcription in the suspensor of plant embryos.

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    Kawashima, Tomokazu; Wang, Xingjun; Henry, Kelli F; Bi, Yuping; Weterings, Koen; Goldberg, Robert B

    2009-03-03

    Little is known about the molecular mechanisms by which the embryo proper and suspensor of plant embryos activate specific gene sets shortly after fertilization. We analyzed the upstream region of the scarlet runner bean (Phaseolus coccineus) G564 gene to understand how genes are activated specifically within the suspensor during early embryo development. Previously, we showed that the G564 upstream region has a block of tandem repeats, which contain a conserved 10-bp motif (GAAAAG(C)/(T)GAA), and that deletion of these repeats results in a loss of suspensor transcription. Here, we use gain-of-function (GOF) experiments with transgenic globular-stage tobacco embryos to show that only 1 of the 5 tandem repeats is required to drive suspensor-specific transcription. Fine-scale deletion and scanning mutagenesis experiments with 1 tandem repeat uncovered a 54-bp region that contains all of the sequences required to activate transcription in the suspensor, including the 10-bp motif (GAAAAGCGAA) and a similar 10-bp-like motif (GAAAAACGAA). Site-directed mutagenesis and GOF experiments indicated that both the 10-bp and 10-bp-like motifs are necessary, but not sufficient to activate transcription in the suspensor, and that a sequence (TTGGT) between the 10-bp and the 10-bp-like motifs is also necessary for suspensor transcription. Together, these data identify sequences that are required to activate transcription in the suspensor of a plant embryo after fertilization.

  15. Does positive selection drive transcription factor binding site turnover? A test with Drosophila cis-regulatory modules.

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    Bin Z He

    2011-04-01

    Full Text Available Transcription factor binding site(s (TFBS gain and loss (i.e., turnover is a well-documented feature of cis-regulatory module (CRM evolution, yet little attention has been paid to the evolutionary force(s driving this turnover process. The predominant view, motivated by its widespread occurrence, emphasizes the importance of compensatory mutation and genetic drift. Positive selection, in contrast, although it has been invoked in specific instances of adaptive gene expression evolution, has not been considered as a general alternative to neutral compensatory evolution. In this study we evaluate the two hypotheses by analyzing patterns of single nucleotide polymorphism in the TFBS of well-characterized CRM in two closely related Drosophila species, Drosophila melanogaster and Drosophila simulans. An important feature of the analysis is classification of TFBS mutations according to the direction of their predicted effect on binding affinity, which allows gains and losses to be evaluated independently along the two phylogenetic lineages. The observed patterns of polymorphism and divergence are not compatible with neutral evolution for either class of mutations. Instead, multiple lines of evidence are consistent with contributions of positive selection to TFBS gain and loss as well as purifying selection in its maintenance. In discussion, we propose a model to reconcile the finding of selection driving TFBS turnover with constrained CRM function over long evolutionary time.

  16. RNA expression in a cartilaginous fish cell line reveals ancient 3′ noncoding regions highly conserved in vertebrates

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    Forest, David; Nishikawa, Ryuhei; Kobayashi, Hiroshi; Parton, Angela; Bayne, Christopher J.; Barnes, David W.

    2007-01-01

    We have established a cartilaginous fish cell line [Squalus acanthias embryo cell line (SAE)], a mesenchymal stem cell line derived from the embryo of an elasmobranch, the spiny dogfish shark S. acanthias. Elasmobranchs (sharks and rays) first appeared >400 million years ago, and existing species provide useful models for comparative vertebrate cell biology, physiology, and genomics. Comparative vertebrate genomics among evolutionarily distant organisms can provide sequence conservation information that facilitates identification of critical coding and noncoding regions. Although these genomic analyses are informative, experimental verification of functions of genomic sequences depends heavily on cell culture approaches. Using ESTs defining mRNAs derived from the SAE cell line, we identified lengthy and highly conserved gene-specific nucleotide sequences in the noncoding 3′ UTRs of eight genes involved in the regulation of cell growth and proliferation. Conserved noncoding 3′ mRNA regions detected by using the shark nucleotide sequences as a starting point were found in a range of other vertebrate orders, including bony fish, birds, amphibians, and mammals. Nucleotide identity of shark and human in these regions was remarkably well conserved. Our results indicate that highly conserved gene sequences dating from the appearance of jawed vertebrates and representing potential cis-regulatory elements can be identified through the use of cartilaginous fish as a baseline. Because the expression of genes in the SAE cell line was prerequisite for their identification, this cartilaginous fish culture system also provides a physiologically valid tool to test functional hypotheses on the role of these ancient conserved sequences in comparative cell biology. PMID:17227856

  17. Comprehensive meta-analysis of Signal Transducers and Activators of Transcription (STAT genomic binding patterns discerns cell-specific cis-regulatory modules

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    Kang Keunsoo

    2013-01-01

    Full Text Available Abstract Background Cytokine-activated transcription factors from the STAT (Signal Transducers and Activators of Transcription family control common and context-specific genetic programs. It is not clear to what extent cell-specific features determine the binding capacity of seven STAT members and to what degree they share genetic targets. Molecular insight into the biology of STATs was gained from a meta-analysis of 29 available ChIP-seq data sets covering genome-wide occupancy of STATs 1, 3, 4, 5A, 5B and 6 in several cell types. Results We determined that the genomic binding capacity of STATs is primarily defined by the cell type and to a lesser extent by individual family members. For example, the overlap of shared binding sites between STATs 3 and 5 in T cells is greater than that between STAT5 in T cells and non-T cells. Even for the top 1,000 highly enriched STAT binding sites, ~15% of STAT5 binding sites in mouse female liver are shared by other STATs in different cell types while in T cells ~90% of STAT5 binding sites are co-occupied by STAT3, STAT4 and STAT6. In addition, we identified 116 cis-regulatory modules (CRM, which are recognized by all STAT members across cell types defining a common JAK-STAT signature. Lastly, in liver STAT5 binding significantly coincides with binding of the cell-specific transcription factors HNF4A, FOXA1 and FOXA2 and is associated with cell-type specific gene transcription. Conclusions Our results suggest that genomic binding of STATs is primarily determined by the cell type and further specificity is achieved in part by juxtaposed binding of cell-specific transcription factors.

  18. A novel method for predicting activity of cis-regulatory modules, based on a diverse training set.

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    Yang, Wei; Sinha, Saurabh

    2017-01-01

    With the rapid emergence of technologies for locating cis-regulatory modules (CRMs) genome-wide, the next pressing challenge is to assign precise functions to each CRM, i.e. to determine the spatiotemporal domains or cell-types where it drives expression. A popular approach to this task is to model the typical k-mer composition of a set of CRMs known to drive a common expression pattern, and assign that pattern to other CRMs exhibiting a similar k-mer composition. This approach does not rely on prior knowledge of transcription factors relevant to the CRM or their binding motifs, and is thus more widely applicable than motif-based methods for predicting CRM activity, but is also prone to false positive predictions. We present a novel strategy to improve the above-mentioned approach: to predict if a CRM drives a specific gene expression pattern, assess not only how similar the CRM is to other CRMs with similar activity but also to CRMs with distinct activities. We use a state-of-the-art statistical method to quantify a CRM's sequence similarity to many different training sets of CRMs, and employ a classification algorithm to integrate these similarity scores into a single prediction of the CRM's activity. This strategy is shown to significantly improve CRM activity prediction over current approaches. Our implementation of the new method, called IMMBoost, is freely available as source code, at https://github.com/weiyangedward/IMMBoost CONTACT: sinhas@illinois.eduSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  19. Identification of choriogenin cis-regulatory elements and production of estrogen-inducible, liver-specific transgenic Medaka.

    Science.gov (United States)

    Ueno, Tetsuro; Yasumasu, Shigeki; Hayashi, Shinji; Iuchi, Ichiro

    2004-07-01

    Choriogenins (chg-H, chg-L) are precursor proteins of egg envelope of medaka and synthesized in the spawning female liver in response to estrogen. We linked a gene construct chg-L1.5 kb/GFP (a 1.5 kb 5'-upstream region of the chg-L gene fused with a green fluorescence protein (GFP) gene) to another construct emgb/RFP (a cis-regulatory region of embryonic globin gene fused with an RFP gene), injected the double fusion gene construct into 1- or 2-cell-stage embryos, and selected embryos expressing the RFP in erythroid cells. From the embryos, we established two lines of chg-L1.5 kb/GFP-emgb/RFP-transgenic medaka. The 3-month-old spawning females and estradiol-17beta (E2)-exposed males displayed the liver-specific GFP expression. The E2-dependent GFP expression was detected in the differentiating liver of the stage 37-38 embryos. In addition, RT-PCR and whole-mount in situ hybridization showed that the E2-dependent chg expression was found in the liver of the stage 34 embryos of wild medaka, suggesting that such E2-dependency is achieved shortly after differentiation of the liver. Analysis using serial deletion mutants fused with GFP showed that the region -426 to -284 of the chg-L gene or the region -364 to -265 of the chg-H gene had the ability to promote the E2-dependent liver-specific GFP expression of its downstream gene. Further analyses suggested that an estrogen response element (ERE) at -309, an ERE half-site at -330 and a binding site for C/EBP at -363 of the chg-L gene played important roles in its downstream chg-L gene expression. In addition, this transgenic medaka may be useful as one of the test animals for detecting environmental estrogenic steroids.

  20. Multiple cis-regulatory elements are involved in the complex regulation of the sieve element-specific MtSEO-F1 promoter from Medicago truncatula.

    Science.gov (United States)

    Bucsenez, M; Rüping, B; Behrens, S; Twyman, R M; Noll, G A; Prüfer, D

    2012-09-01

    The sieve element occlusion (SEO) gene family includes several members that are expressed specifically in immature sieve elements (SEs) in the developing phloem of dicotyledonous plants. To determine how this restricted expression profile is achieved, we analysed the SE-specific Medicago truncatula SEO-F1 promoter (PMtSEO-F1) by constructing deletion, substitution and hybrid constructs and testing them in transgenic tobacco plants using green fluorescent protein as a reporter. This revealed four promoter regions, each containing cis-regulatory elements that activate transcription in SEs. One of these segments also contained sufficient information to suppress PMtSEO-F1 transcription in the phloem companion cells (CCs). Subsequent in silico analysis revealed several candidate cis-regulatory elements that PMtSEO-F1 shares with other SEO promoters. These putative sieve element boxes (PSE boxes) are promising candidates for cis-regulatory elements controlling the SE-specific expression of PMtSEO-F1. © 2012 German Botanical Society and The Royal Botanical Society of the Netherlands.

  1. LDsplit: screening for cis-regulatory motifs stimulating meiotic recombination hotspots by analysis of DNA sequence polymorphisms.

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    Yang, Peng; Wu, Min; Guo, Jing; Kwoh, Chee Keong; Przytycka, Teresa M; Zheng, Jie

    2014-02-17

    As a fundamental genomic element, meiotic recombination hotspot plays important roles in life sciences. Thus uncovering its regulatory mechanisms has broad impact on biomedical research. Despite the recent identification of the zinc finger protein PRDM9 and its 13-mer binding motif as major regulators for meiotic recombination hotspots, other regulators remain to be discovered. Existing methods for finding DNA sequence motifs of recombination hotspots often rely on the enrichment of co-localizations between hotspots and short DNA patterns, which ignore the cross-individual variation of recombination rates and sequence polymorphisms in the population. Our objective in this paper is to capture signals encoded in genetic variations for the discovery of recombination-associated DNA motifs. Recently, an algorithm called "LDsplit" has been designed to detect the association between single nucleotide polymorphisms (SNPs) and proximal meiotic recombination hotspots. The association is measured by the difference of population recombination rates at a hotspot between two alleles of a candidate SNP. Here we present an open source software tool of LDsplit, with integrative data visualization for recombination hotspots and their proximal SNPs. Applying LDsplit on SNPs inside an established 7-mer motif bound by PRDM9 we observed that SNP alleles preserving the original motif tend to have higher recombination rates than the opposite alleles that disrupt the motif. Running on SNP windows around hotspots each containing an occurrence of the 7-mer motif, LDsplit is able to guide the established motif finding algorithm of MEME to recover the 7-mer motif. In contrast, without LDsplit the 7-mer motif could not be identified. LDsplit is a software tool for the discovery of cis-regulatory DNA sequence motifs stimulating meiotic recombination hotspots by screening and narrowing down to hotspot associated SNPs. It is the first computational method that utilizes the genetic variation of

  2. Predicting tissue specific cis-regulatory modules in the human genome using pairs of co-occurring motifs

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    Girgis Hani Z

    2012-02-01

    Full Text Available Abstract Background Researchers seeking to unlock the genetic basis of human physiology and diseases have been studying gene transcription regulation. The temporal and spatial patterns of gene expression are controlled by mainly non-coding elements known as cis-regulatory modules (CRMs and epigenetic factors. CRMs modulating related genes share the regulatory signature which consists of transcription factor (TF binding sites (TFBSs. Identifying such CRMs is a challenging problem due to the prohibitive number of sequence sets that need to be analyzed. Results We formulated the challenge as a supervised classification problem even though experimentally validated CRMs were not required. Our efforts resulted in a software system named CrmMiner. The system mines for CRMs in the vicinity of related genes. CrmMiner requires two sets of sequences: a mixed set and a control set. Sequences in the vicinity of the related genes comprise the mixed set, whereas the control set includes random genomic sequences. CrmMiner assumes that a large percentage of the mixed set is made of background sequences that do not include CRMs. The system identifies pairs of closely located motifs representing vertebrate TFBSs that are enriched in the training mixed set consisting of 50% of the gene loci. In addition, CrmMiner selects a group of the enriched pairs to represent the tissue-specific regulatory signature. The mixed and the control sets are searched for candidate sequences that include any of the selected pairs. Next, an optimal Bayesian classifier is used to distinguish candidates found in the mixed set from their control counterparts. Our study proposes 62 tissue-specific regulatory signatures and putative CRMs for different human tissues and cell types. These signatures consist of assortments of ubiquitously expressed TFs and tissue-specific TFs. Under controlled settings, CrmMiner identified known CRMs in noisy sets up to 1:25 signal-to-noise ratio. CrmMiner was

  3. A cis-regulatory sequence driving metabolic insecticide resistance in mosquitoes: functional characterisation and signatures of selection.

    Science.gov (United States)

    Wilding, Craig S; Smith, Ian; Lynd, Amy; Yawson, Alexander Egyir; Weetman, David; Paine, Mark J I; Donnelly, Martin J

    2012-09-01

    Although cytochrome P450 (CYP450) enzymes are frequently up-regulated in mosquitoes resistant to insecticides, no regulatory motifs driving these expression differences with relevance to wild populations have been identified. Transposable elements (TEs) are often enriched upstream of those CYP450s involved in insecticide resistance, leading to the assumption that they contribute regulatory motifs that directly underlie the resistance phenotype. A partial CuRE1 (Culex Repetitive Element 1) transposable element is found directly upstream of CYP9M10, a cytochrome P450 implicated previously in larval resistance to permethrin in the ISOP450 strain of Culex quinquefasciatus, but is absent from the equivalent genomic region of a susceptible strain. Via expression of CYP9M10 in Escherichia coli we have now demonstrated time- and NADPH-dependant permethrin metabolism, prerequisites for confirmation of a role in metabolic resistance, and through qPCR shown that CYP9M10 is >20-fold over-expressed in ISOP450 compared to a susceptible strain. In a fluorescent reporter assay the region upstream of CYP9M10 from ISOP450 drove 10× expression compared to the equivalent region (lacking CuRE1) from the susceptible strain. Close correspondence with the gene expression fold-change implicates the upstream region including CuRE1 as a cis-regulatory element involved in resistance. Only a single CuRE1 bearing allele, identical to the CuRE1 bearing allele in the resistant strain, is found throughout Sub-Saharan Africa, in contrast to the diversity encountered in non-CuRE1 alleles. This suggests a single origin and subsequent spread due to selective advantage. CuRE1 is detectable using a simple diagnostic. When applied to C. quinquefasciatus larvae from Ghana we have demonstrated a significant association with permethrin resistance in multiple field sites (mean Odds Ratio = 3.86) suggesting this marker has relevance to natural populations of vector mosquitoes. However, when CuRE1 was excised

  4. A minimal murine Msx-1 gene promoter. Organization of its cis-regulatory motifs and their role in transcriptional activation in cells in culture and in transgenic mice.

    Science.gov (United States)

    Takahashi, T; Guron, C; Shetty, S; Matsui, H; Raghow, R

    1997-09-05

    To dissect the cis-regulatory elements of the murine Msx-1 promoter, which lacks a conventional TATA element, a putative Msx-1 promoter DNA fragment (from -1282 to +106 base pairs (bp)) or its congeners containing site-specific alterations were fused to luciferase reporter and introduced into NIH3T3 and C2C12 cells, and the expression of luciferase was assessed in transient expression assays. The functional consequences of the sequential 5' deletions of the promotor revealed that multiple positive and negative regulatory elements participate in regulating transcription of the Msx-1 gene. Surprisingly, however, the optimal expression of Msx-1 promoter in either NIH3T3 or C2C12 cells required only 165 bp of the upstream sequence to warrant detailed examination of its structure. Therefore, the functional consequences of site-specific deletions and point mutations of the cis-acting elements of the minimal Msx-1 promoter were systematically examined. Concomitantly, potential transcriptional factor(s) interacting with the cis-acting elements of the minimal promoter were also studied by gel electrophoretic mobility shift assays and DNase I footprinting. Combined analyses of the minimal promoter by DNase I footprinting, electrophoretic mobility shift assays, and super shift assays with specific antibodies revealed that 5'-flanking regions from -161 to -154 and from -26 to -13 of the Msx-1 promoter contains an authentic E box (proximal E box), capable of binding a protein immunologically related to the upstream stimulating factor 1 (USF-1) and a GC-rich sequence motif which can bind to Sp1 (proximal Sp1), respectively. Additionally, we observed that the promoter activation was seriously hampered if the proximal E box was removed or mutated, and the promoter activity was eliminated completely if the proximal Sp1 site was similarly altered. Absolute dependence of the Msx-1 minimal promoter on Sp1 could be demonstrated by transient expression assays in the Sp1-deficient

  5. Computational exploration of cis-regulatory modules in rhythmic expression data using the "Exploration of Distinctive CREs and CRMs" (EDCC) and "CRM Network Generator" (CNG) programs.

    Science.gov (United States)

    Bekiaris, Pavlos Stephanos; Tekath, Tobias; Staiger, Dorothee; Danisman, Selahattin

    2018-01-01

    Understanding the effect of cis-regulatory elements (CRE) and clusters of CREs, which are called cis-regulatory modules (CRM), in eukaryotic gene expression is a challenge of computational biology. We developed two programs that allow simple, fast and reliable analysis of candidate CREs and CRMs that may affect specific gene expression and that determine positional features between individual CREs within a CRM. The first program, "Exploration of Distinctive CREs and CRMs" (EDCC), correlates candidate CREs and CRMs with specific gene expression patterns. For pairs of CREs, EDCC also determines positional preferences of the single CREs in relation to each other and to the transcriptional start site. The second program, "CRM Network Generator" (CNG), prioritizes these positional preferences using a neural network and thus allows unbiased rating of the positional preferences that were determined by EDCC. We tested these programs with data from a microarray study of circadian gene expression in Arabidopsis thaliana. Analyzing more than 1.5 million pairwise CRE combinations, we found 22 candidate combinations, of which several contained known clock promoter elements together with elements that had not been identified as relevant to circadian gene expression before. CNG analysis further identified positional preferences of these CRE pairs, hinting at positional information that may be relevant for circadian gene expression. Future wet lab experiments will have to determine which of these combinations confer daytime specific circadian gene expression.

  6. Properties of non-coding DNA and identification of putative cis-regulatory elements in Theileria parva

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    Guo Xiang

    2008-12-01

    Full Text Available Abstract Background Parasites in the genus Theileria cause lymphoproliferative diseases in cattle, resulting in enormous socio-economic losses. The availability of the genome sequences and annotation for T. parva and T. annulata has facilitated the study of parasite biology and their relationship with host cell transformation and tropism. However, the mechanism of transcriptional regulation in this genus, which may be key to understanding fundamental aspects of its parasitology, remains poorly understood. In this study, we analyze the evolution of non-coding sequences in the Theileria genome and identify conserved sequence elements that may be involved in gene regulation of these parasitic species. Results Intergenic regions and introns in Theileria are short, and their length distributions are considerably right-skewed. Intergenic regions flanked by genes in 5'-5' orientation tend to be longer and slightly more AT-rich than those flanked by two stop codons; intergenic regions flanked by genes in 3'-5' orientation have intermediate values of length and AT composition. Intron position is negatively correlated with intron length, and positively correlated with GC content. Using stringent criteria, we identified a set of high-quality orthologous non-coding sequences between T. parva and T. annulata, and determined the distribution of selective constraints across regions, which are shown to be higher close to translation start sites. A positive correlation between constraint and length in both intergenic regions and introns suggests a tight control over length expansion of non-coding regions. Genome-wide searches for functional elements revealed several conserved motifs in intergenic regions of Theileria genomes. Two such motifs are preferentially located within the first 60 base pairs upstream of transcription start sites in T. parva, are preferentially associated with specific protein functional categories, and have significant similarity to know

  7. Microevolution of cis-regulatory elements: an example from the pair-rule segmentation gene fushi tarazu in the Drosophila melanogaster subgroup.

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    Mohammed Bakkali

    Full Text Available The importance of non-coding DNAs that control transcription is ever noticeable, but the characterization and analysis of the evolution of such DNAs presents challenges not found in the analysis of coding sequences. In this study of the cis-regulatory elements of the pair rule segmentation gene fushi tarazu (ftz I report the DNA sequences of ftz's zebra element (promoter and a region containing the proximal enhancer from a total of 45 fly lines belonging to several populations of the species Drosophila melanogaster, D. simulans, D. sechellia, D. mauritiana, D. yakuba, D. teissieri, D. orena and D. erecta. Both elements evolve at slower rate than ftz synonymous sites, thus reflecting their functional importance. The promoter evolves more slowly than the average for ftz's coding sequence while, on average, the enhancer evolves more rapidly, suggesting more functional constraint and effective purifying selection on the former. Comparative analysis of the number and nature of base substitutions failed to detect significant evidence for positive/adaptive selection in transcription-factor-binding sites. These seem to evolve at similar rates to regions not known to bind transcription factors. Although this result reflects the evolutionary flexibility of the transcription factor binding sites, it also suggests a complex and still not completely understood nature of even the characterized cis-regulatory sequences. The latter seem to contain more functional parts than those currently identified, some of which probably transcription factor binding. This study illustrates ways in which functional assignments of sequences within cis-acting sequences can be used in the search for adaptive evolution, but also highlights difficulties in how such functional assignment and analysis can be carried out.

  8. Quantitative statistical analysis of cis-regulatory sequences in ABA/VP1- and CBF/DREB1-regulated genes of Arabidopsis.

    Science.gov (United States)

    Suzuki, Masaharu; Ketterling, Matthew G; McCarty, Donald R

    2005-09-01

    We have developed a simple quantitative computational approach for objective analysis of cis-regulatory sequences in promoters of coregulated genes. The program, designated MotifFinder, identifies oligo sequences that are overrepresented in promoters of coregulated genes. We used this approach to analyze promoter sequences of Viviparous1 (VP1)/abscisic acid (ABA)-regulated genes and cold-regulated genes, respectively, of Arabidopsis (Arabidopsis thaliana). We detected significantly enriched sequences in up-regulated genes but not in down-regulated genes. This result suggests that gene activation but not repression is mediated by specific and common sequence elements in promoters. The enriched motifs include several known cis-regulatory sequences as well as previously unidentified motifs. With respect to known cis-elements, we dissected the flanking nucleotides of the core sequences of Sph element, ABA response elements (ABREs), and the C repeat/dehydration-responsive element. This analysis identified the motif variants that may correlate with qualitative and quantitative differences in gene expression. While both VP1 and cold responses are mediated in part by ABA signaling via ABREs, these responses correlate with unique ABRE variants distinguished by nucleotides flanking the ACGT core. ABRE and Sph motifs are tightly associated uniquely in the coregulated set of genes showing a strict dependence on VP1 and ABA signaling. Finally, analysis of distribution of the enriched sequences revealed a striking concentration of enriched motifs in a proximal 200-base region of VP1/ABA and cold-regulated promoters. Overall, each class of coregulated genes possesses a discrete set of the enriched motifs with unique distributions in their promoters that may account for the specificity of gene regulation.

  9. Changes in cis-regulatory elements of a key floral regulator are associated with divergence of inflorescence architectures

    NARCIS (Netherlands)

    Kusters, E.; Della Pina, S.; Castel, R.; Souer, E.; Koes, R.

    2015-01-01

    Higher plant species diverged extensively with regard to the moment (flowering time) and position (inflorescence architecture) at which flowers are formed. This seems largely caused by variation in the expression patterns of conserved genes that specify floral meristem identity (FMI), rather than

  10. Changes in cis-regulatory elements of a key floral regulator are associated with divergence of inflorescence architectures.

    NARCIS (Netherlands)

    Kusters, E.; Della Pina, S.; Castel, R.; Souer, E.J.; Koes, R.E.

    2015-01-01

    Higher plant species diverged extensively with regard to the moment (flowering time) and position (inflorescence architecture) at which flowers are formed. This seems largely caused by variation in the expression patterns of conserved genes that specify floral meristem identity (FMI), rather than

  11. Distinct cis regulatory elements govern the expression of TAG1 in embryonic sensory ganglia and spinal cord.

    Directory of Open Access Journals (Sweden)

    Yoav Hadas

    Full Text Available Cell fate commitment of spinal progenitor neurons is initiated by long-range, midline-derived, morphogens that regulate an array of transcription factors that, in turn, act sequentially or in parallel to control neuronal differentiation. Included among these are transcription factors that regulate the expression of receptors for guidance cues, thereby determining axonal trajectories. The Ig/FNIII superfamily molecules TAG1/Axonin1/CNTN2 (TAG1 and Neurofascin (Nfasc are co-expressed in numerous neuronal cell types in the CNS and PNS - for example motor, DRG and interneurons - both promote neurite outgrowth and both are required for the architecture and function of nodes of Ranvier. The genes encoding TAG1 and Nfasc are adjacent in the genome, an arrangement which is evolutionarily conserved. To study the transcriptional network that governs TAG1 and Nfasc expression in spinal motor and commissural neurons, we set out to identify cis elements that regulate their expression. Two evolutionarily conserved DNA modules, one located between the Nfasc and TAG1 genes and the second directly 5' to the first exon and encompassing the first intron of TAG1, were identified that direct complementary expression to the CNS and PNS, respectively, of the embryonic hindbrain and spinal cord. Sequential deletions and point mutations of the CNS enhancer element revealed a 130bp element containing three conserved E-boxes required for motor neuron expression. In combination, these two elements appear to recapitulate a major part of the pattern of TAG1 expression in the embryonic nervous system.

  12. Integrative modeling of eQTLs and cis-regulatory elements suggests mechanisms underlying cell type specificity of eQTLs.

    Directory of Open Access Journals (Sweden)

    Christopher D Brown

    Full Text Available Genetic variants in cis-regulatory elements or trans-acting regulators frequently influence the quantity and spatiotemporal distribution of gene transcription. Recent interest in expression quantitative trait locus (eQTL mapping has paralleled the adoption of genome-wide association studies (GWAS for the analysis of complex traits and disease in humans. Under the hypothesis that many GWAS associations tag non-coding SNPs with small effects, and that these SNPs exert phenotypic control by modifying gene expression, it has become common to interpret GWAS associations using eQTL data. To fully exploit the mechanistic interpretability of eQTL-GWAS comparisons, an improved understanding of the genetic architecture and causal mechanisms of cell type specificity of eQTLs is required. We address this need by performing an eQTL analysis in three parts: first we identified eQTLs from eleven studies on seven cell types; then we integrated eQTL data with cis-regulatory element (CRE data from the ENCODE project; finally we built a set of classifiers to predict the cell type specificity of eQTLs. The cell type specificity of eQTLs is associated with eQTL SNP overlap with hundreds of cell type specific CRE classes, including enhancer, promoter, and repressive chromatin marks, regions of open chromatin, and many classes of DNA binding proteins. These associations provide insight into the molecular mechanisms generating the cell type specificity of eQTLs and the mode of regulation of corresponding eQTLs. Using a random forest classifier with cell specific CRE-SNP overlap as features, we demonstrate the feasibility of predicting the cell type specificity of eQTLs. We then demonstrate that CREs from a trait-associated cell type can be used to annotate GWAS associations in the absence of eQTL data for that cell type. We anticipate that such integrative, predictive modeling of cell specificity will improve our ability to understand the mechanistic basis of human

  13. Cis-regulatory control of the nuclear receptor Coup-TF gene in the sea urchin Paracentrotus lividus embryo.

    Directory of Open Access Journals (Sweden)

    Lamprini G Kalampoki

    Full Text Available Coup-TF, an orphan member of the nuclear receptor super family, has a fundamental role in the development of metazoan embryos. The study of the gene's regulatory circuit in the sea urchin embryo will facilitate the placement of this transcription factor in the well-studied embryonic Gene Regulatory Network (GRN. The Paracentrotus lividus Coup-TF gene (PlCoup-TF is expressed throughout embryonic development preferentially in the oral ectoderm of the gastrula and the ciliary band of the pluteus stage. Two overlapping λ genomic clones, containing three exons and upstream sequences of PlCoup-TF, were isolated from a genomic library. The transcription initiation site was determined and 5' deletions and individual segments of a 1930 bp upstream region were placed ahead of a GFP reporter cassette and injected into fertilized P.lividus eggs. Module a (-532 to -232, was necessary and sufficient to confer ciliary band expression to the reporter. Comparison of P.lividus and Strongylocentrotus purpuratus upstream Coup-TF sequences, revealed considerable conservation, but none within module a. 5' and internal deletions into module a, defined a smaller region that confers ciliary band specific expression. Putative regulatory cis-acting elements (RE1, RE2 and RE3 within module a, were specifically bound by proteins in sea urchin embryonic nuclear extracts. Site-specific mutagenesis of these elements resulted in loss of reporter activity (RE1 or ectopic expression (RE2, RE3. It is proposed that sea urchin transcription factors, which bind these three regulatory sites, are necessary for spatial and quantitative regulation of the PlCoup-TF gene at pluteus stage sea urchin embryos. These findings lead to the future identification of these factors and to the hierarchical positioning of PlCoup-TF within the embryonic GRN.

  14. Identification of a cis-regulatory region of a gene in Arabidopsis thaliana whose induction by dehydration is mediated by abscisic acid and requires protein synthesis.

    Science.gov (United States)

    Iwasaki, T; Yamaguchi-Shinozaki, K; Shinozaki, K

    1995-05-20

    In Arabidopsis thaliana, the induction of a dehydration-responsive gene, rd22, is mediated by abscisic acid (ABA) but the gene does not include any sequence corresponding to the consensus ABA-responsive element (ABRE), RYACGTGGYR, in its promoter region. The cis-regulatory region of the rd22 promoter was identified by monitoring the expression of beta-glucuronidase (GUS) activity in leaves of transgenic tobacco plants transformed with chimeric gene fusions constructed between 5'-deleted promoters of rd22 and the coding region of the GUS reporter gene. A 67-bp nucleotide fragment corresponding to positions -207 to -141 of the rd22 promoter conferred responsiveness to dehydration and ABA on a non-responsive promoter. The 67-bp fragment contains the sequences of the recognition sites for some transcription factors, such as MYC, MYB, and GT-1. The fact that accumulation of rd22 mRNA requires protein synthesis raises the possibility that the expression of rd22 might be regulated by one of these trans-acting protein factors whose de novo synthesis is induced by dehydration or ABA. Although the structure of the RD22 protein is very similar to that of a non-storage seed protein, USP, of Vicia faba, the expression of the GUS gene driven by the rd22 promoter in non-stressed transgenic Arabidopsis plants was found mainly in flowers and bolted stems rather than in seeds.

  15. Discovery of cell-type specific DNA motif grammar in cis-regulatory elements using random Forest.

    Science.gov (United States)

    Wang, Xin; Lin, Peijie; Ho, Joshua W K

    2018-01-19

    It has been observed that many transcription factors (TFs) can bind to different genomic loci depending on the cell type in which a TF is expressed in, even though the individual TF usually binds to the same core motif in different cell types. How a TF can bind to the genome in such a highly cell-type specific manner, is a critical research question. One hypothesis is that a TF requires co-binding of different TFs in different cell types. If this is the case, it may be possible to observe different combinations of TF motifs - a motif grammar - located at the TF binding sites in different cell types. In this study, we develop a bioinformatics method to systematically identify DNA motifs in TF binding sites across multiple cell types based on published ChIP-seq data, and address two questions: (1) can we build a machine learning classifier to predict cell-type specificity based on motif combinations alone, and (2) can we extract meaningful cell-type specific motif grammars from this classifier model. We present a Random Forest (RF) based approach to build a multi-class classifier to predict the cell-type specificity of a TF binding site given its motif content. We applied this RF classifier to two published ChIP-seq datasets of TF (TCF7L2 and MAX) across multiple cell types. Using cross-validation, we show that motif combinations alone are indeed predictive of cell types. Furthermore, we present a rule mining approach to extract the most discriminatory rules in the RF classifier, thus allowing us to discover the underlying cell-type specific motif grammar. Our bioinformatics analysis supports the hypothesis that combinatorial TF motif patterns are cell-type specific.

  16. Readings in Wildlife and Fish Conservation, High School Conservation Curriculum Project.

    Science.gov (United States)

    Ensminger, Jack

    This publication is a tentative edition of readings on Wildlife and Fish Conservation in Louisiana, and as such it forms part of one of the four units of study designed for an experimental high school course, the "High School Conservation Curriculum Project." The other three units are concerned with Forest Conervation, Soil and Water…

  17. Preaxial polydactyly/triphalangeal thumb is associated with changed transcription factor-binding affinity in a family with a novel point mutation in the long-range cis-regulatory element ZRS

    DEFF Research Database (Denmark)

    Farooq, Muhammad; Troelsen, Jesper T; Boyd, Mette

    2010-01-01

    A cis-regulatory sequence also known as zone of polarizing activity (ZPA) regulatory sequence (ZRS) located in intron 5 of LMBR1 is essential for expression of sonic hedgehog (SHH) in the developing posterior limb bud mesenchyme. Even though many point mutations causing preaxial duplication defects...... demonstrated a marked difference between wild-type and the mutant probe, which uniquely bound one or several transcription factors extracted from Caco-2 cells. This finding supports a model in which ectopic anterior SHH expression in the developing limb results from abnormal binding of one or more...

  18. The cis-regulatory element CCACGTGG is involved in ABA and water-stress responses of the maize gene rab28.

    Science.gov (United States)

    Pla, M; Vilardell, J; Guiltinan, M J; Marcotte, W R; Niogret, M F; Quatrano, R S; Pagès, M

    1993-01-01

    The maize gene rab28 has been identified as ABA-inducible in embryos and vegetative tissues. It is also induced by water stress in young leaves. The proximal promoter region contains the conserved cis-acting element CCACGTGG (ABRE) reported for ABA induction in other plant genes. Transient expression assays in rice protoplasts indicate that a 134 bp fragment (-194 to -60 containing the ABRE) fused to a truncated cauliflower mosaic virus promoter (35S) is sufficient to confer ABA-responsiveness upon the GUS reporter gene. Gel retardation experiments indicate that nuclear proteins from tissues in which the rab28 gene is expressed can interact specifically with this 134 bp DNA fragment. Nuclear protein extracts from embryo and water-stressed leaves generate specific complexes of different electrophoretic mobility which are stable in the presence of detergent and high salt. However, by DMS footprinting the same guanine-specific contacts with the ABRE in both the embryo and leaf binding activities were detected. These results indicate that the rab28 promoter sequence CCACGTGG is a functional ABA-responsive element, and suggest that distinct regulatory factors with apparent similar affinity for the ABRE sequence may be involved in the hormone action during embryo development and in vegetative tissues subjected to osmotic stress.

  19. Tilapia and human CLIC2 structures are highly conserved.

    Science.gov (United States)

    Zeng, Jiao; Li, Zhengjun; Lui, Eei Yin; Lam, Siew Hong; Swaminathan, Kunchithapadam

    2018-01-08

    Chloride intracellular channels (CLICs) exist in soluble and membrane bound forms. We have determined the crystal structure of soluble Clic2 from the euryhaline teleost fish Oreochromis mossambicus. Structural comparison of tilapia and human CLIC2 with other CLICs shows that these proteins are highly conserved. We have also compared the expression levels of clic2 in selected osmoregulatory organs of tilapia, acclimated to freshwater, seawater and hypersaline water. Structural conservation of vertebrate CLICs implies that they might play conserved roles. Also, tissue-specific responsiveness of clic2 suggests that it might be involved in iono-osmoregulation under extreme conditions in tilapia. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Highly conserved non-coding elements on either side of SOX9 associated with Pierre Robin sequence.

    Science.gov (United States)

    Benko, Sabina; Fantes, Judy A; Amiel, Jeanne; Kleinjan, Dirk-Jan; Thomas, Sophie; Ramsay, Jacqueline; Jamshidi, Negar; Essafi, Abdelkader; Heaney, Simon; Gordon, Christopher T; McBride, David; Golzio, Christelle; Fisher, Malcolm; Perry, Paul; Abadie, Véronique; Ayuso, Carmen; Holder-Espinasse, Muriel; Kilpatrick, Nicky; Lees, Melissa M; Picard, Arnaud; Temple, I Karen; Thomas, Paul; Vazquez, Marie-Paule; Vekemans, Michel; Roest Crollius, Hugues; Hastie, Nicholas D; Munnich, Arnold; Etchevers, Heather C; Pelet, Anna; Farlie, Peter G; Fitzpatrick, David R; Lyonnet, Stanislas

    2009-03-01

    Pierre Robin sequence (PRS) is an important subgroup of cleft palate. We report several lines of evidence for the existence of a 17q24 locus underlying PRS, including linkage analysis results, a clustering of translocation breakpoints 1.06-1.23 Mb upstream of SOX9, and microdeletions both approximately 1.5 Mb centromeric and approximately 1.5 Mb telomeric of SOX9. We have also identified a heterozygous point mutation in an evolutionarily conserved region of DNA with in vitro and in vivo features of a developmental enhancer. This enhancer is centromeric to the breakpoint cluster and maps within one of the microdeletion regions. The mutation abrogates the in vitro enhancer function and alters binding of the transcription factor MSX1 as compared to the wild-type sequence. In the developing mouse mandible, the 3-Mb region bounded by the microdeletions shows a regionally specific chromatin decompaction in cells expressing Sox9. Some cases of PRS may thus result from developmental misexpression of SOX9 due to disruption of very-long-range cis-regulatory elements.

  1. Conservation

    NARCIS (Netherlands)

    Noteboom, H.P.

    1985-01-01

    The IUCN/WWF Plants Conservation Programme 1984 — 1985. World Wildlife Fund chose plants to be the subject of their fund-raising campaign in the period 1984 — 1985. The objectives were to: 1. Use information techniques to achieve the conservation objectives of the Plants Programme – to save plants;

  2. Conservation.

    Science.gov (United States)

    National Audubon Society, New York, NY.

    This set of teaching aids consists of seven Audubon Nature Bulletins, providing the teacher and student with informational reading on various topics in conservation. The bulletins have these titles: Plants as Makers of Soil, Water Pollution Control, The Ground Water Table, Conservation--To Keep This Earth Habitable, Our Threatened Air Supply,…

  3. Discovery of cis-elements between sorghum and rice using co-expression and evolutionary conservation

    Directory of Open Access Journals (Sweden)

    Haberer Georg

    2009-06-01

    Full Text Available Abstract Background The spatiotemporal regulation of gene expression largely depends on the presence and absence of cis-regulatory sites in the promoter. In the economically highly important grass family, our knowledge of transcription factor binding sites and transcriptional networks is still very limited. With the completion of the sorghum genome and the available rice genome sequence, comparative promoter analyses now allow genome-scale detection of conserved cis-elements. Results In this study, we identified thousands of phylogenetic footprints conserved between orthologous rice and sorghum upstream regions that are supported by co-expression information derived from three different rice expression data sets. In a complementary approach, cis-motifs were discovered by their highly conserved co-occurrence in syntenic promoter pairs. Sequence conservation and matches to known plant motifs support our findings. Expression similarities of gene pairs positively correlate with the number of motifs that are shared by gene pairs and corroborate the importance of similar promoter architectures for concerted regulation. This strongly suggests that these motifs function in the regulation of transcript levels in rice and, presumably also in sorghum. Conclusion Our work provides the first large-scale collection of cis-elements for rice and sorghum and can serve as a paradigm for cis-element analysis through comparative genomics in grasses in general.

  4. Two potential hookworm DAF-16 target genes, SNR-3 and LPP-1: gene structure, expression profile, and implications of a cis-regulatory element in the regulation of gene expression.

    Science.gov (United States)

    Gao, Xin; Goggin, Kevin; Dowling, Camille; Qian, Jason; Hawdon, John M

    2015-01-08

    Hookworms infect nearly 700 million people, causing anemia and developmental stunting in heavy infections. Little is known about the genomic structure or gene regulation in hookworms, although recent publication of draft genome assemblies has allowed the first investigations of these topics to be undertaken. The transcription factor DAF-16 mediates multiple developmental pathways in the free living nematode Caenorhabditis elegans, and is involved in the recovery from the developmentally arrested L3 in hookworms. Identification of downstream targets of DAF-16 will provide a better understanding of the molecular mechanism of hookworm infection. Genomic Fragment 2.23 containing a DAF-16 binding element (DBE) was used to identify overlapping complementary expressed sequence tags (ESTs). These sequences were used to search a draft assembly of the Ancylostoma caninum genome, and identified two neighboring genes, snr-3 and lpp-1, in a tail-to-tail orientation. Expression patterns of both genes during parasitic development were determined by qRT-PCR. DAF-16 dependent cis-regulatory activity of fragment 2.23 was investigated using an in vitro reporter system. The snr-3 gene spans approximately 5.6 kb in the genome and contains 3 exons and 2 introns, and contains the DBE in its 3' untranslated region. Downstream from snr-3 in a tail-to-tail arrangement is the gene lpp-1. The lpp-1 gene spans more than 6 kb and contains 10 exons and 9 introns. The A. caninum genome contains 2 apparent splice variants, but there are 7 splice variants in the A. ceylanicum genome. While the gene order is similar, the gene structures of the hookworm genes differ from their C. elegans orthologs. Both genes show peak expression in the late L4 stage. Using a cell culture based expression system, fragment 2.23 was found to have both DAF-16-dependent promoter and enhancer activity that required an intact DBE. Two putative DAF-16 targets were identified by genome wide screening for DAF-16 binding

  5. Generation of monoclonal antibodies against highly conserved antigens.

    Directory of Open Access Journals (Sweden)

    Hongzhe Zhou

    Full Text Available BACKGROUND: Therapeutic antibody development is one of the fastest growing areas of the pharmaceutical industry. Generating high-quality monoclonal antibodies against a given therapeutic target is very crucial for the success of the drug development. However, due to immune tolerance, some proteins that are highly conserved between mice and humans are not very immunogenic in mice, making it difficult to generate antibodies using a conventional approach. METHODOLOGY/PRINCIPAL FINDINGS: In this report, the impaired immune tolerance of NZB/W mice was exploited to generate monoclonal antibodies against highly conserved or self-antigens. Using two highly conserved human antigens (MIF and HMGB1 and one mouse self-antigen (TNF-alpha as examples, we demonstrate here that multiple clones of high affinity, highly specific antibodies with desired biological activities can be generated, using the NZB/W mouse as the immunization host and a T cell-specific tag fused to a recombinant antigen to stimulate the immune system. CONCLUSIONS/SIGNIFICANCE: We developed an efficient and universal method for generating surrogate or therapeutic antibodies against "difficult antigens" to facilitate the development of therapeutic antibodies.

  6. Evolutionary growth process of highly conserved sequences in vertebrate genomes.

    Science.gov (United States)

    Ishibashi, Minaka; Noda, Akiko Ogura; Sakate, Ryuichi; Imanishi, Tadashi

    2012-08-01

    Genome sequence comparison between evolutionarily distant species revealed ultraconserved elements (UCEs) among mammals under strong purifying selection. Most of them were also conserved among vertebrates. Because they tend to be located in the flanking regions of developmental genes, they would have fundamental roles in creating vertebrate body plans. However, the evolutionary origin and selection mechanism of these UCEs remain unclear. Here we report that UCEs arose in primitive vertebrates, and gradually grew in vertebrate evolution. We searched for UCEs in two teleost fishes, Tetraodon nigroviridis and Oryzias latipes, and found 554 UCEs with 100% identity over 100 bps. Comparison of teleost and mammalian UCEs revealed 43 pairs of common, jawed-vertebrate UCEs (jUCE) with high sequence identities, ranging from 83.1% to 99.2%. Ten of them retain lower similarities to the Petromyzon marinus genome, and the substitution rates of four non-exonic jUCEs were reduced after the teleost-mammal divergence, suggesting that robust conservation had been acquired in the jawed vertebrate lineage. Our results indicate that prototypical UCEs originated before the divergence of jawed and jawless vertebrates and have been frozen as perfect conserved sequences in the jawed vertebrate lineage. In addition, our comparative sequence analyses of UCEs and neighboring regions resulted in a discovery of lineage-specific conserved sequences. They were added progressively to prototypical UCEs, suggesting step-wise acquisition of novel regulatory roles. Our results indicate that conserved non-coding elements (CNEs) consist of blocks with distinct evolutionary history, each having been frozen since different evolutionary era along the vertebrate lineage. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Phylogenetic analysis reveals conservation and diversification of micro RNA166 genes among diverse plant species.

    Science.gov (United States)

    Barik, Suvakanta; SarkarDas, Shabari; Singh, Archita; Gautam, Vibhav; Kumar, Pramod; Majee, Manoj; Sarkar, Ananda K

    2014-01-01

    Similar to the majority of the microRNAs, mature miR166s are derived from multiple members of MIR166 genes (precursors) and regulate various aspects of plant development by negatively regulating their target genes (Class III HD-ZIP). The evolutionary conservation or functional diversification of miRNA166 family members remains elusive. Here, we show the phylogenetic relationships among MIR166 precursor and mature sequences from three diverse model plant species. Despite strong conservation, some mature miR166 sequences, such as ppt-miR166m, have undergone sequence variation. Critical sequence variation in ppt-miR166m has led to functional diversification, as it targets non-HD-ZIPIII gene transcript (s). MIR166 precursor sequences have diverged in a lineage specific manner, and both precursors and mature osa-miR166i/j are highly conserved. Interestingly, polycistronic MIR166s were present in Physcomitrella and Oryza but not in Arabidopsis. The nature of cis-regulatory motifs on the upstream promoter sequences of MIR166 genes indicates their possible contribution to the functional variation observed among miR166 species. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. ABCE1 is a highly conserved RNA silencing suppressor.

    Directory of Open Access Journals (Sweden)

    Kairi Kärblane

    Full Text Available ATP-binding cassette sub-family E member 1 (ABCE1 is a highly conserved protein among eukaryotes and archaea. Recent studies have identified ABCE1 as a ribosome-recycling factor important for translation termination in mammalian cells, yeast and also archaea. Here we report another conserved function of ABCE1. We have previously described AtRLI2, the homolog of ABCE1 in the plant Arabidopsis thaliana, as an endogenous suppressor of RNA silencing. In this study we show that this function is conserved: human ABCE1 is able to suppress RNA silencing in Nicotiana benthamiana plants, in mammalian HEK293 cells and in the worm Caenorhabditis elegans. Using co-immunoprecipitation and mass spectrometry, we found a number of potential ABCE1-interacting proteins that might support its function as an endogenous suppressor of RNA interference. The interactor candidates are associated with epigenetic regulation, transcription, RNA processing and mRNA surveillance. In addition, one of the identified proteins is translin, which together with its binding partner TRAX supports RNA interference.

  9. Functional conservation of the Drosophila gooseberry gene and its evolutionary alleles.

    Directory of Open Access Journals (Sweden)

    Wei Liu

    Full Text Available The Drosophila Pax gene gooseberry (gsb is required for development of the larval cuticle and CNS, survival to adulthood, and male fertility. These functions can be rescued in gsb mutants by two gsb evolutionary alleles, gsb-Prd and gsb-Pax3, which express the Drosophila Paired and mouse Pax3 proteins under the control of gooseberry cis-regulatory region. Therefore, both Paired and Pax3 proteins have conserved all the Gsb functions that are required for survival of embryos to fertile adults, despite the divergent primary sequences in their C-terminal halves. As gsb-Prd and gsb-Pax3 uncover a gsb function involved in male fertility, construction of evolutionary alleles may provide a powerful strategy to dissect hitherto unknown gene functions. Our results provide further evidence for the essential role of cis-regulatory regions in the functional diversification of duplicated genes during evolution.

  10. High-resolution finite-difference algorithms for conservation laws

    International Nuclear Information System (INIS)

    Towers, J.D.

    1987-01-01

    A new class of Total Variation Decreasing (TVD) schemes for 2-dimensional scalar conservation laws is constructed using either flux-limited or slope-limited numerical fluxes. The schemes are proven to have formal second-order accuracy in regions where neither u/sub x/ nor y/sub y/ vanishes. A new class of high-resolution large-time-step TVD schemes is constructed by adding flux-limited correction terms to the first-order accurate large-time-step version of the Engquist-Osher scheme. The use of the transport-collapse operator in place of the exact solution operator for the construction of difference schemes is studied. The production of spurious extrema by difference schemes is studied. A simple condition guaranteeing the nonproduction of spurious extrema is derived. A sufficient class of entropy inequalities for a conservation law with a flux having a single inflection point is presented. Finite-difference schemes satisfying a discrete version of each entropy inequality are only first-order accurate

  11. Dynamic Epigenetic Control of Highly Conserved Noncoding Elements

    KAUST Repository

    Seridi, Loqmane

    2014-10-07

    Background Many noncoding genomic loci have remained constant over long evolutionary periods, suggesting that they are exposed to strong selective pressures. The molecular functions of these elements have been partially elucidated, but the fundamental reason for their extreme conservation is still unknown. Results To gain new insights into the extreme selection of highly conserved noncoding elements (HCNEs), we used a systematic analysis of multi-omic data to study the epigenetic regulation of such elements during the development of Drosophila melanogaster. At the sequence level, HCNEs are GC-rich and have a characteristic oligomeric composition. They have higher levels of stable nucleosome occupancy than their flanking regions, and lower levels of mononucleosomes and H3.3, suggesting that these regions reside in compact chromatin. Furthermore, these regions showed remarkable modulations in histone modification and the expression levels of adjacent genes during development. Although HCNEs are primarily initiated late in replication, about 10% were related to early replication origins. Finally, HCNEs showed strong enrichment within lamina-associated domains. Conclusion HCNEs have distinct and protective sequence properties, undergo dynamic epigenetic regulation, and appear to be associated with the structural components of the chromatin, replication origins, and nuclear matrix. These observations indicate that such elements are likely to have essential cellular functions, and offer insights into their epigenetic properties.

  12. Dynamic Epigenetic Control of Highly Conserved Noncoding Elements

    KAUST Repository

    Seridi, Loqmane; Ryu, Tae Woo; Ravasi, Timothy

    2014-01-01

    Background Many noncoding genomic loci have remained constant over long evolutionary periods, suggesting that they are exposed to strong selective pressures. The molecular functions of these elements have been partially elucidated, but the fundamental reason for their extreme conservation is still unknown. Results To gain new insights into the extreme selection of highly conserved noncoding elements (HCNEs), we used a systematic analysis of multi-omic data to study the epigenetic regulation of such elements during the development of Drosophila melanogaster. At the sequence level, HCNEs are GC-rich and have a characteristic oligomeric composition. They have higher levels of stable nucleosome occupancy than their flanking regions, and lower levels of mononucleosomes and H3.3, suggesting that these regions reside in compact chromatin. Furthermore, these regions showed remarkable modulations in histone modification and the expression levels of adjacent genes during development. Although HCNEs are primarily initiated late in replication, about 10% were related to early replication origins. Finally, HCNEs showed strong enrichment within lamina-associated domains. Conclusion HCNEs have distinct and protective sequence properties, undergo dynamic epigenetic regulation, and appear to be associated with the structural components of the chromatin, replication origins, and nuclear matrix. These observations indicate that such elements are likely to have essential cellular functions, and offer insights into their epigenetic properties.

  13. High cumulants of conserved charges and their statistical uncertainties

    Science.gov (United States)

    Li-Zhu, Chen; Ye-Yin, Zhao; Xue, Pan; Zhi-Ming, Li; Yuan-Fang, Wu

    2017-10-01

    We study the influence of measured high cumulants of conserved charges on their associated statistical uncertainties in relativistic heavy-ion collisions. With a given number of events, the measured cumulants randomly fluctuate with an approximately normal distribution, while the estimated statistical uncertainties are found to be correlated with corresponding values of the obtained cumulants. Generally, with a given number of events, the larger the cumulants we measure, the larger the statistical uncertainties that are estimated. The error-weighted averaged cumulants are dependent on statistics. Despite this effect, however, it is found that the three sigma rule of thumb is still applicable when the statistics are above one million. Supported by NSFC (11405088, 11521064, 11647093), Major State Basic Research Development Program of China (2014CB845402) and Ministry of Science and Technology (MoST) (2016YFE0104800)

  14. Highly conserved small subunit residues influence rubisco large subunit catalysis.

    Science.gov (United States)

    Genkov, Todor; Spreitzer, Robert J

    2009-10-30

    The chloroplast enzyme ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) catalyzes the rate-limiting step of photosynthetic CO(2) fixation. With a deeper understanding of its structure-function relationships and competitive inhibition by O(2), it may be possible to engineer an increase in agricultural productivity and renewable energy. The chloroplast-encoded large subunits form the active site, but the nuclear-encoded small subunits can also influence catalytic efficiency and CO(2)/O(2) specificity. To further define the role of the small subunit in Rubisco function, the 10 most conserved residues in all small subunits were substituted with alanine by transformation of a Chlamydomonas reinhardtii mutant that lacks the small subunit gene family. All the mutant strains were able to grow photosynthetically, indicating that none of the residues is essential for function. Three of the substitutions have little or no effect (S16A, P19A, and E92A), one primarily affects holoenzyme stability (L18A), and the remainder affect catalysis with or without some level of associated structural instability (Y32A, E43A, W73A, L78A, P79A, and F81A). Y32A and E43A cause decreases in CO(2)/O(2) specificity. Based on the x-ray crystal structure of Chlamydomonas Rubisco, all but one (Glu-92) of the conserved residues are in contact with large subunits and cluster near the amino- or carboxyl-terminal ends of large subunit alpha-helix 8, which is a structural element of the alpha/beta-barrel active site. Small subunit residues Glu-43 and Trp-73 identify a possible structural connection between active site alpha-helix 8 and the highly variable small subunit loop between beta-strands A and B, which can also influence Rubisco CO(2)/O(2) specificity.

  15. Sequence conservation and combinatorial complexity of Drosophila neural precursor cell enhancers

    Directory of Open Access Journals (Sweden)

    Kuzin Alexander

    2008-08-01

    Full Text Available Abstract Background The presence of highly conserved sequences within cis-regulatory regions can serve as a valuable starting point for elucidating the basis of enhancer function. This study focuses on regulation of gene expression during the early events of Drosophila neural development. We describe the use of EvoPrinter and cis-Decoder, a suite of interrelated phylogenetic footprinting and alignment programs, to characterize highly conserved sequences that are shared among co-regulating enhancers. Results Analysis of in vivo characterized enhancers that drive neural precursor gene expression has revealed that they contain clusters of highly conserved sequence blocks (CSBs made up of shorter shared sequence elements which are present in different combinations and orientations within the different co-regulating enhancers; these elements contain either known consensus transcription factor binding sites or consist of novel sequences that have not been functionally characterized. The CSBs of co-regulated enhancers share a large number of sequence elements, suggesting that a diverse repertoire of transcription factors may interact in a highly combinatorial fashion to coordinately regulate gene expression. We have used information gained from our comparative analysis to discover an enhancer that directs expression of the nervy gene in neural precursor cells of the CNS and PNS. Conclusion The combined use EvoPrinter and cis-Decoder has yielded important insights into the combinatorial appearance of fundamental sequence elements required for neural enhancer function. Each of the 30 enhancers examined conformed to a pattern of highly conserved blocks of sequences containing shared constituent elements. These data establish a basis for further analysis and understanding of neural enhancer function.

  16. Eucaryotic operon genes can define highly conserved syntenies

    Czech Academy of Sciences Publication Activity Database

    Trachtulec, Zdeněk

    2004-01-01

    Roč. 50, - (2004), s. 1-6 ISSN 0015-5500 R&D Projects: GA ČR GA204/01/0997; GA MŠk LN00A079 Institutional research plan: CEZ:AV0Z5052915 Keywords : eukaryotic operon * conserved synteny Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.507, year: 2004

  17. Energy conservation and pomeron loops in high energy evolution

    International Nuclear Information System (INIS)

    Gustafson, Goesta

    2007-01-01

    We present a formalism which modifies the Mueller Dipole Model such that it incorporates energy-momentum conservation as well as important colour suppressed effects in the cascade evolution. The formalism is implemented in a Monte Carlo simulation program, and the results are compared to inclusive data from HERA and the Tevatron. We here find a generally very good agreement between our model and the experimental data. (author)

  18. Seed storage protein gene promoters contain conserved DNA motifs in Brassicaceae, Fabaceae and Poaceae

    Science.gov (United States)

    Fauteux, François; Strömvik, Martina V

    2009-01-01

    Background Accurate computational identification of cis-regulatory motifs is difficult, particularly in eukaryotic promoters, which typically contain multiple short and degenerate DNA sequences bound by several interacting factors. Enrichment in combinations of rare motifs in the promoter sequence of functionally or evolutionarily related genes among several species is an indicator of conserved transcriptional regulatory mechanisms. This provides a basis for the computational identification of cis-regulatory motifs. Results We have used a discriminative seeding DNA motif discovery algorithm for an in-depth analysis of 54 seed storage protein (SSP) gene promoters from three plant families, namely Brassicaceae (mustards), Fabaceae (legumes) and Poaceae (grasses) using backgrounds based on complete sets of promoters from a representative species in each family, namely Arabidopsis (Arabidopsis thaliana (L.) Heynh.), soybean (Glycine max (L.) Merr.) and rice (Oryza sativa L.) respectively. We have identified three conserved motifs (two RY-like and one ACGT-like) in Brassicaceae and Fabaceae SSP gene promoters that are similar to experimentally characterized seed-specific cis-regulatory elements. Fabaceae SSP gene promoter sequences are also enriched in a novel, seed-specific E2Fb-like motif. Conserved motifs identified in Poaceae SSP gene promoters include a GCN4-like motif, two prolamin-box-like motifs and an Skn-1-like motif. Evidence of the presence of a variant of the TATA-box is found in the SSP gene promoters from the three plant families. Motifs discovered in SSP gene promoters were used to score whole-genome sets of promoters from Arabidopsis, soybean and rice. The highest-scoring promoters are associated with genes coding for different subunits or precursors of seed storage proteins. Conclusion Seed storage protein gene promoter motifs are conserved in diverse species, and different plant families are characterized by a distinct combination of conserved motifs

  19. Seed storage protein gene promoters contain conserved DNA motifs in Brassicaceae, Fabaceae and Poaceae

    Directory of Open Access Journals (Sweden)

    Fauteux François

    2009-10-01

    Full Text Available Abstract Background Accurate computational identification of cis-regulatory motifs is difficult, particularly in eukaryotic promoters, which typically contain multiple short and degenerate DNA sequences bound by several interacting factors. Enrichment in combinations of rare motifs in the promoter sequence of functionally or evolutionarily related genes among several species is an indicator of conserved transcriptional regulatory mechanisms. This provides a basis for the computational identification of cis-regulatory motifs. Results We have used a discriminative seeding DNA motif discovery algorithm for an in-depth analysis of 54 seed storage protein (SSP gene promoters from three plant families, namely Brassicaceae (mustards, Fabaceae (legumes and Poaceae (grasses using backgrounds based on complete sets of promoters from a representative species in each family, namely Arabidopsis (Arabidopsis thaliana (L. Heynh., soybean (Glycine max (L. Merr. and rice (Oryza sativa L. respectively. We have identified three conserved motifs (two RY-like and one ACGT-like in Brassicaceae and Fabaceae SSP gene promoters that are similar to experimentally characterized seed-specific cis-regulatory elements. Fabaceae SSP gene promoter sequences are also enriched in a novel, seed-specific E2Fb-like motif. Conserved motifs identified in Poaceae SSP gene promoters include a GCN4-like motif, two prolamin-box-like motifs and an Skn-1-like motif. Evidence of the presence of a variant of the TATA-box is found in the SSP gene promoters from the three plant families. Motifs discovered in SSP gene promoters were used to score whole-genome sets of promoters from Arabidopsis, soybean and rice. The highest-scoring promoters are associated with genes coding for different subunits or precursors of seed storage proteins. Conclusion Seed storage protein gene promoter motifs are conserved in diverse species, and different plant families are characterized by a distinct combination

  20. Usherin expression is highly conserved in mouse and human tissues.

    Science.gov (United States)

    Pearsall, Nicole; Bhattacharya, Gautam; Wisecarver, Jim; Adams, Joe; Cosgrove, Dominic; Kimberling, William

    2002-12-01

    Usher syndrome is an autosomal recessive disease that results in varying degrees of hearing loss and retinitis pigmentosa. Three types of Usher syndrome (I, II, and III) have been identified clinically with Usher type II being the most common of the three types. Usher type II has been localized to three different chromosomes 1q41, 3p, and 5q, corresponding to Usher type 2A, 2B, and 2C respectively. Usherin is a basement membrane protein encoded by the USH2A gene. Expression of usherin has been localized in the basement membrane of several tissues, however it is not ubiquitous. Immunohistochemistry detected usherin in the following human tissues: retina, cochlea, small and large intestine, pancreas, bladder, prostate, esophagus, trachea, thymus, salivary glands, placenta, ovary, fallopian tube, uterus, and testis. Usherin was absent in many other tissues such as heart, lung, liver, kidney, and brain. This distribution is consistent with the usherin distribution seen in the mouse. Conservation of usherin is also seen at the nucleotide and amino acid level when comparing the mouse and human gene sequences. Evolutionary conservation of usherin expression at the molecular level and in tissues unaffected by Usher 2a supports the important structural and functional role this protein plays in the human. In addition, we believe that these results could lead to a diagnostic procedure for the detection of Usher syndrome and those who carry an USH2A mutation.

  1. Accelerated Evolution of Conserved Noncoding Sequences in theHuman Genome

    Energy Technology Data Exchange (ETDEWEB)

    Prambhakar, Shyam; Noonan, James P.; Paabo, Svante; Rubin, EdwardM.

    2006-07-06

    Genomic comparisons between human and distant, non-primatemammals are commonly used to identify cis-regulatory elements based onconstrained sequence evolution. However, these methods fail to detect"cryptic" functional elements, which are too weakly conserved amongmammals to distinguish from nonfunctional DNA. To address this problem,we explored the potential of deep intra-primate sequence comparisons. Wesequenced the orthologs of 558 kb of human genomic sequence, coveringmultiple loci involved in cholesterol homeostasis, in 6 nonhumanprimates. Our analysis identified 6 noncoding DNA elements displayingsignificant conservation among primates, but undetectable in more distantcomparisons. In vitro and in vivo tests revealed that at least three ofthese 6 elements have regulatory function. Notably, the mouse orthologsof these three functional human sequences had regulatory activity despitetheir lack of significant sequence conservation, indicating that they arecryptic ancestral cis-regulatory elements. These regulatory elementscould still be detected in a smaller set of three primate speciesincluding human, rhesus and marmoset. Since the human and rhesus genomesequences are already available, and the marmoset genome is activelybeing sequenced, the primate-specific conservation analysis describedhere can be applied in the near future on a whole-genome scale, tocomplement the annotation provided by more distant speciescomparisons.

  2. Detection of Weakly Conserved Ancestral Mammalian RegulatorySequences by Primate Comparisons

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Qian-fei; Prabhakar, Shyam; Chanan, Sumita; Cheng,Jan-Fang; Rubin, Edward M.; Boffelli, Dario

    2006-06-01

    Genomic comparisons between human and distant, non-primatemammals are commonly used to identify cis-regulatory elements based onconstrained sequence evolution. However, these methods fail to detectcryptic functional elements, which are too weakly conserved among mammalsto distinguish from nonfunctional DNA. To address this problem, weexplored the potential of deep intra-primate sequence comparisons. Wesequenced the orthologs of 558 kb of human genomic sequence, coveringmultiple loci involved in cholesterol homeostasis, in 6 nonhumanprimates. Our analysis identified 6 noncoding DNA elements displayingsignificant conservation among primates, but undetectable in more distantcomparisons. In vitro and in vivo tests revealed that at least three ofthese 6 elements have regulatory function. Notably, the mouse orthologsof these three functional human sequences had regulatory activity despitetheir lack of significant sequence conservation, indicating that they arecryptic ancestral cis-regulatory elements. These regulatory elementscould still be detected in a smaller set of three primate speciesincluding human, rhesus and marmoset. Since the human and rhesus genomesequences are already available, and the marmoset genome is activelybeing sequenced, the primate-specific conservation analysis describedhere can be applied in the near future on a whole-genome scale, tocomplement the annotation provided by more distant speciescomparisons.

  3. Phylum-Level Conservation of Regulatory Information in Nematodes despite Extensive Non-coding Sequence Divergence

    Science.gov (United States)

    Gordon, Kacy L.; Arthur, Robert K.; Ruvinsky, Ilya

    2015-01-01

    Gene regulatory information guides development and shapes the course of evolution. To test conservation of gene regulation within the phylum Nematoda, we compared the functions of putative cis-regulatory sequences of four sets of orthologs (unc-47, unc-25, mec-3 and elt-2) from distantly-related nematode species. These species, Caenorhabditis elegans, its congeneric C. briggsae, and three parasitic species Meloidogyne hapla, Brugia malayi, and Trichinella spiralis, represent four of the five major clades in the phylum Nematoda. Despite the great phylogenetic distances sampled and the extensive sequence divergence of nematode genomes, all but one of the regulatory elements we tested are able to drive at least a subset of the expected gene expression patterns. We show that functionally conserved cis-regulatory elements have no more extended sequence similarity to their C. elegans orthologs than would be expected by chance, but they do harbor motifs that are important for proper expression of the C. elegans genes. These motifs are too short to be distinguished from the background level of sequence similarity, and while identical in sequence they are not conserved in orientation or position. Functional tests reveal that some of these motifs contribute to proper expression. Our results suggest that conserved regulatory circuitry can persist despite considerable turnover within cis elements. PMID:26020930

  4. Phylum-Level Conservation of Regulatory Information in Nematodes despite Extensive Non-coding Sequence Divergence.

    Directory of Open Access Journals (Sweden)

    Kacy L Gordon

    2015-05-01

    Full Text Available Gene regulatory information guides development and shapes the course of evolution. To test conservation of gene regulation within the phylum Nematoda, we compared the functions of putative cis-regulatory sequences of four sets of orthologs (unc-47, unc-25, mec-3 and elt-2 from distantly-related nematode species. These species, Caenorhabditis elegans, its congeneric C. briggsae, and three parasitic species Meloidogyne hapla, Brugia malayi, and Trichinella spiralis, represent four of the five major clades in the phylum Nematoda. Despite the great phylogenetic distances sampled and the extensive sequence divergence of nematode genomes, all but one of the regulatory elements we tested are able to drive at least a subset of the expected gene expression patterns. We show that functionally conserved cis-regulatory elements have no more extended sequence similarity to their C. elegans orthologs than would be expected by chance, but they do harbor motifs that are important for proper expression of the C. elegans genes. These motifs are too short to be distinguished from the background level of sequence similarity, and while identical in sequence they are not conserved in orientation or position. Functional tests reveal that some of these motifs contribute to proper expression. Our results suggest that conserved regulatory circuitry can persist despite considerable turnover within cis elements.

  5. Telomeric expression sites are highly conserved in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Christiane Hertz-Fowler

    Full Text Available Subtelomeric regions are often under-represented in genome sequences of eukaryotes. One of the best known examples of the use of telomere proximity for adaptive purposes are the bloodstream expression sites (BESs of the African trypanosome Trypanosoma brucei. To enhance our understanding of BES structure and function in host adaptation and immune evasion, the BES repertoire from the Lister 427 strain of T. brucei were independently tagged and sequenced. BESs are polymorphic in size and structure but reveal a surprisingly conserved architecture in the context of extensive recombination. Very small BESs do exist and many functioning BESs do not contain the full complement of expression site associated genes (ESAGs. The consequences of duplicated or missing ESAGs, including ESAG9, a newly named ESAG12, and additional variant surface glycoprotein genes (VSGs were evaluated by functional assays after BESs were tagged with a drug-resistance gene. Phylogenetic analysis of constituent ESAG families suggests that BESs are sequence mosaics and that extensive recombination has shaped the evolution of the BES repertoire. This work opens important perspectives in understanding the molecular mechanisms of antigenic variation, a widely used strategy for immune evasion in pathogens, and telomere biology.

  6. Homologous high-throughput expression and purification of highly conserved E coli proteins

    Directory of Open Access Journals (Sweden)

    Duchmann Rainer

    2007-06-01

    Full Text Available Abstract Background Genetic factors and a dysregulated immune response towards commensal bacteria contribute to the pathogenesis of Inflammatory Bowel Disease (IBD. Animal models demonstrated that the normal intestinal flora is crucial for the development of intestinal inflammation. However, due to the complexity of the intestinal flora, it has been difficult to design experiments for detection of proinflammatory bacterial antigen(s involved in the pathogenesis of the disease. Several studies indicated a potential association of E. coli with IBD. In addition, T cell clones of IBD patients were shown to cross react towards antigens from different enteric bacterial species and thus likely responded to conserved bacterial antigens. We therefore chose highly conserved E. coli proteins as candidate antigens for abnormal T cell responses in IBD and used high-throughput techniques for cloning, expression and purification under native conditions of a set of 271 conserved E. coli proteins for downstream immunologic studies. Results As a standardized procedure, genes were PCR amplified and cloned into the expression vector pQTEV2 in order to express proteins N-terminally fused to a seven-histidine-tag. Initial small-scale expression and purification under native conditions by metal chelate affinity chromatography indicated that the vast majority of target proteins were purified in high yields. Targets that revealed low yields after purification probably due to weak solubility were shuttled into Gateway (Invitrogen destination vectors in order to enhance solubility by N-terminal fusion of maltose binding protein (MBP, N-utilizing substance A (NusA, or glutathione S-transferase (GST to the target protein. In addition, recombinant proteins were treated with polymyxin B coated magnetic beads in order to remove lipopolysaccharide (LPS. Thus, 73% of the targeted proteins could be expressed and purified in large-scale to give soluble proteins in the range of 500

  7. Visualization of conserved structures by fusing highly variable datasets.

    Science.gov (United States)

    Silverstein, Jonathan C; Chhadia, Ankur; Dech, Fred

    2002-01-01

    Reality (VR) environment. The accuracy of the fusions was determined qualitatively by comparing the transformed atlas overlaid on the appropriate CT. It was examined for where the transformed structure atlas was incorrectly overlaid (false positive) and where it was incorrectly not overlaid (false negative). According to this method, fusions 1 and 2 were correct roughly 50-75% of the time, while fusions 3 and 4 were correct roughly 75-100%. The CT dataset augmented with transformed dataset was viewed arbitrarily in user-centered perspective stereo taking advantage of features such as scaling, windowing and volumetric region of interest selection. This process of auto-coloring conserved structures in variable datasets is a step toward the goal of a broader, standardized automatic structure visualization method for radiological data. If successful it would permit identification, visualization or deletion of structures in radiological data by semi-automatically applying canonical structure information to the radiological data (not just processing and visualization of the data's intrinsic dynamic range). More sophisticated selection of control points and patterns of warping may allow for more accurate transforms, and thus advances in visualization, simulation, education, diagnostics, and treatment planning.

  8. Analytic, high β, flux conserving equilibria for cylindrical tokamaks

    International Nuclear Information System (INIS)

    Sigmar, D.J.; Vahala, G.

    1978-09-01

    Using Grad's theory of generalized differential equations, the temporal evolution from low to high β due to ''adiabatic'' and nonadiabatic (i.e., neutral beam injection) heating of a cylindrical tokamak plasma with circular cross section and peaked current profiles is calculated analytically. The influence of shaping the initial safety factor profile and the beam deposition profile and the effect of minor radius compression on the equilibrium is analyzed

  9. Analytic, high β, flux conserving equilibria for cylindrical tokamaks

    International Nuclear Information System (INIS)

    Sigmar, D.J.; Vahala, G.

    1978-01-01

    Using Grad's theory of generalized differential equations, the temporal evolution from low to high β due to ''adiabatic'' and nonadiabatic (i.e., neutral beam injection) heating of a cylindrical tokamak plasma with circular cross section and peaked current profiles is calculated analytically. The influence of shaping the initial safety factor profile and the beam deposition profile and the effect of minor radius compression on the equilibrium is analyzed

  10. High-resolution satellite imagery is an important yet underutilized resource in conservation biology.

    Science.gov (United States)

    Boyle, Sarah A; Kennedy, Christina M; Torres, Julio; Colman, Karen; Pérez-Estigarribia, Pastor E; de la Sancha, Noé U

    2014-01-01

    Technological advances and increasing availability of high-resolution satellite imagery offer the potential for more accurate land cover classifications and pattern analyses, which could greatly improve the detection and quantification of land cover change for conservation. Such remotely-sensed products, however, are often expensive and difficult to acquire, which prohibits or reduces their use. We tested whether imagery of high spatial resolution (≤5 m) differs from lower-resolution imagery (≥30 m) in performance and extent of use for conservation applications. To assess performance, we classified land cover in a heterogeneous region of Interior Atlantic Forest in Paraguay, which has undergone recent and dramatic human-induced habitat loss and fragmentation. We used 4 m multispectral IKONOS and 30 m multispectral Landsat imagery and determined the extent to which resolution influenced the delineation of land cover classes and patch-level metrics. Higher-resolution imagery more accurately delineated cover classes, identified smaller patches, retained patch shape, and detected narrower, linear patches. To assess extent of use, we surveyed three conservation journals (Biological Conservation, Biotropica, Conservation Biology) and found limited application of high-resolution imagery in research, with only 26.8% of land cover studies analyzing satellite imagery, and of these studies only 10.4% used imagery ≤5 m resolution. Our results suggest that high-resolution imagery is warranted yet under-utilized in conservation research, but is needed to adequately monitor and evaluate forest loss and conversion, and to delineate potentially important stepping-stone fragments that may serve as corridors in a human-modified landscape. Greater access to low-cost, multiband, high-resolution satellite imagery would therefore greatly facilitate conservation management and decision-making.

  11. High-throughput sequencing, characterization and detection of new and conserved cucumber miRNAs.

    Directory of Open Access Journals (Sweden)

    Germán Martínez

    Full Text Available Micro RNAS (miRNAs are a class of endogenous small non coding RNAs involved in the post-transcriptional regulation of gene expression. In plants, a great number of conserved and specific miRNAs, mainly arising from model species, have been identified to date. However less is known about the diversity of these regulatory RNAs in vegetal species with agricultural and/or horticultural importance. Here we report a combined approach of bioinformatics prediction, high-throughput sequencing data and molecular methods to analyze miRNAs populations in cucumber (Cucumis sativus plants. A set of 19 conserved and 6 known but non-conserved miRNA families were found in our cucumber small RNA dataset. We also identified 7 (3 with their miRNA* strand not previously described miRNAs, candidates to be cucumber-specific. To validate their description these new C. sativus miRNAs were detected by northern blot hybridization. Additionally, potential targets for most conserved and new miRNAs were identified in cucumber genome.In summary, in this study we have identified, by first time, conserved, known non-conserved and new miRNAs arising from an agronomically important species such as C. sativus. The detection of this complex population of regulatory small RNAs suggests that similarly to that observe in other plant species, cucumber miRNAs may possibly play an important role in diverse biological and metabolic processes.

  12. High-Order Entropy Stable Finite Difference Schemes for Nonlinear Conservation Laws: Finite Domains

    Science.gov (United States)

    Fisher, Travis C.; Carpenter, Mark H.

    2013-01-01

    Developing stable and robust high-order finite difference schemes requires mathematical formalism and appropriate methods of analysis. In this work, nonlinear entropy stability is used to derive provably stable high-order finite difference methods with formal boundary closures for conservation laws. Particular emphasis is placed on the entropy stability of the compressible Navier-Stokes equations. A newly derived entropy stable weighted essentially non-oscillatory finite difference method is used to simulate problems with shocks and a conservative, entropy stable, narrow-stencil finite difference approach is used to approximate viscous terms.

  13. Spatial overlap between environmental policy instruments and areas of high conservation value in forest.

    Science.gov (United States)

    Sverdrup-Thygeson, Anne; Søgaard, Gunnhild; Rusch, Graciela M; Barton, David N

    2014-01-01

    In order to safeguard biodiversity in forest we need to know how forest policy instruments work. Here we use a nationwide network of 9400 plots in productive forest to analyze to what extent large-scale policy instruments, individually and together, target forest of high conservation value in Norway. We studied both instruments working through direct regulation; Strict Protection and Landscape Protection, and instruments working through management planning and voluntary schemes of forest certification; Wilderness Area and Mountain Forest. As forest of high conservation value (HCV-forest) we considered the extent of 12 Biodiversity Habitats and the extent of Old-Age Forest. We found that 22% of productive forest area contained Biodiversity Habitats. More than 70% of this area was not covered by any large-scale instruments. Mountain Forest covered 23%, while Strict Protection and Wilderness both covered 5% of the Biodiversity Habitat area. A total of 9% of productive forest area contained Old-Age Forest, and the relative coverage of the four instruments was similar as for Biodiversity Habitats. For all instruments, except Landscape Protection, the targeted areas contained significantly higher proportions of HCV-forest than areas not targeted by these instruments. Areas targeted by Strict Protection had higher proportions of HCV-forest than areas targeted by other instruments, except for areas targeted by Wilderness Area which showed similar proportions of Biodiversity Habitats. There was a substantial amount of spatial overlap between the policy tools, but no incremental conservation effect of overlapping instruments in terms of contributing to higher percentages of targeted HCV-forest. Our results reveal that although the current policy mix has an above average representation of forest of high conservation value, the targeting efficiency in terms of area overlap is limited. There is a need to improve forest conservation and a potential to cover this need by better

  14. Prospects for Parity Non-conservation Experiments with Highly Charged Heavy Ions

    OpenAIRE

    Maul, M.; Schäfer, A.; Greiner, W.; Indelicato, P.

    1996-01-01

    We discuss the prospects for parity non-conservation experiments with highly charged heavy ions. Energy levels and parity mixing for heavy ions with two to five electrons are calculated. We investigate two-photon-transitions and the possibility to observe interference effects between weak-matrix elements and Stark matrix elements for periodic electric field configurations.

  15. Balancing forest-regeneration probabilities and maintenance costs in dry grasslands of high conservation priority

    Science.gov (United States)

    Bolliger, Janine; Edwards, Thomas C.; Eggenberg, Stefan; Ismail, Sascha; Seidl, Irmi; Kienast, Felix

    2011-01-01

    Abandonment of agricultural land has resulted in forest regeneration in species-rich dry grasslands across European mountain regions and threatens conservation efforts in this vegetation type. To support national conservation strategies, we used a site-selection algorithm (MARXAN) to find optimum sets of floristic regions (reporting units) that contain grasslands of high conservation priority. We sought optimum sets that would accommodate 136 important dry-grassland species and that would minimize forest regeneration and costs of management needed to forestall predicted forest regeneration. We did not consider other conservation elements of dry grasslands, such as animal species richness, cultural heritage, and changes due to climate change. Optimal sets that included 95–100% of the dry grassland species encompassed an average of 56–59 floristic regions (standard deviation, SD 5). This is about 15% of approximately 400 floristic regions that contain dry-grassland sites and translates to 4800–5300 ha of dry grassland out of a total of approximately 23,000 ha for the entire study area. Projected costs to manage the grasslands in these optimum sets ranged from CHF (Swiss francs) 5.2 to 6.0 million/year. This is only 15–20% of the current total estimated cost of approximately CHF30–45 million/year required if all dry grasslands were to be protected. The grasslands of the optimal sets may be viewed as core sites in a national conservation strategy.

  16. Technical evaluation on high aging, and performance conditions on long-term conservation program

    International Nuclear Information System (INIS)

    Yamashita, Atsushi

    2001-01-01

    In order to secure safety and safe operation of power plants, in every nuclear power plants, conservation actions based on preventive conservation are performed. They contain operative condition monitoring, patrolling inspection, and periodical tests on important systems and apparatus by operators under plant operation and condition monitoring by maintenance workers, and so on, and when finding out their abnormal conditions, their detailed survey is performed to adopt adequate countermeasures such as recovery, exchange, and so on. And, to equipments for nuclear power generation periodical conditions were obliged by legal examinations and by independent inspections. As a result of these conservation actions, even on a plant elapsed about 30 years since beginning of its operation it was thought that the plant was aged with elapsing time even if not recognizing any indication on its aged deterioration at that time. Therefore, for its concrete countermeasure, by supposing long-term operation of a plant with longer operation history, some technical evaluation on aged phenomena were carried out, to investigate on reflection of the obtained results to present conservation actions. Here were described on efforts on the high aging countermeasures, and performing conditions of long-term conservation in the Tsuruga Unit No. 1 Nuclear Power Station. (G.K.)

  17. High qualitative and quantitative conservation of alternative splicing in Caenorhabditis elegans and Caenorhabditis briggsae

    DEFF Research Database (Denmark)

    Rukov, Jakob Lewin; Irimia, Manuel; Mørk, Søren

    2007-01-01

    Alternative splicing (AS) is an important contributor to proteome diversity and is regarded as an explanatory factor for the relatively low number of human genes compared with less complex animals. To assess the evolutionary conservation of AS and its developmental regulation, we have investigated...... the qualitative and quantitative expression of 21 orthologous alternative splice events through the development of 2 nematode species separated by 85-110 Myr of evolutionary time. We demonstrate that most of these alternative splice events present in Caenorhabditis elegans are conserved in Caenorhabditis briggsae....... Moreover, we find that relative isoform expression levels vary significantly during development for 78% of the AS events and that this quantitative variation is highly conserved between the 2 species. Our results suggest that AS is generally tightly regulated through development and that the regulatory...

  18. Human developmental enhancers conserved between deuterostomes and protostomes.

    Directory of Open Access Journals (Sweden)

    Shoa L Clarke

    Full Text Available The identification of homologies, whether morphological, molecular, or genetic, is fundamental to our understanding of common biological principles. Homologies bridging the great divide between deuterostomes and protostomes have served as the basis for current models of animal evolution and development. It is now appreciated that these two clades share a common developmental toolkit consisting of conserved transcription factors and signaling pathways. These patterning genes sometimes show common expression patterns and genetic interactions, suggesting the existence of similar or even conserved regulatory apparatus. However, previous studies have found no regulatory sequence conserved between deuterostomes and protostomes. Here we describe the first such enhancers, which we call bilaterian conserved regulatory elements (Bicores. Bicores show conservation of sequence and gene synteny. Sequence conservation of Bicores reflects conserved patterns of transcription factor binding sites. We predict that Bicores act as response elements to signaling pathways, and we show that Bicores are developmental enhancers that drive expression of transcriptional repressors in the vertebrate central nervous system. Although the small number of identified Bicores suggests extensive rewiring of cis-regulation between the protostome and deuterostome clades, additional Bicores may be revealed as our understanding of cis-regulatory logic and sample of bilaterian genomes continue to grow.

  19. Conservative Management for Stable High Ankle Injuries in Professional Football Players.

    Science.gov (United States)

    Knapik, Derrick M; Trem, Anthony; Sheehan, Joseph; Salata, Michael J; Voos, James E

    High ankle "syndesmosis" injuries are common in American football players relative to the general population. At the professional level, syndesmotic sprains represent a challenging and unique injury lacking a standardized rehabilitation protocol during conservative management. PubMed, Biosis Preview, SPORTDiscus, PEDro, and EMBASE databases were searched using the terms syndesmotic injuries, American football, conservative management, and rehabilitation. Clinical review. Level 3. When compared with lateral ankle sprains, syndesmosis injuries result in significantly prolonged recovery times and games lost. For stable syndesmotic injuries, conservative management features a brief period of immobilization and protected weightbearing followed by progressive strengthening exercises and running, and athletes can expect to return to competition in 2 to 6 weeks. Further research investigating the efficacy of dry needling and blood flow restriction therapy is necessary to evaluate the benefit of these techniques in the rehabilitation process. Successful conservative management of stable syndesmotic injuries in professional American football athletes requires a thorough understanding of the anatomy, injury mechanisms, diagnosis, and rehabilitation strategies utilized in elite athletes.

  20. Constrained dansyl derivatives reveal bacterial specificity of highly conserved thymidylate synthases.

    Science.gov (United States)

    Calò, Sanuele; Tondi, Donatella; Ferrari, Stefania; Venturelli, Alberto; Ghelli, Stefano; Costi, Maria Paola

    2008-03-25

    The elucidation of the structural/functional specificities of highly conserved enzymes remains a challenging area of investigation, and enzymes involved in cellular replication are important targets for functional studies and drug discovery. Thymidylate synthase (TS, ThyA) governs the synthesis of thymidylate for use in DNA synthesis. The present study focused on Lactobacillus casei TS (LcTS) and Escherichia coli TS (EcTS), which exhibit 50 % sequence identity and strong folding similarity. We have successfully designed and validated a chemical model in which linear, but not constrained, dansyl derivatives specifically complement the LcTS active site. Conversely, chemically constrained dansyl derivatives showed up to 1000-fold improved affinity for EcTS relative to the inhibitory activity of linear derivatives. This study demonstrates that the accurate design of small ligands can uncover functional features of highly conserved enzymes.

  1. Enhancing Conservation with High Resolution Productivity Datasets for the Conterminous United States

    Science.gov (United States)

    Robinson, Nathaniel Paul

    Human driven alteration of the earth's terrestrial surface is accelerating through land use changes, intensification of human activity, climate change, and other anthropogenic pressures. These changes occur at broad spatio-temporal scales, challenging our ability to effectively monitor and assess the impacts and subsequent conservation strategies. While satellite remote sensing (SRS) products enable monitoring of the earth's terrestrial surface continuously across space and time, the practical applications for conservation and management of these products are limited. Often the processes driving ecological change occur at fine spatial resolutions and are undetectable given the resolution of available datasets. Additionally, the links between SRS data and ecologically meaningful metrics are weak. Recent advances in cloud computing technology along with the growing record of high resolution SRS data enable the development of SRS products that quantify ecologically meaningful variables at relevant scales applicable for conservation and management. The focus of my dissertation is to improve the applicability of terrestrial gross and net primary productivity (GPP/NPP) datasets for the conterminous United States (CONUS). In chapter one, I develop a framework for creating high resolution datasets of vegetation dynamics. I use the entire archive of Landsat 5, 7, and 8 surface reflectance data and a novel gap filling approach to create spatially continuous 30 m, 16-day composites of the normalized difference vegetation index (NDVI) from 1986 to 2016. In chapter two, I integrate this with other high resolution datasets and the MOD17 algorithm to create the first high resolution GPP and NPP datasets for CONUS. I demonstrate the applicability of these products for conservation and management, showing the improvements beyond currently available products. In chapter three, I utilize this dataset to evaluate the relationships between land ownership and terrestrial production

  2. Entropy Viscosity Method for High-Order Approximations of Conservation Laws

    KAUST Repository

    Guermond, J. L.

    2010-09-17

    A stabilization technique for conservation laws is presented. It introduces in the governing equations a nonlinear dissipation function of the residual of the associated entropy equation and bounded from above by a first order viscous term. Different two-dimensional test cases are simulated - a 2D Burgers problem, the "KPP rotating wave" and the Euler system - using high order methods: spectral elements or Fourier expansions. Details on the tuning of the parameters controlling the entropy viscosity are given. © 2011 Springer.

  3. Entropy Viscosity Method for High-Order Approximations of Conservation Laws

    KAUST Repository

    Guermond, J. L.; Pasquetti, R.

    2010-01-01

    A stabilization technique for conservation laws is presented. It introduces in the governing equations a nonlinear dissipation function of the residual of the associated entropy equation and bounded from above by a first order viscous term. Different two-dimensional test cases are simulated - a 2D Burgers problem, the "KPP rotating wave" and the Euler system - using high order methods: spectral elements or Fourier expansions. Details on the tuning of the parameters controlling the entropy viscosity are given. © 2011 Springer.

  4. Highly conserved non-coding sequences are associated with vertebrate development.

    Directory of Open Access Journals (Sweden)

    Adam Woolfe

    2005-01-01

    Full Text Available In addition to protein coding sequence, the human genome contains a significant amount of regulatory DNA, the identification of which is proving somewhat recalcitrant to both in silico and functional methods. An approach that has been used with some success is comparative sequence analysis, whereby equivalent genomic regions from different organisms are compared in order to identify both similarities and differences. In general, similarities in sequence between highly divergent organisms imply functional constraint. We have used a whole-genome comparison between humans and the pufferfish, Fugu rubripes, to identify nearly 1,400 highly conserved non-coding sequences. Given the evolutionary divergence between these species, it is likely that these sequences are found in, and furthermore are essential to, all vertebrates. Most, and possibly all, of these sequences are located in and around genes that act as developmental regulators. Some of these sequences are over 90% identical across more than 500 bases, being more highly conserved than coding sequence between these two species. Despite this, we cannot find any similar sequences in invertebrate genomes. In order to begin to functionally test this set of sequences, we have used a rapid in vivo assay system using zebrafish embryos that allows tissue-specific enhancer activity to be identified. Functional data is presented for highly conserved non-coding sequences associated with four unrelated developmental regulators (SOX21, PAX6, HLXB9, and SHH, in order to demonstrate the suitability of this screen to a wide range of genes and expression patterns. Of 25 sequence elements tested around these four genes, 23 show significant enhancer activity in one or more tissues. We have identified a set of non-coding sequences that are highly conserved throughout vertebrates. They are found in clusters across the human genome, principally around genes that are implicated in the regulation of development

  5. Computational methods to dissect cis-regulatory transcriptional ...

    Indian Academy of Sciences (India)

    The formation of diverse cell types from an invariant set of genes is governed by biochemical and molecular processes that regulate gene activity. A complete understanding of the regulatory mechanisms of gene expression is the major function of genomics. Computational genomics is a rapidly emerging area for ...

  6. Cis-regulatory timers for developmental gene expression.

    Directory of Open Access Journals (Sweden)

    Lionel Christiaen

    2013-10-01

    Full Text Available How does a fertilized egg decode its own genome to eventually develop into a mature animal? Each developing cell must activate a battery of genes in a timely manner and according to the function it will ultimately perform, but how? During development of the notochord--a structure akin to the vertebrate spine--in a simple marine invertebrate, an essential protein called Brachyury binds to specific sites in its target genes. A study just published in PLOS Biology reports that if the target gene contains multiple Brachyury-binding sites it will be activated early in development but if it contains only one site it will be activated later. Genes that contain no binding site can still be activated by Brachyury, but only indirectly by an earlier Brachyury-dependent gene product, so later than the directly activated genes. Thus, this study shows how several genes can interpret the presence of a single factor differently to become active at distinct times in development.

  7. The conservation pattern of short linear motifs is highly correlated with the function of interacting protein domains

    Directory of Open Access Journals (Sweden)

    Wang Yiguo

    2008-10-01

    Full Text Available Abstract Background Many well-represented domains recognize primary sequences usually less than 10 amino acids in length, called Short Linear Motifs (SLiMs. Accurate prediction of SLiMs has been difficult because they are short (often Results Our combined approach revealed that SLiMs are highly conserved in proteins from functional classes that are known to interact with a specific domain, but that they are not conserved in most other protein groups. We found that SLiMs recognized by SH2 domains were highly conserved in receptor kinases/phosphatases, adaptor molecules, and tyrosine kinases/phosphatases, that SLiMs recognized by SH3 domains were highly conserved in cytoskeletal and cytoskeletal-associated proteins, that SLiMs recognized by PDZ domains were highly conserved in membrane proteins such as channels and receptors, and that SLiMs recognized by S/T kinase domains were highly conserved in adaptor molecules, S/T kinases/phosphatases, and proteins involved in transcription or cell cycle control. We studied Tyr-SLiMs recognized by SH2 domains in more detail, and found that SH2-recognized Tyr-SLiMs on the cytoplasmic side of membrane proteins are more highly conserved than those on the extra-cellular side. Also, we found that SH2-recognized Tyr-SLiMs that are associated with SH3 motifs and a tyrosine kinase phosphorylation motif are more highly conserved. Conclusion The interactome of protein domains is reflected by the evolutionary conservation of SLiMs recognized by these domains. Combining scoring matrixes derived from peptide libraries and conservation analysis, we would be able to find those protein groups that are more likely to interact with specific domains.

  8. Species Richness and Community Structure on a High Latitude Reef: Implications for Conservation and Management

    Directory of Open Access Journals (Sweden)

    Wayne Houston

    2011-07-01

    Full Text Available In spite of the wealth of research on the Great Barrier Reef, few detailed biodiversity assessments of its inshore coral communities have been conducted. Effective conservation and management of marine ecosystems begins with fine-scale biophysical assessments focused on diversity and the architectural species that build the structural framework of the reef. In this study, we investigate key coral diversity and environmental attributes of an inshore reef system surrounding the Keppel Bay Islands near Rockhampton in Central Queensland, Australia, and assess their implications for conservation and management. The Keppels has much higher coral diversity than previously found. The average species richness for the 19 study sites was ~40 with representatives from 68% of the ~244 species previously described for the southern Great Barrier Reef. Using scleractinian coral species richness, taxonomic distinctiveness and coral cover as the main criteria, we found that five out of 19 sites had particularly high conservation value. A further site was also considered to be of relatively high value. Corals at this site were taxonomically distinct from the others (representatives of two families were found here but not at other sites and a wide range of functionally diverse taxa were present. This site was associated with more stressful conditions such as high temperatures and turbidity. Highly diverse coral communities or biodiversity ‘hotspots’ and taxonomically distinct reefs may act as insurance policies for climatic disturbance, much like Noah’s Arks for reefs. While improving water quality and limiting anthropogenic impacts are clearly important management initiatives to improve the long-term outlook for inshore reefs, identifying, mapping and protecting these coastal ‘refugia’ may be the key for ensuring their regeneration against catastrophic climatic disturbance in the meantime.

  9. Impact of local empowerment on conservation practices in a highly developed country

    OpenAIRE

    Engen, Sigrid; Hausner, Vera Helene

    2017-01-01

    Source at http://dx.doi.org/10.1111/conl.12369 Community-based conservation, where local decision makers are responsible for balancing conservation and development, is often preferred to exclusion- ary conservation that prioritizes use-limitation through strict regulation. Un- raveling the evidence for conservation impact of different governance regimes is challenging. Focusing on conservation practices before and after a reform can provide an early indication of behaviora...

  10. Use of ancient sedimentary DNA as a novel conservation tool for high-altitude tropical biodiversity.

    Science.gov (United States)

    Boessenkool, Sanne; McGlynn, Gayle; Epp, Laura S; Taylor, David; Pimentel, Manuel; Gizaw, Abel; Nemomissa, Sileshi; Brochmann, Christian; Popp, Magnus

    2014-04-01

    Conservation of biodiversity may in the future increasingly depend upon the availability of scientific information to set suitable restoration targets. In traditional paleoecology, sediment-based pollen provides a means to define preanthropogenic impact conditions, but problems in establishing the exact provenance and ecologically meaningful levels of taxonomic resolution of the evidence are limiting. We explored the extent to which the use of sedimentary ancient DNA (sedaDNA) may complement pollen data in reconstructing past alpine environments in the tropics. We constructed a record of afro-alpine plants retrieved from DNA preserved in sediment cores from 2 volcanic crater sites in the Albertine Rift, eastern Africa. The record extended well beyond the onset of substantial anthropogenic effects on tropical mountains. To ensure high-quality taxonomic inference from the sedaDNA sequences, we built an extensive DNA reference library covering the majority of the afro-alpine flora, by sequencing DNA from taxonomically verified specimens. Comparisons with pollen records from the same sediment cores showed that plant diversity recovered with sedaDNA improved vegetation reconstructions based on pollen records by revealing both additional taxa and providing increased taxonomic resolution. Furthermore, combining the 2 measures assisted in distinguishing vegetation change at different geographic scales; sedaDNA almost exclusively reflects local vegetation, whereas pollen can potentially originate from a wide area that in highlands in particular can span several ecozones. Our results suggest that sedaDNA may provide information on restoration targets and the nature and magnitude of human-induced environmental changes, including in high conservation priority, biodiversity hotspots, where understanding of preanthropogenic impact (or reference) conditions is highly limited. © 2013 Society for Conservation Biology.

  11. Proteome-wide mapping of the Drosophila acetylome demonstrates a high degree of conservation of lysine acetylation

    DEFF Research Database (Denmark)

    Weinert, Brian T; Wagner, Sebastian A; Horn, Heiko

    2011-01-01

    Posttranslational modification of proteins by acetylation and phosphorylation regulates most cellular processes in living organisms. Surprisingly, the evolutionary conservation of phosphorylated serine and threonine residues is only marginally higher than that of unmodified serines and threonines....... With high-resolution mass spectrometry, we identified 1981 lysine acetylation sites in the proteome of Drosophila melanogaster. We used data sets of experimentally identified acetylation and phosphorylation sites in Drosophila and humans to analyze the evolutionary conservation of these modification sites...... between flies and humans. Site-level conservation analysis revealed that acetylation sites are highly conserved, significantly more so than phosphorylation sites. Furthermore, comparison of lysine conservation in Drosophila and humans with that in nematodes and zebrafish revealed that acetylated lysines...

  12. Low-Intensity Agricultural Landscapes in Transylvania Support High Butterfly Diversity: Implications for Conservation

    Science.gov (United States)

    Loos, Jacqueline; Dorresteijn, Ine; Hanspach, Jan; Fust, Pascal; Rakosy, László; Fischer, Joern

    2014-01-01

    European farmland biodiversity is declining due to land use changes towards agricultural intensification or abandonment. Some Eastern European farming systems have sustained traditional forms of use, resulting in high levels of biodiversity. However, global markets and international policies now imply rapid and major changes to these systems. To effectively protect farmland biodiversity, understanding landscape features which underpin species diversity is crucial. Focusing on butterflies, we addressed this question for a cultural-historic landscape in Southern Transylvania, Romania. Following a natural experiment, we randomly selected 120 survey sites in farmland, 60 each in grassland and arable land. We surveyed butterfly species richness and abundance by walking transects with four repeats in summer 2012. We analysed species composition using Detrended Correspondence Analysis. We modelled species richness, richness of functional groups, and abundance of selected species in response to topography, woody vegetation cover and heterogeneity at three spatial scales, using generalised linear mixed effects models. Species composition widely overlapped in grassland and arable land. Composition changed along gradients of heterogeneity at local and context scales, and of woody vegetation cover at context and landscape scales. The effect of local heterogeneity on species richness was positive in arable land, but negative in grassland. Plant species richness, and structural and topographic conditions at multiple scales explained species richness, richness of functional groups and species abundances. Our study revealed high conservation value of both grassland and arable land in low-intensity Eastern European farmland. Besides grassland, also heterogeneous arable land provides important habitat for butterflies. While butterfly diversity in arable land benefits from heterogeneity by small-scale structures, grasslands should be protected from fragmentation to provide

  13. High-order conservative discretizations for some cases of the rigid body motion

    International Nuclear Information System (INIS)

    Kozlov, Roman

    2008-01-01

    Modified vector fields can be used to construct high-order structure-preserving numerical integrators for ordinary differential equations. In the present Letter we consider high-order integrators based on the implicit midpoint rule, which conserve quadratic first integrals. It is shown that these integrators are particularly suitable for the rigid body motion with an additional quadratic first integral. In this case high-order integrators preserve all four first integrals of motion. The approach is illustrated on the Lagrange top (a rotationally symmetric rigid body with a fixed point on the symmetry axis). The equations of motion are considered in the space fixed frame because in this frame Lagrange top admits a neat description. The Lagrange top motion includes the spherical pendulum and the planar pendulum, which swings in a vertical plane, as particular cases

  14. Traveling waves and conservation laws for highly nonlinear wave equations modeling Hertz chains

    Science.gov (United States)

    Przedborski, Michelle; Anco, Stephen C.

    2017-09-01

    A highly nonlinear, fourth-order wave equation that models the continuum theory of long wavelength pulses in weakly compressed, homogeneous, discrete chains with a general power-law contact interaction is studied. For this wave equation, all solitary wave solutions and all nonlinear periodic wave solutions, along with all conservation laws, are derived. The solutions are explicitly parameterized in terms of the asymptotic value of the wave amplitude in the case of solitary waves and the peak of the wave amplitude in the case of nonlinear periodic waves. All cases in which the solution expressions can be stated in an explicit analytic form using elementary functions are worked out. In these cases, explicit expressions for the total energy and total momentum for all solutions are obtained as well. The derivation of the solutions uses the conservation laws combined with an energy analysis argument to reduce the wave equation directly to a separable first-order differential equation that determines the wave amplitude in terms of the traveling wave variable. This method can be applied more generally to other highly nonlinear wave equations.

  15. Determining the drivers of population structure in a highly urbanized landscape to inform conservation planning.

    Science.gov (United States)

    Thomassen, Henri A; Harrigan, Ryan J; Semple Delaney, Kathleen; Riley, Seth P D; Serieys, Laurel E K; Pease, Katherine; Wayne, Robert K; Smith, Thomas B

    2018-02-01

    Understanding the environmental contributors to population structure is of paramount importance for conservation in urbanized environments. We used spatially explicit models to determine genetic population structure under current and future environmental conditions across a highly fragmented, human-dominated environment in Southern California to assess the effects of natural ecological variation and urbanization. We focused on 7 common species with diverse habitat requirements, home-range sizes, and dispersal abilities. We quantified the relative roles of potential barriers, including natural environmental characteristics and an anthropogenic barrier created by a major highway, in shaping genetic variation. The ability to predict genetic variation in our models differed among species: 11-81% of intraspecific genetic variation was explained by environmental variables. Although an anthropogenically induced barrier (a major highway) severely restricted gene flow and movement at broad scales for some species, genetic variation seemed to be primarily driven by natural environmental heterogeneity at a local level. Our results show how assessing environmentally associated variation for multiple species under current and future climate conditions can help identify priority regions for maximizing population persistence under environmental change in urbanized regions. © 2017 Society for Conservation Biology.

  16. A highly conserved tyrosine of Tim-3 is phosphorylated upon stimulation by its ligand galectin-9

    International Nuclear Information System (INIS)

    Weyer, Philipp S. van de; Muehlfeit, Michael; Klose, Christoph; Bonventre, Joseph V.; Walz, Gerd; Kuehn, E. Wolfgang

    2006-01-01

    Tim-3 is a member of the TIM family of proteins (T-cell immunoglobulin mucin) involved in the regulation of CD4+ T-cells. Tim-3 is a T H 1-specific type 1 membrane protein and regulates T H 1 proliferation and the development of tolerance. Binding of galectin-9 to the extracellular domain of Tim-3 results in apoptosis of T H 1 cells, but the intracellular pathways involved in the regulatory function of Tim-3 are unknown. Unlike Tim-1, which is expressed in renal epithelia and cancer, Tim-3 has not been described in cells other than neuronal or T-cells. Using RT-PCR we demonstrate that Tim-3 is expressed in malignant and non-malignant epithelial tissues. We have cloned Tim-3 from an immortalized liver cell carcinoma line and identified a highly conserved tyrosine in the intracellular tail of Tim-3 (Y265). We demonstrate that Y265 is specifically phosphorylated in vivo by the interleukin inducible T cell kinase (ITK), a kinase which is located in close proximity of the TIM genes on the allergy susceptibility locus 5q33.3. Stimulation of Tim-3 by its ligand galectin-9 results in increased phosphorylation of Y265, suggesting that this tyrosine residue plays an important role in downstream signalling events regulating T-cell fate. Given the role of TIM proteins in autoimmunity and cancer, the conserved SH2 binding domain surrounding Y265 could represent a possible target site for pharmacological intervention

  17. Identification of two evolutionarily conserved 5' cis-elements involved in regulating spatiotemporal expression of Nolz-1 during mouse embryogenesis.

    Directory of Open Access Journals (Sweden)

    Sunny Li-Yun Chang

    Full Text Available Proper development of vertebrate embryos depends not only on the crucial funtions of key evolutionarily conserved transcriptional regulators, but also on the precisely spatiotemporal expression of these transcriptional regulators. The mouse Nolz-1/Znf503/Zfp503 gene is a mammalian member of the conserved zinc-finger containing NET family. The expression pattern of Nolz-1 in mouse embryos is highly correlated with that of its homologues in different species. To study the spatiotemporal regulation of Nolz-1, we first identified two evolutionarily conserved cis-elements, UREA and UREB, in 5' upstream regions of mouse Nolz-1 locus. We then generated UREA-LacZ and UREB-LacZ transgenic reporter mice to characterize the putative enhancer activity of UREA and UREB. The results indicated that both UREA and UREB contained tissue-specific enhancer activity for directing LacZ expression in selective tissue organs during mouse embryogensis. UREA directed LacZ expression preferentially in selective regions of developing central nervous system, including the forebrain, hindbrain and spinal cord, whereas UREB directed LacZ expression mainly in other developing tissue organs such as the Nolz-1 expressing branchial arches and its derivatives, the apical ectodermal ridge of limb buds and the urogenital tissues. Both UREA and UREB directed strong LacZ expression in the lateral plate mesoderm where endogenous Nolz-1 was also expressed. Despite that the LacZ expression pattern did not full recapitulated the endogenous Nolz-1 expression and some mismatched expression patterns were observed, co-expression of LacZ and Nolz-1 did occur in many cells of selective tissue organs, such as in the ventrolateral cortex and ventral spinal cord of UREA-LacZ embryos, and the urogenital tubes of UREB-LacZ embryos. Taken together, our study suggests that UREA and UREB may function as evolutionarily conserved cis-regulatory elements that coordinate with other cis-elements to regulate

  18. An assessment of high carbon stock and high conservation value approaches to sustainable oil palm cultivation in Gabon

    Science.gov (United States)

    Austin, Kemen G.; Lee, Michelle E.; Clark, Connie; Forester, Brenna R.; Urban, Dean L.; White, Lee; Kasibhatla, Prasad S.; Poulsen, John R.

    2017-01-01

    Industrial-scale oil palm cultivation is rapidly expanding in Gabon, where it has the potential to drive economic growth, but also threatens forest, biodiversity and carbon resources. The Gabonese government is promoting an ambitious agricultural expansion strategy, while simultaneously committing to minimize negative environmental impacts of oil palm agriculture. This study estimates the extent and location of suitable land for oil palm cultivation in Gabon, based on an analysis of recent trends in plantation permitting. We use the resulting suitability map to evaluate two proposed approaches to minimizing negative environmental impacts: a High Carbon Stock (HCS) approach, which emphasizes forest protection and climate change mitigation, and a High Conservation Value (HCV) approach, which focuses on safeguarding biodiversity and ecosystems. We quantify the forest area, carbon stock, and biodiversity resources protected under each approach, using newly developed maps of priority species distributions and forest biomass for Gabon. We find 2.7-3.9 Mha of suitable or moderately suitable land that avoid HCS areas, 4.4 million hectares (Mha) that avoid HCV areas, and 1.2-1.7 Mha that avoid both. This suggests that Gabon’s oil palm production target could likely be met without compromising important ecosystem services, if appropriate safeguards are put in place. Our analysis improves understanding of suitability for oil palm in Gabon, determines how conservation strategies align with national targets for oil palm production, and informs national land use planning.

  19. Data on electrical energy conservation using high efficiency motors for the confidence bounds using statistical techniques.

    Science.gov (United States)

    Shaikh, Muhammad Mujtaba; Memon, Abdul Jabbar; Hussain, Manzoor

    2016-09-01

    In this article, we describe details of the data used in the research paper "Confidence bounds for energy conservation in electric motors: An economical solution using statistical techniques" [1]. The data presented in this paper is intended to show benefits of high efficiency electric motors over the standard efficiency motors of similar rating in the industrial sector of Pakistan. We explain how the data was collected and then processed by means of formulas to show cost effectiveness of energy efficient motors in terms of three important parameters: annual energy saving, cost saving and payback periods. This data can be further used to construct confidence bounds for the parameters using statistical techniques as described in [1].

  20. Comparative transcriptome analysis within the Lolium/Festuca species complex reveals high sequence conservation

    DEFF Research Database (Denmark)

    Czaban, Adrian; Sharma, Sapna; Byrne, Stephen

    2015-01-01

    species from the Lolium-Festuca complex, ranging from 52,166 to 72,133 transcripts per assembly. We have also predicted a set of proteins and validated it with a high-confidence protein database from three closely related species (H. vulgare, B. distachyon and O. sativa). We have obtained gene family...... clusters for the four species using OrthoMCL and analyzed their inferred phylogenetic relationships. Our results indicate that VRN2 is a candidate gene for differentiating vernalization and non-vernalization types in the Lolium-Festuca complex. Grouping of the gene families based on their BLAST identity...... enabled us to divide ortholog groups into those that are very conserved and those that are more evolutionarily relaxed. The ratio of the non-synonumous to synonymous substitutions enabled us to pinpoint protein sequences evolving in response to positive selection. These proteins may explain some...

  1. Cortical cytasters: a highly conserved developmental trait of Bilateria with similarities to Ctenophora

    Directory of Open Access Journals (Sweden)

    Salinas-Saavedra Miguel

    2011-12-01

    Full Text Available Abstract Background Cytasters (cytoplasmic asters are centriole-based nucleation centers of microtubule polymerization that are observable in large numbers in the cortical cytoplasm of the egg and zygote of bilaterian organisms. In both protostome and deuterostome taxa, cytasters have been described to develop during oogenesis from vesicles of nuclear membrane that move to the cortical cytoplasm. They become associated with several cytoplasmic components, and participate in the reorganization of cortical cytoplasm after fertilization, patterning the antero-posterior and dorso-ventral body axes. Presentation of the hypothesis The specific resemblances in the development of cytasters in both protostome and deuterostome taxa suggest that an independent evolutionary origin is unlikely. An assessment of published data confirms that cytasters are present in several protostome and deuterostome phyla, but are absent in the non-bilaterian phyla Cnidaria and Ctenophora. We hypothesize that cytasters evolved in the lineage leading to Bilateria and were already present in the most recent common ancestor shared by protostomes and deuterostomes. Thus, cytasters would be an ancient and highly conserved trait that is homologous across the different bilaterian phyla. The alternative possibility is homoplasy, that is cytasters have evolved independently in different lineages of Bilateria. Testing the hypothesis So far, available published information shows that appropriate observations have been made in eight different bilaterian phyla. All of them present cytasters. This is consistent with the hypothesis of homology and conservation. However, there are several important groups for which there are no currently available data. The hypothesis of homology predicts that cytasters should be present in these groups. Increasing the taxonomic sample using modern techniques uniformly will test for evolutionary patterns supporting homology, homoplasy, or secondary loss of

  2. A highly conserved amino acid in VP1 regulates maturation of enterovirus 71.

    Directory of Open Access Journals (Sweden)

    Yong-Xin Zhang

    2017-09-01

    Full Text Available Enterovirus 71 (EV71 is the major causative agent of hand, foot and mouth disease (HFMD in children, causing severe clinical outcomes and even death. Here, we report an important role of the highly conserved alanine residue at position 107 in the capsid protein VP1 (VP1A107 in the efficient replication of EV71. Substitutional mutations of VP1A107 significantly diminish viral growth kinetics without significant effect on viral entry, expression of viral genes and viral production. The results of mechanistic studies reveal that VP1A107 regulates the efficient cleavage of the VP0 precursor during EV71 assembly, which is required, in the next round of infection, for the transformation of the mature virion (160S into an intermediate or A-particle (135S, a key step of virus uncoating. Furthermore, the results of molecular dynamic simulations and hydrogen-bond networks analysis of VP1A107 suggest that flexibility of the VP1 BC loop or the region surrounding the VP1107 residue directly correlates with viral infectivity. It is possible that sufficient flexibility of the region surrounding the VP1107 residue favors VP0 conformational change that is required for the efficient cleavage of VP0 as well as subsequent viral uncoating and viral replication. Taken together, our data reveal the structural role of the highly conserved VP1A107 in regulating EV71 maturation. Characterization of this novel determinant of EV71 virulence would promote the study on pathogenesis of Enteroviruses.

  3. CpG methylation differences between neurons and glia are highly conserved from mouse to human.

    Science.gov (United States)

    Kessler, Noah J; Van Baak, Timothy E; Baker, Maria S; Laritsky, Eleonora; Coarfa, Cristian; Waterland, Robert A

    2016-01-15

    Understanding epigenetic differences that distinguish neurons and glia is of fundamental importance to the nascent field of neuroepigenetics. A recent study used genome-wide bisulfite sequencing to survey differences in DNA methylation between these two cell types, in both humans and mice. That study minimized the importance of cell type-specific differences in CpG methylation, claiming these are restricted to localized genomic regions, and instead emphasized that widespread and highly conserved differences in non-CpG methylation distinguish neurons and glia. We reanalyzed the data from that study and came to markedly different conclusions. In particular, we found widespread cell type-specific differences in CpG methylation, with a genome-wide tendency for neuronal CpG-hypermethylation punctuated by regions of glia-specific hypermethylation. Alarmingly, our analysis indicated that the majority of genes identified by the primary study as exhibiting cell type-specific CpG methylation differences were misclassified. To verify the accuracy of our analysis, we isolated neuronal and glial DNA from mouse cortex and performed quantitative bisulfite pyrosequencing at nine loci. The pyrosequencing results corroborated our analysis, without exception. Most interestingly, we found that gene-associated neuron vs. glia CpG methylation differences are highly conserved across human and mouse, and are very likely to be functional. In addition to underscoring the importance of independent verification to confirm the conclusions of genome-wide epigenetic analyses, our data indicate that CpG methylation plays a major role in neuroepigenetics, and that the mouse is likely an excellent model in which to study the role of DNA methylation in human neurodevelopment and disease. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. Evolutionary conservation of essential and highly expressed genes in Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Scharfe Maren

    2010-04-01

    Full Text Available Abstract Background The constant increase in development and spread of bacterial resistance to antibiotics poses a serious threat to human health. New sequencing technologies are now on the horizon that will yield massive increases in our capacity for DNA sequencing and will revolutionize the drug discovery process. Since essential genes are promising novel antibiotic targets, the prediction of gene essentiality based on genomic information has become a major focus. Results In this study we demonstrate that pooled sequencing is applicable for the analysis of sequence variations of strain collections with more than 10 individual isolates. Pooled sequencing of 36 clinical Pseudomonas aeruginosa isolates revealed that essential and highly expressed proteins evolve at lower rates, whereas extracellular proteins evolve at higher rates. We furthermore refined the list of experimentally essential P. aeruginosa genes, and identified 980 genes that show no sequence variation at all. Among the conserved nonessential genes we found several that are involved in regulation, motility and virulence, indicating that they represent factors of evolutionary importance for the lifestyle of a successful environmental bacterium and opportunistic pathogen. Conclusion The detailed analysis of a comprehensive set of P. aeruginosa genomes in this study clearly disclosed detailed information of the genomic makeup and revealed a large set of highly conserved genes that play an important role for the lifestyle of this microorganism. Sequencing strain collections enables for a detailed and extensive identification of sequence variations as potential bacterial adaptation processes, e.g., during the development of antibiotic resistance in the clinical setting and thus may be the basis to uncover putative targets for novel treatment strategies.

  5. A guide to calculating habitat-quality metrics to inform conservation of highly mobile species

    Science.gov (United States)

    Bieri, Joanna A.; Sample, Christine; Thogmartin, Wayne E.; Diffendorfer, James E.; Earl, Julia E.; Erickson, Richard A.; Federico, Paula; Flockhart, D. T. Tyler; Nicol, Sam; Semmens, Darius J.; Skraber, T.; Wiederholt, Ruscena; Mattsson, Brady J.

    2018-01-01

    Many metrics exist for quantifying the relative value of habitats and pathways used by highly mobile species. Properly selecting and applying such metrics requires substantial background in mathematics and understanding the relevant management arena. To address this multidimensional challenge, we demonstrate and compare three measurements of habitat quality: graph-, occupancy-, and demographic-based metrics. Each metric provides insights into system dynamics, at the expense of increasing amounts and complexity of data and models. Our descriptions and comparisons of diverse habitat-quality metrics provide means for practitioners to overcome the modeling challenges associated with management or conservation of such highly mobile species. Whereas previous guidance for applying habitat-quality metrics has been scattered in diversified tracks of literature, we have brought this information together into an approachable format including accessible descriptions and a modeling case study for a typical example that conservation professionals can adapt for their own decision contexts and focal populations.Considerations for Resource ManagersManagement objectives, proposed actions, data availability and quality, and model assumptions are all relevant considerations when applying and interpreting habitat-quality metrics.Graph-based metrics answer questions related to habitat centrality and connectivity, are suitable for populations with any movement pattern, quantify basic spatial and temporal patterns of occupancy and movement, and require the least data.Occupancy-based metrics answer questions about likelihood of persistence or colonization, are suitable for populations that undergo localized extinctions, quantify spatial and temporal patterns of occupancy and movement, and require a moderate amount of data.Demographic-based metrics answer questions about relative or absolute population size, are suitable for populations with any movement pattern, quantify demographic

  6. Habitat Re-Creation (Ecological Restoration) as a Strategy for Conserving Insect Communities in Highly Fragmented Landscapes.

    Science.gov (United States)

    Shuey, John A

    2013-12-05

    Because of their vast diversity, measured by both numbers of species as well as life history traits, insects defy comprehensive conservation planning. Thus, almost all insect conservation efforts target individual species. However, serious insect conservation requires goals that are set at the faunal level and conservation success requires strategies that conserve intact communities. This task is complicated in agricultural landscapes by high levels of habitat fragmentation and isolation. In many regions, once widespread insect communities are now functionally trapped on islands of ecosystem remnants and subject to a variety of stressors associated with isolation, small population sizes and artificial population fragmentation. In fragmented landscapes ecological restoration can be an effective strategy for reducing localized insect extinction rates, but insects are seldom included in restoration design criteria. It is possible to incorporate a few simple conservation criteria into restoration designs that enhance impacts to entire insect communities. Restoration can be used as a strategy to address fragmentation threats to isolated insect communities if insect communities are incorporated at the onset of restoration planning. Fully incorporating insect communities into restoration designs may increase the cost of restoration two- to three-fold, but the benefits to biodiversity conservation and the ecological services provided by intact insect communities justify the cost.

  7. Butterflies of the high altitude Atacama Desert: habitat use and conservation

    Directory of Open Access Journals (Sweden)

    Emma eDespland

    2014-09-01

    Full Text Available The butterfly fauna of the high-altitude desert of Northern Chile, though depauperate, shows high endemism, is poorly known and is of considerable conservation concern. This study surveys butterflies along the Andean slope between 2400 and 500 m asl (prepuna, puna and Andean steppe habitats as well as in high and low altitude wetlands and in the neoriparian vegetation of agricultural sites. We also include historical sightings from museum records. We compare abundances between altitudes, between natural and impacted sites, as well as between two sampling years with different precipitation regimes. The results confirm high altitudinal turnover and show greatest similarity between wetland and slope faunas at similar altitudes. Results also underscore vulnerability to weather fluctuations, particularly in the more arid low-altitude sites, where abundances were much lower in the low precipitation sampling season and several species were not observed at all. Finally, we show that some species have shifted to the neoriparian vegetation of the agricultural landscape, whereas others were only observed in less impacted habitats dominated by native plants. These results suggest that acclimation to novel habitats depends on larval host plant use. The traditional agricultural environment can provide habitat for many, but not all, native butterfly species, but an estimation of the value of these habitats requires better understanding of butterfly life-history strategies and relationships with host plants.

  8. Cosmetic results in early stage breast cancer patients with high-dose brachytherapy after conservative surgery

    International Nuclear Information System (INIS)

    Torres, Felipe; Pineda, Beatriz E

    2004-01-01

    Purpose: to reveal cosmetic results in patients at early stages of low risk breast cancer treated with partial accelerated radiotherapy using high dose rate brachytherapy. Methods and materials: from March 2001 to July 2003,14 stages l and ll breast cancer patients were treated at the Colombian national cancer institute in Bogota with conservative surgery and radiotherapy upon the tumor bed (partial accelerated radiotherapy), using interstitial implants with iridium 192 (high dose rate brachytherapy) with a dose of 32 Gys, over 4 days, at 8 fractions twice a day. Results: with an average follow up of 17.7 months, good cosmetic results were found among 71.4 % of patients and excellent results among 14.3% of patients, furthermore none of the patients neither local nor regional or distant relapses. Conclusion: among patients who suffer from breast cancer at early stages, it showed is possible to apply partial accelerated radiotherapy upon the tumor bed with high doses over 4 days with good to excellent cosmetic results

  9. Swertia chirayta, a Threatened High-Value Medicinal Herb: Microhabitats and Conservation Challenges in Sikkim Himalaya, India

    Directory of Open Access Journals (Sweden)

    Bharat Kumar Pradhan

    2015-11-01

    Full Text Available Assessing the impact of threats, identifying favorable growing conditions, and predicting future population scenarios are vital for the conservation and management of threatened species. This study investigated the availability, microhabitat characteristics, threat status, and community associations of Swertia chirayta, a highly threatened Himalayan medicinal herb, in 22 populations in Sikkim, India, using the vertical belt transect method. Of the 14 microhabitats identified, open grassy slope emerged as the most favorable and wet grassy slope as the least favorable for S. chirayta. The species was dominant in 8 of the 10 major plant communities identified. Among 9 major types of disturbance identified, human movement and collection of non-timber forest products appeared as the biggest threats to S. chirayta. Disturbances significantly affected the availability of the species. S. chirayta, though under high anthropogenic threat, maintains high microhabitat pliability, which is vital for its conservation and management, provided immediate conservation measures are taken.

  10. Evaluation of highly conserved hsp65-specific nested PCR primers for diagnosing Mycobacterium tuberculosis.

    Science.gov (United States)

    Priyadarshini, P; Tiwari, K; Das, A; Kumar, D; Mishra, M N; Desikan, P; Nath, G

    2017-02-01

    To evaluate the sensitivity and specificity of a new nested set of primers designed for the detection of Mycobacterium tuberculosis complex targeting a highly conserved heat shock protein gene (hsp65). The nested primers were designed using multiple sequence alignment assuming the nucleotide sequence of the M. tuberculosis H37Rv hsp65 genome as base. Multidrug-resistant Mycobacterium species along with other non-mycobacterial and fungal species were included to evaluate the specificity of M. tuberculosis hsp65 gene-specific primers. The sensitivity of the primers was determined using serial 10-fold dilutions, and was 100% as shown by the bands in the case of M. tuberculosis complex. None of the other non M. tuberculosis complex bacterial and fungal species yielded any band on nested polymerase chain reaction (PCR). The first round of amplification could amplify 0.3 ng of the template DNA, while nested PCR could detect 0.3 pg. The present hsp65-specific primers have been observed to be sensitive, specific and cost-effective, without requiring interpretation of biochemical tests, real-time PCR, sequencing or high-performance liquid chromatography. These primer sets do not have the drawbacks associated with those protocols that target insertion sequence 6110, 16S rDNA, rpoB, recA and MPT 64.

  11. A highly conserved basidiomycete peptide synthetase produces a trimeric hydroxamate siderophore.

    Science.gov (United States)

    Brandenburger, Eileen; Gressler, Markus; Leonhardt, Robin; Lackner, Gerald; Habel, Andreas; Hertweck, Christian; Brock, Matthias; Hoffmeister, Dirk

    2017-08-25

    The model white-rot basidiomycete Ceriporiopsis ( Gelatoporia ) subvermispora B encodes putative natural product biosynthesis genes. Among them is the gene for the seven-domain nonribosomal peptide synthetase CsNPS2. It is a member of the as-yet uncharacterized fungal type VI siderophore synthetase family which is highly conserved and widely distributed among the basidiomycetes. These enzymes include only one adenylation (A) domain, i.e., one complete peptide synthetase module and two thiolation/condensation (T-C) di-domain partial modules which, together, constitute an AT 1 C 1 T 2 C 2 T 3 C 3 domain setup. The full-length CsNPS2 enzyme (274.5 kDa) was heterologously produced as polyhistidine fusion in Aspergillus niger as soluble and active protein. N 5 -acetyl- N 5 -hydroxy-l-ornithine (l-AHO) and N 5 - cis -anhydromevalonyl- N 5 -hydroxy-l-ornithine (l-AMHO) were accepted as substrates, as assessed in vitro using the substrate-dependent [ 32 P]ATP-pyrophosphate radioisotope exchange assay. Full-length holo -CsNPS2 catalyzed amide bond formation between three l-AHO molecules to release the linear l-AHO trimer, called basidioferrin, as product in vitro , which was verified by LC-HRESIMS. Phylogenetic analyses suggest that type VI family siderophore synthetases are widespread in mushrooms and have evolved in a common ancestor of basidiomycetes. Importance : The basidiomycete nonribosomal peptide synthetase CsNPS2 represents a member of a widely distributed but previously uninvestigated class (type VI) of fungal siderophore synthetases. Genes orthologous to CsNPS2 are highly conserved across various phylogenetic clades of the basidiomycetes. Hence, our work serves as a broadly applicable model for siderophore biosynthesis and iron metabolism in higher fungi. Also, our results on the amino acid substrate preference of CsNPS2 supports further understanding of the substrate selectivity of fungal adenylation domains. Methodologically, this report highlights the

  12. Differential Regulation of Receptor Activation and Agonist Selectivity by Highly Conserved Tryptophans in the Nicotinic Acetylcholine Receptor Binding Site

    OpenAIRE

    Williams, Dustin K.; Stokes, Clare; Horenstein, Nicole A.; Papke, Roger L.

    2009-01-01

    We have shown previously that a highly conserved Tyr in the nicotinic acetylcholine receptor (nAChR) ligand-binding domain (LBD) (α7 Tyr188 or α4 Tyr195) differentially regulates the activity of acetylcholine (ACh) and the α7-selective agonist 3-(4-hydroxy,2-methoxybenzylidene)anabaseine (4OH-GTS-21) in α4β2 and α7 nAChR. In this study, we mutated two highly conserved LBD Trp residues in human α7 and α4β2 and expressed the receptors in Xenopus laevis oocytes. α7 Re...

  13. Acacia shrubs respond positively to high severity wildfire: Implications for conservation and fuel hazard management.

    Science.gov (United States)

    Gordon, Christopher E; Price, Owen F; Tasker, Elizabeth M; Denham, Andrew J

    2017-01-01

    High severity wildfires pose threats to human assets, but are also perceived to impact vegetation communities because a small number of species may become dominant immediately after fire. However there are considerable gaps in our knowledge about species-specific responses of plants to different fire severities, and how this influences fuel hazard in the short and long-term. Here we conduct a floristic survey at sites before and two years after a wildfire of unprecedented size and severity in the Warrumbungle National Park (Australia) to explore relationships between post-fire growth of a fire responsive shrub genera (Acacia), total mid-story vegetation cover, fire severity and fuel hazard. We then survey 129 plots surrounding the park to assess relationships between mid-story vegetation cover and time-since-fire. Acacia species richness and cover were 2.3 and 4.3 times greater at plots after than before the fire. However the same common dominant species were present throughout the study. Mid-story vegetation cover was 1.5 times greater after than before the wildfire, and Acacia species contribution to mid-story cover increased from 10 to 40%. Acacia species richness was not affected by fire severity, however strong positive associations were observed between Acacia and total mid-story vegetation cover and severity. Our analysis of mid-story vegetation recovery showed that cover was similarly high between 2 and 30years post-fire, then decreased until 52years. Collectively, our results suggest that Acacia species are extremely resilient to high severity wildfire and drive short to mid-term increases in fuel hazard. Our results are discussed in relation to fire regime management from the twin perspectives of conserving biodiversity and mitigating human losses due to wildfire. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. A dominant EV71-specific CD4+ T cell epitope is highly conserved among human enteroviruses.

    Directory of Open Access Journals (Sweden)

    Ruicheng Wei

    Full Text Available CD4+ T cell-mediated immunity plays a central role in determining the immunopathogenesis of viral infections. However, the role of CD4+ T cells in EV71 infection, which causes hand, foot and mouth disease (HFMD, has yet to be elucidated. We applied a sophisticated method to identify promiscuous CD4+ T cell epitopes contained within the sequence of the EV71 polyprotein. Fifteen epitopes were identified, and three of them are dominant ones. The most dominant epitope is highly conserved among enterovirus species, including HFMD-related coxsackieviruses, HFMD-unrelated echoviruses and polioviruses. Furthermore, the CD4+ T cells specific to the epitope indeed cross-reacted with the homolog of poliovirus 3 Sabin. Our findings imply that CD4+ T cell responses to poliovirus following vaccination, or to other enteroviruses to which individuals may be exposed in early childhood, may have a modulating effect on subsequent CD4+ T cell response to EV71 infection or vaccine.

  15. Comparative analyses reveal high levels of conserved colinearity between the finger millet and rice genomes.

    Science.gov (United States)

    Srinivasachary; Dida, Mathews M; Gale, Mike D; Devos, Katrien M

    2007-08-01

    Finger millet is an allotetraploid (2n = 4x = 36) grass that belongs to the Chloridoideae subfamily. A comparative analysis has been carried out to determine the relationship of the finger millet genome with that of rice. Six of the nine finger millet homoeologous groups corresponded to a single rice chromosome each. Each of the remaining three finger millet groups were orthologous to two rice chromosomes, and in all the three cases one rice chromosome was inserted into the centromeric region of a second rice chromosome to give the finger millet chromosomal configuration. All observed rearrangements were, among the grasses, unique to finger millet and, possibly, the Chloridoideae subfamily. Gene orders between rice and finger millet were highly conserved, with rearrangements being limited largely to single marker transpositions and small putative inversions encompassing at most three markers. Only some 10% of markers mapped to non-syntenic positions in rice and finger millet and the majority of these were located in the distal 14% of chromosome arms, supporting a possible correlation between recombination and sequence evolution as has previously been observed in wheat. A comparison of the organization of finger millet, Panicoideae and Pooideae genomes relative to rice allowed us to infer putative ancestral chromosome configurations in the grasses.

  16. A highly conserved metalloprotease effector enhances virulence in the maize anthracnose fungus Colletotrichum graminicola.

    Science.gov (United States)

    Sanz-Martín, José M; Pacheco-Arjona, José Ramón; Bello-Rico, Víctor; Vargas, Walter A; Monod, Michel; Díaz-Mínguez, José M; Thon, Michael R; Sukno, Serenella A

    2016-09-01

    Colletotrichum graminicola causes maize anthracnose, an agronomically important disease with a worldwide distribution. We have identified a fungalysin metalloprotease (Cgfl) with a role in virulence. Transcriptional profiling experiments and live cell imaging show that Cgfl is specifically expressed during the biotrophic stage of infection. To determine whether Cgfl has a role in virulence, we obtained null mutants lacking Cgfl and performed pathogenicity and live microscopy assays. The appressorium morphology of the null mutants is normal, but they exhibit delayed development during the infection process on maize leaves and roots, showing that Cgfl has a role in virulence. In vitro chitinase activity assays of leaves infected with wild-type and null mutant strains show that, in the absence of Cgfl, maize leaves exhibit increased chitinase activity. Phylogenetic analyses show that Cgfl is highly conserved in fungi. Similarity searches, phylogenetic analysis and transcriptional profiling show that C. graminicola encodes two LysM domain-containing homologues of Ecp6, suggesting that this fungus employs both Cgfl-mediated and LysM protein-mediated strategies to control chitin signalling. © 2015 BSPP and John Wiley & Sons Ltd.

  17. Pig epidermal growth factor precursor contains segments that are highly conserved among species

    DEFF Research Database (Denmark)

    Jørgensen, P E; Jensen, L.G.; Sørensen, B S

    1998-01-01

    segment with that of the human, the rat and the mouse EGF precursors, in order to identify highly conserved domains. The examined part of the precursor contains EGF itself and six so-called EGF-like modules. The overall amino acid identity among the four species is 64%. However, the amino acid identity...... differed from around 30% in some segments to around 70% in others. The highest amino acid identity, 71%, was observed for a 345-aa segment that contains three EGF-like modules and which is homologous to a part of the low-density lipoprotein receptor (LDL receptor). The amino acid identities are 64% for EGF...... itself, and 50-67% for the remaining three EGF-like modules. The segment of the LDL receptor that is homologous to a part of the EGF precursor is important for the function of the LDL receptor, and EGF-like modules seem to be involved in protein-protein interactions in a number of proteins. In conclusion...

  18. Current situation of energy conservation in high energy-consuming industries in Taiwan

    International Nuclear Information System (INIS)

    Chan, D.Y.-L.; Yang, K.-H.; Hsu, C.-H.; Chien, M.-H.; Hong, G.-B.

    2007-01-01

    Growing concern in Taiwan has arisen about energy consumption and its adverse environmental impact. The current situation of energy conservation in high energy-consuming industries in Taiwan, including the iron and steel, chemical, cement, pulp and paper, textiles and electric/electrical industries has been presented. Since the energy consumption of the top 100 energy users (T100) comprised over 50% of total industry energy consumption, focusing energy consumption reduction efforts on T100 energy users can achieve significant results. This study conducted on-site energy audits of 314 firms in Taiwan during 2000-2004, and identified potential electricity savings of 1,022,656 MWH, fuel oil savings of 174,643 kiloliters (KL), steam coal savings of 98,620 ton, and natural gas (NG) savings of 10,430 kilo cubic meters. The total potential energy saving thus was 489,505 KL of crude oil equivalent (KLOE), representing a reduction of 1,447,841 ton in the carbon dioxide emissions, equivalent to the annual carbon dioxide absorption capacity of a 39,131-ha plantation forest

  19. High precision conformal radiotherapy employing conservative margins in childhood benign and low-grade brain tumours

    International Nuclear Information System (INIS)

    Jalali, Rakesh; Budrukkar, Ashwini; Sarin, Rajiv; Sharma, Dayananda S.

    2005-01-01

    Background and purpose: To report local control and follow up outcome data of high precision conformal radiotherapy in childhood brain tumours. Materials and methods: Between December 1999 and December 2002, 26 children (17 boys and 9 girls, median age 11.5 years) with incompletely excised or recurrent benign and low-grade brain tumours [13 craniopharyngiomas, 11 low-grade gliomas (LGG) and 2 others] were treated with three-dimensional (3D) conformal radiotherapy (CRT) (12 patients) and stereotactic conformal radiotherapy (SCRT) (14 patients). Gross tumour volume (GTV) included neuro-imaging based visible tumour and/or resected tumour bed. Clinical target volume (CTV) consisted of GTV + 5 mm margin and planning target volume (PTV) consisted of additional 5 mm margin for CRT and 2 mm for SCRT. Treatment was delivered with 3-9 conformal fixed fields to a median dose of 54 Gy/30 fractions. Results: The actuarial 2 and 3 year disease free and overall survival was 96 and 100%, respectively (median follow up: 25 months, range 12-47 months). Radiological follow up available in 25 patients revealed complete response in 1, partial regression in 10, stable disease in 13 and progression in 1 patient (within the CTV). One patient with craniopharyngioma on a routine imaging revealed a mild asymptomatic cyst enlargement, which resolved with conservative management. A patient with chiasmatic glioma developed cystic degeneration and hydrocephalus 9 months after SCRT requiring cyst drainage and placement of a ventriculoperitoneal shunt. Conclusion: High-precision conformal techniques delivering irradiation to a computer generated target volume employing 7-10 mm 3D margins beyond the visible tumour and/or resected tumour bed appear to be safe in children with incompletely resected or recurrent benign and low-grade brain tumours, based on these data

  20. The Highly Conserved Proline at Position 438 in Pseudorabies Virus gH Is Important for Regulation of Membrane Fusion

    OpenAIRE

    Schröter, Christina; Klupp, Barbara G.; Fuchs, Walter; Gerhard, Marika; Backovic, Marija; Rey, Felix A.; Mettenleiter, Thomas C.

    2014-01-01

    Membrane fusion in herpesviruses requires viral glycoproteins (g) gB and gH/gL. While gB is considered the actual fusion protein but is nonfusogenic per se, the function of gH/gL remains enigmatic. Crystal structures for different gH homologs are strikingly similar despite only moderate amino acid sequence conservation. A highly conserved sequence motif comprises the residues serine-proline-cysteine corresponding to positions 437 to 439 in pseudorabies virus (PrV) gH. The PrV-gH structure sho...

  1. Gains of ubiquitylation sites in highly conserved proteins in the human lineage

    Directory of Open Access Journals (Sweden)

    Kim Dong Seon

    2012-11-01

    Full Text Available Abstract Background Post-translational modification of lysine residues of specific proteins by ubiquitin modulates the degradation, localization, and activity of these target proteins. Here, we identified gains of ubiquitylation sites in highly conserved regions of human proteins that occurred during human evolution. Results We analyzed human ubiquitylation site data and multiple alignments of orthologous mammalian proteins including those from humans, primates, other placental mammals, opossum, and platypus. In our analysis, we identified 281 ubiquitylation sites in 252 proteins that first appeared along the human lineage during primate evolution: one protein had four novel sites; four proteins had three sites each; 18 proteins had two sites each; and the remaining 229 proteins had one site each. PML, which is involved in neurodevelopment and neurodegeneration, acquired three sites, two of which have been reported to be involved in the degradation of PML. Thirteen human proteins, including ERCC2 (also known as XPD and NBR1, gained human-specific ubiquitylated lysines after the human-chimpanzee divergence. ERCC2 has a Lys/Gln polymorphism, the derived (major allele of which confers enhanced DNA repair capacity and reduced cancer risk compared with the ancestral (minor allele. NBR1 and eight other proteins that are involved in the human autophagy protein interaction network gained a novel ubiquitylation site. Conclusions The gain of novel ubiquitylation sites could be involved in the evolution of protein degradation and other regulatory networks. Although gains of ubiquitylation sites do not necessarily equate to adaptive evolution, they are useful candidates for molecular functional analyses to identify novel advantageous genetic modifications and innovative phenotypes acquired during human evolution.

  2. High risks of losing genetic diversity in an endemic Mauritian gecko: implications for conservation.

    Directory of Open Access Journals (Sweden)

    Steeves Buckland

    Full Text Available Genetic structure can be a consequence of recent population fragmentation and isolation, or a remnant of historical localised adaptation. This poses a challenge for conservationists since misinterpreting patterns of genetic structure may lead to inappropriate management. Of 17 species of reptile originally found in Mauritius, only five survive on the main island. One of these, Phelsuma guimbeaui (lowland forest day gecko, is now restricted to 30 small isolated subpopulations following severe forest fragmentation and isolation due to human colonisation. We used 20 microsatellites in ten subpopulations and two mitochondrial DNA (mtDNA markers in 13 subpopulations to: (i assess genetic diversity, population structure and genetic differentiation of subpopulations; (ii estimate effective population sizes and migration rates of subpopulations; and (iii examine the phylogenetic relationships of haplotypes found in different subpopulations. Microsatellite data revealed significant population structure with high levels of genetic diversity and isolation by distance, substantial genetic differentiation and no migration between most subpopulations. MtDNA, however, showed no evidence of population structure, indicating that there was once a genetically panmictic population. Effective population sizes of ten subpopulations, based on microsatellite markers, were small, ranging from 44 to 167. Simulations suggested that the chance of survival and allelic diversity of some subpopulations will decrease dramatically over the next 50 years if no migration occurs. Our DNA-based evidence reveals an urgent need for a management plan for the conservation of P. guimbeaui. We identified 18 threatened and 12 viable subpopulations and discuss a range of management options that include translocation of threatened subpopulations to retain maximum allelic diversity, and habitat restoration and assisted migration to decrease genetic erosion and inbreeding for the viable

  3. The existence of High Conservation Value Forest (HCVF in Perum Perhutani KPH Kendal to support Implementation of FSC Certification

    Directory of Open Access Journals (Sweden)

    Sulistyowati Sri

    2018-01-01

    Full Text Available High Conservation Value Forest (HCVF is the identification of High Conservation Values that are important and need to be protected. Under FSC certification mechanism, HCVF becomes one of Principles and Criteria to attain certification. In this study, we identify the existence of HCVF in Perum Perhutani KPH Kendal to support implementation process of FSC certification. Qualitative method was conducted through observation and secondary data from Perum Perhutani KPH Kendal. Data analysis showed through ecolabel certification, Perum Perhutani KPH Kendal has been identified HCVF area covering 2,715.5 hectares consists of HCV 1 until 6. Secondary Natural Forest (HAS Subah and Kaliwungu for Ulolanang and Pagerwunung Nature Reserve buffer zone include as HCV 1.1, conservation area of leopard (Panthera pardus melas and Pangolin (Manis javanica.for HCV 1.2, conservation area of lutung (Trachypiyhecus auratus as endemic species for CITES App I and Critically Endangered species include as HCV 1.3, Goa kiskendo for bats species habitat include as HCV 1.4, regions of interest species for Deer (Cervus timorensis and Kepodang (Oriolus chinensis as HCV 2.3, Germplasm Protection Region/ KPPN area with high biodiversity include as HCV 3, river border area and water springs for HCV 4. While, utilization of firewood, grass for cattle fodder include as HCV 5 and 14 cultural sites include as HCV 6. From monitoring and evaluation of HCVF data, showed that in 2011-2015 the level of diversity for flora and fauna were increased.

  4. The existence of High Conservation Value Forest (HCVF) in Perum Perhutani KPH Kendal to support Implementation of FSC Certification

    Science.gov (United States)

    Sulistyowati, Sri; Hadi, Sudharto P.

    2018-02-01

    High Conservation Value Forest (HCVF) is the identification of High Conservation Values that are important and need to be protected. Under FSC certification mechanism, HCVF becomes one of Principles and Criteria to attain certification. In this study, we identify the existence of HCVF in Perum Perhutani KPH Kendal to support implementation process of FSC certification. Qualitative method was conducted through observation and secondary data from Perum Perhutani KPH Kendal. Data analysis showed through ecolabel certification, Perum Perhutani KPH Kendal has been identified HCVF area covering 2,715.5 hectares consists of HCV 1 until 6. Secondary Natural Forest (HAS) Subah and Kaliwungu for Ulolanang and Pagerwunung Nature Reserve buffer zone include as HCV 1.1, conservation area of leopard (Panthera pardus melas) and Pangolin (Manis javanica).for HCV 1.2, conservation area of lutung (Trachypiyhecus auratus) as endemic species for CITES App I and Critically Endangered species include as HCV 1.3, Goa kiskendo for bats species habitat include as HCV 1.4, regions of interest species for Deer (Cervus timorensis) and Kepodang (Oriolus chinensis) as HCV 2.3, Germplasm Protection Region/ KPPN area with high biodiversity include as HCV 3, river border area and water springs for HCV 4. While, utilization of firewood, grass for cattle fodder include as HCV 5 and 14 cultural sites include as HCV 6. From monitoring and evaluation of HCVF data, showed that in 2011-2015 the level of diversity for flora and fauna were increased.

  5. High-frequency ultrasound for intraoperative margin assessments in breast conservation surgery: a feasibility study

    International Nuclear Information System (INIS)

    Doyle, Timothy E; Neumayer, Leigh A; Factor, Rachel E; Ellefson, Christina L; Sorensen, Kristina M; Ambrose, Brady J; Goodrich, Jeffrey B; Hart, Vern P; Jensen, Scott C; Patel, Hemang

    2011-01-01

    In addition to breast imaging, ultrasound offers the potential for characterizing and distinguishing between benign and malignant breast tissues due to their different microstructures and material properties. The aim of this study was to determine if high-frequency ultrasound (20-80 MHz) can provide pathology sensitive measurements for the ex vivo detection of cancer in margins during breast conservation surgery. Ultrasonic tests were performed on resected margins and other tissues obtained from 17 patients, resulting in 34 specimens that were classified into 15 pathology categories. Pulse-echo and through-transmission measurements were acquired from a total of 57 sites on the specimens using two single-element 50-MHz transducers. Ultrasonic attenuation and sound speed were obtained from time-domain waveforms. The waveforms were further processed with fast Fourier transforms to provide ultrasonic spectra and cepstra. The ultrasonic measurements and pathology types were analyzed for correlations. The specimens were additionally re-classified into five pathology types to determine specificity and sensitivity values. The density of peaks in the ultrasonic spectra, a measure of spectral structure, showed significantly higher values for carcinomas and precancerous pathologies such as atypical ductal hyperplasia than for normal tissue. The slopes of the cepstra for non-malignant pathologies displayed significantly greater values that differentiated them from the normal and malignant tissues. The attenuation coefficients were sensitive to fat necrosis, fibroadenoma, and invasive lobular carcinoma. Specificities and sensitivities for differentiating pathologies from normal tissue were 100% and 86% for lobular carcinomas, 100% and 74% for ductal carcinomas, 80% and 82% for benign pathologies, and 80% and 100% for fat necrosis and adenomas. Specificities and sensitivities were also determined for differentiating each pathology type from the other four using a multivariate

  6. High-frequency ultrasound for intraoperative margin assessments in breast conservation surgery: a feasibility study

    Directory of Open Access Journals (Sweden)

    Hart Vern P

    2011-10-01

    Full Text Available Abstract Background In addition to breast imaging, ultrasound offers the potential for characterizing and distinguishing between benign and malignant breast tissues due to their different microstructures and material properties. The aim of this study was to determine if high-frequency ultrasound (20-80 MHz can provide pathology sensitive measurements for the ex vivo detection of cancer in margins during breast conservation surgery. Methods Ultrasonic tests were performed on resected margins and other tissues obtained from 17 patients, resulting in 34 specimens that were classified into 15 pathology categories. Pulse-echo and through-transmission measurements were acquired from a total of 57 sites on the specimens using two single-element 50-MHz transducers. Ultrasonic attenuation and sound speed were obtained from time-domain waveforms. The waveforms were further processed with fast Fourier transforms to provide ultrasonic spectra and cepstra. The ultrasonic measurements and pathology types were analyzed for correlations. The specimens were additionally re-classified into five pathology types to determine specificity and sensitivity values. Results The density of peaks in the ultrasonic spectra, a measure of spectral structure, showed significantly higher values for carcinomas and precancerous pathologies such as atypical ductal hyperplasia than for normal tissue. The slopes of the cepstra for non-malignant pathologies displayed significantly greater values that differentiated them from the normal and malignant tissues. The attenuation coefficients were sensitive to fat necrosis, fibroadenoma, and invasive lobular carcinoma. Specificities and sensitivities for differentiating pathologies from normal tissue were 100% and 86% for lobular carcinomas, 100% and 74% for ductal carcinomas, 80% and 82% for benign pathologies, and 80% and 100% for fat necrosis and adenomas. Specificities and sensitivities were also determined for differentiating each

  7. Geometrid moth assemblages reflect high conservation value of naturally regenerated secondary forests in temperate China

    NARCIS (Netherlands)

    Zou, Yi; Sang, Weiguo; Warren-Thomas, Eleanor; Axmacher, Jan Christoph

    2016-01-01

    The widespread destruction of mature forests in China has led to massive ecological degradation, counteracted in recent decades by substantial efforts to promote forest plantations and protect secondary forest ecosystems. The value of the resulting forests for biodiversity conservation is widely

  8. Liberals, Conservatives and Romantic Nationalists in Interwar Education Policy in Greece: "The High Mountains" Episode

    Science.gov (United States)

    Athanasiades, Harris

    2015-01-01

    Greek historiography of interwar education policy unproblematically accepts the assumption that the bone of contention between the "Liberal demoticists" and the "Conservative purists" was the language issue; particularly whether "demotic" or "katharevousa" should be the language of instruction in schooling.…

  9. Gene co-regulation is highly conserved in the evolution of eukaryotes and prokaryotes.

    NARCIS (Netherlands)

    Snel, B.; Noort, V. van; Huynen, M.A.

    2004-01-01

    Differences between species have been suggested to largely reside in the network of connections among the genes. Nevertheless, the rate at which these connections evolve has not been properly quantified. Here, we measure the extent to which co-regulation between pairs of genes is conserved over

  10. Androgen receptor status is highly conserved during tumor progression of breast cancer.

    Science.gov (United States)

    Grogg, André; Trippel, Mafalda; Pfaltz, Katrin; Lädrach, Claudia; Droeser, Raoul A; Cihoric, Nikola; Salhia, Bodour; Zweifel, Martin; Tapia, Coya

    2015-11-09

    highly conserved during tumor progression and a change only occurs in a small fraction (4.1 %). Our study supports the notion that targeting AR could be effective for many BC patients and that re-testing of AR status in formerly negative or mixed type BC's is recommended.

  11. Androgen receptor status is highly conserved during tumor progression of breast cancer

    International Nuclear Information System (INIS)

    Grogg, André; Trippel, Mafalda; Pfaltz, Katrin; Lädrach, Claudia; Droeser, Raoul A.; Cihoric, Nikola; Salhia, Bodour; Zweifel, Martin; Tapia, Coya

    2015-01-01

    With the advent of new and more efficient anti-androgen drugs targeting androgen receptor (AR) in breast cancer (BC) is becoming an increasingly important area of investigation. This would potentially be most useful in triple negative BC (TNBC), where better therapies are still needed. The assessment of AR status is generally performed on the primary tumor even if the tumor has already metastasized. Very little is known regarding discrepancies of AR status during tumor progression. To determine the prevalence of AR positivity, with emphasis on TNBCs, and to investigate AR status during tumor progression, we evaluated a large series of primary BCs and matching metastases and recurrences. AR status was performed on 356 primary BCs, 135 matching metastases, and 12 recurrences using a next-generation Tissue Microarray (ngTMA). A commercially available AR antibody was used to determine AR-status by immunohistochemistry. AR positivity was defined as any nuclear staining in tumor cells ≥1 %. AR expression was correlated with pathological tumor features of the primary tumor. Additionally, the concordance rate of AR expression between the different tumor sites was determined. AR status was positive in: 87 % (307/353) of primary tumors, 86.1 % (105/122) of metastases, and in 66.7 % (8/12) of recurrences. TNBC tested positive in 11.4 %, (4/35) of BCs. A discrepant result was seen in 4.3 % (5/117) of primary BC and matching lymph node (LN) metastases. Three AR negative primary BCs were positive in the matching LN metastasis, representing 17.6 % of all negative BCs with lymph node metastases (3/17). Two AR positive primary BCs were negative in the matching LN metastasis, representing 2.0 % of all AR positive BCs with LN metastases (2/100). No discrepancies were seen between primary BC and distant metastases or recurrence (n = 17). Most primary (87 %) and metastasized (86.1 %) BCs are AR positive including a significant fraction of TNBCs (11.4 %). Further, AR status is highly

  12. Conservation hotspots for the turtles on the high seas of the Atlantic Ocean.

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    Hsiang-Wen Huang

    Full Text Available Understanding the distribution of bycaught sea turtles could inform conservation strategies and priorities. This research analyses the distribution of turtles caught as longline fisheries bycatch on the high seas of the Atlantic Ocean. This research collected 18,142 bycatch observations and 47.1 million hooks from large-scale Taiwanese longline vessels in the Atlantic Ocean from June 2002 to December 2013. The coverage rates were ranged from 0.48% to 17.54% by year. Seven hundred and sixty-seven turtles were caught, and the major species were leatherback (59.8%, olive ridley (27.1% and loggerhead turtles (8.7%. Most olive ridley (81.7% and loggerhead (82.1% turtles were hooked, while the leatherbacks were both hooked (44.0% and entangled (31.8%. Depending on the species, 21.4% to 57.7% were dead when brought onboard. Most of the turtles were caught in tropical areas, especially in the Gulf of Guinea (15°N-10°S, 30°W-10°E, but loggerheads were caught in the south Atlantic Ocean (25°S-35°S, 40°W-10°E and 30°S-40°S, 55°W-45°W. The bycatch rate was the highest at 0.030 per 1000 hooks for leatherbacks in the tropical area. The bycatch rates of olive ridley ranged from 0 to 0.010 per thousand hooks. The loggerhead bycatch rates were higher in the northern and southern Atlantic Ocean and ranged from 0.0128 to 0.0239 per thousand hooks. Due to the characteristics of the Taiwanese deep-set longline fleet, bycatch rates were lower than those of coastal longline fisheries, but mortality rates were higher because of the long hours of operation. Gear and bait modification should be considered to reduce sea turtle bycatch and increase survival rates while reducing the use of shallow hooks would also be helpful.

  13. Conservation hotspots for the turtles on the high seas of the Atlantic Ocean.

    Science.gov (United States)

    Huang, Hsiang-Wen

    2015-01-01

    Understanding the distribution of bycaught sea turtles could inform conservation strategies and priorities. This research analyses the distribution of turtles caught as longline fisheries bycatch on the high seas of the Atlantic Ocean. This research collected 18,142 bycatch observations and 47.1 million hooks from large-scale Taiwanese longline vessels in the Atlantic Ocean from June 2002 to December 2013. The coverage rates were ranged from 0.48% to 17.54% by year. Seven hundred and sixty-seven turtles were caught, and the major species were leatherback (59.8%), olive ridley (27.1%) and loggerhead turtles (8.7%). Most olive ridley (81.7%) and loggerhead (82.1%) turtles were hooked, while the leatherbacks were both hooked (44.0%) and entangled (31.8%). Depending on the species, 21.4% to 57.7% were dead when brought onboard. Most of the turtles were caught in tropical areas, especially in the Gulf of Guinea (15°N-10°S, 30°W-10°E), but loggerheads were caught in the south Atlantic Ocean (25°S-35°S, 40°W-10°E and 30°S-40°S, 55°W-45°W). The bycatch rate was the highest at 0.030 per 1000 hooks for leatherbacks in the tropical area. The bycatch rates of olive ridley ranged from 0 to 0.010 per thousand hooks. The loggerhead bycatch rates were higher in the northern and southern Atlantic Ocean and ranged from 0.0128 to 0.0239 per thousand hooks. Due to the characteristics of the Taiwanese deep-set longline fleet, bycatch rates were lower than those of coastal longline fisheries, but mortality rates were higher because of the long hours of operation. Gear and bait modification should be considered to reduce sea turtle bycatch and increase survival rates while reducing the use of shallow hooks would also be helpful.

  14. High Resolution Mapping of Soils and Landforms for the Desert Renewable Energy Conservation Plan (DRECP)

    Science.gov (United States)

    Potter, Christopher S.; Li, Shuang

    2014-01-01

    The Desert Renewable Energy Conservation Plan (DRECP), a major component of California's renewable energy planning efforts, is intended to provide effective protection and conservation of desert ecosystems, while allowing for the sensible development of renewable energy projects. This NASA mapping report was developed to support the DRECP and the Bureau of Land Management (BLM). We outline in this document remote sensing image processing methods to deliver new maps of biological soils crusts, sand dune movements, desert pavements, and sub-surface water sources across the DRECP area. We focused data processing first on the largely unmapped areas most likely to be used for energy developments, such as those within Renewable Energy Study Areas (RESA) and Solar Energy Zones (SEZs). We used imagery (multispectral and radar) mainly from the years 2009-2011.

  15. High-Quality 3d Models and Their Use in a Cultural Heritage Conservation Project

    Science.gov (United States)

    Tucci, G.; Bonora, V.; Conti, A.; Fiorini, L.

    2017-08-01

    Cultural heritage digitization and 3D modelling processes are mainly based on laser scanning and digital photogrammetry techniques to produce complete, detailed and photorealistic three-dimensional surveys: geometric as well as chromatic aspects, in turn testimony of materials, work techniques, state of preservation, etc., are documented using digitization processes. The paper explores the topic of 3D documentation for conservation purposes; it analyses how geomatics contributes in different steps of a restoration process and it presents an overview of different uses of 3D models for the conservation and enhancement of the cultural heritage. The paper reports on the project to digitize the earthenware frieze of the Ospedale del Ceppo in Pistoia (Italy) for 3D documentation, restoration work support, and digital and physical reconstruction and integration purposes. The intent to design an exhibition area suggests new ways to take advantage of 3D data originally acquired for documentation and scientific purposes.

  16. A High-Accuracy Linear Conservative Difference Scheme for Rosenau-RLW Equation

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    Jinsong Hu

    2013-01-01

    Full Text Available We study the initial-boundary value problem for Rosenau-RLW equation. We propose a three-level linear finite difference scheme, which has the theoretical accuracy of Oτ2+h4. The scheme simulates two conservative properties of original problem well. The existence, uniqueness of difference solution, and a priori estimates in infinite norm are obtained. Furthermore, we analyze the convergence and stability of the scheme by energy method. At last, numerical experiments demonstrate the theoretical results.

  17. Hearing sensitivity in context: Conservation implications for a highly vocal endangered species

    OpenAIRE

    Owen, Megan A.; Keating, Jennifer L.; Denes, Samuel K.; Hawk, Kathy; Fiore, Angela; Thatcher, Julie; Becerra, Jennifer; Hall, Suzanne; Swaisgood, Ronald R.

    2016-01-01

    Hearing sensitivity is a fundamental determinant of a species’ vulnerability to anthropogenic noise, however little is known about the hearing capacities of most conservation dependent species. When audiometric data are integrated with other aspects of species’ acoustic ecology, life history, and characteristic habitat topography and soundscape, predictions can be made regarding probable vulnerability to the negative impacts of different types of anthropogenic noise. Here we used an adaptive ...

  18. Innovative Surgical Management of the Synovial Chondromatosis of Temporo-Mandibular Joints: Highly Conservative Surgical Technique.

    Science.gov (United States)

    Ionna, Franco; Amantea, Massimiliano; Mastrangelo, Filiberto; Ballini, Andrea; Maglione, Maria Grazia; Aversa, Corrado; De Cecio, Rossella; Russo, Daniela; Marrelli, Massimo; Tatullo, Marco

    2016-07-01

    Synovial chondromatosis (SC) is an uncommon disease characterized by a benign nodular cartilaginous proliferation arising from the joint synovium, bursae, or tendon sheaths. Although the temporomandibular joint is rarely affected by neoplastic lesions, SC is the most common neoplastic lesion of this joint. The treatment of this disease consists in the extraoral surgery with a wide removal of the lesion; in this study, the authors described a more conservative intraoral surgical approach. Patient with SC of temporomandibular joint typically refer a limitation in the mouth opening, together with a persistent not physiological mandibular protrusion and an appearance of a neoformation located at the right preauricular region: the authors reported 1 scholar patient. After biopsy of the neoformation, confirming the synovial chondromatosis, the patient underwent thus to the surgical excision of the tumor, via authors' conservative transoral approach, to facilitate the enucleation of the neoformation. The mass fully involved the pterygo-maxillary fossa with involvement of the parotid lodge and of the right TMJ: this multifocal extension suggested for a trans-oral surgical procedure, in the light of the suspicion of a possible malignant nature of the neoplasm. Our intraoral conservative approach to surgery is aimed to reduce the presence of unaesthetic scars in preauricular and facial regions, with surgical results undoubtedly comparable to the traditional surgical techniques much more aggressive. Our technique could be a valid, alternative, and safe approach to treat this rare and complex kind of oncological disease.

  19. Adaptive evolution of conserved noncoding elements in mammals.

    Directory of Open Access Journals (Sweden)

    Su Yeon Kim

    2007-09-01

    Full Text Available Conserved noncoding elements (CNCs are an abundant feature of vertebrate genomes. Some CNCs have been shown to act as cis-regulatory modules, but the function of most CNCs remains unclear. To study the evolution of CNCs, we have developed a statistical method called the "shared rates test" to identify CNCs that show significant variation in substitution rates across branches of a phylogenetic tree. We report an application of this method to alignments of 98,910 CNCs from the human, chimpanzee, dog, mouse, and rat genomes. We find that approximately 68% of CNCs evolve according to a null model where, for each CNC, a single parameter models the level of constraint acting throughout the phylogeny linking these five species. The remaining approximately 32% of CNCs show departures from the basic model including speed-ups and slow-downs on particular branches and occasionally multiple rate changes on different branches. We find that a subset of the significant CNCs have evolved significantly faster than the local neutral rate on a particular branch, providing strong evidence for adaptive evolution in these CNCs. The distribution of these signals on the phylogeny suggests that adaptive evolution of CNCs occurs in occasional short bursts of evolution. Our analyses suggest a large set of promising targets for future functional studies of adaptation.

  20. The importance of incorporating functional habitats into conservation planning for highly mobile species in dynamic systems.

    Science.gov (United States)

    Webb, Matthew H; Terauds, Aleks; Tulloch, Ayesha; Bell, Phil; Stojanovic, Dejan; Heinsohn, Robert

    2017-10-01

    The distribution of mobile species in dynamic systems can vary greatly over time and space. Estimating their population size and geographic range can be problematic and affect the accuracy of conservation assessments. Scarce data on mobile species and the resources they need can also limit the type of analytical approaches available to derive such estimates. We quantified change in availability and use of key ecological resources required for breeding for a critically endangered nomadic habitat specialist, the Swift Parrot (Lathamus discolor). We compared estimates of occupied habitat derived from dynamic presence-background (i.e., presence-only data) climatic models with estimates derived from dynamic occupancy models that included a direct measure of food availability. We then compared estimates that incorporate fine-resolution spatial data on the availability of key ecological resources (i.e., functional habitats) with more common approaches that focus on broader climatic suitability or vegetation cover (due to the absence of fine-resolution data). The occupancy models produced significantly (P increase or decrease in the area of one functional habitat (foraging or nesting) did not necessarily correspond to an increase or decrease in the other. Thus, an increase in the extent of occupied area may not equate to improved habitat quality or function. We argue these patterns are typical for mobile resource specialists but often go unnoticed because of limited data over relevant spatial and temporal scales and lack of spatial data on the availability of key resources. Understanding changes in the relative availability of functional habitats is crucial to informing conservation planning and accurately assessing extinction risk for mobile resource specialists. © 2017 Society for Conservation Biology.

  1. Crystal structure of AFV3-109, a highly conserved protein from crenarchaeal viruses

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    Quevillon-Cheruel Sophie

    2007-01-01

    Full Text Available Abstract The extraordinary morphologies of viruses infecting hyperthermophilic archaea clearly distinguish them from bacterial and eukaryotic viruses. Moreover, their genomes code for proteins that to a large extend have no related sequences in the extent databases. However, a small pool of genes is shared by overlapping subsets of these viruses, and the most conserved gene, exemplified by the ORF109 of the Acidianus Filamentous Virus 3, AFV3, is present on genomes of members of three viral familes, the Lipothrixviridae, Rudiviridae, and "Bicaudaviridae", as well as of the unclassified Sulfolobus Turreted Icosahedral Virus, STIV. We present here the crystal structure of the protein (Mr = 13.1 kD, 109 residues encoded by the AFV3 ORF 109 in two different crystal forms at 1.5 and 1.3 Å resolution. The structure of AFV3-109 is a five stranded β-sheet with loops on one side and three helices on the other. It forms a dimer adopting the shape of a cradle that encompasses the best conserved regions of the sequence. No protein with a related fold could be identified except for the ortholog from STIV1, whose structure was deposited at the Protein Data Bank. We could clearly identify a well bound glycerol inside the cradle, contacting exclusively totally conserved residues. This interaction was confirmed in solution by fluorescence titration. Although the function of AFV3-109 cannot be deduced directly from its structure, structural homology with the STIV1 protein, and the size and charge distribution of the cavity suggested it could interact with nucleic acids. Fluorescence quenching titrations also showed that AFV3-109 interacts with dsDNA. Genomic sequence analysis revealed bacterial homologs of AFV3-109 as a part of a putative previously unidentified prophage sequences in some Firmicutes.

  2. Comparative analyses of six solanaceous transcriptomes reveal a high degree of sequence conservation and species-specific transcripts

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    Ouyang Shu

    2005-09-01

    Full Text Available Abstract Background The Solanaceae is a family of closely related species with diverse phenotypes that have been exploited for agronomic purposes. Previous studies involving a small number of genes suggested sequence conservation across the Solanaceae. The availability of large collections of Expressed Sequence Tags (ESTs for the Solanaceae now provides the opportunity to assess sequence conservation and divergence on a genomic scale. Results All available ESTs and Expressed Transcripts (ETs, 449,224 sequences for six Solanaceae species (potato, tomato, pepper, petunia, tobacco and Nicotiana benthamiana, were clustered and assembled into gene indices. Examination of gene ontologies revealed that the transcripts within the gene indices encode a similar suite of biological processes. Although the ESTs and ETs were derived from a variety of tissues, 55–81% of the sequences had significant similarity at the nucleotide level with sequences among the six species. Putative orthologs could be identified for 28–58% of the sequences. This high degree of sequence conservation was supported by expression profiling using heterologous hybridizations to potato cDNA arrays that showed similar expression patterns in mature leaves for all six solanaceous species. 16–19% of the transcripts within the six Solanaceae gene indices did not have matches among Solanaceae, Arabidopsis, rice or 21 other plant gene indices. Conclusion Results from this genome scale analysis confirmed a high level of sequence conservation at the nucleotide level of the coding sequence among Solanaceae. Additionally, the results indicated that part of the Solanaceae transcriptome is likely to be unique for each species.

  3. NFAT5 regulates HIV-1 in primary monocytes via a highly conserved long terminal repeat site.

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    Shahin Ranjbar

    2006-12-01

    Full Text Available To replicate, HIV-1 capitalizes on endogenous cellular activation pathways resulting in recruitment of key host transcription factors to its viral enhancer. RNA interference has been a powerful tool for blocking key checkpoints in HIV-1 entry into cells. Here we apply RNA interference to HIV-1 transcription in primary macrophages, a major reservoir of the virus, and specifically target the transcription factor NFAT5 (nuclear factor of activated T cells 5, which is the most evolutionarily divergent NFAT protein. By molecularly cloning and sequencing isolates from multiple viral subtypes, and performing DNase I footprinting, electrophoretic mobility shift, and promoter mutagenesis transfection assays, we demonstrate that NFAT5 functionally interacts with a specific enhancer binding site conserved in HIV-1, HIV-2, and multiple simian immunodeficiency viruses. Using small interfering RNA to ablate expression of endogenous NFAT5 protein, we show that the replication of three major HIV-1 viral subtypes (B, C, and E is dependent upon NFAT5 in human primary differentiated macrophages. Our results define a novel host factor-viral enhancer interaction that reveals a new regulatory role for NFAT5 and defines a functional DNA motif conserved across HIV-1 subtypes and representative simian immunodeficiency viruses. Inhibition of the NFAT5-LTR interaction may thus present a novel therapeutic target to suppress HIV-1 replication and progression of AIDS.

  4. Proteomic Analysis of Pathogenic Fungi Reveals Highly Expressed Conserved Cell Wall Proteins

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    Jackson Champer

    2016-01-01

    Full Text Available We are presenting a quantitative proteomics tally of the most commonly expressed conserved fungal proteins of the cytosol, the cell wall, and the secretome. It was our goal to identify fungi-typical proteins that do not share significant homology with human proteins. Such fungal proteins are of interest to the development of vaccines or drug targets. Protein samples were derived from 13 fungal species, cultured in rich or in minimal media; these included clinical isolates of Aspergillus, Candida, Mucor, Cryptococcus, and Coccidioides species. Proteomes were analyzed by quantitative MSE (Mass Spectrometry—Elevated Collision Energy. Several thousand proteins were identified and quantified in total across all fractions and culture conditions. The 42 most abundant proteins identified in fungal cell walls or supernatants shared no to very little homology with human proteins. In contrast, all but five of the 50 most abundant cytosolic proteins had human homologs with sequence identity averaging 59%. Proteomic comparisons of the secreted or surface localized fungal proteins highlighted conserved homologs of the Aspergillus fumigatus proteins 1,3-β-glucanosyltransferases (Bgt1, Gel1-4, Crf1, Ecm33, EglC, and others. The fact that Crf1 and Gel1 were previously shown to be promising vaccine candidates, underlines the value of the proteomics data presented here.

  5. The conservation value of South East Asia's highly degraded forests: evidence from leaf-litter ants

    Science.gov (United States)

    Woodcock, Paul; Edwards, David P.; Fayle, Tom M.; Newton, Rob J.; Khen, Chey Vun; Bottrell, Simon H.; Hamer, Keith C.

    2011-01-01

    South East Asia is widely regarded as a centre of threatened biodiversity owing to extensive logging and forest conversion to agriculture. In particular, forests degraded by repeated rounds of intensive logging are viewed as having little conservation value and are afforded meagre protection from conversion to oil palm. Here, we determine the biological value of such heavily degraded forests by comparing leaf-litter ant communities in unlogged (natural) and twice-logged forests in Sabah, Borneo. We accounted for impacts of logging on habitat heterogeneity by comparing species richness and composition at four nested spatial scales, and examining how species richness was partitioned across the landscape in each habitat. We found that twice-logged forest had fewer species occurrences, lower species richness at small spatial scales and altered species composition compared with natural forests. However, over 80 per cent of species found in unlogged forest were detected within twice-logged forest. Moreover, greater species turnover among sites in twice-logged forest resulted in identical species richness between habitats at the largest spatial scale. While two intensive logging cycles have negative impacts on ant communities, these degraded forests clearly provide important habitat for numerous species and preventing their conversion to oil palm and other crops should be a conservation priority. PMID:22006966

  6. Impacts of Tropical Forest Disturbance Upon Avifauna on a Small Island with High Endemism: Implications for Conservation

    Directory of Open Access Journals (Sweden)

    Martin Thomas

    2010-01-01

    Full Text Available Tropical forests are rapidly being lost across Southeast Asia and this is predicted to have severe implications for many of the region′s bird species. However, relationships between forest disturbance and avifaunal assemblages remain poorly understood, particularly on small island ecosystems such as those found in the biodiversity ′hotspot′ of Wallacea. This study examines how avifaunal richness varies across a disturbance gradient in a forest reserve on Buton Island, southeast Sulawesi. Particular emphasis is placed upon examining responses in endemic and red-listed species with high conservation importance. Results indicate that overall avian richness increases between primary and 30-year-old regenerating secondary forest and then decreases through disturbed secondary forest, but is highest in cleared farmland. However, high species richness in farmland does not signify high species distinctiveness; bird community composition here differs significantly from that found in forest sites, and is poor in supporting forest specialists and endemic species. Certain large-bodied endemics such as the Knobbed Hornbill (Rhyticeros cassidix appear to be sensitive to moderate disturbance, with populations occurring at greatest density within primary forest. However, overall endemic species richness, as well as that of endemic frugivores and insectivores, is similar in primary and secondary forest types. Results indicate that well-established secondary forest in particular has an important role in supporting species with high conservational importance, possessing community composition similar to that found in primary forest and supporting an equally high richness of endemic species.

  7. Noise exposure and hearing conservation practices in an industry with high incidence of workers' compensation claims for hearing loss.

    Science.gov (United States)

    Daniell, William E; Swan, Susan S; McDaniel, Mary M; Stebbins, John G; Seixas, Noah S; Morgan, Michael S

    2002-10-01

    Washington State has experienced a striking increase in workers' compensation claims for hearing loss. This cross-sectional study examined noise exposures and hearing conservation practices in one industry with a high rate of hearing loss claims. We evaluated 10 representative foundries with personal noise dosimetry, management interviews, employee interviews, and existing audiometry. Noise levels routinely exceeded 85 dBA. All companies were out of compliance with hearing conservation regulations. Most employees with important findings on audiograms were not aware of their findings. There was a significant positive correlation between management-interview scores and worksite-average employee-interview scores (r = 0.70, P = 0.02). Companies where more effort is put into hearing conservation program activities can achieve a greater positive impact on employee awareness. However, there were broad deficiencies even in the better programs in this sample, suggesting that workers in this industry probably face a continuing substantial risk of occupational hearing loss. Copyright 2002 Wiley-Liss, Inc.

  8. Universal antibodies against the highly conserved influenza fusion peptide cross-neutralize several subtypes of influenza A virus

    Energy Technology Data Exchange (ETDEWEB)

    Hashem, Anwar M. [Centre for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, HPFB, Health Canada, Ottawa, ON (Canada); Department of Microbiology, Faculty of Medicine, King Abdulaziz University, Jeddah (Saudi Arabia); Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON (Canada); Van Domselaar, Gary [National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB (Canada); Li, Changgui; Wang, Junzhi [National Institute for the Control of Pharmaceutical and Biological Products, Beijing (China); She, Yi-Min; Cyr, Terry D. [Centre for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, HPFB, Health Canada, Ottawa, ON (Canada); Sui, Jianhua [Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, 44 Binney Street, Boston, MA 02115 (United States); He, Runtao [National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB (Canada); Marasco, Wayne A. [Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, 44 Binney Street, Boston, MA 02115 (United States); Li, Xuguang, E-mail: Sean.Li@hc-sc.gc.ca [Centre for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, HPFB, Health Canada, Ottawa, ON (Canada); Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON (Canada)

    2010-12-10

    Research highlights: {yields} The fusion peptide is the only universally conserved epitope in all influenza viral hemagglutinins. {yields} Anti-fusion peptide antibodies are universal antibodies that cross-react with all influenza HA subtypes. {yields} The universal antibodies cross-neutralize different influenza A subtypes. {yields} The universal antibodies inhibit the fusion process between the viruses and the target cells. -- Abstract: The fusion peptide of influenza viral hemagglutinin plays a critical role in virus entry by facilitating membrane fusion between the virus and target cells. As the fusion peptide is the only universally conserved epitope in all influenza A and B viruses, it could be an attractive target for vaccine-induced immune responses. We previously reported that antibodies targeting the first 14 amino acids of the N-terminus of the fusion peptide could bind to virtually all influenza virus strains and quantify hemagglutinins in vaccines produced in embryonated eggs. Here we demonstrate that these universal antibodies bind to the viral hemagglutinins in native conformation presented in infected mammalian cell cultures and neutralize multiple subtypes of virus by inhibiting the pH-dependant fusion of viral and cellular membranes. These results suggest that this unique, highly-conserved linear sequence in viral hemagglutinin is exposed sufficiently to be attacked by the antibodies during the course of infection and merits further investigation because of potential importance in the protection against diverse strains of influenza viruses.

  9. Universal antibodies against the highly conserved influenza fusion peptide cross-neutralize several subtypes of influenza A virus

    International Nuclear Information System (INIS)

    Hashem, Anwar M.; Van Domselaar, Gary; Li, Changgui; Wang, Junzhi; She, Yi-Min; Cyr, Terry D.; Sui, Jianhua; He, Runtao; Marasco, Wayne A.; Li, Xuguang

    2010-01-01

    Research highlights: → The fusion peptide is the only universally conserved epitope in all influenza viral hemagglutinins. → Anti-fusion peptide antibodies are universal antibodies that cross-react with all influenza HA subtypes. → The universal antibodies cross-neutralize different influenza A subtypes. → The universal antibodies inhibit the fusion process between the viruses and the target cells. -- Abstract: The fusion peptide of influenza viral hemagglutinin plays a critical role in virus entry by facilitating membrane fusion between the virus and target cells. As the fusion peptide is the only universally conserved epitope in all influenza A and B viruses, it could be an attractive target for vaccine-induced immune responses. We previously reported that antibodies targeting the first 14 amino acids of the N-terminus of the fusion peptide could bind to virtually all influenza virus strains and quantify hemagglutinins in vaccines produced in embryonated eggs. Here we demonstrate that these universal antibodies bind to the viral hemagglutinins in native conformation presented in infected mammalian cell cultures and neutralize multiple subtypes of virus by inhibiting the pH-dependant fusion of viral and cellular membranes. These results suggest that this unique, highly-conserved linear sequence in viral hemagglutinin is exposed sufficiently to be attacked by the antibodies during the course of infection and merits further investigation because of potential importance in the protection against diverse strains of influenza viruses.

  10. A high-order relaxation method with projective integration for solving nonlinear systems of hyperbolic conservation laws

    Science.gov (United States)

    Lafitte, Pauline; Melis, Ward; Samaey, Giovanni

    2017-07-01

    We present a general, high-order, fully explicit relaxation scheme which can be applied to any system of nonlinear hyperbolic conservation laws in multiple dimensions. The scheme consists of two steps. In a first (relaxation) step, the nonlinear hyperbolic conservation law is approximated by a kinetic equation with stiff BGK source term. Then, this kinetic equation is integrated in time using a projective integration method. After taking a few small (inner) steps with a simple, explicit method (such as direct forward Euler) to damp out the stiff components of the solution, the time derivative is estimated and used in an (outer) Runge-Kutta method of arbitrary order. We show that, with an appropriate choice of inner step size, the time step restriction on the outer time step is similar to the CFL condition for the hyperbolic conservation law. Moreover, the number of inner time steps is also independent of the stiffness of the BGK source term. We discuss stability and consistency, and illustrate with numerical results (linear advection, Burgers' equation and the shallow water and Euler equations) in one and two spatial dimensions.

  11. A new world monkey microsatellite (ap74) highly conserved in primates

    International Nuclear Information System (INIS)

    Oklander, Luciana Ines; Steinberg, Eliana Ruth; Dolores Mudry, Marta

    2012-01-01

    Given their great variability, microsatellites or STRS became the most commonly used genetic markers over the last 15 years. The analysis of these markers requires minimum quantities of DNA, allowing the use of noninvasive samples, such as feces or hair. We amplified the microsatellite ap74 in blood and hair samples in order to analyze the levels of genomic conservation among a wide range of primates including: lemur catta, alouatta caraya, ateles belzebuth, ateles chamek, pan troglodytes, papio sp., and Homo sapiens. in all cases we obtained amplification products that exhibited similar size both in monkeys and human (oscillating between 126 and 176 bp), except in the lemur where the detected fragment presented a size of approximately 1000 bp. the analysis of the nucleotide sequences permitted the evaluation of the molecular modifications experienced during the evolutionary process in primates.

  12. CORECLUST: identification of the conserved CRM grammar together with prediction of gene regulation.

    Science.gov (United States)

    Nikulova, Anna A; Favorov, Alexander V; Sutormin, Roman A; Makeev, Vsevolod J; Mironov, Andrey A

    2012-07-01

    Identification of transcriptional regulatory regions and tracing their internal organization are important for understanding the eukaryotic cell machinery. Cis-regulatory modules (CRMs) of higher eukaryotes are believed to possess a regulatory 'grammar', or preferred arrangement of binding sites, that is crucial for proper regulation and thus tends to be evolutionarily conserved. Here, we present a method CORECLUST (COnservative REgulatory CLUster STructure) that predicts CRMs based on a set of positional weight matrices. Given regulatory regions of orthologous and/or co-regulated genes, CORECLUST constructs a CRM model by revealing the conserved rules that describe the relative location of binding sites. The constructed model may be consequently used for the genome-wide prediction of similar CRMs, and thus detection of co-regulated genes, and for the investigation of the regulatory grammar of the system. Compared with related methods, CORECLUST shows better performance at identification of CRMs conferring muscle-specific gene expression in vertebrates and early-developmental CRMs in Drosophila.

  13. Hearing sensitivity in context: Conservation implications for a highly vocal endangered species

    Directory of Open Access Journals (Sweden)

    Megan A. Owen

    2016-04-01

    Full Text Available Hearing sensitivity is a fundamental determinant of a species’ vulnerability to anthropogenic noise, however little is known about the hearing capacities of most conservation dependent species. When audiometric data are integrated with other aspects of species’ acoustic ecology, life history, and characteristic habitat topography and soundscape, predictions can be made regarding probable vulnerability to the negative impacts of different types of anthropogenic noise. Here we used an adaptive psychoacoustic technique to measure hearing thresholds in the endangered giant panda; a species that uses acoustic communication to coordinate reproduction. Our results suggest that giant pandas have functional hearing into the ultrasonic range, with good sensitivity between 10.0 and 16.0 kHz, and best sensitivity measured at 12.5–14.0 kHz. We estimated the lower and upper limits of functional hearing as 0.10 and 70.0 kHz respectively. While these results suggest that panda hearing is similar to that of some other terrestrial carnivores, panda hearing thresholds above 14.0 kHz were significantly lower (i.e., more sensitive than those of the polar bear, the only other bear species for which data are available. We discuss the implications of this divergence, as well as the relationship between hearing sensitivity and the spectral parameters of panda vocalizations. We suggest that these data, placed in context, can be used towards the development of a sensory-based model of noise disturbance for the species.

  14. 77 FR 11785 - Energy Conservation Program: Public Meeting and Availability of the Framework Document for High...

    Science.gov (United States)

    2012-02-28

    ... standards for high-intensity discharge (HID) lamps. Accordingly, DOE will hold a public meeting to discuss..._standards/commercial/high_intensity_discharge_lamps.html . DATES: The Department will hold a public meeting... Technologies Program, Mailstop EE-2J, Framework Document for High-Intensity Discharge Lamps, EERE-2010-BT-STD...

  15. Surgical versus conservative treatment for high-risk stress fractures of the lower leg (anterior tibial cortex, navicular and fifth metatarsal base): a systematic review

    NARCIS (Netherlands)

    Mallee, Wouter H.; Weel, Hanneke; van Dijk, C. Niek; van Tulder, Maurits W.; Kerkhoffs, Gino M.; Lin, Chung-Wei Christine

    2015-01-01

    To compare surgical and conservative treatment for high-risk stress fractures of the anterior tibial cortex, navicular and proximal fifth metatarsal. Systematic searches of CENTRAL, MEDLINE, EMBASE, CINAHL, SPORTDiscus and PEDro were performed to identify relevant prospective and retrospective

  16. Curli Fibers Are Highly Conserved between Salmonella typhimurium and Escherichia coli with Respect to Operon Structure and Regulation

    Science.gov (United States)

    Römling, Ute; Bian, Zhao; Hammar, Mårten; Sierralta, Walter D.; Normark, Staffan

    1998-01-01

    Mouse-virulent Salmonella typhimurium strains SR-11 and ATCC 14028-1s express curli fibers, thin aggregative fibers, at ambient temperature on plates as judged by Western blot analysis and electron microscopy. Concomitantly with curli expression, cells develop a rough and dry colony morphology and bind the dye Congo red (called the rdar morphotype). Cloning and characterization of the two divergently transcribed operons required for curli biogenesis, csgBA(C) and csgDEFG, from S. typhimurium SR-11 revealed the same gene order and flanking genes as in Escherichia coli. The divergence of the curli region between S. typhimurium and E. coli at the nucleotide level is above average (22.4%). However, a high level of conservation at the protein level, which ranged from 86% amino acid homology for the fiber subunit CsgA to 99% homology for the lipoprotein CsgG, implies functional constraints on the gene products. Consequently, S. typhimurium genes on low-copy-number plasmids were able to complement respective E. coli mutants, although not always to wild-type levels. rpoS and ompR are required for transcriptional activation of (at least) the csgD promoter. The high degree of conservation at the protein level and the identical regulation patterns in E. coli and S. typhimurium suggest similar roles of curli fibers in the same ecological niche in the two species. PMID:9457880

  17. Conserved host response to highly pathogenic avian influenza virus infection in human cell culture, mouse and macaque model systems

    Directory of Open Access Journals (Sweden)

    McDermott Jason E

    2011-11-01

    Full Text Available Abstract Background Understanding host response to influenza virus infection will facilitate development of better diagnoses and therapeutic interventions. Several different experimental models have been used as a proxy for human infection, including cell cultures derived from human cells, mice, and non-human primates. Each of these systems has been studied extensively in isolation, but little effort has been directed toward systematically characterizing the conservation of host response on a global level beyond known immune signaling cascades. Results In the present study, we employed a multivariate modeling approach to characterize and compare the transcriptional regulatory networks between these three model systems after infection with a highly pathogenic avian influenza virus of the H5N1 subtype. Using this approach we identified functions and pathways that display similar behavior and/or regulation including the well-studied impact on the interferon response and the inflammasome. Our results also suggest a primary response role for airway epithelial cells in initiating hypercytokinemia, which is thought to contribute to the pathogenesis of H5N1 viruses. We further demonstrate that we can use a transcriptional regulatory model from the human cell culture data to make highly accurate predictions about the behavior of important components of the innate immune system in tissues from whole organisms. Conclusions This is the first demonstration of a global regulatory network modeling conserved host response between in vitro and in vivo models.

  18. Catchment-scale conservation units identified for the threatened Yarra pygmy perch (Nannoperca obscura) in highly modified river systems.

    Science.gov (United States)

    Brauer, Chris J; Unmack, Peter J; Hammer, Michael P; Adams, Mark; Beheregaray, Luciano B

    2013-01-01

    Habitat fragmentation caused by human activities alters metapopulation dynamics and decreases biological connectivity through reduced migration and gene flow, leading to lowered levels of population genetic diversity and to local extinctions. The threatened Yarra pygmy perch, Nannoperca obscura, is a poor disperser found in small, isolated populations in wetlands and streams of southeastern Australia. Modifications to natural flow regimes in anthropogenically-impacted river systems have recently reduced the amount of habitat for this species and likely further limited its opportunity to disperse. We employed highly resolving microsatellite DNA markers to assess genetic variation, population structure and the spatial scale that dispersal takes place across the distribution of this freshwater fish and used this information to identify conservation units for management. The levels of genetic variation found for N. obscura are amongst the lowest reported for a fish species (mean heterozygosity of 0.318 and mean allelic richness of 1.92). We identified very strong population genetic structure, nil to little evidence of recent migration among demes and a minimum of 11 units for conservation management, hierarchically nested within four major genetic lineages. A combination of spatial analytical methods revealed hierarchical genetic structure corresponding with catchment boundaries and also demonstrated significant isolation by riverine distance. Our findings have implications for the national recovery plan of this species by demonstrating that N. obscura populations should be managed at a catchment level and highlighting the need to restore habitat and avoid further alteration of the natural hydrology.

  19. High Elevation Refugia for Bombus terricola (Hymenoptera: Apidae) Conservation and Wild Bees of the White Mountain National Forest.

    Science.gov (United States)

    Tucker, Erika M; Rehan, Sandra M

    2017-01-01

    Many wild bee species are in global decline, yet much is still unknown about their diversity and contemporary distributions. National parks and forests offer unique areas of refuge important for the conservation of rare and declining species populations. Here we present the results of the first biodiversity survey of the bee fauna in the White Mountain National Forest (WMNF). More than a thousand specimens were collected from pan and sweep samples representing 137 species. Three species were recorded for the first time in New England and an additional seven species were documented for the first time in the state of New Hampshire. Four introduced species were also observed in the specimens collected. A checklist of the species found in the WMNF, as well as those found previously in Strafford County, NH, is included with new state records and introduced species noted as well as a map of collecting locations. Of particular interest was the relatively high abundance of Bombus terricola Kirby 1837 found in many of the higher elevation collection sites and the single specimen documented of Bombus fervidus (Fabricius 1798). Both of these bumble bee species are known to have declining populations in the northeast and are categorized as vulnerable on the International Union for Conservation of Nature's Red List. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America.

  20. Characterization of STIP, a multi-domain nuclear protein, highly conserved in metazoans, and essential for embryogenesis in Caenorhabditis elegans

    International Nuclear Information System (INIS)

    Ji Qiongmei; Huang, C.-H.; Peng Jianbin; Hashmi, Sarwar; Ye Tianzhang; Chen Ying

    2007-01-01

    We report here the identification and characterization of STIP, a multi-domain nuclear protein that contains a G-patch, a coiled-coil, and several short tryptophan-tryptophan repeats highly conserved in metazoan species. To analyze their functional role in vivo, we cloned nematode stip-1 genes and determined the spatiotemporal pattern of Caenorhabditis elegans STIP-1 protein. RNA analyses and Western blots revealed that stip-1 mRNA was produced via trans-splicing and translated as a 95-kDa protein. Using reporter constructs, we found STIP-1 to be expressed at all developmental stages and in many tissue/cell types including worm oocyte nuclei. We found that STIP-1 is targeted to the nucleus and forms large polymers with a rod-like shape when expressed in mammalian cells. Using deletion mutants, we mapped the regions of STIP-1 involved in nuclear import and polymer assembly. We further showed that knockdown of C. elegans stip-1 by RNA interference arrested development and resulted in morphologic abnormalities around the 16-cell stage followed by 100% lethality, suggesting its essential role in worm embryogenesis. Importantly, the embryonic lethal phenotype could be faithfully rescued with Drosophila and human genes via transgenic expression. Our data provide the first direct evidence that STIP have a conserved essential nuclear function across metazoans from worms to humans

  1. High Re-Operation Rates Using Conserve Metal-On-Metal Total Hip Articulations

    DEFF Research Database (Denmark)

    Mogensen, S L; Jakobsen, Thomas; Christoffersen, Hardy

    2016-01-01

    INTRODUCTION: Metal-on-metal hip articulations have been intensely debated after reports of adverse reactions and high failure rates. The aim of this study was to retrospectively evaluate the implant of a metal-on.metal total hip articulation (MOM THA) from a single manufacture in a two-center st......INTRODUCTION: Metal-on-metal hip articulations have been intensely debated after reports of adverse reactions and high failure rates. The aim of this study was to retrospectively evaluate the implant of a metal-on.metal total hip articulation (MOM THA) from a single manufacture in a two...

  2. High spatial resolution mapping of land cover types in a priority area for conservation in the Brazilian savanna

    Science.gov (United States)

    Ribeiro, F.; Roberts, D. A.; Hess, L. L.; Davis, F. W.; Caylor, K. K.; Nackoney, J.; Antunes Daldegan, G.

    2017-12-01

    Savannas are heterogeneous landscapes consisting of highly mixed land cover types that lack clear distinct boundaries. The Brazilian Cerrado is a Neotropical savanna considered a biodiversity hotspot for conservation due to its biodiversity richness and rapid transformation of its landscape by crop and pasture activities. The Cerrado is one of the most threatened Brazilian biomes and only 2.2% of its original extent is strictly protected. Accurate mapping and monitoring of its ecosystems and adjacent land use are important to select areas for conservation and to improve our understanding of the dynamics in this biome. Land cover mapping of savannas is difficult due to spectral similarity between land cover types resulting from similar vegetation structure, floristically similar components, generalization of land cover classes, and heterogeneity usually expressed as small patch sizes within the natural landscape. These factors are the major contributor to misclassification and low map accuracies among remote sensing studies in savannas. Specific challenges to map the Cerrado's land cover types are related to the spectral similarity between classes of land use and natural vegetation, such as natural grassland vs. cultivated pasture, and forest ecosystem vs. crops. This study seeks to classify and evaluate the land cover patterns across an area ranked as having extremely high priority for future conservation in the Cerrado. The main objective of this study is to identify the representativeness of each vegetation type across the landscape using high to moderate spatial resolution imagery using an automated scheme. A combination of pixel-based and object-based approaches were tested using RapidEye 3A imagery (5m spatial resolution) to classify the Cerrado's major land cover types. The random forest classifier was used to map the major ecosystems present across the area, and demonstrated to have an effective result with 68% of overall accuracy. Post

  3. Identification of a highly conserved valine-glycine-phenylalanine amino acid triplet required for HIV-1 Nef function

    Directory of Open Access Journals (Sweden)

    Meuwissen Pieter J

    2012-04-01

    Full Text Available Abstract Background The Nef protein of HIV facilitates virus replication and disease progression in infected patients. This role as pathogenesis factor depends on several genetically separable Nef functions that are mediated by interactions of highly conserved protein-protein interaction motifs with different host cell proteins. By studying the functionality of a series of nef alleles from clinical isolates, we identified a dysfunctional HIV group O Nef in which a highly conserved valine-glycine-phenylalanine (VGF region, which links a preceding acidic cluster with the following proline-rich motif into an amphipathic surface was deleted. In this study, we aimed to study the functional importance of this VGF region. Results The dysfunctional HIV group O8 nef allele was restored to the consensus sequence, and mutants of canonical (NL4.3, NA-7, SF2 and non-canonical (B2 and C1422 HIV-1 group M nef alleles were generated in which the amino acids of the VGF region were changed into alanines (VGF→AAA and tested for their capacity to interfere with surface receptor trafficking, signal transduction and enhancement of viral replication and infectivity. We found the VGF motif, and each individual amino acid of this motif, to be critical for downregulation of MHC-I and CXCR4. Moreover, Nef’s association with the cellular p21-activated kinase 2 (PAK2, the resulting deregulation of cofilin and inhibition of host cell actin remodeling, and targeting of Lck kinase to the trans-golgi-network (TGN were affected as well. Of particular interest, VGF integrity was essential for Nef-mediated enhancement of HIV virion infectivity and HIV replication in peripheral blood lymphocytes. For targeting of Lck kinase to the TGN and viral infectivity, especially the phenylalanine of the triplet was essential. At the molecular level, the VGF motif was required for the physical interaction of the adjacent proline-rich motif with Hck. Conclusion Based on these findings, we

  4. Ancient Exaptation of a CORE-SINE Retroposon into a Highly Conserved Mammalian Neuronal Enhancer of the Proopiomelanocortin Gene

    Science.gov (United States)

    Bumaschny, Viviana F; Low, Malcolm J; Rubinstein, Marcelo

    2007-01-01

    The proopiomelanocortin gene (POMC) is expressed in the pituitary gland and the ventral hypothalamus of all jawed vertebrates, producing several bioactive peptides that function as peripheral hormones or central neuropeptides, respectively. We have recently determined that mouse and human POMC expression in the hypothalamus is conferred by the action of two 5′ distal and unrelated enhancers, nPE1 and nPE2. To investigate the evolutionary origin of the neuronal enhancer nPE2, we searched available vertebrate genome databases and determined that nPE2 is a highly conserved element in placentals, marsupials, and monotremes, whereas it is absent in nonmammalian vertebrates. Following an in silico paleogenomic strategy based on genome-wide searches for paralog sequences, we discovered that opossum and wallaby nPE2 sequences are highly similar to members of the superfamily of CORE-short interspersed nucleotide element (SINE) retroposons, in particular to MAR1 retroposons that are widely present in marsupial genomes. Thus, the neuronal enhancer nPE2 originated from the exaptation of a CORE-SINE retroposon in the lineage leading to mammals and remained under purifying selection in all mammalian orders for the last 170 million years. Expression studies performed in transgenic mice showed that two nonadjacent nPE2 subregions are essential to drive reporter gene expression into POMC hypothalamic neurons, providing the first functional example of an exapted enhancer derived from an ancient CORE-SINE retroposon. In addition, we found that this CORE-SINE family of retroposons is likely to still be active in American and Australian marsupial genomes and that several highly conserved exonic, intronic and intergenic sequences in the human genome originated from the exaptation of CORE-SINE retroposons. Together, our results provide clear evidence of the functional novelties that transposed elements contributed to their host genomes throughout evolution. PMID:17922573

  5. Ancient exaptation of a CORE-SINE retroposon into a highly conserved mammalian neuronal enhancer of the proopiomelanocortin gene.

    Directory of Open Access Journals (Sweden)

    Andrea M Santangelo

    2007-10-01

    Full Text Available The proopiomelanocortin gene (POMC is expressed in the pituitary gland and the ventral hypothalamus of all jawed vertebrates, producing several bioactive peptides that function as peripheral hormones or central neuropeptides, respectively. We have recently determined that mouse and human POMC expression in the hypothalamus is conferred by the action of two 5' distal and unrelated enhancers, nPE1 and nPE2. To investigate the evolutionary origin of the neuronal enhancer nPE2, we searched available vertebrate genome databases and determined that nPE2 is a highly conserved element in placentals, marsupials, and monotremes, whereas it is absent in nonmammalian vertebrates. Following an in silico paleogenomic strategy based on genome-wide searches for paralog sequences, we discovered that opossum and wallaby nPE2 sequences are highly similar to members of the superfamily of CORE-short interspersed nucleotide element (SINE retroposons, in particular to MAR1 retroposons that are widely present in marsupial genomes. Thus, the neuronal enhancer nPE2 originated from the exaptation of a CORE-SINE retroposon in the lineage leading to mammals and remained under purifying selection in all mammalian orders for the last 170 million years. Expression studies performed in transgenic mice showed that two nonadjacent nPE2 subregions are essential to drive reporter gene expression into POMC hypothalamic neurons, providing the first functional example of an exapted enhancer derived from an ancient CORE-SINE retroposon. In addition, we found that this CORE-SINE family of retroposons is likely to still be active in American and Australian marsupial genomes and that several highly conserved exonic, intronic and intergenic sequences in the human genome originated from the exaptation of CORE-SINE retroposons. Together, our results provide clear evidence of the functional novelties that transposed elements contributed to their host genomes throughout evolution.

  6. Identification of immunogenic HLA-B7 "Achilles' heel" epitopes within highly conserved regions of HIV

    DEFF Research Database (Denmark)

    De Groot, Anne S; Rivera, Daniel S; McMurry, Julie A

    2008-01-01

    Genetic polymorphisms in class I human leukocyte antigen molecules (HLA) have been shown to determine susceptibility to HIV infection as well as the rate of progression to AIDS. In particular, the HLA-B7 supertype has been shown to be associated with high viral loads and rapid progression to dise...

  7. A highly conserved Poc1 protein characterized in embryos of the hydrozoan Clytia hemisphaerica: localization and functional studies.

    Directory of Open Access Journals (Sweden)

    Cécile Fourrage

    Full Text Available Poc1 (Protein of Centriole 1 proteins are highly conserved WD40 domain-containing centriole components, well characterized in the alga Chlamydomonas, the ciliated protazoan Tetrahymena, the insect Drosophila and in vertebrate cells including Xenopus and zebrafish embryos. Functions and localizations related to the centriole and ciliary axoneme have been demonstrated for Poc1 in a range of species. The vertebrate Poc1 protein has also been reported to show an additional association with mitochondria, including enrichment in the specialized "germ plasm" region of Xenopus oocytes. We have identified and characterized a highly conserved Poc1 protein in the cnidarian Clytia hemisphaerica. Clytia Poc1 mRNA was found to be strongly expressed in eggs and early embryos, showing a punctate perinuclear localization in young oocytes. Fluorescence-tagged Poc1 proteins expressed in developing embryos showed strong localization to centrioles, including basal bodies. Anti-human Poc1 antibodies decorated mitochondria in Clytia, as reported in human cells, but failed to recognise endogenous or fluorescent-tagged Clytia Poc1. Injection of specific morpholino oligonucleotides into Clytia eggs prior to fertilization to repress Poc1 mRNA translation interfered with cell division from the blastula stage, likely corresponding to when neosynthesis normally takes over from maternally supplied protein. Cell cycle lengthening and arrest were observed, phenotypes consistent with an impaired centriolar biogenesis or function. The specificity of the defects could be demonstrated by injection of synthetic Poc1 mRNA, which restored normal development. We conclude that in Clytia embryos, Poc1 has an essentially centriolar localization and function.

  8. Computation and Analysis of High Rocky Slope Safety in a Water Conservancy Project

    Directory of Open Access Journals (Sweden)

    Meng Yang

    2015-01-01

    Full Text Available An integrated method, covering the actual monitoring analysis, practical geological model, and theoretical mathematical simulation model, is systematically proposed and successfully applied. Deformation characteristic of a unique high rocky slope was firstly analyzed from multiple angles and multiple layers by changeable elevations and distances. Arrangements of monitoring points were listed and monitoring equipment was designed to comprise a complete monitoring system. Present larger displacement was concluded for bottom larger displacement caused by water erosion and middle larger displacement formed by seepage. Temporal and spatial displacements rule study of multiple-points linkage effects with water factor proved this conclusion. To better excavate useful message and analyze the deep rule from the practical monitoring data, the slope geological model was conducted and rock mechanic parameters were researched. Finally, a unique three-dimensional finite element model was applied to approach the structure character using numerical simulations. The corresponding strength criterion was used to determine the safety coefficient by selecting a typical section. Subsequently, an integrated three-dimensional finite element model of the slope and dam was developed and more detailed deformation evolution mechanism was revealed. This study is expected to provide a powerful and systematic method to analyze very high, important, and dangerous slopes.

  9. Constrained instanton and baryon number non-conservation at high energies

    International Nuclear Information System (INIS)

    Sil'vestrov, P.G.

    1992-01-01

    The main subject of this paper is the calculation of corrections to instanton action ΔS∼(mρ) 4 log(mρ)/g 2 (ρ is the intanton radius) in the SU(2) Yang-Mills theory. The total cross section for baryon number violating processes at high energies is usually parametrized as σ tat ∝exp(4π/αF(ε)), where α=g 2 /4π, ε=√s/E 0 , E 0 =√6πm w /α. In the present paper the third nontrivial term of the F(ε) expansion is obtained. The unknown correction to F(ε) are expected to be of the order of ε 8/3 . The total cross section is extremely sensitive to the value of single instanton action. For sufficiently heavy Higgs boson the ρ-dependent part of the instanton action is changed drastically. 21 refs.; 1 fig

  10. Mice selectively bred for high voluntary wheel-running behavior conserve more fat despite increased exercise.

    Science.gov (United States)

    Hiramatsu, Layla; Garland, Theodore

    2018-04-20

    Physical activity is an important component of energy expenditure, and acute changes in activity can lead to energy imbalances that affect body composition, even under ad libitum food availability. One example of acute increases in physical activity is four replicate, selectively-bred High Runner (HR) lines of mice that voluntarily run ~3-fold more wheel revolutions per day over 6-day trials and are leaner, as compared with four non-selected control (C) lines. We expected that voluntary exercise would increase food consumption, build lean mass, and reduce fat mass, but that these effects would likely differ between HR and C lines or between the sexes. We compared wheel running, cage activity, food consumption, and body composition between HR and C lines for young adults of both sexes, and examined interrelationships of those traits across 6 days of wheel access. Before wheel testing, HR mice weighed less than C, primarily due to reduced lean mass, and females were lighter than males, entirely due to lower lean mass. Over 6 days of wheel access, all groups tended to gain small amounts of lean mass, but lose fat mass. HR mice lost less fat than C mice, in spite of much higher activity levels, resulting in convergence to a fat mass of ~1.7 g for all 4 groups. HR mice consumed more food than C mice (with body mass as a covariate), even accounting for their higher activity levels. No significant sex-by-linetype interactions were observed for any of the foregoing traits. Structural equation models showed that the four sex-by-linetype groups differed considerably in the complex phenotypic architecture of these traits. Interrelationships among traits differed by genetic background and sex, lending support to the idea that recommendations regarding weight management, diet, and exercise may need to be tailored to the individual level. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Expression and genomic analysis of midasin, a novel and highly conserved AAA protein distantly related to dynein

    Directory of Open Access Journals (Sweden)

    Gibbons I R

    2002-07-01

    Full Text Available Abstract Background The largest open reading frame in the Saccharomyces genome encodes midasin (MDN1p, YLR106p, an AAA ATPase of 560 kDa that is essential for cell viability. Orthologs of midasin have been identified in the genome projects for Drosophila, Arabidopsis, and Schizosaccharomyces pombe. Results Midasin is present as a single-copy gene encoding a well-conserved protein of ~600 kDa in all eukaryotes for which data are available. In humans, the gene maps to 6q15 and encodes a predicted protein of 5596 residues (632 kDa. Sequence alignments of midasin from humans, yeast, Giardia and Encephalitozoon indicate that its domain structure comprises an N-terminal domain (35 kDa, followed by an AAA domain containing six tandem AAA protomers (~30 kDa each, a linker domain (260 kDa, an acidic domain (~70 kDa containing 35–40% aspartate and glutamate, and a carboxy-terminal M-domain (30 kDa that possesses MIDAS sequence motifs and is homologous to the I-domain of integrins. Expression of hemagglutamin-tagged midasin in yeast demonstrates a polypeptide of the anticipated size that is localized principally in the nucleus. Conclusions The highly conserved structure of midasin in eukaryotes, taken in conjunction with its nuclear localization in yeast, suggests that midasin may function as a nuclear chaperone and be involved in the assembly/disassembly of macromolecular complexes in the nucleus. The AAA domain of midasin is evolutionarily related to that of dynein, but it appears to lack a microtubule-binding site.

  12. Toxicity and cosmetic result of partial breast high-dose-rate interstitial brachytherapy for conservatively operated early breast cancer

    International Nuclear Information System (INIS)

    Xiu Xia; Tripuraneni Prabhakar; Giap Huan; Lin Ray; Chu Colin

    2007-01-01

    Objective: Objective To study the method, side effects and cosmetic outcome of high- dose-rate (HDR) accelerated partial breast interstitial irradiation (APBI) alone in early stage breast cancer' after conservative surgery. Methods: From February 2002 to June 2003,47 breast cancer lesions from 46 patients suffering from stage I/II breast cancer were treated with HDR 192 Ir APBI after conservative surgery. All patients were over 40 year-old, with T1-2N0-1 (≤3 lymph nodes positive), surgical margin > 1-2 mm, but those having lobular or inflammatory breast cancer were excluded. HDR brachytherapy with 34 Gy, 10 fractions/5 days was used after surgery, toxic reaction and cosmetic outcome were observed in one month, 6 and 12 months respectively. Results: Follow up of 1846 months, 34 months was carried out for the whole group. During the treatment, acute reactions including: erythema, edema, tenderness and infection, all under I-II grade, none of III-IV grade were observed in 21 patients(46%); late toxicity reactions: skin fibrosis, breast tenderness, fat necrosis, and telangiectasia, totally 20 patients (43%) were observed: 2 patients in III grade but one patient received 6 cycle chemotherapy. The result of cosmetic outcome evaluation was excellent or good, at 6 months 95% and 12 months 98%, respectively, but there was no recurfence. Conclusions: Excellent and favorable cosmetic results are noted after APBI by interstitial alone. Acute and late reactions are few. Long term observation is necessary for the rate of' local control. (authors)

  13. Comparative genome sequencing of Drosophila pseudoobscura: Chromosomal, gene, and cis-element evolution

    DEFF Research Database (Denmark)

    Richards, Stephen; Liu, Yue; Bettencourt, Brian R.

    2005-01-01

    years (Myr) since the pseudoobscura/melanogaster divergence. Genes expressed in the testes had higher amino acid sequence divergence than the genome-wide average, consistent with the rapid evolution of sex-specific proteins. Cis-regulatory sequences are more conserved than random and nearby sequences......We have sequenced the genome of a second Drosophila species, Drosophila pseudoobscura, and compared this to the genome sequence of Drosophila melanogaster, a primary model organism. Throughout evolution the vast majority of Drosophila genes have remained on the same chromosome arm, but within each...... between the species-but the difference is slight, suggesting that the evolution of cis-regulatory elements is flexible. Overall, a pattern of repeat-mediated chromosomal rearrangement, and high coadaptation of both male genes and cis-regulatory sequences emerges as important themes of genome divergence...

  14. Distinct activation phenotype of a highly conserved novel HLA-B57-restricted epitope during dengue virus infection.

    Science.gov (United States)

    Townsley, Elizabeth; Woda, Marcia; Thomas, Stephen J; Kalayanarooj, Siripen; Gibbons, Robert V; Nisalak, Ananda; Srikiatkhachorn, Anon; Green, Sharone; Stephens, Henry A F; Rothman, Alan L; Mathew, Anuja

    2014-01-01

    Variation in the sequence of T-cell epitopes between dengue virus (DENV) serotypes is believed to alter memory T-cell responses during second heterologous infections. We identified a highly conserved, novel, HLA-B57-restricted epitope on the DENV NS1 protein. We predicted higher frequencies of B57-NS1(26-34) -specific CD8(+) T cells in peripheral blood mononuclear cells from individuals undergoing secondary rather than primary DENV infection. However, high tetramer-positive T-cell frequencies during acute infection were seen in only one of nine subjects with secondary infection. B57-NS1(26-34) -specific and other DENV epitope-specific CD8(+) T cells, as well as total CD8(+) T cells, expressed an activated phenotype (CD69(+) and/or CD38(+)) during acute infection. In contrast, expression of CD71 was largely limited to DENV epitope-specific CD8(+) T cells. In vitro stimulation of cell lines indicated that CD71 expression was differentially sensitive to stimulation by homologous and heterologous variant peptides. CD71 may represent a useful marker of antigen-specific T-cell activation. © 2013 John Wiley & Sons Ltd.

  15. A Web-Based GIS for Reporting Water Usage in the High Plains Underground Water Conservation District

    Science.gov (United States)

    Jia, M.; Deeds, N.; Winckler, M.

    2012-12-01

    The High Plains Underground Water Conservation District (HPWD) is the largest and oldest of the Texas water conservation districts, and oversees approximately 1.7 million irrigated acres. Recent rule changes have motivated HPWD to develop a more automated system to allow owners and operators to report well locations, meter locations, meter readings, the association between meters and wells, and contiguous acres. INTERA, Inc. has developed a web-based interactive system for HPWD water users to report water usage and for the district to better manage its water resources. The HPWD web management system utilizes state-of-the-art GIS techniques, including cloud-based Amazon EC2 virtual machine, ArcGIS Server, ArcSDE and ArcGIS Viewer for Flex, to support web-based water use management. The system enables users to navigate to their area of interest using a well-established base-map and perform a variety of operations and inquiries against their spatial features. The application currently has six components: user privilege management, property management, water meter registration, area registration, meter-well association and water use report. The system is composed of two main databases: spatial database and non-spatial database. With the help of Adobe Flex application at the front end and ArcGIS Server as the middle-ware, the spatial feature geometry and attributes update will be reflected immediately in the back end. As a result, property owners, along with the HPWD staff, collaborate together to weave the fabric of the spatial database. Interactions between the spatial and non-spatial databases are established by Windows Communication Foundation (WCF) services to record water-use report, user-property associations, owner-area associations, as well as meter-well associations. Mobile capabilities will be enabled in the near future for field workers to collect data and synchronize them to the spatial database. The entire solution is built on a highly scalable cloud

  16. Conservation Value

    OpenAIRE

    Tisdell, Clement A.

    2010-01-01

    This paper outlines the significance of the concept of conservation value and discusses ways in which it is determined paying attention to views stemming from utilitarian ethics and from deontological ethics. The importance of user costs in relation to economic decisions about the conservation and use of natural resources is emphasised. Particular attention is given to competing views about the importance of conserving natural resources in order to achieve economic sustainability. This then l...

  17. Loss of a highly conserved sterile alpha motif domain gene (WEEP) results in pendulous branch growth in peach trees.

    Science.gov (United States)

    Hollender, Courtney A; Pascal, Thierry; Tabb, Amy; Hadiarto, Toto; Srinivasan, Chinnathambi; Wang, Wanpeng; Liu, Zhongchi; Scorza, Ralph; Dardick, Chris

    2018-05-15

    Plant shoots typically grow upward in opposition to the pull of gravity. However, exceptions exist throughout the plant kingdom. Most conspicuous are trees with weeping or pendulous branches. While such trees have long been cultivated and appreciated for their ornamental value, the molecular basis behind the weeping habit is not known. Here, we characterized a weeping tree phenotype in Prunus persica (peach) and identified the underlying genetic mutation using a genomic sequencing approach. Weeping peach tree shoots exhibited a downward elliptical growth pattern and did not exhibit an upward bending in response to 90° reorientation. The causative allele was found to be an uncharacterized gene, Ppa013325 , having a 1.8-Kb deletion spanning the 5' end. This gene, dubbed WEEP , was predominantly expressed in phloem tissues and encodes a highly conserved 129-amino acid protein containing a sterile alpha motif (SAM) domain. Silencing WEEP in the related tree species Prunus domestica (plum) resulted in more outward, downward, and wandering shoot orientations compared to standard trees, supporting a role for WEEP in directing lateral shoot growth in trees. This previously unknown regulator of branch orientation, which may also be a regulator of gravity perception or response, provides insights into our understanding of how tree branches grow in opposition to gravity and could serve as a critical target for manipulating tree architecture for improved tree shape in agricultural and horticulture applications. Copyright © 2018 the Author(s). Published by PNAS.

  18. Neuronal patterning of the tubular collar cord is highly conserved among enteropneusts but dissimilar to the chordate neural tube.

    Science.gov (United States)

    Kaul-Strehlow, Sabrina; Urata, Makoto; Praher, Daniela; Wanninger, Andreas

    2017-08-01

    A tubular nervous system is present in the deuterostome groups Chordata (cephalochordates, tunicates, vertebrates) and in the non-chordate Enteropneusta. However, the worm-shaped enteropneusts possess a less complex nervous system featuring only a short hollow neural tube, whereby homology to its chordate counterpart remains elusive. Since the majority of data on enteropneusts stem from the harrimaniid Saccoglossus kowalevskii, putative interspecific variations remain undetected resulting in an unreliable ground pattern that impedes homology assessments. In order to complement the missing data from another enteropneust family, we investigated expression of key neuronal patterning genes in the ptychoderid Balanoglossus misakiensis. The collar cord of B. misakiensis shows anterior Six3/6 and posterior Otx + Engrailed expression, in a region corresponding to the chordate brain. Neuronal Nk2.1/Nk2.2 expression is absent. Interestingly, we found median Dlx and lateral Pax6 expression domains, i.e., a condition that is reversed compared to chordates. Comparative analyses reveal that adult nervous system patterning is highly conserved among the enteropneust families Harrimaniidae, Spengelidae and Ptychoderidae. BmiDlx and BmiPax6 have no corresponding expression domains in the chordate brain, which may be indicative of independent acquisition of a tubular nervous system in Enteropneusta and Chordata.

  19. Assessment of some high-order finite difference schemes on the scalar conservation law with periodical conditions

    Directory of Open Access Journals (Sweden)

    Alina BOGOI

    2016-12-01

    Full Text Available Supersonic/hypersonic flows with strong shocks need special treatment in Computational Fluid Dynamics (CFD in order to accurately capture the discontinuity location and his magnitude. To avoid numerical instabilities in the presence of discontinuities, the numerical schemes must generate low dissipation and low dispersion error. Consequently, the algorithms used to calculate the time and space-derivatives, should exhibit a low amplitude and phase error. This paper focuses on the comparison of the numerical results obtained by simulations with some high resolution numerical schemes applied on linear and non-linear one-dimensional conservation low. The analytical solutions are provided for all benchmark tests considering smooth periodical conditions. All the schemes converge to the proper weak solution for linear flux and smooth initial conditions. However, when the flux is non-linear, the discontinuities may develop from smooth initial conditions and the shock must be correctly captured. All the schemes accurately identify the shock position, with the price of the numerical oscillation in the vicinity of the sudden variation. We believe that the identification of this pure numerical behavior, without physical relevance, in 1D case is extremely useful to avoid problems related to the stability and convergence of the solution in the general 3D case.

  20. A highly Conserved Aspartic Acid Residue of the Chitosanase from Bacillus Sp. TS Is Involved in the Substrate Binding.

    Science.gov (United States)

    Zhou, Zhanping; Zhao, Shuangzhi; Liu, Yang; Chang, Zhengying; Ma, Yanhe; Li, Jian; Song, Jiangning

    2016-11-01

    The chitosanase from Bacillus sp. TS (CsnTS) is an enzyme belonging to the glycoside hydrolase family 8. The sequence of CsnTS shares 98 % identity with the chitosanase from Bacillus sp. K17. Crystallography analysis and site-direct mutagenesis of the chitosanase from Bacillus sp. K17 identified the important residues involved in the catalytic interaction and substrate binding. However, despite progress in understanding the catalytic mechanism of the chitosanase from the family GH8, the functional roles of some residues that are highly conserved throughout this family have not been fully elucidated. This study focused on one of these residues, i.e., the aspartic acid residue at position 318. We found that apart from asparagine, mutation of Asp318 resulted in significant loss of enzyme activity. In-depth investigations showed that mutation of this residue not only impaired enzymatic activity but also affected substrate binding. Taken together, our results showed that Asp318 plays an important role in CsnTS activity.

  1. The highly conserved codon following the slippery sequence supports -1 frameshift efficiency at the HIV-1 frameshift site.

    Directory of Open Access Journals (Sweden)

    Suneeth F Mathew

    Full Text Available HIV-1 utilises -1 programmed ribosomal frameshifting to translate structural and enzymatic domains in a defined proportion required for replication. A slippery sequence, U UUU UUA, and a stem-loop are well-defined RNA features modulating -1 frameshifting in HIV-1. The GGG glycine codon immediately following the slippery sequence (the 'intercodon' contributes structurally to the start of the stem-loop but has no defined role in current models of the frameshift mechanism, as slippage is inferred to occur before the intercodon has reached the ribosomal decoding site. This GGG codon is highly conserved in natural isolates of HIV. When the natural intercodon was replaced with a stop codon two different decoding molecules-eRF1 protein or a cognate suppressor tRNA-were able to access and decode the intercodon prior to -1 frameshifting. This implies significant slippage occurs when the intercodon is in the (perhaps distorted ribosomal A site. We accommodate the influence of the intercodon in a model of frame maintenance versus frameshifting in HIV-1.

  2. The implications of RCRA [Resource Conservation and Recovery Act] regulation for the disposal of transuranic and high-level waste

    International Nuclear Information System (INIS)

    Sigmon, C.F.; Sharples, F.E.; Smith, E.D.

    1988-01-01

    In May of 1987 the Department of Energy (DOE) published a rule interpreting the definition of ''byproduct'' under the Atomic Energy Act. This byproduct rule clarified the role of the Resource Conservation and Recovery Act (RCRA) in the regulation of DOE's radioactive waste management activities. According to the rule, only the radioactive portion of DOE's mixed radioactive and hazardous waste (mixed waste), including mixed transuranic (TRU) and high-level waste (HLW), is exempt from RCRA under the byproduct exemption. The portion of a waste that is hazardous as defined by RCRA is subject to full regulation under RCRA. Because the radioactive and hazardous portions of m any, if not most, DOE wastes are likely to be inseparable, the rule in effect makes most mixed wastes subject to dual regulation. The potential application of RCRA to facilities such as the Waste Isolation Pilot Plant (WIPP) and the HLW repository creates unique challenges for both the DOE and regulatory authorities. Strategies must be developed to assure compliance with RCRA without either causing excessive administrative burdens or abandoning the goal of minimizing radiation exposure. This paper will explore some of the potential regulatory options for and recent trends in the regulation of TRU and HLW under RCRA

  3. Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly

    Directory of Open Access Journals (Sweden)

    Solbak Sara MØ

    2011-02-01

    Full Text Available Abstract Background The HIV-1 p6 Gag protein regulates the final abscission step of nascent virions from the cell membrane by the action of two late assembly (L- domains. Although p6 is located within one of the most polymorphic regions of the HIV-1 gag gene, the 52 amino acid peptide binds at least to two cellular budding factors (Tsg101 and ALIX, is a substrate for phosphorylation, ubiquitination, and sumoylation, and mediates the incorporation of the HIV-1 accessory protein Vpr into viral particles. As expected, known functional domains mostly overlap with several conserved residues in p6. In this study, we investigated the importance of the highly conserved serine residue at position 40, which until now has not been assigned to any known function of p6. Results Consistently with previous data, we found that mutation of Ser-40 has no effect on ALIX mediated rescue of HIV-1 L-domain mutants. However, the only feasible S40F mutation that preserves the overlapping pol open reading frame (ORF reduces virus replication in T-cell lines and in human lymphocyte tissue cultivated ex vivo. Most intriguingly, L-domain mediated virus release is not dependent on the integrity of Ser-40. However, the S40F mutation significantly reduces the specific infectivity of released virions. Further, it was observed that mutation of Ser-40 selectively interferes with the cleavage between capsid (CA and the spacer peptide SP1 in Gag, without affecting cleavage of other Gag products. This deficiency in processing of CA, in consequence, led to an irregular morphology of the virus core and the formation of an electron dense extra core structure. Moreover, the defects induced by the S40F mutation in p6 can be rescued by the A1V mutation in SP1 that generally enhances processing of the CA-SP1 cleavage site. Conclusions Overall, these data support a so far unrecognized function of p6 mediated by Ser-40 that occurs independently of the L-domain function, but selectively

  4. High conservation level of CD8(+) T cell immunogenic regions within an unusual H1N2 human influenza variant.

    Science.gov (United States)

    Komadina, Naomi; Quiñones-Parra, Sergio M; Kedzierska, Katherine; McCaw, James M; Kelso, Anne; Leder, Karin; McVernon, Jodie

    2016-10-01

    Current seasonal influenza vaccines require regular updates due to antigenic drift causing loss of effectiveness and therefore providing little or no protection against novel influenza A subtypes. Next generation vaccines capable of eliciting CD8(+) T cell (CTL) mediated cross-protective immunity may offer a long-term alternative strategy. However, measuring pre- and existing levels of CTL cross-protection in humans is confounded by differences in infection histories across individuals. During 2000-2003, H1N2 viruses circulated persistently in the human population for the first time and we hypothesized that the viral nucleoprotein (NP) contained novel CTL epitopes that may have contributed to the survival of the viruses. This study describes the immunogenic NP peptides of H1N1, H2N2, and H3N2 influenza viruses isolated from humans over the past century, 1918-2003, by comparing this historical dataset to reference NP peptides from H1N2 that circulated in humans during 2000-2003. Observed peptides sequences ranged from highly conserved (15%) to highly variable (12%), with variation unrelated to reported immunodominance. No unique NP peptides which were exclusive to the H1N2 viruses were noted. However, the virus had inherited the NP from a recently emerged H3N2 variant containing novel peptides, which may have assisted its persistence. Any advantage due to this novelty was subsequently lost with emergence of a newer H3N2 variant in 2003. Our approach has potential to provide insight into the population context in which influenza viruses emerge, and may help to inform immunogenic peptide selection for CTL-inducing influenza vaccines. J. Med. Virol. 88:1725-1732, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  5. 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.

  6. 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.

  7. Surgical versus conservative treatment for high-risk stress fractures of the lower leg (anterior tibial cortex, navicular and fifth metatarsal base): a systematic review

    NARCIS (Netherlands)

    Mallee, W.H.; Weel, H.; van Dijk, C.N.; van Tulder, M.W.; Kerkhoffs, G.M.; Lin, C.W.C.

    2015-01-01

    Aim To compare surgical and conservative treatment for high-risk stress fractures of the anterior tibial cortex, navicular and proximal fifth metatarsal. Methods Systematic searches of CENTRAL, MEDLINE, EMBASE, CINAHL, SPORTDiscus and PEDro were performed to identify relevant prospective and

  8. Comparing the cost-effectiveness of water conservation policies in a depleting aquifer:A dynamic analysis of the Kansas High Plains

    Science.gov (United States)

    This research analyzes two groundwater conservation policies in the Kansas High Plains located within the Ogallala aquifer: 1) cost-share assistance to increase irrigation efficiency; and 2) incentive payments to convert irrigated crop production to dryland crop production. To compare the cost-effec...

  9. Spatially conserved regulatory elements identified within human and mouse Cd247 gene using high-throughput sequencing data from the ENCODE project

    DEFF Research Database (Denmark)

    Pundhir, Sachin; Hannibal, Tine Dahlbæk; Bang-Berthelsen, Claus Heiner

    2014-01-01

    . In this study, we have utilized the wealth of high-throughput sequencing data produced during the Encyclopedia of DNA Elements (ENCODE) project to identify spatially conserved regulatory elements within the Cd247 gene from human and mouse. We show the presence of two transcription factor binding sites...

  10. A Resource Conservation Unit.

    Science.gov (United States)

    Porter, Philip D.

    1979-01-01

    Describes a variety of learning activities for teaching elementary and junior high students about air, water, and energy conservation techniques. Suggests community resources, social studies objectives, language skills, and 20 activities. (CK)

  11. Model My Watershed: A high-performance cloud application for public engagement, watershed modeling and conservation decision support

    Science.gov (United States)

    Aufdenkampe, A. K.; Tarboton, D. G.; Horsburgh, J. S.; Mayorga, E.; McFarland, M.; Robbins, A.; Haag, S.; Shokoufandeh, A.; Evans, B. M.; Arscott, D. B.

    2017-12-01

    The Model My Watershed Web app (https://app.wikiwatershed.org/) and the BiG-CZ Data Portal (http://portal.bigcz.org/) and are web applications that share a common codebase and a common goal to deliver high-performance discovery, visualization and analysis of geospatial data in an intuitive user interface in web browser. Model My Watershed (MMW) was designed as a decision support system for watershed conservation implementation. BiG CZ Data Portal was designed to provide context and background data for research sites. Users begin by creating an Area of Interest, via an automated watershed delineation tool, a free draw tool, selection of a predefined area such as a county or USGS Hydrological Unit (HUC), or uploading a custom polygon. Both Web apps visualize and provide summary statistics of land use, soil groups, streams, climate and other geospatial information. MMW then allows users to run a watershed model to simulate different scenarios of human impacts on stormwater runoff and water-quality. BiG CZ Data Portal allows users to search for scientific and monitoring data within the Area of Interest, which also serves as a prototype for the upcoming Monitor My Watershed web app. Both systems integrate with CUAHSI cyberinfrastructure, including visualizing observational data from CUAHSI Water Data Center and storing user data via CUAHSI HydroShare. Both systems also integrate with the new EnviroDIY Water Quality Data Portal (http://data.envirodiy.org/), a system for crowd-sourcing environmental monitoring data using open-source sensor stations (http://envirodiy.org/mayfly/) and based on the Observations Data Model v2.

  12. The maize INDETERMINATE1 flowering time regulator defines a highly conserved zinc finger protein family in higher plants

    Directory of Open Access Journals (Sweden)

    Colasanti Joseph

    2006-06-01

    Full Text Available Abstract Background The maize INDETERMINATE1 gene, ID1, is a key regulator of the transition to flowering and the founding member of a transcription factor gene family that encodes a protein with a distinct arrangement of zinc finger motifs. The zinc fingers and surrounding sequence make up the signature ID domain (IDD, which appears to be found in all higher plant genomes. The presence of zinc finger domains and previous biochemical studies showing that ID1 binds to DNA suggests that members of this gene family are involved in transcriptional regulation. Results Comparison of IDD genes identified in Arabidopsis and rice genomes, and all IDD genes discovered in maize EST and genomic databases, suggest that ID1 is a unique member of this gene family. High levels of sequence similarity amongst all IDD genes from maize, rice and Arabidopsis suggest that they are derived from a common ancestor. Several unique features of ID1 suggest that it is a divergent member of the maize IDD family. Although no clear ID1 ortholog was identified in the Arabidopsis genome, highly similar genes that encode proteins with identity extending beyond the ID domain were isolated from rice and sorghum. Phylogenetic comparisons show that these putative orthologs, along with maize ID1, form a group separate from other IDD genes. In contrast to ID1 mRNA, which is detected exclusively in immature leaves, several maize IDD genes showed a broad range of expression in various tissues. Further, Western analysis with an antibody that cross-reacts with ID1 protein and potential orthologs from rice and sorghum shows that all three proteins are detected in immature leaves only. Conclusion Comparative genomic analysis shows that the IDD zinc finger family is highly conserved among both monocots and dicots. The leaf-specific ID1 expression pattern distinguishes it from other maize IDD genes examined. A similar leaf-specific localization pattern was observed for the putative ID1 protein

  13. Ex Situ gene conservation in high elevation white pine species in the United States-a beginning

    Science.gov (United States)

    Richard A. Sniezko; Anna Schoettle; Joan Dunlap; Detlev Vogler; David Conklin; Andrew Bower; Chris Jensen; Rob Mangold; Doug Daoust; Gary Man

    2011-01-01

    The eight white pine species native to the western United States face an array of biotic and abiotic challenges that impact the viability of populations or the species themselves. Well-established programs are already in place to conserve and restore Pinus monticola Dougl. ex D. Don and P. lambertiana Dougl. throughout significant portions of their geographic ranges....

  14. A Highly Conserved GEQYQQLR Epitope Has Been Identified in the Nucleoprotein of Ebola Virus by Using an In Silico Approach

    Directory of Open Access Journals (Sweden)

    Mohammad Tuhin Ali

    2015-01-01

    Full Text Available Ebola virus (EBOV is a deadly virus that has caused several fatal outbreaks. Recently it caused another outbreak and resulted in thousands afflicted cases. Effective and approved vaccine or therapeutic treatment against this virus is still absent. In this study, we aimed to predict B-cell epitopes from several EBOV encoded proteins which may aid in developing new antibody-based therapeutics or viral antigen detection method against this virus. Multiple sequence alignment (MSA was performed for the identification of conserved region among glycoprotein (GP, nucleoprotein (NP, and viral structural proteins (VP40, VP35, and VP24 of EBOV. Next, different consensus immunogenic and conserved sites were predicted from the conserved region(s using various computational tools which are available in Immune Epitope Database (IEDB. Among GP, NP, VP40, VP35, and VP30 protein, only NP gave a 100% conserved GEQYQQLR B-cell epitope that fulfills the ideal features of an effective B-cell epitope and could lead a way in the milieu of Ebola treatment. However, successful in vivo and in vitro studies are prerequisite to determine the actual potency of our predicted epitope and establishing it as a preventing medication against all the fatal strains of EBOV.

  15. "Toward High School Biology": Helping Middle School Students Understand Chemical Reactions and Conservation of Mass in Nonliving and Living Systems

    Science.gov (United States)

    Herrmann-Abell, Cari F.; Koppal, Mary; Roseman, Jo Ellen

    2016-01-01

    Modern biology has become increasingly molecular in nature, requiring students to understand basic chemical concepts. Studies show, however, that many students fail to grasp ideas about atom rearrangement and conservation during chemical reactions or the application of these ideas to biological systems. To help provide students with a better…

  16. CONDOR: a database resource of developmentally associated conserved non-coding elements

    Directory of Open Access Journals (Sweden)

    Smith Sarah

    2007-08-01

    Full Text Available Abstract Background Comparative genomics is currently one of the most popular approaches to study the regulatory architecture of vertebrate genomes. Fish-mammal genomic comparisons have proved powerful in identifying conserved non-coding elements likely to be distal cis-regulatory modules such as enhancers, silencers or insulators that control the expression of genes involved in the regulation of early development. The scientific community is showing increasing interest in characterizing the function, evolution and language of these sequences. Despite this, there remains little in the way of user-friendly access to a large dataset of such elements in conjunction with the analysis and the visualization tools needed to study them. Description Here we present CONDOR (COnserved Non-coDing Orthologous Regions available at: http://condor.fugu.biology.qmul.ac.uk. In an interactive and intuitive way the website displays data on > 6800 non-coding elements associated with over 120 early developmental genes and conserved across vertebrates. The database regularly incorporates results of ongoing in vivo zebrafish enhancer assays of the CNEs carried out in-house, which currently number ~100. Included and highlighted within this set are elements derived from duplication events both at the origin of vertebrates and more recently in the teleost lineage, thus providing valuable data for studying the divergence of regulatory roles between paralogs. CONDOR therefore provides a number of tools and facilities to allow scientists to progress in their own studies on the function and evolution of developmental cis-regulation. Conclusion By providing access to data with an approachable graphics interface, the CONDOR database presents a rich resource for further studies into the regulation and evolution of genes involved in early development.

  17. Inhibitory control and visuo-spatial reversibility in Piaget’s seminal number conservation task: A high-density ERP study.

    Directory of Open Access Journals (Sweden)

    Gregoire eBorst

    2013-12-01

    Full Text Available The present high-density ERP study on 13 adults aimed to determine whether number conservation relies on the ability to inhibit the overlearned length-equals-number strategy and then imagine the shortening of the row that was lengthened. Participants performed the number-conservation task and, after the EEG session, the mental imagery task. In the number-conservation task, first two rows with the same number of tokens and the same length were presented on a computer screen (COV condition and then, the tokens in one of the two rows were spread apart (INT condition. Participants were instructed to determine whether the two rows had an identical number of tokens. In the mental imagery task, two rows with different lengths but the same number of tokens were presented and participants were instructed to imagine the tokens in the longer row aligning with the tokens in the shorter row. In the number-conservation task, we found that the amplitudes of the centro-parietal N2 and fronto-central P3 were higher in the INT than in the COV conditions. In addition, the differences in response times between the two conditions were correlated with the differences in the amplitudes of the fronto-central P3. In light of previous results reported on the number-conservation task in adults, the present results suggest that inhibition might be necessary to succeed the number-conservation task in adults even when the transformation of the length of one of the row is displayed. Finally, we also reported correlations between the speed at which participants could imagine the shortening of one of the row in the mental imagery task, the speed at which participants could determine that the two rows had the same number of tokens after the tokens in one of the row were spread apart and the latency of the late positive parietal component in the number-conservation task. Therefore, performing the number-conservation task might involve mental transformation processes in adults.

  18. A zebrafish screen for craniofacial mutants identifies wdr68 as a highly conserved gene required for endothelin-1 expression

    Directory of Open Access Journals (Sweden)

    Amsterdam Adam

    2006-06-01

    identification of approximately 25% of the essential genes required for craniofacial development. The identification of zebrafish models for two human disease syndromes indicates that homologs to the other genes are likely to also be relevant for human craniofacial development. The initial characterization of wdr68 suggests an important role in craniofacial development for the highly conserved Wdr68-Dyrk1 protein complexes.

  19. Functional and genetic evidence that nucleoside transport is highly conserved in Leishmania species: Implications for pyrimidine-based chemotherapy.

    Science.gov (United States)

    Alzahrani, Khalid J H; Ali, Juma A M; Eze, Anthonius A; Looi, Wan Limm; Tagoe, Daniel N A; Creek, Darren J; Barrett, Michael P; de Koning, Harry P

    2017-08-01

    Leishmania pyrimidine salvage is replete with opportunities for therapeutic intervention with enzyme inhibitors or antimetabolites. Their uptake into cells depends upon specific transporters; therefore it is essential to establish whether various Leishmania species possess similar pyrimidine transporters capable of drug uptake. Here, we report a comprehensive characterization of pyrimidine transport in L. major and L. mexicana. In both species, two transporters for uridine/adenosine were detected, one of which also transported uracil and the antimetabolites 5-fluoruracil (5-FU) and 5F,2'deoxyuridine (5F,2'dUrd), and was designated uridine-uracil transporter 1 (UUT1); the other transporter mediated uptake of adenosine, uridine, 5F,2'dUrd and thymidine and was designated Nucleoside Transporter 1 (NT1). To verify the reported L. donovani model of two NT1-like genes encoding uridine/adenosine transporters, and an NT2 gene encoding an inosine transporter, we cloned the corresponding L. major and L. mexicana genes, expressing each in T. brucei. Consistent with the L. donovani reports, the NT1-like genes of either species mediated the adenosine-sensitive uptake of [ 3 H]-uridine but not of [ 3 H]-inosine. Conversely, the NT2-like genes mediated uptake of [ 3 H]-inosine but not [ 3 H]-uridine. Among pyrimidine antimetabolites tested, 5-FU and 5F,2'dUrd were the most effective antileishmanials; resistance to both analogs was induced in L. major and L. mexicana. In each case it was found that the resistant cells had lost the transport capacity for the inducing drug. Metabolomics analysis found that the mechanism of action of 5-FU and 5F-2'dUrd was similar in both Leishmania species, with major changes in deoxynucleotide metabolism. We conclude that the pyrimidine salvage system is highly conserved in Leishmania species - essential information for the development of pyrimidine-based chemotherapy. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights

  20. Functional and genetic evidence that nucleoside transport is highly conserved in Leishmania species: Implications for pyrimidine-based chemotherapy

    Directory of Open Access Journals (Sweden)

    Khalid J.H. Alzahrani

    2017-08-01

    Full Text Available Leishmania pyrimidine salvage is replete with opportunities for therapeutic intervention with enzyme inhibitors or antimetabolites. Their uptake into cells depends upon specific transporters; therefore it is essential to establish whether various Leishmania species possess similar pyrimidine transporters capable of drug uptake. Here, we report a comprehensive characterization of pyrimidine transport in L. major and L. mexicana. In both species, two transporters for uridine/adenosine were detected, one of which also transported uracil and the antimetabolites 5-fluoruracil (5-FU and 5F,2′deoxyuridine (5F,2′dUrd, and was designated uridine-uracil transporter 1 (UUT1; the other transporter mediated uptake of adenosine, uridine, 5F,2′dUrd and thymidine and was designated Nucleoside Transporter 1 (NT1. To verify the reported L. donovani model of two NT1-like genes encoding uridine/adenosine transporters, and an NT2 gene encoding an inosine transporter, we cloned the corresponding L. major and L. mexicana genes, expressing each in T. brucei. Consistent with the L. donovani reports, the NT1-like genes of either species mediated the adenosine-sensitive uptake of [3H]-uridine but not of [3H]-inosine. Conversely, the NT2-like genes mediated uptake of [3H]-inosine but not [3H]-uridine. Among pyrimidine antimetabolites tested, 5-FU and 5F,2′dUrd were the most effective antileishmanials; resistance to both analogs was induced in L. major and L. mexicana. In each case it was found that the resistant cells had lost the transport capacity for the inducing drug. Metabolomics analysis found that the mechanism of action of 5-FU and 5F-2′dUrd was similar in both Leishmania species, with major changes in deoxynucleotide metabolism. We conclude that the pyrimidine salvage system is highly conserved in Leishmania species - essential information for the development of pyrimidine-based chemotherapy. Keywords: Leishmania, Pyrimidine metabolism, Uracil

  1. Conservation endocrinology

    Science.gov (United States)

    McCormick, Stephen; Romero, L. Michael

    2017-01-01

    Endocrinologists can make significant contributions to conservation biology by helping to understand the mechanisms by which organisms cope with changing environments. Field endocrine techniques have advanced rapidly in recent years and can provide substantial information on the growth, stress, and reproductive status of individual animals, thereby providing insight into current and future responses of populations to changes in the environment. Environmental stressors and reproductive status can be detected nonlethally by measuring a number of endocrine-related endpoints, including steroids in plasma, living and nonliving tissue, urine, and feces. Information on the environmental or endocrine requirements of individual species for normal growth, development, and reproduction will provide critical information for species and ecosystem conservation. For many taxa, basic information on endocrinology is lacking, and advances in conservation endocrinology will require approaches that are both “basic” and “applied” and include integration of laboratory and field approaches.

  2. Multidisciplinary approach for the esophageal carcinoma with intent to conserve the esophagus centering on high-dose radiotherapy and concurrent chemotherapy

    International Nuclear Information System (INIS)

    Murakami, Masao; Kuroda, Yasumasa; Okamoto, Yoshiaki

    1997-01-01

    Forty-seven patients with operable squamous cell carcinoma of the thoracic esophagus were treated by initial concurrent chemoradiotherapy (CDDP-5 FU-44 Gy) followed by definitive high-dose of radiotherapy (CRT group: 35 patients) or surgery (CRT-S group: 12 patients). Clinical CR rate showed 86% in CRT group; and pathological CR rate 18% in CRT-S group. The overall median survival was 45 months, survival at 1, 3, 5 years being 96%, 52%, 48%, respectively. No treatment-related mortality was observed. The rate of the 'esophagus conservation' was 66%. Our results demonstrated that the multidisciplinary approach with intent to conserve the esophagus centering on high-dose radiotherapy and concurrent chemotherapy provides a significant improvement of both survival and quality of life in patients with operable esophageal carcinoma. (author)

  3. Highly transparent poly(2-ethyl-2-oxazoline)-TiO2 nanocomposite coatings for the conservation of matte painted artworks

    OpenAIRE

    Colombo, A.; Gherardi, Francesca; Goidanich, S.; Delaney, J. K.; de la Rie, E. R.; Ubaldi, M. C.; Toniolo, L.; Simonutti, R.

    2015-01-01

    A nanocomposite coating based on TiO2 nanoparticles and poly(2-ethyl-2-oxazoline) is used as consolidant of matte painted surfaces (temperas, watercolors, modern paintings). The aim of this work is to provide advances in the conservation of these works of art, while preserving their optical appearance, in terms of colour and gloss. Fiber Optic Reflectance Spectroscopy (FORS) measurements of a painting-model (an acrylic black monochrome) treated with the nanocomposite coatings revealed that it...

  4. DNA analysis indicates that Asian elephants are native to Borneo and are therefore a high priority for conservation.

    Directory of Open Access Journals (Sweden)

    Prithiviraj Fernando

    2003-10-01

    Full Text Available The origin of Borneo's elephants is controversial. Two competing hypotheses argue that they are either indigenous, tracing back to the Pleistocene, or were introduced, descending from elephants imported in the 16th-18th centuries. Taxonomically, they have either been classified as a unique subspecies or placed under the Indian or Sumatran subspecies. If shown to be a unique indigenous population, this would extend the natural species range of the Asian elephant by 1300 km, and therefore Borneo elephants would have much greater conservation importance than if they were a feral population. We compared DNA of Borneo elephants to that of elephants from across the range of the Asian elephant, using a fragment of mitochondrial DNA, including part of the hypervariable d-loop, and five autosomal microsatellite loci. We find that Borneo's elephants are genetically distinct, with molecular divergence indicative of a Pleistocene colonisation of Borneo and subsequent isolation. We reject the hypothesis that Borneo's elephants were introduced. The genetic divergence of Borneo elephants warrants their recognition as a separate evolutionary significant unit. Thus, interbreeding Borneo elephants with those from other populations would be contraindicated in ex situ conservation, and their genetic distinctiveness makes them one of the highest priority populations for Asian elephant conservation.

  5. Finding cis-regulatory modules in Drosophila using phylogenetic hidden Markov models

    DEFF Research Database (Denmark)

    Wong, Wendy S W; Nielsen, Rasmus

    2007-01-01

    MOTIVATION: Finding the regulatory modules for transcription factors binding is an important step in elucidating the complex molecular mechanisms underlying regulation of gene expression. There are numerous methods available for solving this problem, however, very few of them take advantage of th...

  6. Piecing together cis-regulatory networks: insights from epigenomics studies in plants.

    Science.gov (United States)

    Huang, Shao-Shan C; Ecker, Joseph R

    2018-05-01

    5-Methylcytosine, a chemical modification of DNA, is a covalent modification found in the genomes of both plants and animals. Epigenetic inheritance of phenotypes mediated by DNA methylation is well established in plants. Most of the known mechanisms of establishing, maintaining and modifying DNA methylation have been worked out in the reference plant Arabidopsis thaliana. Major functions of DNA methylation in plants include regulation of gene expression and silencing of transposable elements (TEs) and repetitive sequences, both of which have parallels in mammalian biology, involve interaction with the transcriptional machinery, and may have profound effects on the regulatory networks in the cell. Methylome and transcriptome dynamics have been investigated in development and environmental responses in Arabidopsis and agriculturally and ecologically important plants, revealing the interdependent relationship among genomic context, methylation patterns, and expression of TE and protein coding genes. Analyses of methylome variation among plant natural populations and species have begun to quantify the extent of genetic control of methylome variation vs. true epimutation, and model the evolutionary forces driving methylome evolution in both short and long time scales. The ability of DNA methylation to positively or negatively modulate binding affinity of transcription factors (TFs) provides a natural link from genome sequence and methylation changes to transcription. Technologies that allow systematic determination of methylation sensitivities of TFs, in native genomic and methylation context without confounding factors such as histone modifications, will provide baseline datasets for building cell-type- and individual-specific regulatory networks that underlie the establishment and inheritance of complex traits. This article is categorized under: Laboratory Methods and Technologies > Genetic/Genomic Methods Biological Mechanisms > Regulatory Biology. © 2017 Wiley Periodicals, Inc.

  7. Confocal quantification of cis-regulatory reporter gene expression in living sea urchin.

    Science.gov (United States)

    Damle, Sagar; Hanser, Bridget; Davidson, Eric H; Fraser, Scott E

    2006-11-15

    Quantification of GFP reporter gene expression at single cell level in living sea urchin embryos can now be accomplished by a new method of confocal laser scanning microscopy (CLSM). Eggs injected with a tissue-specific GFP reporter DNA construct were grown to gastrula stage and their fluorescence recorded as a series of contiguous Z-section slices that spanned the entire embryo. To measure the depth-dependent signal decay seen in the successive slices of an image stack, the eggs were coinjected with a freely diffusible internal fluorescent standard, rhodamine dextran. The measured rhodamine fluorescence was used to generate a computational correction for the depth-dependent loss of GFP fluorescence per slice. The intensity of GFP fluorescence was converted to the number of GFP molecules using a conversion constant derived from CLSM imaging of eggs injected with a measured quantity of GFP protein. The outcome is a validated method for accurately counting GFP molecules in given cells in reporter gene transfer experiments, as we demonstrate by use of an expression construct expressed exclusively in skeletogenic cells.

  8. The selective conservative management of small traumatic pneumothoraces following stab injuries is safe: experience from a high-volume trauma service in South Africa.

    Science.gov (United States)

    Kong, V Y; Oosthuizen, G V; Clarke, D L

    2015-02-01

    The selective conservative management of small pneumothoraces (PTXs) following stab injuries is controversial. We reviewed a cohort of patients managed conservatively in a high volume trauma service in South Africa. A retrospective review over a 2-year period identified 125 asymptomatic patients with small PTXs measuring chest radiograph who were managed conservatively. Of the 125 patients included in the study, 92% were male (115/125), and the median age for all patients was 21 years (19-24). Ninety-seven per cent (121/125) of the weapons involved were knives, and 3% (4/125) were screwdrivers. Sixty-one per cent of all injuries were on the left side. Eighty-two per cent (102/125) sustained a single stab, and 18% (23/125) had multiple stabs. Thirty-nine per cent (49/125) had a PTX <0.5 cm (Group A), 26% (32/125) were ≥ 0.5 to <1 cm (Group B), 19% (24/125) were ≥ 1 to <1.5 cm (Group C) and 15% (20/125) were ≥ 1.5 to <2 cm (Group D). Three per cent of all patients (4/125) eventually required ICDs (one in Group C, three in Group D). All four patients had ICDs in situ for 24 h. The remaining 97% (121/125) were all managed successfully by active clinical observation alone. There were no subsequent readmissions, morbidity or mortality as a direct result of our conservative approach. The selective conservative management of asymptomatic small PTXs from stab injuries is safe if undertaken in the appropriate setting.

  9. [Conservation Units.

    Science.gov (United States)

    Texas Education Agency, Austin.

    Each of the six instructional units deals with one aspect of conservation: forests, water, rangeland, minerals (petroleum), and soil. The area of the elementary school curriculum with which each correlates is indicated. Lists of general and specific objectives are followed by suggested teaching procedures, including ideas for introducing the…

  10. Creative conservation

    NARCIS (Netherlands)

    Bentham, Roelof J.

    1968-01-01

    The increasing exploitation of our natural resources, the unlimited occupation of ever more new areas, and the intensification of land-use, make it necessary for us to expand the concept of conservation. But we also need to reconsider that concept itself. For the changing conditions in the

  11. Reshaping conservation

    DEFF Research Database (Denmark)

    Funder, Mikkel; Danielsen, Finn; Ngaga, Yonika

    2013-01-01

    members strengthen the monitoring practices to their advantage, and to some extent move them beyond the reach of government agencies and conservation and development practitioners. This has led to outcomes that are of greater social and strategic value to communities than the original 'planned' benefits...

  12. Integrating conservation costs into sea level rise adaptive conservation prioritization

    Directory of Open Access Journals (Sweden)

    Mingjian Zhu

    2015-07-01

    Full Text Available Biodiversity conservation requires strategic investment as resources for conservation are often limited. As sea level rises, it is important and necessary to consider both sea level rise and costs in conservation decision making. In this study, we consider costs of conservation in an integrated modeling process that incorporates a geomorphological model (SLAMM, species habitat models, and conservation prioritization (Zonation to identify conservation priorities in the face of landscape dynamics due to sea level rise in the Matanzas River basin of northeast Florida. Compared to conservation priorities that do not consider land costs in the analysis process, conservation priorities that consider costs in the planning process change significantly. The comparison demonstrates that some areas with high conservation values might be identified as lower priorities when integrating economic costs in the planning process and some areas with low conservation values might be identified as high priorities when considering costs in the planning process. This research could help coastal resources managers make informed decisions about where and how to allocate conservation resources more wisely to facilitate biodiversity adaptation to sea level rise.

  13. Cytoplasmic protein binding to highly conserved sequences in the 3' untranslated region of mouse protamine 2 mRNA, a translationally regulated transcript of male germ cells

    International Nuclear Information System (INIS)

    Kwon, Y.K.; Hecht, N.B.

    1991-01-01

    The expression of the protamines, the predominant nuclear proteins of mammalian spermatozoa, is regulated translationally during male germ-cell development. The 3' untranslated region (UTR) of protamine 1 mRNA has been reported to control its time of translation. To understand the mechanisms controlling translation of the protamine mRNAs, we have sought to identify cis elements of the 3' UTR of protamine 2 mRNA that are recognized by cytoplasmic factors. From gel retardation assays, two sequence elements are shown to form specific RNA-protein complexes. Protein binding sites of the two complexes were determined by RNase T1 mapping, by blocking the putative binding sites with antisense oligonucleotides, and by competition assays. The sequences of these elements, located between nucleotides + 537 and + 572 in protamine 2 mRNA, are highly conserved among postmeiotic translationally regulated nuclear proteins of the mammalian testis. Two closely linked protein binding sites were detected. UV-crosslinking studies revealed that a protein of about 18 kDa binds to one of the conserved sequences. These data demonstrate specific protein binding to a highly conserved 3' UTR of translationally regulated testicular mRNA

  14. The Highly Conserved COPII Coat Complex Sorts Cargo from the Endoplasmic Reticulum and Targets It to the Golgi

    OpenAIRE

    Lord, Christopher; Ferro-Novick, Susan; Miller, Elizabeth A.

    2013-01-01

    Protein egress from the endoplasmic reticulum (ER) is driven by a conserved cytoplasmic coat complex called the COPII coat. The COPII coat complex contains an inner shell (Sec23/Sec24) that sorts cargo into ER-derived vesicles and an outer cage (Sec13/Sec31) that leads to coat polymerization. Once released from the ER, vesicles must tether to and fuse with the target membrane to deliver their protein and lipid contents. This delivery step also depends on the COPII coat, with coat proteins bin...

  15. Conservation of Charge and Conservation of Current

    OpenAIRE

    Eisenberg, Bob

    2016-01-01

    Conservation of current and conservation of charge are nearly the same thing: when enough is known about charge movement, conservation of current can be derived from conservation of charge, in ideal dielectrics, for example. Conservation of current is enforced implicitly in ideal dielectrics by theories that conserve charge. But charge movement in real materials like semiconductors or ionic solutions is never ideal. We present an apparently universal derivation of conservation of current and ...

  16. High-Throughput Sequencing Reveals Diverse Sets of Conserved, Nonconserved, and Species-Specific miRNAs in Jute

    Directory of Open Access Journals (Sweden)

    Md. Tariqul Islam

    2015-01-01

    Full Text Available MicroRNAs play a pivotal role in regulating a broad range of biological processes, acting by cleaving mRNAs or by translational repression. A group of plant microRNAs are evolutionarily conserved; however, others are expressed in a species-specific manner. Jute is an agroeconomically important fibre crop; nonetheless, no practical information is available for microRNAs in jute to date. In this study, Illumina sequencing revealed a total of 227 known microRNAs and 17 potential novel microRNA candidates in jute, of which 164 belong to 23 conserved families and the remaining 63 belong to 58 nonconserved families. Among a total of 81 identified microRNA families, 116 potential target genes were predicted for 39 families and 11 targets were predicted for 4 among the 17 identified novel microRNAs. For understanding better the functions of microRNAs, target genes were analyzed by Gene Ontology and their pathways illustrated by KEGG pathway analyses. The presence of microRNAs identified in jute was validated by stem-loop RT-PCR followed by end point PCR and qPCR for randomly selected 20 known and novel microRNAs. This study exhaustively identifies microRNAs and their target genes in jute which will ultimately pave the way for understanding their role in this crop and other crops.

  17. Relatively High Complication and Revision Rates of the Mayo® Metaphysical Conservative Femoral Stem in Young Patients.

    Science.gov (United States)

    Rutenberg, Tal Frenkel; Warshevski, Yaniv; Gold, Aviram; Shasha, Nadav; Snir, Nimrod; Chechik, Ofir; Dolkart, Oleg; Eilig, Dynai; Herman, Amir; Rath, Ehud; Kramer, Moti; Drexler, Michael

    2018-05-08

    The Mayo metaphysical conservative femoral stem (Zimmer, Warsaw, Indiana) is a wedge-shaped implant designed to transfer loads proximally, reduce femoral destruction, and enable the preservation of bone stock in the proximal femur. Thus, it is a potentially preferred prosthesis for active, non-elderly patients who may require additional future surgeries. This retrospective case study analyzed the outcomes of consecutive patients who underwent total hip replacements with this stem between May 2001 and February 2013. All patients underwent clinical assessment, radiological evaluation for the presence and development of radiolucent lines, and functional assessment (numerical analog scale, Harris hip score, and Short Form-12 questionnaire). Ninety-five hips (79 patients) were available for analysis. The patients' mean age was 43 years (range, 18-64 years), and the mean follow-up was 97 months (range, 26.9-166 months). The postoperative clinical assessments and functional assessments revealed significant improvements. Sixteen patients (20.3%) had 18 orthopedic complications, the most common of which were an intraoperative femoral fracture and implant dislocation requiring revision surgeries in 10 hips (10.5%). Radiological analysis revealed evidence of femoral remodeling in 64 (67.4%) implants, spot welds (neocortex) in 35 (36.8%), and osteolysis in 3 (3.2%). These results suggest that the conservative hip femoral implant has an unacceptable complication rate for non-elderly patients. [Orthopedics. 201x; xx(x):xx-xx.]. Copyright 2018, SLACK Incorporated.

  18. Diesel conservation: GSRTC'S experience

    Energy Technology Data Exchange (ETDEWEB)

    Ramesh Kumar, I V

    1980-01-01

    The Gujarat State Road Transport Corporation (GSRTC) in India has a fleet of about 6000 buses. The increasing cost of fuel and lubricants added to uncertainty in supplies, has necessitated the need for conserving High Speed Diesel Oil (HSD). GSRTC had achieved an overall average Kilometre Per Litre (kmpl) of 4.44 in the year 1976-1977 due to a variety of measures. In the year 1978-1979 the average kmpl was 4.52 and it is expected to be 4.60 for 1979-1980. The case study outlined describes the measures taken by GSRTC in conserving high speed diesel oil by various methods.

  19. Comparative interactomics: analysis of arabidopsis 14-3-3 complexes reveals highly conserved 14-3-3 interactions between humans and plants.

    Science.gov (United States)

    Paul, Anna-Lisa; Liu, Li; McClung, Scott; Laughner, Beth; Chen, Sixue; Ferl, Robert J

    2009-04-01

    As a first step in the broad characterization of plant 14-3-3 multiprotein complexes in vivo, stringent and specific antibody affinity purification was used to capture 14-3-3s together with their interacting proteins from extracts of Arabidopsis cell suspension cultures. Approximately 120 proteins were identified as potential in vivo 14-3-3 interacting proteins by mass spectrometry of the recovered complexes. Comparison of the proteins in this data set with the 14-3-3 interacting proteins from a similar study in human embryonic kidney cell cultures revealed eight interacting proteins that likely represent reasonably abundant, fundamental 14-3-3 interaction complexes that are highly conserved across all eukaryotes. The Arabidopsis 14-3-3 interaction data set was also compared to a yeast in vivo 14-3-3 interaction data set. Four 14-3-3 interacting proteins are conserved in yeast, humans, and Arabidopsis. Comparisons of the data sets based on biochemical function revealed many additional similarities in the human and Arabidopsis data sets that represent conserved functional interactions, while also leaving many proteins uniquely identified in either Arabidopsis or human cells. In particular, the Arabidopsis interaction data set is enriched for proteins involved in metabolism.

  20. What is a conservation actor?

    Directory of Open Access Journals (Sweden)

    Paul Jepson

    2011-01-01

    Full Text Available As a crisis-oriented discipline, conservation biology needs actions to understand the state of nature and thwart declines in biodiversity. Actors-traditionally individuals, institutions, and collectives-have been central to delivering such goals in practice. However, the definition of actors within the discipline has been narrow and their role in influencing conservation outcomes inadequately conceptualised. In this paper, we examine the question ′What is a conservation actor?′ Who or what creates the capacity to influence conservation values and actions? Drawing from theoretical developments in Actor-Network Theory and collective governance, we argue that the concept of an actor in conservation biology should be broadened to include non-humans, such as species and devices, because they have the agency and ability to influence project goals and outcomes. We illustrate this through four examples: the Asian elephant, International Union for Conservation of Nature red lists, the High Conservation Value approach, and an Integrated Conservation and Development Project. We argue that a broader conceptualisation of actors in conservation biology will produce new forms of understanding that could open up new areas of conservation research, enhance practice and draw attention to spheres of conservation activity that might require stronger oversight and governance.

  1. Determination of 5 '-leader sequences from radically disparate strains of porcine reproductive and respiratory syndrome virus reveals the presence of highly conserved sequence motifs

    DEFF Research Database (Denmark)

    Oleksiewicz, M.B.; Bøtner, Anette; Nielsen, Jens

    1999-01-01

    We determined the untranslated 5'-leader sequence for three different isolates of porcine reproductive and respiratory syndrome virus (PRRSV): pathogenic European- and American-types, as well as an American-type vaccine strain. 5'-leader from European- and American-type PRRSV differed in length...... (220 and 190 nt, respectively), and exhibited only approximately 50% nucleotide homology. Nevertheless, highly conserved areas were identified in the leader of all 3 PRRSV isolates, which constitute candidate motifs for binding of protein(s) involved in viral replication. These comparative data provide...

  2. UK114, a YjgF/Yer057p/UK114 family protein highly conserved from bacteria to mammals, is localized in rat liver peroxisomes

    International Nuclear Information System (INIS)

    Antonenkov, Vasily D.; Ohlmeier, Steffen; Sormunen, Raija T.; Hiltunen, J. Kalervo

    2007-01-01

    Mammalian UK114 belongs to a highly conserved family of proteins with unknown functions. Although it is believed that UK114 is a cytosolic or mitochondrial protein there is no detailed study of its intracellular localization. Using analytical subcellular fractionation, electron microscopic colloidal gold technique, and two-dimensional gel electrophoresis of peroxisomal matrix proteins combined with mass spectrometric analysis we show here that a large portion of UK114 is present in rat liver peroxisomes. The peroxisomal UK114 is a soluble matrix protein and it is not inducible by the peroxisomal proliferator clofibrate. The data predict involvement of UK114 in peroxisomal metabolism

  3. A high-order finite-volume method for hyperbolic conservation laws on locally-refined grids

    Energy Technology Data Exchange (ETDEWEB)

    McCorquodale, Peter; Colella, Phillip

    2011-01-28

    We present a fourth-order accurate finite-volume method for solving time-dependent hyperbolic systems of conservation laws on Cartesian grids with multiple levels of refinement. The underlying method is a generalization of that in [5] to nonlinear systems, and is based on using fourth-order accurate quadratures for computing fluxes on faces, combined with fourth-order accurate Runge?Kutta discretization in time. To interpolate boundary conditions at refinement boundaries, we interpolate in time in a manner consistent with the individual stages of the Runge-Kutta method, and interpolate in space by solving a least-squares problem over a neighborhood of each target cell for the coefficients of a cubic polynomial. The method also uses a variation on the extremum-preserving limiter in [8], as well as slope flattening and a fourth-order accurate artificial viscosity for strong shocks. We show that the resulting method is fourth-order accurate for smooth solutions, and is robust in the presence of complex combinations of shocks and smooth flows.

  4. Toward High School Biology: Helping Middle School Students Understand Chemical Reactions and Conservation of Mass in Nonliving and Living Systems

    Science.gov (United States)

    Herrmann-Abell, Cari F.; Koppal, Mary; Roseman, Jo Ellen

    2016-01-01

    Modern biology has become increasingly molecular in nature, requiring students to understand basic chemical concepts. Studies show, however, that many students fail to grasp ideas about atom rearrangement and conservation during chemical reactions or the application of these ideas to biological systems. To help provide students with a better foundation, we used research-based design principles and collaborated in the development of a curricular intervention that applies chemistry ideas to living and nonliving contexts. Six eighth grade teachers and their students participated in a test of the unit during the Spring of 2013. Two of the teachers had used an earlier version of the unit the previous spring. The other four teachers were randomly assigned either to implement the unit or to continue teaching the same content using existing materials. Pre- and posttests were administered, and the data were analyzed using Rasch modeling and hierarchical linear modeling. The results showed that, when controlling for pretest score, gender, language, and ethnicity, students who used the curricular intervention performed better on the posttest than the students using existing materials. Additionally, students who participated in the intervention held fewer misconceptions. These results demonstrate the unit’s promise in improving students’ understanding of the targeted ideas. PMID:27909024

  5. High spatial resolution mapping of the Cerrado's land cover and land use types in the priority area for conservation Chapada da Contagem, Brazil.

    Science.gov (United States)

    Ribeiro, F.; Roberts, D. A.; Davis, F. W.; Antunes Daldegan, G.; Nackoney, J.; Hess, L. L.

    2016-12-01

    The Brazilian savanna, Cerrado, is the second largest biome over South America and the most floristically diverse savanna in the world. This biome is considered a conservation hotspot in respect to its biodiversity importance and rapid transformation of its landscape. The Cerrado's natural vegetation has been severely transformed by agriculture and pasture activities. Currently it is the main agricultural frontier in Brazil and one of the most threatened Brazilian biomes. This scenario results in environmental impacts such as ecosystems fragmentation as well as losses in connectivity, biodiversity and gene flow, changes in the microclimate and energy, carbon and nutrients cycles, among others. The Priority Areas for Conservation is a governmental program from Brazil that identifies areas with high conservation priority. One of this program's recommendation is a natural vegetation map including their major ecosystem classes. This study aims to generate more precise information for the Cerrado's vegetation. The main objective of this study is to identify which ecosystems are being prioritized and/or threatened by land use, refining information for further protection. In order to test methods, the priority area for conservation Chapada da Contagem was selected as the study site. This area is ranked as "extremely high priority" by the government and is located in the Federal District and Goias State, Brazil. Satellites with finer spatial resolution may improve the classification of the Cerrado's vegetation. Remote sensing methods and two criteria were tested using RapidEye 3A imagery (5m spatial resolution) collected in 2014 in order to classify the Cerrado's major land cover types of this area, as well as its land use. One criterion considers the Cerrado's major terrestrial ecosystems, which are divided into forest, savanna and grassland. The other involves scaling it down to the major physiognomic groups of each ecosystem. Other sources of environmental dataset such

  6. Conservation of Mangifera sylvatica

    DEFF Research Database (Denmark)

    Akhter, Sayma

    and conservation of these valuable species. The present study considers an underutilised and threatened species of Bangladesh, namely wild mango (Mangifera sylvatica Roxb.). Although this wild mango is one of the genetically closest species to the common mango (Mangifera indica L.) research is very limited...... and mostly focused on wood quality and phylogenetic relationships. Therefore, this study investigated the conservation potential of wild mango considering its contribution for food, nutrition and livelihoods. To do so, an assessment was made of the current and future distribution of the species, which...... explored. The study conveyed five key messages: 1. Wild mango may become extinct under future climate change scenarios so it is high time to start thinking about conservation initiatives. 2. Wild mango is a small sized mango with a large kernel in relation to other Mangifera species which provides...

  7. High-Level Systemic Expression of Conserved Influenza Epitope in Plants on the Surface of Rod-Shaped Chimeric Particles

    Directory of Open Access Journals (Sweden)

    Natalia V. Petukhova

    2014-04-01

    Full Text Available Recombinant viruses based on the cDNA copy of the tobacco mosaic virus (TMV genome carrying different versions of the conserved M2e epitope from influenza virus A cloned into the coat protein (CP gene were obtained and partially characterized by our group previously; cysteines in the human consensus M2e sequence were changed to serine residues. This work intends to show some biological properties of these viruses following plant infections. Agroinfiltration experiments on Nicotiana benthamiana confirmed the efficient systemic expression of M2e peptides, and two point amino acid substitutions in recombinant CPs significantly influenced the symptoms and development of viral infections. Joint expression of RNA interference suppressor protein p19 from tomato bushy stunt virus (TBSV did not affect the accumulation of CP-M2e-ser recombinant protein in non-inoculated leaves. RT-PCR analysis of RNA isolated from either infected leaves or purified TMV-M2e particles proved the genetic stability of TMV‑based viral vectors. Immunoelectron microscopy of crude plant extracts demonstrated that foreign epitopes are located on the surface of chimeric virions. The rod‑shaped geometry of plant-produced M2e epitopes is different from the icosahedral or helical filamentous arrangement of M2e antigens on the carrier virus-like particles (VLP described earlier. Thereby, we created a simple and efficient system that employs agrobacteria and plant viral vectors in order to produce a candidate broad-spectrum flu vaccine.

  8. Toward High School Biology: Helping Middle School Students Understand Chemical Reactions and Conservation of Mass in Nonliving and Living Systems.

    Science.gov (United States)

    Herrmann-Abell, Cari F; Koppal, Mary; Roseman, Jo Ellen

    2016-01-01

    Modern biology has become increasingly molecular in nature, requiring students to understand basic chemical concepts. Studies show, however, that many students fail to grasp ideas about atom rearrangement and conservation during chemical reactions or the application of these ideas to biological systems. To help provide students with a better foundation, we used research-based design principles and collaborated in the development of a curricular intervention that applies chemistry ideas to living and nonliving contexts. Six eighth grade teachers and their students participated in a test of the unit during the Spring of 2013. Two of the teachers had used an earlier version of the unit the previous spring. The other four teachers were randomly assigned either to implement the unit or to continue teaching the same content using existing materials. Pre- and posttests were administered, and the data were analyzed using Rasch modeling and hierarchical linear modeling. The results showed that, when controlling for pretest score, gender, language, and ethnicity, students who used the curricular intervention performed better on the posttest than the students using existing materials. Additionally, students who participated in the intervention held fewer misconceptions. These results demonstrate the unit's promise in improving students' understanding of the targeted ideas. © 2016 C. F. Herrmann-Abell et al. CBE—Life Sciences Education © 2016 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  9. An attempt to conserve whatnot somniferum (L.) dual - a highly essential medicinal plant, through in vitro callus culture

    International Nuclear Information System (INIS)

    Rout, J.R.; Sahoo, S.

    2011-01-01

    A simple effective protocol was developed for conservation and plant propagation through callus cultures of Withania somnifera (Ashwagandha). Seed germination percentage reached a maximum value of 64.3% on half MS + GA3 0.25 mg/l at third week of culture. Three different basal media compared for seed germination, MS was most effective. Out of 25 combinations of growth regulators evaluated, MS + 1.0 mg/l BA + 1.0 mg/l 2, 4-D found to be best for callus induction and proliferation regardless to explants. Among the four different explants tested, In vivo leaf explant was found most suitable for callus induction, proliferation and fresh weight gain. The highest callus induction frequency percentage 86.4% was recorded with In vivo leaf explant whereas, 43.4% in In vitro leaf explant at day 30 on MS augmented with 1.0 mg/l BA + 1.0 mg/l 2,4-D. Among different growth regulator combinations tested in augmentation with MS for shoot initiation and elongation, 2.0 mg/l BA + 1.0 mg/l NAA was the best eliciting a maximum of 82.3% shoot induction with highest shoot number 4.8 shoots/callus. The original callus was sub-cultured 2 times on fresh shoot multiplication medium after each harvest of the shoots. Of three different auxins tested for In vitro rooting, IBA was most effective compared to IPA and NAA. Half-strength MS medium containing IBA at an optimum concentration of 2.0 mg/l induced rooting in 83.1% of the In vitro derived shoots. The rooted plantlets were acclimated and eventually established in soil. (author)

  10. Structure of genes for dermaseptins B, antimicrobial peptides from frog skin. Exon 1-encoded prepropeptide is conserved in genes for peptides of highly different structures and activities.

    Science.gov (United States)

    Vouille, V; Amiche, M; Nicolas, P

    1997-09-01

    We cloned the genes of two members of the dermaseptin family, broad-spectrum antimicrobial peptides isolated from the skin of the arboreal frog Phyllomedusa bicolor. The dermaseptin gene Drg2 has a 2-exon coding structure interrupted by a small 137-bp intron, wherein exon 1 encoded a 22-residue hydrophobic signal peptide and the first three amino acids of the acidic propiece; exon 2 contained the 18 additional acidic residues of the propiece plus a typical prohormone processing signal Lys-Arg and a 32-residue dermaseptin progenitor sequence. The dermaseptin genes Drg2 and Drg1g2 have conserved sequences at both untranslated ends and in the first and second coding exons. In contrast, Drg1g2 comprises a third coding exon for a short version of the acidic propiece and a second dermaseptin progenitor sequence. Structural conservation between the two genes suggests that Drg1g2 arose recently from an ancestral Drg2-like gene through amplification of part of the second coding exon and 3'-untranslated region. Analysis of the cDNAs coding precursors for several frog skin peptides of highly different structures and activities demonstrates that the signal peptides and part of the acidic propieces are encoded by conserved nucleotides encompassed by the first coding exon of the dermaseptin genes. The organization of the genes that belong to this family, with the signal peptide and the progenitor sequence on separate exons, permits strikingly different peptides to be directed into the secretory pathway. The recruitment of such a homologous 'secretory' exon by otherwise non-homologous genes may have been an early event in the evolution of amphibian.

  11. Comprehensive Non-Destructive Conservation Documentation of Lunar Samples Using High-Resolution Image-Based 3D Reconstructions and X-Ray CT Data

    Science.gov (United States)

    Blumenfeld, E. H.; Evans, C. A.; Oshel, E. R.; Liddle, D. A.; Beaulieu, K.; Zeigler, R. A.; Hanna, R. D.; Ketcham, R. A.

    2015-01-01

    Established contemporary conservation methods within the fields of Natural and Cultural Heritage encourage an interdisciplinary approach to preservation of heritage material (both tangible and intangible) that holds "Outstanding Universal Value" for our global community. NASA's lunar samples were acquired from the moon for the primary purpose of intensive scientific investigation. These samples, however, also invoke cultural significance, as evidenced by the millions of people per year that visit lunar displays in museums and heritage centers around the world. Being both scientifically and culturally significant, the lunar samples require a unique conservation approach. Government mandate dictates that NASA's Astromaterials Acquisition and Curation Office develop and maintain protocols for "documentation, preservation, preparation and distribution of samples for research, education and public outreach" for both current and future collections of astromaterials. Documentation, considered the first stage within the conservation methodology, has evolved many new techniques since curation protocols for the lunar samples were first implemented, and the development of new documentation strategies for current and future astromaterials is beneficial to keeping curation protocols up to date. We have developed and tested a comprehensive non-destructive documentation technique using high-resolution image-based 3D reconstruction and X-ray CT (XCT) data in order to create interactive 3D models of lunar samples that would ultimately be served to both researchers and the public. These data enhance preliminary scientific investigations including targeted sample requests, and also provide a new visual platform for the public to experience and interact with the lunar samples. We intend to serve these data as they are acquired on NASA's Astromaterials Acquisistion and Curation website at http://curator.jsc.nasa.gov/. Providing 3D interior and exterior documentation of astromaterial

  12. Mammals of the high altitudes of western Arunachal Pradesh, eastern Himalaya: an assessment of threats and conservation needs

    NARCIS (Netherlands)

    Mishra, C.; Madhusudan, M.D.; Datta, A.

    2006-01-01

    he high altitudes of Arunachal Pradesh, India, located in the Eastern Himalaya biodiversity hotspot, remain zoologically unexplored and unprotected. We report results of recent mammal surveys in the high altitude habitats of western Arunachal Pradesh. A total of 35 mammal species (including 12

  13. The relationship between the Resource Conservation and Recovery Act and the storage and disposal of spent nuclear fuel and high-level waste

    International Nuclear Information System (INIS)

    Gertz, C.P.; Cloke, P.L.

    1993-01-01

    This paper addresses the potential applicability of the requirements of the Resource Conservation and Recovery Act (RCRA) to the disposal of spent commercial nuclear fuel and of high-level (vitrified) radioactive waste. The Atomic Energy Act of 1954, as amended, and the associated regulations issued by the US NRC provides many requirements that apply to these waste forms and largely, if not entirely, pre-empts the applicability of RCRA. The RCRA would apply only to the non-radioactive components of these wastes, and then only in respect to hazardous components. In view of these restrictions it becomes important to evaluate whether any components of spent fuel or high-level waste are toxic, as defined by the RCRA regulations. Present indications are that they are not and, hence, the US DOE is proceeding on the basis that these wastes and others that may be generated in the future are non-hazardous in respect to RCRA definitions

  14. Multivariate analysis and clustering reveal high morphological diversity in Tunisian autochthonous grapes (Vitis vinifera: insights into characterization, conservation and commercialization

    Directory of Open Access Journals (Sweden)

    Myriam Lamine

    2014-06-01

    Significance and impact of the study: In this investigation, we highlight the importance of importance of breeding programs, commercialization and evaluation of economically valuable characteristics of the highly diverse autochthonous grapevine cultivars from Tunisia.

  15. A novel, highly conserved metallothionein family in basidiomycete fungi and characterization of two representative SlMTa and SlMTb genes in the ectomycorrhizal fungus Suillus luteus.

    Science.gov (United States)

    Nguyen, Hoai; Rineau, François; Vangronsveld, Jaco; Cuypers, Ann; Colpaert, Jan V; Ruytinx, Joske

    2017-07-01

    The basidiomycete Suillus luteus is an important member of the ectomycorrhizal community that thrives in heavy metal polluted soils covered with pioneer pine forests. This study aimed to identify potential heavy metal chelators in S. luteus. Two metallothionein (MT) coding genes, SlMTa and SlMTb, were identified. When heterologously expressed in yeast, both SlMTa and SlMTb can rescue the Cu sensitive mutant from Cu toxicity. In S. luteus, transcription of both SlMTa and SlMTb is induced by Cu but not Cd or Zn. Several putative Cu-sensing and metal-response elements are present in the promoter sequences. These results indicate that SlMTa and SlMTb function as Cu-thioneins. Homologs of the S. luteus MTs are present in 49 species belonging to 10 different orders of the subphylum Agaricomycotina and are remarkably conserved. The length of the proteins, number and distribution of cysteine residues indicate a novel family of fungal MTs. The ubiquitous and highly conserved features of these MTs suggest that they are important for basic cellular functions in species in the subphylum Agaricomycotina. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  16. Crystal structure and size-dependent neutralization properties of HK20, a human monoclonal antibody binding to the highly conserved heptad repeat 1 of gp41.

    Science.gov (United States)

    Sabin, Charles; Corti, Davide; Buzon, Victor; Seaman, Mike S; Lutje Hulsik, David; Hinz, Andreas; Vanzetta, Fabrizia; Agatic, Gloria; Silacci, Chiara; Mainetti, Lara; Scarlatti, Gabriella; Sallusto, Federica; Weiss, Robin; Lanzavecchia, Antonio; Weissenhorn, Winfried

    2010-11-18

    The human monoclonal antibody (mAb) HK20 neutralizes a broad spectrum of primary HIV-1 isolates by targeting the highly conserved heptad repeat 1 (HR1) of gp41, which is transiently exposed during HIV-1 entry. Here we present the crystal structure of the HK20 Fab in complex with a gp41 mimetic 5-Helix at 2.3 Å resolution. HK20 employs its heavy chain CDR H2 and H3 loops to bind into a conserved hydrophobic HR1 pocket that is occupied by HR2 residues in the gp41 post fusion conformation. Compared to the previously described HR1-specific mAb D5, HK20 approaches its epitope with a different angle which might favor epitope access and thus contribute to its higher neutralization breadth and potency. Comparison of the neutralization activities of HK20 IgG, Fab and scFv employing both single cycle and multiple cycle neutralization assays revealed much higher potencies for the smaller Fab and scFv over IgG, implying that the target site is difficult to access for complete antibodies. Nevertheless, two thirds of sera from HIV-1 infected individuals contain significant titers of HK20-inhibiting antibodies. The breadth of neutralization of primary isolates across all clades, the higher potencies for C-clade viruses and the targeting of a distinct site as compared to the fusion inhibitor T-20 demonstrate the potential of HK20 scFv as a therapeutic tool.

  17. Snake venomics of Lachesis muta rhombeata and genus-wide antivenomics assessment of the paraspecific immunoreactivity of two antivenoms evidence the high compositional and immunological conservation across Lachesis.

    Science.gov (United States)

    Pla, Davinia; Sanz, Libia; Molina-Sánchez, Pedro; Zorita, Virginia; Madrigal, Marvin; Flores-Díaz, Marietta; Alape-Girón, Alberto; Núñez, Vitelbina; Andrés, Vicente; Gutiérrez, José María; Calvete, Juan J

    2013-08-26

    We report the proteomic analysis of the Atlantic bushmaster, Lachesis muta rhombeata, from Brazil. Along with previous characterization of the venom proteomes of L. stenophrys (Costa Rica), L. melanocephala (Costa Rica), L. acrochorda (Colombia), and L. muta muta (Bolivia), the present study provides the first overview of the composition and distribution of venom proteins across this wide-ranging genus, and highlights the remarkable similar compositional and pharmacological profiles across Lachesis venoms. The paraspecificity of two antivenoms, produced at Instituto Vital Brazil (Brazil) and Instituto Clodomiro Picado (Costa Rica) using different conspecific taxa in the immunization mixtures, was assessed using genus-wide comparative antivenomics. This study confirms that the proteomic similarity among Lachesis sp. venoms is mirrored in their high immunological conservation across the genus. The clinical and therapeutic consequences of genus-wide venomics and antivenomics investigations of Lachesis venoms are discussed. The proteomics characterization of L. m. rhombeata venom completes the overview of Lachesis venom proteomes and confirms the remarkable toxin profile conservation across the five clades of this wide-ranging genus. Genus-wide antivenomics showed that two antivenoms, produced against L. stenophrys or L. m. rhombeata, exhibit paraspecificity towards all other congeneric venoms. Our venomics study shows that, despite the broad geographic distribution of the genus, monospecific antivenoms may achieve clinical coverage for any Lachesis sp. envenoming. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Subsets of Women With Close or Positive Margins After Breast-Conserving Surgery With High Local Recurrence Risk Despite Breast Plus Boost Radiotherapy

    International Nuclear Information System (INIS)

    Lupe, Krystine; Truong, Pauline T.; Alexander, Cheryl; Lesperance, Mary; Speers, Caroline; Tyldesley, Scott

    2011-01-01

    Purpose: (1) To examine the effect of surgical margin status on local recurrence (LR) and survival following breast-conserving therapy; (2) To identify subsets with close or positive margins with high LR risk despite whole breast radiotherapy (RT) plus boost. Methods and Materials: Subjects were 2,264 women with pT1–3, any N, M0 invasive breast cancer, treated with breast-conserving surgery and whole breast ± boost RT. Five-year Kaplan-Meier (KM) LR, breast cancer–specific and overall survival (BCSS and OS) were compared between cohorts with negative (n = 1,980), close (n = 222), and positive (n = 62) margins. LR rates were analyzed according to clinicopathologic characteristics. Multivariable Cox regression modeling and matched analysis of close/positive margin cases and negative margin controls were performed. Results: Median follow-up was 5.2 years. Boost RT was used in 92% of patients with close or positive margins. Five-year KM LR rates in the negative, close and positive margin cohorts were 1.3%, 4.0%, and 5.2%, respectively (p = 0.001). BCSS and OS were similar in the three margin subgroups. In the close/positive margin cohort, LR rates were 10.2% with age 10% despite whole breast plus boost RT. These patients should be considered for more definitive surgery.

  19. High throughput sequencing of small RNA component of leaves and inflorescence revealed conserved and novel miRNAs as well as phasiRNA loci in chickpea.

    Science.gov (United States)

    Srivastava, Sangeeta; Zheng, Yun; Kudapa, Himabindu; Jagadeeswaran, Guru; Hivrale, Vandana; Varshney, Rajeev K; Sunkar, Ramanjulu

    2015-06-01

    Among legumes, chickpea (Cicer arietinum L.) is the second most important crop after soybean. MicroRNAs (miRNAs) play important roles by regulating target gene expression important for plant development and tolerance to stress conditions. Additionally, recently discovered phased siRNAs (phasiRNAs), a new class of small RNAs, are abundantly produced in legumes. Nevertheless, little is known about these regulatory molecules in chickpea. The small RNA population was sequenced from leaves and flowers of chickpea to identify conserved and novel miRNAs as well as phasiRNAs/phasiRNA loci. Bioinformatics analysis revealed 157 miRNA loci for the 96 highly conserved and known miRNA homologs belonging to 38 miRNA families in chickpea. Furthermore, 20 novel miRNAs belonging to 17 miRNA families were identified. Sequence analysis revealed approximately 60 phasiRNA loci. Potential target genes likely to be regulated by these miRNAs were predicted and some were confirmed by modified 5' RACE assay. Predicted targets are mostly transcription factors that might be important for developmental processes, and others include superoxide dismutases, plantacyanin, laccases and F-box proteins that could participate in stress responses and protein degradation. Overall, this study provides an inventory of miRNA-target gene interactions for chickpea, useful for the comparative analysis of small RNAs among legumes. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  20. Energy conservation in nationalised transportation sector

    Energy Technology Data Exchange (ETDEWEB)

    Sinha, R C

    1980-01-01

    About 60% of high speed diesel is consumed by the road transport industry. The hike in fuel prices calls for urgent measures to conserve diesel. The paper discusses the various measures undertaken to conserve diesel in the nationalized transport sector.

  1. Biodiversity conservation in a telecoupled world

    Directory of Open Access Journals (Sweden)

    L. Roman Carrasco

    2017-09-01

    Conservation practitioners need to adopt a global perspective on telecoupling and focus on the new conservation opportunities represented by shaping the social norms of affluent consumers in emerging and high-income economies.

  2. The highly conserved 5' untranslated region as an effective target towards the inhibition of Enterovirus 71 replication by unmodified and appropriate 2'-modified siRNAs

    Directory of Open Access Journals (Sweden)

    Deng Jun-Xia

    2012-08-01

    Full Text Available Abstract Background Enterovirus 71 (EV71 is a highly infectious agent that plays an etiological role in hand, foot, and mouth disease. It is associated with severe neurological complications and has caused significant mortalities in recent large-scale outbreaks. Currently, no effective vaccine or specific clinical therapy is available against EV71. Methods Unmodified 21 nucleotide small interfering RNAs (siRNAs and classic 2′-modified (2′-O-methylation or 2′-fluoro modification siRNAs were designed to target highly conserved 5′ untranslated region (UTR of the EV71 genome and employed as anti-EV71 agents. Real-time TaqMan RT-PCR, western blot analysis and plaque assays were carried out to evaluate specific viral inhibition by the siRNAs. Results Transfection of rhabdomyosarcoma (RD cells with siRNAs targeting the EV71 genomic 5′ UTR significantly delayed and alleviated the cytopathic effects of EV71 infection, increased cell viability in EV71-infected RD cells. The inhibitory effect on EV71 replication was sequence-specific and dosage-dependent, with significant corresponding decreases in viral RNA, VP1 protein and viral titer. Appropriate 2′-modified siRNAs exhibited similar RNA interference (RNAi activity with dramatically increased serum stability in comparison with unmodified counterparts. Conclusion Sequences were identified within the highly conserved 5′ UTR that can be targeted to effectively inhibit EV71 replication through RNAi strategies. Appropriate 2′-modified siRNAs provide a promising approach to optimizing siRNAs to overcome barriers on RNAi-based antiviral therapies for broader administration.

  3. Inhibition of Hepatitis C Virus in Mice by a Small Interfering RNA Targeting a Highly Conserved Sequence in Viral IRES Pseudoknot.

    Directory of Open Access Journals (Sweden)

    Jae-Su Moon

    Full Text Available The hepatitis C virus (HCV internal ribosome entry site (IRES that directs cap-independent viral translation is a primary target for small interfering RNA (siRNA-based HCV antiviral therapy. However, identification of potent siRNAs against HCV IRES by bioinformatics-based siRNA design is a challenging task given the complexity of HCV IRES secondary and tertiary structures and association with multiple proteins, which can also dynamically change the structure of this cis-acting RNA element. In this work, we utilized siRNA tiling approach whereby siRNAs were tiled with overlapping sequences that were shifted by one or two nucleotides over the HCV IRES stem-loop structures III and IV spanning nucleotides (nts 277-343. Based on their antiviral activity, we mapped a druggable region (nts 313-343 where the targets of potent siRNAs were enriched. siIE22, which showed the greatest anti-HCV potency, targeted a highly conserved sequence across diverse HCV genotypes, locating within the IRES subdomain IIIf involved in pseudoknot formation. Stepwise target shifting toward the 5' or 3' direction by 1 or 2 nucleotides reduced the antiviral potency of siIE22, demonstrating the importance of siRNA accessibility to this highly structured and sequence-conserved region of HCV IRES for RNA interference. Nanoparticle-mediated systemic delivery of the stability-improved siIE22 derivative gs_PS1 siIE22, which contains a single phosphorothioate linkage on the guide strand, reduced the serum HCV genome titer by more than 4 log10 in a xenograft mouse model for HCV replication without generation of resistant variants. Our results provide a strategy for identifying potent siRNA species against a highly structured RNA target and offer a potential pan-HCV genotypic siRNA therapy that might be beneficial for patients resistant to current treatment regimens.

  4. SeqAPASS to evaluate conservation of high-throughput screening targets across non-mammalian species

    Science.gov (United States)

    Cell-based high-throughput screening (HTS) and computational technologies are being applied as tools for toxicity testing in the 21st century. The U.S. Environmental Protection Agency (EPA) embraced these technologies and created the ToxCast Program in 2007, which has served as a...

  5. Use of genotyping by sequencing data to develop a high-throughput and multifunctional SNP panel for conservation applications in Pacific lamprey.

    Science.gov (United States)

    Hess, Jon E; Campbell, Nathan R; Docker, Margaret F; Baker, Cyndi; Jackson, Aaron; Lampman, Ralph; McIlraith, Brian; Moser, Mary L; Statler, David P; Young, William P; Wildbill, Andrew J; Narum, Shawn R

    2015-01-01

    Next-generation sequencing data can be mined for highly informative single nucleotide polymorphisms (SNPs) to develop high-throughput genomic assays for nonmodel organisms. However, choosing a set of SNPs to address a variety of objectives can be difficult because SNPs are often not equally informative. We developed an optimal combination of 96 high-throughput SNP assays from a total of 4439 SNPs identified in a previous study of Pacific lamprey (Entosphenus tridentatus) and used them to address four disparate objectives: parentage analysis, species identification and characterization of neutral and adaptive variation. Nine of these SNPs are FST outliers, and five of these outliers are localized within genes and significantly associated with geography, run-timing and dwarf life history. Two of the 96 SNPs were diagnostic for two other lamprey species that were morphologically indistinguishable at early larval stages and were sympatric in the Pacific Northwest. The majority (85) of SNPs in the panel were highly informative for parentage analysis, that is, putatively neutral with high minor allele frequency across the species' range. Results from three case studies are presented to demonstrate the broad utility of this panel of SNP markers in this species. As Pacific lamprey populations are undergoing rapid decline, these SNPs provide an important resource to address critical uncertainties associated with the conservation and recovery of this imperiled species. © 2014 John Wiley & Sons Ltd.

  6. US/FRG joint report on the pebble bed high temperature reactor resource conservation potential and associated fuel cycle costs

    International Nuclear Information System (INIS)

    Teuchert, E.; Ruetten, H.J.; Worley, B.A.; Vondy, D.R.

    1979-11-01

    Independent analyses at ORNL and KFA have led to the general conclusion that the flexibility in design and operation of a high-temperature gas-cooled pebble-bed reactor (PBR) can result in favorable ore utilization and fuel costs in comparison with other reactor types, in particular, with light-water reactors (LWRs). Fuel reprocessign and recycle show considerable promise for reducing ore consumption, and even the PBR throwaway cycle is competitive with fuel recycle in an LWR. The best performance results from the use of highly enriched fuel. Proliferation-resistant measures can be taken using medium-enriched fuel at a modest ore penalty, while use of low-enriched fuel would incur further ore penalty. Breeding is possible but net generation of fuel at a significant rate would be expensive, becoming more feasible as ore costs increase substantially. The 233 U inventory for a breeder could be produced by prebreeders using 235 U fuel

  7. Combinatorial binding in human and mouse embryonic stem cells identifies conserved enhancers active in early embryonic development.

    Directory of Open Access Journals (Sweden)

    Jonathan Göke

    2011-12-01

    Full Text Available Transcription factors are proteins that regulate gene expression by binding to cis-regulatory sequences such as promoters and enhancers. In embryonic stem (ES cells, binding of the transcription factors OCT4, SOX2 and NANOG is essential to maintain the capacity of the cells to differentiate into any cell type of the developing embryo. It is known that transcription factors interact to regulate gene expression. In this study we show that combinatorial binding is strongly associated with co-localization of the transcriptional co-activator Mediator, H3K27ac and increased expression of nearby genes in embryonic stem cells. We observe that the same loci bound by Oct4, Nanog and Sox2 in ES cells frequently drive expression in early embryonic development. Comparison of mouse and human ES cells shows that less than 5% of individual binding events for OCT4, SOX2 and NANOG are shared between species. In contrast, about 15% of combinatorial binding events and even between 53% and 63% of combinatorial binding events at enhancers active in early development are conserved. Our analysis suggests that the combination of OCT4, SOX2 and NANOG binding is critical for transcription in ES cells and likely plays an important role for embryogenesis by binding at conserved early developmental enhancers. Our data suggests that the fast evolutionary rewiring of regulatory networks mainly affects individual binding events, whereas "gene regulatory hotspots" which are bound by multiple factors and active in multiple tissues throughout early development are under stronger evolutionary constraints.

  8. The ORF59 DNA polymerase processivity factor homologs of Old World primate RV2 rhadinoviruses are highly conserved nuclear antigens expressed in differentiated epithelium in infected macaques

    Directory of Open Access Journals (Sweden)

    Burnside Kellie L

    2009-11-01

    Full Text Available Abstract Background ORF59 DNA polymerase processivity factor of the human rhadinovirus, Kaposi's sarcoma-associated herpesvirus (KSHV, is required for efficient copying of the genome during virus replication. KSHV ORF59 is antigenic in the infected host and is used as a marker for virus activation and replication. Results We cloned, sequenced and expressed the genes encoding related ORF59 proteins from the RV1 rhadinovirus homologs of KSHV from chimpanzee (PtrRV1 and three species of macaques (RFHVMm, RFHVMn and RFHVMf, and have compared them with ORF59 proteins obtained from members of the more distantly-related RV2 rhadinovirus lineage infecting the same non-human primate species (PtrRV2, RRV, MneRV2, and MfaRV2, respectively. We found that ORF59 homologs of the RV1 and RV2 Old World primate rhadinoviruses are highly conserved with distinct phylogenetic clustering of the two rhadinovirus lineages. RV1 and RV2 ORF59 C-terminal domains exhibit a strong lineage-specific conservation. Rabbit antiserum was developed against a C-terminal polypeptide that is highly conserved between the macaque RV2 ORF59 sequences. This anti-serum showed strong reactivity towards ORF59 encoded by the macaque RV2 rhadinoviruses, RRV (rhesus and MneRV2 (pig-tail, with no cross reaction to human or macaque RV1 ORF59 proteins. Using this antiserum and RT-qPCR, we determined that RRV ORF59 is expressed early after permissive infection of both rhesus primary fetal fibroblasts and African green monkey kidney epithelial cells (Vero in vitro. RRV- and MneRV2-infected foci showed strong nuclear expression of ORF59 that correlated with production of infectious progeny virus. Immunohistochemical studies of an MneRV2-infected macaque revealed strong nuclear expression of ORF59 in infected cells within the differentiating layer of epidermis corroborating previous observations that differentiated epithelial cells are permissive for replication of KSHV-like rhadinoviruses

  9. Repeated conservation threats across the Americas: High levels of blood and bone lead in the Andean Condor widen the problem to a continental scale.

    Science.gov (United States)

    Wiemeyer, Guillermo M; Pérez, Miguel A; Torres Bianchini, Laura; Sampietro, Luciano; Bravo, Guillermo F; Jácome, N Luis; Astore, Vanesa; Lambertucci, Sergio A

    2017-01-01

    Wildlife lead exposure is an increasing conservation threat that is being widely investigated. However, for some areas of the world (e.g., South America) and certain species, research on this subject is still scarce or only local information is available. We analyzed the extent and intensity of lead exposure for a widely distributed threatened species, the Andean Condor (Vultur gryphus). We conducted the study at two different scales: 1) sampling of birds received for rehabilitation or necropsy in Argentina, and 2) bibliographic review and extensive survey considering exposure event for the species' distribution in South America. Wild condors from Argentina (n = 76) presented high lead levels consistent with both recent and previous exposure (up to 104 μg/dL blood level, mean 15.47 ± 21.21 μg/dL and up to 148.20 ppm bone level, mean 23.08 ± 31.39 ppm). In contrast, captive bred individuals -not exposed to lead contamination- had much lower lead levels (mean blood level 5.63 ± 3.08 μg/dL, and mean bone level 2.76 ± 3.06 ppm). Condors were exposed to lead throughout their entire range in continental Argentina, which represents almost sixty percent (>4000 km) of their geographical distribution. We also present evidence of lead exposure events in Chile, Ecuador, and Peru. Lead poisoning is a widespread major conservation threat for the Andean Condor, and probably other sympatric carnivores from South America. The high number and wide range of Andean Condors with lead values complement the results for the California Condor and other scavengers in North America suggesting lead poisoning is a continental threat. Urgent actions are needed to reduce this poison in the wild. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Integrating Landsat Data and High-Resolution Imagery for Applied Conservation Assessment of Forest Cover in Latin American Heterogenous Landscapes

    Science.gov (United States)

    Thomas, N.; Rueda, X.; Lambin, E.; Mendenhall, C. D.

    2012-12-01

    Large intact forested regions of the world are known to be critical to maintaining Earth's climate, ecosystem health, and human livelihoods. Remote sensing has been successfully implemented as a tool to monitor forest cover and landscape dynamics over broad regions. Much of this work has been done using coarse resolution sensors such as AVHRR and MODIS in combination with moderate resolution sensors, particularly Landsat. Finer scale analysis of heterogeneous and fragmented landscapes is commonly performed with medium resolution data and has had varying success depending on many factors including the level of fragmentation, variability of land cover types, patch size, and image availability. Fine scale tree cover in mixed agricultural areas can have a major impact on biodiversity and ecosystem sustainability but may often be inadequately captured with the global to regional (coarse resolution and moderate resolution) satellite sensors and processing techniques widely used to detect land use and land cover changes. This study investigates whether advanced remote sensing methods are able to assess and monitor percent tree canopy cover in spatially complex human-dominated agricultural landscapes that prove challenging for traditional mapping techniques. Our study areas are in high altitude, mixed agricultural coffee-growing regions in Costa Rica and the Colombian Andes. We applied Random Forests regression tree analysis to Landsat data along with additional spectral, environmental, and spatial variables to predict percent tree canopy cover at 30m resolution. Image object-based texture, shape, and neighborhood metrics were generated at the Landsat scale using eCognition and included in the variable suite. Training and validation data was generated using high resolution imagery from digital aerial photography at 1m to 2.5 m resolution. Our results are promising with Pearson's correlation coefficients between observed and predicted percent tree canopy cover of .86 (Costa

  11. Deep-ocean disposal of high-activity nuclear wastes: a conservative assessment of the seafood critical pathway

    International Nuclear Information System (INIS)

    Baxter, M.S.; Economides, B.

    1984-01-01

    This paper applies conventional 'worst-case' assumptions to modelling the effects of possible future disposal of high-activity wastes in the oceans. It otherwise uses previously published and generally accepted data to assess the possible intakes of the waste nuclides via consumption of seaweeds, molluscs, crustaceans, plankton and fish. Model-predicted intakes for critical groups generally exceed ICRP-recommended limits, with 244 Cm, 241 Am and 137 Cs being the most potentially hazardous nuclides. The various seafood consumption pathways are found to rank, in decreasing order of potential hazard, as seaweeds > molluscs > plankton > fish > crustaceans. (Auth.)

  12. Breast-Conservative Surgery With Close or Positive Margins: Can the Breast Be Preserved With High-Dose-Rate Brachytherapy Boost?

    International Nuclear Information System (INIS)

    Guinot, Jose Luis; Roldan, Susana; Maronas, Maria; Tortajada, Isabel; Carrascosa, Maria; Chust, Maria Luisa; Estornell, Marian; Mengual, Jose Luis; Arribas, Leoncio

    2007-01-01

    Purpose: To evaluate the likelihood of preserving the breast in women who show close or positive margins after conservative surgery for early breast carcinoma. Methods and Materials: Since 1996, 125 women with less than 5 mm or positive margins and positive separate cavity margin sampling were entered in a prospective trial with high-dose radiotherapy. A standard dose of 50 Gy to the whole breast was followed by a high-dose-rate brachytherapy application delivering 3 fractions of 4.4 Gy in 24 hours. The median follow-up was 84 months. Results: There were only seven local recurrences, with an actuarial local control rate of 95.8% at 5 years and 91.1% at 9 years. Actuarial overall and cause-specific survival rates were 92.6% and 95% at 5 years and 86.7% and 90.4% at 9 years, respectively. Late fibrosis was the most common complication, in 30% of patients, with good or excellent cosmetic results in 77%. The final result was that 95.2% of breasts were preserved. Conclusions: Close or positive-margin breast cancer can be well managed with a high-dose boost in a wide tumor bed by means of high-dose-rate brachytherapy. This technique can avoid mastectomy or poor cosmetic resection, with minimal risk of local or general failure

  13. High-throughput SHAPE analysis reveals structures in HIV-1 genomic RNA strongly conserved across distinct biological states.

    Directory of Open Access Journals (Sweden)

    Kevin A Wilkinson

    2008-04-01

    Full Text Available Replication and pathogenesis of the human immunodeficiency virus (HIV is tightly linked to the structure of its RNA genome, but genome structure in infectious virions is poorly understood. We invent high-throughput SHAPE (selective 2'-hydroxyl acylation analyzed by primer extension technology, which uses many of the same tools as DNA sequencing, to quantify RNA backbone flexibility at single-nucleotide resolution and from which robust structural information can be immediately derived. We analyze the structure of HIV-1 genomic RNA in four biologically instructive states, including the authentic viral genome inside native particles. Remarkably, given the large number of plausible local structures, the first 10% of the HIV-1 genome exists in a single, predominant conformation in all four states. We also discover that noncoding regions functioning in a regulatory role have significantly lower (p-value < 0.0001 SHAPE reactivities, and hence more structure, than do viral coding regions that function as the template for protein synthesis. By directly monitoring protein binding inside virions, we identify the RNA recognition motif for the viral nucleocapsid protein. Seven structurally homologous binding sites occur in a well-defined domain in the genome, consistent with a role in directing specific packaging of genomic RNA into nascent virions. In addition, we identify two distinct motifs that are targets for the duplex destabilizing activity of this same protein. The nucleocapsid protein destabilizes local HIV-1 RNA structure in ways likely to facilitate initial movement both of the retroviral reverse transcriptase from its tRNA primer and of the ribosome in coding regions. Each of the three nucleocapsid interaction motifs falls in a specific genome domain, indicating that local protein interactions can be organized by the long-range architecture of an RNA. High-throughput SHAPE reveals a comprehensive view of HIV-1 RNA genome structure, and further

  14. The lytic origin of herpesvirus papio is highly homologous to Epstein-Barr virus ori-Lyt: evolutionary conservation of transcriptional activation and replication signals.

    Science.gov (United States)

    Ryon, J J; Fixman, E D; Houchens, C; Zong, J; Lieberman, P M; Chang, Y N; Hayward, G S; Hayward, S D

    1993-01-01

    Herpesvirus papio (HVP) is a B-lymphotropic baboon virus with an estimated 40% homology to Epstein-Barr virus (EBV). We have cloned and sequenced ori-Lyt of herpesvirus papio and found a striking degree of nucleotide homology (89%) with ori-Lyt of EBV. Transcriptional elements form an integral part of EBV ori-Lyt. The promoter and enhancer domains of EBV ori-Lyt are conserved in herpesvirus papio. The EBV ori-Lyt promoter contains four binding sites for the EBV lytic cycle transactivator Zta, and the enhancer includes one Zta and two Rta response elements. All five of the Zta response elements and one of the Rta motifs are conserved in HVP ori-Lyt, and the HVP DS-L leftward promoter and the enhancer were activated in transient transfection assays by the EBV Zta and Rta transactivators. The EBV ori-Lyt enhancer contains a palindromic sequence, GGTCAGCTGACC, centered on a PvuII restriction site. This sequence, with a single base change, is also present in the HVP ori-Lyt enhancer. DNase I footprinting demonstrated that the PvuII sequence was bound by a protein present in a Raji nuclear extract. Mobility shift and competition assays using oligonucleotide probes identified this sequence as a binding site for the cellular transcription factor MLTF. Mutagenesis of the binding site indicated that MLTF contributes significantly to the constitutive activity of the ori-Lyt enhancer. The high degree of conservation of cis-acting signal sequences in HVP ori-Lyt was further emphasized by the finding that an HVP ori-Lyt-containing plasmid was replicated in Vero cells by a set of cotransfected EBV replication genes. The central domain of EBV ori-Lyt contains two related AT-rich palindromes, one of which is partially duplicated in the HVP sequence. The AT-rich palindromes are functionally important cis-acting motifs. Deletion of these palindromes severely diminished replication of an ori-Lyt target plasmid. Images PMID:8389916

  15. Genetic structure analysis of a highly inbred captive population of the African antelope Addax nasomaculatus. Conservation and management implications.

    Science.gov (United States)

    Armstrong, E; Leizagoyen, C; Martínez, A M; González, S; Delgado, J V; Postiglioni, A

    2011-01-01

    The African antelope Addax nasomaculatus is a rare mammal at high risk of extinction, with no more than 300 individuals in the wild and 1,700 captive animals distributed in zoos around the world. In this work, we combine genetic data and genealogical information to assess the structure and genetic diversity of a captive population located at Parque Lecocq Zoo (N=27), originated from only two founders. We amplified 39 microsatellites previously described in other Artiodactyls but new to this species. Seventeen markers were polymorphic, with 2-4 alleles per locus (mean=2.71). Mean expected heterozygosity (He) per locus was between 0.050 (marker ETH3) and 0.650 (marker D5S2), with a global He of 0.43. The mean inbreeding coefficient of the population computed from pedigree records of all registered individuals (N=53) was 0.222. The mean coancestry of the population was 0.298 and F(IS) index was -0.108. These results reflect the importance of an adequate breeding management on a severely bottlenecked captive population, which would benefit by the incorporation of unrelated individuals. Thanks to the successful amplification of a large number of microsatellites commonly used in domestic bovids, this study will provide useful information for the management of this population and serve as future reference for similar studies in other captive populations of this species. © 2010 Wiley-Liss, Inc.

  16. Multi-species comparative analysis of the equine ACE gene identifies a highly conserved potential transcription factor binding site in intron 16.

    Science.gov (United States)

    Hamilton, Natasha A; Tammen, Imke; Raadsma, Herman W

    2013-01-01

    Angiotensin converting enzyme (ACE) is essential for control of blood pressure. The human ACE gene contains an intronic Alu indel (I/D) polymorphism that has been associated with variation in serum enzyme levels, although the functional mechanism has not been identified. The polymorphism has also been associated with cardiovascular disease, type II diabetes, renal disease and elite athleticism. We have characterized the ACE gene in horses of breeds selected for differing physical abilities. The equine gene has a similar structure to that of all known mammalian ACE genes. Nine common single nucleotide polymorphisms (SNPs) discovered in pooled DNA were found to be inherited in nine haplotypes. Three of these SNPs were located in intron 16, homologous to that containing the Alu polymorphism in the human. A highly conserved 18 bp sequence, also within that intron, was identified as being a potential binding site for the transcription factors Oct-1, HFH-1 and HNF-3β, and lies within a larger area of higher than normal homology. This putative regulatory element may contribute to regulation of the documented inter-individual variation in human circulating enzyme levels, for which a functional mechanism is yet to be defined. Two equine SNPs occurred within the conserved area in intron 16, although neither of them disrupted the putative binding site. We propose a possible regulatory mechanism of the ACE gene in mammalian species which was previously unknown. This advance will allow further analysis leading to a better understanding of the mechanisms underpinning the associations seen between the human Alu polymorphism and enzyme levels, cardiovascular disease states and elite athleticism.

  17. Crystal structure and size-dependent neutralization properties of HK20, a human monoclonal antibody binding to the highly conserved heptad repeat 1 of gp41.

    Directory of Open Access Journals (Sweden)

    Charles Sabin

    Full Text Available The human monoclonal antibody (mAb HK20 neutralizes a broad spectrum of primary HIV-1 isolates by targeting the highly conserved heptad repeat 1 (HR1 of gp41, which is transiently exposed during HIV-1 entry. Here we present the crystal structure of the HK20 Fab in complex with a gp41 mimetic 5-Helix at 2.3 Å resolution. HK20 employs its heavy chain CDR H2 and H3 loops to bind into a conserved hydrophobic HR1 pocket that is occupied by HR2 residues in the gp41 post fusion conformation. Compared to the previously described HR1-specific mAb D5, HK20 approaches its epitope with a different angle which might favor epitope access and thus contribute to its higher neutralization breadth and potency. Comparison of the neutralization activities of HK20 IgG, Fab and scFv employing both single cycle and multiple cycle neutralization assays revealed much higher potencies for the smaller Fab and scFv over IgG, implying that the target site is difficult to access for complete antibodies. Nevertheless, two thirds of sera from HIV-1 infected individuals contain significant titers of HK20-inhibiting antibodies. The breadth of neutralization of primary isolates across all clades, the higher potencies for C-clade viruses and the targeting of a distinct site as compared to the fusion inhibitor T-20 demonstrate the potential of HK20 scFv as a therapeutic tool.

  18. Multi-species comparative analysis of the equine ACE gene identifies a highly conserved potential transcription factor binding site in intron 16.

    Directory of Open Access Journals (Sweden)

    Natasha A Hamilton

    Full Text Available Angiotensin converting enzyme (ACE is essential for control of blood pressure. The human ACE gene contains an intronic Alu indel (I/D polymorphism that has been associated with variation in serum enzyme levels, although the functional mechanism has not been identified. The polymorphism has also been associated with cardiovascular disease, type II diabetes, renal disease and elite athleticism. We have characterized the ACE gene in horses of breeds selected for differing physical abilities. The equine gene has a similar structure to that of all known mammalian ACE genes. Nine common single nucleotide polymorphisms (SNPs discovered in pooled DNA were found to be inherited in nine haplotypes. Three of these SNPs were located in intron 16, homologous to that containing the Alu polymorphism in the human. A highly conserved 18 bp sequence, also within that intron, was identified as being a potential binding site for the transcription factors Oct-1, HFH-1 and HNF-3β, and lies within a larger area of higher than normal homology. This putative regulatory element may contribute to regulation of the documented inter-individual variation in human circulating enzyme levels, for which a functional mechanism is yet to be defined. Two equine SNPs occurred within the conserved area in intron 16, although neither of them disrupted the putative binding site. We propose a possible regulatory mechanism of the ACE gene in mammalian species which was previously unknown. This advance will allow further analysis leading to a better understanding of the mechanisms underpinning the associations seen between the human Alu polymorphism and enzyme levels, cardiovascular disease states and elite athleticism.

  19. High-affinity interaction of hnRNP A1 with conserved RNA structural elements is required for translation and replication of enterovirus 71.

    Science.gov (United States)

    Levengood, Jeffrey D; Tolbert, Michele; Li, Mei-Ling; Tolbert, Blanton S

    2013-07-01

    Human Enterovirus 71 (EV71) is an emerging pathogen of infectious disease and a serious threat to public health. Currently, there are no antivirals or vaccines to slow down or prevent EV71 infections, thus underscoring the urgency to better understand mechanisms of host-enterovirus interactions. EV71 uses a type I internal ribosome entry site (IRES) to recruit the 40S ribosomal subunit via a pathway that requires the cytoplasmic localization of hnRNP A1, which acts as an IRES trans-activating factor. The mechanism of how hnRNP A1 trans activates EV71 RNA translation is unknown, however. Here, we report that the UP1 domain of hnRNP A1 interacts specifically with stem loop II (SLII) of the IRES, via a thermodynamically well-defined biphasic transition that involves conserved bulge 5'-AYAGY-3' and hairpin 5'-RY(U/A)CCA-3' loops. Calorimetric titrations of wild-type and mutant SLII constructs reveal these structural elements are essential to form a high-affinity UP1-SLII complex. Mutations that alter the bulge and hairpin primary or secondary structures abrogate the biphasic transition and destabilize the complex. Notably, mutations within the bulge that destabilize the complex correlate with a large reduction in IRES-dependent translational activity and impair EV71 replication. Taken together, this study shows that a conserved SLII structure is necessary to form a functional hnRNP A1-IRES complex, suggesting that small molecules that target this stem loop may have novel antiviral properties.

  20. CT-image based conformal high-dose rate brachytherapy boost in the conservative treatment of stage I - II breast cancer - introducing the procedure

    International Nuclear Information System (INIS)

    Kubaszewska, M.; Skowronek, J.; Chichel, A.; Kanikowski, M.; Dymnicka, M.

    2008-01-01

    Aim: Breast-conserving surgery (BCS) followed by radiotherapy (RT) has become the standard treatment for the majority of patients with early breast cancer. With regard to boost technique some disagreements are found between groups that are emphasizing the value of electron boost treatment and groups pointing out the value of interstitial brachytherapy (BT) boost treatment. We present the preliminary results in treating selected patients with early-stage breast cancer using high-dose-rate brachytherapy (HD R-BT) as a boost after breast conservation therapy (BCT). Materials/Methods: Between January 2006 and August 2007, a total of 58 female patients with first and second stage breast cancer underwent BCT. This therapeutic procedure involves BCS, whole breast radiation therapy (WBRT) and additional irradiation to the tumour bed (boost) using interstitial HDR-BT via flexible implant tubes. A 10 Gy boost dose was received by all patients. The treatment planning was based on CT-guided 3D (three-dimensional) reconstruction of the surgical clips, implant tubes and critical structures localization (skin and ribs). The accuracy of tumour bed localization, the conformity of planning target volume and treated volume were analyzed. Results: The evaluations of implant parameters involved the use of: dose volume histogram (DVH), the volume encompassed by the 100% reference isodose surface (V100%), the high dose volumecalculation (V150%, V200%, V300%), the dose non-uniformity ratio (DNR), and the conformity index (COIN). Our results were as follows: the mean PTV volume, the mean high dose volume (V150%; V200%; V300%), the DNR and COIN mean value were estimated at 57.38, 42.98, 21.38, 7.90, 0.52 and 0.83 respectively. Conclusions: CT-guided 3D HDR-BT is most appropriate for planning the boost procedure after BT especially in large breast volume, in cases with a deep seated tumour bed, as well as in patients with high risk for local recurrences. This technique reduces the

  1. Promoting household energy conservation

    International Nuclear Information System (INIS)

    Steg, Linda

    2008-01-01

    It is commonly assumed that households must change their behaviour to reduce the problems caused by increasing levels of fossil energy use. Strategies for behaviour change will be more effective if they target the most important causes of the behaviour in question. Therefore, this paper first discusses the factors influencing household energy use. Three barriers to fossil fuel energy conservation are discussed: insufficient knowledge of effective ways to reduce household energy use, the low priority and high costs of energy savings, and the lack of feasible alternatives. Next, the paper elaborates on the effectiveness and acceptability of strategies aimed to promote household energy savings. Informational strategies aimed at changing individuals' knowledge, perceptions, cognitions, motivations and norms, as well as structural strategies aimed at changing the context in which decisions are made, are discussed. This paper focuses on the psychological literature on household energy conservation, which mostly examined the effects of informational strategies. Finally, this paper lists important topics for future research

  2. The Chthonomonas calidirosea Genome Is Highly Conserved across Geographic Locations and Distinct Chemical and Microbial Environments in New Zealand's Taupō Volcanic Zone.

    Science.gov (United States)

    Lee, Kevin C; Stott, Matthew B; Dunfield, Peter F; Huttenhower, Curtis; McDonald, Ian R; Morgan, Xochitl C

    2016-06-15

    Chthonomonas calidirosea T49(T) is a low-abundance, carbohydrate-scavenging, and thermophilic soil bacterium with a seemingly disorganized genome. We hypothesized that the C. calidirosea genome would be highly responsive to local selection pressure, resulting in the divergence of its genomic content, genome organization, and carbohydrate utilization phenotype across environments. We tested this hypothesis by sequencing the genomes of four C. calidirosea isolates obtained from four separate geothermal fields in the Taupō Volcanic Zone, New Zealand. For each isolation site, we measured physicochemical attributes and defined the associated microbial community by 16S rRNA gene sequencing. Despite their ecological and geographical isolation, the genome sequences showed low divergence (maximum, 1.17%). Isolate-specific variations included single-nucleotide polymorphisms (SNPs), restriction-modification systems, and mobile elements but few major deletions and no major rearrangements. The 50-fold variation in C. calidirosea relative abundance among the four sites correlated with site environmental characteristics but not with differences in genomic content. Conversely, the carbohydrate utilization profiles of the C. calidirosea isolates corresponded to the inferred isolate phylogenies, which only partially paralleled the geographical relationships among the sample sites. Genomic sequence conservation does not entirely parallel geographic distance, suggesting that stochastic dispersal and localized extinction, which allow for rapid population homogenization with little restriction by geographical barriers, are possible mechanisms of C. calidirosea distribution. This dispersal and extinction mechanism is likely not limited to C. calidirosea but may shape the populations and genomes of many other low-abundance free-living taxa. This study compares the genomic sequence variations and metabolisms of four strains of Chthonomonas calidirosea, a rare thermophilic bacterium from

  3. Geographies of Conservation I: De-extinction and Precision Conservation

    OpenAIRE

    Adams, William Mark

    2016-01-01

    Extinction has long been a central concern in biodiversity conservation. Today, de-extinction offers interesting possibilities of restoring charismatic species and ecosystem function, but also risks and costs. Most de-extinction depends on genetic engineering and synthetic biology. These technologies are also proposed for use in ‘gene tweaking’ in wild species to enhance their chance of survival. Within conservation, the resulting debates pit an optimistic world of high-tech ‘precision con...

  4. Evaluation the consistency of location of moist desquamation and skin high dose area for breast cancer patients receiving adjuvant radiotherapy after breast conservative surgery

    International Nuclear Information System (INIS)

    Sun, Li-Min; Huang, Eng-Yen; Liang, Ji-An; Meng, Fan-Yun; Chang, Gia-Hsin; Tsao, Min-Jen

    2013-01-01

    To evaluate whether the location of moist desquamation matches high dose area for breast cancer patients receiving adjuvant radiotherapy (RT) after breast conservative surgery. One hundred and nine breast cancer patients were enrolled to this study. Their highest skin dose area (the hot spot) was estimated from the treatment planning. We divided the irradiated field into breast; sternal/parasternal; axillary; and inframammary fold areas. The location for moist desquamation was recorded to see if it matches the hot spot. We also analyzed other possible risk factors which may be related to the moist desquamation. Forty-eight patients with 65 locations developed moist desquamation during the RT course. Patients with larger breast sizes and easy to sweat are two independent risk factors for moist desquamation. The distribution of moist desquamation occurred most in the axillary area. All nine patients with the hot spots located at the axillary area developed moist desquamation at the axillary area, and six out of seven patients with the hot spots located at the inframammary fold developed moist desquamation there. The majority of patients with moist desquamation over the breast or sternal/parasternal areas had the hot spots located at these areas. For a patient with moist desquamation, if a hot spot is located at the axillary or inframammary fold areas, it is very likely to have moist desquamation occur there. On the other hand, if moist desquamation occurs over the breast or sternal/parasternal areas, we can highly expect these two areas are also the hot spot locations

  5. It's not too late for the harpy eagle (Harpia harpyja: high levels of genetic diversity and differentiation can fuel conservation programs.

    Directory of Open Access Journals (Sweden)

    Heather R L Lerner

    2009-10-01

    Full Text Available The harpy eagle (Harpia harpyja is the largest Neotropical bird of prey and is threatened by human persecution and habitat loss and fragmentation. Current conservation strategies include local education, captive rearing and reintroduction, and protection or creation of trans-national habitat blocks and corridors. Baseline genetic data prior to reintroduction of captive-bred stock is essential for guiding such efforts but has not been gathered previously.We assessed levels of genetic diversity, population structure and demographic history for harpy eagles using samples collected throughout a large portion of their geographic distribution in Central America (n = 32 and South America (n = 31. Based on 417 bp of mitochondrial control region sequence data, relatively high levels of haplotype and nucleotide diversity were estimated for both Central and South America, although haplotype diversity was significantly higher for South America. Historical restriction of gene flow across the Andes (i.e. between our Central and South American subgroups is supported by coalescent analyses, the haplotype network and significant F(ST values, however reciprocally monophyletic lineages do not correspond to geographical locations in maximum likelihood analyses. A sudden population expansion for South America is indicated by a mismatch distribution analysis, and further supported by significant (p<0.05 negative values of Fu and Li's D(F and F, and Fu's F(S. This expansion, estimated at approximately 60 000 years BP (99 000-36 000 years BP 95% CI, encompasses a transition from a warm and dry time period prior to 50 000 years BP to an interval of maximum precipitation (50 000-36 000 years BP. Notably, this time period precedes the climatic and habitat changes associated with the last glacial maximum. In contrast, a multimodal distribution of haplotypes was observed for Central America suggesting either population equilibrium or a recent decline.High levels of

  6. Non-native and native organisms moving into high elevation and high latitude ecosystems in an era of climate change: new challenges for ecology and conservation

    Science.gov (United States)

    Pauchard, Aníbal; Albihn, Ann; Alexander, Jake; Burgess, Treena; Daehler, Curt; Essl, Franz; Evengard, Birgitta; Greenwood, Greg; Haider, Sylvia; Lenoir, Jonathan; McDougall, K.; Milbau, Ann; Muths, Erin L.; Nunez, Martin; Pellissier, Lois; Rabitsch, Wolfgang; Rew, Lisa; Robertson, Mark; Sanders, Nathan; Kueffer, Christoph

    2016-01-01

    Cold environments at high elevation and high latitude are often viewed as resistant to biological invasions. However, climate warming, land use change and associated increased connectivity all increase the risk of biological invasions in these environments. Here we present a summary of the key discussions of the workshop ‘Biosecurity in Mountains and Northern Ecosystems: Current Status and Future Challenges’ (Flen, Sweden, 1–3 June 2015). The aims of the workshop were to (1) increase awareness about the growing importance of species expansion—both non-native and native—at high elevation and high latitude with climate change, (2) review existing knowledge about invasion risks in these areas, and (3) encourage more research on how species will move and interact in cold environments, the consequences for biodiversity, and animal and human health and wellbeing. The diversity of potential and actual invaders reported at the workshop and the likely interactions between them create major challenges for managers of cold environments. However, since these cold environments have experienced fewer invasions when compared with many warmer, more populated environments, prevention has a real chance of success, especially if it is coupled with prioritisation schemes for targeting invaders likely to have greatest impact. Communication and co-operation between cold environment regions will facilitate rapid response, and maximise the use of limited research and management resources.

  7. Making conservation work for everyone

    Energy Technology Data Exchange (ETDEWEB)

    Wiersma, J. [Veridian Corp., Ajax, ON (Canada)

    2004-07-01

    This presentation discussed the economic value of conservation, the optimal deployment of energy conservation. A sample load profile was presented to demonstrate how much electricity the average residential customer uses on a summer day. The average customer does not have the tools to understand the financial consequences of conservation for different types of equipment at different times of the day. Smart metering technology could help in this regard. Accurate unsubsidized prices are also considered to be the best incentive to conserve because customers will reduce electricity use when the prices are high. It was also suggested that standards for new appliances should be increased effectively to their economic value. The enablers to energy conservation include solid consumer education programs, real time metering in places where it is cost effective, real time pricing in places where it is practical, and power rates that reflect real costs. Barriers to energy conservation include the residual economic advantage that may be insufficient to justify investment; support from local distribution companies and transmission companies if the lost revenue adjustment mechanism (LRAM) is not sufficient to recover lost revenue and if LDCs are not sufficiently involved in the design of the electricity conservation program. 7 figs.

  8. IAA-Ala Resistant3, an evolutionarily conserved target of miR167, mediates Arabidopsis root architecture changes during high osmotic stress

    KAUST Repository

    Kinoshita, Natsuko

    2012-09-01

    The functions of microRNAs and their target mRNAs in Arabidopsis thaliana development have been widely documented; however, roles of stress-responsive microRNAs and their targets are not as well understood. Using small RNA deep sequencing and ATH1 microarrays to profile mRNAs, we identified IAA-Ala Resistant3 (IAR3) as a new target of miR167a. As expected, IAR3 mRNA was cleaved at the miR167a complementary site and under high osmotic stress miR167a levels decreased, whereas IAR3 mRNA levels increased. IAR3 hydrolyzes an inactive form of auxin (indole-3-acetic acid [IAA]-alanine) and releases bioactive auxin (IAA), a central phytohormone for root development. In contrast with the wild type, iar3 mutants accumulated reduced IAA levels and did not display high osmotic stress-induced root architecture changes. Transgenic plants expressing a cleavage-resistant form of IAR3 mRNA accumulated high levels of IAR3 mRNAs and showed increased lateral root development compared with transgenic plants expressing wild-type IAR3. Expression of an inducible noncoding RNA to sequester miR167a by target mimicry led to an increase in IAR3 mRNA levels, further confirming the inverse relationship between the two partners. Sequence comparison revealed the miR167 target site on IAR3 mRNA is conserved in evolutionarily distant plant species. Finally, we showed that IAR3 is required for drought tolerance. © 2012 American Society of Plant Biologists. All rights reserved.

  9. IAA-Ala Resistant3, an evolutionarily conserved target of miR167, mediates Arabidopsis root architecture changes during high osmotic stress

    KAUST Repository

    Kinoshita, Natsuko; Wang, Huan; Kasahara, Hiroyuki; Liu, Jun; MacPherson, Cameron R.; Machida, Yasunori; Kamiya, Yuji; Hannah, Matthew A.; Chuaa, Nam Hai

    2012-01-01

    The functions of microRNAs and their target mRNAs in Arabidopsis thaliana development have been widely documented; however, roles of stress-responsive microRNAs and their targets are not as well understood. Using small RNA deep sequencing and ATH1 microarrays to profile mRNAs, we identified IAA-Ala Resistant3 (IAR3) as a new target of miR167a. As expected, IAR3 mRNA was cleaved at the miR167a complementary site and under high osmotic stress miR167a levels decreased, whereas IAR3 mRNA levels increased. IAR3 hydrolyzes an inactive form of auxin (indole-3-acetic acid [IAA]-alanine) and releases bioactive auxin (IAA), a central phytohormone for root development. In contrast with the wild type, iar3 mutants accumulated reduced IAA levels and did not display high osmotic stress-induced root architecture changes. Transgenic plants expressing a cleavage-resistant form of IAR3 mRNA accumulated high levels of IAR3 mRNAs and showed increased lateral root development compared with transgenic plants expressing wild-type IAR3. Expression of an inducible noncoding RNA to sequester miR167a by target mimicry led to an increase in IAR3 mRNA levels, further confirming the inverse relationship between the two partners. Sequence comparison revealed the miR167 target site on IAR3 mRNA is conserved in evolutionarily distant plant species. Finally, we showed that IAR3 is required for drought tolerance. © 2012 American Society of Plant Biologists. All rights reserved.

  10. Mistaken identity: activating conservative political identities induces "conservative" financial decisions.

    Science.gov (United States)

    Morris, Michael W; Carranza, Erica; Fox, Craig R

    2008-11-01

    Four studies investigated whether activating a social identity can lead group members to choose options that are labeled in words associated with that identity. When political identities were made salient, Republicans (but not Democrats) became more likely to choose the gamble or investment option labeled "conservative." This shift did not occur in a condition in which the same options were unlabeled. Thus, the mechanism underlying the effect appears to be not activated identity-related values prioritizing low risk, but rather activated identity-related language (the group label "conservative"). Indeed, when political identities were salient, Republicans favored options labeled "conservative" regardless of whether the options were low or high risk. Finally, requiring participants to explain the label "conservative" before making their choice did not diminish the effect, which suggests that it does not merely reflect inattention to content or construct accessibility. We discuss the implications of these results for the literatures on identity, priming, choice, politics, and marketing.

  11. Sequence of cDNAs for mammalian H2A. Z, an evolutionarily diverged but highly conserved basal histone H2A isoprotein species

    Energy Technology Data Exchange (ETDEWEB)

    Hatch, C L; Bonner, W M

    1988-02-11

    The nucleotide sequences of cDNAs for the evolutionarily diverged but highly conserved basal H2A isoprotein, H2A.Z, have been determined for the rat, cow, and human. As a basal histone, H2A.Z is synthesized throughout the cell cycle at a constant rate, unlinked to DNA replication, and at a much lower rate in quiescent cells. Each of the cDNA isolates encodes the entire H2A.Z polypeptide. The human isolate is about 1.0 kilobases long. It contains a coding region of 387 nucleotides flanked by 106 nucleotides of 5'UTR and 376 nucleotides of 3'UTR, which contains a polyadenylation signal followed by a poly A tail. The bovine and rat cDNAs have 97 and 94% nucleotide positional identity to the human cDNA in the coding region and 98% in the proximal 376 nucleotides of the 3'UTR which includes the polyadenylation signal. A potential stem-forming sequence imbedded in a direct repeat is found centered at 261 nucleotides into the 3'UTR. Each of the cDNA clones could be transcribed and translated in vitro to yield H2A.Z protein. The mammalian H2A.Z cDNA coding sequences are approximately 80% similar to those in chicken and 75% to those in sea urchin.

  12. Particle-number conserving analysis for the 2-quasiparticle and high-K multi-quasiparticle states in doubly-odd 174,176Lu

    International Nuclear Information System (INIS)

    Li Bingheng; Lei Yi'an; Zhang Zhenhua

    2013-01-01

    Two-quasiparticle bands and low-lying excited high-K four-, six-, and eight-quasiparticle bands in the doubly-odd 174,176 Lu are analyzed by using the cranked shell model (CSM) with the pairing correlations treated by a particle-number conserving (PNC) method, in which the blocking effects are taken into account exactly. The proton and neutron Nilsson level schemes for 174,176 Lu are taken from the adjacent odd-A Lu and Hf isotopes, which are adopted to reproduce the experimental bandhead energies of the one-quasiproton and one-quasineutron bands of these odd-A Lu and Hf nuclei, respectively. Once the quasiparticle configurations are determined, the experimental bandhead energies and the moments of inertia of these two- and multi-quasiparticle bands are well reproduced by PNC-CSM calculations. The Coriolis mixing of the low-K (K=|Ω 1 -Ω 2 |) two-quasiparticle band of the Gallagher-Moszkowski doublet with one nucleon in the Ω=1/2 orbital is analyzed. (authors)

  13. NOA36 Protein Contains a Highly Conserved Nucleolar Localization Signal Capable of Directing Functional Proteins to the Nucleolus, in Mammalian Cells

    Science.gov (United States)

    de Melo, Ivan S.; Jimenez-Nuñez, Maria D.; Iglesias, Concepción; Campos-Caro, Antonio; Moreno-Sanchez, David; Ruiz, Felix A.; Bolívar, Jorge

    2013-01-01

    NOA36/ZNF330 is an evolutionarily well-preserved protein present in the nucleolus and mitochondria of mammalian cells. We have previously reported that the pro-apoptotic activity of this protein is mediated by a characteristic cysteine-rich domain. We now demonstrate that the nucleolar localization of NOA36 is due to a highly-conserved nucleolar localization signal (NoLS) present in residues 1–33. This NoLS is a sequence containing three clusters of two or three basic amino acids. We fused the amino terminal of NOA36 to eGFP in order to characterize this putative NoLS. We show that a cluster of three lysine residues at positions 3 to 5 within this sequence is critical for the nucleolar localization. We also demonstrate that the sequence as found in human is capable of directing eGFP to the nucleolus in several mammal, fish and insect cells. Moreover, this NoLS is capable of specifically directing the cytosolic yeast enzyme polyphosphatase to the target of the nucleolus of HeLa cells, wherein its enzymatic activity was detected. This NoLS could therefore serve as a very useful tool as a nucleolar marker and for directing particular proteins to the nucleolus in distant animal species. PMID:23516598

  14. Conservation potential of agricultural water conservation subsidies

    Science.gov (United States)

    Huffaker, Ray

    2008-07-01

    A current policy subsidizes farmers to invest in improved on-farm irrigation efficiency, expecting water to be conserved off farm. Contrary to expectation, water has been increasingly depleted in some regions after such improvements. This paper investigates the policy's failure to conserve water consistently by (1) formulating an economic model of irrigated crop production to determine a profit-maximizing irrigator's range of responses to a subsidy and (2) embedding these responses into hypothetical streamflow diagrams to ascertain their potential to conserve water under various hydrologic regimes. Testable hypotheses are developed to predict the conservation potential of a subsidy in real-world application.

  15. Method of localization and implantation of the lumpectomy site for high dose rate brachytherapy after conservative surgery for T1 and T2 breast cancer

    International Nuclear Information System (INIS)

    Perera, F.; Chisela, F.; Engel, J.; Venkatesan, V.

    1995-01-01

    Purpose: This article describes our technique of localization and implantation of the lumpectomy site of patients with T1 and T2 breast cancer. Our method was developed as part of our Phase I/II pilot study of high dose rate (HDR) brachytherapy alone after conservative surgery for early breast cancer. Methods and Materials: In March 1992, we started a pilot study of HDR brachytherapy to the lumpectomy site as the sole radiotherapy after conservative surgery for clinical T1 or T2 invasive breast cancer. Initially, the protocol required intraoperative placement of the interstitial needles at the time of definitive surgery to the breast. The protocol was then generalized to allow the implantation of the lumpectomy site after definitive surgery to the breast, either at the time of subsequent axillary nodal dissection or postoperatively. To date, five patients have been implanted intraoperatively at the time of definitive breast surgery. Twelve patients were implanted after definitive breast surgery, with 7 patients being done at the time of axillary nodal dissection and 5 patients postoperatively. We devised a method of accurately localizing and implanting the lumpectomy site after definitive breast surgery. The method relies on the previous placement of surgical clips by the referring surgeon to mark the lumpectomy site. For each patient, a breast mold is made with radio-opaque angiocatheters taped onto the mold in the supero-inferior direction. A planning CT scan is then obtained through the lumpectomy site. The volume of the lumpectomy site, the number of implant planes necessary, and the orientation of the implants are then determined from the CT scan. The angiocatheters provide a reference grid on the CT films to locate the entry and exit points of the interstitial needles on the plastic mold. The entry and exit points for reference needles are then transferred onto the patient's skin enabling implantation of the lumpectomy site. Needle positions with respect to

  16. Conservation and genetic characterisation of common bean landraces from Cilento region (southern Italy): high differentiation in spite of low genetic diversity.

    Science.gov (United States)

    De Luca, Daniele; Cennamo, Paola; Del Guacchio, Emanuele; Di Novella, Riccardo; Caputo, Paolo

    2018-02-01

    Since its introduction from Central-South America to Italy almost 500 years ago, the common bean (Phaseolus vulgaris L.) was largely cultivated across the peninsula in hundreds of different landraces. However, globalisation and technological modernisation of agricultural practices in the last decades promoted the cultivation of few varieties at the expense of traditional and local agro-ecotypes, which have been confined to local markets or have completely disappeared. The aim of this study was to evaluate the genetic diversity and differentiation in 12 common bean landraces once largely cultivated in the Cilento region (Campania region, southern Italy), and now the object of a recovery program to save them from extinction. The analysis conducted using 13 nuclear microsatellite loci in 140 individuals revealed a high degree of homozygosity within each landrace and a strong genetic differentiation that was reflected in the success in assigning individuals to the source landrace. On the contrary, internal transcribed spacers 1 and 2, analysed in one individual per landrace, were highly similar among common bean landraces but allowed the identification of a cowpea variety (Vigna unguiculata Walp.), a crop largely cultivated in the Old World before the arrival of common bean from Americas. In conclusion, our study highlighted that conservation of landraces is important not only for the cultural and socio-economic value that they have for local communities, but also because the time and conditions in which they have been selected have led to that genetic distinctiveness that is at the basis of many potential agronomical applications and dietary benefits.

  17. The albinism of the feral Asinara white donkeys (Equus asinus) is determined by a missense mutation in a highly conserved position of the tyrosinase (TYR) gene deduced protein.

    Science.gov (United States)

    Utzeri, V J; Bertolini, F; Ribani, A; Schiavo, G; Dall'Olio, S; Fontanesi, L

    2016-02-01

    A feral donkey population (Equus asinus), living in the Asinara National Park (an island north-west of Sardinia, Italy), includes a unique white albino donkey subpopulation or colour morph that is a major attraction of this park. Disrupting mutations in the tyrosinase (TYR) gene are known to cause recessive albinisms in humans (oculocutaneous albinism Type 1; OCA1) and other species. In this study, we analysed the donkey TYR gene as a strong candidate to identify the causative mutation of the albinism of these donkeys. The TYR gene was sequenced from 13 donkeys (seven Asinara white albino and six coloured animals). Seven single nucleotide polymorphisms were identified. A missense mutation (c.604C>G; p.His202Asp) in a highly conserved amino acid position (even across kingdoms), which disrupts the first copper-binding site (CuA) of functional protein, was identified in the homozygous condition (G/G or D/D) in all Asinara white albino donkeys and in the albino son of a trio (the grey parents had genotype C/G or H/D), supporting the recessive mode of inheritance of this mutation. Genotyping 82 donkeys confirmed that Asinara albino donkeys had genotype G/G whereas all other coloured donkeys had genotype C/C or C/G. Across-population association between the c.604C>G genotypes and the albino coat colour was highly significant (P = 6.17E-18). The identification of the causative mutation of the albinism in the Asinara white donkeys might open new perspectives to study the dynamics of this putative deleterious allele in a feral population and to manage this interesting animal genetic resource. © 2015 Stichting International Foundation for Animal Genetics.

  18. A conserved motif in the linker domain of STAT1 transcription factor is required for both recognition and release from high-affinity DNA-binding sites.

    Science.gov (United States)

    Hüntelmann, Bettina; Staab, Julia; Herrmann-Lingen, Christoph; Meyer, Thomas

    2014-01-01

    Binding to specific palindromic sequences termed gamma-activated sites (GAS) is a hallmark of gene activation by members of the STAT (signal transducer and activator of transcription) family of cytokine-inducible transcription factors. However, the precise molecular mechanisms involved in the signal-dependent finding of target genes by STAT dimers have not yet been very well studied. In this study, we have characterized a sequence motif in the STAT1 linker domain which is highly conserved among the seven human STAT proteins and includes surface-exposed residues in close proximity to the bound DNA. Using site-directed mutagenesis, we have demonstrated that a lysine residue in position 567 of the full-length molecule is required for GAS recognition. The substitution of alanine for this residue completely abolished both binding to high-affinity GAS elements and transcriptional activation of endogenous target genes in cells stimulated with interferon-γ (IFNγ), while the time course of transient nuclear accumulation and tyrosine phosphorylation were virtually unchanged. In contrast, two glutamic acid residues (E559 and E563) on each monomer are important for the dissociation of dimeric STAT1 from DNA and, when mutated to alanine, result in elevated levels of tyrosine-phosphorylated STAT1 as well as prolonged IFNγ-stimulated nuclear accumulation. In conclusion, our data indicate that the kinetics of signal-dependent GAS binding is determined by an array of glutamic acid residues located at the interior surface of the STAT1 dimer. These negatively charged residues appear to align the long axis of the STAT1 dimer in a position perpendicular to the DNA, thereby facilitating the interaction between lysine 567 and the phosphodiester backbone of a bound GAS element, which is a prerequisite for transient gene induction.

  19. Project CHOICE: #26. A Career Education Unit for Junior High School. Careers in Conservation of the Environment and Natural Resources. (Agriculture and Ecological Studies Cluster; Science and Engineering Occupations Cluster).

    Science.gov (United States)

    Kern County Superintendent of Schools, Bakersfield, CA.

    This junior high teaching unit on careers in conservation of the environment and natural resources is one in a series of career guidebooks developed by Project CHOICE (Children Have Options in Career Education) to provide the classroom teacher with a source of career-related activities linking classroom experiences with the world of work. The unit…

  20. 78 FR 51463 - Energy Conservation Program: Energy Conservation Standards for Metal Halide Lamp Fixtures

    Science.gov (United States)

    2013-08-20

    ... merging the metal halide lamp fixture and the high-intensity discharge (HID) lamp rulemakings. This NOPR... Conservation Program: Energy Conservation Standards for Metal Halide Lamp Fixtures; Proposed Rule #0;#0;Federal...: Energy Conservation Standards for Metal Halide Lamp Fixtures AGENCY: Office of Energy Efficiency and...

  1. Planning for land use and conservation: Assessing GIS-based conservation software for land use planning

    Science.gov (United States)

    Rob Baldwin; Ryan Scherzinger; Don Lipscomb; Miranda Mockrin; Susan Stein

    2014-01-01

    Recent advances in planning and ecological software make it possible to conduct highly technical analyses to prioritize conservation investments and inform local land use planning. We review these tools, termed conservation planning tools, and assess the knowledge of a key set of potential users: the land use planning community. We grouped several conservation software...

  2. Some AFLP amplicons are highly conserved DNA sequences mapping to the same linkage groups in two F2 populations of carrot

    Directory of Open Access Journals (Sweden)

    Santos Carlos A.F.

    2002-01-01

    Full Text Available Amplified fragment length polymorphism (AFLP is a fast and reliable tool to generate a large number of DNA markers. In two unrelated F2 populations of carrot (Daucus carota L., Brasilia x HCM and B493 x QAL (wild carrot, it was hypothesized that DNA 1 digested with the same restriction endonuclease enzymes and amplified with the same primer combination and 2 sharing the same position in polyacrylamide gels should be conserved sequences. To test this hypothesis AFLP fragments from polyacrylamide gels were eluted, reamplified, separated in agarose gels, purified, cloned and sequenced. Among thirty-one paired fragments from each F2 population, twenty-six had identity greater than 91% and five presented identity of 24% to 44%. Among the twenty-six conserved AFLPs only one mapped to different linkage groups in the two populations while four of the five less-conserved bands mapped to different linkage groups. Of eight SCAR (sequence characterized amplified regions primers tested, one conserved AFLP resulted in co-dominant markers in both populations. Screening among 14 carrot inbreds or cultivars with three AFLP-SCAR primers revealed clear and polymorphic PCR products, with similar molecular sizes on agarose gels. The development of co-dominant markers based on conserved AFLP fragments will be useful to detect seed mixtures among hybrids, to improve and to merge linkage maps and to study diversity and phylogenetic relationships.

  3. Identifying temporal bottlenecks for the conservation of large-bodied fishes: Lake Sturgeon (Acipenser fulvescens show highly restricted movement and habitat use over-winter

    Directory of Open Access Journals (Sweden)

    Donnette Thayer

    2017-04-01

    Full Text Available The relationship between species’ size and home range size has been well studied. In practice, home range may provide a good surrogate of broad spatial coverage needed for species conservation, however, many species can show restricted movement during critical life stages, such as breeding and over-wintering. This suggests the existence of either a behavioral or habitat mediated ‘temporal bottleneck,’ where restricted or sedentary movement can make populations more susceptible to harm during specific life stages. Here, we study over-winter movement and habitat use of Lake Sturgeon (Acipenser fulvescens, the largest freshwater fish in North America. We monitored over-winter movement of 86 fish using a hydro-acoustic receiver array in the South Saskatchewan River, Canada. Overall, 20 fish remained within our study system throughout the winter. Lake Sturgeon showed strong aggregation and sedentary movement over-winter, demonstrating a temporal bottleneck. Movement was highly restricted during ice-on periods (ranging from 0.9 km/day in November and April to 0.2 km/day in mid-November to mid-March, with Lake Sturgeon seeking deeper, slower pools. We also show that Lake Sturgeon have strong aggregation behavior, where distance to conspecifics decreased (from 575 to 313 m in preparation for and during ice-on periods. Although the Lake Sturgeon we studied had access to 1100 kilometers of unfragmented riverine habitat, we show that during the over-winter period Lake Sturgeon utilized a single, deep pool (<0.1% of available habitat. The temporal discrepancy between mobile and sedentary behaviors in Lake Sturgeon suggest adaptive management is needed with more localized focus during periods of temporal bottlenecks, even for large-bodied species.

  4. Molecular evolution of vertebrate neurotrophins: co-option of the highly conserved nerve growth factor gene into the advanced snake venom arsenalf.

    Science.gov (United States)

    Sunagar, Kartik; Fry, Bryan Grieg; Jackson, Timothy N W; Casewell, Nicholas R; Undheim, Eivind A B; Vidal, Nicolas; Ali, Syed A; King, Glenn F; Vasudevan, Karthikeyan; Vasconcelos, Vitor; Antunes, Agostinho

    2013-01-01

    Neurotrophins are a diverse class of structurally related proteins, essential for neuronal development, survival, plasticity and regeneration. They are characterized by major family members, such as the nerve growth factors (NGF), brain-derived neurotrophic factors (BDNF) and neurotrophin-3 (NT-3), which have been demonstrated here to lack coding sequence variations and follow the regime of negative selection, highlighting their extremely important conserved role in vertebrate homeostasis. However, in stark contrast, venom NGF secreted as part of the chemical arsenal of the venomous advanced snake family Elapidae (and to a lesser extent Viperidae) have characteristics consistent with the typical accelerated molecular evolution of venom components. This includes a rapid rate of diversification under the significant influence of positive-selection, with the majority of positively-selected sites found in the secreted β-polypeptide chain (74%) and on the molecular surface of the protein (92%), while the core structural and functional residues remain highly constrained. Such focal mutagenesis generates active residues on the toxin molecular surface, which are capable of interacting with novel biological targets in prey to induce a myriad of pharmacological effects. We propose that caenophidian NGFs could participate in prey-envenoming by causing a massive release of chemical mediators from mast cells to mount inflammatory reactions and increase vascular permeability, thereby aiding the spread of other toxins and/or by acting as proapoptotic factors. Despite their presence in reptilian venom having been known for over 60 years, this is the first evidence that venom-secreted NGF follows the molecular evolutionary pattern of other venom components, and thus likely participates in prey-envenomation.

  5. The human homolog of S. cerevisiae CDC27, CDC27 Hs, is encoded by a highly conserved intronless gene present in multiple copies in the human genome

    Energy Technology Data Exchange (ETDEWEB)

    Devor, E.J.; Dill-Devor, R.M. [Univ. of Iowa College of Medicine, Iowa City (United States)

    1994-09-01

    We have obtained a number of unique sequences via PCR amplification of human genomic DNA using degenerate primers under low stringency (42{degrees}C). One of these, an 853 bp product, has been identified as a partial genomic sequence of the human homolog of the S. cerevisiae CDC27 gene, CDC27Hs (GenBank No. U00001). This gene, reported by Turgendreich et al. is also designated EST00556 from Adams et al. We have undertaken a more detailed examination of our sequence, MCP34N, and have found that: 1. the genomic sequence is nearly identical to CDC27Hs over its entire 853 bp length; 2. an MCP34N-specific PCR assay of several non-human primate species reveals amplification products in chimpanzee and gorilla genomes having greater than 90% sequence identity with CDC27Hs; and 3. an MCP34N-specific PCR assay of the BIOS hybrid cell line panel gives a discordancy pattern suggesting multiple loci. Based upon these data, we present the following initial characterization: 1. the complete MCP34N sequence identity with CDC27Hs indicates that the latter is encoded by an intronless gene; 2. CDC27Hs is highly conserved among higher primates; and 3. CDC27Hs is present in multiple copies in the human genome. These characteristics, taken together with those initially reported for CDC27Hs, suggest that this is an old gene that carries out an important but, as yet, unknown function in the human brain.

  6. Defining population structure and genetic signatures of decline in the giant garter snake (Thamnophis gigas): implications for conserving threatened species within highly altered landscapes

    Science.gov (United States)

    Wood, Dustin A.; Halstead, Brian J.; Casazza, Michael L.; Hansen, Eric C.; Wylie, Glenn D.; Vandergast, Amy

    2015-01-01

    Anthropogenic habitat fragmentation can disrupt the ability of species to disperse across landscapes, which can alter the levels and distribution of genetic diversity within populations and negatively impact long-term viability. The giant gartersnake (Thamnophis gigas) is a state and federally threatened species that historically occurred in the wetland habitats of California’s Great Central Valley. Despite the loss of 93 % of historic wetlands throughout the Central Valley, giant gartersnakes continue to persist in relatively small, isolated patches of highly modified agricultural wetlands. Gathering information regarding genetic diversity and effective population size represents an essential component for conservation management programs aimed at this species. Previous mitochondrial sequence studies have revealed historical patterns of differentiation, yet little is known about contemporary population structure and diversity. On the basis of 15 microsatellite loci, we estimate population structure and compare indices of genetic diversity among populations spanning seven drainage basins within the Central Valley. We sought to understand how habitat loss may have affected genetic differentiation, genetic diversity and effective population size, and what these patterns suggest in terms of management and restoration actions. We recovered five genetic clusters that were consistent with regional drainage basins, although three northern basins within the Sacramento Valley formed a single genetic cluster. Our results show that northern drainage basin populations have higher connectivity than among central and southern basins populations, and that greater differentiation exists among the more geographically isolated populations in the central and southern portion of the species’ range. Genetic diversity measures among basins were significantly different, and were generally lower in southern basin populations. Levels of inbreeding and evidence of population

  7. Molecular Evolution of Vertebrate Neurotrophins: Co-Option of the Highly Conserved Nerve Growth Factor Gene into the Advanced Snake Venom Arsenalf

    Science.gov (United States)

    Sunagar, Kartik; Fry, Bryan Grieg; Jackson, Timothy N. W.; Casewell, Nicholas R.; Undheim, Eivind A. B.; Vidal, Nicolas; Ali, Syed A.; King, Glenn F.; Vasudevan, Karthikeyan; Vasconcelos, Vitor; Antunes, Agostinho

    2013-01-01

    Neurotrophins are a diverse class of structurally related proteins, essential for neuronal development, survival, plasticity and regeneration. They are characterized by major family members, such as the nerve growth factors (NGF), brain-derived neurotrophic factors (BDNF) and neurotrophin-3 (NT-3), which have been demonstrated here to lack coding sequence variations and follow the regime of negative selection, highlighting their extremely important conserved role in vertebrate homeostasis. However, in stark contrast, venom NGF secreted as part of the chemical arsenal of the venomous advanced snake family Elapidae (and to a lesser extent Viperidae) have characteristics consistent with the typical accelerated molecular evolution of venom components. This includes a rapid rate of diversification under the significant influence of positive-selection, with the majority of positively-selected sites found in the secreted β-polypeptide chain (74%) and on the molecular surface of the protein (92%), while the core structural and functional residues remain highly constrained. Such focal mutagenesis generates active residues on the toxin molecular surface, which are capable of interacting with novel biological targets in prey to induce a myriad of pharmacological effects. We propose that caenophidian NGFs could participate in prey-envenoming by causing a massive release of chemical mediators from mast cells to mount inflammatory reactions and increase vascular permeability, thereby aiding the spread of other toxins and/or by acting as proapoptotic factors. Despite their presence in reptilian venom having been known for over 60 years, this is the first evidence that venom-secreted NGF follows the molecular evolutionary pattern of other venom components, and thus likely participates in prey-envenomation. PMID:24312363

  8. Novel cross-strand three-purine stack of the highly conserved 5'-GA/AAG-5' internal loop at the 3'-end termini of Parvovirus Genomes

    International Nuclear Information System (INIS)

    Chou, S.-H.; Chin, K.-H.

    2001-01-01

    We have used two-dimensional nuclear magnetic resonance (2D-NMR), distance geometry (DG) and molecular dynamics / energy minimization (MD/EM) methods to study a 2x3 asymmetric internal loop structure of the highly conserved '5'-(GA)/(AAG)-5' bubble' present at the 3'-end hairpin of the single-stranded DNA genome of parvoviruses. This motif contains an unpaired adenosine stacked between two bracketed sheared G·A pairs. However, the phenomenal cross-strand G-G and A-A stacking in the tandem sheared G·A pairs has undergone considerable change. A novel three-purine stacking pattern is observed instead; the inserted A18 base is completely un-stacked from its neighboring G17 and A19 bases, but well stacked with the cross-strand A4 and G3 bases to form a novel A4/A18/G3 stack that is different from the double G/G, A/A or quadruple G/G/G/G stack present in the 5'-(GA)/(AG)-5' or 5'-(GGA)/(AGG)-5' motifs. Unlike the bulged purine residue that usually causes about 20 degree kink in the helical axis of the parent helix when bracketed by canonical G·C or A·T base pairs, no significant kink is observed in the present helix containing a bulged-adenine that is bracketed by sheared G ·A pairs. The phosphodiesters connecting G3-A4 and G17-A18 residues adopt unusual ζ torsional angles close to the trans domain, yet that connecting A18-A19 residues resumes the normal ζ(g - ) value. The well structured '5'-(GAA)/(AG)-5'' internal loop in the parvovirus genomes explains its resistance to single-strand specific endonuclease susceptibility

  9. Molecular evolution of vertebrate neurotrophins: co-option of the highly conserved nerve growth factor gene into the advanced snake venom arsenalf.

    Directory of Open Access Journals (Sweden)

    Kartik Sunagar

    Full Text Available Neurotrophins are a diverse class of structurally related proteins, essential for neuronal development, survival, plasticity and regeneration. They are characterized by major family members, such as the nerve growth factors (NGF, brain-derived neurotrophic factors (BDNF and neurotrophin-3 (NT-3, which have been demonstrated here to lack coding sequence variations and follow the regime of negative selection, highlighting their extremely important conserved role in vertebrate homeostasis. However, in stark contrast, venom NGF secreted as part of the chemical arsenal of the venomous advanced snake family Elapidae (and to a lesser extent Viperidae have characteristics consistent with the typical accelerated molecular evolution of venom components. This includes a rapid rate of diversification under the significant influence of positive-selection, with the majority of positively-selected sites found in the secreted β-polypeptide chain (74% and on the molecular surface of the protein (92%, while the core structural and functional residues remain highly constrained. Such focal mutagenesis generates active residues on the toxin molecular surface, which are capable of interacting with novel biological targets in prey to induce a myriad of pharmacological effects. We propose that caenophidian NGFs could participate in prey-envenoming by causing a massive release of chemical mediators from mast cells to mount inflammatory reactions and increase vascular permeability, thereby aiding the spread of other toxins and/or by acting as proapoptotic factors. Despite their presence in reptilian venom having been known for over 60 years, this is the first evidence that venom-secreted NGF follows the molecular evolutionary pattern of other venom components, and thus likely participates in prey-envenomation.

  10. Highly Conserved Arg Residue of ERFNIN Motif of Pro-Domain is Important for pH-Induced Zymogen Activation Process in Cysteine Cathepsins K and L.

    Science.gov (United States)

    Aich, Pulakesh; Biswas, Sampa

    2018-06-01

    Pro-domain of a cysteine cathepsin contains a highly conserved Ex 2 Rx 2 Fx 2 Nx 3 Ix 3 N (ERFNIN) motif. The zymogen structure of cathepsins revealed that the Arg(R) residue of the motif is a central residue of a salt-bridge/H-bond network, stabilizing the scaffold of the pro-domain. Importance of the arginine is also demonstrated in studies where a single mutation (Arg → Trp) in human lysosomal cathepsin K (hCTSK) is linked to a bone-related genetic disorder "Pycnodysostosis". In the present study, we have characterized in vitro Arg → Trp mutant of hCTSK and the same mutant of hCTSL. The R → W mutant of hCTSK revealed that this mutation leads to an unstable zymogen that is spontaneously activated and auto-proteolytically degraded rapidly. In contrast, the same mutant of hCTSL is sufficiently stable and has proteolytic activity almost like its wild-type counterpart; however it shows an altered zymogen activation condition in terms of pH, temperature and time. Far and near UV circular dichroism and intrinsic tryptophan fluorescence experiments have revealed that the mutation has minimal effect on structure of the protease hCTSL. Molecular modeling studies shows that the mutated Trp31 in hCTSL forms an aromatic cluster with Tyr23 and Trp30 leading to a local stabilization of pro-domain and supplements the loss of salt-bridge interaction mediated by Arg31 in wild-type. In hCTSK-R31W mutant, due to presence of a non-aromatic Ser30 residue such interaction is not possible and may be responsible for local instability. These differences may cause detrimental effects of R31W mutation on the regulation of hCTSK auto-activation process compared to altered activation process in hCTSL.

  11. Six Highly Conserved Targets of RNAi Revealed in HIV-1-Infected Patients from Russia Are Also Present in Many HIV-1 Strains Worldwide

    Directory of Open Access Journals (Sweden)

    Olga V. Kretova

    2017-09-01

    Full Text Available RNAi has been suggested for use in gene therapy of HIV/AIDS, but the main problem is that HIV-1 is highly variable and could escape attack from the small interfering RNAs (siRNAs due to even single nucleotide substitutions in the potential targets. To exhaustively check the variability in selected RNA targets of HIV-1, we used ultra-deep sequencing of six regions of HIV-1 from the plasma of two independent cohorts of patients from Russia. Six RNAi targets were found that are invariable in 82%–97% of viruses in both cohorts and are located inside the domains specifying reverse transcriptase (RT, integrase, vpu, gp120, and p17. The analysis of mutation frequencies and their characteristics inside the targets suggests a likely role for APOBEC3G (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3G, A3G in G-to-A mutations and a predominant effect of RT biases in the detected variability of the virus. The lowest frequency of mutations was detected in the central part of all six targets. We also discovered that the identical RNAi targets are present in many HIV-1 strains from many countries and from all continents. The data are important for both the understanding of the patterns of HIV-1 mutability and properties of RT and for the development of gene therapy approaches using RNAi for the treatment of HIV/AIDS. Keywords: HIV-1, RNAi targets, gene therapy, ultra-deep sequencing, conserved HIV-1 sequences

  12. Conservation in gene encoding Mycobacterium tuberculosis antigen Rv2660 and a high predicted population coverage of H56 multistage vaccine in South Africa.

    Science.gov (United States)

    Perez-Martinez, Angy P; Ong, Edison; Zhang, Lixin; Marrs, Carl F; He, Yongqun; Yang, Zhenhua

    2017-11-01

    H56/AERAS-456+IC31 (H56), composed of two early secretion proteins, Ag85B and ESAT-6, and a latency associated protein, Rv2660, and the IC31 Intercell adjuvant, is a new fusion subunit vaccine candidate designed to induce immunity against both new infection and reactivation of latent tuberculosis infection. Efficacy of subunit vaccines may be affected by the diversity of vaccine antigens among clinical strains and the extent of recognition by the diverse HLA molecules in the recipient population. Although a previous study showed the conservative nature of Ag85B- and ESAT-6-encoding genes, genetic diversity of Rv2660c that encodes RV2660 is largely unknown. The population coverage of H56 as a whole yet remains to be assessed. The present study was conducted to address these important knowledge gaps. DNA sequence analysis of Rv2660c found no variation among 83 of the 84 investigated clinical strains belonging to four genetic lineages. H56 was predicted to have as high as 99.6% population coverage in the South Africa population using the Immune Epitope Database (IEDB) Population Coverage Tool. Further comparison of H56 population coverage between South African Blacks and Caucasians based on the phenotypic frequencies of binding MHC Class I and Class II supertype alleles found that all of the nine MHC-I and six of eight MHC-II human leukocyte antigen (HLA) supertype alleles analyzed were significantly differentially expressed between the two subpopulations. This finding suggests the presence of race-specific functional binding motifs of MHC-I and MHC-II HLA alleles, which, in turn, highlights the importance of including diverse populations in vaccine clinical evaluation. In conclusion, H56 vaccine is predicted to have a promising population coverage in South Africa; this study demonstrates the utility of integrating comparative genomics and bioinformatics in bridging animal and clinical studies of novel TB vaccines. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Evaluation of presenting conserved foods

    Directory of Open Access Journals (Sweden)

    Asl Soleimani H

    1998-08-01

    Full Text Available Food, it's production and preserving has been one of the most important problems in human life. Limitation of production due to climatic, geographic and papulational situations and conservation due to providance and prosecting for solution of one of the most fundamental human needs, has been discussed much. Difference between the lands, temperature, humidity and rainfall on one hand and texture and accumulation of papulation on the other hand, not only has limited the amount and kind of food production but also has improved the preserving methods as much as possible. Extra production in fertile lands and confirmed need for receiving food in deserts and dry areas, makes the need of exchanging and transfer of food inevitable because of economic and ethical matters and sanitation of food. Avoidance of being contaminated and resistance against decay seems very important and vital. So process of preserving and conserving of eaw or cooked food became a fundamental problem. In previous 200 years, many advanced methods have been designed for preserving food in which the role of conserving and packing in vital often. Because of industrial production, conserved food have a great influence on sanitation of people nutrition, and herefor the rate of diseases from consumption of contaminated food has been reduced in industrial countries and the tensancy of people to use conventional food has been decreased gradually. Because of high cost of industrial conserved food production some people produce conserved foods in the way which is not hygienic. That may have a high risk when ingested. In this article we discuss about unwarranted conserved foods productions.

  14. Adapting the bioblitz to meet conservation needs.

    Science.gov (United States)

    Parker, Sophie S; Pauly, Gregory B; Moore, James; Fraga, Naomi S; Knapp, John J; Principe, Zachary; Brown, Brian V; Randall, John M; Cohen, Brian S; Wake, Thomas A

    2018-03-01

    When conservation strategies require new, field-based information, practitioners must find the best ways to rapidly deliver high-quality survey data. To address this challenge, several rapid-assessment approaches have been developed since the early 1990s. These typically involve large areas, take many months to complete, and are not appropriate when conservation-relevant survey data are urgently needed for a specific locale. In contrast, bioblitzes are designed for quick collection of site-specific survey data. Although bioblitzes are commonly used to achieve educational or public-engagement goals, conservation practitioners are increasingly using a modified bioblitz approach to generate conservation-relevant data while simultaneously enhancing research capacity and building working partnerships focused on conservation concerns. We term these modified events expert bioblitzes. Several expert bioblitzes have taken place on lands of conservation concern in Southern California and have involved collaborative efforts of government agencies, nonprofit organizations, botanic gardens, museums, and universities. The results of expert bioblitzes directly informed on-the-ground conservation and decision-making; increased capacity for rapid deployment of expert bioblitzes in the future; and fostered collaboration and communication among taxonomically and institutionally diverse experts. As research and conservation funding becomes increasingly scarce, expert bioblitzes can play an increasingly important role in biodiversity conservation. © 2018 The Authors. Conservation Biology published by Wiley Periodicals, Inc. on behalf of Society for Conservation Biology.

  15. Beyond conservation agriculture.

    Science.gov (United States)

    Giller, Ken E; Andersson, Jens A; Corbeels, Marc; Kirkegaard, John; Mortensen, David; Erenstein, Olaf; Vanlauwe, Bernard

    2015-01-01

    Global support for Conservation Agriculture (CA) as a pathway to Sustainable Intensification is strong. CA revolves around three principles: no-till (or minimal soil disturbance), soil cover, and crop rotation. The benefits arising from the ease of crop management, energy/cost/time savings, and soil and water conservation led to widespread adoption of CA, particularly on large farms in the Americas and Australia, where farmers harness the tools of modern science: highly-sophisticated machines, potent agrochemicals, and biotechnology. Over the past 10 years CA has been promoted among smallholder farmers in the (sub-) tropics, often with disappointing results. Growing evidence challenges the claims that CA increases crop yields and builds-up soil carbon although increased stability of crop yields in dry climates is evident. Our analyses suggest pragmatic adoption on larger mechanized farms, and limited uptake of CA by smallholder farmers in developing countries. We propose a rigorous, context-sensitive approach based on Systems Agronomy to analyze and explore sustainable intensification options, including the potential of CA. There is an urgent need to move beyond dogma and prescriptive approaches to provide soil and crop management options for farmers to enable the Sustainable Intensification of agriculture.

  16. Beyond conservation agriculture

    Science.gov (United States)

    Giller, Ken E.; Andersson, Jens A.; Corbeels, Marc; Kirkegaard, John; Mortensen, David; Erenstein, Olaf; Vanlauwe, Bernard

    2015-01-01

    Global support for Conservation Agriculture (CA) as a pathway to Sustainable Intensification is strong. CA revolves around three principles: no-till (or minimal soil disturbance), soil cover, and crop rotation. The benefits arising from the ease of crop management, energy/cost/time savings, and soil and water conservation led to widespread adoption of CA, particularly on large farms in the Americas and Australia, where farmers harness the tools of modern science: highly-sophisticated machines, potent agrochemicals, and biotechnology. Over the past 10 years CA has been promoted among smallholder farmers in the (sub-) tropics, often with disappointing results. Growing evidence challenges the claims that CA increases crop yields and builds-up soil carbon although increased stability of crop yields in dry climates is evident. Our analyses suggest pragmatic adoption on larger mechanized farms, and limited uptake of CA by smallholder farmers in developing countries. We propose a rigorous, context-sensitive approach based on Systems Agronomy to analyze and explore sustainable intensification options, including the potential of CA. There is an urgent need to move beyond dogma and prescriptive approaches to provide soil and crop management options for farmers to enable the Sustainable Intensification of agriculture. PMID:26579139

  17. Beyond Conservation Agriculture

    Directory of Open Access Journals (Sweden)

    Ken E Giller

    2015-10-01

    Full Text Available Global support for Conservation Agriculture (CA as a pathway to Sustainable Intensification is strong. CA revolves around three principles: no-till (or minimal soil disturbance, soil cover, and crop rotation. The benefits arising from the ease of crop management, energy/cost/time savings and soil and water conservation led to widespread adoption of CA, particularly on large farms in the Americas and Australia, where farmers harness the tools of modern science: highly-sophisticated machines, potent agrochemicals and biotechnology. Over the past ten years CA has been promoted among smallholder farmers in the (sub- tropics, often with disappointing results. Growing evidence challenges the claims that CA increases crop yields and builds-up soil carbon although increased stability of crop yields in dry climates is evident. Our analyses suggest pragmatic adoption on larger mechanized farms, and limited uptake of CA by smallholder farmers in developing countries. We propose a rigorous, context-sensitive approach based on Systems Agronomy to analyze and explore sustainable intensification options, including the potential of CA. There is an urgent need to move beyond dogma and prescriptive approaches to provide soil and crop management options for farmers to enable the Sustainable Intensification of agriculture.

  18. Conservation: Toward firmer ground

    Science.gov (United States)

    1975-01-01

    The following aspects of energy conservation were reviewed in order to place the problems in proper perspective: history and goals, conservation accounting-criteria, and a method to overcome obstacles. The effect of changing prices and available supplies of energy sources and their causes on consumption levels during the last few decades were described. Some examples of attainable conservation goals were listed and justified. A number of specific criteria applicable to conservation accounting were given. Finally, a discussion was presented to relate together the following aspects of energy conservation: widespread impact, involvement of government, industry, politics, moral and ethical aspects, urgency and time element.

  19. Evaluating local benefits from conservation in Nepal's Annapurna Conservation Area.

    Science.gov (United States)

    Spiteri, Arian; Nepal, Sanjay K

    2008-09-01

    Protected areas are integral to the global effort to conserve biodiversity, and, over the past two decades, protected area managers have begun to recognize that conservation objectives are next to impossible to achieve without considering the needs and concerns of local communities. Incentive-based programs (IBPs) have become a favored approach to protected area management, geared at fostering local stewardship by delivering benefits tied to conservation to local people. Effective IBPs require benefits to accrue to and be recognized by those experiencing the greatest consequences as a result of the protected area, and those likely to continue extractive activities if their livelihood needs are compromised. This research examines dispersal of IBP benefits, as perceived by local residents in Nepal's Annapurna Conservation Area. Results reported here are based on questionnaire interviews with 188 households conducted between September and December 2004. Results indicate that local residents primarily identify benefits from social development activities, provisions for resource extraction, and economic opportunities. Overall, benefits have been dispersed equally to households in villages on and off the main tourist route, and regardless of a household's participation in tourism. However, benefits are not effectively targeted to poorer residents, those highly dependent on natural resources, and those experiencing the most crop damage and livestock loss from protected wildlife. This article provides several suggestions for improving the delivery of conservation incentives.

  20. Two negative cis-regulatory regions involved in fruit-specific promoter activity from watermelon (Citrullus vulgaris S.).

    Science.gov (United States)

    Yin, Tao; Wu, Hanying; Zhang, Shanglong; Lu, Hongyu; Zhang, Lingxiao; Xu, Yong; Chen, Daming; Liu, Jingmei

    2009-01-01

    A 1.8 kb 5'-flanking region of the large subunit of ADP-glucose pyrophosphorylase, isolated from watermelon (Citrullus vulgaris S.), has fruit-specific promoter activity in transgenic tomato plants. Two negative regulatory regions, from -986 to -959 and from -472 to -424, were identified in this promoter region by fine deletion analyses. Removal of both regions led to constitutive expression in epidermal cells. Gain-of-function experiments showed that these two regions were sufficient to inhibit RFP (red fluorescent protein) expression in transformed epidermal cells when fused to the cauliflower mosaic virus (CaMV) 35S minimal promoter. Gel mobility shift experiments demonstrated the presence of leaf nuclear factors that interact with these two elements. A TCCAAAA motif was identified in these two regions, as well as one in the reverse orientation, which was confirmed to be a novel specific cis-element. A quantitative beta-glucuronidase (GUS) activity assay of stable transgenic tomato plants showed that the activities of chimeric promoters harbouring only one of the two cis-elements, or both, were approximately 10-fold higher in fruits than in leaves. These data confirm that the TCCAAAA motif functions as a fruit-specific element by inhibiting gene expression in leaves.

  1. Identification of sparsely distributed clusters of cis-regulatory elements in sets of co-expressed genes

    OpenAIRE

    Kreiman, Gabriel

    2004-01-01

    Sequence information and high‐throughput methods to measure gene expression levels open the door to explore transcriptional regulation using computational tools. Combinatorial regulation and sparseness of regulatory elements throughout the genome allow organisms to control the spatial and temporal patterns of gene expression. Here we study the organization of cis‐regulatory elements in sets of co‐regulated genes. We build an algorithm to search for combinations of transcription factor binding...

  2. A Survey of 6,300 Genomic Fragments for cis-Regulatory Activity in the Imaginal Discs of Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Aurélie Jory

    2012-10-01

    Full Text Available Over 6,000 fragments from the genome of Drosophila melanogaster were analyzed for their ability to drive expression of GAL4 reporter genes in the third-instar larval imaginal discs. About 1,200 reporter genes drove expression in the eye, antenna, leg, wing, haltere, or genital imaginal discs. The patterns ranged from large regions to individual cells. About 75% of the active fragments drove expression in multiple discs; 20% were expressed in ventral, but not dorsal, discs (legs, genital, and antenna, whereas ∼23% were expressed in dorsal but not ventral discs (wing, haltere, and eye. Several patterns, for example, within the leg chordotonal organ, appeared a surprisingly large number of times. Unbiased searches for DNA sequence motifs suggest candidate transcription factors that may regulate enhancers with shared activities. Together, these expression patterns provide a valuable resource to the community and offer a broad overview of how transcriptional regulatory information is distributed in the Drosophila genome.

  3. Identification of Predictive Cis-Regulatory Elements Using a Discriminative Objective Function and a Dynamic Search Space.

    Directory of Open Access Journals (Sweden)

    Rahul Karnik

    Full Text Available The generation of genomic binding or accessibility data from massively parallel sequencing technologies such as ChIP-seq and DNase-seq continues to accelerate. Yet state-of-the-art computational approaches for the identification of DNA binding motifs often yield motifs of weak predictive power. Here we present a novel computational algorithm called MotifSpec, designed to find predictive motifs, in contrast to over-represented sequence elements. The key distinguishing feature of this algorithm is that it uses a dynamic search space and a learned threshold to find discriminative motifs in combination with the modeling of motifs using a full PWM (position weight matrix rather than k-mer words or regular expressions. We demonstrate that our approach finds motifs corresponding to known binding specificities in several mammalian ChIP-seq datasets, and that our PWMs classify the ChIP-seq signals with accuracy comparable to, or marginally better than motifs from the best existing algorithms. In other datasets, our algorithm identifies novel motifs where other methods fail. Finally, we apply this algorithm to detect motifs from expression datasets in C. elegans using a dynamic expression similarity metric rather than fixed expression clusters, and find novel predictive motifs.

  4. Ethics of conservation triage

    Directory of Open Access Journals (Sweden)

    Kerrie A Wilson

    2016-09-01

    Full Text Available Conservation triage seems to be at a stalemate between those who accept triage based on utilitarian rationalization, and those that reject it based on a number of ethical principles. We argue that without considered attention to the ethics of conservation triage we risk further polarization in the field of conservation. We draw lessons from the medical sector, where triage is more intuitive and acceptable, and also from disaster planning, to help navigate the challenges that triage entails for conservation science, practice, and policy. We clarify the consequentialist, deontological, and virtue ethical stances that influence the level of acceptance of triage. We emphasize the ethical dimensions of conservation triage in principle and in practice, particularly in the context of stakeholder diversity, a wide range of possible objectives and actions, broader institutions, and significant uncertainties. A focus on a more diverse set of ethics, more considered choice of triage as a conservation tool, open communication of triage objectives and protocols, greater consideration of risk preferences, and regular review and adaptation of triage protocols is required for conservation triage to become more acceptable among diverse conservation practitioners, institutions, and the general public. Accepting conservation triage as fundamentally an ethical problem would foster more open dialogue and constructive debate about the role of conservation triage in a wider system of care.

  5. Comparative genome sequencing of drosophila pseudoobscura: Chromosomal, gene and cis-element evolution

    Energy Technology Data Exchange (ETDEWEB)

    Richards, Stephen; Liu, Yue; Bettencourt, Brian R.; Hradecky, Pavel; Letovsky, Stan; Nielsen, Rasmus; Thornton, Kevin; Todd, Melissa J.; Chen, Rui; Meisel, Richard P.; Couronne, Olivier; Hua, Sujun; Smith, Mark A.; Bussemaker, Harmen J.; van Batenburg, Marinus F.; Howells, Sally L.; Scherer, Steven E.; Sodergren, Erica; Matthews, Beverly B.; Crosby, Madeline A.; Schroeder, Andrew J.; Ortiz-Barrientos, Daniel; Rives, Catherine M.; Metzker, Michael L.; Muzny, Donna M.; Scott, Graham; Steffen, David; Wheeler, David A.; Worley, Kim C.; Havlak, Paul; Durbin, K. James; Egan, Amy; Gill, Rachel; Hume, Jennifer; Morgan, Margaret B.; Miner, George; Hamilton, Cerissa; Huang, Yanmei; Waldron, Lenee; Verduzco, Daniel; Blankenburg, Kerstin P.; Dubchak, Inna; Noor, Mohamed A.F.; Anderson, Wyatt; White, Kevin P.; Clark, Andrew G.; Schaeffer, Stephen W.; Gelbart, William; Weinstock, George M.; Gibbs, Richard A.

    2004-04-01

    The genome sequence of a second fruit fly, D. pseudoobscura, presents an opportunity for comparative analysis of a primary model organism D. melanogaster. The vast majority of Drosophila genes have remained on the same arm, but within each arm gene order has been extensively reshuffled leading to the identification of approximately 1300 syntenic blocks. A repetitive sequence is found in the D. pseudoobscura genome at many junctions between adjacent syntenic blocks. Analysis of this novel repetitive element family suggests that recombination between offset elements may have given rise to many paracentric inversions, thereby contributing to the shuffling of gene order in the D. pseudoobscura lineage. Based on sequence similarity and synteny, 10,516 putative orthologs have been identified as a core gene set conserved over 35 My since divergence. Genes expressed in the testes had higher amino acid sequence divergence than the genome wide average consistent with the rapid evolution of sex-specific proteins. Cis-regulatory sequences are more conserved than control sequences between the species but the difference is slight, suggesting that the evolution of cis-regulatory elements is flexible. Overall, a picture of repeat mediated chromosomal rearrangement, and high co-adaptation of both male genes and cis-regulatory sequences emerges as important themes of genome divergence between these species of Drosophila.

  6. Conservation: Toward firmer ground

    Science.gov (United States)

    1975-01-01

    The following aspects of energy conservation were discussed: conservation history and goals, conservation modes, conservation accounting-criteria, and a method to overcome obstacles. The conservation modes tested fall into one of the following categories: reduced energy consumption, increased efficiency of energy utilization, or substitution of one or more forms of energy for another which is in shorter supply or in some sense thought to be of more value. The conservation accounting criteria include net energy reduction, economic, and technical criteria. A method to overcome obstacles includes (approaches such as: direct personal impact (life style, income, security, aspiration), an element of crisis, large scale involvement of environmental, safety, and health issues, connections to big government, big business, big politics, involvement of known and speculative science and technology, appeal to moral and ethical standards, the transient nature of opportunities to correct the system.

  7. Econometric modelling of conservation

    International Nuclear Information System (INIS)

    Parker, J.C.; Seal, D.J.

    1990-01-01

    The issue of energy conservation in general, and conservation in the natural gas markets in particular, has recently had a much lower profile than in the past, when energy prices were significantly higher and energy costs composed a much larger proportion of industrial operating costs than today. The recent downward trend in energy prices has diverted attention away from this issue. In the face of expected significant real price increases, increasing pressure from environmental groups, and directives on the part of regulator authorities, conservation is once again becoming a topic of consideration in the energy industry. From the point of view of gas demand forecasting, conservation has received too little attention. The intentions of this paper are to establish the need for forecasting conservation in the natural gas utility sector, and to construct a model of industrial demand which incorporates conservation and is appropriate for use as a forecasting tool

  8. Handbook on energy conservation

    International Nuclear Information System (INIS)

    1989-12-01

    This book shows energy situation in recent years, which includes reserves of energy resource in the world, crude oil production records in OPEC and non OPEC, supply and demand of energy in important developed countries, prospect of supply and demand of energy and current situation of energy conservation in developed countries. It also deals with energy situation in Korea reporting natural resources status, energy conservation policy, measurement for alternative energy, energy management of Korea, investment in equipment and public education for energy conservation.

  9. Promoting Effective Monitoring and Conservation through Online ...

    African Journals Online (AJOL)

    ... communicates major findings of submitted records to relevant authorities concerned with conservation and advocacy thus contributing to a much wider sharing and dissemination of important aspects while contributing to avifaunal conservation. Through networking the system provides a highly attractive and authoritative, ...

  10. Conservation laws and nuclear transport models

    International Nuclear Information System (INIS)

    Gale, C.; Das Gupta, S.

    1990-01-01

    We discuss the consequences of energy and angular momentum conservation for nucleon-nucleon scattering in a nuclear environment during high-energy heavy-ion collisions. We describe algorithms that ensure stricter enforcement of such conservation laws within popular microscopic models of intermediate-energy heavy-ion collisions. We find that the net effects on global observables are small

  11. Biodiversity Conservation and Conservation Biotechnology Tools

    Science.gov (United States)

    This special issue is dedicated to the in vitro tools and methods used to conserve the genetic diversity of rare and threatened species from around the world. Species that are on the brink of extinction, due to the rapid loss of genetic diversity and habitat, come mainly from resource poor areas the...

  12. Paradigms for parasite conservation.

    Science.gov (United States)

    Dougherty, Eric R; Carlson, Colin J; Bueno, Veronica M; Burgio, Kevin R; Cizauskas, Carrie A; Clements, Christopher F; Seidel, Dana P; Harris, Nyeema C

    2016-08-01

    Parasitic species, which depend directly on host species for their survival, represent a major regulatory force in ecosystems and a significant component of Earth's biodiversity. Yet the negative impacts of parasites observed at the host level have motivated a conservation paradigm of eradication, moving us farther from attainment of taxonomically unbiased conservation goals. Despite a growing body of literature highlighting the importance of parasite-inclusive conservation, most parasite species remain understudied, underfunded, and underappreciated. We argue the protection of parasitic biodiversity requires a paradigm shift in the perception and valuation of their role as consumer species, similar to that of apex predators in the mid-20th century. Beyond recognizing parasites as vital trophic regulators, existing tools available to conservation practitioners should explicitly account for the unique threats facing dependent species. We built upon concepts from epidemiology and economics (e.g., host-density threshold and cost-benefit analysis) to devise novel metrics of margin of error and minimum investment for parasite conservation. We define margin of error as the risk of accidental host extinction from misestimating equilibrium population sizes and predicted oscillations, while minimum investment represents the cost associated with conserving the additional hosts required to maintain viable parasite populations. This framework will aid in the identification of readily conserved parasites that present minimal health risks. To establish parasite conservation, we propose an extension of population viability analysis for host-parasite assemblages to assess extinction risk. In the direst cases, ex situ breeding programs for parasites should be evaluated to maximize success without undermining host protection. Though parasitic species pose a considerable conservation challenge, adaptations to conservation tools will help protect parasite biodiversity in the face of

  13. FY 2000 report on the survey on energy conservation technology of large plant using ultra high corrosion resistant materials; 2000 nendo chokotaishokusei zairyo wo mochiita ogata plant no sho energy gijutsu ni kansuru chosa hokokusho

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-03-01

    For the purpose of achieving remarkable energy conservation/resource conservation in large plants, the paper carried out an investigational survey of effects obtained in case of applying amorphous super metal which is the newest corrosion resistant material. Amorphous alloys as an ultra high corrosion resistant material are a peculiar material which shows the extremely excellent corrosion resistance even in much strong acid by containing passivated elements with the needed concentration. The corrosion resistant amorphous alloy applied to large plants need the thickness and diameter of more than several millimeters as a bulk material. The subjects are scaling-up of bulk materials and stabilization of characteristics. Even under the tough dew point corrosion environment of the waste power plant, etc., heat recovery from exhaust gas is made possible by heat exchanger applied with ultra high corrosion resistant materials. Effects of the annual heat recovery from the nationwide refuse incinerators and coal thermal power plants are estimated to be approximately 5.2 million kL toe, that is, to be equal to energy conservation of 6 x a million kW class power plant. (NEDO)

  14. Exploiting deterministic maintenance opportunity windows created by conservative engineering design rules that result in free time locked into large high-speed coupled production lines with finite buffers

    Directory of Open Access Journals (Sweden)

    Durandt, Casper

    2016-08-01

    Full Text Available Conservative engineering design rules for large serial coupled production processes result in machines having locked-in free time (also called ‘critical downtime’ or ‘maintenance opportunity windows’, which cause idle time if not used. Operators are not able to assess a large production process holistically, and so may not be aware that they form the current bottleneck – or that they have free time available due to interruptions elsewhere. A real-time method is developed to accurately calculate and display free time in location and magnitude, and efficiency improvements are demonstrated in large-scale production runs.

  15. Introducing Conservation of Momentum

    Science.gov (United States)

    Brunt, Marjorie; Brunt, Geoff

    2013-01-01

    The teaching of the principle of conservation of linear momentum is considered (ages 15 + ). From the principle, the momenta of two masses in an isolated system are considered. Sketch graphs of the momenta make Newton's laws appear obvious. Examples using different collision conditions are considered. Conservation of momentum is considered…

  16. Water Conservation Resource List.

    Science.gov (United States)

    NJEA Review, 1981

    1981-01-01

    Alarmed by the growing water shortage, the New Jersey State Office of Dissemination has prepared this annotated list of free or inexpensive instructional materials for teaching about water conservation, K-l2. A tipsheet for home water conservation is appended. (Editor/SJL)

  17. Controllability of conservative behaviours

    NARCIS (Netherlands)

    Rao, Shodhan

    2012-01-01

    In this article, we first define the class of J-conservative behaviours with observable storage functions, where J is a symmetric two-variable polynomial matrix. We then provide two main results. The first result states that if J(-xi,xi) is nonsingular, the input cardinality of a J-conservative

  18. Conservation Science Fair Projects.

    Science.gov (United States)

    Soil Conservation Society of America, Ankeny, IA.

    Included are ideas, suggestions, and examples for selecting and designing conservation science projects. Over 70 possible conservation subject areas are presented with suggested projects. References are cited with each of these subject areas, and a separate list of annotated references is included. The references pertain to general subject…

  19. Fixism and conservation science.

    Science.gov (United States)

    Robert, Alexandre; Fontaine, Colin; Veron, Simon; Monnet, Anne-Christine; Legrand, Marine; Clavel, Joanne; Chantepie, Stéphane; Couvet, Denis; Ducarme, Frédéric; Fontaine, Benoît; Jiguet, Frédéric; le Viol, Isabelle; Rolland, Jonathan; Sarrazin, François; Teplitsky, Céline; Mouchet, Maud

    2017-08-01

    The field of biodiversity conservation has recently been criticized as relying on a fixist view of the living world in which existing species constitute at the same time targets of conservation efforts and static states of reference, which is in apparent disagreement with evolutionary dynamics. We reviewed the prominent role of species as conservation units and the common benchmark approach to conservation that aims to use past biodiversity as a reference to conserve current biodiversity. We found that the species approach is justified by the discrepancy between the time scales of macroevolution and human influence and that biodiversity benchmarks are based on reference processes rather than fixed reference states. Overall, we argue that the ethical and theoretical frameworks underlying conservation research are based on macroevolutionary processes, such as extinction dynamics. Current species, phylogenetic, community, and functional conservation approaches constitute short-term responses to short-term human effects on these reference processes, and these approaches are consistent with evolutionary principles. © 2016 Society for Conservation Biology.

  20. Setting conservation priorities.

    Science.gov (United States)

    Wilson, Kerrie A; Carwardine, Josie; Possingham, Hugh P

    2009-04-01

    A generic framework for setting conservation priorities based on the principles of classic decision theory is provided. This framework encapsulates the key elements of any problem, including the objective, the constraints, and knowledge of the system. Within the context of this framework the broad array of approaches for setting conservation priorities are reviewed. While some approaches prioritize assets or locations for conservation investment, it is concluded here that prioritization is incomplete without consideration of the conservation actions required to conserve the assets at particular locations. The challenges associated with prioritizing investments through time in the face of threats (and also spatially and temporally heterogeneous costs) can be aided by proper problem definition. Using the authors' general framework for setting conservation priorities, multiple criteria can be rationally integrated and where, how, and when to invest conservation resources can be scheduled. Trade-offs are unavoidable in priority setting when there are multiple considerations, and budgets are almost always finite. The authors discuss how trade-offs, risks, uncertainty, feedbacks, and learning can be explicitly evaluated within their generic framework for setting conservation priorities. Finally, they suggest ways that current priority-setting approaches may be improved.

  1. Madagascar Conservation & Development

    African Journals Online (AJOL)

    Madagascar Conservation & Development welcomes the results of original research, field surveys, advances in field and laboratory techniques, book reviews, and informal status reports from research, conservation, development and management programs and in-field projects in Madagascar. In addition, notes on changes ...

  2. Resource Conservation Glossary.

    Science.gov (United States)

    Soil Conservation Society of America, Ankeny, IA.

    This glossary is a composite of terms selected from 13 technologies, and is the expanded revision of the original 1952 edition of "The Soil and Water Conservation Glossary." The terms were selected from these areas: agronomy, biology, conservation, ecology, economics, engineering, forestry, geology, hydrology, range, recreation, soils, and…

  3. Creative Soil Conservation

    Science.gov (United States)

    Smith, Martha

    2010-01-01

    Take plant lessons outdoors with this engaging and inquiry-based activity in which third-grade students learn how to apply soil conservation methods to growing plants. They also collect data and draw conclusions about the effectiveness of their method of soil conservation. An added benefit to this activity is that the third-grade students played…

  4. Old and New World arenaviruses share a highly conserved epitope in the fusion domain of the glycoprotein 2, which is recognized by Lassa virus-specific human CD4+ T-cell clones

    International Nuclear Information System (INIS)

    Meulen, Jan ter; Badusche, Marlis; Satoguina, Judith; Strecker, Thomas; Lenz, Oliver; Loeliger, Cornelius; Sakho, Mohamed; Koulemou, Kekoura; Koivogui, Lamine; Hoerauf, Achim

    2004-01-01

    Data from human studies and animal experiments indicate a dominant role of T-cells over antibodies in controlling acute Lassa virus infection and providing immunity to reinfection. Knowledge of the epitopes recognized by T-cells may therefore be crucial to the development of a recombinant Lassa virus vaccine. In order to study human T-cell reactivity to the most conserved structural protein of Lassa virus, the glycoprotein 2 (GP2), seven GP2-specific CD4+ T-cell clones (TCCs) were generated from the lymphocytes of a Lassa antibody positive individual. All TCC displayed high specific proliferation, showed DR-restriction, and produced IFN-γ upon stimulation with recombinant GP2. The epitope of four of the clones was localized to a short stretch of 13 amino acids located in the N-terminal part of GP2 (aa 289-301, numbering according to sequence of GPC). This epitope is conserved in all strains of Lassa virus and lymphocytic choriomeningitis virus (LCMV), shows >90% similarity in all New World arenaviruses of clade B, and overlaps with the proposed fusion domain of GP2. Peptides with conservative aa exchanges, as they naturally occur in the epitope 289-301 of the Old World arenavirus Mopeia and some New World arenaviruses, continued to effectively stimulate the Lassa-GP2-specific T-cell clones tested. The finding of a human T-helper cell epitope, which is highly conserved between Old and New World arenaviruses, is of importance for the design of arenavirus vaccines

  5. Japan's energy conservation policy

    International Nuclear Information System (INIS)

    Yoda, Kenichi

    1990-01-01

    This article reviews developments in Japanese energy conservation since the 1970s. The industrial sector has achieved the greatest success, due to industrial restructuring as well as improvements in energy efficiency. In the residential/commercial sector, the efficiency of appliances has been much improved. Although improvements have been made in the fuel efficiency of passenger cars, energy consumption in the transportation sector has risen slightly owing to increased transport of passengers and freight. The overall responsibility for energy conservation policy rests with the Ministry of International Trade and Industry. MITI is also responsible for implementing specific conservation policies in regard to the industrial and commercial sectors. In the residential sector, MITI works with the Ministry of Construction and in the transportation sector with the Ministry of Transport. To realize the goals of energy conservation policy through general research, dissemination of public information and other activities, MITI works with the Energy Conservation Center (ECC). (author). 2 figs, 3 tabs

  6. Tests of conservation laws

    International Nuclear Information System (INIS)

    Goldhaber, M.

    1988-01-01

    For quite a while it has been realized that some discrete quantum numbers are conserved in some interactions but not in others. The most conspicuous cases are parity P, charge conjugation C, and the product CP which are conserved in strong and electromagnetic interactions but not in weak interactions. The question arises whether for some of the other conserved quantities, which are conserved in strong, electromagnetic and weak interactions, there is an interaction intermediate in strength between weak and gravitational which violates these quantum numbers, e.g., baryon number B and lepton number L. The possibility exists that these conservation laws, if they are broken at all, are only broken by the gravitational force which would make the mass of an intermediate boson which induces the break-down equal to the Planck mass. (orig.)

  7. A single amino-acid change in a highly conserved motif of gp41 elicits HIV-1 neutralization and protects against CD4 depletion.

    Science.gov (United States)

    Petitdemange, Caroline; Achour, Abla; Dispinseri, Stefania; Malet, Isabelle; Sennepin, Alexis; Ho Tsong Fang, Raphaël; Crouzet, Joël; Marcelin, Anne-Geneviève; Calvez, Vincent; Scarlatti, Gabriella; Debré, Patrice; Vieillard, Vincent

    2013-09-01

    The induction of neutralizing antibodies against conserved regions of the human immunodeficiency virus type 1 (HIV-1) envelope protein is a major goal of vaccine strategies. We previously identified 3S, a critical conserved motif of gp41 that induces the NKp44L ligand of an activating NK receptor. In vivo, anti-3S antibodies protect against the natural killer (NK) cell-mediated CD4 depletion that occurs without efficient viral neutralization. Specific substitutions within the 3S peptide motif were prepared by directed mutagenesis. Virus production was monitored by measuring the p24 production. Neutralization assays were performed with immune-purified antibodies from immunized mice and a cohort of HIV-infected patients. Expression of NKp44L on CD4(+) T cells and degranulation assay on activating NK cells were both performed by flow cytometry. Here, we show that specific substitutions in the 3S motif reduce viral infection without affecting gp41 production, while decreasing both its capacity to induce NKp44L expression on CD4(+) T cells and its sensitivity to autologous NK cells. Generation of antibodies in mice against the W614 specific position in the 3S motif elicited a capacity to neutralize cross-clade viruses, notable in its magnitude, breadth, and durability. Antibodies against this 3S variant were also detected in sera from some HIV-1-infected patients, demonstrating both neutralization activity and protection against CD4 depletion. These findings suggest that a specific substitution in a 3S-based immunogen might allow the generation of specific antibodies, providing a foundation for a rational vaccine that combine a capacity to neutralize HIV-1 and to protect CD4(+) T cells.

  8. A Conservative Formulation for Plasticity

    Science.gov (United States)

    1992-01-01

    concepts that apply to a broad class of macroscopic models: plastic deformation and plastic flow rule. CONSERVATIVE PLASTICITY 469 3a. Plastic Defrrnation...temperature. We illustrate these concepts with a model that has been used to describe high strain-rate plastic flow in metals [11, 31, 32]. In the case...JOURDREN, AND P. VEYSSEYRE. Un Modele ttyperelastique- Plastique Euldrien Applicable aux Grandes Dtformations: Que/ques R~sultats 1-D. preprint, 1991. 2. P

  9. Integrating agricultural expansion into conservation biogeography: conflicts and priorities

    Directory of Open Access Journals (Sweden)

    Ricardo Dobrovolski

    2014-06-01

    Full Text Available Increasing food production without compromising biodiversity is one of the great challenges for humanity. The aims of my thesis were to define spatial priorities for biodiversity conservation and to evaluate conservation conflicts considering agricultural expansion in the 21st century. I also tested the effect of globalizing conservation efforts on both food production and biodiversity conservation. I found spatial conflicts between biodiversity conservation and agricultural expansion. However, incorporating agricultural expansion data into the spatial prioritization process can significantly alleviate conservation conflicts, by reducing spatial correlation between the areas under high impact of agriculture and the priority areas for conservation. Moreover, developing conservation blueprints at the global scale, instead of the usual approach based on national boundaries, can benefit both food production and biodiversity. Based on these findings I conclude that the incorporation of agricultural expansion as a key component for defining global conservation strategies should be added to the list of solutions for our cultivated planet.

  10. Lasers in the Conservation of Artworks

    CERN Document Server

    Nimmrichter, Johann; Schreiner, Manfred; LACONA VI Proceedings

    2007-01-01

    Within the last decades, the use of lasers in artworks conservation became an important tool for many conservators, scientists, architects and other experts, who are involved in the care of monuments and artefacts or laser technology. For the first time in 1995 Professor Costas Fotakis brought together restorers and scientists to discuss the potential of lasers in art conservation. Since then the field of "Lasers in the Conservation of Artworks" has gained enormously in importance. Nowadays restorers and laser scientists work close together in order to develop new fields of applications during the last years. Furthermore a large number of national and international research projects have been carried out by conservator-restorers, architects and scientists. In the last 10 years a number of historical and artistic high quality monuments (e.g. St. Stephens Cathedral in Vienna) have been cleaned or measured by laser and brought the laser in the spectra of tools which are useful in the sensible field of artworks. ...

  11. Conservation when landowners have bargaining power

    DEFF Research Database (Denmark)

    Lennox, Gareth D.; Gaston, Kevin J.; Acs, Szvetlana

    2013-01-01

    agreement. Implicitly assumed in such studies is therefore that those who ``produce'' biodiversity (landowners) receive none of the surplus available from trade. Instead, landowners could use their bargaining power to gain profits from conservation investments. We employ game theory to determine the surplus...... landowners could obtain in negotiations over conservation agreements, and the consequent effects on conservation outcomes, when enrolment decisions are governed by continuous variables (e.g. the proportion of a property to enrol). In addition, we consider how landowner uncertainty regarding the opportunity...... costs of other landowners affects these outcomes. Landowners' ability to gain surplus is highly variable and reflects variation in the substitutability of different properties for achieving a specified conservation objective. The ability of landowners to obtain profits from conservation agreements...

  12. Hearing Conservation Team

    Data.gov (United States)

    Federal Laboratory Consortium — The Hearing Conservation Team focuses on ways to identify the early stages of noise-induced damage to the human ear.Our current research involves the evaluation of...

  13. Madagascar Conservation & Development

    African Journals Online (AJOL)

    Madagascar Conservation & Development. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 9, No 1 (2014) >. Log in or Register to get access to full text downloads.

  14. Metro Conservation Corridors

    Data.gov (United States)

    Minnesota Department of Natural Resources — The Metro Conservation Corridors (MeCC) grow out of the natural resource analysis work done by the DNR in the late '90's, documented in the Metro Greenprint...

  15. Madagascar Conservation & Development

    African Journals Online (AJOL)

    www.journalmcd.com

    2012-02-19

    Feb 19, 2012 ... MADAGASCAR CONSERVATION & DEVELOPMENT. VOLUME 7 ... die within a short period of time (e.g., infanticide) (Erhart and. Overdorff 1998 .... been as deep or may have healed by the time of examination. Falls during ...

  16. Birds of Conservation Concern

    Data.gov (United States)

    Department of the Interior — The 1988 amendment to the Fish and Wildlife Conservation Act mandates the U.S. Fish and Wildlife Service (USFWS) to “identify species, subspecies, and populations of...

  17. Structure and expression of GSL1 and GSL2 genes encoding gibberellin stimulated-like proteins in diploid and highly heterozygous tetraploid potato reveals their highly conserved and essential status.

    Science.gov (United States)

    Meiyalaghan, Sathiyamoorthy; Thomson, Susan J; Fiers, Mark W E J; Barrell, Philippa J; Latimer, Julie M; Mohan, Sara; Jones, E Eirian; Conner, Anthony J; Jacobs, Jeanne M E

    2014-01-02

    GSL1 and GSL2, Gibberellin Stimulated-Like proteins (also known as Snakin-1 and Snakin-2), are cysteine-rich peptides from potato (Solanum tuberosum L.) with antimicrobial properties. Similar peptides in other species have been implicated in diverse biological processes and are hypothesised to play a role in several aspects of plant development, plant responses to biotic or abiotic stress through their participation in hormone crosstalk, and redox homeostasis. To help resolve the biological roles of GSL1 and GSL2 peptides we have undertaken an in depth analysis of the structure and expression of these genes in potato. We have characterised the full length genes for both GSL1 (chromosome 4) and GSL2 (chromosome 1) from diploid and tetraploid potato using the reference genome sequence of potato, coupled with further next generation sequencing of four highly heterozygous tetraploid cultivars. The frequency of SNPs in GSL1 and GSL2 were very low with only one SNP every 67 and 53 nucleotides in exon regions of GSL1 and GSL2, respectively. Analysis of comprehensive RNA-seq data substantiated the role of specific promoter motifs in transcriptional control of gene expression. Expression analysis based on the frequency of next generation sequence reads established that GSL2 was expressed at a higher level than GSL1 in 30 out of 32 tissue and treatment libraries. Furthermore, both the GSL1 and GSL2 genes exhibited constitutive expression that was not up regulated in response to biotic or abiotic stresses, hormone treatments or wounding. Potato transformation with antisense knock-down expression cassettes failed to recover viable plants. The potato GSL1 and GSL2 genes are very highly conserved suggesting they contribute to an important biological function. The known antimicrobial activity of the GSL proteins, coupled with the FPKM analysis from RNA-seq data, implies that both genes contribute to the constitutive defence barriers in potatoes. The lethality of antisense knock

  18. Mesocycles in conserving plastics

    DEFF Research Database (Denmark)

    Shashoua, Yvonne

    2016-01-01

    driven by the need to balance the requirements for reversibility in conservation practices with the artist’s intent and significance. Developments within each of the three mesocycles from the 1990s to date are discussed in this article. Environmental science and toxicology of waste plastics offer a novel...... source of information about real time degradation in terrestrial and marine microenvironments that seems likely to contribute to the conservation of similar materials in contemporary artworks....

  19. Soil conservation measures: exercises

    OpenAIRE

    Figueiredo, Tomás de; Fonseca, Felícia

    2009-01-01

    Exercises proposed under the topic of Soil Conservation Measures addresses to the design of structural measure, namely waterways in the context of a soil conservation plan. However, to get a better insight on the actual meaning of soil loss as a resource loss, a prior exercise is proposed to students. It concerns calculations of soil loss due to sheet (interrill) erosion and to gully erosion, and allows the perception through realistic number of the impact of these mechanism...

  20. Novel urban ecosystems, biodiversity, and conservation

    International Nuclear Information System (INIS)

    Kowarik, Ingo

    2011-01-01

    With increasing urbanization the importance of cities for biodiversity conservation grows. This paper reviews the ways in which biodiversity is affected by urbanization and discusses the consequences of different conservation approaches. Cities can be richer in plant species, including in native species, than rural areas. Alien species can lead to both homogenization and differentiation among urban regions. Urban habitats can harbor self-sustaining populations of rare and endangered native species, but cannot replace the complete functionality of (semi-)natural remnants. While many conservation approaches tend to focus on such relict habitats and native species in urban settings, this paper argues for a paradigm shift towards considering the whole range of urban ecosystems. Although conservation attitudes may be challenged by the novelty of some urban ecosystems, which are often linked to high numbers of nonnative species, it is promising to consider their associated ecosystem services, social benefits, and possible contribution to biodiversity conservation. - Highlights: → This paper reviews biotic responses to urbanization and urban conservation approaches. → Cities may be rich in both native and nonnative species. → Urban habitats cannot replace the functionality of natural remnants. → However, even novel urban habitats may harbour rare and endangered species. → Conservation approaches should consider the perspective of novel urban ecosystems. - This paper reviews the ways in which biodiversity is affected by urbanization and argues for expanding urban conservation approaches.

  1. Novel urban ecosystems, biodiversity, and conservation

    Energy Technology Data Exchange (ETDEWEB)

    Kowarik, Ingo, E-mail: kowarik@tu-berlin.de [Department of Ecology, Technische Universitaet Berlin, Rothenburgstr. 12, D 12165 Berlin (Germany)

    2011-08-15

    With increasing urbanization the importance of cities for biodiversity conservation grows. This paper reviews the ways in which biodiversity is affected by urbanization and discusses the consequences of different conservation approaches. Cities can be richer in plant species, including in native species, than rural areas. Alien species can lead to both homogenization and differentiation among urban regions. Urban habitats can harbor self-sustaining populations of rare and endangered native species, but cannot replace the complete functionality of (semi-)natural remnants. While many conservation approaches tend to focus on such relict habitats and native species in urban settings, this paper argues for a paradigm shift towards considering the whole range of urban ecosystems. Although conservation attitudes may be challenged by the novelty of some urban ecosystems, which are often linked to high numbers of nonnative species, it is promising to consider their associated ecosystem services, social benefits, and possible contribution to biodiversity conservation. - Highlights: > This paper reviews biotic responses to urbanization and urban conservation approaches. > Cities may be rich in both native and nonnative species. > Urban habitats cannot replace the functionality of natural remnants. > However, even novel urban habitats may harbour rare and endangered species. > Conservation approaches should consider the perspective of novel urban ecosystems. - This paper reviews the ways in which biodiversity is affected by urbanization and argues for expanding urban conservation approaches.

  2. Association of Locoregional Control With High Body Mass Index in Women Undergoing Breast Conservation Therapy for Early-Stage Breast Cancer

    International Nuclear Information System (INIS)

    Bergom, Carmen; Kelly, Tracy; Bedi, Meena; Saeed, Hina; Prior, Phillip; Rein, Lisa E.; Szabo, Aniko; Wilson, J. Frank; Currey, Adam D.; White, Julia

    2016-01-01

    Purpose: Obesity, as measured by the body mass index (BMI), is a risk factor for distant recurrence and decreased survival in breast cancer. We sought to determine whether the BMI correlated with local recurrence and reduced survival in a cohort of predominantly obese women treated with breast conservation therapy. Methods and Materials: From 1998 to 2010, 154 women with early-stage invasive breast cancer and 39 patients with ductal carcinoma in situ underwent prone whole breast irradiation. Cox proportional hazards regression, Kaplan-Meier methods with the log-rank test, and multivariate analysis were used to explore the association of the outcomes with the BMI. Results: The median patient age was 60 years, and the median follow-up duration was 73 months. The median BMI was 33.2 kg/m 2 ; 91% of the patients were overweight (BMI ≥25 kg/m 2 ) and 69% of the patients were clinically obese (BMI ≥30 kg/m 2 ). The BMI was significantly associated with the locoregional recurrence-free interval for patients with invasive cancer and ductal carcinoma in situ (hazard ratio [HR], 1.09; P=.047). Also, a trend was seen for increased locoregional recurrence with a higher BMI (P=.09) for patients with invasive disease, which was significant when examining the outcomes with a BMI stratified by the median value of 33.2 kg/m 2 (P=.008). A greater BMI was also significantly associated with decreased distant recurrence-free interval (HR, 1.09; P=.011) and overall survival (HR, 1.09; P=.004); this association remained on multivariate analysis (distant recurrence-free interval, P=.034; overall survival, P=.0007). Conclusions: These data suggest that the BMI might affect the rate of locoregional recurrence in breast cancer patients. A higher BMI predicted a worse distant recurrence-free interval and overall survival. The present investigation adds to the increasing evidence that BMI is an important prognostic factor in early-stage breast cancer treated with breast conservation

  3. Association of Locoregional Control With High Body Mass Index in Women Undergoing Breast Conservation Therapy for Early-Stage Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bergom, Carmen; Kelly, Tracy; Bedi, Meena; Saeed, Hina; Prior, Phillip [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Rein, Lisa E.; Szabo, Aniko [Division of Biostatistics, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Wilson, J. Frank; Currey, Adam D. [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); White, Julia, E-mail: Julia.White@osumc.edu [Department of Radiation Oncology, James Cancer Hospital, Ohio State University Comprehensive Cancer Center, Columbus, Ohio (United States)

    2016-09-01

    Purpose: Obesity, as measured by the body mass index (BMI), is a risk factor for distant recurrence and decreased survival in breast cancer. We sought to determine whether the BMI correlated with local recurrence and reduced survival in a cohort of predominantly obese women treated with breast conservation therapy. Methods and Materials: From 1998 to 2010, 154 women with early-stage invasive breast cancer and 39 patients with ductal carcinoma in situ underwent prone whole breast irradiation. Cox proportional hazards regression, Kaplan-Meier methods with the log-rank test, and multivariate analysis were used to explore the association of the outcomes with the BMI. Results: The median patient age was 60 years, and the median follow-up duration was 73 months. The median BMI was 33.2 kg/m{sup 2}; 91% of the patients were overweight (BMI ≥25 kg/m{sup 2}) and 69% of the patients were clinically obese (BMI ≥30 kg/m{sup 2}). The BMI was significantly associated with the locoregional recurrence-free interval for patients with invasive cancer and ductal carcinoma in situ (hazard ratio [HR], 1.09; P=.047). Also, a trend was seen for increased locoregional recurrence with a higher BMI (P=.09) for patients with invasive disease, which was significant when examining the outcomes with a BMI stratified by the median value of 33.2 kg/m{sup 2} (P=.008). A greater BMI was also significantly associated with decreased distant recurrence-free interval (HR, 1.09; P=.011) and overall survival (HR, 1.09; P=.004); this association remained on multivariate analysis (distant recurrence-free interval, P=.034; overall survival, P=.0007). Conclusions: These data suggest that the BMI might affect the rate of locoregional recurrence in breast cancer patients. A higher BMI predicted a worse distant recurrence-free interval and overall survival. The present investigation adds to the increasing evidence that BMI is an important prognostic factor in early-stage breast cancer treated with

  4. Prediction and characterisation of a highly conserved, remote and cAMP responsive enhancer that regulates Msx1 gene expression in cardiac neural crest and outflow tract.

    Science.gov (United States)

    Miller, Kerry Ann; Davidson, Scott; Liaros, Angela; Barrow, John; Lear, Marissa; Heine, Danielle; Hoppler, Stefan; MacKenzie, Alasdair

    2008-05-15

    Double knockouts of the Msx1 and Msx2 genes in the mouse result in severe cardiac outflow tract malformations similar to those frequently found in newborn infants. Despite the known role of the Msx genes in cardiac formation little is known of the regulatory systems (ligand receptor, signal transduction and protein-DNA interactions) that regulate the tissue-specific expression of the Msx genes in mammals during the formation of the outflow tract. In the present study we have used a combination of multi-species comparative genomics, mouse transgenic analysis and in-situ hybridisation to predict and validate the existence of a remote ultra-conserved enhancer that supports the expression of the Msx1 gene in migrating mouse cardiac neural crest and the outflow tract primordia. Furthermore, culturing of embryonic explants derived from transgenic lines with agonists of the PKC and PKA signal transduction systems demonstrates that this remote enhancer is influenced by PKA but not PKC dependent gene regulatory systems. These studies demonstrate the efficacy of combining comparative genomics and transgenic analyses and provide a platform for the study of the possible roles of Msx gene mis-regulation in the aetiology of congenital heart malformation.

  5. 78 FR 72533 - Energy Conservation Program: Energy Conservation Standards for Certain Consumer Products

    Science.gov (United States)

    2013-12-03

    ... published on October 23, 2013. That final rule adopted changes to definitions and energy conservation... revised definition and revised energy conservation standards for small duct high velocity central air... Congress has provided in the AEMTCA for the Secretary of Energy to revise definitions and energy...

  6. Hydrology and Conservation Ecology

    Science.gov (United States)

    Narayanan, M.

    2006-12-01

    Responses to change in the behavior of ecological systems are largely governed by interactions at different levels. Research is essential and is to be necessarily designed to gain insights into various interactions at the community level. Sustainable resource management is only possible if conservation of biodiversity can be accomplished by properly using the knowledge discovered. It is well known that the United States Department of Agriculture provides technical information, resources, and data necessary to assist the researchers in addressing their conservation needs. Conservation aims to protect, preserve and conserve the earth's natural resources. These include, but not limited to the conservation of soil, water, minerals, air, plants and all living beings. The United States Department of Agriculture also encourages farmers and ranchers to voluntarily address threats to soil and water. Protection of wetlands and wildlife habitat has been on the radar screen of conservation experts for a very long time. The main objective has always been to help farmers and landowners conform and comply with federal and state environmental laws. During the implementation phase, farmers should be encouraged to make beneficial, cost-effective changes to methods of irrigation systems. In some cases, the hydrologic regime of the project area can be thought of as principally an issue of river flow regimes for floodplain forests. In this presentation, the author tries to focus on the impact of hydrology and conservation ecology on global warming. He also discusses the impact of hydrology and conservation ecology global air concerns such as greenhouse gas concentrations in the atmosphere. References: Chow, V. T, D. R. Maidment, and L. W. Mays. 1988. Applied Hydrology. McGraw-Hill, Inc. U.S. Soil Conservation Service. Technical Release 55: Urban Hydrology for Small Watersheds. USDA (U.S. Department of Agriculture). June 1986. Lehner, B. and P. Döll (2004). Development and validation

  7. Tourism and Conservation

    DEFF Research Database (Denmark)

    Budeanu, Adriana

    2017-01-01

    Tourism is promoted by policy makers and international organizations as a tool for advancing conservation agendas, while contributing to poverty alleviation and human development, under the banner of ecotourism or sustainable tourism. However, the indiscriminating use of complex and ambiguous...... concepts such as “poverty” and “sustainability” hide important nuances with regards to the variety of processes and subsequent effects that are triggered when tourism and conservation are being adjoined. Experiences with tourism developments show that destinations that are weak economically find it harder...... to draw benefits from tourism developments or to decline participation in tourism with only little or no losses of sources of income and wealth. If tourism should fulfil sustainability goals related to conservation, poverty, and human development, it needs consistent governmental intervention...

  8. Resource conservation management

    International Nuclear Information System (INIS)

    Miller, W.

    1999-01-01

    Resource conservation management is a management program similar to financial management in that its success requires commitment by all levels of the organization to the process as well as an accounting procedure and auditing of critical components. Resource conservation management provides a framework for all elements of efficient building operations and maintenance. The savings connected with the program are principally connected with changes in the way buildings are operated and maintained. Given the reduction in rebates for the installation of energy-efficient equipment, this approach has considerable promise. This paper discusses the evolution of the resource conservation management service and the savings associated with a two-year pilot effort with seven school districts, as well as the critical components of a successful program

  9. Reconciling nature conservation and traditional farming practices: a spatially explicit framework to assess the extent of High Nature Value farmlands in the European countryside

    NARCIS (Netherlands)

    Araujo Rodrigues Lomba, de Angela; Alves, Paulo; Jongman, R.H.G.; McCracken, D.

    2015-01-01

    Agriculture constitutes a dominant land cover worldwide, and rural landscapes
    under extensive farming practices acknowledged due to high biodiversity
    levels. The High Nature Value farmland (HNVf) concept has been
    highlighted in the EU environmental and rural policies due to their

  10. Conservation reaches new heights.

    Science.gov (United States)

    Pepall, J; Khanal, P

    1992-10-01

    The conservation program with the management assistance of the Woodlands Mountain Institute in 2 contiguous parks, the Mount Everest National Park in Nepal and the Qomolangma Nature Reserve in China, in 2 countries is described. The focus is on conservation of the complex ecosystem with sustainable development by showing local people how to benefit from the park without environmental damage. Cultural diversity is as important as biological diversity. The area has been designated by UNESCO as a World Heritage Site with the "last pure ecological seed" of the Himalayas. The regional geography and culture are presented. Population growth has impacted natural resources through overgrazing, cultivation of marginal land, and deforestation; future plans to build a dam and road bordering the nature reserve pose other threats. Proposed management plans for the Makalu-Barun Nature Park (established in November 1991) and Conservation Area include a division of the park into nature reserve areas free of human activity, protected areas which permit traditional land use, and special sites and trail for tourists and religious pilgrims. The conservation area will act as a buffer for the park and provide economic opportunities; further subdivisions include land use for biodiversity protection, community forest and pasture, agroforestry, and agriculture and settlement. Efforts will be made to increase the welfare of women and local people; proposed projects include the introduction of higher milk-producing animals for stall feeding. Also proposed is a cultural and natural history museum. 70% of the project's resources will be directed to local community participation in consultation and park maintenance. The project is a model of how conservation and protection of natural resources can coexist with local economic development and participation; an integration of preservation of biological diversity, mountain wisdom, and the value of local people as resources for conservation.

  11. Energy conservation in industry

    International Nuclear Information System (INIS)

    Pembleton, P.

    1992-01-01

    Energy Conservation in Industry is the first number in the Energy and Environmental Series of the Industrial and Technological Information Bank (INTIB). The Series supersedes the INECA Journal and reflects the broader information programme undertaken by INTIB. The present number of the Series contains contributions from three major international databases and five topic-specific sources, including three United Nations Organizations. The present publication consists of a recent technical report on a current topic: reducing energy loss in four industrial sectors and improving energy conservation through waste-heat recovery, followed by two sections containing abstracts of technical materials

  12. Local instant conservation equations

    International Nuclear Information System (INIS)

    Delaje, Dzh.

    1984-01-01

    Local instant conservation equations for two-phase flow are derived. Derivation of the equation starts from the recording of integral laws of conservation for a fixed reference volume, containing both phases. Transformation of the laws, using the Leibniz rule and Gauss theory permits to obtain the sum of two integrals as to the volume and integral as to the surface. Integrals as to the volume result in local instant differential equations, in particular derivatives for each phase, and integrals as to the surface reflect local instant conditions of a jump on interface surface

  13. Information, conservation and retrieval

    Energy Technology Data Exchange (ETDEWEB)

    Eng, T [Swedish Nuclear Fuel and Waste Management Co., Stockholm (Sweden); Norberg, E [National Swedish Archives, Stockholm (Sweden); Torbacke, J [Stockholm Univ. (Sweden). Dept. of History; Jensen, M [Swedish Radiation Protection Inst., Stockholm (Sweden)

    1996-12-01

    The seminar took place on the Swedish ship for transportation of radioactive wastes, M/S Sigyn, which at summer time is used for exhibitions. The seminar treated items related to general information needs in society and questions related to radioactive waste, i.e. how knowledge about a waste repository should be passed on to future generations. Three contributions are contained in the report from the seminar and are indexed separately: `Active preservation - otherwise no achieves`; `The conservation and dissemination of information - A democratic issue`; and, `Conservation and retrieval of information - Elements of a strategy to inform future societies about nuclear waste repositories`.

  14. Information, conservation and retrieval

    International Nuclear Information System (INIS)

    Eng, T.; Norberg, E.; Torbacke, J.

    1996-12-01

    The seminar took place on the Swedish ship for transportation of radioactive wastes, M/S Sigyn, which at summer time is used for exhibitions. The seminar treated items related to general information needs in society and questions related to radioactive waste, i.e. how knowledge about a waste repository should be passed on to future generations. Three contributions are contained in the report from the seminar and are indexed separately: 'Active preservation - otherwise no achieves'; 'The conservation and dissemination of information - A democratic issue'; and, 'Conservation and retrieval of information - Elements of a strategy to inform future societies about nuclear waste repositories'

  15. Quantifying solute transport processes: are chemically "conservative" tracers electrically conservative?

    Science.gov (United States)

    Singha, Kamini; Li, Li; Day-Lewis, Frederick D.; Regberg, Aaron B.

    2012-01-01

    The concept of a nonreactive or conservative tracer, commonly invoked in investigations of solute transport, requires additional study in the context of electrical geophysical monitoring. Tracers that are commonly considered conservative may undergo reactive processes, such as ion exchange, thus changing the aqueous composition of the system. As a result, the measured electrical conductivity may reflect not only solute transport but also reactive processes. We have evaluated the impacts of ion exchange reactions, rate-limited mass transfer, and surface conduction on quantifying tracer mass, mean arrival time, and temporal variance in laboratory-scale column experiments. Numerical examples showed that (1) ion exchange can lead to resistivity-estimated tracer mass, velocity, and dispersivity that may be inaccurate; (2) mass transfer leads to an overestimate in the mobile tracer mass and an underestimate in velocity when using electrical methods; and (3) surface conductance does not notably affect estimated moments when high-concentration tracers are used, although this phenomenon may be important at low concentrations or in sediments with high and/or spatially variable cation-exchange capacity. In all cases, colocated groundwater concentration measurements are of high importance for interpreting geophysical data with respect to the controlling transport processes of interest.

  16. Science Experience Unit: Conservation.

    Science.gov (United States)

    Ferguson-Florissant School District, Ferguson, MO.

    GRADES OR AGES: Intermediate grades. SUBJECT MATTER: Conservation. ORGANIZATION AND PHYSICAL APPEARANCE: The guide is divided into 24 experiments. It is mimeographed and staple-bound with a paper cover. OBJECTIVES AND ACTIVITIES: A specific skill or knowledge objective is stated at the beginning of each experiment. Detailed procedures are listed…

  17. (ICTs) And Environmental Conservation

    African Journals Online (AJOL)

    ICTs have a potential for improving the accessibility of environmental information, and if appropriately applied, they can empower local people to make informed decisions regarding environmental issues, thus enhancing environmental conservation. However, the challenge is on how to define particular roles that ...

  18. Conservative Delta Hedging

    Science.gov (United States)

    1997-09-01

    an exact method for converting such intervals into arbitrage based prices of financial derivatives or industrial or contractual options. We call this...procedure conservative delta hedging . As existing procedures are of an ad hoc nature, the proposed approach will permit an institution’s man agement a greater oversight of its exposure to risk.

  19. [Lateral epicondylitis: conservative - operative].

    Science.gov (United States)

    Altintas, Burak; Greiner, Stefan

    2016-10-01

    Lateral epicondylitis is a common disease of the common extensor origin at the lateral humerus. Despite its common self-limitation it can lead to chronic therapy-resistant pain with remarkable functional disability of the affected arm. Different conservative and operative treatment options of lateral epicondylitis are described and compared regarding benefits and risks. Additionally, recent surgical techniques and their complications are mentioned. Based on the current literature, it is shown which treatment option can be recommended. This review was based on the literature analysis in PubMed regarding "conservative and operative therapy of lateral epicondylitis" as well as the clinical experience of the authors. Conservative treatment is the primary choice for the treatment of lateral epicondylitis if concomitant pathologies such as instability among others can be excluded. It should include strengthening against resistance with eccentric stretching of the extensor group. In persistent cases, operative treatment is warranted. Resection of the pathologic tissue at the extensor origin with debridement and refixation of the healthy tendinous tissue yields good results. Most patients with lateral epicondylitis can be treated conservatively with success. Radiological evaluation should be performed in therapy-resistant cases. In the case of partial or complete rupture of the extensor origin, operative therapy is indicated.

  20. Biological science in conservation

    Science.gov (United States)

    David M. Johns

    2000-01-01

    Large-scale wildlands reserve systems offer one of the best hopes for slowing, if not reversing, the loss of biodiversity and wilderness. Establishing such reserves requires both sound biology and effective advocacy. Attempts by The Wildlands Project and its cooperators to meld science and advocacy in the service of conservation is working, but is not without some...

  1. Speyeria (Lepidoptera: Nymphalidae Conservation

    Directory of Open Access Journals (Sweden)

    Steven R. Sims

    2017-04-01

    Full Text Available Speyeria (Nymphalidae are a conspicuous component of the North American butterfly fauna. There are approximately 16 species and >100 associated subspecies (or geographical variants. Speyeria are univoltine, occupy a wide range of habitats, overwinter as first instar larvae, and feed only on native violets. Speyeria species have become a model group for studies of evolution, speciation, and conservation. Several species and subspecies are threatened or endangered. The reasons for this vary with the taxa involved, but always involve the degradation or loss of quality habitat for larvae and adults. The impacts of climate change must be considered among the causes for habitat degradation and in the establishment of conservation measures. In addition to increasing the available habitat, conservation efforts should consider maintaining habitat in a seral “disturbed” successional stage that selectively favors the growth of violets and preferred adult nectar sources. A major future challenge will be determining the most effective allocation of conservation resources to those species and subspecies that have the greatest potential to respond favorably to these efforts.

  2. Conservation and gene banking

    Science.gov (United States)

    Plant conservation has several objectives the main ones include safeguarding our food supply, preserving crop wild relatives for breeding and selection of new cultivars, providing material for industrial and pharmaceutical uses and preserving the beauty and diversity of our flora for generations to ...

  3. Crowdfunding biodiversity conservation.

    Science.gov (United States)

    Gallo-Cajiao, E; Archibald, C; Friedman, R; Steven, R; Fuller, R A; Game, E T; Morrison, T H; Ritchie, E G

    2018-05-26

    Raising funds is critical for conserving biodiversity and hence so too is scrutinizing emerging financial mechanisms that might help achieve this goal. In this context, anecdotal evidence indicates crowdfunding is being used to support a variety of activities needed for biodiversity conservation, yet its magnitude and allocation remain largely unknown. We conducted a global analysis to help address this knowledge gap, based on empirical data from conservation-focused projects extracted from crowdfunding platforms. For each project, we determined the funds raised, date, country of implementation, proponent characteristics, activity type, biodiversity realm, and target taxa. We identified 72 relevant platforms and 577 conservation-focused projects that have raised US$4 790 634 since 2009. Whilst proponents were based in 38 countries, projects were delivered across 80 countries, indicating a potential mechanism of resource mobilization. Proponents were from non-governmental organizations (35%), universities (30%), or were freelancers (26%). Most projects were for research (40%), persuasion (31%), and on-ground actions (21%). Projects have focused primarily on species (57.7%) and terrestrial ecosystems (20.3%), and less on marine (8.8%) and freshwater ecosystems (3.6%). Projects have focused on 208 species, including a disproportionate number of threatened bird and mammal species. Crowdfunding for biodiversity conservation has now become a global phenomenon and presents signals for potential expansion, despite possible pitfalls. Opportunities arise from its spatial amplifying effect, steady increase over time, inclusion of Cinderella species, adoption by multiple actors, and funding of a range of activities beyond research. Our study paves the way for further research on key questions, such as campaign success rates, effectiveness, and drivers of adoption. Even though the capital input of crowdfunding so far has been modest compared to other conservation finance

  4. Status of nuclear fuel reprocessing, spent fuel storage, and high-level waste disposal. Nuclear Fuel Cycle Committee, California Energy Resources Conservation and Development Commission. Draft report

    International Nuclear Information System (INIS)

    Anon.

    1978-01-01

    An analysis of the current status of technologies and issues in the major portions of the back-end of the nuclear fuel cycle is presented. The discussion on nuclear fuel reprocessing covers the reprocessing requirement, reprocessing technology assessment, technology for operation of reprocessing plants, and approval of reprocessing plants. The chapter devoted to spent fuel storage covers the spent fuel storge problem, the legislative response, options for maintaining full core discharge capacity, prospective availability of alterntive storage options, and the outlook for California. The existence of a demonstrated, developed high-level waste disposal technology is reviewed. Recommendations for Federal programs on high-level waste disposal are made

  5. From Civic Conservation to the Age of Ecology: The Rise and Synthesis of Ecological Ideas in the American High School Science Curriculum, 1900-1980

    Science.gov (United States)

    Laubach, Stephen A.

    2013-01-01

    Ecological ideas have been manifested in diverse ways in American high schools since the early twentieth century. Core scientific concepts in ecology--the study of the relationship between organisms and their environment--include adaptations, plant succession, ecosystem ecology, and population ecology. This dissertation argues, however, that there…

  6. Optimized spatial priorities for biodiversity conservation in China: a systematic conservation planning perspective.

    Science.gov (United States)

    Wu, Ruidong; Long, Yongcheng; Malanson, George P; Garber, Paul A; Zhang, Shuang; Li, Diqiang; Zhao, Peng; Wang, Longzhu; Duo, Hairui

    2014-01-01

    By addressing several key features overlooked in previous studies, i.e. human disturbance, integration of ecosystem- and species-level conservation features, and principles of complementarity and representativeness, we present the first national-scale systematic conservation planning for China to determine the optimized spatial priorities for biodiversity conservation. We compiled a spatial database on the distributions of ecosystem- and species-level conservation features, and modeled a human disturbance index (HDI) by aggregating information using several socioeconomic proxies. We ran Marxan with two scenarios (HDI-ignored and HDI-considered) to investigate the effects of human disturbance, and explored the geographic patterns of the optimized spatial conservation priorities. Compared to when HDI was ignored, the HDI-considered scenario resulted in (1) a marked reduction (∼9%) in the total HDI score and a slight increase (∼7%) in the total area of the portfolio of priority units, (2) a significant increase (∼43%) in the total irreplaceable area and (3) more irreplaceable units being identified in almost all environmental zones and highly-disturbed provinces. Thus the inclusion of human disturbance is essential for cost-effective priority-setting. Attention should be targeted to the areas that are characterized as moderately-disturbed, conservation. We delineated 23 primary large-scale priority areas that are significant for conserving China's biodiversity, but those isolated priority units in disturbed regions are in more urgent need of conservation actions so as to prevent immediate and severe biodiversity loss. This study presents a spatially optimized national-scale portfolio of conservation priorities--effectively representing the overall biodiversity of China while minimizing conflicts with economic development. Our results offer critical insights for current conservation and strategic land-use planning in China. The approach is transferable and easy

  7. Conservation businesses and conservation planning in a biological diversity hotspot.

    Science.gov (United States)

    Di Minin, Enrico; Macmillan, Douglas Craig; Goodman, Peter Styan; Escott, Boyd; Slotow, Rob; Moilanen, Atte

    2013-08-01

    The allocation of land to biological diversity conservation competes with other land uses and the needs of society for development, food, and extraction of natural resources. Trade-offs between biological diversity conservation and alternative land uses are unavoidable, given the realities of limited conservation resources and the competing demands of society. We developed a conservation-planning assessment for the South African province of KwaZulu-Natal, which forms the central component of the Maputaland-Pondoland-Albany biological diversity hotspot. Our objective was to enhance biological diversity protection while promoting sustainable development and providing spatial guidance in the resolution of potential policy conflicts over priority areas for conservation at risk of transformation. The conservation-planning assessment combined spatial-distribution models for 646 conservation features, spatial economic-return models for 28 alternative land uses, and spatial maps for 4 threats. Nature-based tourism businesses were competitive with other land uses and could provide revenues of >US$60 million/year to local stakeholders and simultaneously help meeting conservation goals for almost half the conservation features in the planning region. Accounting for opportunity costs substantially decreased conflicts between biological diversity, agricultural use, commercial forestry, and mining. Accounting for economic benefits arising from conservation and reducing potential policy conflicts with alternative plans for development can provide opportunities for successful strategies that combine conservation and sustainable development and facilitate conservation action. © 2013 Society for Conservation Biology.

  8. Understanding conservationists' perspectives on the new-conservation debate.

    Science.gov (United States)

    Holmes, George; Sandbrook, Chris; Fisher, Janet A

    2017-04-01

    A vibrant debate about the future direction of biodiversity conservation centers on the merits of the so-called new conservation. Proponents of the new conservation advocate a series of positions on key conservation ideas, such as the importance of human-dominated landscapes and conservation's engagement with capitalism. These have been fiercely contested in a debate dominated by a few high-profile individuals, and so far there has been no empirical exploration of existing perspectives on these issues among a wider community of conservationists. We used Q methodology to examine empirically perspectives on the new conservation held by attendees at the 2015 International Congress for Conservation Biology (ICCB). Although we identified a consensus on several key issues, 3 distinct positions emerged: in favor of conservation to benefit people but opposed to links with capitalism and corporations, in favor of biocentric approaches but with less emphasis on wilderness protection than prominent opponents of new conservation, and in favor of the published new conservation perspective but with less emphasis on increasing human well-being as a goal of conservation. Our results revealed differences between the debate on the new conservation in the literature and views held within a wider, but still limited, conservation community and demonstrated the existence of at least one viewpoint (in favor of conservation to benefit people but opposed to links with capitalism and corporations) that is almost absent from the published debate. We hope the fuller understanding we present of the variety of views that exist but have not yet been heard, will improve the quality and tone of debates on the subject. © 2016 The Authors. Conservation Biology published by Wiley Periodicals, Inc. on behalf of Society for Conservation Biology.

  9. Conserving tigers in working landscapes.

    Science.gov (United States)

    Chanchani, Pranav; Noon, Barry R; Bailey, Larissa L; Warrier, Rekha A

    2016-06-01

    Tiger (Panthera tigris) conservation efforts in Asia are focused on protected areas embedded in human-dominated landscapes. A system of protected areas is an effective conservation strategy for many endangered species if the network is large enough to support stable metapopulations. The long-term conservation of tigers requires that the species be able to meet some of its life-history needs beyond the boundaries of small protected areas and within the working landscape, including multiple-use forests with logging and high human use. However, understanding of factors that promote or limit the occurrence of tigers in working landscapes is incomplete. We assessed the relative influence of protection status, prey occurrence, extent of grasslands, intensity of human use, and patch connectivity on tiger occurrence in the 5400 km(2) Central Terai Landscape of India, adjacent to Nepal. Two observer teams independently surveyed 1009 km of forest trails and water courses distributed across 60 166-km(2) cells. In each cell, the teams recorded detection of tiger signs along evenly spaced trail segments. We used occupancy models that permitted multiscale analysis of spatially correlated data to estimate cell-scale occupancy and segment-scale habitat use by tigers as a function of management and environmental covariates. Prey availability and habitat quality, rather than protected-area designation, influenced tiger occupancy. Tiger occupancy was low in some protected areas in India that were connected to extensive areas of tiger habitat in Nepal, which brings into question the efficacy of current protection and management strategies in both India and Nepal. At a finer spatial scale, tiger habitat use was high in trail segments associated with abundant prey and large grasslands, but it declined as human and livestock use increased. We speculate that riparian grasslands may provide tigers with critical refugia from human activity in the daytime and thereby promote tiger occurrence

  10. Methods of equipment conservation of a carboelectric

    International Nuclear Information System (INIS)

    Hurtado Higuera, Julio Cesar

    2001-01-01

    Several conservation methods are mentioned like they are those of conservation in dry, in humid, conservation of bombs of water conservation, of turbines, of generators, of transformers, of electric motors and conservation of coal piles

  11. A highly conserved glycine within linker I and the extreme C terminus of G protein alpha subunits interact cooperatively in switching G protein-coupled receptor-to-effector specificity

    DEFF Research Database (Denmark)

    Kostenis, Evi; Martini, Lene; Ellis, James

    2004-01-01

    Numerous studies have attested to the importance of the extreme C terminus of G protein alpha subunits in determining their selectivity of receptor recognition. We have previously reported that a highly conserved glycine residue within linker I is important for constraining the fidelity of receptor...... recognition by Galpha(q) proteins. Herein, we explored whether both modules (linker I and extreme C terminus) interact cooperatively in switching G protein-coupled receptor (GPCR)-to-effector specificity and created as models mutant Galpha(q) proteins in which glycine was replaced with various amino acids...... and the C-terminal five Galpha(q) residues with the corresponding Galpha(i) or Galpha(s) sequence. Coupling properties of the mutated Galpha(q) proteins were determined after coexpression with a panel of 13 G(i)-and G(s) -selective receptors and compared with those of Galpha proteins modified in only one...

  12. Numerical solutions of conservation laws

    International Nuclear Information System (INIS)

    Shu, C.W.

    1986-01-01

    In the computation of conservation laws u/sub t/ + f(u)/sub x/ 0, TVD (total-variation-diminishing) schemes have been very successful. TVB (total-variation-bounded) schemes share most the advantages and may remove some of the disadvantages (e.g. local degeneracy of accuracy at critical points) TVD schemes. Included in this dissertation are a class of m-step Runge-Kutta type TVD schemes with CFL number equaling m; a procedure to obtain uniformly high order in space TVB schemes; a class of TVD high order time discretizations; a special boundary treatment which keeps the high order of the scheme up to the boundary and preserves the TVB properties in the nonlinear scalar and linear system cases; a discrete entropy inequality for a modified Lax-Wendroff scheme applied to Burgers' equation; and discusses about error propagation in large regions

  13. A novel lens epithelium gene, LEP503, is highly conserved in different vertebrate species and is developmentally regulated in postnatal rat lens.

    Science.gov (United States)

    Wen, Y; Sachs, G; Athmann, C

    2000-02-01

    The development of the lens is dependent on the proliferation of lens epithelial cells and their differentiation into fiber cells near the lens bow/equator. Identification of genes specifically expressed in the lens epithelial cells and their functions may provide insight into molecular events that regulate the processes of lens epithelial cell differentiation. In this study, a novel lens epithelium gene product, LEP503, identified from rat by a subtractive cDNA cloning strategy was investigated in the genome organization, mRNA expression and protein localization. The genomic sequences for LEP503 isolated from rat, mouse and human span 1754 bp, 1694 bp and 1895 bp regions encompassing the 5'-flanking region, two exons, one intron and 3'-flanking region. All exon-intron junction sequences conform to the GT/AG rule. Both mouse and human LEP503 genes show very high identity (93% for mouse and 79% for human) to rat LEP503 gene in the exon 1 that contains an open reading frame coding for a protein of 61 amino acid residues with a leucine-rich domain. The deduced protein sequences also show high identity (91% between mouse and rat and 77% between human and rat). Western blot shows that LEP503 is present as a specific approximately 6.9 kDa band in the water-insoluble-urea-soluble fraction of lens cortex where lens epithelium is included. Immuno-staining shows that LEP503 is localized in the epithelial cells along the entire anterior surface of rat lens. Developmentally, LEP503 is expressed at a low level at newborn, and then the expression level increases by about ten-fold around postnatal day 14 and remains at this high level for about 25 days before it drops back to the low level by postnatal day 84. These data suggest that the LEP503 may be an important lens epithelial cell gene involving the processes of epithelial cell differentiation. Copyright 2000 Academic Press.

  14. Geomorphological characterization of conservation agriculture

    Science.gov (United States)

    Tarolli, Paolo; Cecchin, Marco; Prosdocimi, Massimo; Masin, Roberta

    2017-04-01

    Soil water erosion is one of the major threats to soil resources throughout the world. Conventional agriculture has worsened the situation. Therefore, agriculture is facing multiple challenges: it has to produce more food to feed a growing population, and, on the other hand, safeguard natural resources adopting more sustainable production practices. In this perspective, more conservation-minded soil management practices should be taken to achieve an environmental sustainability of crop production. Indeed, conservation agriculture is considered to produce relevant environmental positive outcomes (e.g. reducing runoff and soil erosion, improving soil organic matter content and soil structure, and promoting biological activity). However, as mechanical weed control is limited or absent, in conservation agriculture, dependence on herbicides increases especially in the first years of transition from the conventional system. Consequently, also the risk of herbicide losses via runoff or adsorbed to eroded soil particles could be increased. To better analyse the complexity of soil water erosion and runoff processes in landscapes characterised by conservation agriculture, first, it is necessary to demonstrate if such different practices can significantly affect the surface morphology. Indeed, surface processes such erosion and runoff strongly depend on the shape of the surface. The questions are: are the lands treated with conservation and conventional agriculture different from each other regarding surface morphology? If so, can these differences provide a better understanding of hydrogeomorphic processes as the basis for a better and sustainable land management? To give an answer to these questions, we considered six study areas (three cultivated with no-tillage techniques, three with tillage techniques) in an experimental farm. High-resolution topography, derived from low-cost and fast photogrammetric techniques Structure-from-Motion (SfM), served as the basis to

  15. On momentum conservation

    International Nuclear Information System (INIS)

    Karastoyanov, A.

    1990-01-01

    The relativistic law of momentum transformation shows that the sum of momenta of even isolated particles is not invariable in all inertial reference systems. This is connected with the relativistic change of kinetic energy and mass of a system of particles in result of internal interactions. The paper proposes a short and simple proof on the necessity of potential momentum. The momentum conservation law (for all interactions in the Minkowski world) is expressed in a generalized form. The constancy of the sum of kinetic and potential momentum of closed system of particles is shown. The energy conservation is a necessary condition. The potential momentum is defined as usual (e.g. as in the Berkeley Physics Course). (author). 13 refs

  16. Conservation laws shape dissipation

    Science.gov (United States)

    Rao, Riccardo; Esposito, Massimiliano

    2018-02-01

    Starting from the most general formulation of stochastic thermodynamics—i.e. a thermodynamically consistent nonautonomous stochastic dynamics describing systems in contact with several reservoirs—we define a procedure to identify the conservative and the minimal set of nonconservative contributions in the entropy production. The former is expressed as the difference between changes caused by time-dependent drivings and a generalized potential difference. The latter is a sum over the minimal set of flux-force contributions controlling the dissipative flows across the system. When the system is initially prepared at equilibrium (e.g. by turning off drivings and forces), a finite-time detailed fluctuation theorem holds for the different contributions. Our approach relies on identifying the complete set of conserved quantities and can be viewed as the extension of the theory of generalized Gibbs ensembles to nonequilibrium situations.

  17. Evaluating private land conservation in the Cape Lowlands, South Africa.

    Science.gov (United States)

    Von Hase, Amrei; Rouget, Mathieu; Cowling, Richard M

    2010-10-01

    Evaluation is important for judiciously allocating limited conservation resources and for improving conservation success through learning and strategy adjustment. We evaluated the application of systematic conservation planning goals and conservation gains from incentive-based stewardship interventions on private land in the Cape Lowlands and Cape Floristic Region, South Africa. We collected spatial and nonspatial data (2003-2007) to determine the number of hectares of vegetation protected through voluntary contractual and legally nonbinding (informal) agreements with landowners; resources spent on these interventions; contribution of the agreements to 5- and 20-year conservation goals for representation and persistence in the Cape Lowlands of species and ecosystems; and time and staff required to meet these goals. Conservation gains on private lands across the Cape Floristic Region were relatively high. In 5 years, 22,078 ha (27,800 ha of land) and 46,526 ha (90,000 ha of land) of native vegetation were protected through contracts and informal agreements, respectively. Informal agreements often were opportunity driven and cheaper and faster to execute than contracts. All contractual agreements in the Cape Lowlands were within areas of high conservation priority (identified through systematic conservation planning), which demonstrated the conservation plan's practical application and a high level of overlap between resource investment (approximately R1.14 million/year in the lowlands) and priority conservation areas. Nevertheless, conservation agreements met only 11% of 5-year and 9% of 20-year conservation goals for Cape Lowlands and have made only a moderate contribution to regional persistence of flora to date. Meeting the plan's conservation goals will take three to five times longer and many more staff members to maintain agreements than initially envisaged. © 2010 Society for Conservation Biology.

  18. Genetic evaluation of seeds of highly endangered Pinus uliginosa Neumann from Węgliniec reserve for ex-situ conservation program

    Directory of Open Access Journals (Sweden)

    Andrzej Lewandowski

    2011-01-01

    Full Text Available Peat-bog pine Pinus uliginosa Neumann has become extinct or rare in many parts of Europe. We have investigated the levels of genetic variation and inbreeding in seeds collected from a highly endangered reserve of this species in Poland, using allozymes as genetic markers. Generally, a high level of genetic variation was observed. The mean expected heterozygosity was 0.376, while average (Na and effective (Ne numbers of alleles per locus were 2.45 and 1.67, respectively. Nevertheless, we have detected relatively low levels of outcrossing, and potential biparental inbreeding. The population-wide multilocus outcrossing rate was estimated to be 0.706 (±0.091, while the minimum variance mean of single-locus estimates was distinctly lower (ts=0.611. The estimates of outcrossing calculated for individual trees ranged widely from 0.051 to 1.017, indicating the complexity of outcrossing patterns. The investigated population of P. uliginasa from Węgliniec is small and surrounded by extensive forest stands of P. sylvestris. Our three-year records of phenological observations demonstrated that flowering periods for P. uliginosa and P. sylvestris overlap, allowing for cross-pollination. The possibility of P. uliginosa pollination by P. sylvestris creates a potential danger of genetic erosion of the P. uliginosa gene pool. Nonetheless, based on a species specific cpDNA marker we have found that among 533 seedlings of P. uliginosa there were only six seedlings carrying cpDNA marker specific for P. sylvestris, indicating that such hybridization seems to be rare.

  19. Cosmetic Analysis Following Breast-Conserving Surgery and Adjuvant High-Dose-Rate Interstitial Brachytherapy for Early-Stage Breast Cancer: A Prospective Clinical Study

    International Nuclear Information System (INIS)

    Garsa, Adam A.; Ferraro, Daniel J.; DeWees, Todd; Margenthaler, Julie A.; Naughton, Michael; Aft, Rebecca; Gillanders, William E.; Eberlein, Timothy; Matesa, Melissa A.; Zoberi, Imran

    2013-01-01

    Purpose: To prospectively evaluate cosmetic outcomes in women treated with accelerated partial breast irradiation using high-dose-rate interstitial brachytherapy for early-stage breast cancer. Methods and Materials: Between 2004 and 2008, 151 patients with early-stage breast cancer were enrolled in a phase 2 prospective clinical trial. Eligible patients had stage Tis-T2 tumors of ≤3 cm that were excised with negative margins and with no nodal involvement. Patients received 3.4 Gy twice daily to a total dose of 34 Gy. Both the patients and the treating radiation oncologist qualitatively rated cosmesis as excellent, good, fair, or poor over time and ascribed a cause for changes in cosmesis. Cosmetic outcome was evaluated quantitatively by percentage of breast retraction assessment (pBRA). Patients also reported their satisfaction with treatment over time. Results: Median follow-up was 55 months. The rates of excellent-to-good cosmesis reported by patients and the treating radiation oncologist were 92% and 97% pretreatment, 91% and 97% at 3 to 4 months' follow-up, 87% and 94% at 2 years, and 92% and 94% at 3 years, respectively. Breast infection and adjuvant chemotherapy were independent predictors of a fair-to-poor cosmetic outcome at 3 years. Compared to pretreatment pBRA (7.35), there was no significant change in pBRA over time. The volume receiving more than 150 Gy (V150) was the only significant predictor of pBRA. The majority of patients (86.6%) were completely satisfied with their treatment. Conclusions: Patients and the treating physician reported a high rate of excellent-to-good cosmetic outcomes at all follow-up time points. Acute breast infection and chemotherapy were associated with worse cosmetic outcomes. Multicatheter interstitial brachytherapy does not significantly change breast size as measured by pBRA

  20. Cosmetic Analysis Following Breast-Conserving Surgery and Adjuvant High-Dose-Rate Interstitial Brachytherapy for Early-Stage Breast Cancer: A Prospective Clinical Study

    Energy Technology Data Exchange (ETDEWEB)

    Garsa, Adam A.; Ferraro, Daniel J.; DeWees, Todd [Department of Radiation Oncology, Siteman Cancer Center, Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, Missouri (United States); Margenthaler, Julie A. [Department of Surgery, Siteman Cancer Center, Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, Missouri (United States); Naughton, Michael [Department of Medicine, Siteman Cancer Center, Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, Missouri (United States); Aft, Rebecca [Department of Surgery, Siteman Cancer Center, Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, Missouri (United States); Department of Surgery, John Cochran Veterans Hospital, St. Louis, Missouri (United States); Gillanders, William E.; Eberlein, Timothy [Department of Surgery, Siteman Cancer Center, Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, Missouri (United States); Matesa, Melissa A. [Department of Radiation Oncology, Siteman Cancer Center, Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, Missouri (United States); Zoberi, Imran, E-mail: izoberi@radonc.wustl.edu [Department of Radiation Oncology, Siteman Cancer Center, Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, Missouri (United States)

    2013-03-15

    Purpose: To prospectively evaluate cosmetic outcomes in women treated with accelerated partial breast irradiation using high-dose-rate interstitial brachytherapy for early-stage breast cancer. Methods and Materials: Between 2004 and 2008, 151 patients with early-stage breast cancer were enrolled in a phase 2 prospective clinical trial. Eligible patients had stage Tis-T2 tumors of ≤3 cm that were excised with negative margins and with no nodal involvement. Patients received 3.4 Gy twice daily to a total dose of 34 Gy. Both the patients and the treating radiation oncologist qualitatively rated cosmesis as excellent, good, fair, or poor over time and ascribed a cause for changes in cosmesis. Cosmetic outcome was evaluated quantitatively by percentage of breast retraction assessment (pBRA). Patients also reported their satisfaction with treatment over time. Results: Median follow-up was 55 months. The rates of excellent-to-good cosmesis reported by patients and the treating radiation oncologist were 92% and 97% pretreatment, 91% and 97% at 3 to 4 months' follow-up, 87% and 94% at 2 years, and 92% and 94% at 3 years, respectively. Breast infection and adjuvant chemotherapy were independent predictors of a fair-to-poor cosmetic outcome at 3 years. Compared to pretreatment pBRA (7.35), there was no significant change in pBRA over time. The volume receiving more than 150 Gy (V150) was the only significant predictor of pBRA. The majority of patients (86.6%) were completely satisfied with their treatment. Conclusions: Patients and the treating physician reported a high rate of excellent-to-good cosmetic outcomes at all follow-up time points. Acute breast infection and chemotherapy were associated with worse cosmetic outcomes. Multicatheter interstitial brachytherapy does not significantly change breast size as measured by pBRA.

  1. Water Well Locations - Conservation Wells

    Data.gov (United States)

    NSGIC Education | GIS Inventory — The conservation well layer identifies the permitted surface location of oil and gas conservation wells that have not been plugged. These include active, regulatory...

  2. Impending conservation crisis for Southeast Asian amphibians.

    Science.gov (United States)

    Rowley, Jodi; Brown, Rafe; Bain, Raoul; Kusrini, Mirza; Inger, Robert; Stuart, Bryan; Wogan, Guin; Thy, Neang; Chan-Ard, Tanya; Trung, Cao Tien; Diesmos, Arvin; Iskandar, Djoko T; Lau, Michael; Ming, Leong Tzi; Makchai, Sunchai; Truong, Nguyen Quang; Phimmachak, Somphouthone

    2010-06-23

    With an understudied amphibian fauna, the highest deforestation rate on the planet and high harvesting pressures, Southeast Asian amphibians are facing a conservation crisis. Owing to the overriding threat of habitat loss, the most critical conservation action required is the identification and strict protection of habitat assessed as having high amphibian species diversity and/or representing distinctive regional amphibian faunas. Long-term population monitoring, enhanced survey efforts, collection of basic biological and ecological information, continued taxonomic research and evaluation of the impact of commercial trade for food, medicine and pets are also needed. Strong involvement of regional stakeholders, students and professionals is essential to accomplish these actions.

  3. The use of high-dose-rate brachytherapy alone after lumpectomy in patients with early-stage breast cancer treated with breast-conserving therapy

    International Nuclear Information System (INIS)

    Baglan, Kathy L.; Martinez, Alvaro A.; Frazier, Robert C.; Kini, Vijay R.; Kestin, Larry L.; Chen, Peter Y.; Edmundson, Greg; Mele, Elizabeth; Jaffray, David; Vicini, Frank A.

    2001-01-01

    Purpose: We present the preliminary results of our in-house protocol using outpatient high-dose-rate (HDR) brachytherapy as the sole radiation modality following lumpectomy in patients with early-stage breast cancer. Methods and Materials: Thirty-seven patients with 38 Stage I-II breast cancers received radiation to the lumpectomy cavity alone using an HDR interstitial implant with 192 Ir. A minimum dose of 32 Gy was delivered on an outpatient basis in 8 fractions of 4 Gy to the lumpectomy cavity plus a 1- to 2-cm margin over consecutive 4 days. Results: Median follow-up is 31 months. There has been one ipsilateral breast recurrence for a crude failure rate of 2.6% and no regional or distant failures. Wound healing was not impaired in patients undergoing an open-cavity implant. Three minor breast infections occurred, and all resolved with oral antibiotics. The cosmetic outcome was good to excellent in all patients. Conclusion: In selected patients with early-stage breast cancer, treatment of the lumpectomy cavity alone with outpatient HDR brachytherapy is both technically feasible and well tolerated. Early results are encouraging, however, longer follow-up is necessary before equivalence to standard whole-breast irradiation can be established and to determine the most optimal radiation therapy technique to be employed

  4. Six Highly Conserved Targets of RNAi Revealed in HIV-1-Infected Patients from Russia Are Also Present in Many HIV-1 Strains Worldwide.

    Science.gov (United States)

    Kretova, Olga V; Fedoseeva, Daria M; Gorbacheva, Maria A; Gashnikova, Natalya M; Gashnikova, Maria P; Melnikova, Nataliya V; Chechetkin, Vladimir R; Kravatsky, Yuri V; Tchurikov, Nickolai A

    2017-09-15

    RNAi has been suggested for use in gene therapy of HIV/AIDS, but the main problem is that HIV-1 is highly variable and could escape attack from the small interfering RNAs (siRNAs) due to even single nucleotide substitutions in the potential targets. To exhaustively check the variability in selected RNA targets of HIV-1, we used ultra-deep sequencing of six regions of HIV-1 from the plasma of two independent cohorts of patients from Russia. Six RNAi targets were found that are invariable in 82%-97% of viruses in both cohorts and are located inside the domains specifying reverse transcriptase (RT), integrase, vpu, gp120, and p17. The analysis of mutation frequencies and their characteristics inside the targets suggests a likely role for APOBEC3G (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3G, A3G) in G-to-A mutations and a predominant effect of RT biases in the detected variability of the virus. The lowest frequency of mutations was detected in the central part of all six targets. We also discovered that the identical RNAi targets are present in many HIV-1 strains from many countries and from all continents. The data are important for both the understanding of the patterns of HIV-1 mutability and properties of RT and for the development of gene therapy approaches using RNAi for the treatment of HIV/AIDS. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Cultivating creativity in conservation science.

    Science.gov (United States)

    Aslan, Clare E; Pinsky, Malin L; Ryan, Maureen E; Souther, Sara; Terrell, Kimberly A

    2014-04-01

    Conservation practitioners and scientists are often faced with seemingly intractable problems in which traditional approaches fail. While other sectors (e.g., business) frequently emphasize creative thinking to overcome complex challenges, creativity is rarely identified as an essential skill for conservationists. Yet more creative approaches are urgently needed in the effort to sustain Earth's biodiversity. We identified 4 strategies to develop skills in creative thinking and discuss underlying research and examples supporting each strategy. First, by breaking down barriers between disciplines and surrounding oneself with unfamiliar people, concepts, and perspectives, one can expand base knowledge and experiences and increase the potential for new combinations of ideas. Second, by meeting people where they are (both literally and figuratively), one exposes oneself to new environments and perspectives, which again broadens experiences and increases ability to communicate effectively with stakeholders. Third, by embracing risk responsibly, one is more likely to develop new, nontraditional solutions and be open to high-impact outcomes. Finally, by following a cycle of learning, struggle, and reflection, one can trigger neurophysiological changes that allow the brain to become more creative. Creativity is a learned trait, rather than an innate skill. It can be actively developed at both the individual and institutional levels, and learning to navigate the relevant social and practical barriers is key to the process. To maximize the success of conservation in the face of escalating challenges, one must take advantage of what has been learned from other disciplines and foster creativity as both a professional skill and an essential component of career training and individual development. © 2013 Society for Conservation Biology.

  6. A Prospective Longitudinal Clinical Trial Evaluating Quality of Life After Breast-Conserving Surgery and High-Dose-Rate Interstitial Brachytherapy for Early-Stage Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Garsa, Adam A.; Ferraro, Daniel J.; DeWees, Todd A. [Department of Radiation Oncology, Siteman Cancer Center, Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, Missouri (United States); Deshields, Teresa L. [Department of Medicine, Siteman Cancer Center, Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, Missouri (United States); Margenthaler, Julie A.; Cyr, Amy E. [Department of Surgery, Siteman Cancer Center, Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, Missouri (United States); Naughton, Michael [Department of Medicine, Siteman Cancer Center, Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, Missouri (United States); Aft, Rebecca [Department of Surgery, Siteman Cancer Center, Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, Missouri (United States); Department of Surgery, John Cochran Veterans Hospital, St. Louis, Missouri (United States); Gillanders, William E.; Eberlein, Timothy [Department of Surgery, Siteman Cancer Center, Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, Missouri (United States); Matesa, Melissa A.; Ochoa, Laura L. [Department of Radiation Oncology, Siteman Cancer Center, Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, Missouri (United States); Zoberi, Imran, E-mail: izoberi@radonc.wustl.edu [Department of Radiation Oncology, Siteman Cancer Center, Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, Missouri (United States)

    2013-12-01

    Purpose: To prospectively examine quality of life (QOL) of patients with early stage breast cancer treated with accelerated partial breast irradiation (APBI) using high-dose-rate (HDR) interstitial brachytherapy. Methods and Materials: Between March 2004 and December 2008, 151 patients with early stage breast cancer were enrolled in a phase 2 prospective clinical trial. Eligible patients included those with Tis-T2 tumors measuring ≤3 cm excised with negative surgical margins and with no nodal involvement. Patients received 3.4 Gy twice daily to a total dose of 34 Gy. QOL was measured using European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, version 3.0, and QLQ-BR23 questionnaires. The QLQ-C30 and QLQ-BR23 questionnaires were evaluated during pretreatment and then at 6 to 8 weeks, 3 to 4 months, 6 to 8 months, and 1 and 2 years after treatment. Results: The median follow-up was 55 months. Breast symptom scores remained stable in the months after treatment, and they significantly improved 6 to 8 months after treatment. Scores for emotional functioning, social functioning, and future perspective showed significant improvement 2 years after treatment. Symptomatic fat necrosis was associated with several changes in QOL, including increased pain, breast symptoms, systemic treatment side effects, dyspnea, and fatigue, as well as decreased role functioning, emotional functioning, and social functioning. Conclusions: HDR multicatheter interstitial brachytherapy was well tolerated, with no significant detrimental effect on measured QOL scales/items through 2 years of follow-up. Compared to pretreatment scores, there was improvement in breast symptoms, emotional functioning, social functioning, and future perspective 2 years after treatment.

  7. A Prospective Longitudinal Clinical Trial Evaluating Quality of Life After Breast-Conserving Surgery and High-Dose-Rate Interstitial Brachytherapy for Early-Stage Breast Cancer

    International Nuclear Information System (INIS)

    Garsa, Adam A.; Ferraro, Daniel J.; DeWees, Todd A.; Deshields, Teresa L.; Margenthaler, Julie A.; Cyr, Amy E.; Naughton, Michael; Aft, Rebecca; Gillanders, William E.; Eberlein, Timothy; Matesa, Melissa A.; Ochoa, Laura L.; Zoberi, Imran

    2013-01-01

    Purpose: To prospectively examine quality of life (QOL) of patients with early stage breast cancer treated with accelerated partial breast irradiation (APBI) using high-dose-rate (HDR) interstitial brachytherapy. Methods and Materials: Between March 2004 and December 2008, 151 patients with early stage breast cancer were enrolled in a phase 2 prospective clinical trial. Eligible patients included those with Tis-T2 tumors measuring ≤3 cm excised with negative surgical margins and with no nodal involvement. Patients received 3.4 Gy twice daily to a total dose of 34 Gy. QOL was measured using European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, version 3.0, and QLQ-BR23 questionnaires. The QLQ-C30 and QLQ-BR23 questionnaires were evaluated during pretreatment and then at 6 to 8 weeks, 3 to 4 months, 6 to 8 months, and 1 and 2 years after treatment. Results: The median follow-up was 55 months. Breast symptom scores remained stable in the months after treatment, and they significantly improved 6 to 8 months after treatment. Scores for emotional functioning, social functioning, and future perspective showed significant improvement 2 years after treatment. Symptomatic fat necrosis was associated with several changes in QOL, including increased pain, breast symptoms, systemic treatment side effects, dyspnea, and fatigue, as well as decreased role functioning, emotional functioning, and social functioning. Conclusions: HDR multicatheter interstitial brachytherapy was well tolerated, with no significant detrimental effect on measured QOL scales/items through 2 years of follow-up. Compared to pretreatment scores, there was improvement in breast symptoms, emotional functioning, social functioning, and future perspective 2 years after treatment

  8. Control of HIV replication in astrocytes by a family of highly conserved host proteins with a common Rev-interacting domain (Risp).

    Science.gov (United States)

    Vincendeau, Michelle; Kramer, Susanne; Hadian, Kamyar; Rothenaigner, Ina; Bell, Jeanne; Hauck, Stefanie M; Bickel, Christian; Nagel, Daniel; Kremmer, Elisabeth; Werner, Thomas; Leib-Mösch, Christine; Brack-Werner, Ruth

    2010-10-23

    In human astrocytes, restriction of HIV replication involves inhibition of HIV Rev activity. We previously identified a Rev-interacting human protein fragment (16.4.1) that can reduce Rev activity. The 16.4.1 sequence is contained in a group of highly similar host cell proteins, which we call the Risp family. Here we investigate whether the Risp family is connected to HIV replication in astrocytes. Cell/tissue lysates were analyzed for Risp expression by western blot with various anti-Risp antibodies. The interaction of astrocytic Risp members with Rev was investigated by affinity chromatography. Astrocytes were transfected with expression plasmids containing cDNAs encoding full-length Risp or the isolated 16.4.1 region for Risp overexpression or with siRNAs designed for Risp knock-down. Rev activity was investigated with a Rev-reporter assay. RNA levels were quantified by real-time RT-PCR, HIV Gag levels by p24ELISA. Expression of the Risp family was demonstrated in human brain tissues and astrocytes. Astrocytes were shown to produce Risp family members that interact with Rev. Production of HIV Gag proteins and Rev-dependent RNAs in persistently infected astrocytes increased upon Risp knock-down and decreased upon Risp overexpression. Risp knock-down increased Rev activity and raised proportions of Rev proteins in the nucleus of astrocytes. Our results link the Risp family to restriction of HIV production and inhibition of Rev activity in astrocytes. We conclude that the Risp family represents a novel family of host factors that can control HIV replication and may be important for the containment of HIV infection in brain reservoirs.

  9. A new highly conserved antibiotic sensing/resistance pathway in firmicutes involves an ABC transporter interplaying with a signal transduction system.

    Directory of Open Access Journals (Sweden)

    Stéphanie Coumes-Florens

    2011-01-01

    Full Text Available Signal transduction systems and ABC transporters often contribute jointly to adaptive bacterial responses to environmental changes. In Bacillus subtilis, three such pairs are involved in responses to antibiotics: BceRSAB, YvcPQRS and YxdJKLM. They are characterized by a histidine kinase belonging to the intramembrane sensing kinase family and by a translocator possessing an unusually large extracytoplasmic loop. It was established here using a phylogenomic approach that systems of this kind are specific but widespread in Firmicutes, where they originated. The present phylogenetic analyses brought to light a highly dynamic evolutionary history involving numerous horizontal gene transfers, duplications and lost events, leading to a great variety of Bce-like repertories in members of this bacterial phylum. Based on these phylogenetic analyses, it was proposed to subdivide the Bce-like modules into six well-defined subfamilies. Functional studies were performed on members of subfamily IV comprising BceRSAB from B. subtilis, the expression of which was found to require the signal transduction system as well as the ABC transporter itself. The present results suggest, for the members of this subfamily, the occurrence of interactions between one component of each partner, the kinase and the corresponding translocator. At functional and/or structural levels, bacitracin dependent expression of bceAB and bacitracin resistance processes require the presence of the BceB translocator loop. Some other members of subfamily IV were also found to participate in bacitracin resistance processes. Taken together our study suggests that this regulatory mechanism might constitute an important common antibiotic resistance mechanism in Firmicutes. [Supplemental material is available online at http://www.genome.org.].

  10. A unique, highly conserved secretory invertase is differentially expressed by promastigote developmental forms of all species of the human pathogen, Leishmania

    Science.gov (United States)

    Lyda, Todd A.; Joshi, Manju B.; Andersen, John F.; Kelada, Andrew Y.; Owings, Joshua P.; Bates, Paul A.; Dwyer, Dennis M.

    2015-01-01

    Leishmania are protozoan pathogens of humans that exist as extracellular promastigotes in the gut of their sand fly vectors and as obligate intracellular amastigotes within phagolysosomes of infected macrophages. Between infectious blood meal feeds, sand flies take plant juice meals that contain sucrose and store these sugars in their crop. Such sugars are regurgitated into the sand fly anterior midgut where they impact the developing promastigote parasite population. In this report we showed that promastigotes of all Leishmania species secreted an invertase/sucrase enzyme during their growth in vitro. In contrast, neither L. donovani nor L. mexicana amastigotes possessed any detectable invertase activity. Importantly, no released/secreted invertase activity was detected in culture supernatants from either Trypanosoma brucei or Trypanosoma cruzi. Using HPLC, the L. donovani secretory invertase was isolated and subjected to amino acid sequencing. Subsequently, we used a molecular approach to identify the LdINV and LmexINV genes encoding the ~72 kDa invertases produced by these organisms. Interestingly, we identified high fidelity LdINV-like homologs in the genomes of all Leishmania sp. but none were present in either T. brucei or T. cruzi. Northern blot and RT-PCR analyses showed that these genes were developmentally/differentially expressed in promastigotes but not amastigotes of these parasites. Homologous transfection studies demonstrated that these genes in fact encoded the functional secretory invertases produced by these parasites. Cumulatively, our results suggest that these secretory enzymes play critical roles in the survival/growth/development and transmission of all Leishmania parasites within their sand fly vector hosts. PMID:25763714

  11. Phylogenetic analysis of the diacylglycerol kinase family of proteins and identification of multiple highly-specific conserved inserts and deletions within the catalytic domain that are distinctive characteristics of different classes of DGK homologs.

    Directory of Open Access Journals (Sweden)

    Radhey S Gupta

    Full Text Available Diacylglycerol kinase (DGK family of proteins, which phosphorylates diacylglycerol into phosphatidic acid, play important role in controlling diverse cellular processes in eukaryotic organisms. Most vertebrate species contain 10 different DGK isozymes, which are grouped into 5 different classes based on the presence or absence of specific functional domains. However, the relationships among different DGK isozymes or how they have evolved from a common ancestor is unclear. The catalytic domain constitutes the single largest sequence element within the DGK proteins that is commonly and uniquely shared by all family members, but there is limited understanding of the overall function of this domain. In this work, we have used the catalytic domain sequences to construct a phylogenetic tree for the DGK family members from representatives of the main vertebrate classes and have also examined the distributions of various DGK isozymes in eukaryotic phyla. In a tree based on catalytic domain sequences, the DGK homologs belonging to different classes formed strongly supported clusters which were separated by long branches, and the different isozymes within each class also generally formed monophyletic groupings. Further, our analysis of the sequence alignments of catalytic domains has identified >10 novel sequence signatures consisting of conserved signature indels (inserts or deletions, CSIs that are distinctive characteristics of either particular classes of DGK isozymes, or are commonly shared by members of two or more classes of DGK isozymes. The conserved indels in protein sequences are known to play important functional roles in the proteins/organisms where they are found. Thus, our identification of multiple highly specific CSIs that are distinguishing characteristics of different classes of DGK homologs points to the existence of important differences in the catalytic domain function among the DGK isozymes. The identified CSIs in conjunction with

  12. Conservation Education: A Position Statement.

    Science.gov (United States)

    Soil Conservation Society of America, Ankeny, IA.

    The Soil Conservation Society of America's (SCSA) aim is to advance the science and art of good land and water use. Conservation education has a significant role in achieving the wise use of these resources. In this report, perspectives are offered on: (1) the requirements for effective conservation education programs; (2) rationale for…

  13. Madagascar Conservation & Development: Editorial Policies

    African Journals Online (AJOL)

    ... of the Madagascar Conservation & Development community. Finally, Madagascar Conservation & Development serves as a conduit for debate and discussion and welcomes contributions on any aspect of the legal or scientific status of any species living in Madagascar, or on conservation and development philosophy.

  14. Energy conservation in India: a profile

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    The decade and half since the oil crisis of 1973 has been a period that has witnessed a steady growth of the energy conservation ethos in India. Housekeeping and low risk conservation options have been largely preferred so far. The IMWG (Inter-Ministerial Working Group on Utilization and Conservation of Energy) study did not evaluate potential saving through the introduction of high risk and high pay-off technologies. The potential for energy conservation in India is substantial. However, some of the barriers to achieving the potential in the past have been energy prices which deviate from rational tariffs and prices, a lack of information on specific measures and of options for achieving energy conservation, paucity of capital for schemes requiring technology upgradation and efficiency improvements, and the inadequacy if institutional arrangement for promoting energy conservation in different sectors of the economy. Recent efforts pursued by several organizations however provide some basis for optimism. Given the growing capital intensity of the energy sector in India, more vigorous efforts are likely to be made in the future. In particular, success stories in some industrial units indicate that decentralized efforts by the units themselves can achieve a great deal in improving the efficiency of energy use, particularly in the Indian industry. Policies to promote such programmes would help accelerate energy conservation efforts in industrial units and in other sectors. It is therefore hoped that the intensity of energy use in several sectors of the indian economy will be reduced significantly in the coming years. (author). 3 refs., 3 tabs

  15. Immunization of rabbits with synthetic peptides derived from a highly conserved β-sheet epitope region underneath the receptor binding site of influenza A virus

    Directory of Open Access Journals (Sweden)

    Ideno S

    2013-11-01

    Full Text Available Shoji Ideno,1,3 Kaoru Sakai,1 Mikihiro Yunoki,2–4 Ritsuko Kubota-Koketsu,3,5 Yuji Inoue,3 Shota Nakamura,6 Teruo Yasunaga,6 Yoshinobu Okuno,5 Kazuyoshi Ikuta3 1Infectious Pathogen Research Section, Central Research Laboratory, Research and Development Division, Japan Blood Products Organization, Kobe, Japan; 2Research and Development Promotion Section, Research and Development Division, Japan Blood Products Organization, Tokyo, Japan; 3Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan; 4Department of Veterinary Microbiology, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido, Japan; 5Kanonji Institute, The Research Foundation for Microbial Diseases of Osaka University, Kanonji, Kagawa, Japan; 6Department of Genome Informatics, Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan Background: There is increasing concern about the speed with which health care providers can administer prophylaxis and treatment in an influenza pandemic. Generally, it takes several months to manufacture an influenza vaccine by propagation of the virus in chicken eggs or cultured cells. Newer, faster protocols for the production of vaccines that induce broad-spectrum immunity are therefore highly desirable. We previously developed human monoclonal antibody B-1 that shows broadly neutralizing activity against influenza A virus H3N2. B-1 recognizes an epitope region that includes an antiparallel β-sheet structure underneath the receptor binding site of influenza hemagglutinin (HA. In this study, the efficacy of a synthetic peptide vaccine derived from this epitope region against influenza A was evaluated. Materials and methods: Two peptides were synthesized, the upper and lower peptides. These peptides comprise amino acid residues 167–187 and 225–241, respectively, of the B-1 epitope region of HA, which is involved in

  16. Hearing Conservation Live #2430

    Energy Technology Data Exchange (ETDEWEB)

    Chochoms, Michael [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-08-09

    Occupational hearing loss is one of the most common work-related illnesses in the United States (US). From 22 to 30 million US workers are exposed to hazardous noise levels at work, and 25% of these workers will develop permanent hearing loss. Hearing loss from noise is slow and painless, and you can have a disability before you notice it. This course presents the hazards associated with workplace noise, the purpose and elements of the Los Alamos National Laboratory (LANL) Hearing Conservation Program (HCP), and controls that are available to reduce your exposure to hazardous levels of noise.

  17. Energy conservation technologies

    Energy Technology Data Exchange (ETDEWEB)

    Courtright, H.A. [Electric Power Research Inst., Palo Alto, CA (United States)

    1993-12-31

    The conservation of energy through the efficiency improvement of existing end-uses and the development of new technologies to replace less efficient systems is an important component of the overall effort to reduce greenhouse gases which may contribute to global climate change. Even though uncertainties exist on the degree and causes of global warming, efficiency improvements in end-use applications remain in the best interest of utilities, their customers and society because efficiency improvements not only reduce environmental exposures but also contribute to industrial productivity, business cost reductions and consumer savings in energy costs.

  18. Integrating Agriculture and Conservation

    Science.gov (United States)

    Vandever, Mark W.

    2010-01-01

    The USGS produces the needed science-based information to guide management actions and policy decisions that support wildlife habitat and other environmental services compatible with USDA conservation goals and farm operations. The Policy Analysis and Science Assistance Branch of the Fort Collins Science Center (FORT) has conducted research involving a national landowner survey and numerous short- and long-term evaluations regarding vegetation responses to land management practices. This research helps land and resource managers to make informed decisions and resolve resource management conflicts.

  19. Conservative Protestantism and attitudes toward corporal punishment, 1986-2014.

    Science.gov (United States)

    Hoffmann, John P; Ellison, Christopher G; Bartkowski, John P

    2017-03-01

    Research indicates that conservative Protestants are highly supportive of corporal punishment. Yet, Americans' support for this practice has waned during the past several decades. This study aggregates repeated cross-sectional data from the General Social Surveys (GSS) to consider three models that address whether attitudes toward spanking among conservative Protestants shifted relative to those of other Americans from 1986 to 2014. Although initial results reveal a growing gap between conservative Protestants and the broader American public, we find that average levels of support have remained most robust among less educated conservative Protestants, with some erosion among more highly educated conservative Protestants. Moreover, trends in variability suggest that conservative Protestants exhibit more cohesive support for this practice than do others. These results provide a window into the cultural contours of religious change and the social factors that facilitate such change. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Selling energy conservation.

    Science.gov (United States)

    Hinrichsen, D

    1995-01-01

    This article concerns the Organization of the Petroleum Exporting Countries (OPEC) crisis and its impact on energy efficiency measures in the US. In 1985, when the OPEC collapsed, the US government had avoided the need to construct 350 gigawatts of new electric capacity. The most successful efficiency improvements, especially in household appliances and equipment, lighting and tightened energy efficiency standards in new buildings, resulted from the OPEC event. The real innovation of that time was the change in profit rules for utilities. This revolution and the way some US utilities view energy have not caught on elsewhere. Despite the initiative toward improving energy efficiency in homes, offices and industries, the change has been slow. Partly to blame are the big development banks, which pointed out that short-term conservation and efficiency measures could save at least 15% of the total energy demand without the need for major investment. The benefits of energy conservation was shown during the oil shock when per capita energy consumption fell by 5% in the member states of the Organization of Economic Cooperation and Development, while the per capita gross domestic product grew by a third. There has been a decrease in energy expenditure worldwide, and the scope for further energy savings is enormous, but governments need to recognize and seize the opportunity.

  1. Lyme disease and conservation

    Science.gov (United States)

    Ginsberg, H.

    1994-01-01

    Lyme disease is a tick-borne illness that is wide-spread in North America, especially in the northeastern and northcentral United States. This disease could negatively influence efforts to conserve natural populations in two ways: (1) the disease could directly affect wild animal health; and (2) tick control efforts could adversely affect natural populations and communities. Lyme disease affects several domestic animals, but symptoms have been reported in only a few wild species. Direct effects of Lyme disease on wild animal populations have not been reported, but the disease should be considered as a possible cause in cases of unexplained population declines in endemic areas. Methods available to manage ticks and Lyme disease include human self-protection techniques, manipulation of habitats and hosts species populations, biological control, and pesticide applications. The diversity of available techniques allows selection of approaches to minimize environmental effects by (1) emphasizing personal protection techniques, (2) carefully targeting management efforts to maximize efficiency, and (3) integrating environmentally benign techniques to improve management while avoiding broad-scale environmentally destructive approaches. The environmental effects of Lyme disease depend, to a large extent, on the methods chosen to minimize human exposure to infected ticks. Conservation biologists can help design tick management programs that effectively lower the incidence of human Lyme disease while simultaneously minimizing negative effects on natural populations.

  2. Intensity Conserving Spectral Fitting

    Science.gov (United States)

    Klimchuk, J. A.; Patsourakos, S.; Tripathi, D.

    2015-01-01

    The detailed shapes of spectral line profiles provide valuable information about the emitting plasma, especially when the plasma contains an unresolved mixture of velocities, temperatures, and densities. As a result of finite spectral resolution, the intensity measured by a spectrometer is the average intensity across a wavelength bin of non-zero size. It is assigned to the wavelength position at the center of the bin. However, the actual intensity at that discrete position will be different if the profile is curved, as it invariably is. Standard fitting routines (spline, Gaussian, etc.) do not account for this difference, and this can result in significant errors when making sensitive measurements. Detection of asymmetries in solar coronal emission lines is one example. Removal of line blends is another. We have developed an iterative procedure that corrects for this effect. It can be used with any fitting function, but we employ a cubic spline in a new analysis routine called Intensity Conserving Spline Interpolation (ICSI). As the name implies, it conserves the observed intensity within each wavelength bin, which ordinary fits do not. Given the rapid convergence, speed of computation, and ease of use, we suggest that ICSI be made a standard component of the processing pipeline for spectroscopic data.

  3. Increasing participation in incentive programs for biodiversity conservation.

    Science.gov (United States)

    Sorice, Michael G; Oh, Chi-Ok; Gartner, Todd; Snieckus, Mary; Johnson, Rhett; Donlan, C Josh

    2013-07-01

    Engaging private landowners in conservation activities for imperiled species is critical to maintaining and enhancing biodiversity. Market-based approaches can incentivize conservation behaviors on private lands by shifting the benefit-cost ratio of engaging in activities that result in net conservation benefits for target species. In the United States and elsewhere, voluntary conservation agreements with financial incentives are becoming an increasingly common strategy. While the influence of program design and delivery of voluntary conservation programs is often overlooked, these aspects are critical to achieving the necessary participation to attain landscape-scale outcomes. Using a sample of family-forest landowners in the southeast United States, we show how preferences for participation in a conservation program to protect an at-risk species, the gopher tortoise (Gopherus polyphemus), are related to program structure, delivery, and perceived efficacy. Landowners were most sensitive to programs that are highly controlling, require permanent conservation easements, and put landowners at risk for future regulation. Programs designed with greater levels of compensation and that support landowners' autonomy to make land management decisions can increase participation and increase landowner acceptance of program components that are generally unfavorable, like long-term contracts and permanent easements. There is an inherent trade-off between maximizing participation and maximizing the conservation benefits when designing a conservation incentive program. For conservation programs targeting private lands to achieve landscape-level benefits, they must attract a critical level of participation that creates a connected mosaic of conservation benefits. Yet, programs with attributes that strive to maximize conservation benefits within a single agreement (and reduce risks of failure) are likely to have lower participation, and thus lower landscape benefits. Achieving

  4. Algal MIPs, high diversity and conserved motifs.

    Science.gov (United States)

    Anderberg, Hanna I; Danielson, Jonas Å H; Johanson, Urban

    2011-04-21

    Major intrinsic proteins (MIPs) also named aquaporins form channels facilitating the passive transport of water and other small polar molecules across membranes. MIPs are particularly abundant and diverse in terrestrial plants but little is known about their evolutionary history. In an attempt to investigate the origin of the plant MIP subfamilies, genomes of chlorophyte algae, the sister group of charophyte algae and land plants, were searched for MIP encoding genes. A total of 22 MIPs were identified in the nine analysed genomes and phylogenetic analyses classified them into seven subfamilies. Two of these, Plasma membrane Intrinsic Proteins (PIPs) and GlpF-like Intrinsic Proteins (GIPs), are also present in land plants and divergence dating support a common origin of these algal and land plant MIPs, predating the evolution of terrestrial plants. The subfamilies unique to algae were named MIPA to MIPE to facilitate the use of a common nomenclature for plant MIPs reflecting phylogenetically stable groups. All of the investigated genomes contained at least one MIP gene but only a few species encoded MIPs belonging to more than one subfamily. Our results suggest that at least two of the seven subfamilies found in land plants were present already in an algal ancestor. The total variation of MIPs and the number of different subfamilies in chlorophyte algae is likely to be even higher than that found in land plants. Our analyses indicate that genetic exchanges between several of the algal subfamilies have occurred. The PIP1 and PIP2 groups and the Ca2+ gating appear to be specific to land plants whereas the pH gating is a more ancient characteristic shared by all PIPs. Further studies are needed to discern the function of the algal specific subfamilies MIPA-E and to fully understand the evolutionary relationship of algal and terrestrial plant MIPs.

  5. Algal MIPs, high diversity and conserved motifs

    Directory of Open Access Journals (Sweden)

    Johanson Urban

    2011-04-01

    Full Text Available Abstract Background Major intrinsic proteins (MIPs also named aquaporins form channels facilitating the passive transport of water and other small polar molecules across membranes. MIPs are particularly abundant and diverse in terrestrial plants but little is known about their evolutionary history. In an attempt to investigate the origin of the plant MIP subfamilies, genomes of chlorophyte algae, the sister group of charophyte algae and land plants, were searched for MIP encoding genes. Results A total of 22 MIPs were identified in the nine analysed genomes and phylogenetic analyses classified them into seven subfamilies. Two of these, Plasma membrane Intrinsic Proteins (PIPs and GlpF-like Intrinsic Proteins (GIPs, are also present in land plants and divergence dating support a common origin of these algal and land plant MIPs, predating the evolution of terrestrial plants. The subfamilies unique to algae were named MIPA to MIPE to facilitate the use of a common nomenclature for plant MIPs reflecting phylogenetically stable groups. All of the investigated genomes contained at least one MIP gene but only a few species encoded MIPs belonging to more than one subfamily. Conclusions Our results suggest that at least two of the seven subfamilies found in land plants were present already in an algal ancestor. The total variation of MIPs and the number of different subfamilies in chlorophyte algae is likely to be even higher than that found in land plants. Our analyses indicate that genetic exchanges between several of the algal subfamilies have occurred. The PIP1 and PIP2 groups and the Ca2+ gating appear to be specific to land plants whereas the pH gating is a more ancient characteristic shared by all PIPs. Further studies are needed to discern the function of the algal specific subfamilies MIPA-E and to fully understand the evolutionary relationship of algal and terrestrial plant MIPs.

  6. 7 CFR 1466.10 - Conservation practices.

    Science.gov (United States)

    2010-01-01

    ... prior to application for assistance. (d) Where new technologies or management approaches that provide a high potential for optimizing environmental benefits have been developed, NRCS may approve interim conservation practice standards that incorporate the new technologies and provide financial assistance for...

  7. Indian energy conservation- status and strategies

    International Nuclear Information System (INIS)

    Dharmalingam, P.

    1996-01-01

    High rates of inflation combined with social justice against a backdrop of ever increasing population- this is a challenge which the Government of India is facing today. It is evident that the annual growth rate of 5.6% as envisaged for the VIIIth five year plan can never be met unless conscious efforts are made to augment energy supplies by energy demand management through energy conservation. In this context, a review of the energy consuming sectors in terms of their consumption trends, energy efficiencies or intensities, energy conservation opportunities, technologies used and energy investment programmes would prove useful and informative. (author). 10 tabs

  8. Identifying ambassador species for conservation marketing

    Directory of Open Access Journals (Sweden)

    E.A. Macdonald

    2017-10-01

    Full Text Available Conservation relies heavily on external funding, much of it from a supportive public. Therefore it is important to know which species are most likely to catalyse such funding. Whilst previous work has looked at the physical attributes that contribute to a species' appeal, no previous studies have tried to examine the extent to which a species' sympatriots might contribute to it's potential as flagship for wider conservation. Therefore, here we estimate ‘flexibility’ and ‘appeal’ scores for all terrestrial mammals (n = 4320 and identify which of these might serve as ambassadors (defined as both highly appealing and flexible. Relatively few mammals (between 240 and 331 emerged as ambassadors, with carnivores featuring heavily in this group (representing 5% of terrestrial mammals but 39% of ambassadors. ‘Top ambassadors’ were defined as those with both flexibility and appeal scores greater than 1 standard deviation above the mean. Less than a quarter of the 20 most endangered and evolutionary distinct species in this study were classed as ambassadors, highlighting the need for surrogate species to catalyse conservation effort in areas with such priority species. This is the first global analysis bringing together flexibility and appeal for all terrestrial mammals, and demonstrates an approach for determining how best to market species in order to achieve maximal conservation gain in a world with urgent conservation need but limited resources.

  9. International energy conservation: comparative law and policy

    Energy Technology Data Exchange (ETDEWEB)

    1979-02-01

    Ernest C. Baynard III, in the Foreword to the conference, told of the purpose of the conference - to compare and discuss the policies and laws that highly industrialized nations have used and considered to meet the challenge of energy conservation. The following countries participated in the conference: U.K.; Australia; Federal Republic of Germany; Japan; France; Canada; Sweden; Italy; the Netherlands; and the U.S. The IEA and the Commission of the European Communities also participated. The conference format consisted of ministerial addresses to the conference, interspersed with panel discussions focusing on energy conservation in transportation, industry, agriculture, and utilities; residential, commercial, and industrial buildings; and emergency situations. There was also a panel discussion on the role of government in energy conservation and energy information collection. The panels were composed of participating countries' representatives. (MCW)

  10. Conservation and ethnobotanical exploration.

    Science.gov (United States)

    Martin, G J

    1994-01-01

    In recent years conservationists have realized that the maintenance of protected areas is closely linked to rural development. As part of their efforts to improve local people's standards of living, they have sought the advice of researchers who work in communities, especially those that border on nature reserves. Ethnobotanists, who are turning their attention to the cultural and ecological crises confronting the regions in which they work, are natural allies in this venture. The joint efforts of conservationists and ethnobotanists are being supported by non-profit organizations, intergovernmental agencies and research institutes. The search for new drugs and other natural products from plants is an important element in this collaboration, but it cannot be divorced from the broader objective of promoting the survival of biological and cultural diversity. Conservationists will support biodiversity prospecting and related efforts only if there is a clear benefit for local communities and protected areas. An example of the concrete actions being taken by conservation agencies is the People and Plants Initiative, a joint effort of the World Wide Fund for Nature, the United Nations Educational, Scientific and Cultural Organization and the Royal Botanic Gardens, Kew. The main objective is to support the work of ethnobotanists in developing countries in studies of sustainable plant use and application of their work to conservation and community development. The initiative provides training workshops and relevant literature; coordinators work in collaboration with local people to create inventories of useful plants and appraise the impact of harvesting specific plant resources in and around protected areas. Phytochemical screening of medicinal plants and preparation of extracts are carried out as part of some projects.

  11. Why not energy conservation?

    International Nuclear Information System (INIS)

    Carlson, Shawn

    2016-01-01

    Energy conservation is a deep principle that is obeyed by all of the fundamental forces of nature. It puts stringent constraints on all systems, particularly systems that are ‘isolated,’ meaning that no energy can enter or escape. Notwithstanding the success of the principle of stationary action, it is fair to wonder to what extent physics can be formulated from the principle of stationary energy. We show that if one interprets mechanical energy as a state function, then its stationarity leads to a novel formulation of classical mechanics. However, unlike Lagrangian and Hamiltonian mechanics, which deliver their state functions via algebraic proscriptions (i.e., the Lagrangian is always the difference between a system’s kinetic and potential energies), this new formalism identifies its state functions as the solutions to a differential equation. This is an important difference because differential equations can generate more general solutions than algebraic recipes. When applied to Newtonian systems for which the energy function is separable, these state functions are always the mechanical energy. However, while the stationary state function for a charged particle moving in an electromagnetic field proves not to be energy, the function nevertheless correctly encodes the dynamics of the system. Moreover, the stationary state function for a free relativistic particle proves not to be the energy either. Rather, our differential equation yields the relativistic free-particle Lagrangian (plus a non-dynamical constant) in its correct dynamical context. To explain how this new formalism can consistently deliver stationary state functions that give the correct dynamics but that are not always the mechanical energy, we propose that energy conservation is a specific realization of a deeper principle of stationarity that governs both relativistic and non-relativistic mechanics. (paper)

  12. A Kinematic Conservation Law in Free Surface Flow

    OpenAIRE

    Gavrilyuk , Sergey; Kalisch , Henrik; Khorsand , Zahra

    2015-01-01

    The Green-Naghdi system is used to model highly nonlinear weakly dispersive waves propagating at the surface of a shallow layer of a perfect fluid. The system has three associated conservation laws which describe the conservation of mass, momentum, and energy due to the surface wave motion. In addition, the system features a fourth conservation law which is the main focus of this note. It will be shown how this fourth conservation law can be interpreted in terms of a concrete kinematic quanti...

  13. Effects of preference heterogeneity among landowners on spatial conservation prioritization

    DEFF Research Database (Denmark)

    Nielsen, Anne Sofie Elberg; Strange, Niels; Bruun, Hans Henrik

    2017-01-01

    The participation of private landowners in conservation is crucial to efficient biodiversity conservation. This is especially the case in settings where the share of private ownership is large and the economic costs associated with land acquisition are high. We used probit regression analysis...... into a spatial prioritization for conservation of unmanaged forests. The choice models are based on sociodemographic data on the entire population of Danish forest owners and historical data on their participation in conservation schemes. Inclusion in the model of information on private landowners' willingness...... to supply land for conservation yielded at intermediate budget levels up to 30% more expected species coverage than the uninformed prioritization scheme. Our landowner-choice model provides an example of moving toward more implementable conservation planning....

  14. High antiviral effect of TiO2·PL–DNA nanocomposites targeted to conservative regions of (−RNA and (+RNA of influenza A virus in cell culture

    Directory of Open Access Journals (Sweden)

    Asya S. Levina

    2016-08-01

    Full Text Available Background: The development of new antiviral drugs based on nucleic acids is under scrutiny. An important problem in this aspect is to find the most vulnerable conservative regions in the viral genome as targets for the action of these agents. Another challenge is the development of an efficient system for their delivery into cells. To solve this problem, we proposed a TiO2·PL–DNA nanocomposite consisting of titanium dioxide nanoparticles and polylysine (PL-containing oligonucleotides.Results: The TiO2·PL–DNA nanocomposites bearing the DNA fragments targeted to different conservative regions of (−RNA and (+RNA of segment 5 of influenza A virus (IAV were studied for their antiviral activity in MDCK cells infected with the H1N1, H5N1, and H3N2 virus subtypes. Within the negative strand of each of the studied strains, the efficiency of DNA fragments increased in the direction of its 3’-end. Thus, the DNA fragment aimed at the 3’-noncoding region of (−RNA was the most efficient and inhibited the reproduction of different IAV subtypes by 3–4 orders of magnitude. Although to a lesser extent, the DNA fragments targeted at the AUG region of (+RNA and the corresponding region of (−RNA were also active. For all studied viral subtypes, the nanocomposites bearing the DNA fragments targeted to (−RNA appeared to be more efficient than those containing fragments aimed at the corresponding (+RNA regions.Conclusion: The proposed TiO2·PL–DNA nanocomposites can be successfully used for highly efficient and site-specific inhibition of influenza A virus of different subtypes. Some patterns of localization of the most vulnerable regions in IAV segment 5 for the action of DNA-based drugs were found. The (−RNA strand of IAV segment 5 appeared to be more sensitive as compared to (+RNA.

  15. Conserving Earth's Biodiversity. [CD-ROM and] Instructor's Manual.

    Science.gov (United States)

    2000

    This CD-ROM is designed as an interactive learning tool to support teaching in highly interdisciplinary fields such as conservation of biodiversity. Topics introduced in the software include the impact of humans on natural landscapes, threats to biodiversity, methods and theories of conservation biology, environmental laws, and relevant economic…

  16. Electric energy utilization and conservation

    International Nuclear Information System (INIS)

    Tripathy, S.C.

    1991-01-01

    Various aspects of electric energy utilization and conservation are discussed. First chapter reviews thermodynamic aspects of energy conservation. Subsequent chapters describe possibilities and methods of energy conservation in thermal power plants, airconditioning and ventilation systems, electric lighting systems, electric heating systems in industries, and railway electrification. Chapter 8 describes various modes of energy storage and compares their economies. The next chapter discusses various facets of energy economics and the last chapter discusses the practical aspects of energy conservation in different industries and power utilities. (M.G.B.). 100 refs

  17. Prairie Conservation in Canada: The Prairie Conservation Action Plan Experience

    Science.gov (United States)

    Dean Nernberg; David Ingstrup

    2005-01-01

    In Canada, grassland conservation has been mobilized and directed through the development of Prairie Conservation Action Plans and Action Plan Committees in the three prairie provinces of Alberta (45 partner agencies and organizations), Saskatchewan (26 partners), and Manitoba (26 partners). In Alberta, 43 percent of the native prairie remains; in Saskatchewan and...

  18. Community markets for conservation: Markets to advance conservation mission

    OpenAIRE

    Fay, J.

    2008-01-01

    This presentation describes the function and economics of COMACO (Community Markets for Conservation), discusses the current reality of climate change, and then explores how possible market mechanism approaches to ameliorating climate change may fit into COMACO's work and research. LTRA-2 (An Agricultural Markets Model for Biodiversity Conservation)

  19. Identification of a highly conserved domain in the EcoRII methyltransferase which can be photolabeled with S-adenosyl-L-[methyl-3H]methionine. Evidence for UV-induced transmethylation of cysteine 186

    International Nuclear Information System (INIS)

    Som, S.; Friedman, S.

    1991-01-01

    DNA methyltransferases can be photolabeled with S-adenosyl-L-methionine (AdoMet). Specific incorporation of radioactivity has been demonstrated after photolabeling with either [methyl-3H]AdoMet or [35S]AdoMet. The labeling is believed to occur at the AdoMet binding site. With the purpose of localizing the site responsible for [methyl-3H]AdoMet photolabeling, we cleaved the labeled EcoRII methyltransferase by chemical and enzymatic reactions and isolated the radiolabeled peptides by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and high pressure liquid chromatography. The labeled peptides were identified by amino-terminal sequencing. A common region was localized which accounted for 65-70% of the total label. This region includes a highly conserved core sequence present in all DNA (cytosine 5)-methyltransferases. One such fragment was digested further with chymotrypsin, and amino acid analysis of the resulting 3H-labeled peptide was consistent with the sequence Ala-Gly-Phe-Pro-(Cys)-Gln-Pro-Phe-Ser-Leu. However, the cysteine residue was not recovered as carboxymethylcysteine. The Pro-Cys bond was found to be protected from cleavage at cysteine residues after cyanylation. These results suggest that the cysteine residue is modified by the labeling reaction. The chymotryptic fragment was hydrolyzed enzymatically to single amino acids, and the labeled amino acid was identified as S-methylcysteine by thin layer chromatography. These results indicate that the cysteine residue is located at or close to the AdoMet binding site of EcoRII methyltransferase

  20. Objective and Longitudinal Assessment of Dermatitis After Postoperative Accelerated Partial Breast Irradiation Using High-Dose-Rate Interstitial Brachytherapy in Patients With Breast Cancer Treated With Breast Conserving Therapy: Reduction of Moisture Deterioration by APBI

    International Nuclear Information System (INIS)

    Tanaka, Eiichi; Yamazaki, Hideya; Yoshida, Ken; Takenaka, Tadashi; Masuda, Norikazu; Kotsuma, Tadayuki; Yoshioka, Yasuo; Inoue, Takehiro

    2011-01-01

    Purpose: To objectively evaluate the radiation dermatitis caused by accelerated partial breast irradiation (APBI) using high-dose-rate interstitial brachytherapy. Patients and Methods: The skin color and moisture changes were examined using a newly installed spectrophotometer and corneometer in 22 patients who had undergone APBI using open cavity implant high-dose-rate interstitial brachytherapy (36 Gy in six fractions) and compared with the corresponding values for 44 patients in an external beam radiotherapy (EBRT) control group (50–60 Gy in 25–30 fractions within 5–6 weeks) after breast conserving surgery. Results: All values changed significantly as a result of APBI. The extent of elevation in a∗ (reddish) and reduction in L∗ (black) values caused by APBI were similar to those for EBRT, with slightly delayed recovery for 6–12 months after treatment owing to the surgical procedure. In contrast, only APBI caused a change in the b∗ values, and EBRT did not, demonstrating that the reduction in b∗ values (yellowish) depends largely on the surgical procedure. The changes in moisture were less severe after APBI than after EBRT, and the recovery was more rapid. The toxicity assessment using the Common Toxicity Criteria, version 3, showed that all dermatitis caused by APBI was Grade 2 or less. Conclusion: An objective analysis can quantify the effects of APBI procedures on color and moisture cosmesis. The radiation dermatitis caused by APBI using the present schedule showed an equivalent effect on skin color and a less severe effect on moisture than the effects caused by standard EBRT.

  1. Intergenerational equity and conservation

    Science.gov (United States)

    Otoole, R. P.; Walton, A. L.

    1980-01-01

    The issue of integenerational equity in the use of natural resources is discussed in the context of coal mining conversion. An attempt to determine if there is a clear-cut benefit to future generations in setting minimum coal extraction efficiency standards in mining is made. It is demonstrated that preserving fossil fuels beyond the economically efficient level is not necessarily beneficial to future generations even in terms of their own preferences. Setting fossil fuel conservation targets for intermediate products (i.e. energy) may increase the quantities of fossil fuels available to future generations and hence lower the costs, but there may be serious disadvantages to future generations as well. The use of relatively inexpensive fossil fuels in this generation may result in more infrastructure development and more knowledge production available to future generations. The value of fossil fuels versus these other endowments in the future depends on many factors which cannot possibly be evaluated at present. Since there is no idea of whether future generations are being helped or harmed, it is recommended that integenerational equity not be used as a factor in setting coal mine extraction efficiency standards, or in establishing requirements.

  2. Energy conservation in SIMMER

    International Nuclear Information System (INIS)

    Arnold, L.A.; Knowles, J.B.

    1983-11-01

    The SIMMER code contains models of the many interacting thermo-hydraulic processes that occur during a hypothetical core disruptive accident (HCDA), to provide an overall picture from accident initiation to containment loading. In calculations of roof loadings following the HCDA, errors in computing the overall energy balance were found to be up to ten times the kinetic energy of the sodium slug which creates the loading. On this account, the results were considered to be seriously compromised. This report describes a systematic investigation into the effect, nature and origin of the energy discrepancies. Its main conclusion are that, the errors stem from a systematic rather than a random source, energy errors for individual cells can be two decades larger than the mean value provided by the code, and cellular mass and energy errors are strongly correlated and they can actually increase when the mesh is refined. A likely cause of the conservation errors is identified as the solution of the liquid phase mass and energy equations at effectively different time instants during each timestep. (author)

  3. Concrete: Too young for conservation

    NARCIS (Netherlands)

    Heineman, H.A.; Hees, R.P.J. van; Nijland, T.G.

    2008-01-01

    The 20th century built heritage is one of the new conservation challenges, due to its architectural differences from the traditional heritage and new materials. One major n